Showing papers by "Robin M. Murray published in 2008"

Large recurrent microdeletions associated with schizophrenia

Abstract: Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.

Grey and white matter distribution in very preterm adolescents mediates neurodevelopmental outcome.

Abstract: Very preterm (VPT) birth is associated with altered cortical development and long-term neurodevelopmental sequelae. We used voxel-based morphometry to investigate white (WM) and grey matter (GM) distribution in VPT adolescents and controls, and the association with gestational age and neonatal ultrasound findings in the VPT individuals. GM and WM volumes were additionally investigated in relation to adolescent neurodevelopmental outcome. Structural MRI data were acquired with a 1.5 Tesla machine in 218 VPT adolescents (<33 weeks, gestation) and 128 controls aged 14-15 years, and analysed using SPM2 software. VPT individuals compared to controls showed reduced GM in temporal, frontal, occipital cortices and cerebellum, including putamen, insula, cuneus, fusiform gyrus, thalamus and caudate nucleus, and increased GM predominantly in temporal and frontal lobes, including cingulate and fusiform gyri and cerebellum. WM loss was concentrated in the brainstem, internal capsule, temporal and frontal regions and the major fasciculi. WM excesses were observed in temporal, parietal and frontal regions. Investigation of the inter-relationships between brain regions and changes revealed that all selected areas where between-group increased and decreased WM and GM volumes differences were observed, were structurally associated, highlighting the influence that abnormalities in one brain area may exert over others. VPT individuals with evidence of periventricular haemorrhage and ventricular dilatation on neonatal ultrasound exhibited the greatest WM and GM alterations. VPT adolescents obtained lower scores than controls on measures of language and executive function and were more likely to show cognitive impairment compared to controls (27% versus 14%, respectively). Several areas where VPT individuals demonstrated decreased GM and WM volume were linearly associated with gestational age and mediated cognitive impairment. To summarize, our data demonstrates that VPT birth is associated with altered brain structure in adolescence. GM and WM alterations are associated with length of gestation and mediate adolescent neurodevelopmental impairment. Thus, anatomical brain changes may contribute to specific cognitive deficits associated with VPT birth and could be used in the identification of those individuals who may be at increased risk for cognitive impairment.

Gene-Environment Interplay Between Cannabis and Psychosis

Abstract: Cannabis use is considered a contributory cause of schizophrenia and psychotic illness. However, only a small proportion of cannabis users develop psychosis. This can partly be explained by the amount and duration of the consumption of cannabis and by its strength but also by the age at which individuals are first exposed to cannabis. Genetic factors, in particular, are likely to play a role in the short- and the long-term effects cannabis may have on psychosis outcome. This review will therefore consider the interplay between genes and exposure to cannabis in the development of psychotic symptoms and schizophrenia. Studies using genetic, epidemiological, experimental, and observational techniques will be discussed to investigate gene-environment correlation gene-environment interaction, and higher order interactions within the cannabis-psychosis association. Evidence suggests that mechanisms of gene-environment interaction are likely to underlie the association between cannabis and psychosis. In this respect, multiple variations within multiple genes—rather than single genetic polymorphisms—together with other environmental factors (eg, stress) may interact with cannabis to increase the risk of psychosis. Further research on these higher order interactions is needed to better understand the biological pathway by which cannabis use, in some individuals, may cause psychosis in the short- and long term.

Substantial genetic overlap between neurocognition and schizophrenia: genetic modeling in twin samples

