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This study sought to evaluate predischarge anhedonia level and its predictors in 125 inpatients with schizophrenia and schizoaffective disorders. Consecutively admitted inpatients were assessed before discharge from the hospital using the Specific Loss of Interest and Pleasure Scale (SLIPS) and a battery of measures for clinical and psychosocial variables. When symptoms, distress, and social anhedonia scores were controlled, the SLIPS score inversely correlated with self-constructs, social support, quality of life, recovery, and unmet needs. Using two cutoff points of the data set of SLIPS, we identified three groups: 19 (15.2%) patients reported "no loss of pleasure"; 46 (36.8%), "some loss of pleasure"; and 60 (48.0%), "marked diminishment of pleasure." The SLIPS score is predicted by sensitivity, unmet needs, deficient interpersonal pleasure, poor quality of life, and friend support. The study underlines the importance of assessing anhedonia and related psychosocial factors in patients with serious mental illness.

Although social hedonic capacity is often assessed in clinical settings, its operational definitions have not been evaluated for concurrent validity. One hundred and twenty-five patients with schizophrenia and schizoaffective disorder were classified according to their self-reported social hedonic functioning into three groups on the basis of their total scores on the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS). Participants were assessed before discharge using questionnaires and psychiatric rating scales. Using an empirically based cutoff score, we identified three groups: an intact social hedonic group (WNL), a socially anhedonic group (SA), and a socially hypohedonic group (i.e., those with scores intermediate between normal functioning and aberrantly low functioning, H). The SA patients were significantly different from the two other groups (WNL and H) by their higher severity of psychopathology, lower levels of self-efficacy, and less self-esteem. The SA patients also reported less perceived social support, poorer quality of life, and less subjective recovery. Our findings indicate that social anhedonia is a meaningful target for intervention. Further implications of our findings are discussed.

This cross-sectional study compared the levels of needs, care satisfaction, quality of life, and social support of compulsory admitted patients with severe mental disorders to a comparable group of voluntary admitted patients. One hundred and twenty-five patients with schizophrenia and schizoaffective disorder were admitted to a hospital by district psychiatrist order (DPO), court observation order (COO), or voluntary (VA). Participants were assessed before discharge using questionnaires, and psychiatric rating scales. A linear discriminant analysis revealed eight variables that best differentiated the three groups. COO patients were significantly discriminated from the two other groups (DPO and VA) by severe negative symptoms, better satisfaction with both nursing staff and family support. COO subjects had more non-illness unmet needs, while reported better hedonic capacity for social and interpersonal pleasure – compared to VA patients. DPO patients were significantly indicated by poorer awareness to illness, but better satisfaction with subjective feelings. VA subjects were significantly discriminated from compulsory admitted patients by higher illness severity scores. Assessment of unmet needs, satisfaction with care, quality of life, hedonic capacity, and social support constitute the factors that differentiate compulsory admitted patients and could be targets for interventions aimed to reduce the negative effects of compulsory admissions.

Aims Management of recent-onset schizophrenia (SZ) and schizoaffective disorder (SA) is challenging owing to frequent insufficient response to antipsychotic agents. This study aimed to test the efficacy and safety of the neurosteroid pregnenolone in patients with recent-onset SZ/SA. Methods Sixty out- and inpatients who met DSM-IV criteria for SZ/SA, with suboptimal response to antipsychotics were recruited for an 8-week, double-blind, randomized, placebo-controlled, two-center add-on trial, that was conducted between 2008 and 2011. Participants were randomized to receive either pregnenolone (50 mg/day) or placebo added on to antipsychotic medications. The primary outcome measures were the Positive and Negative Symptoms Scale and the Assessment of Negative Symptoms scores. Secondary outcomes included assessments of functioning, and side-effects. Results Analysis was by linear mixed model. Fifty-two participants (86.7%) completed the trial. Compared to placebo, adjunctive pregnenolone significantly reduced Positive and Negative Symptoms Scale negative symptom scores with moderate effect sizes (d = 0.79). Significant improvement was observed in weeks 6 and 8 of pregnenolone therapy among patients who were not treated with concomitant mood stabilizers (arms × visit × mood stabilizers; P = 0.010). Likewise, pregnenolone significantly reduced Assessment of Negative Symptoms scores compared to placebo (d = 0.57), especially on blunted affect, avolition and anhedonia domain scores. Other symptoms, functioning, and side-effects were not significantly affected by adjunctive pregnenolone. Antipsychotic agents, benzodiazepines and sex did not associate with pregnenolone augmentation. Pregnenolone was well tolerated. Conclusions Thus, add-on pregnenolone reduces the severity of negative symptoms in recent-onset schizophrenia and schizoaffective disorder, especially among patients who are not treated with concomitant mood stabilizers. Further studies are warranted.

Aims This study aimed to determine predictors for 10-year good versus poor perceived general quality of life (QOL) outcomes from baseline variables in people with schizophrenia and schizoaffective disorder. Methods We compared patients with poor versus good 10-year QOL outcomes using baseline clinical, personality-related variables, demographic and background characteristics. Logistic regression analysis was used for predicting the 10-year QOL outcomes from baseline data. One-hundred-eight patients completed the Quality-of-Life Enjoyment and Life Satisfaction Questionnaire, the Positive and Negative Syndromes Scale (PANSS), the Talbieh Brief Distress Inventory, and psychosocial questionnaires at baseline and 10 years later. Results Logistic regression revealed six predictors of QOL outcomes: paranoid ideations (odds ratio [OR] 3.1), PANSS general psychopathology (OR 1.1), obsessiveness (OR 0.84), hostility (OR 0.4), PANSS positive scale scores (OR 0.4), and general QOL index (OR 0.4). This model classified 80.6% of the sample with good sensitivity (87% correctly identified ‘poor outcome’), and specificity (71% correctly identified ‘good outcome’). Conclusion This study provides a pattern of baseline predictors for long-term QOL outcomes. Identified predictors are factors that can potentially be ameliorated, and thereby enhance the QOL of people with schizophrenia and schizoaffective disorder.

