Search

Background: Auditory verbal hallucinations in schizophrenia have been linked to defective monitoring of one's own verbal thoughts. Previous studies have shown that patients with auditory verbal hallucinations show attenuated activation of brain regions involved with auditory processing during the monitoring of inner speech. However, there are no functional magnetic resonance imaging studies explicitly comparing the perception of external speech with internal speech in the same patients with schizophrenia. The present study investigated the functional neuroanatomy of inner and external speech in both patients with schizophrenia and healthy control subjects., Methods: Fifteen patients with schizophrenia and 12 healthy control subjects were studied using functional magnetic resonance imaging while listening to sentences or imagining sentences., Results: Significant interactions between group (control subjects vs. patients) and task (listening vs. inner speech) were seen for the left superior temporal gyrus, as well as regions within the cingulate gyrus., Conclusions: Attenuated deactivation of the left superior temporal gyrus in schizophrenia patients during the processing of inner speech may reflect deficits in the forward models subserving self-monitoring., (Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Reported rates of bipolar syndromes are highly variable between studies because of age differences, differences in diagnostic criteria, or restriction of sampling to clinical contacts., Method: In 1395 adolescents aged 14-17 years, DSM-IV (hypo)manic episodes (manic and hypomanic episodes combined), use of mental health care, and five ordinal subcategories representing the underlying continuous score of (hypo)manic symptoms ('mania symptom scale') were measured at baseline and approximately 1.5, 4 and 10 years later using the Munich-Composite International Diagnostic Interview (DIA-X/M-CIDI)., Results: Incidence rates (IRs) of both (hypo)manic episodes and (hypo)manic symptoms (at least one DSM-IV core symptom) were far higher (714/105 person-years and 1720/10(5) person-years respectively) than traditional estimates. In addition, the risk of developing (hypo)manic episodes was very low after the age of 21 years [hazard ratio (HR) 0.031, 95% confidence interval (CI) 0.0050-0.19], independent of childhood disorders such as attention deficit hyperactivity disorder (ADHD). Most individuals with hypomanic and manic episodes were never in care (87% and 62% respectively) and not presenting co-morbid depressive episodes (69% and 60% respectively). The probability of mental health care increased linearly with the number of symptoms on the mania symptom scale. The incidence of the bipolar categories, in particular at the level of clinical morbidity, was strongly associated with previous childhood disorders and male sex., Conclusions: This study showed, for the first time, that experiencing (hypo)manic symptoms is a common adolescent phenomenon that infrequently predicts mental health care use. The findings suggest that the onset of bipolar disorder can be elucidated by studying the pathway from non-pathological behavioural expression to dysfunction and need for care.

In this paper we examined whether manic and depressive dimensions independently contribute to mental health service use and determined the degree of comorbidity between manic and depressive dimensions in individuals with and without mental health service use. If both depressive and manic episodes independently influence help-seeking behaviour, a higher level of comorbidity between these dimensions would be found in clinical as compared to non-clinical samples (i.e. Berkson's Bias). Data were derived from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a prospective epidemiological survey in a representative sample of the Dutch population (N = 7076). Dimensions of depression and mania and mental health service use (MHSU) were assessed with the Composite International Diagnostic Interview (CIDI) at baseline, and prospectively one and three years later. Logistic regression was used to test whether depressive and manic dimensions both had independent effects on mental health service use. The degree of mania-comorbidity given the presence of depressive dimension was assessed as a function of MHSU, both retrospectively and prospectively. Manic and depressive dimensions contributed independently to mental health service use. Mania-comorbidity given the presence of depressive dimension was significantly higher in individuals with mental health service use than in those without, both retrospectively (16.7% versus 7.1%, p = 0.000) and prospectively (10.8% versus 6.6%, p = 0.017). We conclude that the bipolar phenotype consists of manic and depressive dimensions that may be much more loosely associated than (Berkson) biased clinical observations suggest. A dimension-specific approach may be more productive in clarifying the aetiology of mood dysregulation.

Background: Female gender and later onset of psychosis are both associated with better outcome. However whether their effects are independent, is not known., Method: In 379 incident cases of psychoses, from an epidemiologically defined catchment area, admixture analysis was employed to generate age of onset classes. Five year course and outcome measured across clinical and social domains were used as dependent variables in regression analyses, to estimate associations of outcomes with gender, age of onset and gender by age of onset interaction., Results: Three age of onset classes were identified: early (14-41 years), late (42-64 years) and very late onset psychosis (65-94 years). Overall, women had better outcomes, including milder delusions, fewer negative symptoms, less deterioration from baseline functioning, fewer hospital readmissions and shorter psychotic episodes. Later age of onset was also associated with better outcome, although in the very late onset class the results were mixed. There was a statistically significant gender by age of onset interaction (in the ratio scale) within this sample with men displaying poorer outcome in the early/late onset class, whereas women tended to have a worse outcome in the very late onset class., Conclusions: The favourable outcome in women becomes reversed in old age, suggesting gender-age-related differences in the distribution of aetiological factors for psychosis.

Objective: Previous studies have reported an association between depression and poor cognitive functioning. Unknown is to what degree such associations are merely state-related or reflect an enduring depression vulnerability. This study examined whether cognitive deficits predict current and/or follow-up (sub)clinical depressive symptoms in the general population., Method: A population-based sample of 569 female twins and 43 of their sisters completed a neuropsychological battery. Cross-sectional and prospective associations between depressive symptoms measured at the subclinical [Symptom Checklist-90 (SCL-90)] and clinical level (Structured Clinical Interview for DSM-IV disorders) and neuropsychological factors (episodic memory and information processing speed) were examined., Results: Structured Clinical Interview for DSM-IV disorders baseline depressive symptoms were significantly associated with information processing speed but not with episodic memory. Episodic memory was significantly associated with follow-up SCL-90 depressive symptoms., Conclusion: Being depressed is accompanied by slower information processing. Poor memory functioning may be a predictor for the onset of subclinical depressive symptoms.

Objective: The aim of this study was to examine whether proneness to subjective cognitive failure (cognitive based mistakes) increases the risk for the development of symptoms of psychosis and to what degree any association was familial., Methods: At baseline, the Cognitive Failure Questionnaire (CFQ) and the Community Assessment of Psychic Experiences (CAPE) questionnaire were administered in a general population sample of genetically related individuals (n = 755). Individuals scoring high (>75th percentile) or average on the CAPE (between 40th and 60th percentile) (n = 488) were reinterviewed with the CAPE and Structured Interview for Schizotypy-Revised (SIS-R) at follow-up (mean interval = 7.7 months, SD = 4.8 months)., Results: Cross-trait, within-relative analysis showed a significant association between the CFQ and the negative dimension, assessed with both the CAPE and SIS-R, whereas no association was found between the CFQ and the positive dimension. Cross-trait, between-relative analyses showed no association between the CFQ in one relative and any of the dimensions of the subclinical psychosis phenotype in the other relative., Conclusion: Proneness to subjective cognitive failure possibly contributes to the development or persistence of negative symptoms and can be seen as potential risk factor for negative symptoms of psychosis. This overlap is due to individual effects rather than familial liability.

