Antidepressant Exposure and DNA Methylation: Insights from a Methylome-Wide Association Study.

Importance: Understanding antidepressant mechanisms could help design more effective and tolerated treatments. Objective: Identify DNA methylation (DNAm) changes associated with antidepressant exposure. Design: Case-control methylome-wide association studies (MWAS) of antidepressant exposure were performed from blood samples collected between 2006-2011 in Generation Scotland (GS). The summary statistics were tested for enrichment in specific tissues, gene ontologies and an independent MWAS in the Netherlands Study of Depression and Anxiety (NESDA). A methylation profile score (MPS) was derived and tested for its association with antidepressant exposure in eight independent cohorts, alongside prospective data from GS. Setting: Cohorts; GS, NESDA, FTC, SHIP-Trend, FOR2107, LBC1936, MARS-UniDep, ALSPAC, E-Risk, and NTR. Participants: Participants with DNAm data and self-report/prescription derived antidepressant exposure. Main Outcomes and Measures: Whole-blood DNAm levels were assayed by the EPIC/450K Illumina array (9 studies, N exposed = 661, N unexposed = 9,575) alongside MBD-Seq in NESDA (N exposed = 398, N unexposed = 414). Antidepressant exposure was measured by self- report and/or antidepressant prescriptions. Results: The self-report MWAS (N = 16,536, N exposed = 1,508, mean age = 48, 59% female) and the prescription-derived MWAS (N = 7,951, N exposed = 861, mean age = 47, 59% female), found hypermethylation at seven and four DNAm sites (p < 9.42x10 -8 ), respectively. The top locus was cg26277237 ( KANK1, p self-report = 9.3x10 -13 , p prescription = 6.1x10 -3 ). The self-report MWAS found a differentially methylated region, mapping to DGUOK-AS1 ( p adj = 5.0x10 -3 ) alongside significant enrichment for genes expressed in the amygdala, the "synaptic vesicle membrane" gene ontology and the top 1% of CpGs from the NESDA MWAS (OR = 1.39, p < 0.042). The MPS was associated with antidepressant exposure in meta-analysed data from external cohorts (N studies = 9, N = 10,236, N exposed = 661, f3 = 0.196, p < 1x10 -4 ). Conclusions and Relevance: Antidepressant exposure is associated with changes in DNAm across different cohorts. Further investigation into these changes could inform on new targets for antidepressant treatments. 3 Key Points: Question: Is antidepressant exposure associated with differential whole blood DNA methylation?Findings: In this methylome-wide association study of 16,536 adults across Scotland, antidepressant exposure was significantly associated with hypermethylation at CpGs mapping to KANK1 and DGUOK-AS1. A methylation profile score trained on this sample was significantly associated with antidepressant exposure (pooled f3 [95%CI]=0.196 [0.105, 0.288], p < 1x10 -4 ) in a meta-analysis of external datasets. Meaning: Antidepressant exposure is associated with hypermethylation at KANK1 and DGUOK-AS1 , which have roles in mitochondrial metabolism and neurite outgrowth. If replicated in future studies, targeting these genes could inform the design of more effective and better tolerated treatments for depression.

Loneliness in the workplace: a mixed-method systematic review and meta-analysis.