Innovations in DSM5 include dimensional diagnosis of schizophrenia (SZ) and other psychotic (OP) disorders using the symptom severity scale (SS-DSM5). We evaluated the psychometric properties and diagnostic validity of the SS-DSM5 scale using a cross-sectional design and an unselected convenience unselected sample of 314 inpatients and outpatients with SZ/OP and mood disorders who received standard care in routine clinical practice. The SS-DSM5 scale, the Clinical Global Impression-Severity scale (CGI-S), the Positive and Negative Syndrome Scale (PANSS), and the Bech-Rafaelsen Mania Scale (BRMS) were administered. Factor structure, reliability, internal consistency, convergent and diagnostic ability of the DSM5-SS were evaluated. Factor analysis indicated two latent factors underlying the SS-DSM5 (Psychotic and Deficit sub-scales). Cronbach's alpha was >0.70. Convergent validity of the SS-DSM5 was highly significant. Patients with SZ/PO disorders were correctly diagnosed (77.9%) using the SS-DSM5 scale (72% using PANSS). The agreement of the diagnostic decisions between the SS-DSM5 and PANSS was substantial for SZ/PO disorders (Kappa=0.75). Classifying participants with SZ/PO versus mood disorders using SS-DSM5 provided a sensitivity of 95%, and specificity of 34%. Thus, this study suggests that the SS-DSM5 has acceptable psychometric properties and that its use in clinical practice and research is feasible in clinical settings. The dimensional option for the diagnosis of schizophrenia and related disorders using SS-DSM5 is discussed.

This review provides the rationale and reports on the progress to date regarding the targeting of retinoid receptors for the treatment of schizophrenia and schizoaffective disorder and the role of retinoic acid in functions of the normal brain, and in psychotic states. After a brief introduction, we describe the normal function of retinoic acid in the brain. We then examine the evidence regarding retinoid dysregulation in schizophrenia. Finally, findings from two add-on clinical trials with a retinoid (bexarotene) are discussed. The authors of this review suggest that targeting retinoid receptors may be a novel approach to treat schizophrenia and schizoaffective disorder. Further studies are warranted.

To provide data on long-term health-related quality of life (HRQL) outcomes among patients with schizophrenia (SZ) and schizoaffective (SA) disorders and determine the predictive value of disorder-related factors. A total of 108 patients with SZ/SA were assessed during stabilization phase and over 10 years with the Quality of Life Enjoyment and Life Satisfaction Questionnaire (Q-LES-Q), Clinical Global Impression Scale, Positive and Negative Syndromes Scale (PANSS), Distress Scale for Adverse Symptoms (DSAS), Talbieh Brief Distress Inventory (TBDI), Brief Symptom Inventory-Somatization Scale (BSI-S), and Global Assessment of Functioning Scale (GAF). Variability and relationships between Q-LES-Q and disorder-related dimensions over time were analyzed. There were no differences in Q-LES-Q dimensions between patients with SZ and SA disorders. Poor outcomes were found among 76% of the patients with SZ/SA disorders who remained dissatisfied (64%) or worsened (12%) with their HRQL over time. However, 24% of patients reported improved quality of life (16%), or remained satisfied (8%). Changes in TBDI, DSAS, BSI-S, PANSS, and GAF measures accounted for 20–50% of the total variance in satisfaction changes in Q-LES-Q domains across time. Long-term quality of life outcomes are characterized by four different types that fit changes over time in emotional distress, side effects, somatization, symptom dimensions, and general functioning scores. Revealed predictors are factors that can be ameliorated and thereby enhance satisfaction with quality of life over time.

Neurosteroids such as dehydroepiandrosterone (DHEA), pregnenolone (PREG), and their sulfates (DHEAS and PREGS) display multiple effects on the central nervous system. Specifically, neurosteroids have various functions associated with neuroprotection, response to stress, mood regulation, and cognitive performance. In addition, neurosteroid levels are altered in stress-related neuropsychiatric disorders. This review focuses on the alterations of these neurosteroids in schizophrenia and on their association with clinical and neurocognitive manifestations. As described henceforth, findings from clinical studies have revealed that PREG, DHEA, and their sulfates might be involved in the pathophysiology of schizophrenia, and in some of its manifestations. Clinical trials for the evaluation of these neurosteroids face challenges in terms of experimental design, dosing strategy, data analysis, and interpretation. The review concludes with a list of suggested topics for future research. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Schizophrenia is a chronic, severe, and disabling brain disease. Today the neuroscience and clinical researches have advanced sufficiently to develop neuroprotective approach for discovery a novel generation of compounds with neuroprotective properties. However, the use of neuroprotective agents in schizophrenia is not yet well established. There are two main targets for neuroprotective therapy: (1) neurodegenerative processes in schizophrenia (e.g., apoptosis, excitotoxicity, oxidative stress, stress sensitization, neurotrophic factor expression, and alteration of neurosteroids); and (2) clinical, and behavioral presentations of illness including psychopathological symptoms, a significant decline in cognition, psychosocial functioning and in health related quality of life (HRQL) of patients. The HRQL deficit or impairment is a core feature of schizophrenia spectrum disorders. Based on the author’s and his team research contributions for last ten years, and complementary theoretical considerations, this paper presents the Distress/Protection Vulnerability Model of HRQL impairment in schizophrenia and related disorders. This model has reshaped our understanding of schizophrenia phenotype and will be essential useful for designing more effective clinical and neuroprotective trials.

Background While neurosteroids exert multiple effects in the central nervous system, their associations with neurocognitive deficits in schizophrenia are not yet fully understood. The purpose of this study was to identify the contribution of circulating levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), androstenedione, and cortisol to neurocognitive deficits through DHEA administration in schizophrenia. Methods Data regarding cognitive function, symptom severity, daily doses, side effects of antipsychotic agents and blood levels of DHEA, DHEAS, androstenedione and cortisol were collected among 55 schizophrenia patients in a double-blind, randomized, placebo-controlled, crossover trial with DHEA at three intervals: upon study entry, after 6 weeks of DHEA administration (200 mg/d), and after 6 weeks of a placebo period. Multiple regression analysis was applied for predicting sustained attention, memory, and executive function scores across three examinations controlling for clinical, treatment and background covariates. Results Findings indicated that circulating DHEAS and androstenedione levels are shown as positive predictors of cognitive functioning, while DHEA level as negative predictor. Overall, blood neurosteroid levels and their molar ratios accounted for 16.5% of the total variance in sustained attention, 8–13% in visual memory tasks, and about 12% in executive functions. In addition, effects of symptoms, illness duration, daily doses of antipsychotic agents, side effects, education, and age of onset accounted for variability in cognitive functioning in schizophrenia. Conclusions The present study suggests that alterations in circulating levels of neurosteroids and their molar ratios may reflect pathophysiological processes, which, at least partially, underlie cognitive dysfunction in schizophrenia.

