Predicting Predischarge Anhedonia Among Inpatients With Schizophrenia and Schizoaffective Disorders: A Large-scale Analysis.

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.

The characterization of social anhedonia and its correlates in schizophrenia and schizoaffective patients.

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.

Patients' satisfaction with hospital health care: Identifying indicators for people with severe mental disorder.

BACKGROUND: Patients' perception of psychiatric healthcare is a critical indicator in measuring service quality. The aim of the study was to determine patient's level of satisfaction with the quality of health care delivered at the inpatient departments, and to identify the service quality factors that were important to patients. METHOD: The Satisfaction with Psychiatry Care Questionnaire-22 was administered to 125 consecutive inpatients with schizophrenia or schizoaffective disorder in a stable condition. Sociodemographic and background variables, illness and symptom severity, insight, social anhedonia, self-esteem, perceived social support, and satisfaction with quality of life were collected. RESULTS: Although the participants generally expressed satisfaction with the inpatient services, they indicated that the weakest aspects of the service were in the domains of 'personal experience', 'information' and 'activity'. Women were significantly more dissatisfied than men with 'staff', 'care', and by general satisfaction. Multiple regression analysis revealed that satisfaction with hospital health care was associated with five indicators: insight, satisfaction with physical health, self-efficacy, family support, and social anhedonia. CONCLUSION: Personality related factors rather than psychopathological symptoms were associated with a satisfaction with care of admitted patients with severe mental illness. These factors could be targets for interventions aimed to improve treatment and hospital services.

Assessment of health needs, satisfaction with care, and quality of life in compulsorily admitted patients with severe mental disorders.

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.

Add-On Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01831986.

Adjunctive Pregnenolone Ameliorates the Cognitive Deficits in Recent-Onset Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: 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). METHOD: 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. RESULTS: 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, p<0.001) among patients receiving PREG but not among those receiving placebo (all p's>0.05). This beneficial effect of PREG was independent of the type of antipsychotic agents, gender, age, education, and illness duration. CONCLUSIONS: 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.

Targeting Retinoid Receptors to Treat Schizophrenia: Rationale and Progress to Date.

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.

Anhedonia of Patients with Schizophrenia and Schizoaffective Disorder is Attributed to Personality-Related Factors Rather than to State-Dependent Clinical Symptoms.

PURPOSE: The aim of the current study was to explore the concurrent attribution of illness- and personality-related variables to the levels of physical and social anhedonia in patients with schizophrenia (SZ) and schizoaffective disorder (SA). METHOD: Eighty-seven stable patients with SZ/SA were assessed using the revised Physical Anhedonia Scale (PAS) and the Social Anhedonia Scale (SAS) illness- and personality-related variables. Correlation and regression analyses were performed. RESULTS: Three subgroups of patients were stratified by level of hedonic functioning: 52.9% passed the PAS and SAS cut-off ("double anhedonics"), 14.9% the PAS cut-off and 18.4% the SAS cut-off ("hypohedonics"), and 13.8% did not reach the PAS or SAS cut-off ("normal hedonics"). Increased negative and emotional distress symptoms together with low levels of task-oriented and avoidance-coping styles, self-efficacy, and social support were significantly correlated with PAS/SAS scores. Multivariate regression analysis indicated that the contribution of illness-related predictors was 4.1% to the variance of PAS and 5.5% to SAS scores, whereas the contribution of personality-related predictors was 24.1% for PAS and 14.1% for SAS scores. The predictive value of negative symptoms did not reach significant levels. CONCLUSIONS: The hedonic functioning of SZ/SA patients is attributed to a number of personality-related factors rather than to state-dependent clinical symptoms. These findings enable better understanding of the multifactorial nature of anhedonia and might be of therapeutic relevance.

Ten-Year Quality-of-Life Outcomes of Patients with Schizophrenia and Schizoaffective Disorders: The Relationship with Unmet Needs for Care.

