Phospholipid patterns of erythrocytes in schizophrenia: relationships to symptomatology.

The phospholipid composition of red blood cells (RBC) from 32 haloperidol-treated schizophrenic patients, classified according to the positive and negative syndrome scale (PANSS) as showing either predominantly positive or predominantly negative symptoms, was determined and compared with that of normal controls. While the levels of phosphatidylcholine and phosphatidylserine were similar in all three groups, sphingomyelin (SM) and phosphatidylethanolamine (PE) were, respectively, increased and decreased in RBCs of schizophrenic patients. In both patient groups, the SM/PE ratios correlated directly with the PANSS negative symptom scale scores and inversely with the positive symptom scale scores. However, the inverse changes in the contents of SM and PE were much more expressed in the negative group. It is suggested that a main source of that difference is a higher activity of the polyunsaturated acid-selective phospholipase A(2) in the negative syndrome patients than in the positive syndrome and control groups.

Gender differences in psychosocial risk factors for psychological distress among immigrants.

The reasons for a greater prevalence of psychological distress among women than men remain unknown. We sought to test two hypotheses that gender operates either as (1) a moderator or (2) a mediator between psychosocial risk factors and experienced distress. A cross-sectional community survey of 1,062 adult Russian-born Jewish immigrants to Israel was conducted. The Demographic Psychosocial Inventory (DPSI) and the Talbieh Brief Distress Inventory (TBDI) were used to measure the parameters of interest. Univariate and multivariate analyses were used to test the moderation versus mediational hypotheses of gender in the stress-distress relationship. The aggregate levels of psychological distress and depression, anxiety, and obsessive symptoms were significantly higher for women than for men. Five sources of distress were more likely to be reported by women: family problems, inappropriate climatic conditions, anxiety about the future, poor health status, and uncertainty in the present life situation. Men scored higher on three stress-protective factors: the number of reasons for immigration, commitment to the host country, and job adequacy. Results of multiple regression and multivariate analysis of variance (MANOVA) supported the mediation hypothesis that gender differences in psychological distress stem from women's greater exposure to specific psychosocial stressors. Our findings demonstrate the validity of gender as an important mediating mechanism underlying the differential perception of risk factors for the development of psychological distress.

Elevated dopamine receptor-coupled G(s) protein measures in mononuclear leukocytes of patients with schizophrenia.

Heterotrimeric G proteins play a pivotal role in post-receptor information transduction and were previously implicated in the pathophysiology and treatment of mood disorders. Changes previously detected in G protein levels in post-mortem brain of patients with schizophrenia could reflect effects of antipsychotic medication. The present study aims at quantitatively and functionally evaluating receptor-coupled G proteins in mononuclear leukocytes obtained from 23 untreated patients with schizophrenia and 30 healthy subjects in an attempt to unravel a pattern of G protein measures in schizophrenia distinctive from patterns previously obtained in mood disorders. Dopamine-enhanced guanine nucleotide binding capacity to G(s) protein through D1/D5 receptor in mononuclear leukocytes of untreated patients with schizophrenia was significantly increased in comparison with healthy subjects, and positively correlated with both the total PANSS score and the positive subscale. beta-Adrenergic and muscarinic receptor-coupled G protein functions, as well as G(s)alpha, G(i)alpha and Gbeta immunoreactivities, were similar to healthy subjects. These findings, distinctive for schizophrenia, unrelated to drug treatment, and differential from previous findings in mania and depression, may potentially help to differentially diagnose, after the first psychotic episode, between the major psychoses: schizophrenia and manic-depressive illness.

Differences in quality of life domains and psychopathologic and psychosocial factors in psychiatric patients.

BACKGROUND: Although treatment of severe mental disorders should strive to optimize quality of life (QOL) for the individual patient, little is known about variations in QOL domains and related psychopathologic and psychosocial factors in patients suffering from schizophrenia, schizoaffective disorder, and/or mood disorders. We hypothesized that QOL in severe mental disorder patients would have a more substantial relationship with psychosocial factors than with illness-associated factors. METHOD: A case-control, cross-sectional design was used to examine QOL of 210 inpatients who met DSM-IV criteria for a severe mental disorder and who were consecutively admitted to closed, open, and rehabilitation wards. Following psychiatric examination, 210 inpatients were assessed using standardized self-report measures of QOL, insight, medication side effects, psychological distress, self-esteem, self-efficacy, coping, expressed emotion, and social support. QOL ratings for patients and a matched control group (175 nonpatients) were compared. Regression and factor analyses were used to compare multidimensional variables between patients with schizophrenia and schizoaffective and mood disorders. RESULTS: In all QOL domains, patients were less satisfied than nonpatient controls. Patients with schizophrenia reported less satisfaction with social relationships and medication when compared with patients with schizoaffective and/or mood disorders. Regression analysis established differential clusters of predictors for each group of patients and for various domains of QOL. On the basis of the results of factor analysis, we propose a distress protection model to enhance life satisfaction for severe mental disorder patients. CONCLUSION: Psychosocial factors rather than psychopathologic symptoms affect subjective QOL of hospitalized patients with severe mental disorders. The findings enable better understanding of the combining effects of psychopathology and psychosocial factors on subjective life satisfaction and highlight targets for more effective intervention and rehabilitation.