Objective: Two questions were addressed in the present report: whether cognitive improvement would occur during 12-month ziprasidone treatment and whether the changes in cognitive functioning are dependent of changes in the illness-related variables. Methods: Seventy schizophrenia patients with persistent symptoms or troublesome side effects were assigned to a 12-month, open-label, flexible-dosage (40-160 mg/d) trial. Outcome measures were taken at baseline, 6, and 12 months and included the Mindstreams Computerized Cognitive Battery, the Wisconsin Card Sorting Test, the Clinical Global Impression Scale, the Positive and Negative Syndrome Scale, and the Extrapyramidal Symptom Rating Scale. Results: Baseline performance was impaired across all cognitive tasks on average without significant differences between 32 completers and 38 discontinued patients. At the end of the study, significant improvement in performance of executive functions, attention, and information processing domains among ziprasidone-completed patients was observed. The effect sizes for these changes were moderate (0.61). Improvement in the executive performances was associated with a reduction in the severity of positive, activation, and dysphoric mood symptoms but was unrelated to the ziprasidone daily dose, Clinical Global Impression Scale and Extrapyramidal Symptom Rating Scale scores, and concomitantly prescribed antidepressants, anxiolytics, mood stabilizers, or anti-parkinson drugs. Conclusions: Ziprasidone had a long-term neurocognitive effect among patients with chronic schizophrenia undergoing the usual care. This effect tended to increase over time and was associated, at least partly, with changes in symptoms, but not with changes in the severity of illness, side effects, the ziprasidone daily dose, and concomitant medicines. Abbreviations: CGI-S, Clinical Global Impression Scale, ESRS, Extrapyramidal Symptom Rating Scale, FGAs, first-generation antipsychotic agents, Mindstreams, Mindstreams Computerized Cognitive Battery, PANSS, Positive and Negative Syndromes Scale, SGAs, second-generation antipsychotic agents, WCST, Wisconsin Card Sorting Test.

Objectives:Bexarotene is a synthetic retinoid used for treat-ment of neoplastic or dermatologic disorders.Based on the retinoid dysregulation hypothesis, itwas hypothesized that bexarotene augmentationwould have a beneficial effect in the antipsychotictreatment of schizophrenia patients. This study isthe first to investigate the safety and efficacy ofadd-on oral bexarotene to ongoing antipsychotictreatment in chronic schizophrenia patientswho were stabilized on regular antipsychotictreatment.Methods:A 6-week open label trial was conducted in 2mental health centers from October 2005 toOctober 2006. Twenty-five patients with chronicschizophrenia received a low dose of bexarotene(75 mg/d) augmentation. Mental condition andlaboratory tests were assessed at baseline and afterweeks 2, 4, and 6 of the study. The primaryoutcome measure was change from baseline in 4symptom scales: the Positive and Negative Symp-tom Scale , Extrapyramidal Symptom Rating Scale,Abnormal Involuntary Movement Scale, andBarnes Akathisia Scale. Blood cell count, liver andthyroid functions, cholesterol, and triglyceriderates were followed.Results:Significant improvement from baseline to end-point was observed on total Positive and NegativeSymptom Scale score (P = 0.022), general psycho-pathology (P = 0.024), positive (P = 0.012), and thedysphoric mood (P = 0.028) factor scores. Further-more, a trend to a diminishing ExtrapyramidalSymptom Rating Scale score (P = 0.053) was found.Bexarotene was found to be a safe medication asmeasured by all laboratory parameters with theexception of increased total cholesterol serumlevel.Conclusions:This short-term pilot study supports bexarotene asa potential valuable adjunct in management ofschizophrenia. Low doses of bexarotene were welltolerated. A double-blind controlled study shouldbe performed to replicate these preliminary pos-itive results.Key Words: treatment-resistant schizophrenia,retinoids, bexarotene, negative symptoms

Objective This is a first report from a long-term study aimed to evaluate efficacy, safety, tolerability, cognitive functioning, and quality of life outcomes during ziprasidone treatment of chronic schizophrenia patients in the “real-world”. Method Seventy clinically unstable schizophrenia patients with persistent symptoms or troublesome side effects were assigned to a 12-month, open-label, flexible-dose (40–160 mg/day), large-scale, naturalistic trial. Outcome measures were taken at baseline, 6, and 12 months, and included the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI-S) scale, the Global Assessment of Functioning Scale (GAF) scores, treatment-emergent adverse events, body weight, and drug attitude. Results Thirty-two patients fully completed the study protocol. A discontinuation of treatment for any cause occurred in 54.3% of patients; the mean time until discontinuation was 4.4 ± 2.7 months. A discontinuation due to lack of clinical efficacy was more predominantly linked to patient perception (25.7%) than to physicians' conclusions alone (8.6%), adverse events (11.4%), and other reasons (8.6%). After controlling daily dose of ziprasidone, concomitant medications and sex, ANCOVA revealed improvement in PANSS factors, and global functioning among patients who had completed the study. Improvement in PANSS and GAF dimensions was evident at a 6-month visit, and it continued until the endpoint. When a cutoff of 20% improvement of PANSS total scores was used, the response rate among completers was 43.8%. Most common side effects were: fatigue, sleep disturbances, and headache. Ziprasidone did not appear to be linked to weight gain. Conclusion This study suggests that ziprasidone may be beneficial for long-term treatment of schizophrenia patients in terms of severity of symptoms, and general functioning. Ziprasidone is well tolerated during the long-term treatment of chronic schizophrenia patients undergoing usual care.

Objective Health related quality of life (HRQL) has become an important outcome measure in the treatment of psychiatric disorders. This long-term observational study examined ziprasidone-induced improvement in satisfaction with HRQL in schizophrenia patients treated under real-world conditions. Method Seventy schizophrenia patients with persistent symptoms or troublesome side effects were assigned to a 12-month, open-label, flexible-dose (40–160 mg/d), large-scale, naturalistic trial. Outcome measures were taken at baseline, 6, and 12 months, and included the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), severity of symptoms, distress, and side effects. Results Thirty-two patients fully completed the study protocol. Patients reported poorer general HRQL compared with healthy subjects. At the end of the study, significant improvement in general activity, and satisfaction with life was observed. The effect sizes for these changes were moderate (0.55, and 0.72, respectively). After Bonferroni correction for multiple comparisons improvement in satisfaction with general activity remained significant. No significant changes were noted in other Q-LES-Q dimensions. Improvement in general activity was associated with a reduction in the severity of symptoms and emotional distress, but was unrelated to the ziprasidone daily dose, side effect scores, and concomitantly prescribed antidepressants, anxiolytics, mood stabilizers, or antiparkinson drugs. Conclusion This study indicates that ziprasidone treatment resulted in the improvement of the satisfaction with general activity that tended to increase over time, from month 6 onwards. This effect was associated with reduction in the severity of clinical symptoms, and emotional distress.

