Michael Ritsner

Is the G72/G30 locus associated with schizophrenia? single nucleotide polymorphisms, haplotypes, and gene expression analysis

BACKGROUND The genes G72/G30 were recently implicated in schizophrenia in both Canadian and Russian populations. We hypothesized that 1) polymorphic changes in this gene region might be associated with schizophrenia in the Ashkenazi Jewish population and that 2) changes in G72/G30 gene expression might be expected in schizophrenic patients compared with control subjects. METHODS Eleven single nucleotide polymorphisms (SNPs) encompassing the G72/G30 genes were typed in the genomic deoxyribonucleic acid (DNA) from 60 schizophrenic patients and 130 matched control subjects of Ashkenazi ethnic origin. Case-control comparisons were based on linkage disequilibrium (LD) and haplotype frequency estimations. Gene expression analysis of G72 and G30 was performed on 88 postmortem dorsolateral prefrontal cortex samples. RESULTS Linkage disequilibrium analysis revealed two main SNP blocks. Haplotype analysis on block II, containing three SNPs external to the genes, demonstrated an association with schizophrenia. Gene expression analysis exhibited correlations between expression levels of the G72 and G30 genes, as well as a tendency toward overexpression of the G72 gene in schizophrenic brain samples of 44 schizophrenic patients compared with 44 control subjects. CONCLUSIONS It is likely that the G72/G30 region is involved in susceptibility to schizophrenia in the Ashkenazi population. The elevation in expression of the G72 gene coincides with the glutamatergic theory of schizophrenia.

Validity of an abbreviated Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-18) for schizophrenia, schizoaffective,and mood disorder patients

We sought to identify a core subset of Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) items that maintains the validity and psychometric properties of the basic version. A parsimonious subset of items from the Q-LES-Q that can accurately predict the basic Q-LES-Q domain mean scores was sought and evaluated in 339 inpatients meeting DSM-IV criteria for schizophrenia, schizoaffective, and mood disorders. Three additional data sets were used for validation. Assessments included Q-LES-Q, Quality of Life Scale, Lancashire Quality of Life Profile, rating scales for psychopathology, medication side effects, and self-reported emotional distress, self-esteem, self-efficacy, and social support. We found that 18-items predicted basic Q-LES-Q domains (physical health, subjective feelings, leisure time activities, social relationships) and general index scores with high accuracy. Q-LES-Q-18 showed high reliability, validity, and stability of test-retest ratings. Thus, Q-LES-Q-18, a brief, self-administered questionnaire may aid in monitoring quality of life outcomes of schizophrenia, schizoaffective, and mood disorder patients.

Elevation of the cortisol/dehydroepiandrosterone ratio in schizophrenia patients.

Dehydroepiandrosterone (DHEA) and its sulfate derivative DHEA-S are neurosteroids, produced in the brain, and neuroactive steroids, produced in the adrenals and affecting the brain. We compared the ratios of serum cortisol/DHEA or DHEA-S in schizophrenia patients with normal subjects, and determined the correlation of these ratios with psychopathology and distress. Early morning plasma concentrations of DHEA, DHEA-S, and cortisol were determined by radioimmunassay in 40 medicated schizophrenia inpatients, and 15 healthy subjects with similar age and sex distribution. Subjects were assessed for psychopathology using the Positive and Negative Syndrome Scale (PANSS) and the Montgomery and Asberg Depression Rating Scale (MADRS), anxiety, anger, emotional and somatic distress levels. Schizophrenia inpatients demonstrated significantly higher levels of state and trait anxiety, anger expression index, emotional and somatic self-reported distress scores. Cortisol/DHEA and cortisol/DHEA-S ratios were significantly higher in schizophrenia patients than in healthy comparison subjects. Both ratios correlated positively with age and duration of illness; cortisol/DHEA-S ratio also showed positive association with age of illness onset. When age, illness duration and age of onset were controlled, cortisol/DHEA-S ratio significantly correlated with severity of depression (MADRS, r=0.33, p=0.048), state and trait anxiety (r=0.43, p=0.008 and r=0.40, p=0.014, respectively), trait anger (r=0.41, p=0.012), angry temperament (r=0.46, p=0.004), anger expression index (r=0.36, p=0.033), and hostility (r=0.42, p=0.010). No significant association was found between these ratios and severity of psychopathology, and type or dosage of antipsychotic agents. Thus, elevated cortisol/DHEA and/or cortisol/DHEA-S ratios in schizophrenia patients are positively associated with higher scores for anxiety and anger, depression and hostility, age and age of onset/duration of illness, but are independent of severity of psychopathology (PANSS) and antipsychotic treatment.

