Adjusting for population stratification in polygenic risk score analyses: a guide for model specifications in the UK Biobank.

The current study was conducted to provide a general guidance for model specifications in polygenic risk score (PRS) analyses of the UK Biobank, such as adjusting for covariates (i.e. age, sex, recruitment centers, and genetic batch) and the number of principal components (PCs) that need to be included. To cover behavioral, physical and mental health outcomes, we evaluated three continuous outcomes (BMI, smoking, drinking) and two binary outcomes (Major Depressive Disorder and educational attainment). We applied 3280 (656 per phenotype) different models including different sets of covariates. We evaluated these different model specifications by comparing regression parameters such as R2, coefficients, and P values, as well as ANOVA tests. Findings suggest that only up to three PCs appears to be sufficient for controlling population stratification for most outcomes, whereas including other covariates (particularly age and sex) appears to be more essential for model performance.

The association between reasons for first using cannabis, later pattern of use, and risk of first-episode psychosis: the EU-GEI case-control study.

BACKGROUND: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis. METHODS: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case-control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case-control status. RESULTS: Controls (86.1%) and FEPp (75.63%) were most likely to report 'because of friends' as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: 'to feel better' as their RFUC (χ2 = 50.97; p < 0.001). RFUC 'to feel better' was associated with being a FEPp (OR 1.74; 95% CI 1.03-2.95) while RFUC 'with friends' was associated with being a control (OR 0.56; 95% CI 0.37-0.83). The path model indicated an association between RFUC 'to feel better' with heavy cannabis use and with FEPp-control status. CONCLUSIONS: Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use 'to feel better'. People who reported their reason for first using cannabis to 'feel better' were more likely to progress to heavy use and develop a psychotic disorder than those reporting 'because of friends'.

Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults.

Childhood maltreatment (CM) and genetic vulnerability are both risk factors for psychosis, but the relations between them are not fully understood. Guided by the recent identification of genetic risk to CM, this study investigates the hypothesis that genetic risk to schizophrenia also increases the risk of CM and thus impacts psychosis risk. The relationship between schizophrenia polygenetic risk, CM, and psychotic-like experiences (PLE) was investigated in participants from the Utrecht Cannabis Cohort (N = 1262) and replicated in the independent IMAGEN cohort (N = 1740). Schizophrenia polygenic risk score (SZ-PRS) were calculated from the most recent GWAS. The relationship between CM, PRS, and PLE was first investigated using multivariate linear regression. Next, mediation of CM in the pathway linking SZ-PRS and PLE was examined by structural equation modeling, while adjusting for a set of potential mediators including cannabis use, smoking, and neuroticism. In agreement with previous studies, PLE were strongly associated with SZ-PRS (B = 0.190, p = 0.009) and CM (B = 0.575, p < 0.001). Novel was that CM was also significantly associated with SZ-PRS (B = 0.171, p = 0.001), and substantially mediated the effects of SZ-PRS on PLE (proportion mediated = 29.9%, p = 0.001). In the replication cohort, the analyses yielded similar results, confirming equally strong mediation by CM (proportion mediated = 34.7%, p = 0.009). Our results suggest that CM acts as a mediator in the causal pathway linking SZ-PRS and psychosis risk. These findings open new perspectives on the relations between genetic and environmental risks and warrant further studies into potential interventions to reduce psychosis risk in vulnerable people.

Prevalence and correlates of anxiety and depression in frontline healthcare workers treating people with COVID-19 in Bangladesh.