Background The aim of this study was to see whether and how cognition deficit predicts quality of life impairments in schizophrenia patients. Method The Computerized Cambridge Automated Neuropsychological Test Battery, the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Quality of Life Scale (QLS) were used to assess 62 patients with chronic schizophrenia. Step-wise multiple regression analysis was used in order to determine cognitive variables that would predict the scores of each Q-LES-Q and QLS domain scores. Results Regression analysis revealed a significant association of the cognitive deficits with both general and domain-specific quality of life impairment measured with Q-LES-Q and QLS. Deficits in executive functions, visual sustained attention, memory and motor skills have been found to be valid predictors both before and after controlling for the severity of symptoms, emotional distress, side effects, age, education, and illness duration. Conclusions This study suggests that deficits in executive functioning, attention, memory and motor skills substantially contributes to predicting impairments across a wide range of HRQL domains, and, consequently, to quality of life appraisal in schizophrenia. Cognitive predictors cannot be attributed to illness-related and background variables. It can be concluded that, when aiming at the improvement of quality of life in schizophrenia patients, cognitive functioning should be targeted.

This study examines the contribution of various neurocognitive functions, clinical characteristics, and personality traits to the prediction of three insight dimensions. Clinically stable schizophrenia patients (n=107) residing in the community were evaluated using the Positive and Negative Syndrome Scale, the Scale for the Assessment of Unawareness of Mental Disorder, and a comprehensive battery of instruments to measure personality related variables and neurocognitive functioning. Step-wise multivariate regression analysis indicates significant association of variability in insight dimensions with neurocognitive functioning (20-41%), personality related traits (8-18% temperament factors, 4-7% self-constructs, 10-14% coping styles), severity of symptoms (about 7%), illness duration (6%), and education (about 5%). Poor insight was attributed to impairment in visual and movement skills, sustained attention, executive functions, intensity of autistic preoccupations and positive symptoms, as well as increased novelty seeking behavior, task and emotion oriented coping styles, better self-esteem, self-efficacy, and higher education. Better awareness was related to better performance of neurocognitive tasks, reward dependence behavior, avoidant coping style, and longer illness duration. Aside from common indicators for the various insight dimensions, we defined specific indicators for each insight dimension. Thus, insight dimensions in schizophrenia patients residing in the community were attributed to neurocognitive and personality related factors rather than to psychopathological symptoms. The findings enable better understanding of the multifactorial nature of insight and highlight targets for more effective intervention and rehabilitation.

Pregnenolone (PREG) and L-theanine (LT) have shown ameliorative effects on various schizophrenia symptoms. This is the first study to evaluate the efficacy and safety of augmentation of antipsychotic treatment among patients with chronic schizophrenia or schizoaffective disorder with PREG-LT.Double-blind, placebo-controlled trial of PREG-LT or placebo augmentation was conducted for eight weeks with 40 chronic DSM-IV schizophrenia and schizoaffective disorder patients with suboptimal response to antipsychotics. Oral PREG (50 mg/day) with LT (400 mg/day) or placebo were added to a stable regimen of antipsychotic medication from March 2011 to October 2013. The participants were rated using the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Scale for Anxiety (HAM-A), and the Positive and Negative Syndrome Scale (PANSS) scales bi-weekly. The decrease of SANS and HAM-A scores were the co-primary outcomes. Secondary outcomes included assessments of general functioning and side effects.Negative symptoms such as blunted affect, alogia, and anhedonia (SANS) were found to be significantly improved with moderate effect sizes among patients who received PREG-LT, in comparison with the placebo group. Add-on PREG-LT also significantly associated with a reduction of anxiety scores such as anxious mood, tension, and cardiovascular symptoms (HAM-A), and elevation of general functioning (GAF). Positive symptoms, antipsychotic agents, concomitant drugs, and illness duration did not associate significantly with effect of PREG-LT augmentation. PREG-LT was well-tolerated.Pregnenolone with L-theanine augmentation may offer a new therapeutic strategy for treatment of negative and anxiety symptoms in schizophrenia and schizoaffective disorder. Further studies are warranted.clinicaltrials.gov Identifier: NCT01831986.

Objective This study examined specific predictors of the efficacy of risperidone (RP), olanzapine (OL) and first-generation antipsychotic agents (FGAs), the role of confounding factors, and concomitant agents such as antidepressants, anxiolytics, and mood stabilizers in the treatment of health related quality of life (HRQL) impairment of schizophrenia patients. Method This was a community-based, open label, parallel group naturalistic study of 124 schizophrenia outpatients who received either RP, OL, FGA, or combined agents (CA). Evaluations were performed at baseline and 12 months later. They included the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Positive and Negative Syndrome Scale (PANSS), the Distress Scale for Adverse Symptoms, and inventories for the assessment of distress severity, subjective tolerability, and self-efficacy. Results OL was found to be superior to RP, FGAs and CA in terms of quality of life. FGAs revealed greater therapeutic benefit than RP, which was more beneficial than combined therapy. Improvement in Q-LES-Q was revealed in patients who received antidepressants and anxiolytics, but not mood stabilizers, or anti-Parkinson drugs. This effect was independent of treatment groups and gender. Regression models revealed that changes in emotional distress and side effects were common predictors for HRQL changes across treatment groups. Specific predictors of HRQL efficacy included self-efficacy for OL, negative and positive symptoms for RP, dysphoric mood and positive symptoms, daily doses and self-efficacy for FGA treated patients. Conclusion These findings suggest that OL is beneficial in the treatment of HRQL impairment in schizophrenia compared with RP, FGAs and CA. Special attention should be paid to specific predictors of HRQL efficacy for each antipsychotic agent, and to concomitant treatment with antidepressants and anxiolytics.

Background: Dehydroepiandrosterone (DHEA) augmentation has been reported, in a preliminary fashion, to be useful in the management of schizophrenia symptoms and side effects. In this study, the intention was to investigate the efficacy and safety of DHEA administration to ongoing antipsychotic medication in a multicenter, 12-week, double-blind, randomized, placebo-controlled, crossover trial. Methods: Fifty-five of 62 inpatients and outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia completed the trial. Patients were randomly allocated to 2 treatment groups receiving either DHEA (200 mg/d) or placebo for 6 weeks with the crossover between DHEA and placebo occurring after 6 weeks. Patients continued to receive their regular antipsychotic medication for the duration of the study. Results: Compared with placebo, DHEA administration did not produce significant improvement in clinical symptoms, side effects, and quality-of-life scores. However, 6 weeks of DHEA administration (but not placebo) was associated with a significant improvement in Positive and Negative Symptom Scale ratings compared with baseline. Furthermore, 6 weeks of DHEA treatment was associated with significant improvement in cognitive functions of visual sustained attention and visual and movement skills compared with placebo conditions. The DHEA augmentation was associated with elevations of serum concentrations of both DHEA and its sulfate ester. The DHEA treatment was well tolerated without any serious adverse effects. Conclusion: This short-term study does not support DHEA's value as an effective adjunct in the treatment of symptoms, side effects, and quality-of-life impairment in schizophrenia, while suggesting that DHEA improves sustained attention and visual and movement skills. A long-term, large-scale study with a broader dose range is warranted to further investigate DHEA's role in the management of schizophrenia.

