Hallucinations as a risk marker for suicidal behaviour in individuals with a history of sexual assault: a general population study with instant replication.

BACKGROUND: Research has shown a strong relationship between hallucinations and suicidal behaviour in general population samples. Whether hallucinations also index suicidal behaviour risk in groups at elevated risk of suicidal behaviour, namely in individuals with a sexual assault history, remains to be seen. AIMS: We assessed whether hallucinations were markers of risk for suicidal behaviour among individuals with a sexual assault history. METHODS: Using the cross-sectional 2007 (N = 7403) and 2014 (N = 7546) Adult Psychiatric Morbidity Surveys, we assessed for an interaction between sexual assault and hallucinations in terms of the odds of suicide attempt, as well as directly comparing the prevalence of suicide attempt in individuals with a sexual assault history with v. without hallucinations. RESULTS: Individuals with a sexual assault history had increased odds of hallucinations and suicide attempt compared to individuals without a sexual assault history in both samples. There was a significant interaction between sexual assault and hallucinations in terms of the odds of suicide attempt. In total, 14-19% of individuals with a sexual assault history who did not report hallucinations had one or more suicide attempt. This increased to 33-52% of individuals with a sexual assault history who did report hallucinations (2007, aOR = 2.85, 1.71-4.75; 2014, aOR = 4.52, 2.78-7.35). CONCLUSIONS: Hallucinations are a risk marker for suicide attempt even among individuals with an elevated risk of suicidal behaviour, specifically individuals with a sexual assault history. This finding highlights the clinical significance of hallucinations with regard to suicidal behaviour risk, even among high-risk populations.

Potential for prediction of psychosis and bipolar disorder in Child and Adolescent Mental Health Services: a longitudinal register study of all people born in Finland in 1987.

Current strategies to predict psychosis identify only a small proportion of individuals at risk. Additional strategies are needed to increase capacity for pre-diction and prevention of serious mental illness, ideally during childhood and adolescence. One possible approach would be to investigate systems in which psychosis risk factors are concentrated during childhood. One notable such system is represented by Child and Adolescent Mental Health Services (CAMHS). Although psychotic disorders are uncommon in CAMHS, many risk factors for psychosis are highly prevalent in young people who enter this system. We hypothesized, therefore, that youth attending CAMHS would be a high-risk group for psychosis if followed into adulthood and, furthermore, that CAMHS systems would capture a substantial proportion of future psychosis cases. We constructed a total population cohort study of all Finns born in 1987 (N=55,875), linking together extensive register data on health care contacts from birth through age 28 years. We identified all individuals diagnosed with a psychotic or bipolar disorder by age 28 (N=1,785). The risk of psychosis/bipolar disorder by age 28 years was 1.8% for individuals who had not attended CAMHS during childhood or adolescence, whereas it was 12.8% for those with a history of any outpatient CAMHS contact (odds ratio, OR=7.9, 95% CI: 7.2-8.7). Furthermore, the risk of psychosis/bipolar disorder by age 28 years was 2.3% for individuals without a history of inpatient CAMHS admission, whereas it was 24.0% for those with a history of inpatient CAMHS admission (OR=13.3, 95% CI: 11.9-14.9), and 36.5% for those with a history of inpatient CAMHS admission in adolescence (age 13-17 years) (OR=24.2, 95% CI: 21.2-27.6). Individuals who attended CAMHS but received no mental disorder diagnosis had an equally high risk of subsequently developing a psychosis/bipolar disorder as individuals who did receive a diagnosis (OR=0.9, 99.5% CI: 0.7-1.1). Compared to other CAMHS attendees, individuals who developed psychosis or bipolar disorder were more likely to have had an initial CAMHS diagnosis of depressive or other mood disorder (OR=2.3, 99.5% CI: 1.6-3.0) and disruptive behaviour disorder (OR=1.7, 99.5% CI: 1.2-2.5). Of all psychosis/bipolar diagnoses by age 28 years, 50.2% occurred in individuals who had, at some point in childhood or adolescence, attended CAMHS, indicating that CAMHS represent not only a high-risk but also a high-capacity system for prediction of psychosis/bipolar disorder. These findings suggest an enormous, untapped potential for large-scale psychosis/bipolar disorder prediction and prevention research within existing specialist CAMHS.

Hallucinations in the general population across the adult lifespan: prevalence and psychopathologic significance.