Abstract: Context The use of endophenotypes, biological traits that increase the liability to a disorder, represents one strategy to facilitate the detection of susceptibility genes for complex behavioral disorders such as schizophrenia. Establishing that a candidate trait is both heritable and linked genetically to schizophrenia is integral to its validity as an endophenotypic marker. Neurocognitive deficits are among the most promising indicators of increased risk for schizophrenia; however, it is not clear to what extent these deficits are genetically linked to the disorder. Objectives To quantify the genetic and environmental contributions to the variability of selected neurocognitive measures and to estimate the genetic relationship between these and schizophrenia. Design Genetic model fitting to monozygotic and dizygotic twin data. Setting United Kingdom psychiatric research institute. Participants Two hundred sixty-seven monozygotic and dizygotic twins concordant and discordant for schizophrenia, and healthy monozygotic and dizygotic control twin pairs. Main Outcome Measures The heritabilities of intelligence, working memory, processing speed, perceptual organization, and verbal comprehension were estimated, and the genetic relationship between each of these and schizophrenia was quantified. Results Genetic influences contributed substantially to all of the cognitive domains, but intelligence and working memory were the most heritable. A significant correlation was found between intelligence and schizophrenia ( r = −0.61; 95% confidence interval, −0.71 to −0.48), with shared genetic variance accounting for 92% of the covariance between the two. Genetic influences also explained most of the covariance between working memory and schizophrenia. Significant but lesser portions of covariance between the other cognitive domains and schizophrenia were also found to be genetically shared. Environmental effects, although separately linked to neurocognition and schizophrenia, did not generally contribute to their covariance. Conclusion Genomewide searches using factorial designs stratifying for levels of intelligence and working memory will assist in the search for finding quantitative trait loci for schizophrenia.

Cumulative social disadvantage, ethnicity and first-episode psychosis: a case-control study

Abstract: Background. Numerous studies have reported high rates of psychosis in the Black Caribbean population in the UK. Recent speculation about the reasons for these high rates has focused on social factors. However, there have been few empirical Studies. We sought to compare the prevalence of specific indicators of social disadvantage and isolation, and variations by ethnicity, in subjects with a first episode of psychosis and a series of healthy controls. Method. All cases with a first episode of psychosis who made contact with psychiatric services in defined catchment areas in London and Nottingham, UK and a series of community controls were recruited over a 3-year period. Data g to clinical and social variables were collected from cases and controls. Results. On all indicators, cases were more socially, disadvantaged and isolated than controls, after controlling for potential confounders. These associations held when the sample was restricted to those with in affective diagnosis and to those with a short prodrome and short duration Of untreated psychosis. There was a clear linear relationship between concentrated disadvantage and odds of psychosis. Similar patterns were evident in the two main ethnic groups, White British and Black Caribbean. However, indicators of social disadvantage and isolation were more common in Black Caribbean Subjects than White British subjects. Conclusions. We found strong associations between indicators of disadvantage and psychosis. If these variables index exposure to factors that increase risk of psychosis, their greater prevalence in the Black Caribbean Population may contribute to the reported high rates of psychosis in this population.

Testing the association between the incidence of schizophrenia and social capital in an urban area.

Abstract: BACKGROUND: Social capital has been considered aetiologically important in schizophrenia but the empirical evidence to support this hypothesis is absent We tested whether social capital, measured at the neighbourhood level, was associated with the incidence of schizophrenia (ICD-10 F20) MethodWe administered a cross-sectional questionnaire on social capital to 5% of the adult population in 33 neighbourhoods (wards) in South London (n=16 459) The questionnaire contained items relating to two social capital constructs: social cohesion and trust (SC&T) and social disorganization (SocD) Schizophrenia incidence rates, estimated using data from the Aetiology and Ethnicity in Schizophrenia and Other Psychoses (AESOP) study, provided the outcome We used multi-level Poisson regression to test our hypothesis while controlling for individual- and neighbourhood-level characteristics RESULTS: We identified 148 cases during 565 576 person-years at-risk Twenty-six per cent of the variation in incidence rates was attributable to neighbourhood-level characteristics Response from the social capital survey was 257% The association between SC&T and schizophrenia was U-shaped Compared with neighbourhoods with medial levels of SC&T, incidence rates were significantly higher in neighbourhoods with low [incidence rates ratio (IRR) 20, 95% confidence interval (CI) 12-33] and high (IRR 25, 95% CI 13-48) levels of SC&T, independent of age, sex, ethnicity, ethnic density, ethnic fragmentation and socio-economic deprivation ConclusionNeighbourhood variation in SC&T was non-linearly associated with the incidence of schizophrenia within an urban area Neighbourhoods with low SC&T may fail to mediate social stress whereas high SC&T neighbourhoods may have greater informal social control or may increase the risk of schizophrenia for residents excluded from accessing available social capital

Cerebellar Growth and Behavioural & Neuropsychological Outcome in Preterm Adolescents.