BACKGROUND: Healthcare workers (HCWs) who are in the frontline during the COVID-19 pandemic are often under significant pressures that may predispose them to symptoms of poor mental health. This study aimed to investigate the prevalence of anxiety and depression among HCWs and factors correlated with mental health concerns during the COVID-19 pandemic in Bangladesh. And, it also aimed to evaluate the psychometric properties of the Bangla version of the Hospital Anxiety and Depression Scale (HADS). METHODS: A cross-sectional survey was conducted between July and August, 2020. A self-reported online questionnaire was utilized to collect data. The survey included questions concerning socio-demographic, lifestyle, and work setting, as well as the HADS. A confirmatory factor analysis (CFA) and multiple linear regression analysis were performed. RESULTS: Data from 803 HCWs (50.7% male; mean age: 27.3 [SD = 6.9]; age range: 18-58 years) were included in the final analysis. The Bangla HADS was psychometrically sound, and demonstrated good internal consistency and reliability (α = 0.83), and excellent construct validity. Prevalence estimates of anxiety and depression were 69.5%, and 39.5%, respectively, for less severe symptomology (at least borderline abnormal), and 41.2% and 15.7% for more severe (at least abnormal) symptomology. Regression analyses with the total HADS score as a dependent variable revealed significant (p < 0.05) associations with female gender, moderate and poor health status, infrequent physical exercising, smoking, having had regrets about one's profession because of the pandemic and associated experiences, not updating on the latest COVID-19-related research, experiencing discrimination in the workplace, and facing social problems due to working in a lab or hospital during the COVID-19 pandemic. CONCLUSIONS: Symptoms of anxiety and depression are prevalent among HCWs during the COVID-19 pandemic in Bangladesh. The findings suggest a need for screening for mental health concerns, and employing early intervention to help these individuals.

Prevalence of depression, anxiety and associated factors among school going adolescents in Bangladesh: Findings from a cross-sectional study.

BACKGROUND: Common mental disorders in early life represent a major concern as they become more complex and intense with transition into adolescence. Despite global recognition of the significance of adolescent mental health, it remains a neglected area in research and health policy in Bangladesh. This study aimed to investigate the prevalence and factors associated with depression and anxiety among school going adolescents in Bangladesh. METHODS: A cross-sectional survey was conducted among 563 students aged 13-18 years at selected schools (secondary and higher secondary) in Dhaka City. After providing written informed consent, participants completed a survey examining socio-demographic variables, along with the PHQ-9 and GAD-7 scales. Logistic regression was used to examine associations between variables under examination. RESULTS: The prevalence rates of moderate to severe levels of depression and anxiety were 26.5% and 18.1%, respectively. Based on multivariable analyses, unsatisfactory sleep (AOR = 3.17; 95% CI = 1.81-5.53, p < .001), cigarette smoking (AOR = 2.00; 95% CI = 1.01-3.97, p = .048), and anxiety (AOR = 10.47; 95% CI = 6.11-17.95, p < .001) were associated with depression. Anxiety was associated with being 15-16 years (AOR = 2.66; 95% CI = 1.18-6.00, p = .018), not having good perceived relationships with friends (AOR = 2.10; 95% CI = 1.24-3.56, p = .006) and depression (AOR = 10.22; 95% CI = 6.01-17.38, p < .001). CONCLUSIONS: Depression and anxiety were prevalent among school going adolescents in Bangladesh. The findings suggest epidemiological data can direct policy-level decisions regarding evaluation, prevention, and intervention of mental health conditions among school going adolescents in Bangladesh.

DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia.

We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.

Validation of the Portuguese version of the Community Assessment of Psychic Experiences and characterization of psychotic experiences in a Brazilian sample

Objective: We investigated: i) the reliability and validity of a Brazilian version of the Community Assessment of Psychic Experiences (CAPE), developed to detect and characterize psychotic experiences in the general population; and ii) the association between psychotic experiences, childhood adversity, and cannabis use in a population-based sample. Methods: We performed factorial analyses and generalized linear models with CAPE scores as the dependent variable in a sample composed of 217 first-episode psychosis patients, 104 unaffected biological siblings, and 319 non-psychotic population-based participants. Results: After removing seven items from its positive dimension and two items from its negative dimension, a 33-item Brazilian version of the CAPE showed acceptable adjustment indices (confirmatory fit index = 0.895; goodness of fit index = 0.822; parsimony goodness of fit index = 0.761; root mean square error of approximation [RMSEA] = 0.055, p [RMSEA ≤ 0.05] = 0.04) and internal consistency in all its dimensions (> 0.70). Childhood adversity was associated with higher scores in all three dimensions, as well as with total score. Lifetime cannabis use was associated with higher scores only in the positive dimension. Conclusion: The proposed Brazilian version of the CAPE corroborates the tridimensional approach for assessing psychosis-proneness, and the frequency and severity of psychotic manifestations are distributed as a spectrum in the general population.

Evidence that reduced gray matter volume in psychotic disorder is associated with exposure to environmental risk factors.