BACKGROUND: Loneliness is a risk factor for a range of mental and physical health problems and has gained increasing interest from policy-makers and researchers in recent years. However, little attention has been paid to loneliness at work and its implications for workers and employers. AIMS: Identify workplace, health and personal factors associated with workplace loneliness. METHODS: We searched five databases (PubMed, MEDLINE, EMBASE, PsycINFO and EBSCO Business Source Complete) for relevant articles published from 1 January 2000 to 23 February 2023. Quantitative data were synthesized using narrative synthesis and random-effects meta-analysis of correlation coefficients. Qualitative data were synthesized using thematic synthesis. Evidence quality was appraised using the Mixed-Methods Appraisal Tool. RESULTS: We identified 49 articles meeting the inclusion criteria. Pooled results indicate that workplace loneliness was associated with lower job performance (r = -0.35, 95% CI -0.49, -0.21), reduced job satisfaction (r = -0.34, 95% CI -0.44, -0.24), worse worker-manager relationship (r = -0.31, 95% CI -0.38, -0.24) and elevated burnout (r = 0.39, 95% CI 0.25, 0.51). Qualitative results suggest links between loneliness and inadequate workplace social interactions and mental health problems. As most studies used cross-sectional data and few adjusted for potential confounders, the direction and robustness of the associations remain untested. CONCLUSIONS: Our results indicate that loneliness is associated with poor occupational functioning and well-being among workers. Results also show that loneliness is associated with modifiable aspects of the work environment, suggesting that the workplace may offer a fruitful avenue for interventions targeting loneliness.

Association between genetic and socioenvironmental risk for schizophrenia during upbringing in a UK longitudinal cohort.

BACKGROUND: Associations of socioenvironmental features like urbanicity and neighborhood deprivation with psychosis are well-established. An enduring question, however, is whether these associations are causal. Genetic confounding could occur due to downward mobility of individuals at high genetic risk for psychiatric problems into disadvantaged environments. METHODS: We examined correlations of five indices of genetic risk [polygenic risk scores (PRS) for schizophrenia and depression, maternal psychotic symptoms, family psychiatric history, and zygosity-based latent genetic risk] with multiple area-, neighborhood-, and family-level risks during upbringing. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins born in 1994-1995 and followed to age 18 (93% retention). Socioenvironmental risks included urbanicity, air pollution, neighborhood deprivation, neighborhood crime, neighborhood disorder, social cohesion, residential mobility, family poverty, and a cumulative environmental risk scale. At age 18, participants were privately interviewed about psychotic experiences. RESULTS: Higher genetic risk on all indices was associated with riskier environments during upbringing. For example, participants with higher schizophrenia PRS (OR = 1.19, 95% CI = 1.06-1.33), depression PRS (OR = 1.20, 95% CI = 1.08-1.34), family history (OR = 1.25, 95% CI = 1.11-1.40), and latent genetic risk (OR = 1.21, 95% CI = 1.07-1.38) had accumulated more socioenvironmental risks for schizophrenia by age 18. However, associations between socioenvironmental risks and psychotic experiences mostly remained significant after covariate adjustment for genetic risk. CONCLUSION: Genetic risk is correlated with socioenvironmental risk for schizophrenia during upbringing, but the associations between socioenvironmental risk and adolescent psychotic experiences appear, at present, to exist above and beyond this gene-environment correlation.

A risk calculator to predict adult attention-deficit/hyperactivity disorder: generation and external validation in three birth cohorts and one clinical sample.

