WO1997020211A1 - Methods and kits for diagnosis and monitoring treatments of psychiatric disorders - Google Patents
Methods and kits for diagnosis and monitoring treatments of psychiatric disorders Download PDFInfo
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- WO1997020211A1 WO1997020211A1 PCT/IL1996/000166 IL9600166W WO9720211A1 WO 1997020211 A1 WO1997020211 A1 WO 1997020211A1 IL 9600166 W IL9600166 W IL 9600166W WO 9720211 A1 WO9720211 A1 WO 9720211A1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70571—Assays involving receptors, cell surface antigens or cell surface determinants for neuromediators, e.g. serotonin receptor, dopamine receptor
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/72—Assays involving receptors, cell surface antigens or cell surface determinants for hormones
- G01N2333/726—G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
Definitions
- the present invention relates to differential biochemical diagnosis of psychiatric disorders and, more particularly, to the use of the determination of the function and level of certain proteins in the accurate diagnosis of a variety of psychiatric disorders and for accurately following the progress of treatment of such disorders.
- DSM IIIR Diagnostic and Statistical Manual of Mental Disorders
- An important aspect of a biochemical assay for mental disorders such as major depression is that it makes it possible for the general practitioner, who treats about half of major depression patients, and for mental health professionals, to decide on the desirability of pharmacological antidepressant treatments.
- panic disorder Another disorder which is normally first treated by general practitioners, and which usually requires a series of physical examinations and a battery of expensive laboratory studies to exclude a physical disorder, is panic disorder.
- An established biochemical assay for this disorder will aid in the early treatment of these patients using presently available, and effective, pharmacological treatments.
- Various specific treatments are applied against mood disorders.
- Mood stabilizers like lithium and electroconvulsive treatment (ECT) are effective for the treatment of mania and depression, and for the prevention of both affective states.
- Antidepressant drugs are used in the treatment and prevention of depression. All these treatments do not exert their therapeutic effects immediately, but within three weeks or one month. About 30% of the patients do not respond to a certain treatment, but may respond to another kind of treatment. It is therefore of prime importance also to have a biochemical test that enables to biochemically ssess the responsiveness of a patient to a psychiatric treatment.
- the altered biochemical parameters determined in psychiatric patients by the diagnostic assay are indicators of the affective state of the illness, and are normalized following an efficient psychiatric treatment, then such an assay may also aid the practitioner to biochemically follow and gauge the effectiveness of these treatments.
- G-proteins The family of G-proteins currently includes 12-15 already known individual proteins. G-proteins are composed of three subunits: ⁇ , ⁇ , and ⁇ .
- the ⁇ - subunit contains the binding site for guanine nucleotides, and possesses GTPase activity.
- the ⁇ -subunit also contains the site for nicotinamide adenine nucleotide (NAD) - dependent ADP-ribosylation catalyzed by bacterial toxins.
- NAD nicotinamide adenine nucleotide
- the heterogeneity of the ⁇ -subunit serves to divide G-proteins into the major classes (Gs,, G,, G q ).
- Receptors for stimulatory hormones i.e., ⁇ -adrenergic receptors
- Gs the G-protein which activates adenylate cyclase
- inhibitory ligands e.g., M2-muscarinic receptors
- G C may be involved in coupling receptor activation to the breakdown of phosphatidylino-sitol -4,5-biphosphate by phospholipase C.
- guanine nucleotide binding assay is used as an established test for G-protein function.
- receptor-coupled G-proteins The function of receptor-coupled G-proteins was found to be differentially attenuated by lithium (Avissar et al., 1988), other antibipolar treatments, and antidepressant drugs (Avissar and Schreiber 1992a, b). Moreover, hyperactivity of ⁇ -adrenergic coupled and muscarinic-coupled G-proteins was detected in MNL of patients with mania (Schreiber et al., 1991), and an elevated level of ⁇ subunit of G s -protein (G ⁇ s ) was found in postmortem cerebral cortices of bipolar patients (Young et al., 1991).
