Maternal transmission disequilibrium of the glutamate receptor GRIK2 in schizophrenia.

Schizophrenia is characterized by thought disorders, hallucinations and delusions. Genetic studies have shown a high linkage at chromosome 6q16-21. Among the genes located in this region is the glutamate receptor ionotropic kainate 2 gene (GRIK2 or GLUR6), a functional candidate for susceptibility to schizophrenia. In this study, transmission of GRIK2 was evaluated in 356 schizophrenic patients from three different clinical centers. Whereas paternal transmission shows equilibrium, we observed maternal transmission disequilibrium of GRIK2 in the largest population (p=0.03), which was still significant when all populations were added (p=0.05). These results are similar to the maternal GRIK2 transmission disequilibrium previously reported for autism, and support the presence of a susceptibility gene for schizophrenia at 6q16.

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.

Clinical evaluation of prior suicide attempts and suicide risk in psychiatric inpatients.

BACKGROUND: In practice psychiatrists rely on their own experience and intuition to evaluate the suicide potential of individual patients, but the algorithms for the decision-making process remain unclear. OBJECTIVES: (1) to establish models for the decision making process for evaluating suicide risk; (2) to simulate the impact of information concerning the number of previous suicide attempts on the clinician's ability to detect patients who performed medically serious suicide attempts (MSSAs). METHODS: Four decision models (linear, dichotomized, hyperbolic, and undifferentiated) depicting the influence of the number of previous suicide attempts on the clinician's recognition of MSSAs in 250 psychiatric inpatients were elicited and tested by a series of discriminant analyses. RESULTS: The dichotomized model ("all or none") was found to be the most efficient in detecting medically serious suicide attempts. CONCLUSION: The "all or none" paradigm seems to be the most appropriate way to evaluate the weight of previous suicide attempts in the decision-making process identifying medically serious suicide attempt patients.

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.

Validation of the Computerized Suicide Risk Scale--a backpropagation neural network instrument (CSRS-BP).

BACKGROUND: Medically serious suicide attempts have been recognized as the most important predictor of suicide. The Computerized Suicide Risk Scale based on backpropagation neural networks (CSRS-BP) has been recently found efficient in the detection of records of patients who performed medically serious suicide attempts (MSSA). OBJECTIVES. To validate the CSRS-BP by: 1) using the CSRS-BP with patients instead of records; 2) comparing the ability of expert psychiatrists to detect MSSA, using the CSRS checklist; and 3) comparing the results of the Risk Estimator for Suicide (RES) and the self-rating Suicide Risk Scale (SRS) with the CSRS-BP. METHODS: Two hundred fifty psychiatric inpatients (35 MSSA and 215 non-MSSA) were diagnosed by clinicians using the SCID DSM-IV. Three expert psychiatrists completed the CSRS checklist, and the RES for each patient, and the patients completed the self-report SRS assessment scale. The CSRS-BP was run for each patient. Five other expert psychiatrists assessed the CSRS checklists and estimated the probability of MSSA for each patient. Comparisons of sensitivity and specificity rates between CSRS-BP, assessment scales and experts were done. RESULTS: Initially, the CSRS-BP, RES, SRS, and experts performed poorly. Although sensitivity and specificity rates significantly improved (two to four times) after the inclusion of information regarding the number of previous suicide attempts in the input data set, results still remained insignificant. CONCLUSIONS: The CSRS-BP, which was very successful in the detection of MSSA patient records, failed to detect MSSA patients in face-to-face interviews. Information regarding previous suicide attempts is an important MSSA predictor, but remains insufficient for the detection of MSSA in individual patients. The detection rate of the SRS and RES scales was also poor and could therefore not identify MSSA patients or be used to validate the CSRS-BP.

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.

Comparison of sexual dysfunction in male schizophrenic patients maintained on treatment with classical antipsychotics versus clozapine.