For successful interpersonal communication, inferring intentions, goals or desires of others is highly advantageous. Increasingly, humans also interact with computers or robots. In this study, we sought to determine to what degree an interactive task, which involves receiving feedback from social partners that can be used to infer intent, engaged the medial prefrontal cortex, a region previously associated with Theory of Mind processes among others. Participants were scanned using fMRI as they played an adapted version of the Prisoner's Dilemma Game with alleged human and computer partners who were outside the scanner. The medial frontal cortex was activated when both human and computer partner were played, while the direct contrast revealed significantly stronger signal change during the human-human interaction. The results suggest a link between activity in the medial prefrontal cortex and the partner played in a mentalising task. This signal change was also present for to the computers partner. Implying agency or a will to non-human actors might be an innate human resource that could lead to an evolutionary advantage.

This study examined brain activation during a cognitive inhibition task in patients with schizophrenia following changes in their positive symptoms. A Stroop task was used during functional magnetic resonance imaging in 11 patients with schizophrenia (patient group) and 9 healthy volunteers (control group). At baseline, the patient group showed significantly attenuated activation within the anterior cingulate gyrus, left pre-/postcentral gyrus and inferior frontal junction. At follow-up, there was a significant increase in activation in the left inferior frontal junction associated with a decrease in positive symptoms, suggesting this region plays a role in the development of these symptoms.

Objectives: In schizophrenia, a distinction is made between psychosis with developmental and cognitive impairment on the one hand and psychosis without developmental impairment and positive symptoms on the other. In this study, we investigated whether this model can be extended to bipolar disorder by testing the hypothesis that neurocognitive functioning is inversely related to positive psychotic symptoms in bipolar disorder., Methods: Neurocognitive functioning and psychopathology were assessed in (i) 76 patients with bipolar disorder, (ii) 39 of their healthy first-degree relatives, and (iii) 61 healthy controls. Cognitive performance of bipolar patients and their first-degree relatives was investigated, taking into account the possible moderating effect of the level of expression of psychosis in patients and relatives., Results: Bipolar patients showed impaired cognitive performance on multiple cognitive domains, whereas performance of their relatives was comparable to that of controls. A history of psychotic symptoms in patients was suggestive of less likelihood of cognitive alterations in relatives, and the presence of subclinical psychotic symptoms within the group of relatives predicted better cognitive performance., Conclusions: The finding of similar psychosis-cognition associations in bipolar disorder as implied by the two pathways leading to nonaffective psychotic disorders suggests that this model might be extended to the continuum spanning affective and nonaffective psychosis. This is in line with the idea of a partially overlapping vulnerability to bipolar disorder and schizophrenia and provides an explanation for the apparent differences in cognitive alterations in those at risk for the two disorders.

Background: The ability to mentalize, i.e. develop a Theory of Mind (ToM), enables us to anticipate and build a model of the thoughts, emotions and intentions of others. It has long been hypothesised that women differ from men in their mentalizing abilities. In the present fMRI study we examined the impact of (1) gender (women vs. men) and (2) game partner (human vs. computer) on ToM associated neural activity in the medial prefrontal cortex. Groups of men (n = 12) and women (n = 12) interacted in an iterated classical prisoner's dilemma forced choice situation with alleged human and computer partners who were outside the scanner., Results: Both the conditions of playing against putative human as well as computer partners led to activity increases in mPFC, ACC and rTPJ, constituting the classic ToM network. However, mPFC/ACC activity was more pronounced when participants believed they were playing against the alleged human partner. Differences in the medial frontal lobe activation related to the sex of the participants could be demonstrated for the human partner > computer partner contrast., Conclusion: Our data demonstrate differences in medial prefrontal brain activation during a ToM task depending on both the gender of participants and the game partner.

A systematic review of all reported incidence and prevalence studies of population rates of subclinical psychotic experiences reveals a median prevalence rate of around 5% and a median incidence rate of around 3%. A meta-analysis of risk factors reveals associations with developmental stage, child and adult social adversity, psychoactive drug use, and also male sex and migrant status. The small difference between prevalence and incidence rates, together with data from follow-up studies, indicates that approximately 75-90% of developmental psychotic experiences are transitory and disappear over time. There is evidence, however, that transitory developmental expression of psychosis (psychosis proneness) may become abnormally persistent (persistence) and subsequently clinically relevant (impairment), depending on the degree of environmental risk the person is additionally exposed to. The psychosis proneness-persistence-impairment model considers genetic background factors impacting on a broadly distributed and transitory population expression of psychosis during development, poor prognosis of which, in terms of persistence and clinical need, is predicted by environmental exposure interacting with genetic risk.

It has been suggested that genes impact on the degree to which minor daily stressors cause variation in the intensity of subtle paranoid experiences. The objective of the present study was to test the hypothesis that catechol-O-methyltransferase (COMT) Val(158)Met and brain-derived neurotrophic factor (BDNF) Val(66)Met in part mediate genetic effects on paranoid reactivity to minor stressors. In a general population sample of 579 young adult female twins, on the one hand, appraisals of (1) event-related stress and (2) social stress and, on the other hand, feelings of paranoia in the flow of daily life were assessed using momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of daily life stress-induced paranoia by COMT Val(158)Met and BDNF Val(66)Met genotypes. Catechol-O-methyltransferase Val carriers displayed more feelings of paranoia in response to event stress compared with Met carriers. Brain-derived neurotrophic factor Met carriers showed more social-stress-induced paranoia than individuals with the Val/Val genotype. Thus, paranoia in the flow of daily life may be the result of gene-environment interactions that can be traced to different types of stress being moderated by different types of genetic variation.

In order to assess coping with psychotic symptoms, the Maastricht Assessment of Coping Strategies (MACS), 24 symptom version, was developed as a refinement of the previous MACS-13. Associations between type of coping and the experienced level of control over psychotic symptoms were examined using MACS-24.MACS-24 was administered to 32 individuals with a diagnosis of schizophrenia. For each of 24 symptoms, experience of distress, type of coping and the resulting degree of perceived control were assessed. Coping types were reduced to two contrasting coping factors: symptomatic coping and non-symptomatic coping (combining active problem solving, passive illness behaviour, active problem avoiding, and passive problem avoiding).Mean level of distress and perceived control (range: 1-7) were, respectively, 4.2 [standard deviation (SD) = 1.9] and 4.2 (SD = 1.9). The association between distress and perceived control was negative [beta = -0.28; 95% confidence interval (95%CI) = -0.41 to -0.15]. Type of coping interacted with perceived control (p = 0.005), in that symptomatic coping was negatively associated with perceived control [odds ratio (OR) over seven levels = 0.82, 95%CI = 0.71-0.94], whereas for non-symptomatic coping a positive association was apparent (OR over seven levels = 1.10, 95% CI = 1.03-1.19).Previous contrasts between symptomatic and non-symptomatic coping were replicated using MACS-24, suggesting clinical validity and utility.