- a method for diagnosing psychiatric disorders or gauging the effect of a treatment on a psychiatric patient comprising: (a) determining the function and /or the level of at least one receptor-coupled G-protein; (b) diagnosing the psychiatric disorder, or gauging the effect of the treatment upon the patient based on the determination in (a).
- the function of receptor-coupled G-protein is measured as agonist-induced increase in guanine nucleotide binding capacity in patient's mononuclear leukocytes (MNL).
- the level of receptor-coupled G-protein is quantified using antibodies against G ⁇ s or O ⁇ , . subunits.
- the present invention also provides kits for carrying out the method of the invention.
- Fig. 1 A graphic representation depicting non-specific, basal and agonist- induced specific binding of 3 H Gpp(NH)p to MNL obtained from a healthy volunteer, as described in Example 1.
- Figs. 2(a-e) Representative Scatchard plots depicting the results showing basal and agonist-induced 3 H-Gpp(NH)p binding in MNL membranes from a healthy volunteer, and from 4 patients with different psychiatric disorders, as described in Examples 1 and 2.
- Figs. 3(a-d) Scatter plots depicting the results showing altered agonist- induced increase in 3 H-Gpp(NH)p binding capacity in MNL membranes from patients with various psychiatric disorders compared to those of healthy volunteers, as described in Examples 1 and 2.
- Fig. 4 Bar graphs depicting the results showing the differential pattern of agonist- induced increase in Gpp(NH)p binding capacity in MNL membranes from healthy volunteers (A); healthy volunteers after physical exercise (B); manic patients (C); depressed patients (D); patients with panic disorder (E); and schizophrenic patients (F), as described in Examples 1 and 2.
- FIG. 5 A representative immunoblot with MNL protein samples from psychiatric patients (A,C) and a healthy volunteer (B), obtained with anti-sera against Gas and G ⁇ i, as described in Example 3.
- Figs. 6(a,b) Scatter plots depicting the results showing the Gas (6a) and G ⁇ , (6b) relative immunoreactivity level in MNL from healthy volunteers and from patients with various psychiatric disorders, as described in Example 3.
- FIGs. 7(a,b) Graphic representations of the results illustrating the correlation between isoproterenol (7a) and carbamylcholine (7b)-induced increase in 3 H-Gpp(NH)p binding capacity and Beck score, in patients with depression and in healthy volunteers, as described in Example 4.
- Fig. 8 - A graphic representation of the results illustrating the normalization of ⁇ -adrenergic receptor coupled G-protein ( ⁇ -Gp) function in depressed patients treated with antidepressants, as described in Example 5.
- FIGs. 9(a,b) Graphic representations of the results illustrating time-course improvement of biochemical and psychiatric parameters in depressed patients treated by electroconvulsive treatment, as described in Example 5.
- the invention is based on the discovery of a differential pattern of receptor- coupled G-proteins function and immunoreactive level in MNL from patients with the major mental disorders:
- ⁇ -Gp and M-Gp Mania - increase in ⁇ -adrenergic and muscarinic receptor-coupled G- proteins ( ⁇ -Gp and M-Gp) function, and increase in immunoreactive level of Gas and G ⁇ ,, as compared to normal (control) individuals. Depression - decrease in ⁇ -Gp and M-Gp function, and decrease in immunoreactive levels of Gas and G ⁇ , as compared to normal
- the invention is further based on the discovery that altered receptor-coupled G- proteins function and level in MNL are biochemical indicators of the effective state of the illness, and that treated asymptomatic patients show normal values.
- the present invention provides a cross diagnostic biochemical assay capable of differentiating between mental disorders, based on G-protein functional and/or quantitative measurements.
- the present invention also provides for biochemical assay for evaluating a patient's responsiveness to a psychiatric treatment.
- G-protein function is determined as agonist-induced increase in guanine nucleotide binding capacity.
- Preferred agonists for carrying out the method of the present invention are isoproterenol, carbamylcholine and dopamine, which activate ⁇ -adrenergic, muscarinic and dopaminergic receptors respectively.
- ⁇ -adrenergic, M2-muscarinic and Di/s-dopaminergic agonists stimulating receptors of similar nature are suitable, and their use is within the scope of the present invention.