PURPOSE: The present study examined the relationship between unmet needs and current as well as long-term quality of life (QOL) of patients with schizophrenia (SZ) and schizoaffective (SA) disorders. METHODS: Ninety-five stable SZ/SA patients were evaluated using the Quality of Life Enjoyment and Life Satisfaction Questionnaire (Q-LES-Q), the Positive and Negative Syndrome Scale (PANSS), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Coping Inventory for Stressful Situations (CISS). At the 10-year evaluation participants also completed the Camberwell Assessment of Need scale. Correlation and multivariate regression analyses were performed. RESULTS: The number of unmet needs negatively correlated with Q-LES-Q domains; however, the predictive value for general quality of life did not reach significant levels controlling for MSPSS and CISS scores. Patterns of individual needs included assistance with psychological distress, daytime activities, welfare benefits, physical health, food, and intimate relationships, and emerged as significant predictors of current general QOL, even after controlling for PANSS, MSPSS, and CISS scores. Patients who had worsened and had dissatisfied courses of general QOL over time expressed many more unmet needs compared to those who were satisfied and had an improved course of QOL. Individual unmet needs concerning daytime activities, psychological distress, psychotic symptoms, information about treatment, company, and money were associated with worsened and dissatisfied general QOL outcomes. CONCLUSIONS: Unmet needs of SZ/SA patients show a strong relationship with prior long-term and current quality-of-life outcome. The pattern of individual unmet needs rather than the number of unmet needs had a greater predictive value for current subjective quality of life.

Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial.

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.

Predicting 10-year quality-of-life outcomes of patients with schizophrenia and schizoaffective disorders.

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.

Symptom severity scale of the DSM5 for schizophrenia, and other psychotic disorders: diagnostic validity and clinical feasibility.

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.

The retinoid X receptor agonist bexarotene relieves positive symptoms of schizophrenia: a 6-week, randomized, double-blind, placebo-controlled multicenter trial.

OBJECTIVE: The limitations of antipsychotic therapy in schizophrenia and schizoaffective disorder led to the investigation of the putative utility of pharmacologic augmentation strategies. The antitumor agent bexarotene via nuclear retinoid X receptor (RXR) activation might modulate numerous metabolic pathways involved in the pathogenesis of schizophrenia and schizoaffective disorder. This trial aimed to investigate efficacy and safety of add-on bexarotene to ongoing antipsychotic treatment of patients with schizophrenia or schizoaffective disorder. METHOD: Ninety inpatients and outpatients that met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder participated in a 6-week, double-blind, randomized, placebo-controlled multicenter study. Bexarotene (75 mg/d) was added to ongoing antipsychotic treatment from October 2008 to December 2010. The reduction in the severity of symptoms on the Positive and Negative Syndrome Scale (PANSS) was a primary outcome. Secondary outcomes included general functioning, quality of life, and side effect scales. RESULTS: Seventy-nine participants (88%) completed the protocol. Controlling for antipsychotic agents, a mixed model showed that patients who received adjunctive bexarotene had significantly lower PANSS positive scale scores compared to patients who received placebo (F = 8.6, P = .003; treatment arms × time, F = 2.7, P = .049), with moderate effect size (d = 0.48; 95% CI,0.04-0.93). Patients with mean or higher baseline PANSS positive scale scores and patients who did not take lipid-reducing agents revealed greater amelioration of positive symptoms (F = 7.4, P = .008). Other symptoms and secondary outcome measures were not affected by adjunctive bexarotene. Bexarotene was well tolerated, though 2 reversible side effects were reported: a significant increase in total cholesterol levels (P < .001) and a decrease in total thyroxine levels (P < .001). CONCLUSIONS: Bexarotene might potentially be a novel adjuvant therapeutic strategy for schizophrenia, particularly for the reduction of positive symptoms. The potential benefits and risks of ongoing administration of bexarotene warrant further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00535574.

Factor structure in the Camberwell Assessment of Need-Patient Version: the correlations with dimensions of illness, personality and quality of life of schizophrenia patients.