BACKGROUND: Antipsychotic treatment is frequently associated with sexual dysfunction. The objective of the present study was to evaluate and compare sexual function and behavior in male schizophrenic patients who regularly take either classical neuroleptic drugs or the prototypical atypical antipsychotic agent, clozapine. METHOD: Participants included 60 schizophrenic male patients (DSM-IV criteria); 30 maintained on treatment with classical antipsychotics and 30 on treatment with clozapine. The patients were evaluated with a detailed 18-item sexual function questionnaire. RESULTS: Both groups reported sexual dysfunction, although scores were significantly higher, indicating better functioning, in the clozapine-treated group in the domains of orgasmic function (number of orgasms per month, p = .037; frequency of orgasm during sex, p = .046), enjoyment of sex (p = .013), and sexual satisfaction (p = .0004). Equivocal results were obtained for the desire parameters. CONCLUSION: Maintenance therapy with the atypical neuroleptic clozapine may be associated with a lesser degree of sexual dysfunction than the classical antipsychotics in male outpatients with chronic schizophrenia.

Metabolic bioenergy homeostatic disruption: a cause of anorexia nervosa.

We believe anorexia nervosa is the result of a disruption in bioenergy homeostasis induced by lipid dysregulation. This disruption has two major determinants: (1) a biological predisposition to primary multihormonal disharmony linked to post-pubertal growth and development; and (2) an acquired abnormal lipid-induced loop operation precipitated by inappropriate diet. We present a step-by-step model describing the cascade of disorders that culminates in anorexia nervosa: defective digestion and absorption of essential fatty acids; diversion of lipids from adipose cells into bloodstream; defective carbohydrate and lipid metabolism which modifies the blood brain barrier; neuroendocrine membrane alteration causing severe endocrine impairment; changes in the negative feedback mechanism which escalate the body's use of bioenergy; derangement of the appetite center which causes a constant sensation of satiety; replacement of the correct body image with the premorbid one that encourages poor judgement concerning food intake and self-support. The loop-like nature of this mechanism perpetuates the disease.

Obsessive-compulsive disorder in hospitalized patients with chronic schizophrenia.

Obsessive-compulsive (OC) symptoms have been observed in a substantial proportion of schizophrenic patients. In this study, we assessed the rate of occurrence of OC symptoms and the interrelationship between OC and schizophrenic symptoms in 68 hospitalized chronic schizophrenic patients. The patients were interviewed with the Structured Clinical Interview for Axis-I DSM-IV Disorders - Patient Edition (SCID-P) and the appropriate rating scales including the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Barnes Akathisia Scale, the Abnormal Involuntary Movement Scale, and the Social Behaviour Schedule (SBS). Sixteen patients (23.5%) met the DSM-IV criteria for OCD. A comparison of schizophrenic patients with and without OCD showed that the schizo-obsessive patients were significantly (1.7-fold) more impaired in basic social functioning, as reflected by the SBS score. No significant between-group differences for any of the other clinical variables were found. There was no significant correlation between OC and schizophrenic symptoms within the schizo-obsessive subgroup. The mean Y-BOCS score for the patients with both schizophrenia and OCD was within the typical range (22.8+/-1.7) observed in OCD without psychosis. The findings provide further evidence for the importance of the OC dimension in schizophrenia and may have important implications for the application of effective treatment approaches in this difficult-to-treat subgroup of schizophrenic patients.

Pindolol augmentation in aggressive schizophrenic patients: a double-blind crossover randomized study.