This prospective study aimed to define the long-term changes in coping strategies used by schizophrenia patients and their relation to clinical and psychosocial factors. The Coping Inventory for Stressful Situations, psychiatric scales, and self-report questionnaires were administered to 148 schizophrenia patients at admission and 16 months thereafter. Based on trends of individual coping patterns to show change over time, four temporal coping types were distinguished: stable favorable and unfavorable, and becoming favorable and unfavorable. We found that coping patterns of 62.2% of patients remained stable over time, became unfavorable among 19.6% of patients, and became favorable among 18.2% of patients. Each temporal coping type is associated with a specific pattern of changes in clinical and psychosocial variables. The findings underscore the clinical relevance of temporal coping types and corroborate the appropriateness of focusing on aspects of coping behavior in treatment and rehabilitation of schizophrenia patients.

This study aimed to identify factors that influence changes in satisfaction with quality of life (QOL) of schizophrenia patients. Baseline and follow up data for 148 schizophrenia patients were obtained at hospital admission and 16 months later. Relationships between changes over time in the general QOL index, and various factors were investigated using factor, multiple regression, and partial correlation analyses. Findings indicate that baseline levels of activation symptoms, emotional distress, task oriented coping, self-esteem and friend support together explain 41% of the variability in the general QOL index 16 months later. Changes in the general QOL of schizophrenia patients over time is associated with anergia, and paranoid symptoms, emotional distress, side effects, self-esteem, emotion and avoidance related coping styles, expressed emotion, and other social support. Determinants of change in QOL of patients were different being in hospital or out of hospital in the real world. No significant association of age, education, and follow up duration, with general QOL. Based on obtained data three types of overlapping factors were defined: (1) distressing, and protective; (2) primary and secondary; and (3) factors that remained constant or changed over time. Presented data are discussed within the framework of the Distress/Protection model of QOL. The conceptualization of three types of factors influencing QOL outcomes in this model demonstrates their predictive value, and may assist investigators and mental health workers in the interpretation of QOL data that may be used to improve patients' QOL outcomes.

Objective: The goals of this study were to determine whether alterations in serum dehydroepiandrosterone (DHEA), its sulfated conjugate (DHEAS), androstenedione, testosterone, and progesterone concentrations occur in schizophrenia patients compared with healthy controls over two months, and their associations with psychopathology, emotional distress, and antipsychotic treatment. Method: Serum hormones were repeatedly determined for 21 antipsychotic-treated male DSM-IV schizophrenia patients and 14 healthy controls. Observations were at four time points: upon entry into the study, and after 2, 4 and 8 weeks. Results: In schizophrenia patients compared with healthy controls serum concentration of DHEA and androstenedione found increased, but that of DHEAS decreased, while progesterone and testosterone showed normal levels. Schizophrenia patients were also characterized by elevated androstenedione / DHEAS molar ratios, and reduced DHEAS / DHEA and testosterone / androstenedione molar ratios compared with healthy controls. Concentrations and molar ratios of serum hormones did not significantly change during the study either among schizophrenia patients, or healthy controls. Among patients alterations in DHEA, DHEAS and androstenedione were associated with emotional distress, anxiety, dysphoric mood, positive and activation symptoms, serum prolactin levels, but were not related to age, antipsychotic agents, and extrapyramidal side effects. Conclusions: Alterations in DHEA metabolism in schizophrenia are attributed to the distress, anxiety, severity of symptoms, prolactin levels, and may represent a marker for impaired hormonal responses to stress. These findings should be considered when evaluating the discrepancies in DHEA studies in schizophrenia.

Background The Mindstreams Computerized Cognitive Test Battery (Mindstreams) is a standardized computer-based battery that was designed for widespread clinical and research use. The capability of Mindstreams to test cognitive impairment in schizophrenia has yet to be evaluated. The aim of the present study was to determine the ability of Mindstreams in detecting cognitive dysfunction in schizophrenia patients and to compare it to the Cambridge Neuropsychological Test Automated Battery (CANTAB). Method Fifty-five schizophrenia patients and 63 healthy subjects were enrolled in the study. The Positive and Negative Syndrome Scale (PANSS) was used to quantify symptom severity. Neurocognitive functions were assessed using Mindstreams and CANTAB. Results The schizophrenia patients scored significantly more poorly than healthy subjects on all tests comprising the Mindstreams battery. Comparable tasks of the Mindstreams and CANTAB batteries significantly correlated on raw scores and the standardized cognitive indices. The Mindstreams executive function tasks had significant correlations with the PANSS negative, autistic preoccupation and activation cluster scores, and with global functioning. Two-week test–retest reliability correlations were all significant ( N = 17, p p Conclusions This study indicates that Mindstreams is reliable in assessing the cognitive function of patients with schizophrenia and may play a role in standardizing the cognitive assessment of these patients in clinical and research settings.

We sought to examine stability associations between family history and variability of schizophrenia symptoms repeatedly examined during a naturalistic follow-up study. The Positive and Negative Syndrome Scale, the Insight and Treatment Attitudes Questionnaire, and the Abnormal Involuntary Movement Scale were administered to 69 patients with familial and 79 patients with sporadic schizophrenia, at hospital admission and at stabilization stage (about 16 months later). Analysis of covariance was applied to identify the association of symptom factors with familiality of schizophrenia. We found that schizophrenia patients with positive family histories had significantly higher dysphoric, activation and negative factors. However, familiality of activation and negative factors were dependent on additional variables such as age of onset (both factors), baseline ratings, insight, and side effects (negative factor). No significant association of family history with intensity of positive and autistic preoccupation factors was found. Familial schizophrenia is characterized by higher severity of dysphoric mood factors that may represent impaired emotional reactivity. It is suggested that dysphoric mood may be a useful phenotype for molecular genetic studies of schizophrenia with positive family history.

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.

Dehydroepiandrosterone (DHEA) or their sulfate conjugate (DHEAS) (together abbreviated DHEA(S)) exert multiple effects in the central nervous system, and may be involved in the pathophysiological processes in schizophrenia. This prospective study aimed to investigate whether serum cortisol/DHEA(S) molar ratios are associated with response to antipsychotic treatment during the exacerbation of schizophrenia. Serum DHEA(S) and cortisol were determined at baseline, and 2 and 4 weeks later for 43 medicated schizophrenia inpatients with acute exacerbation. The patients were treated with stable doses of antipsychotic agents up to 2 weeks prior to entering the study and for the 4-week duration of the study after which they were classified as either responders or nonresponders to treatment. Findings suggest that responders had significantly higher serum cortisol levels and cortisol/DHEA(S) ratios compared with nonresponders. These differences remained significant at three time points controlling for gender, age, severity of symptoms and emotional distress, benzodiazepines, type or dosage of antipsychotic agents, and background variables. The logistic regression model shows advantages of both cortisol/DHEA(S) molar ratios vs serum cortisol and DHEA(S) concentrations for prediction of responsivity to antipsychotic treatment. No significant canonical correlations were observed between changes from baseline through end-of-study in hormonal values and severity of symptoms and emotional distress among responders and nonresponders. Thus, these data provide evidence that elevated serum cortisol and cortisol/DHEA(S) ratios may serve as markers of biological mechanisms that are involved in responsivity of schizophrenia patients to antipsychotic treatment.

