Late-onset psychosis and risedronate treatment for osteoporosis.

As women age and enter menopause, they are sometimes more susceptible than men to certain physical and mental disorders such as osteoporosis and late-onset schizophrenia. Risedronate (Actonel©) is a bisphosphonate used for the treatment of osteopenia. Early initiation of pharmacotherapy for osteopenia is recommended to prevent greater bone loss. The most common side effects of risedronate include fever and flu-like symptoms, hypocalcemia, bone and joint pain, peripheral edema, fatigue, change in bowel movements, osteonecrosis of the jaw, and atrial fibrillation. Though reports in the professional literature of psychotic reactions to risedronate are scant, there have been FDA reports as well as patient discussions of psychiatric side effects from this medication on popular websites. We report the case of M, age 59, who was treated with risedronate for osteoporosis, and was subsequently diagnosed with atypical psychosis after other organic causes were excluded. Though it is conceivable that age-related psychosocial and physical factors triggered late-onset schizophrenia, the temporal relationship between the termination of treatment with risedronate and the improvement in her mental state suggests that the risedronate might have triggered a psychotic reaction that resolved following cessation of treatment.

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.

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.

Neurocognitive effects of ziprasidone and related factors in patients with chronic schizophrenia undergoing usual care: a 12-month, open-label, flexible-dose, naturalistic observational trial.

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 antiparkinson 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.

Bexarotene as add-on to antipsychotic treatment in schizophrenia patients: a pilot open-label trial.

OBJECTIVES: Bexarotene is a synthetic retinoid used for treatment of neoplastic or dermatologic disorders. Based on the retinoid dysregulation hypothesis, it was hypothesized that bexarotene augmentation would have a beneficial effect in the antipsychotic treatment of schizophrenia patients. This study is the first to investigate the safety and efficacy of add-on oral bexarotene to ongoing antipsychotic treatment in chronic schizophrenia patients who were stabilized on regular antipsychotic treatment. METHODS: A 6-week open label trial was conducted in 2 mental health centers from October 2005 to October 2006. Twenty-five patients with chronic schizophrenia received a low dose of bexarotene (75 mg/d) augmentation. Mental condition and laboratory tests were assessed at baseline and after weeks 2, 4, and 6 of the study. The primary outcome measure was change from baseline in 4 symptom scales: the Positive and Negative Symptom Scale, Extrapyramidal Symptom Rating Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Scale. Blood cell count, liver and thyroid functions, cholesterol, and triglyceride rates were followed. RESULTS: Significant improvement from baseline to endpoint was observed on total Positive and Negative Symptom Scale score (P = 0.022), general psychopathology (P = 0.024), positive (P = 0.012), and the dysphoric mood (P = 0.028) factor scores. Furthermore, a trend to a diminishing Extrapyramidal Symptom Rating Scale score (P = 0.053) was found. Bexarotene was found to be a safe medication as measured by all laboratory parameters with the exception of increased total cholesterol serum level. CONCLUSIONS: This short-term pilot study supports bexarotene as a potential valuable adjunct in management of schizophrenia. Low doses of bexarotene were well tolerated. A double-blind controlled study should be performed to replicate these preliminary positive results.

The effectiveness of ziprasidone in treating impaired quality of life in schizophrenia: a 12-month, open-label, flexible-dose, naturalistic observational study of 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.

Effectiveness, safety, and tolerability of ziprasidone for treating schizophrenia patients undergoing usual care: a 12-month, open-label, flexible-dose, naturalistic observational trial.

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.

Positive family history is associated with persistent elevated emotional distress in schizophrenia: evidence from a 16-month follow-up study.