AIM: Few personalised medicine investigations have been conducted for mental health. We aimed to generate and validate a risk tool that predicts adult attention-deficit/hyperactivity disorder (ADHD). METHODS: Using logistic regression models, we generated a risk tool in a representative population cohort (ALSPAC - UK, 5113 participants, followed from birth to age 17) using childhood clinical and sociodemographic data with internal validation. Predictors included sex, socioeconomic status, single-parent family, ADHD symptoms, comorbid disruptive disorders, childhood maltreatment, ADHD symptoms, depressive symptoms, mother's depression and intelligence quotient. The outcome was defined as a categorical diagnosis of ADHD in young adulthood without requiring age at onset criteria. We also tested Machine Learning approaches for developing the risk models: Random Forest, Stochastic Gradient Boosting and Artificial Neural Network. The risk tool was externally validated in the E-Risk cohort (UK, 2040 participants, birth to age 18), the 1993 Pelotas Birth Cohort (Brazil, 3911 participants, birth to age 18) and the MTA clinical sample (USA, 476 children with ADHD and 241 controls followed for 16 years from a minimum of 8 and a maximum of 26 years old). RESULTS: The overall prevalence of adult ADHD ranged from 8.1 to 12% in the population-based samples, and was 28.6% in the clinical sample. The internal performance of the model in the generating sample was good, with an area under the curve (AUC) for predicting adult ADHD of 0.82 (95% confidence interval (CI) 0.79-0.83). Calibration plots showed good agreement between predicted and observed event frequencies from 0 to 60% probability. In the UK birth cohort test sample, the AUC was 0.75 (95% CI 0.71-0.78). In the Brazilian birth cohort test sample, the AUC was significantly lower -0.57 (95% CI 0.54-0.60). In the clinical trial test sample, the AUC was 0.76 (95% CI 0.73-0.80). The risk model did not predict adult anxiety or major depressive disorder. Machine Learning approaches did not outperform logistic regression models. An open-source and free risk calculator was generated for clinical use and is available online at https://ufrgs.br/prodah/adhd-calculator/. CONCLUSIONS: The risk tool based on childhood characteristics specifically predicts adult ADHD in European and North-American population-based and clinical samples with comparable discrimination to commonly used clinical tools in internal medicine and higher than most previous attempts for mental and neurological disorders. However, its use in middle-income settings requires caution.

Genetics and Crime: Integrating New Genomic Discoveries Into Psychological Research About Antisocial Behavior.

Drawing on psychological and sociological theories of crime causation, we tested the hypothesis that genetic risk for low educational attainment (assessed via a genome-wide polygenic score) is associated with criminal offending. We further tested hypotheses of how polygenic risk relates to the development of antisocial behavior from childhood through adulthood. Across the Dunedin and Environmental Risk (E-Risk) birth cohorts of individuals growing up 20 years and 20,000 kilometers apart, education polygenic scores predicted risk of a criminal record with modest effects. Polygenic risk manifested during primary schooling in lower cognitive abilities, lower self-control, academic difficulties, and truancy, and it was associated with a life-course-persistent pattern of antisocial behavior that onsets in childhood and persists into adulthood. Crime is central in the nature-nurture debate, and findings reported here demonstrate how molecular-genetic discoveries can be incorporated into established theories of antisocial behavior. They also suggest that improving school experiences might prevent genetic influences on crime from unfolding.

Buffering effects of safe, supportive, and nurturing relationships among women with childhood histories of maltreatment.

BACKGROUND: Adults who were victims of childhood maltreatment tend to have poorer health compared with adults who did not experience abuse. However, many are in good health. We tested whether safe, supportive, and nurturing relationships buffer women with a history of childhood maltreatment from poor health outcomes in later life. METHODS: Participants included women from the Environmental Risk (E-Risk) Longitudinal Twin Study who were involved in an intimate relationship at some point by the time their twin children were 10 years old. Women were initially interviewed in 1999-2000 (mean age = 33 years) and 2, 5, and 7 years later. They reported on their physical and mental health, and their health-risk behaviours. RESULTS: Compared with women who did not experience abuse in childhood, women with histories of maltreatment were at elevated risk for mental, physical, and health-risk behaviours, including major depressive disorder, sleep, and substance use problems. Cumulatively, safe, supportive, and nurturing relationships characterized by a lack of violence, emotional intimacy, and social support buffered women with a history of maltreatment from poor health outcomes. CONCLUSIONS: Our findings emphasize that negative social determinants of health - such as a childhood history of maltreatment - confer risk for psychopathology and other physical health problems. If, however, a woman's current social circumstances are sufficiently positive, they can promote good health, particularly in the face of past adversity.

Sleeping with one eye open: loneliness and sleep quality in young adults.