Background Coping strategies play an important role in one's ability to adapt to stressful life conditions such as schizophrenia. To better understand the nature of various coping mechanisms at various stages in schizophrenia, this study examined task-, emotion-, and avoidance-oriented coping strategies and explored associated clinical factors at exacerbation and stabilization phases of the illness. Method Patients with schizophrenia were examined twice (at exacerbation phase, N = 237 and at stabilization phase, N = 148) with the Coping Inventory for Stressful Situations, and standardized measures of psychopathology and emotional distress severity, side effects, insight, self-constructs, social support, and quality of life. Multiple regression analysis was performed with coping strategies as dependent variables at exacerbation and stabilization including analysis of any change during the 16-month follow-up period. Results Analysis indicated that emotion coping strategies were used more at exacerbation than at stabilization phase. Regression analysis demonstrated emotional distress to be a strong predictor of emotion-oriented coping, with self-efficacy and social support being the best predictors of task and avoidance coping strategies, respectively. Individual changes in these variables also appear to be important predictors for fluctuations of these coping strategies over time. Severity of symptoms accounted for 3.5% and 5.5% to 9% of the total variance of emotion- and task-oriented coping strategies, respectively. Conclusions Emotion, task, and avoidance coping strategies and their predictors are influenced and may vary over the course of schizophrenia illness. Experienced emotional distress, self-efficacy, and social support are the best predictors of coping strategies both at exacerbation and stabilization phases of illness.

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.

Schizophrenia patients can be categorized into positive and negative syndromes (PS and NS) by the behavioral criteria of the Positive and Negative Syndrome Scale (PANSS), but these symptoms can also be evaluated as a continuous trait. Both types exhibit cerebral microcirculatory disorders, which are ameliorated by drug treatment in PS but not in NS patients. Red blood cell (RBC) aggregability plays a major role in the microcirculation. Previously reported changes in RBC membrane phospholipid composition indicate a difference in aggregability between RBCs of NS and PS patients. In this study the aggregability of PS RBCs and NS RBCs was analyzed using a computerized cell flow-properties analyzer, as a physiological marker of NS and PS. Results showed that while the aggregability of PS RBCs was normal, that of NS RBCs was markedly enhanced and strongly correlated with the NS score. The results exhibited stability and reproducibility over 1 to 8 weeks test-retest and were independent of gender, age at testing and onset of illness, fibrinogen levels, smoking, and current medication. NS RBCs have constitutively elevated aggregability, which can contribute to cerebral microcirculatory disorders and may be a biological marker for distinguishing between PS and NS in genetic studies of schizophrenia.

Background Knowledge is limited concerning somatic symptoms that cannot be accounted for by detectable somatic illness among schizophrenia patients. This study aimed to explore the prevalence, correlates, and predictors of somatization among schizophrenia patients. Method Initial data on all consecutively admitted adult patients with DSM-IV schizophrenia, schizoaffective disorder, major depressive disorder, or bipolar disorder were collected between August 1998 and August 2000. Standardized measures of psychopathology, somatization, emotional distress, adverse effects, insight, and stress process-related (psychosocial) variables were administered to 237 schizophrenia patients at admission and at least 12 months thereafter (N = 148). Partial correlation and multiple regression analyses were performed. Results The frequency of somatization, defined as the presentation of 5 or more medically unexplained somatic symptoms (Somatic Symptom Index-5), among the inpatient population (27%) did not change significantly after at least 12 months (30%; p =.61). Regression analysis showed that somatization scores were best predicted by the combination of scores for emotional distress attributed to psychopathology and side effects, expressed emotion, and insight. This combined model explains at least 40% of the variance in somatization scores. Self-esteem and social support showed negative association with somatization scores. Somatization scores were not associated with gender, age, education, age at onset, observed severity of psychopathology, subtype and duration of illness, number of admissions and treatment settings, or type and dose of antipsychotic agents. Conclusions Somatization is a prevalent problem among schizophrenia patients and is associated with emotional distress attributed to psychopathology, side effects of antipsychotic agents, and family members' attitudes toward schizophrenia patients. This study suggests that insight, self-esteem, and social support may protect against somatization in schizophrenia patients.

Peripheral-type benzodiazepine receptors (PBR) have been shown to be sensitive to stressful conditions. This study aimed to explore a possible association of platelets PBR binding with aggressive behavior and homicidal history in schizophrenia patients. The authors compared [(3)H] PK 11195 binding to platelet membrane among 11 currently aggressive schizophrenia patients, 15 schizophrenia patients with homicidal history, 14 nonaggressive schizophrenia patients, and 15 healthy volunteers. Subjects were assessed for aggressive behavior, psychopathology, anxiety, anger, and emotional distress using standardized instruments. We found that currently aggressive patients had significantly lower (-30%) platelet PBR density (B(max)), and scored significantly higher on hostility, anxiety, state anger, and emotional distress compared to homicidal and nonaggressive schizophrenia patients and healthy controls. Predominance of positive or negative symptoms, homicidal or suicidal attempt history, emotional distress levels, and conventional or atypical antipsychotic therapy is not associated with the expression of platelet PBR binding sites. Significant negative correlations emerged between PBR density and scores for aggressive behavior, hostility and anxiety. Thus, decreased platelet PBR density in aggressive schizophrenia patients is associated with higher scores for overt aggression, hostility and anxiety, but independent of illness subtype, homicidal and suicidal attempt history, distress level and type of antipsychotic treatment.

We sought to explore the relationships of three temperament factors with domain-specific subjective quality of life (QOL) of patients with schizophrenia. Ninety patients with schizophrenia were evaluated using the Quality of Life Enjoyment and Life Satisfaction Questionnaire, the Tridimensional Personality Questionnaire, the Positive and Negative Syndromes Scale, the Distress Scale for Adverse Symptoms, the Insight and Treatment Attitudes Questionnaire, the Insight Self-Report Scale, and standardized questionnaires for self-reported emotional distress and stress process-related variables. Predictors of domain-specific QOL were identified using multiple regression techniques. Temperament factors explain 6% to 16% of variability in QOL domain scores among patients with schizophrenia after controlling for the remaining variables (emotional distress, social support, self-esteem, avoidance coping, age, side effects, and depression). We found that higher levels of novelty seeking are associated with better general QOL, physical health, and more positive subjective feelings, whereas higher levels of reward dependence are related to better satisfaction from social relationships. Higher levels of harm avoidance are associated with poorer satisfaction with general activities, and medication. Thus, temperament factors, as assessed by the Tridimensional Personality Questionnaire, substantially influence satisfaction with life quality in schizophrenia. Novelty seeking, reward dependence, and harm avoidance are associated with different domains of QOL.

