WO2006130567A2

WO2006130567A2 - Use of carbohydrate-rich compositions to diminish depressive disorders and symptoms thereof

Info

Publication number: WO2006130567A2
Application number: PCT/US2006/020796
Authority: WO
Inventors: Richard J. Wurtman; Judy Wurtman; David Mischoulon
Original assignee: Massachusetts Institute Of Technology
Priority date: 2005-06-02
Filing date: 2006-05-30
Publication date: 2006-12-07
Also published as: WO2006130567A3

Abstract

This invention provides methods of treating winter blues, seasonal affective disorder (SAD), and depressive disorders; and carbohydrate craving, weight gain, and mood symptoms associated with same, comprising administering to a subject a carbohydrate-rich composition with minimal protein content, or a carbohydrate-rich composition that contains tryptophan or a tryptophan-rich protein or peptide.

Description

USE OF CARBOHYDRATE-RICH COMPOSITIONS TO DIMINISH DEPRESSIVE DISORDERS AND SYMPTOMS THEREOF

FIELD OF INVENTION

BACKGROUND OF THE INVENTION

An estimated 15 million Americans suffer annually from winter blues or seasonal affective disorder (SAD), a condition characterized by depression, social withdrawal, overeating and weight gain. The highest incidences of the disorder are found in residents of northernmost locations. Winter blues and

SAD are often treated with an antidepressant such as Prozac or Zoloft; however, the annual cost of such therapy can easily exceed $300. Winter blues and SAD are also treated with light therapy; however, such therapy can be time-consuming, and ultraviolet light emitted by light boxes can cause damage to skin and other organs over the long-term. Thus, there exists a great need for additional treatments for SAD and winter blues.

SUMMARY OF THE INVENTION

In one embodiment, the present invention provides a method of treating winter blues in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 __ grams per serving, wherein the composition either contains no protein or has a protein content of less than 10% of its carbohydrate content, thereby treating winter blues in a subject.

In another embodiment, the present invention provides a method of treating an SAD in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 grams per serving, wherein the composition either contains no protein or has a protein content of less than 10% of its carbohydrate content, thereby treating an SAD in a subject.

In another embodiment, the present invention provides a method of treating a depressive disorder in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 grams per serving, wherein the composition either contains no protein or has a protein content of less than 10% of its carbohydrate content, thereby treating a depressive disorder in a subject.

In another embodiment, the present invention provides a method of treating a weight gain associated with a depressive disorder in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 grams per serving, wherein the composition either contains no protein or has a protein content of less than 10% of its carbohydrate content, thereby treating a weight gain associated with a depressive disorder in a subject.

In another embodiment, the present invention provides a method of treating a carbohydrate craving associated with a depressive disorder in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 grams per serving, wherein the composition either contains no protein or has a protein content of less than 10% of its carbohydrate content, thereby treating a carbohydrate craving associated with a depressive disorder in a subject.

In another embodiment, the present invention provides a method of treating winter blues in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 grams per serving, the composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein either (a) the composition contains no additional protein other than the tryptophan or tryptophan-rich protein; or (b) the amount of additional protein other than the tryptophan or tryptophan- rich protein is less than 10% of the carbohydrate content of the composition, thereby treating winter blues in a subject.

In another embodiment, the present invention provides a method of treating an SAD in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 grams per serving, the composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein either (a) the composition contains no additional protein other than the tryptophan or tryptophan-rich protein; or (b) the amount of additional protein other than the tryptophan or tryptophan- rich protein is less than 10% of the carbohydrate content of the composition, thereby treating an SAD in a subject. In another embodiment, the present invention provides a method of treating a depressive disorder in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 grams per serving, the composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein either (a) the composition contains no additional protein other than the tryptophan or tryptophan-rich protein; or (b) the amount of additional protein other than the tryptophan or tryptophan- rich protein is less than 10% of the carbohydrate content of the composition, thereby treating a depressive disorder in a subject.

In another embodiment, the present invention provides a method of treating a weight gain associated with a depressive disorder in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 grams per serving, the composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein either (a) the composition contains no additional protein other than the tryptophan or tryptophan-rich protein; or (b) the amount of additional protein other than the tryptophan or tryptophan-rich protein is less than 10% of the carbohydrate content of the composition, thereby treating a weight gain associated with a depressive disorder in a subject.

In another embodiment, the present invention provides a method of treating a carbohydrate craving associated with a depressive disorder in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 grams per serving, the composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein either (a) the composition contains no additional protein other than the tryptophan or tryptophan-rich protein; or (b) the amount of additional protein other than the tryptophan or tryptophan-rich protein is less than 10% of the carbohydrate content of the composition, thereby treating a carbohydrate craving associated with a depressive disorder in a subject.

DETAILED DESCRIPTION OF THE INVENTION

This invention provides methods of treating winter blues, seasonal affective disorder (SAD), and depressive disorders; and carbohydrate craving, weight gain, and mood symptoms associated with same, "comprising administering to a subject a carbohydrate-rich composition with minimal protein content, or a carbohydrate-rich composition that contains tryptophan or a tryptophan-rich protein or peptide.

In one embodiment, the present invention provides a method of treating winter blues in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 grams per serving, thereby treating winter blues in a subject.

In another embodiment, a composition utilized in methods of the present invention contains no protein. In another embodiment, the composition has a protein content of less than 10% of its carbohydrate content. Each possibility represents a separate embodiment of the present invention.

"Winter blues" or "SAD" refers, in another embodiment, to a depressive disorder that is due, in part, to a lack of bright sunshine. In another embodiment, one or more of these terms refers to recurrent depression linked to particular period of the year (such as regular onset of depression in fall and offset in spring). In another embodiment, one or more of these terms is defined by a pattern of symptoms, e.g. hypo-arousal, fatigue, increased appetite and weight gain. In another embodiment, one or more of these terms refers to any other definition of "winter blues" or "SAD" utilized in the art.

In another embodiment, "SAD" refers to Seasonal Affective Disorder, as specified in the DSM-IV. In another embodiment, "winter blues" refers to a condition with symptoms similar to SAD, but wherein the symptoms do not reach the threshold specified in the DSM-IV for a diagnosis of SAD. In another embodiment, persons afflicted with winter blues can use compositions of the present invention without a prescription. Each possibility represents a separate embodiment of the present invention.

Methods of assessing winter blues or SAD are well known in the art. In another embodiment, HAM-D is used to assess winter blues or SAD. HAM-D is a useful tool for measuring the progress of a patient during the course of treatment, either in the research or clinical setting. Several different versions of the HAM-D exist; they differ only in the number of questions included. The longest version includes 31- items; the shortest includes only 6-items. The longer versions include questions about atypical depression symptoms, psychotic symptoms, psychosomatic symptoms, and symptoms associated with obsessive-

•^■compulsive disorder (OCD). The standard form which is generally used in research studies, is the 17- kem Hamilton D (HAM-D-17). This particular study used the 28-item version. Answers to questions are rated on a scale of 0-4 or 0-2, with higher scores indicating more severe pathology. Scores on the HAM-

D typically fall into the following ranges: a) Not depressed: 0-7; b) Mildly depressed: 7-15; c) Moderately depressed: 15-25; d) Severely depressed: over 25. A decrease of 50% or more in the Hamilton-D score is considered to be a positive response to treatment, while a score of 7 or less is considered typical of remission. The HAM-D is the most widely studied instrument for depression, and its reliability and validity are high. In another embodiment, winter blues or SAD is assessed using the Seasonal Patterns Assessment Questionnaire (Rosenthal, et al, (1987) Seasonal Pattern Assessment Questionnaire. Bethesda, MD: National Institute of Mental Health). In another embodiment, winter blues or SAD is assessed using the CGI-S or CGI-I instruments (described in more detail below) In another embodiment, winter blues or SAD is assessed using any other method of assessing winter blues or SAD that is known in the art. Each method represents a separate embodiment of the present invention.

"Carbohydrate content" refers, in another embodiment, to the total amount of carbohydrate in the composition. In another embodiment, the term refers to the total amount of easily digestible carbohydrate in the composition. In another embodiment, the term refers to the total amount in the composition of a particular class of carbohydrates, e.g. high glycemic index (GI) carbohydrates, or any other class of carbohydrates known in the art. In another embodiment, the term refers to the total amount of carbohydrate in the composition. In other embodiments, the term refers to the amount in the composition of a particular class of carbohydrates. Each possibility represents a separate embodiment of the present invention.

"Protein content" refers, in another embodiment, to the total amount of protein in the composition. In another embodiment, the term refers to the total amount of easily digestible protein in the composition. In another embodiment, the term refers to the total amount in the composition of LNAA protein. In another embodiment, the term refers to the total amount in the composition of BCAA proteins. In another embodiment, the term refers to the total amount in the composition of LNAA and BCAA proteins combined. In another embodiment, the term refers to the total amount in the composition of any other class of proteins known in the art. Each possibility represents a separate embodiment of the present invention.

A content of "zero" or "no protein" refers, in another embodiment, to a total absence of the substance referred to. In another embodiment, a content of "zero" refers to an amount of the substance that is below detection. In another embodiment, a content of "zero" refers to an amount of the substance that is nutritionally insignificant. In another embodiment, a content of "zero" refers to a trace amount of the substance. In another embodiment, "trace amount" refers to an amount that is detectable but not able to be quantified. In another embodiment, "trace amount" refers to a barely detectable amount. Each possibility represents a separate embodiment of the present invention.

