Michael S. Ritsner

Predicting quality of life impairment in chronic schizophrenia from cognitive variables

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.

Predicting domain-specific insight of schizophrenia patients from symptomatology, multiple neurocognitive functions, and personality related traits

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.

Improvement of aggressive behavior and quality of life impairment following S-Adenosyl-Methionine (SAM-e) augmentation in schizophrenia

S-adenosyl-methionine (SAM-e), functions as a primary methyl group donor for several metabolic compounds. Since SAM-e is involved in several metabolic processes, its administration may have a role in the amelioration of several disorders. In addition, SAM-e increases catechol-O-methyltransferase (COMT) enzyme activity, which may ameliorate aggressive symptoms in certain patients. We have therefore investigated the efficacy of SAM-e in managing schizophrenia symptomatology in patients with the low activity COMT polymorphism. Eighteen patients with chronic schizophrenia were randomly assigned to receive either SAM-e (800 mg) or placebo for 8 weeks in double-blind fashion. Results indicated some reduction in aggressive behavior and improved quality of life following SAM-e administration. Female patients showed improvement of depressive symptoms. Clinical improvement did not correlate with serum SAM-e levels. Two patients receiving SAM-e exhibited some exacerbation of irritability. This preliminary pilot short-term study cautiously supports SAM-e as an adjunct in management of aggressive behavior and quality of life impairment in schizophrenia.

The detection of neurocognitive decline in schizophrenia using the Mindstreams Computerized Cognitive Test Battery

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<0.05-p<0.001). 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.

Pregnenolone, dehydroepiandrosterone, and schizophrenia: alterations and clinical trials.

Neurosteroids, such as pregnenolone (PREG), dehydroepiandrosterone (DHEA), and their sulfates (PREGS and DHEAS) are reported to have a modulatory effect on neuronal excitability and synaptic plasticity. They also have many other functions associated with neuroprotection, response to stress, mood regulation, and cognitive performance. Furthermore, these neurosteroids have been linked to, and their levels are altered in, neuropsychiatric disorders. This review highlights what is currently known about the metabolism and mode of action of PREG and DHEA, as well as about alterations of these neurosteroids in schizophrenia. This review also provides substantial information about clinical trials with DHEA and PREG augmentation with of antipsychotic agents in schizophrenia.

Neurocognitive deficits in schizophrenia are associated with alterations in blood levels of neurosteroids: a multiple regression analysis of findings from a double-blind, randomized, placebo-controlled, crossover trial with DHEA.

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 6weeks of DHEA administration (200mg/d), and after 6weeks 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.

Where Do We Stand in the Quest for Neuropsychiatric Biomarkers and Endophenotypes and What Next

Although biomarker science is a field that is advancing rapidly in medicine as a whole, neurop-sychiatric disorders are still characterized by an absence of the biomarkers and laboratory tests that will promote new diagnostic and prognostic procedures. Recent advances in genomic, genetic, epige-netic, neuroscience, proteomic and metabolomic knowledge and technologies have opened the way to searching for biomarkers, however, it is still a relatively new field for neuropsychiatry. In addition, candidate endophenotypes, important trait markers widely used for genetic studies, are useful for the development of heritable diagnostic and prognostic biomarkers (endo-phenotype strategy). This chapter provides definitions of biomarkers and endophenotypes, elucidating their types and properties that will make them useful in neuropsychiatric research and practice. Recent results in the schizophrenia and mood disorders literature that illustrate the usefulness of biomarkers and endo-phenotypes are also reviewed. We predict that both biomarker and endophenotypic approaches will open new avenues for practically important applications of genetics, neuroscience and “omics” advantages in neuropsychiatry.

Quality of life impairment syndrome in schizophrenia

Patients with schizophrenia exhibit an exceedingly wide range of symptoms, and a broad spectrum of cognitive impairments. In addition, it has become increasingly apparent that the disorder is, to variable degrees, accompanied by quality of life impairments. This chapter addresses the question of whether the health-related quality of life (HRQL) impairment or deficit is a syndrome in schizophrenia. Therefore, first, we discuss what the general and domain-specific HRQL impairments are. Then, we address distressing and protective factors, and a factor structure of HRQL impairment. The literature, as well as new and previously published findings from the Shaar Menashe Longitudinal Study of Quality of Life will be presented in detail.

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.

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

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.