Regional differences in expression of β-tubulin isoforms in schizophrenia

A growing body of evidence suggests that abnormal elements of the cytoskeleton may be associated with the pathophysiology of schizophrenia. Isoforms of a major cytoskeleton protein, β-tubulin, were recently demonstrated to have distinct roles in neuronal differentiation and cell viability. For these reasons, we tested the hypothesis that there are differences in the expression of β-tubulin isoforms (βI-βIV) in the brain in schizophrenia, using western blot analysis in an elderly group of subjects with this illness and a control group. We found that βI-tubulin protein expression was decreased in the anterior cingulate cortex and increased in the dorsolateral prefrontal cortex, but not changed in superior temporal gyrus or hippocampus in schizophrenia. Our data supports the growing body of evidence suggesting abnormalities of the cytoskeleton in schizophrenia.     

GSK-3β in cerebrospinal fluid of schizophrenia patients

Summary. Cerebrospinal fluid contains proteins and metabolites of brain origin and was extensively studied in psychiatry in the 1970s with few definitive results. We have recently found 40% reduced protein levels of GSK-3 in schizophrenia in postmortem prefrontal cortex, but our attempt to develop a diagnostic marker using peripheral lymphocyte GSK-3 was not successful. In this study we aimed to find whether the reduction in brain GSK-3 is reflected in CSF of schizophrenia patients. We report a significant reduction in CSF GSK-3 protein levels in six schizophrenia patients compared to seventeen healthy subjects. Our results corroborate other studies in which CSF protein levels reflect the alteration found in these proteins in schizophrenia patients postmortem brain.     

What aspects of emotional functioning are impaired in schizophrenia?

Disturbances in emotional functioning are a major cause of persistent functional disability in schizophrenia. However, it is not clear what specific aspects of emotional functioning are impaired. Some studies have indicated diminished experience of positive affect in individuals with schizophrenia, while others have not. The current study assessed emotional responses by 34 individuals with schizophrenia and 35 demographically matched healthy participants to 131 images sampling a wide range of emotional arousal and valence levels. Ratings of affective response elicited by individual images were highly correlated across the groups (r's>.90), indicating similar emotional experiences at the moment of stimulus exposure. However, the data did not indicate strong relationships between ratings of the emotional impact of the images and most measures of day-to-day emotional processing. These results demonstrate that individuals with schizophrenia report "normal" emotional responses to emotional stimuli, and thus suggests that deficits in emotional functioning associated with the disorder are likely to occur further downstream, and involve the effective integration of emotion and cognition for adaptive functioning in areas such as goal-setting, motivation, and memory.     

Does unwantedness of pregnancy predict schizophrenia in the offspring?

BACKGROUND: We sought to replicate (or refute) a previous report of an association between unwantedness of a pregnancy and the risk of schizophrenia in the offspring. METHOD: The study was conducted using a large, prospectively collected birth cohort as part of the Prenatal Determinants of Schizophrenia study (PDS). Attitude toward the pregnancy was assessed at the time of the mother's first visit to the prenatal clinic. Cases of schizophrenia and other schizophrenia spectrum disorders in the offspring of these mothers were subsequently ascertained and diagnosed. In univariate and multivariate analyses, we examined the relationship between attitude toward the pregnancy and risk of adult schizophrenia and other schizophrenia spectrum disorders. RESULTS: The unadjusted hazard ratio for the association between ambivalent or negative maternal attitude toward the pregnancy and the risk of schizophrenia spectrum disorders was 1.75, (95% CI=0.97, 3.17, P=0.06). This result was unchanged after adjustment for social class, paternal age, race/ethnicity and other potential confounders. Similar results were observed when only cases with schizophrenia were included in the analysis. CONCLUSIONS: We did not find a statistically significant association in favor of the hypothesis that unwantedness of pregnancy is a risk factor for adult schizophrenia. On the other hand, the magnitude of the observed association was similar to the findings of the only previous study of this question and the confidence limits overlap those findings. Whether unwantedness of pregnancy is a risk factor for adult schizophrenia remains an open question that may be resolved by future research.     

Impairment of sleep-related memory consolidation in schizophrenia: relevance of sleep spindles?