There is some evidence that emotional reactivity to daily life stress is related to a genetic or familial liability to develop schizophrenia. However, it is unclear whether the emotional distress is elevated in schizophrenia patients with positive compared to negative family history. The aim of the study was to test the hypothesis that a persistent higher level of emotional distress in schizophrenia subjects is associated with a positive family history of schizophrenia. This study used the Talbieh Brief Distress Inventory (TBDI), the Positive and Negative Syndrome Scale (PANSS; including dysphoric mood, positive and negative subscales), Montgomery-Asberg Depression Rating Scale (MADRS), and the Distress Scale for Adverse Symptoms (DSAS) to investigate the difference in the magnitude of emotional distress scores between schizophrenia subjects with and without a positive family history of schizophrenia over time. Data were recorded for 69 multiplex family and 79 singleton patients at admission and about 16 months thereafter. No between-group differences were obtained in PANSS and DSAS scores. With regard to the TBDI: (a) both group of patients had no significant differences in emotional distress scores at admission; (b) patients with negative family history reported improvement in distress severity and depression severity (MADRS) 16 months after admission, while those with positive family history experienced persistent elevated emotional distress, mainly, on obsessiveness, and depression subscales; and (c) both groups of patients are characterized by elevated emotional distress at follow-up examination compared to healthy subjects. Thus, it appears that there is a strong association between positive family history and persistent elevated emotional distress. Because patients with positive and negative family history are likely to differ in genetic risk, our results suggest that long-term elevated levels of emotional distress may be related to a familial (environmental)/genetic vulnerability to schizophrenia.

State and trait related predictors of serum cortisol to DHEA(S) molar ratios and hormone concentrations in schizophrenia patients.

OBJECTIVE: In previous studies we have demonstrated high serum molar ratios of cortisol to dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) [together abbreviated DHEA(S)], and the value of both cortisol/DHEA(S) molar ratios for prediction of responsivity to antipsychotic treatment in schizophrenia patients. The present study aimed to examine the contribution of anxiety, and severity of symptoms to the prediction of serum cortisol, DHEA(S) levels and two molar ratios across three examinations. METHOD: Serum concentrations of cortisol and DHEA(S)were examined in 43 schizophrenia inpatients and in 20 age matched healthy controls at baseline, and after 2 and 4 weeks. The Positive and Negative Symptom Scale and the State-Trait Anxiety Inventory scores were used as independent variables for multiple regression analysis. RESULTS: Despite clinical improvement during the study period cortisol/DHEA(S) molar ratios were found persistently elevated as compared to healthy controls. Multiple regression analysis revealed that across three examinations cortisol/DHEA(S) molar ratios negatively associated with trait-anxiety (partial R(2)=7-14%) rather than with negative symptoms (partial R(2)=3-6%). Age and age of onset account for 12.7% for variability of cortisol/DHEAS ratio. Serum cortisol concentrations are predicted by trait and state-anxiety, activation symptoms and daily doses of antipsychotics. A small portion of variability in serum DHEA levels (R(2)=9%) is associated with symptom severity, while DHEAS levels were predicted by age at examination and age of onset. CONCLUSION: Elevated serum cortisol/DHEA(S) molar ratios were attributed to trait-anxiety and age rather than to clinical symptoms. The findings may indicate persistent dysfunction of the hypothalamic-pituitary-adrenal axis that is independent of the patients' clinical state.

Differences in blood pregnenolone and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects.

BACKGROUND AND OBJECTIVE: Contradictory and confusing reports on serum dehydroepiandrosterone (DHEA) levels in schizophrenia led us to compare the serum concentration of its precursor, pregnenolone (PREG), between medicated schizophrenia patients and healthy subjects. The neurosteroid levels were monitored for two months and the relationship of these neurosteroids with schizophrenic symptomatology, emotional distress, and anxiety was examined. METHOD: We determined blood levels of PREG, and DHEA in 15 schizophrenia patients and 12 healthy controls at four time points: at the start of the study, after 2, 4 and 8 weeks. Analysis of covariance and canonical correlations across four time points were applied. RESULTS: Controlling for age, serum concentrations of PREG were lower, while the DHEA level and the molar ratio values of DHEA/PREG were higher in schizophrenia patients compared to healthy controls. Both levels of PREG and DHEA and their molar ratio did not change significantly during the study's period either among schizophrenia patients or healthy controls. The blood levels of PREG appear to be associated with trait-anxiety scores in the schizophrenia patients, while associations of clinical symptoms with two neurosteroids did not reach a significant level when the confounding effect of emotional distress, and anxiety scores was controlled. CONCLUSION: Low serum pregnenolone concentrations in schizophrenia appear to be associated with trait-anxiety scores independent of symptoms. Further research into the role of pregnenolone in schizophrenia is warranted.