- the above “quantitative measures” or “immunoreactive level” of G-protein is determined as the immunoreactive level of its ⁇ -subunit.
- the psychiatric disorders that are diagnosed by the method of the invention are: mania, depression, panic disorder and schizophrenia.
- receptor-coupled G-protein function and level are determined in MNL from a patient, however other types of cells may also be suitable for carrying out the method of the invention.
- other peripheral blood cells or elements such as platelets
- skin cells may be suitable for diagnosis.
- different cells may present different levels and types of receptors, and therefore survey must first be performed in an already diagnosed population of patients as well as in a population of healthy subjects, to assess the compatibility of each type of cells for these purposes, and to calibrate the method for when these different cells are used.
- the determination of the function of one, two or three receptor-coupled G-proteins may be suitably and effectively used for diagnosis of psychiatric disorders, or for gauging the effect of psychiatric treatments.
- depression can be diagnosed based on hypofunction of ⁇ -Gp
- mania can be diagnosed based on hyperfunction of M-Gp, with high values of specificity and sensitivity.
- the function of more than one receptor- coupled G-protein should be determined to enable accurate diagnosis.
- the function of all three ( ⁇ -Gp, M-Gp and D-Gp) be determined.
- the specificity of the test for diagnosing a certain disorder can be controlled by the determination of the minimal requirements and the threshold values.
- the determination of the function of one receptor-coupled G-protein is usually sufficient, preferably the one whose function in the acute state of the illness deviates most from the normal level.
- the evaluation is based on comparison of values obtained before and during the treatment, and a shift toward a normal value indicates responsiveness to the treatment.
- receptor-coupled G-protein function is determined by guanine nucleotide binding essay.
- any other assay which enables the determination of agonist-induced activation of G-protein may also be used to carry out the method of the invention.
- the guanine nucleotide used in the assay is Gpp(NH)p.
- Gpp(NH)p guanine nucleotides or analogs
- Other guanine nucleotides or analogs may be suitable, and their use is within the scope of the present invention. These may include for example GTP ⁇ S (Wieland T. and Jakobs K.H., 1994), or GTP-azidoanilide (a photolable compound that binds irreversibly to the G- protein following exposure to U V light, Laugwitz K. L. et al., 1994).
- the guanine nucleotide used in the assay is labeled.
- the label of the guanine nucleotide may be any kind of label which can be detected by appropriate detection means, such as radiolable, fluorescent label, etc.
- the bound guanine nucleotide may be detected using a labeled probe, which is capable of specifically binding to the complex G-protein-guanine nucleotide, or which is 11
- G-proteins determined as agonist-induced increase in binding capacity, may be calculated from multi-point measures of binding as described in the General Procedures and in Example 1. However, the assay may be simplified using single-point measures, at single concen-tration of guanine nucleotide. For Gpp(NH)p, similar values were obtained based on multiple-point measures and single-point measures, at concentration of 5 mM.
- Diagnosis of psychiatric disorders or following the effect of psychiatric treatment according to the present invention may also be based on the determination of the level of G ⁇ -subunits. Determination of the immunoreactive level of Gas and G ⁇ i has been performed by immunoblot analysis of MNL membrane-proteins which were first separated on SDS-PAGE. However, it is preferred for routine assays to determine the immunoreactivity of G ⁇ -subunits without prior separatior - f the sample. Quantitative immuno-assay of different types of G ⁇ -subunits can be performed in crude preparation of membranes (see for example Lesch K.P., Manjii H.K., 1992), and their use is in the scope of the present invention.
- Determination of the immunoreactive level of Gas and G ⁇ i for the method of the invention may also be performed by an ELISA test.
- a method based on competitive ELISA has been used to quantify various types of G ⁇ -subunits in membranes from brain of rats (Lesch K.P., and Manjii H.K., 1992).
- ELISA tests or other immuno-assays can be employed and their use is within the scope of the present invention. 12
- guanine nucleotide-G-protein complex may be trapped by contacting the sample at the end of the binding reaction with an immobilized antibody, or with an antibody which is attached to magnetic particles. This enables the washing of the unbound material, and avoids the need for filtration of the sample.