Methods for measuring protein content are well known in the art, and are described, for example in Wheat Chemistry and Technology (3rd Edition), Yeshajahu Pomeranz, Ed., © 1988, American Association of Cereal Chemists. In another embodiment, protein content is measured using the Kjeldahl procedure, which measures protein content based on the nitrogen content of the composition (J Med Lab Technol 20: 191-5, 1963). In another embodiment, the Kjeldahl procedure is used to measure crude protein content, and the number is then adjusted by subtracting the contribution of other nitrogen sources in the composition, e.g. ammonia, urea, creatine, creatinine, uric acid, orotic acid, peptides, hippuric acid. In another embodiment, protein content is measured using Udy dye binding. In another embodiment, protein content is measured using infrared reflectance. In another embodiment, protein content is measured using near-infrared reflectance. In another embodiment, protein content is measured using any other method known in the art for measuring protein content. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the composition utilized in methods of the present invention contains at least about 21 grams (g) of carbohydrate per serving. In another embodiment, the amount is at least about 22 g per serving. In another embodiment, the amount is at least about 23 g per serving. In another embodiment, the amount is at least about 24 g per serving. In another embodiment, the amount is at least about 25 g per serving. In another embodiment, the amount is at least about 26 g per serving. In another embodiment, the amount is at least about 27 g per serving. In another embodiment, the amount is at least about 28 g per serving. In another embodiment, the amount is at least about 29 g per serving. In another embodiment, the amount is at least about 30 g per serving. In another embodiment, the amount is at least about 31 g per serving. In another embodiment, the amount is at least about 32 g per serving. In another embodiment, the amount is at least about 33 g per serving. In another embodiment, the amount is at least about 34 g per serving. In another embodiment, the amount is at least about 35 g per serving. In another embodiment, the amount is at least about 36 g per serving. In another embodiment, the amount is at least about 37 g per serving. In another embodiment, the amount is at least about 38 g per serving. In another embodiment, the amount is at least about 39 g per serving. In another embodiment, the amount is at least about 40 g per serving. In another embodiment, the amount is at least about 41 g per serving. In another embodiment, the amount is at least about 42 g per serving. In another embodiment, the amount is at least about 43 g per serving. In another embodiment, the amount is at least about 44 g per serving. In another embodiment, the amount is at least about 45 g per serving. In another embodiment, the amount is at least about 46 g per serving. In another embodiment, the amount is at least about 47 g per serving. In another embodiment, the amount is at least about 48 g per serving. In another embodiment, the amount is at least about 49 g per serving. In another embodiment, the amount is at least about 50 g per serving. In another embodiment, the amount is at least about 55 g per serving. In another embodiment, the amount is at least about 60 g per serving.

In another embodiment, the composition contains carbohydrate in a quantity sufficient to raise the serotonin level in the subject. In another embodiment, the composition contains carbohydrate in a quantity sufficient to lower plasma levels of LNAA other than tryptophan in the subject. In another embodiment, the composition contains carbohydrate in a quantity sufficient to raise the "plasma tryptophan ratio" (e.g. plasma tryptophan divided by the sum of the other 5 LNAA) in the subject.

In another embodiment, the composition utilized in methods of the present invention contains at least about 21 g of carbohydrate. In another embodiment, the amount is at least about 22 g. In another embodiment, the amount is at least about 23 g. In another embodiment, the amount is at least about 24 g. In another embodiment, the amount is at least about 25 g. In another embodiment, the amount is at least about 26 g. In another embodiment, the amount is at least about 27 g. In another embodiment, the amount is at least about 28 g. In another embodiment, the amount is at least about 29 g. In another embodiment, the amount is at least about 30 g. In another embodiment, the amount is at least about 31 g. In another embodiment, the amount is at least about 32 g. In another embodiment, the amount is at least about 33 g. In another embodiment, the amount is at least about 34 g. In another embodiment, the amount is at least about 35 g. In another embodiment, the amount is at least about 36 g. In another embodiment, the amount is at least about 37 g. In another embodiment, the amount is at least about 38 g. In another embodiment, the amount is at least about 39 g. In another embodiment, the amount is at least about 40 g. In another embodiment, the amount is at least about 41 g. In another embodiment, the amount is at least about 42 g. In another embodiment, the amount is at least about 43 g. In another embodiment, the amount is at least about 44 g. In another embodiment, the amount is at least about 45 g. In another embodiment, the amount is at least about 46 g. In another embodiment, the amount is at least about 47 g. In another embodiment, the amount is at least about 48 g. In another embodiment, the amount is at least about 49 g. In another embodiment, the amount is at least about 50 g. In another embodiment, the amount is at least about 55 g. In another embodiment, the amount is at least about 60 g. Each of the above amounts of carbohydrates represents a separate embodiment of the present invention.

In other embodiments, the composition utilized in methods of the present invention contains a range of carbohydrate amounts per serving. In another embodiment, the amount is 21-40 g per serving. In another embodiment, the amount is 22-41 g per serving. In another embodiment, the amount is 23-42 g per serving. In another embodiment, the amount is 24-43 g per serving. In another embodiment, the amount is 25-44 g per serving. In another embodiment, the amount is 26-45 g per serving. In another embodiment, the amount is 27-46 g per serving. In another embodiment, the amount is 28-47 g per serving. In another embodiment, the amount is 29-48 g per serving. In another embodiment, the amount is 30-49 g per serving. In another embodiment, the amount is 31-50 g per serving. In another embodiment, the amount is 32-51 g, or from about 33-52 g per serving. In other embodiments, the composition contains from about 21-30 g per serving. In another embodiment, the amount is 22-31 g per serving. In another embodiment, the amount is 23-32 g per serving. In another embodiment, the amount is 24-33 g per serving. In another embodiment, the amount is 25-34 g per serving. In another embodiment, the amount is 26-35 g per serving. In another embodiment, the amount is 27-36 g per serving. In another embodiment, the amount is 28-37 g per serving. In another embodiment, the amount is 29-38 g per serving. In another embodiment, the amount is 30-39 g per serving. In another embodiment, the amount is 31-40 g per serving. In another embodiment, the amount is 32-41 g per serving. In another embodiment, the amount is 33-42 g per serving. In another embodiment, the amount is 34-43 g per serving. In another embodiment, the amount is 35-44 g per serving. In another embodiment, the amount is 36-45 g per serving. In another embodiment, the amount is 37-46 g per serving. In another embodiment, the amount is 38-47 g per serving. In another embodiment, the amount is 39-48 g per serving. In another embodiment, the amount is 40-49 g, or from about 41-50 g per serving.

In other embodiments, the composition contains from about 30-34 g per serving. In another embodiment, the amount is 31-35 g per serving. In another embodiment, the amount is 32-36 g per serving. In another embodiment, the amount is 33-37 g per serving. In another embodiment, the amount is 34-38 g per serving. In another embodiment, the amount is 35-39 g per serving. In another embodiment, the amount is 36-40 g per serving. In another embodiment, the amount is 37-41 g per serving. In another embodiment, the amount is 38-42 g per serving. In another embodiment, the amount is 39-43 g per serving. In another embodiment, the amount is 40-44 g per serving. In another embodiment, the amount is 41-45 g per serving. In another embodiment, the amount is 42-46 g per serving. In another embodiment, the amount is 43-47 g per serving. In another embodiment, the amount is 44-48 g per serving. In another embodiment, the amount is 45-49 g per serving. In another embodiment, the amount is 46-50 g, or from about 47-51 g per serving. In other embodiments, the amount of carbohydrate in the composition is one of the above amounts.

In another embodiment, the composition utilized in methods of the present invention is carbohydrate- rich. In another embodiment, the composition utilized in methods of the present invention has a high carbohydrate content. "Carbohydrate-rich" and "high carbohydrate content" refer, in another embodiment, to a composition containing any of the amounts of carbohydrates enumerated herein. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the composition utilized in methods of the present invention comprises a starch. In another embodiment, the starch is potato starch. In another embodiment, the starch is any other starch known in the art. In another embodiment, the composition comprises a maltodextrin. In another embodiment, the composition comprises dextrose. In another embodiment, the composition comprises a dextrin.

In another embodiment, the composition comprises 2 carbohydrate compounds. In another embodiment, the composition comprises 3 carbohydrate compounds. In another embodiment, the composition comprises 4 carbohydrate compounds. In another embodiment, the composition comprises 5 carbohydrate compounds. In another embodiment, the composition comprises 6 carbohydrate compounds. In another embodiment, the composition comprises 7 carbohydrate compounds. In another embodiment, the composition comprises more than 7 carbohydrate compounds. In another embodiment, the composition comprises 2-4 carbohydrate compounds. In another embodiment, the composition comprises 2-3 carbohydrate compounds. In another embodiment, the composition comprises 2-5 carbohydrate compounds. In another embodiment, the composition comprises 2-6 carbohydrate compounds. In another embodiment, the composition comprises 2-7 carbohydrate compounds. In another embodiment, the composition comprises 3-4 carbohydrate compounds. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the composition utilized in methods of the present invention comprises 2 carbohydrate compounds selected from a starch, a maltodextrin, a dextrose, and a dextrin. In another embodiment, the composition comprises at least 2 carbohydrate compounds selected from a starch, a maltodextrin, a dextrose, and a dextrin. In another embodiment, the composition comprises 3 carbohydrate compounds selected from a starch, a maltodextrin, a dextrose, and a dextrin. In another embodiment, the composition comprises at least 3 carbohydrate compounds selected from a starch, a maltodextrin, a dextrose, and a dextrin. In another embodiment, the composition comprises a starch, a maltodextrin, a dextrose, and a dextrin.

In another embodiment, the carbohydrate contained in compositions of the present invention is a high glycemic index (GI) carbohydrate. In another embodiment, a composition utilized in methods of the present invention comprises more than 1 different high GI carbohydrate. In another embodiment, the composition comprises more than 2 different high GI carbohydrates. In another embodiment, the composition comprises more than 3 different high GI carbohydrates. In another embodiment, the composition comprises more than 4 different high GI carbohydrates. In another embodiment, all the carbohydrates in the composition are high GI carbohydrates. In another embodiment, more than 50% of the carbohydrate in the composition (expressed as a percentage of the total carbohydrate mass) is high GI carbohydrate. In another embodiment, more than 60% of the carbohydrate in the composition is high GI carbohydrate. In another embodiment, more than 70% of the carbohydrate is high GI. In another embodiment, more than 80% of the carbohydrate is high GI. In another embodiment, more than 90% of the carbohydrate is high GI. In another embodiment, more than 95% of the carbohydrate is high GI. In another embodiment, more than 97% of the carbohydrate is high GI. In another embodiment, more than 98% of the carbohydrate is high GI. In another embodiment, more than 99% of the carbohydrate is high GI. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the carbohydrate contained in compositions of the present invention effectively elicits insulin secretion ("insulin-eliciting carbohydrate"). In another embodiment, a composition utilized in methods of the present invention comprises more than 1 different insulin-eliciting carbohydrate. In another embodiment, the composition comprises more than 2 different insulin-eliciting carbohydrates. In another embodiment, the composition comprises more than 3 different insulin-eliciting carbohydrates. In another embodiment, the composition comprises more than 4 different insulin-eliciting carbohydrates. In another embodiment, all the carbohydrates in the composition are insulin-eliciting carbohydrates. In another embodiment, more than 50% of the carbohydrate in the composition (expressed as a percentage of the total carbohydrate mass) is insulin-eliciting carbohydrate. In another embodiment, more than 60% of the carbohydrate in the composition is insulin-eliciting carbohydrate. In another embodiment, more than 70% of the carbohydrate is high GI. In another embodiment, more than 80% of the carbohydrate is high GI. In another embodiment, more than 90% of the carbohydrate is high GI. In another embodiment, more than 95% of the carbohydrate is high GI. In another embodiment, more than 97% of the carbohydrate is high GI. In another embodiment, more than 98% of the carbohydrate is high GI. In another embodiment, more than 99% of the carbohydrate is high GI. Each possibility represents a separate embodiment of the present invention.