A systematic review (58 studies, 5,009 individuals) is presented of associations between psychopathological dimensions of psychosis and measures of neurocognitive impairment in subjects with a lifetime history of nonaffective psychosis. Results showed that negative and disorganized dimensions were significantly but modestly associated with cognitive deficits (correlations from -.29 to -.12). In contrast, positive and depressive dimensions of psychopathology were not associated with neurocognitive measures. The patterns of association for the 4 psychosis dimensions were stable across neurocognitive domains and were independent of age, gender, and chronicity of illness. In addition, significantly higher correlations were found for the negative dimension in relation to verbal fluency (p = .005) and for the disorganized dimension in relation to reasoning and problem solving (p = .004) and to attention/vigilance (p = .03). Psychotic psychopathology and neurocognition are not entirely orthogonal, as heterogeneity in nonaffective psychosis is weakly but meaningfully associated with measures of neurocognition. This association suggests that differential latent cerebral mechanisms underlie the cluster of disorganized and negative symptoms versus that of positive and affective symptoms.

Genetic moderation of experience of reward in response to environmental stimuli is relevant for the study of many psychiatric disorders. Experience of reward, however, is difficult to capture, as it involves small fluctuations in affect in response to small events in the flow of daily life. This study examined a momentary assessment reward phenotype in relation to the catechol-O-methyl transferase (COMT) Val(158)Met polymorphism. A total of 351 participants from a twin study participated in an Experience Sampling Method procedure to collect daily life experiences concerning events, event appraisals, and affect. Reward experience was operationalized, as the effect of event appraisal on positive affect (PA). Associations between COMT Val(158)Met genotype and event appraisal on the one hand and PA on the other were examined using multilevel random regression analysis. Ability to experience reward increased with the number of 'Met' alleles of the subject, and this differential effect of genotype was greater for events that were experienced as more pleasant. The effect size of genotypic moderation was quite large: subjects with the Val/Val genotype generated almost similar amounts of PA from a 'very pleasant event' as Met/Met subjects did from a 'bit pleasant event'. Genetic variation with functional impact on cortical dopamine tone has a strong influence on reward experience in the flow of daily life. Genetic moderation of ecological measures of reward experience is hypothesized to be of major relevance to the development of various behavioral disorders, including depression and addiction.

Patients with psychosis display alterations in social cognition as well as in the realm of neurocognition. It is unclear, however, to what degree these cognitive domains represent two separate dimensions of liability or the pleiotropic expression of a single deficit. The purpose of the present study was to investigate (i) to what extent alterations in social cognition represent an independent area of vulnerability to psychosis, separate from neurocognitive deficits and (ii) whether social cognition is one construct or can be divided into several subcomponents. Five social cognition and three neurocognitive tasks were completed by 186 participants with different levels of vulnerability for psychosis: 44 patients with psychotic disorder; 47 subjects at familial risk; 41 subjects at psychometric risk and 54 control subjects. The social cognition tasks covered important basic subcomponents of social cognition, i.e. mentalisation (or theory of mind), data gathering bias (jumping to conclusions), source monitoring and attribution style. Neurocognitive tasks assessed speed of information processing, inhibition, cognitive shifting and strategy-driven retrieval from semantic memory. The results of factor analysis suggested that neurocognition and social cognition are two separate areas of vulnerability in psychosis. Furthermore, the social cognition measures lacked significant overlap, suggesting a multidimensional construct. Cognitive liabilities to psychosis are manifold, and include key processes underlying basic person-environment interactions in daily life, independent of cognition quantified by neuropsychological tests.

Objective: To investigate the contribution of processing speed in the prediction of various domains of outcome in psychosis., Method: Data were drawn from the UK700 Case Management Trial of 708 patients with chronic psychotic illness. Regression analyses were applied to investigate cross-sectional and longitudinal associations between processing speed at baseline and measures of service use, social outcome and subjective outcome, taking into account current psychopathology and adjusting for baseline values of the outcome measure., Results: Cross-sectionally, processing speed was associated with all three domains of outcome, although only associations in the social and subjective outcome domain remained significant after controlling for psychopathology and the effects differed between and within domains of outcome. Prospectively, only the subjective outcome measure of number of met and unmet needs (CAN) was weakly associated with baseline neurocognitive performance after adjustment for baseline needs. Other associations disappeared after adjustment for the baseline measure of outcome and/or baseline psychopathology., Conclusion: The finding of weak cross-sectional associations in the absence of specific and unconfounded longitudinal associations suggests that processing speed is an independent dimension of disease severity rather than a causal factor impacting on social outcome. Nevertheless, longitudinal change in patient reported needs may be weakly sensitive to baseline cognitive impairment.

Background: Previous work suggests that impairments in executive function and verbal memory in particular may persist in euthymic bipolar patients and serve as an indicator of genetic risk (endophenotype)., Method: A systematic review of the literature was undertaken. Effects sizes were extracted from selected papers and pooled using meta-analytical techniques., Results: In bipolar patients, large effect sizes (d>0.8) were noted for executive functions (working memory, executive control, fluency) and verbal memory. Medium effect sizes (0.5

Background: Associations between coping with and control over psychotic symptoms were examined using the Maastricht Assessment of Coping Strategies-24, testing the hypothesis that the cognitive domain of executive functioning predicted quality and quantity of coping., Methods: MACS-24 was administered to 32 individuals with a diagnosis of schizophrenia. For each of 24 symptoms, experience of distress, type of coping and the resulting degree of perceived control were assessed. Coping types were reduced to two contrasting coping categories: symptomatic coping (SC) and non-symptomatic coping (NSC; combining active problem solving, passive illness behaviour, active problem avoiding, and passive problem avoiding). Cognitive functioning was assessed using the GIT (Groninger Intelligence Test), the Zoo map (BADS: Behavioural Assessment of Dysexecutive function), Stroop-test and Trail making., Results: Cognitive function was not associated with frequency of coping, nor did cognitive function differentially predict SC or NSC. Cognitive function similarly was not associated with symptom distress or level of perceived control over the symptom., Conclusion: There was no evidence that cognitive function predicts quantity or quality of coping with symptoms in people with a diagnosis of schizophrenia. Variation in the realm of emotion regulation and social cognition may be more predictive of coping with psychotic symptoms.