Abstract: Adolescence is a time of social and cognitive development associated with changes in brain structure and function. These developmental changes may show an altered path in individuals born before 33 weeks' gestation (very preterm; VPT). The cerebellum is affected by VPT birth, but no studies have yet assessed the adolescent development of this structure, or whether developmental changes in cerebellar structure are associated with cognitive and behavioural outcome. We measured cerebellar volumes on structural magnetic resonance images in 65 adolescents who were born before 33 weeks' gestation (VPT) and 34 term-born adolescents (mean age VPT = 15.09, SD = 1.43/mean age term-born = 15.43, SD = 0.56) and again in adulthood (mean age VPT = 18.61, SD = 1.02/mean age term-born = 19.17, SD = 0.95). Participants also underwent neuropsychological tests; the Wechsler Abbreviated Scale of Intelligence and the Controlled Oral Word Association Test and completed the General Health Questionnaire-12. Repeated measures ANOVA showed a main effect of time-point (F = 4.59, df = 1, P = 0.035) and a time-point by group interaction (F = 8.03, df = 1, P = 0.006) on cerebellar growth. By adulthood, cerebellar volumes were 3.11% smaller in the preterm group than they had been in early adolescence (P = 0.000). Cerebellar volume did not change significantly in the control group (P = 0.612). There were significant negative correlations between change in cerebellar volume and GHQ-12 in the VPT group; total score (r = -0.324 P = 0.028) and several subscales; concentration (r = -0.378 P = 0.010), feeling useful (r = -0.311 P = 0.035), decision-making capability (r = -0.348 P = 0.018), overcoming difficulties (r = -0.331 P = 0.025), feeling confident (r = -0.309 P = 0.037) and feeling worthless (r = -0.329 P = 0.026). In the VPT group there were positive correlations between cerebellar volume and full-scale IQ (adolescence; r = 0.471, P = 0.002/adulthood; r = 0.309, P = 0.047), performance IQ (adolescence; r = 0.434, P = 0.004/adulthood; r = 0.345, P = 0.025) and verbal IQ (adolescence; r = 0.401, P = 0.008) which were not maintained after controlling for white matter volume. We have demonstrated a reduction in cerebellar volume between adolescence and young adulthood in VPT individuals, which is correlated with reduced self-reported wellbeing.

Cognitive maturation in preterm and term born adolescents

Abstract: Background: Adolescence is a critical period of brain structural reorganisation and maturation of cognitive abilities. This relatively late developmental reorganisation may be altered in individuals who were born preterm. Methods: We carried out longitudinal neuropsychological testing in 94 very preterm individuals (VPT; before 33 weeks’ gestation) and 44 term born individuals at mean ages of 15.3 years (adolescence) and 19.5 years (young adulthood). Results: Full scale, verbal and performance IQ and phonological verbal fluency were significantly lower in the VPT group than the term group at both ages. Repeated measures ANOVA showed only one group by time point interaction for semantic verbal fluency (F = 10.25; df = 107; p = 0.002). Paired-sample t tests showed that semantic verbal fluency increased significantly in the term group over adolescence (t = −5.10; df = 42; p Conclusion: Decrements of intellectual functioning in VPT individuals persist into adulthood. Additionally, there is a deficit in the adolescent maturation of semantic verbal fluency in individuals born VPT.