"High GI" refers, in another embodiment, to a GI of over 100 (on a scale in which dextrose is assigned 137). In another embodiment, the term refers to a GI of over 80. In another embodiment, the term refers to a GI of over 90. In another embodiment, the term refers to a GI of over 95. In another embodiment, the term refers to a GI of over 105. In another embodiment, the term refers to a GI of over 110. In another embodiment, the term refers to a GI of over 115. In another embodiment, the term refers to a GI of over 120. In another embodiment, the term refers to a GI of at least 100. In another embodiment, the term refers to a GI of at least 80. In another embodiment, the term refers to a GI of at least 90. In another embodiment, the term refers to a GI of at least 95. In another embodiment, the term refers to a GI of at least 105. In another embodiment, the term refers to a GI of at least 110. In another embodiment, the term refers to a GI of at least 115. In another embodiment, the term refers to a GI of at least 120. Each possibility represents a separate embodiment of the present invention.

In another embodiment, a method of the present invention utilizes a composition comprising a mixture of carbohydrates of varying size. In another embodiment, the composition comprises a low molecular weight (MW) carbohydrate and a medium MW carbohydrate. In another embodiment, the composition comprises a low MW carbohydrate and a high MW carbohydrate. In another embodiment, the composition comprises a medium MW carbohydrate and a high MW carbohydrate. In another embodiment, the composition comprises a low MW carbohydrate, a medium MW carbohydrate, and a high MW carbohydrate. In another embodiment, the composition comprises 2 low MW carbohydrates and a high MW carbohydrate. In another embodiment, the composition comprises 2 low MW carbohydrates and a medium MW carbohydrate. In another embodiment, the composition comprises 2 low MW carbohydrates, a medium MW carbohydrate, and a high MW carbohydrate. Each possibility represents a separate embodiment of the present invention.

In another embodiment, a method or composition of the present invention raises insulin levels. In another embodiment, the raised insulin level causes LNAA other than insulin (e.g. leucine, isoleucine, valine, tyrosine, and phenylalanine) to be absorbed from the plasma into tissues. In another embodiment, the raised insulin level is sufficient to transiently lower the plasma concentration of these other LNAA by

10%. In another embodiment, the plasma concentration of these other LNAA is lowered by 15%. In another embodiment, the plasma concentration is lowered by 20%. In another embodiment, the plasma concentration is lowered by 25%. In another embodiment, the plasma concentration is lowered by 30%.

In another embodiment, the plasma concentration is lowered by 35%. In another embodiment, the plasma concentration is lowered by 40%. In another embodiment, the plasma concentration is lowered by 45%. In another embodiment, the plasma concentration is lowered by 50%. Li another embodiment, the plasma concentration is lowered by 55%. In another embodiment, the plasma concentration is lowered by 60%. In another embodiment, the plasma concentration is lowered by 65%. In another embodiment, the plasma concentration is lowered by 70%. In another embodiment, the plasma concentration is lowered by 75%. In another embodiment, the plasma concentration is lowered by 80%. In another embodiment, the plasma concentration is lowered by 85%. In another embodiment, the plasma concentration is lowered by 90%. In another embodiment, the plasma concentration is lowered by 95%. Each possibility represents a separate embodiment of the present invention.

"Transient" refers, in another embodiment, to the average concentration over the next 2 hours after administration of the composition. In another embodiment, the term refers to the average concentration over the next hour after administration of the composition. In another embodiment, the term refers to the average concentration over the next 90 minutes. In another embodiment, the term refers to the average concentration over the next 150 minutes. In another embodiment, the term refers to the average concentration over the next 3 hours. In another embodiment, the term refers to the concentration 1 hour after administration. In another embodiment, the term refers to the concentration 1 hour after administration. In another embodiment, the term refers to the concentration 90 minutes after administration. In another embodiment, the term refers to the concentration 2 hours after administration. In another embodiment, the term refers to the concentration 150 minutes after administration. In another embodiment, the term refers to the concentration 3 hours after administration. Each possibility represents a separate embodiment of the present invention.

In another embodiment, a medium MW carbohydrate takes longer to be absorbed than a lower MW carbohydrate. In another embodiment, the medium MW carbohydrate takes longer to raise blood sugar levels than a lower MW carbohydrate. In another embodiment, a higher MW carbohydrate takes longer to be absorbed than a lower MW carbohydrate. In another embodiment, the higher MW carbohydrate takes longer to act on blood sugar levels than a lower MW carbohydrate. In another embodiment, a higher MW carbohydrate takes longer to be absorbed than a lower MW carbohydrate. In another embodiment, the higher MW carbohydrate takes longer to raise blood sugar levels than a lower MW carbohydrate. Each possibility represents a separate embodiment of the present invention.

In another embodiment, a method or composition of the present invention enables the treatment of winter blues and/or other depressive disorders or their symptoms for an extended period of time, relative to compositions not comprising the same degree or number of different carbohydrates of varying size. In another embodiment, a method or composition of the present invention raises brain serotonin levels more effectively than other compositions. Thus, in another embodiment, the present invention provides a method of treating one of the above diseases, disorders, or symptoms for an extended period of time relative to compositions not comprising the same degree or number of different carbohydrates of varying size. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the carbohydrate with a relatively low MW is a dextrin. In another embodiment, the carbohydrate with a relatively low MW is a dextrose. In another embodiment, the carbohydrate with a relatively low MW is any other carbohydrate with a relatively low MW known in the art.

In another embodiment, the medium MW carbohydrate is a maltodextrin. In another embodiment, the high MW carbohydrate is a starch. In another embodiment, the high MW carbohydrate is any other high MW carbohydrate known in the art.

Each carbohydrate and combination thereof represents a separate embodiment of the present invention.

In another embodiment of methods of the present invention, the total amount of protein in the composition is less than about 9 percent of the carbohydrate content. In another embodiment, the ratio of total amount of protein to carbohydrate content is less than about 8 percent. In another embodiment, the ratio is less than about 7 percent. In another embodiment, the ratio is less than about 6 percent. In another embodiment, the ratio is less than about 5 percent. In another embodiment, the ratio is less than about 4 percent. In another embodiment, the ratio is less than about 3 percent. In another embodiment, the ratio is less than about 2 percent. In another embodiment, the ratio is less than about 1 percent. Each ratio represents a separate embodiment of the present invention.

In another embodiment, the composition utilized in methods of the present invention contains less than about 4 grams of protein per serving. In another embodiment, the composition contains less than about 3 grams of protein per serving. In another embodiment, the composition contains less than about 2 grams of protein per serving. In another embodiment, the composition contains less than about 1.5 grams of protein per serving. In another embodiment, the composition contains less than about 1 gram of protein per serving. In another embodiment, the composition contains less than about 0.5 grams of protein per serving. Each amount represents a separate embodiment of the present invention.

In another embodiment, the composition utilized in methods of the present invention has minimal protein content. In another embodiment, "minimal" refers to one of the above amounts of protein. In another embodiment, "minimal" refers to any other definition of "minimal" in the ait. Each possibility represents a separate embodiment of the present invention.

As provided herein, the present invention has demonstrated that administration of a composition high in carbohydrates and low in protein improves winter blues in subjects suffering from the disorder. This was determined by compiling winter blues symptoms to obtain an overall index of winter blues severity (Example 1). In addition, the composition decreased the incidence and severity of several key symptoms of winter blues (Example 2). Of note, the difference was statistically significant fashion relative to a control beverage containing 15 grams of protein. These results demonstrate that carbohydrate-rich nutritive compositions have utility in treating depressive disorders such as winter blues and SAD.

In another embodiment of methods of the present invention, the depressive disorder that is treated, or that is associated with weight gain or a mood symptom that is treated, is a major depressive disorder. In another embodiment, the depressive disorder is bipolar depression. In another embodiment, the depressive disorder is dysthymia. In another embodiment, the depressive disorder is minor depression. In another embodiment, the depressive disorder is subsyndromal depression. In another embodiment, the depressive disorder is subsyndromal SAD. In another embodiment, the depressive disorder is anxiety. In another embodiment, the depressive disorder is fatigue. In another embodiment, the depressive disorder is postpartum depression.

In another embodiment, the depressive disorder is associated with another disease or disorder. In another embodiment, the depressive disorder is secondary to another disease or disorder. In another embodiment, the disease or disorder is fibromyalgia. In another embodiment, the depressive disorder is any other depressive disorder known in the art.

In another embodiment, the major depressive disorder is atypical depression. In another embodiment, the major depressive disorder is melancholic depression. In another embodiment, the major depressive disorder is psychotic depression. In another embodiment, the major depressive disorder is any other major depressive disorder known in the art.

Each disorder represents a separate embodiment of the present invention.

As provided herein, the present invention has demonstrated that administration of a composition high in carbohydrates and low in protein improved 19 of 27 individual symptoms associated with SAD, including weight gain. Thus, such compositions are effective in treating weight gain and other symptoms associated with depressive disorders.

A composition utilized in a method of the present invention, contains, in another embodiment, no additional protein other than the tryptophan or tryptophan-rich protein. In another embodiment, the amount in the composition of additional protein other than the tryptophan or tryptophan-rich protein is less than 10% of the carbohydrate content of the composition. Each possibility represents a separate embodiment of the present invention.

As described above, the present invention has demonstrated that administration of a nutritive composition that increases brain serotonin levels has utility in treating SAD. Administration of tryptophan-rich protein(s) also increases brain serotonin levels. Thus, the findings of the present invention also show that a composition high in carbohydrates and containing tryptophan or a tryptophan- rich protein or peptide is efficacious in treating SAD.

In another embodiment, the present invention provides a method of treating an SAD in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 grams per serving, the composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein either (a) the composition contains no additional protein other than the tryptophan or tryptophan-rich protein; or (b) the amount of additional protein other than the tryptophan or tryptophan- rich protein is less than 10% of the carbohydrate content of the composition, thereby treating an SAD in a subject.

In another embodiment, the present invention provides a method of treating a depressive disorder in a subject, comprising administering to the subject a composition having a carbohydrate content of least about 20 grams per serving, the composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein either (a) the composition contains no additional protein other than the tryptophan or tryptophan-rich protein; or (b) the amount of additional protein other than the tryptophan or tryptophan- rich protein is less than 10% of the carbohydrate content of the composition, thereby treating a depressive disorder in a subject.

In another embodiment, the additional protein other than the tryptophan or tryptophan-rich protein or peptide present in a composition of the present invention is a single protein. In another embodiment, the composition comprises more than one protein that is not a tryptophan-rich protein. In another embodiment, there is no additional protein present in the composition. In another embodiment, there is no detectable amount of additional protein present in the composition.