Objective: To examine the specificity of deficits in focused attention and sustained attention in adults with ADHD and to evaluate the effect of comorbidity., Method: Twenty-eight adults with ADHD without comorbidity were compared with 28 ADHD outpatients with comorbidity. Two control groups were used: 68 adults referred for ADHD but with another psychopathology rather than ADHD (non-ADHD) and 28 healthy controls. All participants completed attention tests of the Amsterdam Neuropsychological Tasks program., Results: Both ADHD groups demonstrated a sustained attention deficit relative to the control groups, as indicated by a disproportionate deterioration of speed fluctuation with time-on-task reflecting temporal lapses in attention. Only the ADHD+ group showed focused attention deficits in that they were less able to ignore irrelevant information., Conclusion: These findings show that adults with ADHD have specific deficits in sustained attention. Additional deficits in focused attention are confined to outpatients with ADHD and comorbidity.

Objectives: Psychotic patients with COMT(Val158Met) Met alleles were recently found to display more intense psychotic and affective responses to daily life stressors. We aimed to test the hypothesis that the Met allele is implicated in the development of affective and psychotic symptomatology in subjects genetically at risk for schizophrenia, by testing if unaffected first-degree relatives of patients with schizophrenia who share a Met allele have greater concordance of symptomatology than relatives not sharing a Met allele., Methods: Unaffected relatives (n=38) were arranged in as many genetically related pairs as possible (n=26), and Met-sharing between Index Unaffected Subject (IUS) and Related Unaffected Subject (RUS) was assessed. Symptomatology was assessed with the Brief Psychiatric Rating Scale (BPRS) total score., Results: Multilevel regression revealed an interaction between RUS BPRS score and Met-sharing in the model of IUS BPRS score (interaction chi(2)=3.78, p=0.05). Stratified analyses revealed that IUS-RUS total BPRS scores were significantly associated in the case of Met-sharing (B=0.57, 95% CI: 0.22-0.93, p=0.002), but were not when there was no Met-sharing., Conclusion: These findings support the hypothesis that the Met allele may be involved in the causation of psychopathology, at least in populations with a genetic predisposition to psychosis.

Objective: Failing of mentalising has been suggested to underlie certain symptoms of psychosis. An as yet unresolved issue is whether mentalising deficits reflect a characteristic which can also be detected in people at risk for psychosis or people with evidence of subclinical expression of psychosis. This study wanted to assess an aspect of mentalising in four groups with different levels of psychosis vulnerability, and to examine associations between mentalising and symptoms of psychosis., Method: The study included i) 40 patients with psychosis, ii) 49 non-psychotic first-degree relatives (familial risk), iii) 41 subjects from the general population with a high level of positive psychotic experiences (psychometric risk) and iv) 54 healthy controls. All subjects performed the 'Hinting Task'., Results: There was a significant association between psychosis risk and impairment on the Hinting Task (beta linear trend=0.37, p<0.001). Using the control group as the reference, the association with impairment on the Hinting Task was highest for the patient group (beta=0.46, p<0.001), whereas the familial risk group (beta=0.16, p=0.06) displayed an intermediate probability of failure. The psychometric risk group did not significantly differ from the control group (beta=0.04, p=0.653). In the patient group, impairment on the Hinting Task was associated with current hallucinations and paranoid symptoms. In the familial risk group, there was an association between the Hinting Task and paranoid symptoms., Discussion: These results suggest that vulnerability to psychosis is expressed as an impairment in mentalising, which may have a mediating role in the formation of certain positive symptoms of psychosis.

There is evidence that the normally transitory developmental expression of psychosis (psychosisproneness) may first of all become abnormally persistent (persistence) and later on become clinically relevant (impairment), depending on the amount of environmental risk to which the person is exposed. According to the psychosis-proneness-persistence impairment model, genetic background factors can impact on a transitory expression of psychosis. Whether or not this will lead to a poor prognosis in terms of persistence and clinical need will depend on the interaction between environmental exposure and genetic risk.

In this study, the authors aimed to examine 4 domains of executive functioning in adults with attention-deficit/hyperactivity disorder (ADHD)--namely interference control, concept shifting, verbal fluency, and verbal working memory. Four groups of participants were included: (a) adults diagnosed with ADHD (ADHD-super(-); n = 20), (b) adults diagnosed with both ADHD and 1 or more comorbid disorder(s) (ADHD-super(+); n = 22), (c) adults referred for ADHD because of ADHD symptomatology but not diagnosed as such (non-ADHD; n = 34), and (d) healthy controls (n = 136). ADHD-related deficits (independent of comorbidity) were revealed for concept shifting and verbal working memory. In addition, the ADHD-super(+) and non-ADHD groups displayed deficits in terms of general processing speed. Given that these deficits were not found in the ADHD-super(-) group, the authors contend that these deficits are likely attributable to comorbidity rather than ADHD itself. Contrary to the authors' expectations, these findings do not correspond with the cognitive subtype hypothesis.

Background: Structural brain changes and cognitive impairments have been identified as indicators of genetic risk for schizophrenia. However, the pattern of associations between such structural and functional liability markers has been less well investigated., Methods: Magnetic resonance imaging data and cognitive assessments were acquired in 31 patients with psychosis, 32 non-psychotic first-degree relatives and 28 controls. The relationship between cerebral grey matter density and cognitive performance was examined using computational morphometry., Results: Two out of 6 cognitive tests revealed significant associations with grey matter density in regions of the frontal lobe, basal ganglia, thalamus and cerebellum in patients and relatives. In patients, poorer executive functioning was associated with cerebellar grey matter density deficits. In relatives, poorer executive functioning was associated with increased grey matter density in the cerebellum and frontal lobe. In both patients and relatives, strategic retrieval from semantic memory was positively associated with grey matter density in basal ganglia structures. Some additional negative associations in the patients differentiated this group from relatives., Conclusions: The overlap in structure-function relationships in individuals with schizophrenia and those with liability for the disorder may suggest that regional grey matter density alterations functionally alter particular neurocircuits, which could lead to cognitive deficits. The non-overlapping structure-function correlations may reflect disease-related or compensatory mechanisms., (2008 S. Karger AG, Basel.)

Background: A disorder of self-monitoring may underlie the positive symptoms of psychosis. The cognitive mechanisms associated with these symptoms may also be detectable in individuals at risk of psychosis., Aims: To investigate (a) whether patients with psychosis show impaired self-monitoring, (b) to what degree this is associated with positive symptoms, and (c) whether this is associated with liability to psychotic symptoms., Method: The sample included: individuals with a lifetime history of non-affective psychosis (n=37), a genetically defined risk group (n=41), a psychometrically defined risk group (n=40), and control group (n=49). All participants carried out an action-recognition task., Results: Number of action-recognition errors was associated with psychosis risk (OR linear trend over 3 levels:1.12, 95% CI1.04-1.20) and differential error rate was associated with the degree of delusional ideation in a dose-response fashion (OR linear trend over 3 levels:1.13, 95% CI1.00-1.26)., Conclusions: Alterations in self-monitoring are associated with psychosis with evidence of specificity for delusional ideation. In the risk state, this is expressed more as failure to recognise self-generated actions, whereas in illness failure to recognise alien sources come to the fore.

