[Show abstract][Hide abstract] ABSTRACT: The Brain-derived Neurotrophic Factor (BDNF) modulates cognitive processes and is associated with increased risk of schizophrenia. Childhood trauma (CT) is frequent in patients with psychosis and severely affects course and outcome.
Schizophrenia Research 08/2014; · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The "jumping to conclusions" (JTC) data-gathering bias is implicated in the development and maintenance of psychosis but has only recently been studied in first episode psychosis (FEP). In this study, we set out to establish the relationship of JTC in FEP with delusions and neuropsychological functioning. Methods: One hundred and eight FEP patients and 101 age-matched controls completed assessments of delusions, general intelligence (IQ), working memory (WM), and JTC (the probabilistic reasoning "beads" task). Results: Half the FEP participants jumped to conclusions on at least 1 task, compared with 25% of controls (OR range 2.1 to 3.9; 95% CI range 1.5 to 8.0, P values ≤ .02). JTC was associated with clinical, but not nonclinical delusion severity, and with neuropsychological functioning, irrespective of clinical status. Both IQ and delusion severity, but not WM, were independently associated with JTC in the FEP group. Conclusions: JTC is present in FEP. The specific association of JTC with clinical delusions supports a state, maintaining role for the bias. The associations of JTC with neuropsychological functioning indicate a separable, trait aspect to the bias, which may confer vulnerability to psychosis. The work has potential to inform emerging interventions targeting reasoning biases in early psychosis.
[Show abstract][Hide abstract] ABSTRACT: Background: Failure to account for the etiological diversity that typically occurs in psychi-atric cohorts may increase the potential for confounding as a proportion of genetic variance will be specific to exposures that have varying distributions in cases.This study investigated whether minimizing the potential for such confounding strengthened the evidence for a genetic candidate currently unsupported at the genome-wide level. Methods: Two hundred and ninety-one first-episode psychosis cases from South Lon-don, UK and 218 unaffected controls were evaluated for a functional polymorphism at the rs1360780 locus in FKBP5. The relationship between FKBP5 and psychosis was modeled using logistic regression. Cannabis use (Cannabis Experiences Questionnaire) and parental separation (Childhood Experience of Care and Abuse Questionnaire) were included as confounders in the analysis. Results: Association at rs1360780 was not detected until the effects of the two environ-mental factors had been adjusted for in the model (OR = 2.81, 95% CI 1.23–6.43, p = 0.02). A statistical interaction between rs1360780 and parental separation was confirmed by stratified tests (OR = 2.8, p = 0.02 vs. OR = 0.89, p = 0.80). The genetic main effect was directionally consistent with findings in other (stress-related) clinical phenotypes. More-over, the variation in effect magnitude was explained by the level of power associated with different cannabis constructs used in the model (r = 0.95). Conclusion: Our results suggest that the extent to which genetic variants in FKBP5 can influence susceptibility to psychosis may depend on other etiological factors. This finding requires further validation in large independent cohorts. Potentially this work could have translational implications; the ability to discriminate between genetic etiologies based on a case-by-case understanding of previous environmental exposures would confer an important clinical advantage that would benefit the delivery of personalizable treatment strategies.
[Show abstract][Hide abstract] ABSTRACT: Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.
[Show abstract][Hide abstract] ABSTRACT: Objectives
Substance abuse is a well established risk factor for First-Episode Psychosis (FEP), but its influence on FEP course is less clear. Starting from our baseline observation that substance users were younger than non-users at the psychosis onset, we hypothesized that substance use at baseline could be an independent risk factor for a worse clinical course.
An incidence cohort of patients with FEP collected in an 8 year period (2002–2009) at the Bologna West Community Mental Health Centers (CMHCs) was assessed at baseline and at 12 month follow-up. Drop-out, hospitalizations and service utilization were used as clinical outcomes.
Most of the patients were still in contact with CMHC at 12 month follow up. Substance users had a significantly higher rate of hospitalizations during the follow-up after adjusting for age, gender and other potential confounders (OR 5.84, 95% CI 2.44–13.97, p ≤ 0.001).