"Additional protein" refers, in another embodiment, to amino acids (AA) other than tryptophan. In another embodiment, the term refers to both AA other than tryptophan and proteins that are not tryptophan-rich. Each possibility represents a separate embodiment of the present invention.

In another embodiment of methods of the present invention, the total amount of additional protein in the composition is less than about 9 percent of the carbohydrate content. In another embodiment, the ratio of total amount of additional protein to carbohydrate content is less than about 8 percent. In another embodiment, the ratio is less than about 7 percent. In another embodiment, the ratio is less than about 6 percent. In another embodiment, the ratio is less than about 5 percent. In another embodiment, the ratio is less than about 4 percent. In another embodiment, the ratio is less than about 3 percent. In another embodiment, the ratio is less than about 2 percent. In another embodiment, the ratio is less than about 1 percent. Each ratio represents a separate embodiment of the present invention.

In another embodiment, a composition utilized in methods of the present invention contains less than about 4 grams (g) of additional protein per serving. In another embodiment, the composition contains less than about 3 g of additional protein per serving. In another embodiment, the composition contains less than about 2 g of additional protein per serving. In another embodiment, the composition contains less than about 1.5 g of additional protein per serving. In another embodiment, the composition contains less than about 1 g of additional protein per serving. In another embodiment, the composition contains less than about 0.5 g of additional protein per serving. In another embodiment, the composition contains no additional protein. In another embodiment, the composition does not contain a detectable amount of additional protein. In another embodiment, the composition does not contain a detectable amount of additional protein per serving. Each amount represents a separate embodiment of the present invention.

In another embodiment, the composition utilized in methods of the present invention has minimal content of additional protein. In another embodiment, "minimal" refers to one of the above amounts of protein. In another embodiment, "minimal" refers to any other definition of "minimal" in the art. Each possibility represents a separate embodiment of the present invention.

In another embodiment of methods of the present invention, the tryptophan-rich protein is an alpha- lactalbumin (alpha-lac) protein. In another embodiment, the alpha-lac protein is a naturally occurring or synthetic derivative of alpha-lac. In another embodiment, the alpha-lac protein is an isoform of alpha-lac. In another embodiment, the alpha-lac protein is a homologue of bovine alpha-lac from any species, including cows, provided that the protein has a tryptophan content of greater than about 2% tryptophan. In another embodiment, the alpha-lac is isolated or purified from a biological source. In another embodiment, the alpha-lac is produced by recombinant methods. In other embodiments, the alpha-lac is in the form of whey protein, whey protein concentrate, whey powder, or alpha-lac-enriched whey protein. Methods for producing alpha-lac-enriched whey protein are known in the art (see, for example, U.S. Pat. No. 6,312,755).

In another embodiment, the tryptophan-rich protein is macadamia nut protein. In another embodiment, the tryptophan-rich protein is pichia pastoris yeast protein (U.S. Pat. No. 4,709,449). In another embodiment, the tryptophan-rich protein is any other tryptophan-rich protein known in the art. In another embodiment, "a tryptophan-rich protein" refers to the presence in the composition of a mixture of more than one tryptophan-rich protein.

In another embodiment, a tryptophan-rich peptide is utilized in methods of the present invention. In another embodiment, the tryptophan-rich peptide is any tryptophan-rich peptide known in the art. Each possibility represents a separate embodiment of the present invention.

Each alpha-lac protein and tryptophan-rich protein and peptide represents a separate embodiment of the present invention.

"Tryptophan-rich" refers, in another embodiment, to a protein or peptide that has a tryptophan content of greater than about 2%. In another embodiment, the tryptophan content is greater than about 1.5%. In another embodiment, the tryptophan content is greater than about 2.5%. In another embodiment, the tryptophan content is greater than about 3%. In another embodiment, the tryptophan content is greater than about 3.5%. In another embodiment, the tryptophan content is greater than about 4%. In another embodiment, the tryptophan content is greater than about 4.5%. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the present invention provides a method for treating a subject with one of the above disorders, comprising administering to the subject a composition having a high carbohydrate content, as defined in the present invention, the composition further comprising tryptophan or a metabolic precursor thereof, wherein the total amount in the composition of protein other than the tryptophan or precursor thereof is zero or is less than about 10% of the carbohydrate content of the composition, thereby treating one of the above disorders.

In another embodiment, the composition utilized in methods of the present invention contains at least about 1 g of tryptophan-rich protein or peptide per serving. In another embodiment, the amount is at least about 2 g per serving. In another embodiment, the amount is at least about 3 g per serving. In another embodiment, the amount is at least about 4 g per serving. In another embodiment, the amount is at least about 5 g per serving. In another embodiment, the amount is at least about 6 g per serving. In another embodiment, the amount is at least about 7 g per serving. In another embodiment, the amount is at least about 8 g per serving. In another embodiment, the amount is at least about 9 g per serving. In another embodiment, the amount is at least about 1O g per serving. In another embodiment, the amount is at least about H g per serving. In another embodiment, the amount is at least about 12 g per serving. In another embodiment, the amount is at least about 13 g per serving. In another embodiment, the amount is at least about 14 g per serving. In another embodiment, the amount is at least about 15 g per serving. In another embodiment, the amount is at least about 16 g per serving. In another embodiment, the amount is at least about 17 g per serving. In another embodiment, the amount is at least about 18 g per serving. In another embodiment, the amount is at least about 19 g per serving. In another embodiment, the amount is at least about 20 g per serving. In another embodiment, the amount is at least about 21 g per serving. In another embodiment, the amount is at least about 22 g per serving. In another embodiment, the amount is at least about 23 g per serving. In another embodiment, the amount is at least about 24 g per serving. In another embodiment, the amount is at least about 25 g per serving. In another embodiment, the amount is at least about 26 g per serving. In another embodiment, the amount is at least about 27 g per serving. In another embodiment, the amount is at least about 28 g per serving. In another embodiment, the amount is at least about 29 g per serving. In another embodiment, the amount is at least about 30 g per serving. In another embodiment, the amount is at least about 35 g per serving. In another embodiment, the amount is at least about 40 g per serving. In another embodiment, the composition contains tryptophan-rich protein or peptide in a quantity sufficient, together with the carbohydrate in the composition, to raise the serotonin level in the subject. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the composition utilized in methods of the present invention contains about 1 g of tryptophan-rich protein or peptide per serving. In another embodiment, the amount is about 2 g per serving. In another embodiment, the amount is about 3 g per serving. In another embodiment, the amount is about 4 g per serving. In another embodiment, the amount is about 5 g per serving. In another embodiment, the amount is about 6 g per serving. In another embodiment, the amount is about 7 g per serving. In another embodiment, the amount is about 8 g per serving. In another embodiment, the amount is about 9 g per serving. In another embodiment, the amount is about 1O g per serving. In another embodiment, the amount is about H g per serving. In another embodiment, the amount is about 12 g per serving. In another embodiment, the amount is about 13 g per serving. In another embodiment, the amount is about 14 g per serving. In another embodiment, the amount is about 15 g per serving. In another embodiment, the amount is about 16 g per serving. In another embodiment, the amount is about 17 g per serving. In another embodiment, the amount is about 18 g per serving. In another embodiment, the amount is about 19 g per serving. In another embodiment, the amount is about 20 g per serving. In another embodiment, the amount is about 21 g per serving. In another embodiment, the amount is about 22 g per serving. In another embodiment, the amount is about 23 g per serving. In another embodiment, the amount is about 24 g per serving. In another embodiment, the amount is about 25 g per serving. In another embodiment, the amount is about 26 g per serving. In another embodiment, the amount is about 27 g per serving. In another embodiment, the amount is about 28 g per serving. In another embodiment, the amount is about 29 g per serving. In another embodiment, the amount is about 30 g per serving. In another embodiment, the amount is about 35 g per serving. In another embodiment, the amount is about 40 g per serving. Each possibility represents a separate embodiment of the present invention.

In another embodiment, a composition utilized in methods of the present invention contains tryptophan in the form of a free amino acid. In another embodiment, the composition contains a pharmaceutically acceptable derivative of tryptophan. Each possibility represents a separate embodiment of the present invention.

In other embodiments, a composition utilized in methods of the present invention contains 0.1 g of tryptophan per serving. In another embodiment, the amount is 0.05 g per serving. In another embodiment, the amount is 0.15 g per serving. In another embodiment, the amount is 0.2 g per serving. In another embodiment, the amount is 0.3 g per serving. In another embodiment, the amount is 0.4 g per serving. In another embodiment, the amount is 0.5 g per serving. In another embodiment, the amount is 0.6 g per serving. In another embodiment, the amount is 0.8 g per serving. In another embodiment, the composition contains tryptophan in a quantity sufficient, together with the carbohydrate in the composition, to raise the serotonin level in the subject. In another embodiment, the amount of tryptophan is one of the amounts enumerated above for a tryptophan-rich protein or peptide. Each amount represents a separate embodiment of the present invention.

In other embodiments, the composition contains at least 0.1 g of a tryptophan per serving. In another embodiment, the amount is at least 0.15 g per serving. In another embodiment, the amount is at least 0.2 g per serving. In another embodiment, the amount is at least 0.3 g per serving. In another embodiment, the amount is at least 0.4 g per serving. In another embodiment, the amount is at least 0.5 g per serving. In another embodiment, the amount is at least 0.6 g per serving. In another embodiment, the amount is at least 0.8 g per serving. Each amount represents a separate embodiment of the present invention.

In other embodiments, the composition contains 0.1 g of a tryptophan derivative per serving. In another embodiment, the amount is 0.15 g per serving. In another embodiment, the amount is 0.2 g per serving. In another embodiment, the amount is 0.3 g per serving. In another embodiment, the amount is 0.4 g per serving. In another embodiment, the amount is 0.5 g per serving. In another embodiment, the amount is 0.6 g per serving. In another embodiment, the amount is 0.8 g per serving. In another embodiment, the amount of a tryptophan derivative is one of the amounts enumerated above for a tryptophan-rich protein or peptide. Each amount represents a separate embodiment of the present invention.

In other embodiments, the composition contains at least 0.1 g of a tiyptophan derivative per serving. In another embodiment, the amount is at least 0.15 g per serving. In another embodiment, the amount is at least 0.2 g per serving. In another embodiment, the amount is at least 0.3 g per serving. In another embodiment, the amount is at least 0.4 g per serving. In another embodiment, the amount is at least 0.5 g per serving. In another embodiment, the amount is at least 0.6 g per serving. In another embodiment, the amount is at least 0.8 g per serving. Each amount represents a separate embodiment of the present invention.