AIM: To investigate the factor structure underlying the Camberwell Assessment of Need-Patient Version (CANSAS-P) items in schizophrenia and schizoaffective disorder. METHOD: Factor, correlation and regression analyses were performed for dimensions of CANSAS-P, illness, personality and quality of life (QOL) related variables in 95 stabilized patients with chronic schizophrenia and schizoaffective disorder. RESULTS: Exploratory factor analysis revealed a four-factor model that explains 50.4% of the total variance of the 20 CANSAS-P items. The factors 'Social disability', 'Information processing disability', 'Emotional processing disability', and 'Coping disability' showed acceptable internal consistency (Cronbach's α coefficient 0.67-0.77). The CANSAS-P subscale scores positively correlated with severity of symptoms, distress (r ranged from 0.34 to 0.45), while negatively associated with general functioning (r = -0.34), friend (r = -0.46) and family support (r = -0.41), satisfaction with medicine (r = -0.35), general activities (r = -0.40), and general QOL (r = -0.35) (all P < 0.001). Severity of illness, symptoms, emotional distress and emotion-oriented coping were positive predictors; friend support, QOL general activities, life satisfaction and satisfaction with medicine were negative predictors of the CANSAS-P subscale scores. The effect size (f(2)) for these predictors ranged from medium to quite large (f(2) = 0.28-1.13), and they explain from 23% to 46% of the variability in CANSAS-P subscales. CONCLUSIONS: A four-factor structure mode, including social and cognitive functioning, emotion responsivity and coping with daily challenges, appears to fit CANSAS-P items. These subscales may contribute to research and improve treatment of psychiatric patients.

Ten-year quality of life outcomes among patients with schizophrenia and schizoaffective disorder II. Predictive value of psychosocial factors.

PURPOSE: To identify psychosocial predictors of change in health-related quality of life among patients with schizophrenia (SZ) and schizoaffective (SA) disorders over a 10-year period. METHODS: In a naturalistic longitudinal design, 108 patients with SZ/SA disorders completed a comprehensive rating scale battery including self-reported quality of life, emotional distress symptoms, coping styles, sense of self-efficacy, and social support, as well as observer-rated psychopathology, medication side effects, and general functioning at 2 time points, baseline and 10 years later. RESULTS: Regression models revealed that reduction in self-reported symptoms of depression, sensitivity or anxiety along with increase in self-efficacy, social support, and emotion-oriented coping scores predicted improvement in domain-specific perceived quality of life. Adjustment of the psychosocial models for the effects of disorder-related factors (psychopathology, functioning, and medication side effects) confirmed the above findings and amplified their statistical power. CONCLUSIONS: In the long-term course of severe mental disorders (SZ/SA), changes in the psychosocial factors are stronger predictors of subjective quality of life outcome than disorder-related changes. The findings enable better understanding of the combined effects of psychopathology and psychosocial factors on quality of life outcome over a 10-year period.

Ten-year quality of life outcomes among patients with schizophrenia and schizoaffective disorders: I. Predictive value of disorder-related factors.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Anhedonia is an important factor of health-related quality-of-life deficit in schizophrenia and schizoaffective disorder.

The aim of the current study was to investigate an association of physical and social hedonic deficits with health-related quality of life (HRQL), controlling for related distressing and protective factors. Eighty-seven stable patients with schizophrenia (SZ) and schizoaffective disorder (SA) were assessed using the revised Physical Anhedonia Scale (PAS) and the Social Anhedonia Scale (SAS), the Quality of Life Enjoyment and Life Satisfaction Questionnaire (Q-LES-Q), and related factors. Hedonic and HRQL deficit scores did not reach significant differences between SZ and SA patients. General and domain-specific Q-LES-Q scores were significantly correlated with PAS and SAS scores independent of the adverse effects and psychopathological symptoms. Dissatisfaction with HRQL increased from "normal hedonics" (4.8%) to "hypohedonics" (28.6%) and "double anhedonics" (66.7%). Permanently dissatisfied patients who revealed deterioration in general quality of life across 10 years had significantly higher PAS and SAS scores than did patients who were permanently satisfied and improved. An exploratory factor analysis yielded a three-factor solution; PAS and SAS scores were joined to the second factor together with Q-LES-Q, self-efficacy, coping styles, and social support scores. PAS scores accounted for 7% to 13% of the total variance in three domains and in the general quality-of-life alterations. SAS scores did not predict variability in the Q-LES-Q domains. Therefore, physical and social hedonic deficits significantly associated with poor HRQL independent of the adverse effects and psychopathological symptoms of SZ/SA. Physical anhedonia may be a predictor for quality-of-life deficit.