This study adds to previous evidence showing the independent effect of substance use on FEP course. The identification of a “potentially modifiable” environmental predictor of the course of the illness such as substance use at psychosis onset allows us to envisage the possibility of ameliorating the course of the illness by managing this factor.
Schizophrenia Research 03/2014; · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Epidemiological studies implicate cannabis use as a risk factor for psychosis. Daily users of high potency types of cannabis have the highest risk of developing psychotic disorders. Nevertheless, only a small proportion of users develop the illness, suggesting an underlying genetic susceptibility to the psychogenic effect. This study set out to assess whether three candidate genes that affect dopamine signalling contribute to this vulnerability.
DNA and data on history of cannabis use were obtained from 333 patients with their first episode of psychosis and 317 healthy population controls. We built a measure of pattern of use from frequency of use and type of cannabis used (low potency, hash; high potency, skunk). We selected for genotyping three genetic variants that regulate dopamine signalling: the 3′-untranslated region (3′-UTR) 9/10 repeat for SLC6A3, COMT Val156Met single nucleotide polymorphism (SNP), which affects breakdown of dopamine, and the AKT1 rs2494732 (C/T) SNP, which affects post-D2-receptor-dependent signalling. The average allele count scores for the postulated minor/risk alleles (AKT1*C, COMT *Val, DAT1*9) were collapsed into three groups (scores 0, 1, and 2) termed the oligogenic score. Adjusted multivariate logistic regression tested for the interaction between oligogenic score and pattern of cannabis use.
The overall interaction between the oligogenic score and the measure of frequency and type of cannabis use in modifying the risk of psychosis was not significant (likelihood ratio test 13·44, p=0·062). Among never users and those who used low-potency cannabis, there was no significant change in risk of psychosis according to oligogenic score. However, among users of high-potency cannabis less than daily, those with an oligogenic score of 2 had a three-fold higher risk of psychosis than did those with a score of 0 (odds ratio [OR] 3·33, 95% CI 1·7–6·2). Furthermore, daily users of high-potency cannabis with scores of 1 and 2 had, respectively, a six-fold (OR 6·1, 95% CI 1·2–36·2) and eight-fold (OR 7·9, 95% CI 1·8–22·1) increased risk of psychosis compared with those with a score of 0.
These findings suggest that individual susceptibility to the psychosis-inducing effect of cannabis use could be conditional on the pattern of use and interaction with genetic variants that regulate dopamine signalling.
National Institute of Health Research, South London and Maudsley NHS Foundation Trust, The Psychiatry Research Trust, Maudsley Charity research fund, European Community's Seventh Framework Program.
The Lancet 02/2014; 383:S41. · 39.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. Methods: We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. Results: Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16-1.74; P < .001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11-1.68; P < .001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06-1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P < .0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users. Conclusions: Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.
[Show abstract][Hide abstract] ABSTRACT: Vitamin D deficiency is seen in a high proportion of people with established psychotic disorders, but it is not known if this is present at onset of the illness. We set out to examine vitamin D levels in people with their first episode of psychosis (FEP).
We conducted a matched case-control study to examine vitamin D levels and rates of vitamin D deficiency in sixty nine patients presenting with their FEP and sixty nine controls matched for age, sex and ethnicity. Differences between groups were tested using student's-t tests, paired t-tests and odds ratios for further analysis.
Vitamin D levels were significantly lower in cases than in controls (p<0.001). The odds ratio of being vitamin D deficient was 2.99 in the FEP group relative to the control group. There was no correlation between vitamin D levels and length of hospitalisation in the patient group (r=-0.027, p=0.827).
We found higher rates of vitamin D deficiency in people with FEP compared to matched controls. Given that vitamin D is neuroprotective; that developmental vitamin D deficiency may be a risk factor for psychosis, and that incipient psychosis may affect lifestyle factors and diet, future studies are required to examine this association further. In the meantime, there is a need for more widespread testing of vitamin D levels in FEP and for the development of appropriate management strategies.