In another embodiment of methods of the present invention, the composition is administered 2 times daily. In another embodiment, the composition is administered at least 2 times daily. In another embodiment, the composition is administered 3 times daily. In another embodiment, the composition is administered at least 3 times daily. In another embodiment, the composition is administered 4 times daily. In another embodiment, the composition is administered at least 4 times daily. In another embodiment, the composition is administered 5 times daily. In another embodiment, the composition is administered at least 5 times daily. In another embodiment, the composition is administered more than 5 times daily. In another embodiment, the composition is administered 2-3 times daily. In another embodiment, the composition is administered 2-4 times daily. In another embodiment, the composition is administez'ed 2-5 times daily. In another embodiment, the composition is administered 2-6 times daily. In another embodiment, the composition is administered 3-4 times daily. In another embodiment, the composition is administered 3-5 times daily. In another embodiment, the composition is administered at least 3-6 times daily. Each possibility represents a separate embodiment of the present invention.

In another embodiment of methods of the present invention, the composition is administered at least about 20 minutes before mealtime. In another embodiment, the composition is administered at least about 30 minutes before mealtime. In another embodiment, the composition is administered at least about 40 minutes before mealtime. In another embodiment, the composition is administered at least about 50 minutes before mealtime. In another embodiment, the composition is administered at least about 60 minutes before mealtime. In another embodiment, the composition is administered at least about 70 minutes before mealtime. In another embodiment, the composition is administered at least about 80 minutes before mealtime. In another embodiment, the composition is administered at least about 90 minutes before mealtime. In another embodiment, the composition is administered at least about 100 minutes before mealtime. In another embodiment, "mealtime" refers to dinnertime. In another embodiment, "mealtime" refers to lunchtime. In another embodiment, "mealtime" refers to breakfast time. In another embodiment, "mealtime" refers to the time of any other meal.

In another embodiment, the composition is administered at least about 3 hours after mealtime. In another embodiment, the composition is administered at least about 2 1/2 hours after mealtime. In another embodiment, the composition is administered at least about 2 hours after mealtime. In another embodiment, the composition is administered at least about 1 1/2 hours after mealtime. In another embodiment, the composition is administered at least about 1 hour after mealtime. Each possibility represents a separate embodiment of the present invention.

In another embodiment, methods of the present invention comprise administering a carbohydrate-rich composition that contains little or no branched chain amino acids (BCAA). In another embodiment, the composition contains little or no large neutral amino acids (LNAA). LNAA reduce, in another embodiment, synthesis of serotonin by competing with tryptophan for the same transporter system in the brain. BCAA reduce, in another embodiment, synthesis of serotonin by competing with tryptophan for the same transporter system in the brain. Thus, LNAA and BCAA are expected to reduce the induction of serotonin synthesis by compositions of the present invention.

In another embodiment of methods of the present invention, the composition utilized increases serotonin synthesis in the brain, thereby treating one of the above diseases, disorders, or symptoms. In another embodiment, the composition utilized is effective to raise the serotonin level in the brain of the subject. In another embodiment, the composition utilized is capable of raising the serotonin level in the brain of the subject. In another embodiment, the composition utilized raises the serotonin level in the brain of the subject. Each possibility represents a separate embodiment of the present invention.

In another embodiment of methods of the present invention, the composition utilized lowers plasma levels of LNAA other than tryptophan in the subject, thereby treating one of the above diseases, disorders, or symptoms. In another embodiment, the composition utilized is effective to lower plasma levels of LNAA other than tryptophan in the subject. In another embodiment, the composition utilized is capable of lowering plasma levels of LNAA other than tryptophan in the subject. Each possibility represents a separate embodiment of the present invention.

In another embodiment of methods of the present invention, the composition utilized raises the plasma tryptophan ratio in the subject, thereby treating one of the above diseases, disorders, or symptoms. In another embodiment, the composition utilized is effective to raise the plasma tryptophan ratio in the subject. In another embodiment, the composition utilized is capable of raising the plasma tryptophan ratio in the subject. Each possibility represents a separate embodiment of the present invention.

"Raise the serotonin level" refers, in another embodiment, to a measurable increase in the serotonin level. In another embodiment, the term refers to an increase of about 20%. In another embodiment, the term refers to an increase of about 30%. In another embodiment, the term refers to an increase of about 40%. In another embodiment, the term refers to an increase of about 50%. In another embodiment, the term refers to an increase of about 60%. In another embodiment, the term refers to an increase of about 70%. In another embodiment, the term refers to an increase of about 80%. In another embodiment, the term refers to an increase of about 90%. In another embodiment, the term refers to an increase of about 100%. In another embodiment, the term refers to an increase of about 150%. In another embodiment, the term refers to an increase of about 2-fold. In another embodiment, the term refers to an increase of about 3-fold. In another embodiment, the term refers to an increase of about 4-fold. In another embodiment, the term refers to an increase of about 5-fold. In another embodiment, the term refers to an increase of about 8-fold. In another embodiment, the term refers to an increase of about 10-fold. In another embodiment, the term refers to an increase of more than about 10-fold. Each possibility represents a separate embodiment of the present invention.

Methods for measuring serotonin levels are well known in the art. In another embodiment, serotonin levels are measured indirectly by measuring plasma levels of LNAA other than tryptophan. In another embodiment, serotonin levels are measured by measuring plasma levels of leucine + isoleucine + valine + tyrosine + phenylalanine. In another embodiment, serotonin levels are measured by measuring plasma tryptophan ratio. In another embodiment, serotonin levels are measured by high-performance liquid chromatography (HPLC) of brain homogenates. In another embodiment, serotonin levels in platelets, whole blood, platelet-depleted blood, are used as a surrogate for brain serotonin levels. In another embodiment, HPLC with fluorometric detection is used (Anderson GM et al, (1981) Clin Chem 27: 775- 776. In another embodiment, serotonin levels are measured using any other method of measuring serotonin levels known in the art. Each possibility represents a separate embodiment of the present invention.

In another embodiment, a method of the present invention comprises administration of a carbohydrate- rich composition as an adjunct to anti-depressive therapy. In another embodiment, a carbohydrate-rich composition is combined with an antidepressant. In another embodiment, a carbohydrate-rich composition is combined with any other mood-altering drug known in the art. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the present invention provides a composition, comprising of least about 20 grams per serving, the composition further comprising a tryptophan-rich protein, wherein the total amount in the composition of additional protein other than the tryptophan-rich protein is zero or is less than about 10% of the carbohydrate content. In other embodiments, the composition can have any of the characteristics of compositions disclosed or enumerated for use in methods of the present invention. Each possibility represents a separate embodiment of the present invention.

In another embodiment, a method of the present invention comprises administering a carbohydrate-rich composition of the present invention, wherein the fat content of the composition is zero or is less than about 10% of the carbohydrate content. In another embodiment, the fat content: carbohydrate content ratio is less than about 9 percent. In another embodiment, the ratio is less than about 8 percent. In another embodiment, the ratio is less than about 7 percent. In another embodiment, the ratio is less than about 6 percent. In another embodiment, the ratio is less than about 5 percent. In another embodiment, the ratio is less than about 4 percent. In another embodiment, the ratio is less than about 3 percent. In another embodiment, the ratio is less than about 2 percent. In another embodiment, the ratio is less than about 1 percent. Each ratio represents a separate embodiment of the present invention.

In another embodiment, the composition contains less than about 4 g of fat per serving. In another embodiment, the amount is less than about 3 g of fat per serving. In another embodiment, the amount is less than about 2 g per serving. In another embodiment, the amount is less than about 1.5 g per serving. In another embodiment, the amount is less than about 1 g per serving. In another embodiment, the amount is less than about 0.5 g of fat per serving. Each. amount represents a separate embodiment of the present invention.

In another embodiment of methods of the present invention, the composition is administered over a minimum length of time of about 12 days. In another embodiment, the composition is administered over a minimum length of time of about 1 day. In another embodiment, the composition is administered over a minimum length of time of about 2 days. In another embodiment, the composition is administered over a minimum length of time of about 3 day s . In another embodiment, the composition is administered over a minimum length of time of about 4-5 days. In another embodiment, the composition is administered over a minimum length of time of about 1 week. In another embodiment, the composition is administered over a minimum length of time of about 10 days. In another embodiment, the composition is administered over a minimum length of time of about 2 weeks. In another embodiment, the composition is administered over a minimum length of time of about 3 weeks. In another embodiment, the composition is administered over a minimum length of time of about 1 month. In another embodiment, the composition is administered over a minimum length of time of about 2 months. In another embodiment, the composition is administered throughout the period of reduced daylight. In another embodiment, the composition is administered throughout the year. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the present invention provides a method of treating a mood symptom of a depressive disorder in a subject, comprising administering to the subject a composition of the present invention, thereby treating a mood symptom of a depressive disorder in a subject. In another embodiment, the mood symptom is lack of energy. In another embodiment, the mood symptom is hypersomnia. In another embodiment, the mood symptom is overeating. In another embodiment, the mood symptom is carbohydrate craving. In another embodiment, the mood symptom is increased appetite. In another embodiment, the mood symptom is mood fluctuations. In another embodiment, the mood symptom is depersonalization or derealization. In another embodiment, the mood symptom is insomnia. In another embodiment, the mood symptom is obsessive thinking. In another embodiment, the mood symptom is anxiety. In another embodiment, the mood symptom is decreased work activity or work productivity. In another embodiment, the mood symptom is fatigue. In another embodiment, the mood symptom is any other symptom associated with a depressive disorder. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the present invention provides a composition for treating winter blues or SAD, the composition having a high carbohydrate content, as defined in the present invention, wherein the composition either contains no protein or has a protein content of less than 10% of its carbohydrate content. In another embodiment, the composition is effective to raise brain serotonin levels. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the present invention provides a composition for treating winter blues or SAD, the composition having a high carbohydrate content, as defined in the present invention, the composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein the amount in the composition of additional protein other than the tryptophan or a tryptophan-rich protein or peptide is zero or is less than about 10% of the carbohydrate content. In another embodiment, the composition is effective to raise brain serotonin levels. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the present invention provides a composition for treating a depressive disorder, the composition having a high carbohydrate content, as defined in the present invention, wherein the protein content of the composition is zero or is less than about 10% of the carbohydrate content. In another embodiment, the composition is effective to raise brain serotonin levels. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the present invention provides a composition for treating a depressive disorder, the composition having a high carbohydrate content, as defined in the present invention, the composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein the amount in the composition of additional protein other than the tryptophan or a tryptophan-rich protein or peptide is zero or is less than about 10% of the carbohydrate content. In another embodiment, the composition is effective to raise brain serotonin levels . Each possibility represents a separate embodiment of the present invention.