Objective: To investigate whether cognitive alterations associated with vulnerability to psychosis, are associated with expression of psychopathology and functional outcome in groups at different levels of risk for psychotic illness., Method: Neurocognition, psychopathology and functional outcome were measured in subjects with variable risk for psychosis: i) 29 patients with psychotic disorder, ii) 46 subjects at familial risk, iii) 41 subjects at psychometric risk and iv) 54 control subjects., Results: Dose-response relationships between cognitive dysfunction and increasing risk for psychosis were found. Cognitive alterations were predicted by negative symptoms in patients and by positive psychotic experiences in the familial risk group. In both at risk groups, cognitive speed was associated with functional outcome., Conclusion: Some cognitive impairments serve as neutral endophenotypic marker across the psychosis continuum. However, other cognitive alterations associated with transmission of psychosis may have a direct impact on the pathway from risk to psychopathology and alterations in functioning.

Attentional biases for emotional stimuli and general orienting processes were examined in bipolar disorder, using a modified dot-probe task with a spatial cueing paradigm incorporated in it. Bipolar patients in a euthymic state (i.e., remission), bipolar patients in a mildly depressed state, and non-psychiatric controls participated. General orienting results showed that within the patient group as a whole, measures of depressed mood were positively associated with a relative inability to disengage attention. Attentional bias results showed that bipolar patients in a mildly depressed state, in comparison with controls, directed their attention away from depression-related words and positive words. The bias away from positive words was equally present in both patient groups and part of a trait effect, demonstrated by the comparison of patients in a euthymic state and controls. The bias away from depression-related words was mood state-dependent and within the patient group as a whole correlated negatively with measures of depressed mood. It is proposed that biases for emotional stimuli are related to the transition of mood states, characteristic for bipolar disorder.

Objective: Cognitive deficits may be vulnerability markers for the development of schizophrenia. This study examined whether cognitive deficits are related to specific dimensions of subclinical psychotic experiences and whether associations between these variables are caused by additive genetic, common environmental and/or individual-specific environmental factors., Method: A general population sample of 298 female twin pairs completed the Community Assessment of Psychic Experiences and a neuropsychological test battery. Associations between subclinical positive and negative psychotic dimensions and neuropsychological factors (episodic memory and information processing speed) were examined. Univariate correlation and structural equation analyses were performed to explore the role of genetic and environmental factors in the phenotypes separately. Bivariate correlation and structural equation analyses were applied to examine the causes of association., Results: There were significant correlations between information processing speed and both the positive (r=.11; p<.05) and the negative dimension (r=.10; p<.05). For the negative dimension and for speed of processing, the data suggested a model that included genetic factors. The observed phenotypic correlation between the negative dimension and information processing speed could be solely explained in terms of additive genetic factors. Although the comparison of the correlations for MZ and DZ pairs did not give a clear indication as to the underlying causes of the association, structural equation modelling suggested that the observed phenotypic correlation between the negative dimension and information processing speed could be solely explained in terms of additive genetic factors., Conclusion: Negative symptoms and information processing speed are associated at the subclinical level and this association appears to be influenced by genetic factors exclusively. Bivariate psychosis phenotypes may represent suitable candidates for molecular genetic studies in the general population.

The aim of the current study was to replicate the finding that cognitive impairments are not or inversely associated with sensitivity to stress in a sample of 25 patients diagnosed with psychotic disorder. The results indicated that impairments in performance on the Trailmaking Test and the Stroop Color Word Test were inversely associated with sensitivity to stress in daily life, whereas impairment in a subtest of the Behavioral Assessment of Dysexecutive Syndrome (BADS) was not associated with stress-sensitivity. The data thus show that in some instances cognitive functioning is not, and in other instances is inversely associated with momentary sensitivity to stress. Cognitive impairment and affective reactivity thus appear to be independent or mutually exclusive mechanisms in psychosis, suggesting competing causal pathways.

Background: Research suggests that low-grade psychotic experiences in the general population are a common but transitory developmental phenomenon. Using two independent general population samples, the hypothesis was examined that common, non-clinical developmental expression of psychosis may become abnormally persistent when synergistically combined with developmental exposures that may impact on behavioural and neurotransmitter sensitization such as cannabis, trauma and urbanicity., Method: The amount of synergism was estimated from the additive statistical interaction between baseline cannabis use, childhood trauma and urbanicity on the one hand, and baseline psychotic experiences on the other, in predicting 3-year follow-up psychotic experiences, using data from two large, longitudinal, random population samples from the Netherlands [The Netherlands Mental Health Survey and Incidence Study (NEMESIS)] and Germany [The Early Developmental Stages of Psychopathology (EDSP) study]., Results: The 3-year persistence rates of psychotic experiences were low at 26% in NEMESIS and 31% in EDSP. However, persistence rates were progressively higher with greater baseline number of environmental exposures in predicting follow-up psychotic experiences (chi2=6.9, df=1, p=0.009 in NEMESIS and chi2=4.2, df=1, p=0.04 in EDSP). Between 21% and 83% (NEMESIS) and 29% and 51% (EDSP) of the subjects exposed to both environmental exposures and psychotic experiences at baseline had persistence of psychotic experiences at follow-up because of the synergistic action of the two factors., Conclusion: The findings suggest that environmental risks for psychosis act additively, and that the level of environmental risk combines synergistically with non-clinical developmental expression of psychosis to cause abnormal persistence and, eventually, need for care.

Background: Little is known about late-onset psychosis (onset after the age 45 years) and how it relates to early-onset psychosis (before age 45 years). The aims of this study were to calculate the incidence of non-affective, non-organic psychotic symptoms across the life span and to explore the contribution of different sets of risk factors in relation to age at onset., Methods: Data were obtained from the three measurements of the Netherlands Mental Health Survey and Incidence Study. Symptoms of psychosis were assessed in individuals aged 18-64 years using the Composite International Diagnostic Interview. All individuals reporting first-onset of psychotic symptoms within a three-year interval were included. The degree to which sets of risk factors affected the psychosis outcome similarly across age groups was assessed., Results: The number of subjects displaying incident psychotic symptoms was similar across age groups. Cumulative incidence rates ranged from 0.3% to 0.4%. Age differences were found for life-time depressive symptoms (risk difference = 5%, 95% CI = 1%, 9%) and baseline neuroticism (risk difference = 3%, 95% CI = 0%, 6%), indicating that late-onset psychosis was less often preceded by these. In contrast, no effect modification by age was observed for female sex, hearing impairment, being single, or life-time cannabis use., Conclusions: Onset of psychotic symptoms in late life is no rare event. Compared to early onset psychosis, the late-onset counterpart less often arises in a context of emotional dysfunction and negative affectivity, suggesting qualitative differences in aetiology and more effective premorbid coping styles.