Scholastic achievement at age 16 and risk of schizophrenia and other psychoses: a national cohort study

Abstract: Background. There is abundant evidence that schizophrenia is associated with cognitive deficits in childhood. However, previous studies investigating school performance have been inconclusive. Furthermore, there are several biological and social factors that could confound the association. We investigated whether school performance at age 16 is associated with risk of adult schizophrenia and other psychoses in a large national cohort, while controlling for multiple confounders. Method. Using a national sample of 907011 individuals bom in Sweden between 1973 and 1983, we used Cox regression to assess whether scholastic achievement at age 15-16 predicted hospital admission for psychosis between ages 17 and 31, adjusting for potential confounders. Results. Poor school performance was associated with increased rates of schizophrenia [hazard ratio (HR) 3.9, 95% confidence interval (CI) 2.8-5.3], schizo-affective disorder (HR 4.2, 95 % CI 1.9-9.1) and other psychoses (HR 3.0, 95 % CI 2.3-4.0). Receiving the lowest (E) grade was significantly associated with risk for schizophrenia and other psychoses in every school subject. There was no evidence of confounding by migrant status, low birthweight, hypoxia, parental education level or socio-economic group. Conclusions. Poor school performance across all domains is strongly associated with risk for schizophrenia and other psychoses.

Unemployment, social isolation, achievement–expectation mismatch and psychosis: findings from the ÆSOP Study

Abstract: Introduction In this study, we aimed to establish: (1) whether social isolation modifies the effect of unemployment on first episode psychosis and duration of untreated psychosis (DUP); and (2) whether the gap between high employment expectations and perceived poor employment achievement is associated with first-episode psychosis; and (3) whether the relationship of this achievement-expectation gap and first-episode psychosis is strongest in the African-Caribbean population. Method All patients with a first episode of psychosis presenting to specialist mental health services within tightly defined catchment areas in south-east London and Nottingham over a 2-year period were included in the study. A random sample of healthy participants living within the same catchment areas was also recruited. Data were collected on socio-demographic and clinical characteristics, DUP, social contacts, and perceived levels of employment achievement and expectation. Analysis was conducted on data of 546 participants (224 cases, 322 controls) from the SOP study. Results The relationship between unemployment and risk of non-affective psychosis was moderated by social contacts (unemployed/low social contacts, OR 7.52, 95% CI 2.97-19.08; unemployed/medium social contacts, OR 3.27, 95% CI 1.66-6.47; unemployed/high social contacts, OR 1.36, 95% CI 0.47-3.93). Unemployed patients experienced a longer DUP when having reported lower levels of social contacts. Participants whose employment achievement was lower than their expectations were more likely to be cases than those in whom achievement matched or exceeded expectations (adjusted OR 1.84, 95% CI 1.13-3.02). This applied equally to both African-Caribbean and White British participants (the Mantel-Haenszel test for homogeneity of odds ratios, chi(2) = 0.96, P = 0.33). Conclusions This study suggests that unemployment, social isolation, employment achievement and expectations are important environmental factors associated with risk of psychosis. More attention needs to be focused on interactions between environmental factors as well as subjective experience of those factors in future research on the aetiology of psychosis.

Self-harm in first-episode psychosis.

Abstract: Background: Little is known about self-harm occurring during the period of untreated first-episode psychosis. Aims: To establish the prevalence, nature, motivation and risk factors for self-harm occurring during the untreated phase of first-episode psychosis. Method: As part of the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study, episodes of self-harm were identified among all incident cases of psychosis presenting to services in south-east London and Nottingham over a 2-year period. Results: Of the 496 participants, 56 (11.3%) had engaged in self-harm between the onset of psychotic symptoms and first presentation to services. The independent correlates of self-harm were: male gender, belonging to social class I/II, depression and a prolonged period of untreated psychosis. increased insight was also associated with risk of self-harm. Conclusions: Self-harm is common during the pre-treatment phase of first-episode psychosis. A unique set of fixed and malleable risk factors appear to operate in those with first-episode psychosis. Reducing treatment delay and modifying disease attitudes may be key targets for suicide prevention.