Background Improved quality of life (QOL) of patients suffering from major psychoses has become an important treatment goal. We sought to determine predictors of perceived QOL and to explore the changes that occur regarding QOL among individuals with schizophrenia as compared to patients with schizoaffective/mood disorders. Method In a naturalistic longitudinal design, 148 inpatients with schizophrenia and 51 inpatients with schizoaffective/mood disorders (DSM-IV) were tracked for 16 months (SD = 4.6 months). Subjects were assessed at 2 timepoints for psychopathology, stress process-related factors, and perceived QOL, as measured by the Quality of Life Enjoyment and Satisfaction Questionnaire. Predictors of fluctuations in QOL index scores during the follow-up period were identified using multiple regression techniques. Results We found that poor QOL is not a more severe problem for schizophrenia patients than for schizoaffective/mood disorder patients. Improved QOL of schizophrenia patients is associated with reduced paranoid and distress (obsessiveness, somatization) symptoms and increased self-efficacy and self-esteem ratings. Individual changes in QOL index scores among patients with schizoaffective/mood disorders are associated with changes in depression, sensitivity, expressed emotion, and task-oriented coping scores. Conclusion Predictors of changes in satisfaction with life quality over time among schizophrenia patients are distinct from those associated with schizoaffective/mood disorders. Changes in stress process-related factors, rather than psychopathology, predict change in perceived QOL and should be considered when evaluating QOL outcomes.

Schizophrenia is the most chronic and disabling of mental illnesses and it imposes a disproportionately large economic burden on society. In addition to symptom reduction and cost-effectiveness, quality of life is becoming a critical outcome measure for the efficacy of antipsychotic agents in the treatment of schizophrenia patients. This review concentrates on the influences of antipsychotic agents and their side effects on quality of life of schizophrenia patients. Of the 182 papers elicited in a comprehensive Medline search from 1996-2002, we found only 21 significant papers (11.5%) reporting findings concerning the effect of antipsychotic agents on quality of life of schizophrenia patients. Very few studies directly examined the impact of side effects on quality of life ratings of schizophrenia patients. To date, there is no clear evidence that in the long-term, atypical antipsychotics are more effective or are better tolerated than typical antipsychotics. This review suggests that side effects of antipsychotic agents influence subjective quality of life of schizophrenia patients significantly less than clinical and psychosocial factors. The patient's subjective response to side effects of medication is more predictive of quality of life than the number of those effects. We discuss both patients' and clinicians' perceptions of side effects and quality of life, which should be considered in the evaluation of the efficacy of antipsychotic agents.

Background: In 1999 Cardno et al reported that long CAG repeats in the calcium-activated potassium channel gene hSKCa3/KCNN3 are associated with higher negative symptom dimension scores in schizophrenia patients. There has been no attempt to replicate the results. In this study, we investigated whether a symptom polymorphism of schizophrenia is associated with both the CAG repeat numbers and the difference in allele sizes. Methods: We tested the association of CAG repeats with symptom models of schizophrenia in 117 unrelated Jewish patients. A multivariate analysis (MANOVA) of two models of schizophrenia with the repeat distribution and the difference in allele sizes was performed. Results: We found a significant positive association of the number of CAG repeats with negative syndrome, anergia, activation, and paranoid symptoms. In addition, nonparanoid schizophrenia patients who had differences in allele sizes were characterized by earlier onset of illness. Conclusions: The study supports the hypothesis that the combined effect of long CAG repeats and the differences in allele sizes contribute to symptom expression of schizophrenia, particularly on the anergia-activation-paranoid axis.

The increased rate of smoking in schizophrenia patients remains unexplained and may reflect attempts at self-treatment. The effect sought from smoking may be related to nicotine's stimulating action. We tested this hypothesis by examining the relationship between smoking status and finger tapping rate, a measure of central processing, in schizophrenia patients treated with atypical antipsychotics. Smokers showed significantly faster finger tapping rates than non-smokers. This was not related to clinical state, illness chronicity, medication side-effects, antipsychotic dose or plasma concentrations. Nicotine can improve central processing in medicated schizophrenia patients and this may constitute part of the incentive for smoking.

This study aimed to examine the effect of add-on treatment with the neurosteroid pregnenolone (PREG) on neurocognitive dysfunctions of patients with recent-onset schizophrenia (SZ) and schizoaffective disorder (SA).Sixty out- and inpatients that met DSM-IV criteria for SZ/SA were randomized to an 8-week, double-blind, randomized, placebo-controlled, 2-center trial. Participants received either pregnenolone (50 mg/d) or placebo added on to antipsychotic medications. Computerized Cambridge Automated Neuropsychological Test Battery measures were administered at baseline and after 4 and 8 weeks of treatment. ANOVA and paired t- or z-tests were applied to examine between- and within-group differences over time.Compared to placebo, adjunctive PREG significantly reduced the deficits in visual attention measured with the Matching to Sample Visual Search task (p=0.002), with moderate effect sizes (d=0.42). In addition, a significant improvement was observed from baseline to end-of-study with respect to the visual (p=0.008) and sustained attention (Rapid Visual Information Processing, p=0.038) deficits, and executive functions (Stockings of Cambridge, p=0.049; Spatial Working Memory, p0.001) among patients receiving PREG but not among those receiving placebo (all p's0.05). This beneficial effect of PREG was independent of the type of antipsychotic agents, gender, age, education, and illness duration.Pregnenolone augmentation demonstrated significant amelioration of the visual attention deficit in recent-onset SZ/SA. Long-term, large-scale studies are required to obtain greater statistical significance and more confident clinical generalization.

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.

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, P0.02; 1.96 versus 3.23, F = 4.17, P0.05, respectively). Similar results were obtained for severity of incidents (0.89 versus 3.58, F = 19.42, P0.0001; 2.89 versus 6.85, F = 10.11, P0.004, 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.

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.