Touch feel illusion in schizophrenic patients

BACKGROUND The rubber hand illusion is a tactile sensation referred to as an alien limb. The illusion has been explained by a spurious reconciliation of visual and tactile inputs reflecting functional connectivity in the brain and was used to explore alterations of functional connectivity in schizophrenia. METHODS The rubber hand illusion was achieved when two paintbrushes simultaneously stroke the hand of the subject hidden from vision by a screen, as well as an artificial hand placed in view of the subject. The rubber hand illusion was assessed with a questionnaire affirming or denying the occurrence of the illusion. RESULTS Schizophrenic subjects felt the illusion stronger and faster then did normal control subjects. Some rubber hand illusion effects correlated with positive symptoms of schizophrenia but not with negative symptoms. CONCLUSIONS Altered functional integration of environmental inputs could constitute the basis for erroneous interpretations of reality, such as delusions and hallucinations.

Quality of life and coping with schizophrenia symptoms

The question addressed in this paper is whether different coping styles mediate the relationship between psychopathology and related distress and the quality of life (QOL) among patients with schizophrenia. In a cross-sectional design, 161 schizophrenia inpatients were comprehensively evaluated with standardized measures of QOL, psychopathology, psychological distress and coping styles. Correlations and regression analyses were performed to examine the relationship among parameters and to estimate the mediating effect of coping styles on QOL in the framework of a distress/protection model. Life quality correlated positively with task- and avoidance-oriented coping styles and slightly negatively with emotion-oriented coping. Emotion-oriented coping mediated the relationship between the severity of activation, anxiety/depression symptoms, and QOL, while avoidance-oriented (distraction) coping was mediated between QOL and paranoid symptoms. Coping styles accounted for 25% of the variance in subjective QOL scores compared with 15% for psychological distress, and only 3% for clinical variables. The ability to cope with symptoms and associated distress substantially contributes to QOL appraisal in schizophrenia. Thus, different coping strategies may reduce the negative influence of specific symptoms and related distress on the subjective QOL of schizophrenia patients.

The impact of side-effects of antipsychotic agents on life satisfaction of schizophrenia patients: a naturalistic study

This study compared the impact of side-effects of antipsychotic treatment, clinical and psychosocial factors on the subjective quality of life (QOL) of hospitalized patients. We surveyed 161 patients meeting DSM-IV criteria for schizophrenia stabilized on conventional and atypical antipsychotic drugs using standardized measures of adverse events, psychopathology, psychosocial variables, and perceived QOL. We found that patients with adverse events reported less satisfaction with life domains of subjective feelings and general activities than asymptomatic patients. Patients treated with conventional and novel antipsychotic agents had comparable QOL ratings. Multiple regression analysis showed total variance in QOL ratings as follows: psychosocial factors, 20.9%; clinical symptoms and associated distress, 10.1%; adverse effects, 3.2%. Thus, medication side-effects influence subjective quality of life of schizophrenia inpatients significantly less than other clinical and psychosocial factors. Patients subjective response to these events rather than their number is more predictive of QOL.

Perceived quality of life in schizophrenia: relationships to sleep quality.

We examined the relationship between perceived quality of life (QOL) and subjective quality of sleep among schizophrenia patients, and its relation to symptom severity, side effects and emotional distress. One hundred and forty five schizophrenia patients were comprehensively evaluated with standardized measures of symptom severity, adverse effects, emotional distress, QOL, and sleep quality (the Pittsburgh Sleep Quality Index, PSQI). Partial correlation and multiple regression analyses were performed. Poor sleepers reported lower mean scores on all QOL domains, they were more depressed and distressed, and had more adverse effects to medications with concomitant distress than good sleepers. The negative relationship between complaints of poor sleep quality and QOL measures remained significant when the confounding effect of depression, side effects, and distress was partialled from the correlation matrix. Daytime dysfunction (a component of the PSQI) accounted for 12.6% of the variance in QOL index scores. Thus, poor QOL reported by schizophrenia patients is substantially associated with poor sleep quality. This association appears both independently and synergistically with depression, distress and side effects of medications.