Perceptions of disadvantage, ethnicity and psychosis

Abstract: Background: People from Black ethnic groups (African-Caribbean and Black African) are more prone to develop psychosis in Western countries. This excess might be explained by perceptions of disadvantage. Aims: To investigate whether the higher incidence of psychosis in Black people is mediated by perceptions of disadvantage. Method: A population-based incidence and case-control study of first-episode psychosis (Aetiology and Ethnicity in Schizophrenia and Other Psychoses (ASOP)). A total of 482 participants answered questions about perceived disadvantage. Results: Black ethnic groups had a higher incidence of psychosis (OR=4.7, 95% CI 3.1-7.2). After controlling for religious affiliation, social class and unemployment, the association of ethnicity with psychosis was attenuated (OR=3.0, 95% Cl 1.6-5.4) by perceptions of disadvantage. Participants in the Black non-psychosis group often attributed their disadvantage to racism, whereas Black people in the psychosis group attributed it to their own situation. Conclusions: Perceived disadvantage is partly associated with the excess of psychosis among Black people living in the UK. This may have implications for primary prevention.

Differential methylation of the X-chromosome is a possible source of discordance for bipolar disorder female monozygotic twins

Abstract: Monozygotic (MZ) twins may be subject to epigenetic modifications that could result in different patterns of gene expression. Several lines of evidence suggest that epigenetic factors may underlie mental disorders such as bipolar disorder (BD) and schizophrenia (SZ). One important epigenetic modification, of relevance to female MZ twins, is X-chromosome inactivation. Some MZ female twin pairs are discordant for monogenic X linked disorders because of differential X inactivation. We postulated that similar mechanisms may also occur in disorders with more complex inheritance including BD and SZ. Examination of X-chromosome inactivation patterns in DNA samples from blood and/or buccal swabs in a series of 63 female MZ twin pairs concordant or discordant for BD or SZ and healthy MZ controls suggests a potential contribution from X-linked loci to discordance within twin pairs for BD but is inconclusive for SZ. Discordant female bipolar twins showed greater differences in the methylation of the maternal and paternal X alleles than concordant twin pairs and suggest that differential skewing of X-chromosome inactivation may contribute to the discordance observed for bipolar disorder in female MZ twin pairs and the potential involvement of X-linked loci in the disorder.

Personality in schizophrenia assessed with the Temperament and Character Inventory (TCI)

Abstract: The Temperament and Character Inventory (TCI) is a well-established self-report questionnaire measuring four temperament and three character dimensions. However, surprisingly few studies have used it to examine the personality of patients with schizophrenia, and none in Japan. Moreover, possible gender differences in personality among patients with schizophrenia have not been well documented. We administered the TCI to 86 Japanese patients with schizophrenia and 115 age- and gender-matched healthy controls to characterize personality traits in patients with schizophrenia and to examine their relationships with clinical variables, particularly gender and symptoms. Compared with controls, patients demonstrated significantly lower novelty seeking, reward dependence, self-directedness and cooperativeness, and higher harm avoidance and self-transcendence. Male patients showed even more pronounced personality alteration than female patients when both of them were compared with healthy people. Personality dimensions were moderately correlated with symptom dimensions assessed by the Positive and Negative Syndrome Scale (PANSS). These results, together with prior findings in several other countries, suggest that schizophrenia patients have a unique personality profile which appears to be present across cultures and that the greater alteration of personality in schizophrenia males might be related to their poorer social and community functioning.

Auditory P300 in patients with bipolar disorder and their unaffected relatives.