BACKGROUND: Feelings of loneliness are common among young adults, and are hypothesized to impair the quality of sleep. In the present study, we tested associations between loneliness and sleep quality in a nationally representative sample of young adults. Further, based on the hypothesis that sleep problems in lonely individuals are driven by increased vigilance for threat, we tested whether past exposure to violence exacerbated this association. METHOD: Data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2232 twins born in England and Wales in 1994 and 1995. We measured loneliness using items from the UCLA Loneliness Scale, and sleep quality using the Pittsburgh Sleep Quality Index. We controlled for covariates including social isolation, psychopathology, employment status and being a parent of an infant. We examined twin differences to control for unmeasured genetic and family environment factors. RESULTS: Feelings of loneliness were associated with worse overall sleep quality. Loneliness was associated specifically with subjective sleep quality and daytime dysfunction. These associations were robust to controls for covariates. Among monozygotic twins, within-twin pair differences in loneliness were significantly associated with within-pair differences in sleep quality, indicating an association independent of unmeasured familial influences. The association between loneliness and sleep quality was exacerbated among individuals exposed to violence victimization in adolescence or maltreatment in childhood. CONCLUSIONS: Loneliness is robustly associated with poorer sleep quality in young people, underscoring the importance of early interventions to mitigate the long-term outcomes of loneliness. Special care should be directed towards individuals who have experienced victimization.

Childhood bullying victimization is associated with use of mental health services over five decades: a longitudinal nationally representative cohort study.

BACKGROUND: Research supports robust associations between childhood bullying victimization and mental health problems in childhood/adolescence and emerging evidence shows that the impact can persist into adulthood. We examined the impact of bullying victimization on mental health service use from childhood to midlife. METHOD: We performed secondary analysis using the National Child Development Study, the 1958 British Birth Cohort Study. We conducted analyses on 9242 participants with complete data on childhood bullying victimization and service use at midlife. We used multivariable logistic regression models to examine associations between childhood bullying victimization and mental health service use at the ages of 16, 23, 33, 42 and 50 years. We estimated incidence and persistence of mental health service use over time to the age of 50 years. RESULTS: Compared with participants who were not bullied in childhood, those who were frequently bullied were more likely to use mental health services in childhood and adolescence [odds ratio (OR) 2.53, 95% confidence interval (CI) 1.88-3.40] and also in midlife (OR 1.30, 95% CI 1.10-1.55). Disparity in service use associated with childhood bullying victimization was accounted for by both incident service use through to age 33 years by a subgroup of participants, and by persistent use up to midlife. CONCLUSIONS: Childhood bullying victimization adds to the pressure on an already stretched health care system. Policy and practice efforts providing support for victims of bullying could help contain public sector costs. Given constrained budgets and the long-term mental health impact on victims of bullying, early prevention strategies could be effective at limiting both individual distress and later costs.

Bullying victimization in childhood predicts inflammation and obesity at mid-life: a five-decade birth cohort study.

BACKGROUND: We aimed to test whether childhood bullying victimization increases risk for age-related disease at mid-life using biological markers including inflammation and adiposity, independent of other childhood risk factors and key adult variables. METHOD: The present study was a 50-year prospective longitudinal birth cohort study of all births in Britain in 1 week in 1958. Exposure to bullying was assessed prospectively when participants were aged 7 and 11 years (27.7% occasionally bullied; 14.6% frequently bullied). Blood inflammation biomarkers [C-reactive protein (CRP) and fibrinogen] and adiposity [body mass index (BMI) and waist:hip ratio] were measured at age 45 years. RESULTS: Participants who had been frequently bullied in childhood showed increased levels of CRP at mid-life [ß = 0.07, 95% confidence interval (CI) 0.04-0.10] and higher risk for clinically relevant inflammation cut-off [CRP > 3 mg/l: 20.4% v. 15.9%, odds ratio (OR) = 1.35, 95% CI 1.12-1.64]. Women who were bullied in childhood had higher BMI than non-bullied participants and were at increased risk of being obese (BMI ≥ 30 kg/m2: occasionally bullied: 26.0% v. 19.4%, OR = 1.45, 95% CI 1.18-1.77; frequently bullied: 26.2% v. 19.4%, OR = 1.41, 95% CI 1.09-1.83). Findings remained significant when controlling for childhood risk factors (e.g. parental social class; participants' BMI and psychopathology in childhood) and key adult variables (e.g. adult social class, smoking, diet and exercise). CONCLUSIONS: Bullied children show increases in risk factors for age-related disease in middle adulthood, independent of co-occurring childhood and adult risks. Given the high prevalence of bullying victimization in childhood, tackling this form of psychosocial stress early in life has the potential of reducing risk for age-related disease and its associated burden.