The aim of this study was to examine whether cannabis use, childhood trauma and urban upbringing are associated with total gray matter volume (GMV) in individuals with (risk for) psychotic disorder and whether this is sex-specific. T1-weighted MRI scans were acquired from 89 patients with a psychotic disorder, 95 healthy siblings of patients with psychotic disorder and 87 controls. Multilevel random regression analyses were used to examine main effects and interactions between group, sex and environmental factors in models of GMV. The three-way interaction between group, sex and cannabis (χ2 =12.43, p<0.01), as well as developmental urbanicity (χ2 = 6.29, p = 0.01) were significant, indicating that cannabis use and developmental urbanicity were associated with lower GMV in the male patient group (cannabis: B= -32.54, p < 0.01; developmental urbanicity: B= -10.23, p=0.03). For childhood trauma, the two-way interaction with group was significant (χ2 = 5.74, p = 0.02), indicating that childhood trauma was associated with reduced GMV in the patient group (B=-9.79, p=0.01). The findings suggest that reduction of GMV in psychotic disorder may be the outcome of differential sensitivity to environmental risks, particularly in male patients.

Lifetime Prevalence and Correlates of Schizophrenia-Spectrum, Affective, and Other Non-affective Psychotic Disorders in the Chinese Adult Population.

Lifetime prevalence of psychotic disorders varies widely across studies. Epidemiological surveys have rarely examined prevalences of specific psychotic disorders other than schizophrenia, and the majority used a single-phase design without employing clinical reappraisal interview for diagnostic verification. The current study investigated lifetime prevalence, correlates and service utilization of schizophrenia-spectrum, affective, and other non-affective psychotic disorders in a representative sample of community-dwelling Chinese adult population aged 16-75 years (N = 5719) based on a territory-wide, population-based household survey for mental disorders in Hong Kong. The survey adopted a 2-phase design comprising first-phase psychosis screening and second-phase diagnostic verification incorporating clinical information from psychiatrist-administered semi-structured interview and medical record review to ascertain DSM-IV lifetime diagnosis for psychotic disorders. Data on sociodemographics, psychosocial characteristics and service utilization were collected. Our results showed that lifetime prevalence was 2.47% for psychotic disorder overall, 1.25% for schizophrenia, 0.15% for delusional disorder, 0.38% for psychotic disorder not otherwise specified, 0.31% for bipolar disorder with psychosis, and 0.33% for depressive disorder with psychosis. Schizophrenia-spectrum disorder was associated with family history of psychosis, cigarette smoking and variables indicating socioeconomic disadvantage. Victimization experiences were significantly related to affective psychoses and other non-affective psychoses. Around 80% of participants with any psychotic disorder sought some kind of professional help for mental health problems in the past year. Using comprehensive diagnostic assessment involving interview and record data, our results indicate that approximately 2.5% of Chinese adult population had lifetime psychotic disorder which represents a major public health concern.

Functional urological disorders: a sensitized defence response in the bladder-gut-brain axis.

Functional urological and gastrointestinal disorders are interrelated and characterized by a chronic course and considerable treatment resistance. Urological disorders associated with a sizeable functional effect include overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS), and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Poor treatment outcomes might be attributable to untreated underlying psychological and psychiatric disorders, as the co-occurrence of functional urological and gastrointestinal disorders with mood and anxiety disorders is common. The hypothetical bladder-gut-brain axis (BGBA) is a useful framework under which this interaction can be studied, suggesting that functional disorders represent a sensitized response to earlier threats such as childhood adversity or previous traumatic events, resulting in perceived emotional and bodily distress - the symptoms of functional disorders. Psychological and physical stress pathways might contribute to such alarm falsification, and neuroticism could be a risk factor for the co-occurrence of functional disorders and affective conditions. Additionally, physical threat - either from external sources or internal sources such as infection - might contribute to alarm falsification by influencing body-brain crosstalk on homeostasis and, therefore, affecting mood, cognition, and behaviour. Multidisciplinary research and an integrated care approach is, therefore, required to further elucidate and remediate functional urological and gastrointestinal polymorphic phenotypes.

Bone Mineral Density as a Marker of Cumulative Estrogen Exposure in Psychotic Disorder: A 3 Year Follow-Up Study.