Background: Current cognitive models of positive symptoms of psychosis suggest a mechanism of defective self-monitoring that may be relevant for (i) expression of psychosis at the clinical and subclinical level and (ii) transmission of risk for psychosis., Method: The study included 41 patients with psychosis, 39 non-psychotic first-degree relatives, 39 subjects from the general population with a high level of positive psychotic experiences, and 52 healthy controls with an average level of positive psychotic experiences. All subjects performed a speech attribution task in which single adjectives with a complimentary or derogatory meaning were presented to them on a computer screen; subjects had to read aloud and determine the source (self/other/uncertain) of the words they heard. In some of the trials, participants' speech was distorted, in others they heard someone else's voice (alien feedback condition) that could also be distorted., Results: No large or significant differences in errors in the speech attribution task were found between the four groups in any of the conditions., Conclusions: Contrary to previous work using this paradigm, this study found no evidence that either expression of psychosis or risk for psychosis was associated with impairment in self-monitoring.

Background: In the general population, symptoms of mania and psychosis are more broadly distributed than their associated clinical syndromes. Little is known, however, about how these subclinical population phenotypes co-vary with and impact on each other., Method: In a representative population cohort of 7076 adults, prevalence of mania and psychosis symptoms and syndromes were assessed with the CIDI at baseline, at one (T1) and two years later (T2). The degree of comorbidity between subclinical mania and subclinical psychosis was examined, as well as the impact of subclinical comorbidity on social impairment and transition from subclinical mania to onset of bipolar disorder., Results: The lifetime prevalence of at least one manic and one psychotic symptom was 4.1% and 4.2% respectively. Excluding individuals with any lifetime DSM-III-R bipolar or psychotic disorder (n=218), these prevalences were 2.3% (subclinical mania) and 2.8% (subclinical psychosis). Individuals with subclinical mania had a 17% risk of subclinical psychosis, compared with 2.3% in those without (P<0.000). Comorbid subclinical psychosis in individuals with subclinical mania was much more predictive of a future diagnosis of bipolar disorder (positive predictive values of 3% versus 10% respectively)., Conclusion: Subclinical phenotypes of mania and psychosis are more prevalent than their clinical counterparts and cluster together. The risk factors for psychosis may facilitate the formation of more "toxic" combinations of subclinical mania and subclinical psychosis with a higher probability of transition to bipolar disorder. A better understanding of this pathway is crucial for the development of early interventions.

Animal studies have demonstrated behavioural effects of long-chain polyunsaturated fatty acid (LC-PUFA) deficiencies and in humans, several psychiatric disorders have been linked to abnormal essential fatty acid metabolism. The aim of this study was to examine the relationship between LC-PUFA status at birth and the later development of problem behaviour. In a sample of 393 children, higher levels of docosahexaenoic acid (DHA) at birth were associated with lower levels of internalising problem behaviour at age 7 years. The association was markedly present in the infants fed with artificial formula (n=215, Beta=-0.32, P=0.000), but absent in the infants fed with human milk (n=170, Beta=0.11, P=0.325). The associations between arachidonic acid and internalising or externalising behaviour were neither large nor significant. The results suggest that perinatal DHA status may have long-term behavioural consequences. Therefore, we suggest to include measures of problem behaviour in future trials of LC-PUFA supplementation of mothers and/or infants.

Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase (COMT Val(158)Met) gene moderate the psychosis-inducing effect of cannabis. To replicate and extend this finding, a double-blind, placebo-controlled cross-over design was used in which patients with a psychotic disorder (n=30), relatives of patients with a psychotic disorder (n=12), and healthy controls (n=32) were exposed to Delta-9-tetrahydrocannabinol (Delta-9-THC, the principal component of cannabis) or placebo, followed by cognitive assessment and assessment of current psychotic experiences. Previous expression of psychometric psychosis liability was also assessed. Models of current psychotic experiences and cognition were examined with multilevel random regression analyses to assess (i) main effects of genotype and condition, (ii) interactions between condition and genotype, and (iii) three-way interactions between condition, genotype, and psychometric psychosis liability. Carriers of the Val allele were most sensitive to Delta-9-THC-induced psychotic experiences, but this was conditional on prior evidence of psychometric psychosis liability. Delta-9-THC impacted negatively on cognitive measures. Carriers of the Val allele were also more sensitive to Delta-9-THC-induced memory and attention impairments compared to carriers of the Met allele. Experimental effects of Delta-9-THC on cognition and psychosis are moderated by COMT Val(158)Met genotype, but the effects may in part be conditional on the additional presence of pre-existing psychosis liability. The association between cannabis and psychosis may represent higher order gene-environment and gene-gene interactions.

Objective: Maternal stress during pregnancy has been reported to have an adverse influence on fetal growth. The terrorist attacks of September 11, 2001, on the United States have provoked feelings of insecurity and stress worldwide. Our aim was to test the hypothesis that maternal exposure to these acts of terrorism via the media had an unfavorable influence on mean birth weight in the Netherlands., Methods: We compared birth weights of 1885 Dutch neonates who were in utero during the attacks with those of 1258 neonates who were in utero exactly 1 year later., Results: In the exposed group, birth weight was lower than in the nonexposed group (difference, 48 g; 95% confidence interval=13.6, 82.9; P=.006). The difference in birth weight could not be explained by tobacco use, maternal age, parity, or other potential confounders or by shorter pregnancy durations., Conclusion: These results provide evidence supporting the hypothesis that exposure of Dutch pregnant women to the 9/11 events via the media has had an adverse effect on the birth weight of their offspring.

Background: Cannabis use is common in patients with bipolar disorder, however little is known about cannabis as a risk factor for mania. In order to investigate the association between exposure to cannabis and subsequent development of manic symptoms whilst controlling for psychotic symptoms, a longitudinal population-based study was carried out., Methods: 4815 individuals aged 18 to 64 years were interviewed using the Composite International Diagnostic Interview at baseline, 1 year follow up and 3 year follow up, including assessment of substance use, manic symptoms and psychotic symptoms., Results: Use of cannabis at baseline increased the risk for manic symptoms during follow-up (adjusted OR 2.70, 95% CI: 1.54, 4.75), adjusted for age, sex, educational level, ethnicity, single marital status, neuroticism, use of other drugs, use of alcohol, depressive symptoms and manic symptoms at baseline. The association between cannabis use and mania was independent of the prevalence and the incidence of psychotic symptoms. There was no evidence for reverse causality, as manic symptoms at baseline did not predict the onset of cannabis use during follow-up (OR = 0.35, 95% CI: 0.03, 3.49)., Limitations: As 3 years is a relative short period of follow-up, long-term effects of cannabis use on mania outcomes could not be detected., Conclusion: The results suggest that cannabis use may affect population expression of manic symptoms (and subsequent risk to develop bipolar disorder [Regeer, E.J., Krabbendam, L., R, DE Graaf, Ten Have, M., Nolen, W.A., Van Os, J., 2006. A prospective study of the transition rates of subthreshold (hypo)mania and depression in the general population. Psychol Med, 1-9.]). These findings may not be due to the emergence of psychotic symptoms or the effects of self-medication.