- Immuno- separation of G-protein-guanine-nucleotide complex has been disclosed in a different method (Friedman E., et al., 1993). The bound guanine nucleotide may then be detected directly (if it is labeled) or indirectly (by a labeled probe which is capable of specifically binding G-protein-guanine-nucleotide complex).
- kits for carrying out the method of the invention are based on the determination of G-protein function or on the determination of the immunoreactive level of Gas and/or G ⁇ ,.
- the kits may be used for diagnosis of psychiatric disorders, or for following the effect of psychiatric treatments.
- An illustrative kit based on G-protein function determination according to the method of the invention comprises:
- the manufacturer's instructions for using the kit Criteria for diagnosis of each of the major psychiatric disorders may also be included in the manufacturer's instructions.
- An illustrative kit based on Gas and/or G ⁇ , determination according to the method of the invention comprises:
- Standard samples should be included to enable normalization of the results, and comparison to known mean-value of normal subjects.
- Detailed instructions for normalization should be included in the manufacturer's instructions alo. _ with the criteria for diagnosis.
- Patients Samples of Patients with Psvchiatric Disorders and Control Group of Healthy Volunteers: All patients were diagnosed according to DSM-IIIR criteria by at least two senior psychiatrists. Inclusion criteria were normal results of physical examination, electrocardiogram, and laboratory tests for renal, hepatic, hematologic, and thyroid function. When indicated, patients and healthy volunteers were also evaluated through the use of Beck Inventory of Depression. Patients consented to a 60 ml blood donation for the experiment. No psychiatric treatment was given to the patients during one month prior to referral. In case of a history of treatment with depot antipsychotics (three of the patients with schizophrenia), it was verified that no such medication was given for at least two months prior to referral.
- the group of schizophrenic patients with positive symptoms consisted of 13 male and 10 female hospitalized subjects, average age 31.4 (19-59) years, diagnosed as suffering from schizophrenia of paranoid or disorganized types with a course classified as acute, subchronic with acute exacerbation, or chronic with acute exacerbation.
- the group of manic patients consisted of 13 male and 7 female hospitalized subjects, average age 34.8 (20-57) years, suffering from acute mania.
- the group of untreated patients with major depression consisted of 15 female and 13 male subjects, average age 42.7 (20-68) years: 18 were outpatients and 10 were hospitalized.
- the healthy volunteer group consisted of 17 men and 13 women, average age 38.9 (20-77) years.
- MNL Isolation MNL were isolated from 60 ml heparinized fresh blood of adult donors, using Ficoll-Paque gradient according to Boyum (Boyum A., 1968). Cells were homogenized in 25 mM Tris-HCl, pH 7.4, and 1 mM dithiotreitol (DTT). The homogenate was passed through two layers of cheesecloth to remove debris, and membranes were collected by further centrifugation at 18,000 g for 10 minutes. Membranes were then either freshly used for the functional binding measures or suspended in homogenization buffer containing ImM ATP, ImM EGTA, 2mM Mg 2+ and 30% sucrose w/v, and frozen at -70°C until assayed by the quantitative measures. Aliquots were taken for protein concentration determination using Bradford's standard assay.
- Guanine nucleotide binding assay was performed according to Avissar S. et al., (Avissar S. et al., 1988). Guanosine ⁇ , ⁇ , imido triphosphate [Gpp(NH)p], a nonhydrolyzable analog of GTP which has higher affinity for G-proteins, was used in guanine nucleotide binding assay.
- Binding reaction was carried out at various concentrations of 3 H-Gpp(NH)p (0.05-5 ⁇ M). Total binding was measured by adding aliquots of 50 ⁇ g of membrane proteins to a series of tubes containing reaction buffer (25 mM Tris- HCl, pH 7.4, ImM ATP, ImM Mg 2+ , ImM EGTA, and ImM DTT), with varying concentration of 3 H-Gpp(NH)p, to a final volume of 200 ⁇ l. The tubes were incubated for 10 minutes at room temperature (18°C - 25°C) and the reaction was terminated with 5 ml of ice-cold buffer (lOmM Tris-HCl, pH 7.4; lOOmM NaCl).
- the samples were filtered through GF/C Whatman filters.