In another embodiment, the present invention provides a composition for treating weight gain or carbohydrate craving associated with a depressive disorder, the composition having a high carbohydrate content, as defined in the present invention, wherein the protein content of the composition is zero or is less than about 10% of the carbohydrate content. In another embodiment, the composition is effective to raise brain serotonin levels. Each possibility represents a separate embodiment of the present invention.

In another embodiment, the present invention provides a composition for treating weight gain or carbohydrate craving associated with a depressive disorder, the composition having a high carbohydrate content, as defined in the present invention, the composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein the amount in the composition of additional protein other than the tryptophan or a tryptophan-rich protein or peptide is zero or is less than about 10% of the carbohydrate content. In another embodiment, the composition is effective to raise brain serotonin levels. Each possibility represents a separate embodiment of the present invention.

In another embodiment, methods and compositions of the present invention increase serotonin levels for approximately the amount of time they are being digested. In another embodiment, methods and compositions of the present invention increase serotonin levels for approximately the amount of time they serve as a source for infusion of carbohydrates into the bloodstream.

In another embodiment, the present invention provides a method of reducing an incidence of winter blues, comprising administering a composition of the present invention. In another embodiment, the present invention provides a method of ameliorating winter blues, comprising administering a composition of the present invention.

In another embodiment, the present invention provides a method of reducing an incidence of SAD, comprising administering a composition of the present invention. In another embodiment, the present invention provides a method of ameliorating SAD, comprising administering a composition of the present invention.

In another embodiment, the present invention provides a method of reducing an incidence of a depressive disorder, comprising administering a composition of the present invention. In another embodiment, the present invention provides a method of ameliorating a depressive disorder, comprising administering a composition of the present invention. In another embodiment, the present invention provides a method of reducing an incidence of carbohydrate craving or weight gain associated with a depressive disorder, comprising administering a composition of the present invention. In another embodiment, the present invention provides a method of ameliorating carbohydrate craving or weight gain associated with a depressive disorder, comprising administering a composition of the present invention.

In another embodiment, a treatment protocol of the present invention is therapeutic. In another embodiment, the protocol is prophylactic. Each possibility represents a separate embodiment of the present invention.

Reduction of the incidence of a disease by a treatment is assessed, in another embodiment, by assessing the presence of the disease, using any of the methods of the present invention, among 2 populations, of which 1 is receiving the treatment and the other is not. Amelioration of symptoms of a disease by a treatment is assessed, in another embodiment, by assessing the severity of symptoms of the disease, using any of the methods of the present invention, among the above two populations. In another embodiment, one of the above studies is performed in a placebo-controlled design (see Examples). In another embodiment, reduction of the incidence of a disease or amelioration of symptoms of a disease is assessed using any other method known in the art for assessing the presence or severity of the disease.

Each possibility represents a separate embodiment of the present invention.

In another embodiment, the present invention provides a kit comprising a reagent utilized in performing a method of the present invention.

In another embodiment, methods of the present invention comprise administering a carbohydrate, tryptophan, and/or tryptophan-rich protein or peptide and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, or a combination thereof.

In another embodiment, the carbohydrate-rich composition of methods of the present invention is a beverage. In another embodiment, the beverage has a volume of about 10 ounces or less. In another embodiment, the beverage has a volume of about 9 ounces or less. In another embodiment, the beverage has a volume of about 8 ounces or less. In another embodiment, the beverage has a volume of about 7 ounces or less. In another embodiment, the beverage has a volume of about 6 ounces or less. In another embodiment, the beverage has a volume of about 5 ounces or less. In another embodiment, the beverage has a volume of about 11 ounces or less. In another embodiment, the beverage has a volume of about 12 ounces or less.

In another embodiment, the beverage of methods of the present invention has a volume of less than about 1 ounce per 2 grams of carbohydrate. In another embodiment, the beverage has a volume of less than about 1 ounce per 1.5 grams of carbohydrate. In another embodiment, the beverage has a volume of less than about 1 ounce per 1.6 grams of carbohydrate. In another embodiment, the beverage has a volume of less than about 1 ounce per 1.8 grams of carbohydrate. In another embodiment, the beverage has a volume of less than about 1 ounce per 2.2 grams of carbohydrate. In another embodiment, the beverage has a volume of less than about 1 ounce per 2.5 grams of carbohydrate. In another embodiment, the beverage has a volume of less than about 1 ounce per 3 grams of carbohydrate. In another embodiment, the beverage has a volume of less than about 1 ounce per 3.5 grams of carbohydrate. In another embodiment, the beverage has a volume of less than about 1 ounce per 4 grams of carbohydrate. In another embodiment, the beverage has a volume of less than about 1 ounce per 5 grams of carbohydrate.

Each volume represents a separate embodiment of the present invention.

In another embodiment, the carbohydrate-rich composition of methods of the present invention is an instant beverage. In another embodiment, the volume of the liquid component of the instant beverage is about 10 ounces or less. In another embodiment, the liquid component is about 9 ounces or less. In another embodiment, the liquid component is about 8 ounces or less. In another embodiment, the liquid component is about 7 ounces or less. In another embodiment, the liquid component is about 6 ounces or less. In another embodiment, the liquid component is about 5 ounces or less. In another embodiment, the liquid component is about 11 ounces or less. In another embodiment, the liquid component is about 12 ounces or less.

In another embodiment, the volume of the liquid component is less than about 1 ounce per 2 grams of carbohydrate. In another embodiment, the liquid component is less than about 1 ounce per 1.5 grams of carbohydrate. In another embodiment, the liquid component is less than about 1 ounce per 1.6 grams of carbohydrate. In another embodiment, the liquid component is less than about 1 ounce per 1.8 grams of carbohydrate. In another embodiment, the liquid component is less than about 1 ounce per 2.2 grams of carbohydrate. In another embodiment, the liquid component is less than about 1 ounce per 2.5 grams of carbohydrate. In another embodiment, the liquid component is less than about 1 ounce per 3 grams of carbohydrate. In another embodiment, the liquid component is less than about 1 ounce per 3.5 grams of carbohydrate. In another embodiment, the liquid component is less than about 1 ounce per 4 grams of carbohydrate. In another embodiment, the liquid component is less than about 1 ounce per 5 grams of carbohydrate.

Each beverage represents a separate embodiment of the present invention.

In another embodiment, the compositions of methods of the present invention are administered as a nutritional preparation. In one embodiment, the nutritional preparation is a functional food. In another embodiment, the nutritional preparation is a drink. In another embodiment, the nutritional preparation is a readily obtainable edible or drinkable substance that is supplemented with a composition of the present invention to provide a medical or pharmaceutical effect. In another embodiment, the present invention provides a composition of the present invention for use as a functional food ingredient. Functional foods and drinks are, in one embodiment, selected from the group consisting of diary products, such as yogurt and yogurt ice cream, juice, such as orange juice or tomato juice, ready made liquids for drinking, a spreadable product such as e.g. a margarine or a vegetable or plant extracted oil, a cereal product, such as a traditional breakfast cereal product, nutritional bars, biscuits, bread, soups, e.g. tomato soup, a meat product, such as a hamburger, a meat substitute product, and a vegetable product. In other embodiments, a nutritional preparation is in the form of a ready made liquid or in a powder form or in the form of a troche, a solid composition such as a nutritional bar, a fruit bar, a cookie, a cake, a bread or a muffin. In other embodiments, a nutritional preparation is in the form of a cracker, a pudding, or a gel (e.g. an energy gels). Each possibility represents a separate embodiment of the present invention.

In another embodiment, the route of delivery of compositions utilized in methods of the present invention is compatible with insulin release. In one embodiment, the route of delivery that is compatible with insulin release is via the mouth. In another embodiment, the route of delivery that is compatible with insulin release is via the stomach. In another embodiment, the route of delivery that is compatible with insulin release is via the small intestine.

In other embodiments, a flavor, a coloring agent, a spice, nuts or a mixture thereof is incorporated into the product. Flavorings can be, in other embodiments, e.g. flavored extracts, volatile oils, chocolate flavorings (e.g., non-caffeinated cocoa or chocolate, or chocolate substitutes, such as carob), peanut butter flavoring, cookie crumbs, crisp rice, vanilla or any commercially available flavoring. Flavorings are, in another embodiment, protected with mixed tocopherols. Examples of useful flavorings include but are not limited to pure anise extract, imitation banana extract, imitation cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure peppermint extract, imitation pineapple extract, imitation rum extract, imitation strawberry extract, or pure vanilla extract; or volatile oils, such as balm oil, bay oil, bergamot oil, cedarwood oil, cherry oil, walnut oil, cinnamon oil, clove oil, or peppermint oil; peanut butter, chocolate flavoring, vanilla cookie crumb, butterscotch and toffee. In another embodiment, the composition contains berry or other fruit flavors. In another embodiment, the composition is further coated, for example with a yogurt coating, if it is produced as a bar.

In another embodiment, the composition comprises an artificial sweetener. In other embodiments, the artificial sweetener is a saccharide, cyclamate, aspartamine, aspartame, acesulfame K, sorbitol, or a combination thereof.

In another embodiment, the composition comprises a preservative. In other embodiments, the preservative is potassium sorbate, sodium sorbate, potassium benzoate, sodium benzoate or calcium disodium EDTA.

In another embodiment, the composition is in the form of an extruded bar. In another embodiment, the composition is in the form of a powder. In another embodiment, the composition is in the form of a food or beverage.

In other embodiments, the composition further comprises a fiber source, a stabilizer, an emulsifier, a flavor source, or a combination thereof. In other embodiments, the fiber source is high methoxy pectin, low methoxy-pectin, melanin, lignin, cellulose, hemicellulose, leutein, or a combination thereof.

In another embodiment, one or more components of the composition (e.g. one or more of the carbohydrates, or a carbohydrate and tryptophan-rich protein) are mixed, blended, or combined together. In another embodiment, they are administered together without prior mixing. In another embodiment, they are administered separately.

In other embodiments, the stabilizer comprises lactose, microcystalline cellulose, hydroxymethyl cellulose, starch, waxy maize, xanthan, carageenan, pectin, guar, gum arabic, Konjac, gum tragacanth, propylene glycol alginate, or a combination thereof.

In other embodiments, the emulsifier is lecithin, sodium stearoyl lactylate (ssl), sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, mono-and di-glycerides, polyoxyethylene fatty acid esters, polyoxyethylene alcohols, egg yolk, enzyme-modified egg yolk, or a combination thereof.

In another embodiment, a method of the present invention comprises administration of a high- carbohydrate composition in a pharmaceutical composition. The pharmaceutical compositions containing the active ingredient(s) can be, in another embodiment, administered to a subject by any method known to a person skilled in the art, such as parenterally, transmucosally, transdermally, intramuscularly, intravenously, intra-dermally, subcutaneously, intra-peritonealy, intra-ventricularly, intra-cranially, or intra-vaginally.