Schizophrenia Research 09/2013; · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The insight into psychosis can be assessed reliably by clinicians from interviews with patients. However, patients may retain implicit awareness of illness while lacking explicit awareness. Sampling and Methods: In a sample of first-episode psychosis patients, we used a test of processing of mental illness-related and other negative words as a measure of implicit awareness to see how this varied in relation to insight. An emotional-counting Stroop task tested reaction times to words of three types: psychosis-related (e.g. 'crazy'), general negative (e.g. 'cancer') and neutral (e.g. 'oyster'). Data were available from 43 patients and 23 healthy controls. Patients' insight was assessed using the Schedule for the Assessment of Insight (SAI-E). Results: Patients reacted slower than controls to words across all conditions, and both patients and controls reacted slower to salient and negative words than neutral words. There was a near significant interaction between word type and group (Wilks' lambda = 0.53, p = 0.055); patients experienced greater interference from negative rather than psychosis-related words (p = 0.003), and controls experienced greater interference from salient rather than negative words (p = 0.01). Within the patient group, there was a correlation between insight and interference on salient words (r = 0.33, p = 0.05), such that those with less insight experienced less interference on psychosis-related words. Conclusions: Psychosis-related words were less threatening and less self-relevant to psychosis patients with less insight. This suggests that the lack of awareness such patients have of their illness is genuine and more likely to be mediated by lower-level information processing mechanisms than strategies such as conscious, motivated denial.
[Show abstract][Hide abstract] ABSTRACT: A number of studies have reported that patients with psychosis who use cannabis have better cognitive performance than those who do not. This is surprising as cannabis can impair cognition in healthy subjects. An obvious question is whether the better current performance of psychotic patients who have used cannabis is a reflection of their having a higher premorbid IQ than those psychotic patients who haven't used cannabis.
In a sample of patients at their first episode of psychosis, we tested the hypothesis that patients who smoked cannabis would have a higher premorbid IQ than patients who did not.
279 participants (119 patients and 160 healthy controls) were assessed in order to obtain current and premorbid IQ measures and detailed information on cannabis use. We examined the association between cannabis use and both premorbid and current IQ in patients and controls.
Patients who had ever smoked cannabis had significantly higher current (p<.001) and premorbid IQ (p=.004) compared to patients who had never used cannabis. This difference was not found among controls.
These findings suggest that the better cognitive performance of patients with their first episode of psychosis who have used cannabis compared with those who haven't is due to the better premorbid IQ of the former.
Schizophrenia Research 08/2013; · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite increasing evidence suggesting that childhood maltreatment is significantly associated with psychosis, the specific role of bullying in the onset of psychotic disorders is still unclear. This study aimed to examine whether bullying was more prevalent amongst individuals presenting to services for the first time with a psychotic disorder than in unaffected community controls.
Data on exposure to bullying, psychotic symptoms, cannabis use and history of conduct disorder were collected cross-sectionally from 222 first-presentation psychosis cases and 215 geographically-matched controls. Bullying victimisation was assessed retrospectively as part of the Brief Life Events schedule. Logistic regression was used to examine associations between exposure to bullying and case-control status, while controlling for potential confounders.
Psychosis cases were approximately twice as likely to report bullying victimisation when compared to controls. No significant interactions between bullying and either gender or cannabis use were found. Controls reporting being a victim of bullying were approximately twice as likely to also report at least one psychosis-like symptom.
Our results extend previous research by suggesting that bullying victimisation may contribute to vulnerability to develop a psychotic disorder in some individuals.
Schizophrenia Research 07/2013; · 4.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study investigated the relationship between severe childhood abuse and cognitive functions in first-episode psychosis patients and geographically-matched controls. Reports of any abuse were associated with lower scores in the executive function domain in the control group. However, in contrast with our hypothesis, no relationships were found amongst cases.