Serum levels of brain-derived neurotrophic factor and cortisol to sulfate of dehydroepiandrosterone molar ratio associated with clinical response to L-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients.

OBJECTIVES: L-Theanine (γ-glutamylethylamide) augmentation to antipsychotic therapy ameliorates positive, activation, and anxiety symptoms in schizophrenia and schizoaffective disorder patients. This study examines the association between circulating levels of neurochemical indicators and the beneficial clinical effects of L-theanine augmentation. METHODS: Serum levels of neurochemical indicators such as brain-derived neurotrophic factor (BDNF), dehydroepiandrosterone (DHEA), its sulfate (DHEAS), cortisol, cholesterol, and insulin were monitored in 40 schizophrenia and schizoaffective disorder patients during an 8-week, double-blind, randomized, placebo-controlled trial with L-theanine (400 mg/d). Multiple regression analysis was applied for searching association between improvement in symptom scores and changes in circulating levels of neurochemical indicators for an 8-week trial. RESULTS: Regression models among L-theanine-treated patients indicate that circulating levels of BDNF and cortisol-to-DHEAS*100 molar ratio were significantly associated with the beneficial clinical effects of L-theanine augmentation. Variability of serum BDNF levels accounted for 26.2% of the total variance in reduction of dysphoric mood and 38.2% in anxiety scores. In addition, the changes in cortisol-to-DHEAS*100 molar ratio accounted for 30% to 34% of the variance in activation factor and dysphoric mood scores and for 15.9% in anxiety scores. Regression models among placebo-treated patients did not reach significant level. CONCLUSIONS: These preliminary results indicate that circulating BDNF and cortisol-to-DHEAS*100 molar ratio may be involved in the beneficial clinical effects of L-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients.

L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study.

OBJECTIVE: L-theanine is a unique amino acid present almost exclusively in the tea plant. It possesses neuroprotective, mood-enhancing, and relaxation properties. This is a first study designed to evaluate the efficacy and tolerability of L-theanine augmentation of antipsychotic treatment of patients with chronic schizophrenia and schizoaffective disorder. METHOD: 60 patients with DSM-IV schizophrenia or schizoaffective disorder participated in an 8-week, double-blind, randomized, placebo-controlled study. 400 mg/d of L-theanine was added to ongoing antipsychotic treatment from February 2006 until October 2008. The outcome measures were the Positive and Negative Syndrome Scale (PANSS), the Hamilton Anxiety Rating Scale (HARS), the Cambridge Neuropsychological Test Automated Battery (CANTAB) for neurocognitive functioning, and additional measures of general functioning, side effects, and quality of life. RESULTS: 40 patients completed the study protocol. Compared with placebo, L-theanine augmentation was associated with reduction of anxiety (P = .015; measured by the HARS scale) and positive (P = .009) and general psychopathology (P < .001) scores (measured by the PANSS 3-dimensional model). According to the 5-dimension model of psychopathology, L-theanine produced significant reductions on PANSS positive (P = .004) and activation factor (P = .006) scores compared to placebo. The effect sizes (Cohen d) for these differences ranged from modest to moderate (0.09-0.39). PANSS negative and CANTAB task scores, general functioning, side effect, and quality of life measures were not affected by L-theanine augmentation. L-theanine was found to be a safe and well-tolerated medication. CONCLUSIONS: L-theanine augmentation of antipsychotic therapy can ameliorate positive, activation, and anxiety symptoms in schizophrenia and schizoaffective disorder patients. Further long-term studies of L-theanine are needed to substantiate the clinically significant benefits of L-theanine augmentation.

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

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