The effects of seasons and light therapy on G protein levels in mononuclear leukocytes of patients with seasonal affective disorder.

BACKGROUND: Information-transducing heterotrimeric G proteins have been implicated previously in the mechanism of action of mood stabilizers and in the pathophysiology of mood disorders. Mononuclear leukocytes of patients with unipolar and bipolar depression have been characterized by reduced measures of the stimulatory and inhibitory G proteins. In this study, patients with seasonal affective disorder (SAD) were measured for mononuclear leukocyte G protein levels while depressed during the winter, following light therapy, and in remission during the summer. METHODS: Twenty-six patients with SAD and 28 healthy subjects were assessed in the study. The immunoreactivities of Gs alpha, Gi alpha, and Gbeta subunit proteins were determined by Western blot analysis of mononuclear leukocyte membranes with selective polyclonal antibodies for the various G subunit proteins, followed by densitometric quantitation using an image analysis system. RESULTS: Untreated patients with SAD and winter, atypical-type depression showed significantly reduced mononuclear leukocyte immunoreactive levels of Gs alpha and Gi alpha proteins, similar to previous observations in patients with nonseasonal major depression. The reduced G protein levels were normalized with 2 weeks of light therapy. The same patients while in remission during the summer had G protein levels that were similar to those of healthy subjects. CONCLUSIONS: G protein-immunoreactive measures in patients with SAD are suggested as a state marker for winter depression, which is normalized by light treatment and during the summer. We speculate that light may exert its effects via normalization of transducin (Gt protein) levels, which are thought to be reduced in winter depression.

Dynamics of ECT normalization of low G protein function and immunoreactivity in mononuclear leukocytes of patients with major depression.

OBJECTIVE: Heterotrimeric G proteins were previously implicated in the biochemical mechanisms underlying the pathophysiology and treatment of mood disorders. Low function and immunoreactivity of G proteins were observed in patients with major depression. In the present study the authors evaluated the effects of ECT on the low measures of G proteins in patients with major depression. METHOD: Repeated G protein measurements in mononuclear leukocytes of 10 patients with major depression were made. Each patient was examined while untreated and after successive sessions of ECT; 14 normal subjects were also studied. G protein function was evaluated through beta-adrenergic- and muscarinic-agonist-enhanced guanine nucleotide binding capacity, substantiated by quantitative measures of G proteins through immunoblot analyses using polyclonal antibodies against Gs alpha, Gi alpha, and G beta proteins. RESULTS: Mononuclear leukocytes of patients with depression showed immunoreactive levels of Gs alpha and Gi alpha that were significantly lower than those of normal subjects; the depressed patients also had markedly hypofunctional Gs and Gi. The low levels of G protein function and immunoreactivity were alleviated by ECT. Repeated measurements in the same patients after successive ECT sessions showed that the normalization of G protein measures preceded, and thus predicted, clinical improvement. The function and quantity of Gs and Gi proteins in patients given ECT were significantly correlated. CONCLUSIONS: These findings support the implication of G proteins in the pathophysiology and treatment of mood disorders. G protein measurements in patients with depression may potentially serve not only as a biochemical marker for affective state but also for biochemical prediction and evaluation of responses to ECT.

Differential G protein measures in mononuclear leukocytes of patients with bipolar mood disorder are state dependent.

Quantitative and functional measurements of G proteins were undertaken in mononuclear leukocytes of bipolar disordered patients comparing bipolar depressed with manic patients groups in order to verify whether any alterations observed in G protein functional or immunoreactive measures in bipolar mood disorder are state- or trait-dependent characteristics. Compared with the control group of 30 subjects, isoproterenol- and carbamylcholine-enhanced Gpp(NH)p binding capacities were highly significantly increased in the group of 20 manic patients, while highly significantly reduced in the group of 11 bipolar depressed patients. While manic patients showed highly significant elevations in mononuclear leukocytes levels of G alpha s and G alpha i, evaluated through immunoblot analysis using specific polyclonal antibodies against the subunit proteins, mononuclear leukocytes of bipolar depressed patients show significant reductions in G alpha s and G alpha i immunoreactive levels. G beta subunit levels were found to be similar in all three groups. The changes in G protein measures observed in mononuclear leukocytes of mood disordered patients thus represent state characteristics of the disorder.