Altered estrogen-induced neuroprotection has been implicated in the etiology of psychotic disorders. Using bone mineral density as a marker of lifetime estrogen exposure, a longitudinal family study was conducted to discriminate between etiological mechanisms and secondary effects of disease and treatment. Dual X-ray absorptiometry scans were acquired twice, with an interval of 3 years, in 30 patients with psychotic disorder (male (M)/female (F): 24/6, mean age of 32 years at second measurement), 44 non-psychotic siblings of patients with a psychotic disorder (M/F: 26/18, mean age 32) and 27 controls (M/F: 7/20, mean age 35). Total bone mineral density, Z-scores and T-scores were measured in the lumbar spine and proximal femur. Associations between group and bone mineral density changes were investigated with multilevel random regression analyses. The effect of prolactin-raising antipsychotic medication was evaluated. (Increased risk of) psychotic disorder was not associated with disproportionate bone mineral density loss over a three year period. Instead, femoral bone mineral density measures appeared to decrease less in the patient versus control comparison (total BMD: B = 0.026, 95% CI 0.002 to 0.050, p = 0.037; Z-score: B = 0.224, 95% CI 0.035 to 0.412, p = 0.020; and T-score: B = 0.193, 95% CI 0.003 to 0.382, p = 0.046). Current or past use of a prolactin-raising antipsychotic medication was not associated with bone mineral density changes. In this small longitudinal study, there was no evidence of ongoing estrogen deficiency in psychotic disorder as there was no excessive loss of bone mineral density over a 3-year period in patients using antipsychotic medication.

EEG Changes Due to Experimentally Induced 3G Mobile Phone Radiation.

The aim of this study was to investigate whether a 15-minute placement of a 3G dialing mobile phone causes direct changes in EEG activity compared to the placement of a sham phone. Furthermore, it was investigated whether placement of the mobile phone on the ear or the heart would result in different outcomes. Thirty-one healthy females participated. All subjects were measured twice: on one of the two days the mobile phone was attached to the ear, the other day to the chest. In this single-blind, cross-over design, assessments in the sham phone condition were conducted directly preceding and following the mobile phone exposure. During each assessment, EEG activity and radiofrequency radiation were recorded jointly. Delta, theta, alpha, slowbeta, fastbeta, and gamma activity was computed. The association between radiation exposure and the EEG was tested using multilevel random regression analyses with radiation as predictor of main interest. Significant radiation effects were found for the alpha, slowbeta, fastbeta, and gamma bands. When analyzed separately, ear location of the phone was associated with significant results, while chest placement was not. The results support the notion that EEG alterations are associated with mobile phone usage and that the effect is dependent on site of placement. Further studies are required to demonstrate the physiological relevance of these findings.

Does the Brain Detect 3G Mobile Phone Radiation Peaks? An Explorative In-Depth Analysis of an Experimental Study.

This study aimed to investigate whether third generation mobile phone radiation peaks result in event related potentials. Thirty-one healthy females participated. In this single-blind, cross-over design, a 15 minute mobile phone exposure was compared to two 15 minute sham phone conditions, one preceding and one following the exposure condition. Each participant was measured on two separate days, where mobile phone placement was varied between the ear and heart. EEG activity and radiofrequency radiation were recorded jointly. Epochs of 1200 ms, starting 200 ms before and lasting until 1000 ms after the onset of a radiation peak, were extracted from the exposure condition. Control epochs were randomly selected from the two sham phone conditions. The main a-priori hypothesis to be tested concerned an increase of the area in the 240-500 ms post-stimulus interval, in the exposure session with ear-placement. Using multilevel regression analyses the placement*exposure interaction effect was significant for the frontal and central cortical regions, indicating that only in the mobile phone exposure with ear-placement an enlarged cortical reactivity was found. Post-hoc analyses based on visual inspection of the ERPs showed a second significantly increased area between 500-1000 ms post-stimulus for almost every EEG location measured. It was concluded that, when a dialing mobile phone is placed on the ear, its radiation, although unconsciously, is electrically detected by the brain. The question of whether or not this cortical reactivity results in a negative health outcome has to be answered in future longitudinal experiments.

Does habituation differ in chronic low back pain subjects compared to pain-free controls? A cross-sectional pain rating ERP study reanalyzed with the ERFIA multilevel method.