Abstract: Objectives: There is evidence that genetic susceptibility may be shared between bipolar disorder (BD) and schizophrenia, but electrophysiological phenotypes which have been extensively used in studies of genetic susceptibility for schizophrenia remain far less explored in bipolar illness. This study assesses whether auditory P300 latency delays and amplitude reductions, which have been demonstrated in patients with schizophrenia and their unaffected first-degree relatives, are associated with familial liability to psychotic bipolar illness. Methods: The P300 auditory evoked potential was obtained using an oddball task from 37 participants with BD who had a history of psychotic symptoms, 38 of their unaffected first-degree relatives and 42 healthy unrelated comparison subjects. Patients and relatives came from families multiply affected with BD or another functional psychotic disorder. P300 amplitude and latency at midline sites were compared between the groups, using linear regression analyses and robust variance estimators for clustered data, including age and gender as covariates. Results: Bipolar disorder patients with a history of psychosis and their unaffected relatives showed significantly delayed P300 latency at Pz compared to controls. The groups did not differ in P300 amplitude. Conclusions: P300 latency delays are associated with both psychotic BD and familial liability for this illness. Sample size limited our ability to test for multimodal distribution of P300 measures among relatives, which might be expected if only a subgroup inherits any deficits. In future it will be of interest to directly compare groups of families with psychotic and non-psychotic forms of BD to explore further the role of psychotic symptoms with regard to P300 measures in the disorder. Our results indicate that delayed P300 latency is a promising candidate endophenotype for psychotic BD, as well as schizophrenia, and may reflect the impact of shared susceptibility genes for both types of psychosis.

Psychotic-like experiences and other antecedents of schizophrenia in children aged 9-12 years: a comparison of ethnic and migrant groups in the United Kingdom.

Abstract: Background The incidence of schizophrenia and the prevalence of psychotic symptoms in the general adult population are elevated in migrant and ethnic minority groups relative to host populations. These increases are particularly prominent among African-Caribbean migrants to the UK. This study examined the associations of ethnicity and migrant status with a triad of putative antecedents of schizophrenia in a UK community sample of children aged 9–12 years. The antecedent triad comprised: (i) psychotic-like experiences; (ii) a speech and/or motor developmental delay or abnormality; and (iii) a social, emotional or behavioural problem. Method Children ( n =595) and their primary caregivers, recruited via schools and general practitioners in southeast London, completed questionnaires. Four indices of risk were examined for associations with ethnicity and migrant status: (i) certain experience of at least one psychotic-like experience; (ii) severity of psychotic-like experiences (total psychotic-like experience score); (iii) experience of the antecedent triad; and (iv) severity of antecedent triad experiences (triad score). Results African-Caribbean children, as compared to white British children, experienced greater risk on all four indices. There were trends for South Asian and Oriental children to present lowered risk on several indices, relative to white British children. Migration status was unrelated to any risk index. Conclusion Prevalence of the putative antecedents of schizophrenia is greater among children of African-Caribbean origin living in the UK than among white British children. This parallels the increased incidence of schizophrenia and elevated prevalence of psychotic symptoms among adults of African-Caribbean origin.

Neurological abnormalities and cognitive ability in first-episode psychosis

Abstract: Background it remains unclear if the excess of neurological soft signs, or of certain types of neurological soft signs, is common to all psychoses, and whether this excess is simply an epiphenomenon of the lower general cognitive ability present in psychosis. Aims To investigate whether an excess of neurological soft signs is independent of diagnosis (schizophrenia v. affective psychosis) and cognitive ability (IQ). Method Evaluation of types of neurological soft signs in a prospective cohort of all individuals presenting with psychoses over 2 years (n=310), and in a control group from the general population (n=239). Results Primary (P < 0.001), motor coordination (P < 0.001), and motor sequencing (P < 0.001) sign scores were significantly higher in people with any psychosis than in the control group. However, only primary and motor coordination scores remained higher when individuals with psychosis and controls were matched for premorbid and current IQ. Conclusions Higher rates of primary and motor coordination signs are not associated with lower cognitive ability, and are specific to the presence of psychosis.

Genetic variation in the serotonin transporter modulates neural system-wide response to fearful faces.