- the filters were washed twice with 3 ml of cold buffer, and their radioactivity were determined.
- Non-specific binding, at each 3 H-Gpp(NH)p concentration, was measured in parallel, in the presence of lOO ⁇ M unlabeled GTP ⁇ S.
- the binding reactions were carried out in triplicates, and specific binding was calculated by subtracting the nonspecific binding from the total binding.
- Agonist-induced Binding Three agonists were used, the ⁇ -adrenergic agonist - isoproterenol, the muscarinic agonist - carbamylcholine. and the dopamenergic agonist-dopamine. The effects of the agonists on 3 H-Gpp(NH)p binding were assessed by adding isoproterenol (25 ⁇ M), carbamylcholine (50 ⁇ M) or dopamine (50 ⁇ M) to the reaction mixture. These represent minimal concentration resulting in maximal effect of the agonist.
- Antagonists effects on agonist-induced increase in 3 H-Gpp(NH)p binding capacity were assessed by adding them to the reaction mixture, to the final concentrations indicated for each one.
- blots were incubated overnight with each of the following antisera (NEN-DuPont) directed specifically against as (dilution 1:2,500), a ⁇ , ⁇ ,2, (dilution 1:5,000), followed by subsequent incubation with goat anti-rabbit IgG labeled with horseradish peroxidase. Immunoreactivity was detected with the Enhanced Chemiluminescence Western Blot Detection System (Amersham) followed by exposure to Kodak X-Omat film. Peak heights of immunoreactive bands were determined with an image analysis system. The optical density of the immunoreactive bands was normalized against 10 ⁇ g rat cortical membranes, run in each blot as a standard value. Linearity of the assay with respect to protein concentration, was found in the range of 2.5- 15 ⁇ g membrane protein from a healthy volunteer.
- Example 1 Receptors-coupled G-protein function in healthy volunteers.
- Binding of 3 H-Gpp(NH)p to MNL membranes from healthy volunteers was determined at various 3 H-Gpp(NH)p concentrations in the absence of an agonist or in the presence of isoproterenol, carbamylcholine or dopamine. Specific binding (calculated by subtracting the non-specific binding from the total binding) reached equilibrium within 5 min. and remained constant for at least 30 min.
- Fig. 2a depicts representative Scatchard plots of basal and agonist-induced binding curves in MNL membranes from a healthy volunteer.
- the ratio of specifically bound Gpp(NH)p to free Gpp(NH)p is plotted against specifically bound Gpp(NH)p.
- Bmax the maximal binding capacity can be estimated from the intercept of the extrapolated linear regression line with the horizontal axis.
- Bmax - Bmax basal value in the absence of an agonist is 40.3 ⁇ 1.0 pmole/mg protein
- ⁇ -Bmax - Bmax value in the presence of ⁇ -adrenergic agonist isoproterenol is
- the Bmax values did not show significant change with age, (L. Barki-Harrington et al., 1996, in press) or after physical exercise.
- Table I discloses the effect of ⁇ -adrenergic, muscarinic and dopaminergic antagonists, and the effect of cholera and pertussis toxins on agonist-induced increase in Gpp(NH)p binding.
- Cholera toxin is known to inhibit Gs protein through ribosylation of its ⁇ subunit.
- Table 1 the increase in Gpp(NH)p binding capacity induced by dopamine and isoproterenol was abolished by cholera toxin, suggesting their effects on Gs protein function.
- Human MNL are known to possess surface ⁇ -adrenergic receptors, which activate adenylyl cyclase function via Gs protein.
- Agonist Antagonist % increase in 3 H-Gpp(NH)p binding capacity
- Example 2 Receptor-coupled G-protein function in psvchiatric patients.
- Fig. 2 (a-e) depicts representative examples of Gpp(NH)p binding assay in individual patients with mania (b); depression (c); schizophrenia (d); and panic disorder (e), as compared with a healthy volunteer (a). Binding was assayed under basal conditions (open circles) or in the presence of agonists: isoproterenol (open triangles), carbamylcholine (closed squares ), or dopamine (closed circles)- [in (a) and (d) only]. No significant change in basal binding capacity was found between the five individuals. However, each individual patient presented a specific, differential pattern of agonist induced increase in binding capacity.