In another embodiment, the term "isomer" includes, but, in another embodiment, is not limited to, optical isomers and analogs, structural isomers and analogs, conformational isomers and analogs, and the like.

The invention includes "pharmaceutically acceptable salts" of amino-substituted compounds with organic and inorganic acids, for example, citric acid and hydrochloric acid. The invention also includes N-oxides of the amino substituents of the compounds described herein. Pharmaceutically acceptable salts can also be prepared from the phenolic compounds by treatment with inorganic bases, for example, sodium hydroxide. Also, esters of the phenolic compounds can be made with aliphatic and aromatic carboxylic acids, for example, acetic acid and benzoic acid esters.

This invention further includes, in another embodiment, derivatives of a carbohydrate, tryptophan, and/or tryptophan-rich protein or peptide. The term "derivatives" includes but is not limited to ether derivatives, acid derivatives, amide derivatives, ester derivatives and the like. In addition, this invention further includes hydrates of the active compounds. The term "hydrate" includes but is not limited to hemihydrate, monohydrate, dihydrate, trihydrate and the like.

This invention further includes metabolites of a carbohydrate, tryptophan, and/or tryptophan-rich protein or peptide. The term "metabolite" means any substance produced from another substance by metabolism or a metabolic process.

Pharmaceutical Compositions and Methods of Administration

The pharmaceutical compositions containing a carbohydrate, tryptophan, and/or tryptophan-rich protein or peptide can be, in another embodiment, administered to a subject by any method known to a person skilled in the art, such as parenterally, transmucosally, transdermally, intramuscularly, intravenously, intra-dermally, subcutaneously, intra-peritonealy, intra-ventricularly, intra-cranially, or intra-vaginally.

In another embodiment of methods and compositions of the present invention, the pharmaceutical compositions are administered orally, and are thus formulated in a form suitable for oral administration, i.e. as a solid or a liquid preparation. Suitable solid oral formulations include tablets, capsules, pills, granules, pellets and the like. Suitable liquid oral formulations include solutions, suspensions, dispersions, emulsions, oils and the like. In another embodiment of the present invention, the active ingredient is formulated in a capsule. In accordance with this embodiment, the compositions of the present invention comprise, in addition to the active compound and the inert carrier or diluent, a hard gelating capsule.

In another embodiment, the pharmaceutical compositions are administered by intravenous, intra-arterial, or intra-muscular injection of a liquid preparation. Suitable liquid formulations include solutions, suspensions, dispersions, emulsions, oils and the like. In another embodiment, the pharmaceutical compositions are administered intravenously and are thus formulated in a form suitable for intravenous administration. In another embodiment, the pharmaceutical compositions are administered intra-arterially and are thus formulated in a form suitable for intra-arterial administration. In another embodiment, the pharmaceutical compositions are administered intra-muscularly and are thus formulated in a form suitable for intra-muscular administration.

In another embodiment, the pharmaceutical compositions are administered topically to body surfaces and are thus formulated in a form suitable for topical administration. Suitable topical formulations include gels, ointments, creams, lotions, drops and the like.

In another embodiment, the pharmaceutical composition is administered as a suppository, for example a rectal suppository or a urethral suppository. In another embodiment, the pharmaceutical composition is administered by subcutaneous implantation of a pellet.

In other embodiments, carriers or diluents used in methods of the present invention include, but are not limited to, a gum, a starch (e.g. corn starch, pregeletanized starch), a sugar (e.g., lactose, mannitol, sucrose, dextrose), a cellulosic material (e.g. microcrystalline cellulose), an acrylate (e.g. poly methylacry late), calcium carbonate, magnesium oxide, talc, or mixtures thereof.

In another embodiment, parenteral vehicles (for subcutaneous, intravenous, intraarterial, or intramuscular injection) include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated

Ringer's and fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers such as those based on Ringer's dextrose, and the like. Examples are sterile liquids such as water and oils, with or without the addition of a surfactant and other pharmaceutically acceptable adjuvants. In general, water, saline, aqueous dextrose and related sugar solutions, and glycols such as propylene glycols or polyethylene glycol are preferred liquid carriers, particularly for injectable solutions. Examples of oils are those of animal, vegetable, or synthetic origin, for example, peanut oil, soybean oil, olive oil, sunflower oil, fish-liver oil, another marine oil, or a lipid from milk or eggs.

The preparation of pharmaceutical compositions that contain an active component, for example by mixing, granulating, or tablet-forming processes, is well understood in the art. The active therapeutic ingredient is often mixed with excipients that are pharmaceutically acceptable and compatible with the active ingredient. For oral administration, the active agents or their physiologically tolerated derivatives such as salts, esters, N-oxides, and the like are mixed with additives customary for this purpose, such as vehicles, stabilizers, or inert diluents, and converted by customary methods into suitable forms for administration, such as tablets, coated tablets, hard or soft gelatin capsules, aqueous, alcoholic or oily solutions. For parenteral administration, the active agents or their physiologically tolerated derivatives such as salts, esters, N-oxides, and the like are converted into a solution, suspension, or emulsion, if desired with the substances customary and suitable for this purpose, for example, solubilizers or other substances.

An active component is, in another embodiment, formulated into the composition as neutralized pharmaceutically acceptable salt forms. Pharmaceutically acceptable salts include the acid addition salts

(formed with the free amino groups of the polypeptide or antibody molecule), which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, oxalic, tartaric, mandelic, and the like. Salts formed from the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethylamine, 2-ethylamino ethanol, histidine, procaine, and the like.

Each of the above additives, excipients, formulations and methods of administration represents a separate embodiment of the present invention.

EXPERIMENTAL DETAILS SECTION

EXAMPLE 1

CARBOHYDRATE-RICH BEVERAGES DECREASE SAD AND WINTER BLUES SYMPTOMS IN A STATISTICALLY SIGNIFICANT FASHION

MATERIALS AND EXPERIMENTAL METHODS Study design

25 subjects were enrolled in the study, which assessed whether twice-daily consumption of a carbohydrate (CHO)-rich beverage, before lunch and dinner, affected mood and appetite symptoms of mild SAD more than a control beverage containing a mixture of carbohydrates and protein (CHO/PRO). A l -week run-in phase, used to familiarize the subjects with the intervention schedule, preceded the first period of the study. Subjects were then assigned to either the active (CHO) or control (CHO/PRO) treatment arms for the first period of the next phase of the study, referred to below as the "intervention phase," The intervention phase was conducted in a double-blind, placebo-controlled, crossover fashion. Each period of this phase of the study was 12 days in duration, with a 2 day washout period between each period of the intervention phase. Evaluations were performed on "test days," which occurred after 6 and 12 days of each period of the intervention phase. In the second period of the intervention phase, each subject was administered the test beverage that he/she had not received during the first period (i.e. CHO for those that had received CHO/PRO, and CHO/PRO for those that had received CHO).

Subjects not wishing to continue with the study were given the option to withdraw at any time.

Inclusion criteria

Adult men and women between the ages of 18-70, in general good health, with a Body Mass Index (BMI) of no more than 35 (weighed in a hospital gown) and who met the criteria for mild SAD were eligible to participate in the study. Specifically, subjects were required to meet the criteria for SAD based on the SCID and to score between 10-25 on the Hamilton D-17.

The following classes of applicants were excluded from the study: 1). applicants with diabetes or other medical disorders (e.g. hypoglycemia) that would preclude consuming a high carbohydrate drink, or a history of milk allergies. 2). applicants currently receiving treatment for SAD (i.e. with medication or light therapy). 3). applicants with a history of eating disorders, exercise bulimia, alcoholism, or recreational drug use. 4). applicants who had stopped smoking within the previous 6 months. 5). applicants taking medications that may have an effect on their mood and appetite, including antidepressants, mood stabilizers, antipsychotic drugs or steroids. 6). applicants anticipating difficulty attending testing sessions or eating three meals a day at relatively traditional times, or whose dietary habits severely limited their ability or desire to make typical food choices. 7). applicants with plans to travel to the southern latitudes during the study.

Screening Visit Prospective subjects read and signed a consent form (discussed with a research staff member), and subjects' vital signs ((blood pressure [BP] and heart rate [HR]) were recorded. Subjects men underwent a medical history interview, a physical examination, and a psychiatric screening by a psychiatrist for the presence of mild SAD.

The mood module of the Structured Clinical Interview for DSM-IV ("SCID"; First MB et al. Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition (SCID-I/P, Version 2.0), Biometrics Research Department, New York State Psychiatric Institute, New York, 1995), modified to assess symptoms over the past 2 weeks, was used for the psychiatric screening. Specifically, the section that covers the seasonal component to the depressive disorder was used. The SCID proceeds by modules to the different Axis I disorders, and each is based on the individual criteria from DSM-IV. Questions were asked exactly as written. Answers were rated on a scale of 1-3 (1= doubtful, 2= probable, 3= definite), and with the diagnostic determination based on the number of positive answers.

Run-in phase

Subjects were instructed in the guidelines for consuming the beverage prior to beginning the run-in phase. AU subjects were administered the CHO/PRO drink during the run-in phase; otherwise, subjects followed their own meal and snack plan.

Intervention phase

On day 7 of the run-in phase, vital signs and weights of the subjects were measured, and subjects were given their test beverages, low-carbohydrate snacks, and test-day bagged lunch for the first period of the intervention phase. Test beverages, snacks, and bagged lunches were all prepared according to exact criteria in the study's metabolic kitchen. Subjects were instructed as to administration of the test beverages and provided a contact number in case questions arose. Subjects were instructed to eat only the snacks provided them on all days (except during testing times on the test days, when no snacks were allowed). Subjects were not given a specific food plan, with the exception of the test days (day 6 and day 12). On test days, after consuming their bagged lunch, vital signs of subjects were recorded, and baseline evaluations of mood and appetite were conducted by a research staff member. Subsequently, the test beverage was consumed, then 2 more evaluations were performed at 1 and 2 hours following beverage consumption.

The protocol and evaluations for the second period of the intervention phase were the same as for the first period. The HAM-D 28-item instrument was utilized for evaluations during all study visits. The HAM-D 28- item (Hamilton 28 item Rating Scale for Depression; Hamilton M. A rating scale for depression, J Neurol Neurosurg Psychiatry 23: 56-62 1960; Hamilton M. Development of a rating scale for primary depressive illness. Brit J Social Clin Psychol 6(4): 278-96, 1967; Williams JB. A structured interview guide for the Hamilton Depression Rating Scale. Arch Gen Psychiatry 45: 742-747, 1988) instrument was completed by the clinician, based on his/her assessment of the patient's depressive symptoms. The HAM-D is usually used to quantify the degree of depression in patients with a diagnosis of Major Depressive Disorder (MDD). Questions focus on neuro-vegetative and other depressive symptoms experienced over the past 7 days.