ObjectivesDeficits in declarative memory performance are among the most severe neuropsychological impairments in schizophrenia and contribute to poor clinical outcomes. The importance of sleep for brain plasticity and memory consolidation is widely accepted, and sleep spindles seem to play an important role in these processes. The aim of this study was to test the associations of sleep spindles and picture memory consolidation in patients with schizophrenia and healthy controls.MethodsWe studied 16 patients with schizophrenia on stable antipsychotic medication (mean age ± standard deviation, 29.4 ± 6.4 years) and 16 healthy controls matched for age and educational level. Sleep was recorded and scored according to American Academy of Sleep Medicine (AASM) standard criteria. We performed a picture recognition paradigm and compared recognition performance for neutral and emotional pictures in sleep and wake conditions.ResultsRecognition accuracy was better in healthy controls than in patients with schizophrenia in the sleep and wake conditions. However, the memory-promoting effect of sleep was significantly lower in schizophrenia patients than in controls. Sleep spindle activity was reduced in patients, and sleep spindle density was correlated with sleep-associated facilitation of recognition accuracy for neutral pictures.ConclusionReduced sleep spindles seem to play an important role as a possible mechanism or biomarker for impaired sleep-related memory consolidation in patients with schizophrenia, and are a new target for treatment to improve memory functions and clinical outcomes in these patients.     

Lack of false recognition in schizophrenia: a consequence of poor memory?

The tendency to falsely recognize items as ones previously presented is increased in patients with frontal lesions and in older participants, whereas patients with medial temporal lobe damage may display such poor memory that they are not especially susceptible to false recognition. Since patients with schizophrenia are often compared to these groups neurocognitively, we explored the extent to which they are more susceptible to false memory. Participants were presented with word lists along a semantic theme, such as "bread". After list presentation, recognition tasks were administered which contained both the studied words as well as unstudied words. Some of the unstudied words were related to the theme of the previously studied words, but never actually presented (e.g. semantic "lures"). In a separate test, free recall of these lists of words was assessed. Interestingly, it was control participants who made more errors at recall, and were especially susceptible to intrusions of the semantic lures. Patients with schizophrenia did not make more false recognition errors in general, and surprisingly they made disproportionately fewer false recognition errors to semantic lures specifically. We conclude that despite poor memory, patients with schizophrenia are not especially susceptible to interference from previous tasks and are not particularly prone to false recollections.     

Clinical effects of COX–2 inhibitors on cognition in schizophrenia

An activation of pro–inflammatory cytokines in the central nervous system is associated with cognitive disturbances. This process is mediated by prostaglandins and cyclo–oxygenase–2 (COX–2). COX–2 inhibitors have been suggested to show beneficial effects in disorders associated with cognitive disturbance, although clinical effects on cognition have not been shown until today. Data from a schizophrenia study were reevaluated under the aspect whether an effect on the positive and negative syndrome scale (PANSS) factor cognition can be observed during therapy with the COX–2 inhibitor celecoxib add on to risperidone in comparison to riperidone alone. Beside the effect on the PANSS total score, the effect on the cognition factor was the most pronounced using the analysis of covariance compared to all other factors of the PANSS (p <0.06). Although suggestions of basic research led to an expected therapeutic effect of COX–2 inhibitors on cognition, this effect could not yet be shown clinically. In schizophrenia, the effect on cognition contributes to the therapeutic effect of COX–2 inhibitors.     

Is emotion processing a predictor of functional outcome in schizophrenia?

Deficits in the ability to perceive facial and vocal emotion expression are common in schizophrenia. However, relatively little is known about how such deficits might affect functional outcomes. This prospective study examined cross-sectional and longitudinal relationships between perception of emotion and aspects of psychosocial functioning, including family relationships, social relationships, work functioning, and independent living/self-care in 94 clinically stabilized schizophrenia outpatients from five community-based rehabilitation programs. Emotion perception (facial emotion, voice emotion, and affect perception) and psychosocial outcome (Strauss and Carpenter Outcome Scale and Role Functioning Scale) were assessed at baseline and after 12 months of psychosocial rehabilitation. Significant associations were found between perception of emotion and work functioning/independent living both cross-sectionally and prospectively over the 12 months. Causal explanatory models suggested that perception of emotion might cause work functioning/independent living outcome over 1 year. The results remained significant when conceptual disorganization was statistically controlled. We did not find differences between men and women in the correlations between emotion perception and work functioning/independent living. Associations between social functioning/family relationships and perception of emotion were not significant. These findings suggest that emotion processing is a key determinant of work functioning/independent living for individuals with serious mental illness.     

Can verbalization remedy the theory of mind deficit in schizophrenia?

Several studies provide convincing evidence of a specific deficit in the theory of mind (ToM) in some patients with schizophrenia. This ToM deficit consists of an inability to attribute relevant mental states to others, and studies suggest it has to be regarded as functional and remediable through the use of reinforced context processing. To investigate this, the present study compares the performances of 25 schizophrenics and 25 matched controls in a task exploring ToM before and after the introduction of verbal material into the task, initially conceived as nonverbal. All the controls and half of the schizophrenic subjects who did not initially perform at the best level remediated with verbalization, while 9 of the schizophrenics exhibited no remediation. These poor performers are characterized by a longer duration of illness. The cognitive plasticity and the characteristics of patients who do/do not remediate are discussed in the light of findings obtained with the Wisconsin Card Sorting Test. The clinical implication of these results is important since they suggest that some patients would benefit from cognitive rehabilitation in terms of their ability to attribute relevant mental states to others.     