Objectives: High rates of psychotic disorders and psychotic symptoms have been found in urban environments but reports for bipolar affective illness have been inconsistent, possibly due to failure to stratify for comorbid psychotic symptoms. It was hypothesised, therefore, that any effect of urbanicity on the bipolar phenotype would be moderated by comorbid psychotic symptoms., Methods: In a random, representative population cohort of 7049 adults with no history of non-affective psychotic disorder, the cumulative incidence of bipolar and psychotic symptoms and syndromes, assessed with the CIDI, was examined over five levels of population density of place of residence. Similarly, the degree of comorbidity between broadly and narrowly defined bipolar phenotypes on the one hand, and the dichotomous presence of broadly (17.2%) and narrowly defined (3.8%) psychotic symptoms on the other, was examined as a function of population density of place of residence., Results: The rate of bipolar disorder, however defined, was progressively higher in more urbanised areas. However, in models of bipolar phenotypes, a strong interaction between comorbid psychosis and level of urbanicity was apparent, indicating that the greater the degree of psychotic comorbidity, the greater the effect size of the urban environmental factor. For bipolar disorder without psychosis, no effect of urbanicity was apparent., Conclusions: The results suggest differential environmental causal effects on affective and cognitive dimensions of bipolar psychopathology that are nevertheless strongly comorbid within the same categorically defined disorder, possibly due to the effect of shared genetic risk factors.

Objective: To study, in a geographically defined area, associations between the neighbourhood social environment and individual socioeconomic status on the one hand, and treated incidence of schizophrenia and level of subsequent service use on the other., Method: A combined data set of (i) patients with a case register diagnosis of schizophrenia and (ii) population controls was subjected to multilevel analyses, including neighbourhood exposures (neighbourhood socioeconomic disadvantage and social capital) and individual level confounders. Separate analyses were conducted for inpatient and outpatient psychiatric service consumption as indexed by the case register., Results: Neighbourhood socioeconomic disadvantage and neighbourhood social capital did not impact on the treated incidence of schizophrenia, but quantity of inpatient service consumption was higher in neighbourhoods with higher level of social control (i.e. where it is more likely that neighbours intervene in neighbourhood-threatening situations). In addition, most indicators of lower individual socioeconomic status were associated with higher treated incidence, while treated incidence was lower when individual educational status was low., Conclusion: Residents of high social control neighbourhoods may seek greater levels of resolution of psychiatric disorder in patient-residents, and by consequence may induce greater levels of inpatient service consumption in patients diagnosed with schizophrenia. Individual-level indicators of social disadvantage are associated with higher risk of treated psychotic disorder, with the exception of lower educational status, which may confer a lower probability of treatment given the presence of psychotic disorder.

Background: Previous work suggests that reaction time variability (RTV) in attentional tasks, as a measure of cognitive stability, is associated with degree of Val loading in COMT Val(158)Met genotype, and that this association may be relevant for the aetiology of schizophrenia. This study examined (i) to what degree RTV pertaining to tasks of varying cognitive complexity would be associated with increased risk for schizophrenia and (ii) to what degree this would be mediated by Val loading., Methods: COMT genotyping was investigated in a sample of 23 patients with schizophrenia, 33 first-degree relatives, and 21 controls. All participants performed the Flanker continuous performance test., Results: Schizophrenia liability was associated with number of correct trials of the Flanker test, but not with RTV, and this association was not mediated by COMT Val(158)Met genotype. Similarly, Met loading was associated with number of correct trials and with RTV, but this was not mediated by schizophrenia liability., Conclusions: Associations between COMT Val(158)Met genotype and RTV do not appear to reflect transmission of schizophrenia liability in families. Differential associations with Val and Met alleles across studies suggest indirect effects through gene-gene interactions or the influence of a functional polymorphism near COMT Val(158)Met.

Objective: General population longitudinal cohort studies have demonstrated the prognostic validity of self-reported psychotic experiences, but data on reliability and cross-validation with interview-based measures of these experiences are sparse. This study tested the reliability and validity of the Community Assessment of Psychic Experiences (CAPE42)., Method: At baseline, the CAPE42 was used to measure the subclinical psychosis phenotype in a general population sample (n = 765). At follow-up (mean interval: 7.7 months), the Structured Interview for Schizotypy, Revised (SIS-R), the Brief Psychiatric Rating Scale (BPRS), and the CAPE42 were administered (n = 510)., Results: Baseline self-reported dimensions of psychosis were specifically and independently associated with their equivalent interview-based dimension at follow-up (standardized effect sizes of 0.4-0.5) and with their equivalent self-reported measure (standardized effect sizes of 0.6-0.8)., Conclusion: The results indicate that self-reported dimensions of psychotic experiences in general population samples appear to be stable, reliable and valid.

Background: The aims of the study were to investigate whether (i) patients with lifetime presence of non-affective psychosis show an external-personal attribution bias for negative events, (ii) this attribution style can also be detected in first-degree relatives of patients with psychosis and subjects with subclinical psychotic experiences, and (iii) this attribution style is related to the presence of psychotic symptoms, in particular delusions., Method: Participants were 23 patients with lifetime presence of non-affective psychosis, a high- risk group of 36 first-degree relatives of patients with non-affective psychosis, a high-risk group of 31 subjects with subclinical psychotic experiences and 46 normal controls. Attribution style was measured by the Internal, Personal and Situational Attribution Questionnaire. Positive symptoms were assessed with the Present State Examination (PSE) and the Scale for the Assessment of Positive Symptoms (SAPS)., Results: Relative to the controls, an externalizing bias was apparent in the patient group (beta = 0.20, p = 0.03) but not in the two high-risk groups. There was a dose-response association between externalizing bias and the delusions subscale of the PSE (relative to lowest level: highest level of delusions: beta = 0.53, p = 0.04; intermediate levels of delusions: beta = 0.23, p = 0.35). No significant differences were found in personalizing bias between the four groups., Conclusions: Patients with psychosis tend to use an externalizing bias in their explanations of negative social events, and this bias is associated with the presence of positive psychotic symptoms, in particular delusions. A deviant attribution style is not part of the vulnerability to psychosis.