The objective of the present study was to investigate cortical differences between chronic low back pain (CLBP) subjects and pain-free controls with respect to habituation and processing of stimulus intensity. The use of a novel event-related fixed-interval areas (ERFIA) multilevel technique enables the analysis of event-related electroencephalogram (EEG) of the whole post stimulus range at a single trial level. This technique makes it possible to disentangle the cortical processes of habituation and stimulus intensity.In a cross-sectional study, 78 individuals with CLBP and 85 pain-free controls underwent a rating paradigm of 150 nonpainful and painful somatosensory electrical stimuli. For each trial, the entire epoch was partitioned into 20-ms ERFIAs, which acted as dependent variables in a multilevel analysis. The variability of each consecutive ERFIA period was modeled with a set of predictor variables, including 3 forms of habituation and stimulus intensity.Seventy-six pain-free controls and 65 CLBP subjects were eligible for analysis. CLBP subjects showed a significantly decreased linear habituation at 340 to 460 ms in the midline electrodes and C3 (Ps < .05) and had a significantly more pronounced dishabituation for the regions of 400 to 460 ms and 800 to 820 ms for all electrodes, except for T3 and T4 (Ps < .05). No significant group differences for stimulus intensity processing were observed.In this study, group differences with respect to linear habituation and dishabituation were demonstrated. By means of the ERFIA multilevel technique, habituation effects were found in a broad post stimulus range and were not solely limited to peaks. This study suggests that habituation may be a key mechanism involved in the transition process to chronic pain. Future studies with a longitudinal design are required to solve this issue.

Increased release of dopamine in the striata of young adults with hearing impairment and its relevance for the social defeat hypothesis of schizophrenia.

IMPORTANCE: An increased risk for psychosis is observed in people with hearing impairment. According to the social defeat hypothesis, the long-term experience of exclusion leads to enhanced baseline activity and/or sensitization of the dopamine system and puts the individual at increased risk for psychosis. OBJECTIVE: To investigate whether young adults with severe hearing impairment (SHI) experience more feelings of social defeat, show greater dopamine release in response to dexamphetamine, and report a stronger subjective reaction to this substance than normal-hearing young adults and to examine whether dopamine release is associated with both self-reported social exclusion and dexamphetamine-induced psychotic experiences. DESIGN, SETTING, AND PARTICIPANTS: A sample of 19 participants with SHI and 19 smoking-, age-, and sex-matched healthy controls underwent single-photon emission computed tomography with iodine 123-labeled iodobenzamide as a radiotracer before and after an amphetamine challenge at an academic hospital. EXPOSURES: Dexamphetamine sulfate (0.3 mg/kg) administered intravenously. MAIN OUTCOMES AND MEASURES: Baseline D2/3 receptor binding and endogenous dopamine release. RESULTS: The participants with SHI reported experiencing more feelings of social defeat (U=109, z=-2.09, P=.04) and loneliness (U=87.5, z=-2.72, P=<.001) than did healthy controls, but they did not differ from healthy controls with regard to baseline psychotic symptoms (U=156.5, z=-0.70, P=.48). There were no significant group differences in baseline D2/3 receptor binding. However, repeated-measures multivariate analysis of covariance with age (in months) and tobacco smoking (in pack-years) as covariates showed that there was a greater amphetamine-induced striatal dopamine release among the participants with SHI than among the healthy controls (F1,34=4.55, P=.04). After amphetamine administration, the participants with SHI reported more changes in affect than the healthy controls, but not a greater increase in psychotic symptoms. Likewise, reports of social exclusion and an increase in psychotic symptoms were not associated with dopamine release. CONCLUSIONS AND RELEVANCE: Our study presents preliminary evidence of dopamine sensitization in a socially excluded group of people with hearing impairment. If replicated by future studies in other excluded groups, this finding may have major implications for our understanding of the underlying mechanism and for prevention of psychotic disorders.

Catatonia in DSM-5.

Although catatonia has historically been associated with schizophrenia and is listed as a subtype of the disorder, it can occur in patients with a primary mood disorder and in association with neurological diseases and other general medical conditions. Consequently, catatonia secondary to a general medical condition was included as a new condition and catatonia was added as an episode specifier of major mood disorders in DSM-IV. Different sets of criteria are utilized to diagnose catatonia in schizophrenia and primary mood disorders versus neurological/medical conditions in DSM-IV, however, and catatonia is a codable subtype of schizophrenia but a specifier for major mood disorders without coding. In part because of this discrepant treatment across the DSM-IV manual, catatonia is frequently not recognized by clinicians. Additionally, catatonia is known to occur in several conditions other than schizophrenia, major mood disorders, or secondary to a general medical condition. Four changes are therefore made in the treatment of catatonia in DSM-5. A single set of criteria will be utilized to diagnose catatonia across the diagnostic manual and catatonia will be a specifier for both schizophrenia and major mood disorders. Additionally, catatonia will also be a specifier for other psychotic disorders, including schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, and substance-induced psychotic disorder. A new residual category of catatonia not otherwise specified will be added to allow for the rapid diagnosis and specific treatment of catatonia in severely ill patients for whom the underlying diagnosis is not immediately available. These changes should improve the consistent recognition of catatonia across the range of psychiatric disorders and facilitate its specific treatment.