Treatment of aggression in schizophrenic patients is a major challenge. We sought to examine the efficacy of augmentation of antipsychotic treatment with pindolol in the amelioration of aggression. Thirty male inpatients meeting DSM-IV criteria for schizophrenia, aged 20-65 years involved in four or more aggressive incidents in the two previous months, were enrolled in a double-blind crossover study. Aggression was evaluated per incident, with the Overt Aggression Scale (OAS). Positive and Negative Syndrome Scale (PANSS) was administered at baseline, crossover and at endpoint. Patients received either pindolol or placebo augmentation 5 mg x three times a day until crossover, then switched. No significant differences were found in the PANSS scores between the placebo and pindolol treatments. OAS scores were significantly reduced for number of aggressive incidents towards objects and other persons during pindolol treatment (0.59 versus 1.46, F = 6.09, P < 0.02; 1.96 versus 3.23, F = 4.17, P < 0.05, respectively). Similar results were obtained for severity of incidents (0.89 versus 3.58, F = 19.42, P < 0.0001; 2.89 versus 6.85, F = 10.11, P < 0.004, respectively). Pindolol, with its dual beta and 5-HT1A blocking effect ameliorated both number and severity of aggressive acts. Influence on severity may be associated with a 5-HT1A antagonistic effect.

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.

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.

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.

Abnormal neuronal ionic flux activity: learning paradigms of schizophrenic thought disorders.

New developments in biological psychiatry have prompted the development of our pathophysiological theory of the etiology of schizophrenic thought disorders. We suggest that the presence of brain bionic lesions may produce microneuropathies in certain neuronal electrical pathways, leading to abnormal biological communication. These blockages force the rerouting of incoming electric signals through bypass pathways which divert the message from target to non-target neurons for decoding and integration. Using this model, we were able to link specific schizophrenic disturbances to different types of brain bionic lesion effects. This model should be further investigated to facilitate the understanding of the nature and origin of schizophrenic disorders and to stimulate further interest in this fascinating field.

Changes in psychological symptoms during the adjustment of recent immigrants.

In the present study, we sought to compare the number, severity, and frequency of psychological symptoms and the intensity of perceived stressors among immigrants with previously identified positive, negative, or normal patterns of distress. We evaluated 199 recent immigrants from the former Soviet Union to Israel using the Talbieh Brief Distress Inventory (TBDI) and the Perceived Immigration-Related Stressors Scale (PIRSS) with a 1-year follow-up period. As predicted, the number, severity, and frequency of psychological symptoms and the intensity of perceived stress factors vary among immigrants showing different distress patterns. A negative pattern was associated with an increase in the total number, severity, and frequency of distress-related symptoms and persisting cultural-related stress over time. A positive pattern was associated with a reduction in the overall number and severity of symptoms, as well as a decline in the frequency of distress-free symptoms and the intensity of all but informational-related stressors. A normal pattern was characterized by the reduction of distress symptoms within a normal range along with material- and health-related stresses. Our findings confirm the validity of the suggested classification for different patterns of distress and its usefulness in establishing the prognosis for the adjustment of immigrants.

Homeostatic biophasal conscious regulation.

A new theory on consciousness is presented. According to our neuroscientific model, focal awareness is the result of neurophysiological patterns of voluntary or involuntary information, registration, storage and retrieval performed in accordance with organismic biphasal homeostatic rules and regulations that follow the demand-supply principle. The information-processing operation consists of three major elements: 1. Involuntary activated 'inherited schematic representation' (ISR) programs that monitor homeostatic negative feedback programs and remain inert during the storage period; 2. Voluntary activated 'acquired engram linkage' (AEL) programs that monitor the preferential self-efforts designed to maintain homeostasis and dynamic adaptational survival; this information remains fixed in the storage reservoir; and 3. Outer, nonselective sources of activation that derive from the assembly of the sensory information system. Consciousness is limited by the microneurostructural boundaries of 'conscious instrument panel' (CIP) needed to handle this unique biological experience. At any unit of time, the conscious subjectively identifies states of pleasure (first phase of homeostasis maintenance) or displeasure (second phase of homeostasis) which are associated with the alarm subsystem of the 'organismic defense system' (ODS).Thus, consciousness is a form of neurophysiological activity that excludes unconscious existence in order to monitor information. This model promotes our understanding of the biological essences of consciousness.