Coping patterns as a valid presentation of the diversity of coping responses in schizophrenia patients.

This study aimed to identify coping patterns used by schizophrenia inpatients in comparison with those used by healthy individuals, and to explore their association with selected clinical and psychosocial variables. The Coping Inventory for Stressful Situations (CISS) was used to assess coping strategies among 237 inpatients who met DSM-IV criteria for schizophrenia and 175 healthy individuals. Severity of psychopathology and distress, insight into illness, feelings of self-efficacy and self-esteem (self-construct variables), social support, and quality of life were also examined. Factor analysis, analysis of covariance and correlations were used to examine the relationships between the parameters of interest. Using dimensional measures, we found that emotion-oriented coping style and emotional distress were significantly higher in the schizophrenia group, whereas the task-oriented coping style, self-efficacy, perceived social support and satisfaction with quality of life were lower compared with controls. When eight CISS coping patterns were defined, the results revealed that patients used emotion coping patterns 5.5 times more frequently, and task and task-avoidance coping patterns significantly less often than healthy subjects. Coping patterns have different associations with current levels of dysphoric mood and emotional distress, self-construct variables, and satisfaction with quality of life. Thus, the identified coping patterns may be an additional useful presentation of the diversity of coping strategies used by schizophrenia patients. Coping patterns may be considered an important source of knowledge for patients who struggle with the illness and for mental health professionals who work with schizophrenia patients.

Improvement of sustained attention and visual and movement skills, but not clinical symptoms, after dehydroepiandrosterone augmentation in schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial.

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.

The effectiveness and predictors of response to antipsychotic agents to treat impaired quality of life in schizophrenia: A 12-month naturalistic follow-up study with implications for confounding factors, antidepressants, anxiolytics, and mood stabilizers.

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.

Determinants of changes in perceived quality of life in the course of schizophrenia.

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.

Validity of an abbreviated quality of life enjoyment and satisfaction questionnaire (Q-LES-Q-18) for schizophrenia, schizoaffective, and mood disorder patients.

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

Familiality in a five-factor model of schizophrenia psychopathology: findings from a 16-month follow-up study.

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.

Longitudinal assessment of coping abilities at exacerbation and stabilization in schizophrenia.

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.

Condensed version of the Quality of Life Scale for schizophrenia for use in outcome studies.

The Quality of Life Scale (QLS(21)) is widely used in clinical trials involving schizophrenia patients. This study aimed to identify a core subset of QLS(21) items that maintains the validity and psychometric properties of the complete version. A parsimonious subset of items from the QLS(21) that can accurately predict the total scale score was sought and evaluated in 133 schizophrenia patients, using the heuristic algorithm for a regression model. Two additional data sets were used for model validation: a subset of 124 patients who participated in the model construction and who completed the QLS(21) 1 year later as well as a new sample of 40 inpatients. Patients were examined with the Positive and Negative Syndrome Scale (PANSS), the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Talbieh Brief Distress Inventory (TBDI), the Extrapyramidal Symptom Rating Scale (ESRS) and the Global Assessment of Functioning Scale (GAF). Using only five QLS items (social initiatives, adequacy, acquaintances, motivation, and time utilization; QLS(5)) as predictors, the correlation was 0.9805 between the predicted and true QLS totals. Two validation samples confirmed this finding. Additional analyses indicate that the QLS(5) exhibited similar performance to the QLS(21) regarding construct validity, test-retest reliability and responsiveness to changes over time. Thus, the five-item condensed Quality of Life Scale for schizophrenia maintains the validity of the full QLS, and has the advantage of shorter administration time. Utilization of the revised QLS(5) in routine care and clinical trials may potentially facilitate evaluation of treatment outcomes in schizophrenia.

Cortisol/dehydroepiandrosterone ratio and responses to antipsychotic treatment in schizophrenia.

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.