- Fig. 3(a-d) and Fig. 4 summarize the results of agonist-induced increase in binding capacity in groups of patients with the various psychiatric disorders. Scatter plots for patients (open circles) with mania (3a); depression (3b); schizophrenia (3c); and panic disorder (3d) as compared to healthy volunteers (closed circles) are presented in Fig. 3.
- Fig. 4 The calculated means and standard error of the means for isoproterenol (open columns), carbamylcholine (dashed columns), and dopamine (closed columns) induced increase in Gpp(NH)p binding capacity, are presented in Fig. 4 for manic patients (C); depressed patients (D); patients with panic disorder (E); schizophrenic patients (F), and for healthy volunteers at rest (A); or after physical exercise (B).
- Each group of patients is characterized by a distinct pattern of receptor-coupled G-protein function.
- MNL of patients with mania were characterized by elevated ⁇ -adrenergic receptor-coupled G protein ( ⁇ -Gp) function and elevated muscarinic receptor-coupled G protein (M-Gp) function; reduced function of both ⁇ -Gp and M-Gp were detected in MNL of depressed patients.
- MNL of patients with panic disorder were characterized by elevated ⁇ -Gp function and reduced M-Gp function.
- no differences were detected in the function of ⁇ - Gp and M-Gp between patients with schizophrenia and control subjects.
- D-Gp dopaminergic receptor-coupled G protein
- Schizophrenia Isoproterenol 29.5 ⁇ 1.9% no significant differ.
- the sensitivity and specificity of a potential diagnostic assay which is based on a G-protein function measurements can be estimated using validity test, for any predetermined threshold values, and for predetermined test criteria.
- the sensitivity was found to be 0.89 and the specificity 0.90.
- the sensitivity was found to be 0.75 and the specificity 0.93.
- Analysis of the results may be based on values obtained with one (only in two cases), two or three agonists and different threshold may be used for each of them, according to the distribution of values found in patients and control subjects.
- Other manipulation of the assay results are also possible and may aid in reliable diagnosis.
- the sensitivity and specificity of the diagnosis of panic disorder may be elevated if evaluation is based on the ratio ⁇ -Gp/M-Gp, rather than on each parameter separately.
- Example 3 Gas and G ⁇ i levels in psvchiatric patients.
- the level of Gs and G, proteins in MNL was determined by immunoblot analysis using polyclonal antibodies against Gas and G ⁇ i.
- a representative immunoblot with MNL-membrane proteins from a patient with mania (A); a patient with depression (C); and an age and sex matched healthy volunteer (B) is shown in Fig. 5.
- A representative immunoblot with MNL-membrane proteins from a patient with mania (A); a patient with depression (C); and an age and sex matched healthy volunteer (B) is shown in Fig. 5.
- A representative immunoblot with MNL-membrane proteins from a patient with mania
- C patient with depression
- B age and sex matched healthy volunteer
- the specificity and selectivity of a test can be evaluated.
- the sensitivity is 0.73 and the selectivity 0.81.
- the sensitivity is 0.73 and the selectivity 0.90.
- Example 5 The effect of psychiatric treatments on the function and the level of G-proteins. ⁇ -Gp and M-Gp function(s) in lithium treated euthymic bipolar patients were found to be similar to these of control subjects (Schreiber at al 1991, Avissar and Schreiber 1992a).
- Fig. 8 depicts ⁇ -Gp function in depressive patients before (closed circles) and following treatments with antidepressants (closed circles).
- the alterations in ⁇ - Gp function in most (7of 8) of the depressive patients examined were normalized following treatments with antidepressants. The only exception being a patient who was also found to be non-responsive to the treatment based on psychiatric parameters.
- ⁇ -Gp function (open circles) and M-Gp function (open squares), were measured in MNL membranes from depressed patients at intervals during ECT treatment.
- the state of the psychiatric illness was evaluated in parallel, using Beck Inventory for Depression (closed circles) or Hamilton and Brief Psychiatric Rating Scale (BPRS) Scores (not shown).