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 current focus on identifying genes which predispose to psychiatric illness sharpens the need to identify environmental factors which interact with genetic predisposition and thus contribute to the multifactorial causation of these disorders. One such factor may be early parental loss (EPL). The putative relationship between early environmental stressors such as parental loss and psychopathology in adult life has intrigued psychiatrists for most of this century. We report a case control study in which rates of EPL, due to parental death or permanent separation before the age of 17 years were evaluated in patients with major depression (MD), bipolar disorder (BPD) and schizophrenia (SCZ), compared to individually matched, healthy control subjects (MD-Control, 79 pairs; BPD-Control, 79 pairs; SCZ-Control, 76 pairs). Loss of parent during childhood significantly increased the likelihood of developing MD during adult life (OR=3.8, P=0.001). The effect of loss due to permanent separation (P=0.008) was more striking than loss due to death, as was loss before the age of 9 years (OR=11.0, P=0.003) compared to later childhood and adolescence. The overall rate of EPL was also increased in BPD (OR=2.6, P=0.048) but there were no significant findings in any of the subcategories of loss. A significantly increased rate of EPL was observed in schizophrenia patients (OR=3.8, P=0.01), particularly before the age of 9 years (OR=4.3, P=0.01). Comparison of psychosocial, medical and clinical characteristics of subjects with and without a history of EPL, within the larger patient groups from which the matched samples were drawn (MD, n=136; BPD, n=107; SCZ, n=160), yielded few significant findings. Among the controls (n=170), however, subjects who had experienced EPL, reported lower incomes, had been divorced more frequently, were more likely to be living alone, were more likely to smoke or have smoked cigarettes and reported more physical illness (P=0.03-0.001). Long term neurobiological consequences of early environmental stressors such as maternal deprivation have been extensively studied in many animal species. Recently, enduring changes in hypothalamic-pituitary-adrenal axis function, including corticotrophin releasing factor gene expression, have received particular attention. Analogous processes may be implicated in the effect of EPL on human vulnerability to psychopathology, via alterations in responsiveness to stress. Genetic predisposition may influence the degree of susceptibility of the individual to the effects of early environmental stress and may also determine the psychopathological entity to which the individual is rendered vulnerable as a consequence of the stress.

Management of recent-onset schizophrenia (SZ) and schizoaffective disorder (SA) is challenging owing to frequent insufficient response to antipsychotic agents. This study aimed to test the efficacy and safety of the neurosteroid pregnenolone in patients with recent-onset SZ/SA.Sixty out- and inpatients who met DSM-IV criteria for SZ/SA, with suboptimal response to antipsychotics were recruited for an 8-week, double-blind, randomized, placebo-controlled, two-center add-on trial, that was conducted between 2008 and 2011. Participants were randomized to receive either pregnenolone (50 mg/day) or placebo added on to antipsychotic medications. The primary outcome measures were the Positive and Negative Symptoms Scale and the Assessment of Negative Symptoms scores. Secondary outcomes included assessments of functioning, and side-effects.Analysis was by linear mixed model. Fifty-two participants (86.7%) completed the trial. Compared to placebo, adjunctive pregnenolone significantly reduced Positive and Negative Symptoms Scale negative symptom scores with moderate effect sizes (d = 0.79). Significant improvement was observed in weeks 6 and 8 of pregnenolone therapy among patients who were not treated with concomitant mood stabilizers (arms × visit × mood stabilizers; P = 0.010). Likewise, pregnenolone significantly reduced Assessment of Negative Symptoms scores compared to placebo (d = 0.57), especially on blunted affect, avolition and anhedonia domain scores. Other symptoms, functioning, and side-effects were not significantly affected by adjunctive pregnenolone. Antipsychotic agents, benzodiazepines and sex did not associate with pregnenolone augmentation. Pregnenolone was well tolerated.Thus, add-on pregnenolone reduces the severity of negative symptoms in recent-onset schizophrenia and schizoaffective disorder, especially among patients who are not treated with concomitant mood stabilizers. Further studies are warranted.

This study aimed to determine predictors for 10-year good versus poor perceived general quality of life (QOL) outcomes from baseline variables in people with schizophrenia and schizoaffective disorder.We compared patients with poor versus good 10-year QOL outcomes using baseline clinical, personality-related variables, demographic and background characteristics. Logistic regression analysis was used for predicting the 10-year QOL outcomes from baseline data. One-hundred-eight patients completed the Quality-of-Life Enjoyment and Life Satisfaction Questionnaire, the Positive and Negative Syndromes Scale (PANSS), the Talbieh Brief Distress Inventory, and psychosocial questionnaires at baseline and 10 years later.Logistic regression revealed six predictors of QOL outcomes: paranoid ideations (odds ratio [OR] 3.1), PANSS general psychopathology (OR 1.1), obsessiveness (OR 0.84), hostility (OR 0.4), PANSS positive scale scores (OR 0.4), and general QOL index (OR 0.4). This model classified 80.6% of the sample with good sensitivity (87% correctly identified 'poor outcome'), and specificity (71% correctly identified 'good outcome').This study provides a pattern of baseline predictors for long-term QOL outcomes. Identified predictors are factors that can potentially be ameliorated, and thereby enhance the QOL of people with schizophrenia and schizoaffective disorder.

The goal of this study was to describe patterns of diagnosis and to explore the extent to which diagnosis changes during first-in-life psychiatric admissions. All 2,998 first admissions to Israeli psychiatric wards in 1989 were studied. Diagnosis did not change in at least 60% of the cases. Diagnoses in order of stability were: mental retardation (84%), substance abuse (82%), organic conditions (77.5%), neurotic (75%), schizophrenia (74%), personality disorders (73%), affective (68%), childhood (55%), paranoid (45%) and V-codes (22%). There was less change in diagnosis for patients over 45 (37.5%), than for patients aged 19–44 (43.2%) and 15–18 (57.8%). Diagnoses assigned at admission to first hospitalization are not likely to change during that hospitalization.

Pharmacologic actions to reduce neurotransmission through the D2 receptor have been the only proven therapeutic mechanism for schizophrenia (SZ) and schizoaffective (SA) disorder. However, in view of the multifactorial genesis and pathogenesis of these psychoses, it is unlikely that any antipsychotic drug would work equally well against all symptoms and behavioral disturbances. The absence of a single therapeutic target for SZ/SA disorder has prompted the use of polypharmacy strategies including multi-target pharmacotherapy, consisting of various add-on medications and supplements. Multi-target polypharmacy strategies include the off-label prescription of adjunctive agents such as antidepressants, mood stabilizers, and benzodiazepines already in use, and novel potential adjunctive agents (newer molecules or compounds) based on several non-dopaminergic hypotheses (serotonergic, noradrenergic, glutamatergic, gamma-aminobutyric acid related, and cholinergic neurotransmission, neuroprotective mechanisms and brain neuroplasticity). This chapter is an overview of the current state of evidence for the augmentation of antipsychotics with antidepressants, lithium, antiepileptic agents, benzodiazepines, and new molecules and compounds for the treatment of people with SZ/SA disorder with a special focus on research data published within the past 5–7 years. Using these agents for the augmentation of antipsychotics based on a multi-target drug treatment approach entails the combination of two or more drugs/agents with different mechanisms of action on the central nervous system in an attempt to enhance efficacy.