Leptin deficiency in maltreated children.

Consistent with findings from experimental research in nonhuman primates exposed to early-life stress, children exposed to maltreatment are at high risk of detrimental physical health conditions, such as obesity and systemic inflammation. Because leptin is a key molecule involved in the regulation of both energy balance and immunity, we investigated abnormalities in leptin physiology among maltreated children. We measured leptin, body mass index and C-reactive protein in 170 12-year-old children members of the Environmental-Risk Longitudinal Twin Study, for whom we had prospectively-collected information on maltreatment exposure. We found that maltreated children exhibited blunted elevation in leptin levels in relation to increasing levels of physiological stimuli, adiposity and inflammation, compared with a group of non-maltreated children matched for gender, zygosity and socioeconomic status. These findings were also independent of key potential artifacts and confounders, such as time of day at sample collection, history of food insecurity, pubertal maturation and depressive symptoms. Furthermore, using birth weight as a proxy measure for leptin, we found that physiological abnormalities were presumably not present at birth in children who went on to be maltreated but only emerged over the course of childhood, after maltreatment exposure. Leptin deficiency may contribute to onset, persistence and progression of physical health problems in maltreated children.

Specificity of childhood psychotic symptoms for predicting schizophrenia by 38 years of age: a birth cohort study.

BACKGROUND: Childhood psychotic symptoms have been used as a subclinical phenotype of schizophrenia in etiological research and as a target for preventative interventions. However, recent studies have cast doubt on the specificity of these symptoms for schizophrenia, suggesting alternative outcomes such as anxiety and depression. Using a prospective longitudinal birth cohort we investigated whether childhood psychotic symptoms predicted a diagnosis of schizophrenia or other psychiatric disorders by 38 years of age. METHOD: Participants were drawn from a birth cohort of 1037 children from Dunedin, New Zealand, who were followed prospectively to 38 years of age (96% retention rate). Structured clinical interviews were administered at age 11 to assess psychotic symptoms and study members underwent psychiatric assessments at ages 18, 21, 26, 32 and 38 to obtain past-year DSM-III-R/IV diagnoses and self-reports of attempted suicides since adolescence. RESULTS: Psychotic symptoms at age 11 predicted elevated rates of research diagnoses of schizophrenia and posttraumatic stress disorder (PTSD) and also suicide attempts by age 38, even when controlling for gender, social class and childhood psychopathology. No significant associations were found for persistent anxiety, persistent depression, mania or persistent substance dependence. Very few of the children presenting with age-11 psychotic symptoms were free from disorder by age 38. CONCLUSIONS: Childhood psychotic symptoms were not specific to a diagnosis of schizophrenia in adulthood and thus future studies of early symptoms should be cautious in extrapolating findings only to this clinical disorder. However, these symptoms may be useful as a marker of adult mental health problems more broadly.

Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study.