- BPRS Hamilton and Brief Psychiatric Rating Scale
- Fig. 9a depicts representative examples of the dynamics of the change in ⁇ -Gp function (open circles), M-Gp function (open squares), and Beck score (closed circles) in 4 depressed patients, on electroconvulsive treatment [ECT].
- Fig. 9b depicts representative examples of the dynamics of the change in Gas (open circles), Ga, (open squares) immunoreactive level, and Beck score (closed circles) in 4 depressed patients, on electroconvulsive treatment [ECT].
- G-protein functional and quantitative measurements may serve as predictors for the responsiveness of psychiatric patients to various psychiatric treatments.
Abstract
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EP96939287A EP0874987A1 (en) | 1995-11-30 | 1996-11-25 | Methods and kits for diagnosis and monitoring treatments of psychiatric disorders |
AU76382/96A AU729117B2 (en) | 1995-11-30 | 1996-11-25 | Methods and kits for diagnosis and monitoring treatments of psychiatric disorders |
JP9520334A JP2000502179A (en) | 1995-11-30 | 1996-11-25 | Methods and kits for monitoring the diagnosis and treatment of mental disorders |
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IL11620595A IL116205A0 (en) | 1995-11-30 | 1995-11-30 | Methods and kits for diagnosis and monitoring treatments of psychiatric disorders |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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EP0973037A1 (en) * | 1998-07-14 | 2000-01-19 | Ben-Gurion University Of The Negev | Method for monitoring the extra-pyramidal effects of antipsychotic agents |
WO2000044273A2 (en) * | 1999-01-31 | 2000-08-03 | Ben-Gurion University Of The Negev | Diagnosis and prediction of light therapy response in seasonal affect disorder patients using g-protein subunit measurements |
US6875566B2 (en) * | 2000-07-29 | 2005-04-05 | The Board Of Trustees Of The University Of Illinois | Marker for antidepressant therapy and methods related thereto |
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CN2389638Y (en) * | 1999-09-07 | 2000-08-02 | 曹孟君 | Polyacrylamide aquogel breast prosthesis |
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- 1996-11-25 JP JP9520334A patent/JP2000502179A/en active Pending
- 1996-11-25 EP EP96939287A patent/EP0874987A1/en not_active Withdrawn
- 1996-11-25 CA CA002239115A patent/CA2239115A1/en not_active Abandoned
- 1996-11-25 AU AU76382/96A patent/AU729117B2/en not_active Ceased
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0973037A1 (en) * | 1998-07-14 | 2000-01-19 | Ben-Gurion University Of The Negev | Method for monitoring the extra-pyramidal effects of antipsychotic agents |
WO2000044273A2 (en) * | 1999-01-31 | 2000-08-03 | Ben-Gurion University Of The Negev | Diagnosis and prediction of light therapy response in seasonal affect disorder patients using g-protein subunit measurements |
WO2000044273A3 (en) * | 1999-01-31 | 2000-11-16 | Univ Ben Gurion | Diagnosis and prediction of light therapy response in seasonal affect disorder patients using g-protein subunit measurements |
US6875566B2 (en) * | 2000-07-29 | 2005-04-05 | The Board Of Trustees Of The University Of Illinois | Marker for antidepressant therapy and methods related thereto |
US7118858B2 (en) | 2000-07-29 | 2006-10-10 | The Board Of Trustees Of The University Of Illinois | Marker for antidepressant therapy and methods related thereto |
US7445888B2 (en) | 2000-07-29 | 2008-11-04 | The Board Of Trustees Of The University Of Illinois | Methods for assaying for antidepressant therapy markers |
USRE43712E1 (en) | 2000-07-29 | 2012-10-02 | The Board of Trustees of the Uniersity of Illinois | Methods for assaying for antidepressant therapy markers |
Also Published As
Publication number | Publication date |
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EP0874987A1 (en) | 1998-11-04 |
AU729117B2 (en) | 2001-01-25 |
JP2000502179A (en) | 2000-02-22 |
AU7638296A (en) | 1997-06-19 |
IL116205A0 (en) | 1996-01-31 |
CA2239115A1 (en) | 1997-06-05 |
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