Abstract: A distributed, serotonergically innervated neural system comprising extrastriate cortex, amygdala and ventral prefrontal cortex is critical for identification of socially relevant emotive stimuli. The extent to which a genetic variation of serotonin transporter gene 5-HTTLPR impacts functional connectivity between the amygdala and the other components of this neural system remains little examined. In our study, neural activity was measured using event-related functional magnetic resonance imaging in 29 right-handed, white Caucasian healthy subjects as they viewed mild or prototypical fearful and neutral facial expressions. 5-HTTLPR genotype was classified as homozygous for the short allele (S/S), homozygous for the long allele (L/L) or heterozygous (S/L). S/S showed greater activity than L/L within right fusiform gyrus (FG) to prototypically fearful faces. To these fearful faces, S/S more than other genotype subgroups showed significantly greater positive functional connectivity between right amygdala and FG and between right FG and right ventrolateral prefrontal cortex (VLPFC). There was a positive association between measure of psychoticism and degree of functional connectivity between right FG and right VLPFC in response to prototypically fearful faces. Our data are the first to show that genotypic variation in 5-HTTLPR modulates both the amplitude within and the functional connectivity between different components of the visual object-processing neural system to emotionally salient stimuli. These effects may underlie the vulnerability to mood and anxiety disorders potentially triggered by socially salient, emotional cues in individuals with the S allele of 5-HTTLPR.

Facial fear processing and psychotic symptoms in schizophrenia: functional magnetic resonance imaging study.

Abstract: Background The recognition of negative facial affect is impaired in people with schizophrenia. The neural underpinnings of this deficit and its relationship to the symptoms of psychosis are still unclear. Aims To examine the association between positive and negative psychotic symptoms and activation within the amygdala and extrastriate visual regions of patients with schizophrenia during fearful and neutral facial expression processing. Method Functional magnetic resonance imaging was used to measure neural responses to neutral and fearful facial expressions in 11 patients with schizophrenia and 9 healthy volunteers during an implicit emotional task. Results No association between amygdala activation and positive symptoms was found; the activation within the left superior temporal gyrus was negatively associated with the negative symptoms of the patients. Conclusions Our results indicate an association between impaired extrastriate visual processing of facial fear and negative symptoms, which may underlie the previously reported difficulties of patients with negative symptoms in the recognition of facial fear.

What is the mechanism whereby cannabis use increases risk of psychosis

Abstract: Cannabis use has increased greatly over the last three decades. The various types of cannabis differ in their concentration of the main psychoactive component, Delta-9-tetrahydrocannabinol (THC), and the other major ingredient, cannabidiol (CBD). Plant engineering has maximized levels of THC, thus increasing the potency of street cannabis. It is well known that cannabis intoxication can cause brief psychotic symptoms like paranoia, whilst recent evidence demonstrates that heavy use of cannabis increases the risk of chronic psychoses like schizophrenia; genetic vulnerability seems to predispose some people to a higher risk. This paper starts to consider the neurochemical mechanisms whereby cannabis use increases the risk of psychosis.

Executive function and genetic predisposition to schizophrenia--the Maudsley family study.

Abstract: Executive cognitive impairment has been found in families affected by schizophrenia and is a putative endophenotype. We wished to explore its genetic basis further by studying the association between impairment and genetic loading for schizophrenia. We studied 30 schizophrenia patients with a family history of schizophrenia, 53 of their nonpsychotic first-degree relatives (familial), 32 patients with schizophrenia but no known family history of psychosis, 52 of their first-degree relatives (nonfamilial), and 47 normal controls. They were tested using the National Adult Reading Test (NART), Trails A and B, Verbal fluency tasks, and a computerized version of the Wisconsin Card Sorting Test (WCST). Familial, but not nonfamilial, relatives were impaired on NART, letter fluency, Trails B, and WCST total errors. They were inferior to nonfamilial relatives on letter fluency and Trails A. Both sets of relatives were impaired on Trails B controlling for Trails A, and on WCST categories achieved. There were no significant differences between schizophrenia patients with and without a family history. Our results suggest that executive deficits qualitatively similar to those seen in those with schizophrenia reflect familial susceptibility, even taking early IQ and education into consideration, consistent with a genetic mechanism.