Reduced G protein functions and immunoreactive levels in mononuclear leukocytes of patients with depression.

OBJECTIVE: Heterotrimeric G proteins play a pivotal role in postreceptor information transduction. These proteins were previously implicated in the biochemical mechanism underlying lithium action and in the pathophysiology of mood disorders. The present study sought to quantitatively and functionally evaluate G proteins in patients with major depression. METHOD: G proteins were measured in mononuclear leukocytes of 37 untreated patients with major depression and 31 comparison subjects. Receptor-coupled G protein function was evaluated through beta-adrenergic and muscarinic-agonist-induced increases in guanine nucleotide binding capacity, which were substantiated by quantitative measures of G proteins through immunoblot analyses that used polyclonal antibodies against stimulatory (Gs alpha) and inhibitory (Gi alpha) G proteins. RESULTS: Mononuclear leukocytes of depressed patients showed significantly reduced immunoreactive quantities of Gs alpha and Gi alpha together with markedly hypofunctional Gs and Gi. The reductions in both function and quantity of Gs and Gi were significantly correlated with the severity of depressive symptoms. Moreover, simultaneous quantitative and functional measurements in a large number of patients showed significant correlations between the function and the quantity of mononuclear leukocyte Gs and Gi proteins: CONCLUSIONS: These findings lend further support to the implication of G proteins in the pathophysiology of mood disorders. G protein functional and quantitative measurements in mononuclear leukocytes of patients with mood disorders may potentially serve as a biochemical marker for the affective state of these patients.

Reduced beta-adrenergic receptor-coupled Gs protein function and Gs alpha immunoreactivity in mononuclear leukocytes of patients with depression.

beta-Adrenergic receptor-coupled Gs protein function was measured in 26 depressed patients through cholera toxin-sensitive, isoproterenol-induced increases in 3H-Gpp(NH)p binding capacity to mononuclear leukocytes (MNL). Highly significant reductions in receptor-coupled Gs protein function were observed in the depressed patients: 2.0 +/- 1.3% increases in guanine nucleotide-binding capacity, in comparison with the control group values of 28.3 +/- 6.9%. Similar reductions in Gs protein function were detected in both uni- and bipolar depressed patients. A significant negative correlation was found between receptor-coupled Gs protein measures and the severity of depression. Adding semiquantitative measures of MNL Gs alpha through immunoblot analysis by use of polyclonal antibodies against Gs alpha subunit, it was found that Gs alpha relative immunoreactivity was reduced from 100 +/- 2.0% in the control group of subjects to 75.9 +/- 2.3% in the depressed patients. We have previously described hyperfunctional Gs proteins in leukocytes of patients with mania. The present findings of reduced function of Gs in depressed patients suggests receptor-coupled Gs protein activity as a biochemical parameter indicatory of the affective state. Reduced receptor-coupled Gs protein function may reflect reduced levels of the beta-adrenergic receptor previously shown in leukocytes of depressed patients; however, our complementary immunoblot studies suggest a direct, postreceptor, quantitative, and functional reduction in Gs protein in MNL of depressed patients.

Functional and quantitative measures of receptor-coupled G proteins in human mononuclear leukocytes: no change with age.

Aging has been associated with alterations in signal transduction for a number of neurotransmitter receptors in human tissues. Heterotrimeric G proteins play a pivotal role in postreceptor information transduction, by coupling a variety of hormone and neurotransmitter receptors to several intracellular effector functions. Developmental and age-related changes in the abundance of specific G alpha subunits have been shown in the human brain. In the present study, functional and quantitative measures of G proteins were conducted in human mononuclear leukocytes obtained from 19 healthy subjects of increasing age. Gs protein function, assessed through cholera toxin-sensitive beta-adrenergic and dopaminergic agonists induced increases in 3H-Gpp(NH)p binding capacities to membranes of mononuclear leukocytes, and Gi protein function, assessed through pertussis toxin-sensitive muscarinic agonist induced increase in guanine nucleotide binding capacity, were found to be unaltered by increasing age. Immunobloting analyses with specific polyclonal antibodies against G alpha s, G alpha i, and G alpha q subunit proteins in mononuclear leukocyte membranes obtained from the same subjects showed that the quantities of these proteins in mononuclear leukocytes were as well independent of age. Insofar as age-related alterations in cellular information transduction mechanisms in peripheral tissues are important from the etiological, diagnostic, and pharmacological aspects of age-related disorders, it is important to know that both the coupling of receptors to G proteins, the function of these proteins, and their abundance in human peripheral mononuclear leukocytes stays unaltered by the aging process.