Background: The reported link between psychological trauma and onset of psychosis remains controversial., Aims: To examine associations between self-reported psychological trauma and psychotic symptoms as a function of prior evidence of vulnerability to psychosis (psychosis proneness)., Method: At baseline, 2524 adolescents aged 14-24 years provided self-reports on psychological trauma and psychosis proneness, and at follow-up (on average 42 months later) participants were interviewed for presence of psychotic symptoms., Results: Self-reported trauma was associated with psychotic symptoms, in particular at more severe levels (adjusted OR 1.89, 95% CI1.16-3.08) and following trauma associated with intense fear, helplessness or horror. The risk difference between those with and without self-reported trauma at baseline was 7% in the group with baseline psychosis proneness, but only 1.8% in those without (adjusted test for difference between these two effect sizes: chi2=4.6, P=0.032)., Conclusions: Exposure to psychological trauma may increase the risk of psychotic symptoms in people vulnerable to psychosis.

Background: Previous work suggests that subthreshold depression and subthreshold (hypo)mania are common, although little is known about the prognosis in terms of transition to clinical disorder. This paper presents data on the temporal relationship between subthreshold and clinical expression of mood phenotypes., Method: In a random general population sample of 7076 individuals, symptoms of depression and (hypo)mania were measured with the Composite International Diagnostic Interview (CIDI) at baseline, after 1 year, and 2 years later., Results: At baseline, the lifetime prevalences of depressive and (hypo)manic symptoms were 17.2% and 1.2% respectively. Predictive values of mood symptoms for a DSM-III-R mood disorder ranged from 14.3% to 50%. (Hypo)manic mood symptoms had much higher predictive values than unipolar manifestations, not only for bipolar disorder but also for major depression., Conclusions: The subthreshold expressions of depression and (hypo)mania are prevalent and continuous with more severe clinical states. The cross-prediction of mood symptoms may support a continuum from depressive to (hypo)manic symptoms. The high predictive value of (hypo)manic symptoms for mood disorders suggests that the experience of (hypo)manic symptoms is a stronger indicator of vulnerability for mood dysregulation than the experience of depressive symptoms.

This study examined whether the probabilistic reasoning bias referred to as a "jumping-to-conclusions" (JTC) style of reasoning, which, according to previous research, is associated with particular psychotic symptoms such as delusions, represents a trait that can also be detected in nonpsychotic relatives of patients with schizophrenia and in nonpsychotic individuals with a high level of psychotic experiences. Participants were, in order of level of psychosis liability, 40 patients with schizophrenia or a schizoaffective disorder, 40 first-degree nonpsychotic relatives, 41 participants from the general population with above average expression of psychotic experiences, and 53 participants from the general population with an average level of psychotic experiences. A "jumping-to-conclusions" bias was assessed using the beads task. A dose-response relationship was found in the association between level of psychosis liability and JTC (defined as needing only a single bead to complete the beads task) (odds ratio [OR] linear trend = 1.59, 95% CI: 1.13-2.24), and, independently, alinear association was apparent between JTC and level of delusional ideation (OR linear trend = 2.59, 95% CI: 1.18-5.69). In addition, the association between psychosis liability and JTC was generally much stronger as the level of delusional ideation was higher. JTC is associated with liability to psychosis (trait), in particular if the psychosis phenotype is characterized by delusional ideation (state).

Background: The urban environment may increase the risk for psychotic disorder in interaction with pre-existing risk for psychosis, but direct confirmation has been lacking. The hypothesis was examined that the outcome of subclinical expression of psychosis during adolescence, as an indicator of psychosis-proneness, would be worse for those growing up in an urban environment, in terms of having a greater probability of psychosis persistence over a 3.5-year period., Method: A cohort of 918 adolescents from the Early Developmental Stages of Psychopathology Study (EDSP), aged 14-17 years (mean 15.1 years), growing up in contrasting urban and non-urban environments, completed a self-report measure of psychotic symptoms at baseline (Baseline Psychosis) and at first follow-up around 1 year post-baseline (T1). They were again interviewed by trained psychologists for the presence of psychotic symptoms at the second follow-up on average 3.5 years post-baseline (T2)., Results: The rate of T2 psychotic symptoms was 14.2% in those exposed to neither Baseline Psychosis nor Urbanicity, 12.1% in those exposed to Urbanicity alone, 14.9% in those exposed to Baseline Psychosis alone and 29.0% in those exposed to both Baseline Psychosis and Urbanicity. The odds ratio (OR) for the combined exposure was 2.46 [95% confidence interval (CI) 1.46-4.14], significantly greater than that expected if Urbanicity and Baseline Psychosis acted independently., Conclusion: These findings support the suggestion that the outcome of the developmental expression of psychosis is worse in urban environments. The environment may impact on risk for psychotic disorder by causing an abnormal persistence of a developmentally common expression of psychotic experiences.

It is unknown to what degree dimensions of schizotypy (subclinical psychosis) show independent, family-specific variation in the general population. Psychologists administered the Community Assessment of Psychic Experiences, the Structured Interview for Schizotypy-Revised (SIS-R), and the Brief Psychiatric Rating Scale to 257 subjects pertaining to 82 general population families. All 3 instruments showed family-specific variation for positive and negative subclinical psychosis dimensions with between-families proportions of total variance between 10% and 40%. However, only the SIS-R showed family-specific variation of the negative dimension independent of its correlation with the positive dimension. The positive dimension of subclinical psychosis shows familial-specific variation in samples unselected for psychiatric disorder, suggesting dimensional liability in the population. The SIS-R additionally captures family-specific variation in the negative domain., (2006 APA, all rights reserved)

Objective: Evidence suggests that cognitive functioning in bipolar disorder may be impaired even in euthymic states, but it is unclear if the pattern of deficits is similar to the deficits found in schizophrenia. The aim of this study was to review quantitatively the studies on cognitive performance in schizophrenia and bipolar disorder., Methods: Articles for consideration were identified through a literature search in MEDLINE and PsycLIT in the period between 1985 and October 2004, using the keywords "schizophrenia" combined with "bipolar disorder", or "manic-depress*" or "manic" combined with "cogniti*" or "neuropsycholog*". Thirty-one studies were included that: i) evaluated cognitive performance using standardized and reliable neuropsychological testing procedures; ii) compared adult patients with schizophrenia and with bipolar disorder; iii) reported test scores of both patient groups, or exact p-values, t-values, or F-values; and iv) were published as an original article in a peer-reviewed English language journal., Results: Meta-analyses of all studies indicated that patients with bipolar disorder generally perform better than patients with schizophrenia, but the distribution of effect sizes showed substantial heterogeneity. Results based on a more homogeneous subset of studies that matched patient groups on clinical and demographic characteristics pointed in the same direction, with effect sizes in the moderate range., Conclusions: Patients with bipolar disorder show better cognitive performance than patients with schizophrenia, even when matched for clinical and demographic characteristics.