The forthcoming DSM-5, critical care medicine, and pediatric neuropsychiatry: which new concepts do we need?

Examination and comparison of the current DSM-IV-TR and the proposed revisions for the forthcoming DSM-5, with regard to neuropsychiatric aspects of critical illness, identified five important issues. These remain to be addressed in order to improve the care of critically ill patients. These are 1) sickness behavior, as part of the organic reaction types of the brain; 2) delirium in children and the "Differential Diagnosis of Mental Disorders Due to a General Medical Condition" in children; 3) catatonia; 4) regressive disorders in childhood in relation to somatic disorders (e.g., anti-NMDAR encephalitis); 5) age-related diagnostic criteria in relation to neuro-psychiatric disorders.

Depressive symptoms in Crohn's disease: relationship with immune activation and tryptophan availability.

Crohn's disease (CD) is associated with immune activation and depressive symptoms. This study determines the impact of anti-tumor necrosis factor (TNF)-α treatment in CD patients on depressive symptoms and the degree to which tryptophan (TRP) availability and immune markers mediate this effect. Fifteen patients with CD, eligible for anti-TNF-α treatment were recruited. Disease activity (Harvey-Bradshaw Index (HBI), Crohn's Disease Activity Index (CDAI)), fatigue (Multidimensional Fatigue Inventory (MFI)), quality of life (Inflammatory Bowel Disease Questionnaire (IBDQ)), symptoms of depression and anxiety (Symptom Checklist (SCL-90), Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS)), immune activation (acute phase proteins (APP)), zinc and TRP availability were assessed before treatment and after 2, 4 and 8 weeks. Anti-TNF-α increased IBDQ scores and reduced all depression scores; however only SCL-90 depression scores remained decreased after correction for HBI. Positive APPs decreased, while negative APPs increased after treatment. After correction for HBI, both level and percentage of γ fraction were associated with SCL-90 depression scores over time. After correction for HBI, patients with current/past depressive disorder displayed higher levels of positive APPs and lower levels of negative APPs and zinc. TRP availability remained invariant over time and there was no association between SCL-90 depression scores and TRP availability. Inflammatory reactions in CD are more evident in patients with comorbid depression, regardless of disease activity. Anti-TNF-α treatment in CD reduces depressive symptoms, in part independently of disease activity; there was no evidence that this effect was mediated by immune-induced changes in TRP availability.

Cannabis use and vulnerability for psychosis in early adolescence--a TRAILS study.

AIMS: To examine the direction of the longitudinal association between vulnerability for psychosis and cannabis use throughout adolescence. DESIGN: Cross-lagged path analysis was used to identify the temporal order of vulnerability for psychosis and cannabis use, while controlling for gender, family psychopathology, alcohol use and tobacco use. SETTING: A large prospective population study of Dutch adolescents [the TRacking Adolescents' Individual Lives Survey (TRAILS) study]. PARTICIPANTS: A total of 2120 adolescents with assessments at (mean) age 13.6, age 16.3 and age 19.1. MEASUREMENTS: Vulnerability for psychosis at the three assessment points was represented by latent factors derived from scores on three scales of the Youth Self-Report and the Adult Self-Report, i.e. thought problems, social problems and attention problems. Participants self-reported on cannabis use during the past year at all three waves. FINDINGS: Significant associations (r = 0.12-0.23) were observed between psychosis vulnerability and cannabis use at all assessments. Also, cannabis use at age 16 predicted psychosis vulnerability at age 19 (Z = 2.6, P < 0.05). Furthermore, psychosis vulnerability at ages 13 (Z = 2.0, P < 0.05) and 16 (Z = 3.0, P < 0.05) predicted cannabis use at, respectively, ages 16 and 19. CONCLUSIONS: Cannabis use predicts psychosis vulnerability in adolescents and vice versa, which suggests that there is a bidirectional causal association between the two.