There is increasing interest in discovering mechanisms that mediate the effects of childhood stress on late-life disease morbidity and mortality. Previous studies have suggested one potential mechanism linking stress to cellular aging, disease and mortality in humans: telomere erosion. We examined telomere erosion in relation to children's exposure to violence, a salient early-life stressor, which has known long-term consequences for well-being and is a major public-health and social-welfare problem. In the first prospective-longitudinal study with repeated telomere measurements in children while they experienced stress, we tested the hypothesis that childhood violence exposure would accelerate telomere erosion from age 5 to age 10 years. Violence was assessed as exposure to maternal domestic violence, frequent bullying victimization and physical maltreatment by an adult. Participants were 236 children (49% females; 42% with one or more violence exposures) recruited from the Environmental-Risk Longitudinal Twin Study, a nationally representative 1994-1995 birth cohort. Each child's mean relative telomere length was measured simultaneously in baseline and follow-up DNA samples, using the quantitative PCR method for T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). Compared with their counterparts, the children who experienced two or more kinds of violence exposure showed significantly more telomere erosion between age-5 baseline and age-10 follow-up measurements, even after adjusting for sex, socioeconomic status and body mass index (B=-0.052, s.e.=0.021, P=0.015). This finding provides support for a mechanism linking cumulative childhood stress to telomere maintenance, observed already at a young age, with potential impact for life-long health.

Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins.

BACKGROUND: Childhood adverse experiences are known to induce persistent changes in the hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress. However, the mechanisms by which these experiences shape the neuroendocrine response to stress remain unclear. Method We tested whether bullying victimization influenced serotonin transporter gene (SERT) DNA methylation using a discordant monozygotic (MZ) twin design. A subsample of 28 MZ twin pairs discordant for bullying victimization, with data on cortisol and DNA methylation, were identified in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative 1994-1995 cohort of families with twins. RESULTS: Bullied twins had higher SERT DNA methylation at the age of 10 years compared with their non-bullied MZ co-twins. This group difference cannot be attributed to the children's genetic makeup or their shared familial environments because of the study design. Bullied twins also showed increasing methylation levels between the age of 5 years, prior to bullying victimization, and the age of 10 years whereas no such increase was detected in non-bullied twins across time. Moreover, children with higher SERT methylation levels had blunted cortisol responses to stress. CONCLUSIONS: Our study extends findings drawn from animal models, supports the hypothesis that early-life stress modifies DNA methylation at a specific cytosine-phosphate-guanine (CpG) site in the SERT promoter and HPA functioning and suggests that these two systems may be functionally associated.

Validation of a high-sensitivity assay for C-reactive protein in human saliva.

This study aimed to validate a high-sensitivity assay for C-reactive protein (CRP) in saliva as an alternative medium to study inflammation in large epidemiological cohorts and young people. We measured CRP in saliva and serum in 61 (29.5% males) healthy adult volunteers. We found a moderate-to-strong association between CRP measured in saliva and in serum (r=.72, p<.001). In agreement with the non-steroidal structure and the high molecular weight of CRP, we observed a low saliva-to-serum CRP ratio (1:1633.64). Furthermore, a dichotomous index of salivary CRP, equivalent to a clinically relevant serum CRP cut-off (3mg/l), was associated to known correlates of systemic inflammation (IL-6, BMI and smoking). Finally, we showed that CRP in saliva is stable at room temperature up to 8h after collection. Our study provides initial evidence suggesting that non-invasive assessment of CRP in saliva allows valid prediction of serum CRP. Salivary CRP may thus facilitate and promote research exploring the correlates of low-grade inflammation in epidemiological studies and makes it feasible to expand psychoneuroimmunology research to pediatric populations.

Bullying victimization in youths and mental health problems: 'much ado about nothing'?

Bullying victimization is a topic of concern for youths, parents, school staff and mental health practitioners. Children and adolescents who are victimized by bullies show signs of distress and adjustment problems. However, it is not clear whether bullying is the source of these difficulties. This paper reviews empirical evidence to determine whether bullying victimization is a significant risk factor for psychopathology and should be the target of intervention and prevention strategies. Research indicates that being the victim of bullying (1) is not a random event and can be predicted by individual characteristics and family factors; (2) can be stable across ages; (3) is associated with severe symptoms of mental health problems, including self-harm, violent behaviour and psychotic symptoms; (4) has long-lasting effects that can persist until late adolescence; and (5) contributes independently to children's mental health problems. This body of evidence suggests that efforts aimed at reducing bullying victimization in childhood and adolescence should be strongly supported. In addition, research on explanatory mechanisms involved in the development of mental health problems in bullied youths is needed.

Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence.

BACKGROUND: Adolescent cannabis use has been shown in many studies to increase the risk of later psychosis. Childhood trauma is associated with both substance misuse and risk for psychosis. In this study our aim was to investigate whether there is a significant interaction between cannabis use and childhood trauma in increasing the risk for experiencing psychotic symptoms during adolescence. METHOD: Psychiatric interviews using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) semi-structured instrument were carried out with 211 adolescents aged between 12 and 15 years and their parents as part of a population-based study. The interview enquired about early traumatic events, cannabis use and psychiatric symptoms in adolescence. RESULTS: In separate analyses both cannabis use and childhood trauma were significantly associated with risk of experiencing psychotic symptoms. However, the presence of both childhood trauma and early cannabis use significantly increased the risk for psychotic symptoms beyond the risk posed by either risk factor alone, indicating that there was a greater than additive interaction between childhood trauma and cannabis use. CONCLUSION: Our finding of a greater than additive interaction between childhood trauma and cannabis use may have implications for the identification of individuals at high risk of experiencing psychotic symptoms. For example, measures to actively discourage or intensively treat cannabis use in children and adolescents who have experienced abuse may help to prevent the development of psychosis in this vulnerable group. Our findings require replication in larger samples to confirm this interaction effect.

Salivary cortisol and aggression in a population-based longitudinal study of adolescent males.

Chronic antisocial behaviour in youth has been associated with cortisol, a measure of stress reactivity. However, some studies have found low cortisol levels, while others have found elevated cortisol levels. The present study compared variously defined aggressive subgroups for differences in salivary cortisol. A population-based sample of boys was followed longitudinally from childhood to adolescence. Assessments of different forms of antisocial behaviour were obtained from various informants at several points in time, and cortisol was collected at age 13. Higher cortisol levels were found in boys with conduct disorder (CD) than in boys without CD. In addition, boys with an aggressive form of CD had higher cortisol levels than boys who showed a covert form of CD. Furthermore, reactive aggression was strongly correlated with elevated cortisol. Adolescent boys with chronic reactive aggression and those who scored high on aggressive CD symptoms seem to have a more active hypothalamic-pituitary-adrenal system.

Asociación causal entre Cannabis y psicosis: examen de la evidencia / Causal association between cannabis and psychosis: examination of the evidence

INTRODUCCIÓN: Sigue suscitando controversia el hecho de si el Cannabis actúa como un factor de riesgo causal para la esquizofrenia u otras psicosis funcionales. OBJETIVOS: Examinar críticamente la evidencia de que el Cannabis causa psicosis utilizando criterios establecidos de causalidad. MÉTODO: Identificamos 5 estudios que incluían una muestra bien definida extraída de registros de poblaciones o cohortes y que utilizaban medidas prospectivas de uso de Cannabis y psicosis adulta. RESULTADOS: Individualmente, el uso de Cannabis confiere un doble incremento global del riesgo relativo de sufrir esquizofrenia posteriormente. En la población general, la eliminación del uso de Cannabis podría reducir la incidencia de esquizofrenia en aproximadamente un 8 por ciento, asumiendo una relación causal. El consumo de Cannabis no parece ser una causa necesaria ni suficiente de psicosis. Es una causa componente, parte de una compleja constelación de factores que conducen a esta enfermedad. CONCLUSIONES: Podrían prevenirse casos de trastorno psicótico mediante la disuasión del uso de Cannabis entre la juventud vulnerable. Se requieren más investigaciones para comprender los mecanismos por los que el Cannabis causa psicosis (AU)