Predicting changes in domain-specific quality of life of schizophrenia patients.

The author sought to determine domain-specific quality of life (QOL) changes over time and to identify predictors of change in life satisfaction among schizophrenia patients. He assessed 148 schizophrenia inpatients at admission and 16 months later. Multiple regression analysis identified predictors of domain-specific changes in QOL from changes in psychopathology, emotional distress, side effects, insight, and stress process-related factors ratings. On the group level, satisfaction with subjective feelings and leisure activities improved significantly during the follow-up period. Individual changes in specific QOL domains are influenced by different patterns of predictors that accounted for 12% to 36% of variance. Emotional distress, paranoid symptoms, side effects, and insight inversely associated with variability of scores in domain-specific QOL. Changes in self-efficacy, self-esteem, and support from others were positively correlated to improvement in QOL domain ratings. Schizophrenia patients may experience improvement in specific QOL domains. Changes in stress process-related factors are stronger predictors of fluctuations in QOL domains than changes in illness symptoms and should be considered when evaluating life satisfaction.

Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial.

OBJECTIVE Pregnenolone (PREG) and dehydroepiandrosterone (DHEA) are reported to have a modulatory effect on neuronal excitability, synaptic plasticity, and response to stress; they are associated with mood regulation and cognitive performance. We investigated the influence of PREG and DHEA on psychotic symptoms and cognitive functioning as an add-on to ongoing antipsychotic treatment of patients with chronic schizophrenia or schizoaffective disorder. METHOD This 8-week, double-blind, randomized, placebo-controlled, 2-center study compared 30 mg/d of PREG (PREG-30), 200 mg/d of PREG (PREG-200), 400 mg/d of DHEA, and placebo as an adjunctive treatment of 58 chronic schizophrenia or schizoaffective disorder patients (DSM-IV). The data were collected from February 2005 until June 2007. The outcome measures were symptomatic and neurocognitive changes, functioning, and tolerability as assessed primarily by the Clinical Global Impressions-Severity of Illness scale and the Positive and Negative Syndrome Scale. Analyses are presented for 44 patients who completed 8 weeks of treatment and for 14 noncompleters. RESULTS Compared with subjects who received placebo, those administered PREG-30 had significant reductions in positive symptom scores and extrapyramidal side effects (EPS) and improvement in attention and working memory performance, whereas subjects treated with PREG-200 did not differ on outcome variable scores for the study period. The general psychopathology severity and general functioning of patients receiving placebo and PREG-30 improved more than that of those subjects treated with DHEA, while EPS improved more in subjects treated with DHEA than in patients receiving placebo. Negative symptoms and akathisia were not significantly benefited by any treatment. The administration of PREG and DHEA was well tolerated. CONCLUSIONS Low-dose PREG augmentation demonstrated significant amelioration of positive symptoms and EPS and improvement in attention and working memory performance of schizophrenia and schizoaffective disorder patients. Further double-blind controlled studies are needed to investigate the clinical benefit of pregnenolone augmentation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00174889.

Subjective quality of life in severely mentally ill patients: A comparison of two instruments

Although many quality of life (QOL) scales have been developed, comparison of specific QOL instruments is lacking. We compared the psychometric properties of two QOL measures in parallel samples of mentally disturbed and non-patient subjects. We simultaneously administered the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and self-report items of the Lancashire Quality of Life Profile (LQOLP) to 199 patients with severe mental disorders and 175 non-patients. The patients were evaluated with psychiatric rating scales. We identified five concordant domains, and five instrument-specific domains for the LQOLP and four for the Q-LES-Q. The Q-LES-Q provides better psychometric properties than the LQOLP in both samples. Both instruments show a good capacity to evaluate QOL and discriminate between the patients and non-patient controls. Within the patient sample, both QOL measures showed similarly negative correlations with severity of depression, but not mania, positive, negative, and general symptomatology. Both instruments proved to be mental health related, but neither was mental-disorder specific. Despite the acceptable psychometric properties and correlation of general QOL indices, similar QOL domains proved to be instrument specific and not sufficiently compatible. These discrepancies should be considered when comparing evaluations from similar domains in these QOL scales.