The Clinical Global Impressions - Severity (CGI-S) and Improvement (CGI-I; Guy W (ed). ECDEU Assessment Manual for Psychopharmacology, revised. DHEW Pub. No. (ADM)76-338. National Institute of Mental Health, Rockville, MD, 1976) instruments were used to rate severity of the disorder and the global improvement since the beginning of the study. These two instruments were completed by the clinician based on assessment of the patient's clinical status, using both the history and scores on other instruments : The CGI-S was used to determine the current condition of the patient, while the CGI-I was used to determine the degree of improvement.

Subjects were contacted by the research staff prior to the test day and on test day in order to ensure adherence to protocol and to answer any questions or concerns.

Test day evaluations Subjects ate the prepared bag lunch between 12 and 12:30, then arrived at approximately 3:30 pm at the testing center, after which no food or beverages were consumed. Vital signs and weight were recorded, and baseline mood and appetite evaluations were performed, using self- and interviewer-administered tests. Subjects then consumed the test beverage, and underwent additional mood and appetite evaluations at 1 hour and 2 hours thereafter. Subject were required to return any unused snack to the testing center, and received the next 6 days of test beverage along with new snacks.

Test beverages

The CHO beverage contained 40 grams (g) of carbohydrate, specifically potato starch, maltodextrin, dextrose and dextrin. The CHO/PRO beverage contained 25 g carbohydrate and 15 g milk-derived casein. Beverages were administered in the form of an orange flavored powder that was mixed with 8 oz. of water. Biostatistical Analysis

HAM-D data were computed in a blinded fashion for the 16 subjects who completed the entire study. Two-sample t- tests were used to assess the significance of the changes in the severity of SAD overall and individual SAD symptoms between the different treatment arms during a given period of the study (n=8 for each group). Individual two-sided paired t-tests were used to assess the significance of changes in the severity of SAD overall between periods within each subject (n=16).

RESULTS

The mood of all subjects improved during the first 3 weeks of the study, with significant change occurring during the 3-week interval between the screening HAM-D assessment and the first post- treatment assessment. Additional improvement occurred prior to the second post-treatment assessment in week 4. A smaller, but significant improvement occurred between weeks 4 and 6. During each period, the improvement in SAD was greater in the CHO group than in the CHO/PRO group. The difference between the treatment arms attained statistical significance both between the screening HAM-D assessment and the first post-treatment assessment and between the screening HAM-D assessment and the second post-treatment assessment, as depicted in the tables below.

Table 1. Overall change in the first 17 of the HAM-D components during the first three weeks of the study, assessed by two-sample t-test. Negative values indicate reduced severity of symptoms at the later time point.

Table 2. Overall change in all HAM-D components during the first 4 weeks of the study.

Table 3. Overall change in all HAM-D components between week 4 and week 6 of the study.

In addition, the significance of changes in the severity of SAD overall between the treatment arms was assessed between periods of the intervention phase within each subject, using individual two-sided paired t-tests. As with the previous analysis, the improvement was significantly greater in the CHO group than in the CHO/PRO group (Table 4).

Table 4. Overall change in all HAM-D components between week 4 and week 6 of the study.

Thus, administration of a high-carbohydrate, low protein beverage improved SAD and winter blues to a statistically significantly degree relative to a control beverage.

EXAMPLE 2

A CARBOHYDRATE-RICH BEVERAGE DECREASES INDIVIDUAL SAD SYMPTOMS

IN A STATISTICALLY SIGNIFICANT FASHION

In addition, the CHO beverage improved 19 of 27 of the individual components of the HAM-D (weight loss and insight, the components for which all subjects scored zero, were omitted from the analysis) more than the CHO/PRO beverage during the first 3 weeks of the study, including all the components of the HAM-D most associated with SAD and winter blues ("work activity," or ability to work effectively; oversleeping; weight gain; and fatigue). For 3 symptoms, the difference between the treatment arms attained statistical significance. (Table 4, data ranked by decreasing statistical significance). The symptom exhibiting the greatest statistical significance, "work activity," or ability to work effectively, was 1 of the most significant symptoms associated with SAD and winter blues. These findings demonstrate that high-carbohydrate, low-protein beverages have utility in treating not only overall SAD and winter blues, but also individual symptoms of these disorders.

Table 4. Data for individual symptoms during the first three weeks of the study.

Claims

WHAT IS CLAIMED IS;

1. A method of treating winter blues or a seasonal affective disorder in a subject, comprising administering to said subject a composition having a carbohydrate content of least 20 grams per serving, wherein said composition either contains no protein or has a protein content of less than

10% of said carbohydrate content, thereby treating winter blues or a seasonal affective disorder in a subject.

2. The method of claim 1, wherein said composition contains at least 40 grams of carbohydrate per serving.

3. The method of claim 1 , wherein said composition comprises a starch, a maltodextrin, a dextrose, or a dextrin.

4. The method of claim 1, wherein said composition comprises two or more carbohydrate compounds.

5. The method of claim 1, wherein said composition is capable of raising a serotonin level in the brain of said subject.

6. The method of claim 1, wherein said administering is performed at least two times daily.

7. The method of claim 1, wherein said administering is performed at least 30-90 minutes before mealtime or at least three hours after mealtime.

8. A method of treating a depressive disorder in a subject, comprising administering to said subject a composition having a carbohydrate content of least 20 grams per serving, wherein said composition either contains no protein or has a protein content of less than 10% of said carbohydrate content, thereby treating a depressive disorder in a subject.

9. The method of claim 8, wherein said composition contains at least 40 grams of carbohydrate per serving.

10. The method of claim 8, wherein said composition comprises a starch, a maltodextrin, a dextrose, or a dextrin.

11. The method of claim 8, wherein said composition comprises two or more carbohydrate compounds.

12. The method of claim 8, wherein said composition is capable of raising a serotonin level in the brain of said subject.

13. The method of claim 8, wherein said administering is performed at least two times daily.

14. The method of claim 8, wherein said administering" is performed at least 30-90 minutes before mealtime or at least three hours after mealtime.

15. The method of claim 8, wherein said depressive disorder is a major depressive disorder, bipolar depression, dysthymia, minor depression, subsyndromal depression, subsyndromal SAD, anxiety, or fatigue.

16. A method of treating a carbohydrate craving or weight gain associated with a seasonal affective disorder in a subject, comprising administering to said subject a composition having a carbohydrate content of least 20 grams per serving, wherein said composition either contains no protein or has a protein content of less than 10% of said carbohydrate content, thereby treating a carbohydrate craving or weight gain associated with a seasonal affective disorder in a subject.

17. The method of claim 16, wherein said composition contains at least 40 grams of carbohydrate per serving.

18. The method of claim 16, wherein said composition comprises a starch, a maltodextrin, a dextrose, or a dextrin.

19. The method of claim 16, wherein said composition comprises two or more carbohydrate compounds.

20. The method of claim 16, wherein said composition is capable of raising a serotonin level in the brain of said subject.

21. The method of claim 16, wherein said administering is performed at least two times daily.

22. The method of claim 16, wherein said administering is performed at least 30-90 minutes before mealtime or at least three hours after mealtime.

23. A method of treating winter blues or a seasonal affective disorder in a subject, comprising administering to said subject a composition having a carbohydrate content of least 20 grams per serving, said composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein said composition either (a) contains no additional protein other than said tryptophan or tryptophan-rich protein or (b) contains an amount of said additional protein that is less than 10% of said carbohydrate content, thereby treating winter blues or a seasonal affective disorder in a subject.

24. The method of claim 23, wherein said carbohydrate content is at least 40 grams of carbohydrate per serving.

25. The method of claim 23, wherein said composition comprises a starch, a maltodextrin, a dextrose, or a dextrin.

26. The method of claim 23, wherein said composition comprises two or more carbohydrate compounds.

27. The method of claim 23, wherein said tryptophan-rich protein is an alpha-lactalbumin protein.

28. The method of claim 23, wherein said composition is capable of raising a serotonin level in the brain of said subject.

29. The method of claim 23, wherein said administering is performed at least two times daily.

30. The method of claim 23, wherein said administering is performed at least 30-90 minutes before mealtime or at least three hours after mealtime.

31. A method of treating a depressive disorder in a subject, comprising administering to said subject a composition having a carbohydrate content of least 20 grams per serving, said composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein said composition either (a) contains no additional protein other than said tryptophan or tryptophan-rich protein or (b) contains an amount of said additional protein that is less than 10% of said carbohydrate content, thereby treating a depressive disorder in a subject.

32. The method of claim 31 , wherein said composition contains at least 40 grams of carbohydrate per serving.

33. The method of claim 31 , wherein said composition comprises a starch, a maltodextrin, a dextrose, or a dextrin.

34. The method of claim 31, wherein said composition comprises two or more carbohydrate compounds.

35. The method of claim 31 , wherein said tryptophan-rich protein is an alpha-lactalbumin protein.

36. The method of claim 31, wherein said composition is capable of raising a serotonin level in the brain of said subject.

37. The method of claim 31, wherein said administering is performed at least two times daily.

38. The method of claim 31 , wherein said administering is performed at least 30-90 minutes before mealtime or at least three hours after mealtime.

39. The method of claim 31 , wherein said depressive disorder is a major depressive disorder, bipolar depression, dysthymia, minor depression, subsyndromal depression, subsyndromal SAD, anxiety, or fatigue.

40. A method of treating a carbohydrate craving or weight gain associated with a depressive disorder in a subject, comprising administering to said subject a composition having a carbohydrate content of least 20 grams per serving, said composition further comprising a tryptophan or a tryptophan-rich protein or peptide, wherein said composition either (a) contains no additional protein other than said tryptophan or tryptophan-rich protein or (b) contains an amount of said additional protein that is less than 10% of said carbohydrate content, thereby treating a carbohydrate craving or weight gain associated with a depressive disorder in a subject.

41. The method of claim 40, wherein said composition contains at least 40 grams of carbohydrate per serving.

42. The method of claim 40, wherein said composition comprises a starch, a maltodextrin, a dextrose, or a dextrin.

43. The method of claim 40, wherein said composition comprises two or more carbohydrate compounds.

44. The method of claim 40, wherein said tryptophan-rich protein is an alpha-lactalbumin protein.

45. The method of claim 40, wherein said composition is capable of raising a serotonin level in the brain of said subject.

46. The method of claim 40, wherein said administering is performed at least two times daily.

47. The method of claim 40, wherein said administering is performed at least 30-90 minutes before mealtime or at least three hours after mealtime.