Does the duration of untreated psychosis affect prognosis in schizophrenia?

Clinical Dilemma: 'An 18-year-old patient, who has been suffering from a prolonged psychotic state, is hospitalized for the first time in his life in our department. We diagnose his condition as schizophrenia, and start anti-psychotic medication and supportive psychotherapy. His parents join the psycho-educational group for families in our department. After one of the group sessions, his parents worriedly approach us with the question whether the fact that their son had been psychotic and had not received anti-psychotic medications for many months before his hospitalization predicts a bad prognosis for his disease course and outcome. Does the duration of untreated psychosis (DUP) affect prognosis in schizophrenia?'     

Is quality of life associated with cognitive impairment in schizophrenia?

BACKGROUND: The subjectively assessed quality of life of schizophrenia patients is mostly lower than healthy subjects, and cognitive impairment is an integral feature of schizophrenia. The aims of the present study were to compare the quality of life and neurocognitive functioning between the patients with schizophrenia and the healthy subjects, and to examine the relationships between quality of life and neurocognitive functions among the patients with schizophrenia. METHODS: Thirty-eight patients with schizophrenia (15 women and 23 men) and 31 healthy individuals (18 women and 13 men) were included in the study. All participants were administered World Health Organization Quality of Life-Brief Form (WHOQOL-BREF) to assess their quality of life, and Digit Span Test (DST) and Controlled Oral Word Association Test (COWAT) for cognitive functions. RESULTS: The patients with schizophrenia demonstrated lower scores in physical (F=25.6, p=0.0001), psychological (F=15.85, p=0.0001) and social (F=37.7, p=0.0001) domains compared to control group. The patients with schizophrenia showed significantly lower scores on COWAT compared to healthy subjects (F=4.22, p=0.04). The social domain scores of WHOQOL correlated to DST total scores (r=0.45, p=0.007), DST forwards scores (r=0.54, p=0.001) and COWAT total scores (r=0.40, p=0.04) in patients with schizophrenia but not in the control group. The patients with lower level of cognitive functioning had lower scores on social domain of WHOQOL-BREF (z=-2.01, p=0.04). CONCLUSION: Our results confirm that the cognitive deficits in executive function and working memory appear to have direct impact on the patients' perceived quality of life especially in social domain which can either be a cause or a consequence of social isolation of patients with schizophrenia.     

Is age of onset in schizophrenia influenced by marital status?

Summary Schizophrenia is a disease characterized by a distinctly higher age at onset and at first admission in females than in males. In a systematic study on gender differences in schizophrenia we have confirmed this finding using different sets of data, in particular through the examination of a large and representative sample of first-admitted patients. The question addressed in this paper is whether marital status influences this sex-specific age difference. Assuming that marriage or a stable relationship is a protective factor in schizophrenia, delaying the onset of the disease or first hospitalization, the hypothesis was formulated that the later age of onset in women is at least partly explained by their generally earlier age of marriage. Testing this hypothesis illustrates some of the methodological problems that often occur when a causal analysis of social data is attempted. The problems emerge especially when both the dependent variable (age of onset/first admission) and the independent variable (marital status) are essentially related to age. First results appearing to indicate an influence of marital status on age at first admission did not bear a critical interpretation.The present study was part of the investigation Gender differences in age at onset, symptomatology and course of schizophrenia conducted within the Sonderforschungsbereich (Special Research Branch) 258 at the Central Institute of Mental Health, Mannheim. We thank the Deutsche Forschungsgemeinschaft (German Research Association) for supporting the Sonderforschungsbereich.     

Is the outcome of schizophrenia really better in developing countries?

That schizophrenia has a better prognosis in non-industrialized societies has become an axiom in international psychiatry; the evidence most often cited comes from three World Health Organization (WHO) cross-national studies. Although a host of socio-cultural factors have been considered as contributing to variation in the course of schizophrenia in different settings, we have little evidence from low-income countries that clearly demonstrates the beneficial influence of these variables. In this article, we suggest that the finding of better outcomes in developing countries needs re-examination for five reasons: methodological limitations of the World Health Organization studies; the lack of evidence on the specific socio-cultural factors which apparently contribute to the better outcomes; increasing anecdotal evidence describing the abuse of basic human rights of people with schizophrenia in developing countries; new evidence from cohorts in developing countries depicting a much gloomier picture than originally believed; and, rapid social and economic changes are undermining family care systems for people with schizophrenia in developing countries. We argue that the study of the long-term course of this mental disorder in developing countries is a major research question and believe it is time to thoroughly and systematically explore cross-cultural variation in the course and outcome of schizophrenia.