BACKGROUND: Community studies have found a relatively high prevalence of hallucinations, which are associated with a range of (psychotic and non-psychotic) mental disorders, as well as with suicidal ideation and behaviour. The literature on hallucinations in the general population has largely focused on adolescents and young adults. AIMS: We aimed to explore the prevalence and psychopathologic significance of hallucinations across the adult lifespan. METHOD: Using the 1993, 2000, 2007 and 2014 cross-sectional Adult Psychiatric Morbidity Survey series (N = 33 637), we calculated the prevalence of past-year hallucinations in the general population ages 16 to ≥90 years. We used logistic regression to examine the relationship between hallucinations and a range of mental disorders, suicidal ideation and suicide attempts. RESULTS: The prevalence of past-year hallucinations varied across the adult lifespan, from a high of 7% in individuals aged 16-19 years, to a low of 3% in individuals aged ≥70 years. In all age groups, hallucinations were associated with increased risk for mental disorders, suicidal ideation and suicide attempts, but there was also evidence of significant age-related variation. In particular, hallucinations in older adults were less likely to be associated with a cooccurring mental disorder, suicidal ideation or suicide attempt compared with early adulthood and middle age. CONCLUSIONS: Our findings highlight important life-course developmental features of hallucinations from early adulthood to old age.

Associations Between Maternal Prenatal C-Reactive Protein and Risk Factors for Psychosis in Adolescent Offspring: Findings From the Northern Finland Birth Cohort 1986.

Prenatal infection is associated with brain structural and functional abnormalities and may increase the risk for psychosis through a direct effect on neurodevelopment. Various infections may exert their effect through a proinflammatory immune response but studies of prenatal maternal inflammatory markers and offspring neurodevelopment are scarce. Using the longitudinal Northern Finland Birth Cohort 1986 study, we examined the associations of maternal prenatal C-reactive protein (CRP) levels with psychosis risk factors in adolescent offspring. CRP was measured in maternal sera collected in pregnancy. In offspring, school performance was measured at age 7 years, while school performance, psychotic experiences, and cannabis use were measured at age 16 years. We tested associations of CRP with offspring measures using regression analysis controlling for offspring sex, maternal education level, and prenatal maternal body mass index, smoking and alcohol use in pregnancy, place of birth, maternal psychiatric admission, paternal psychiatric admission, mothers age at birth, and gestational week of CRP sample. We also tested if adolescent cannabis use mediated the associations between maternal CRP and offspring outcomes. Controlling for covariates, maternal CRP was associated with academic performance at age 16 years (beta = .062, 95% CI = 0.036-0.088), but not with possible psychotic experiences at 16 years (odds ratio [OR] = 1.09, 95% CI = 0.96-1.24). Maternal CRP was also associated with adolescent cannabis use (OR = 1.24, 95% CI = 1.07-1.43). These findings suggest that prenatal inflammation may influence later mental illness risk by affecting neurodevelopment and also indirectly by increasing the risk of exposure to cannabis.

Cognition, psychosis risk and metabolic measures in two adolescent birth cohorts.

BACKGROUND: Psychoses, especially schizophrenia, are often preceded by cognitive deficits and psychosis risk states. Altered metabolic profiles have been found in schizophrenia. However, the associations between metabolic profiles and poorer cognitive performance and psychosis risk in the population remain to be determined. METHODS: Detailed molecular profiles were measured for up to 8976 individuals from two general population-based prospective birth cohorts: the Northern Finland Birth Cohort 1986 (NFBC 1986) and the Avon Longitudinal Study of Parents and Children (ALSPAC). A high-throughput nuclear magnetic resonance spectroscopy platform was used to quantify 70 metabolic measures at age 15-16 years in the NFBC 1986 and at ages 15 and 17 years in ALSPAC. Psychosis risk was assessed using the PROD-screen questionnaire at age 15-16 years in the NFBC 1986 or the psychotic-like symptoms assessment at age 17 years in ALSPAC. Cognitive measures included academic performance at age 16 years in both cohorts and general intelligence and executive function in ALSPAC. Logistic regression measured cross-sectional and longitudinal associations between metabolic measures and psychosis risk and cognitive performance, controlling for important covariates. RESULTS: Seven metabolic measures, primarily fatty acid (FA) measures, showed cross-sectional associations with general cognitive performance, four across both cohorts (low density lipoprotein diameter, monounsaturated FA ratio, omega-3 ratio and docosahexaenoic acid ratio), even after controlling for important mental and physical health covariates. Psychosis risk showed minimal metabolic associations. CONCLUSIONS: FA ratios may be important in marking risk for cognitive deficits in adolescence. Further research is needed to clarify whether these biomarkers could be causal and thereby possible targets for intervention.

The effect of prenatal smoking exposure on daily smoking among teenage offspring.

AIMS: To study the predictive associations between maternal smoking and the impact of quitting smoking during pregnancy and offspring daily smoking at age 15-16 years. DESIGN: The Northern Finland Birth Cohort 1986 (NFBC86) includes 99% of all births in the region and has an ongoing follow-up. Data were collected using questionnaires at 24th gestational week during pregnancy and after delivery, and at follow-up in 2001-02, when the offspring were aged 15-16 years. SETTING: Northern Finland. PARTICIPANTS: NFBC86 included 9432 live born children. Data regarding maternal smoking during pregnancy and offspring smoking at age 15-16 years were available for 4462 subjects (47.3% of the original sample). MEASUREMENTS: The outcome was offspring's self-reported daily smoking. Maternal smoking during pregnancy was considered using a four-class variable: (1) no smoking, (2) mother had smoked, but had quit smoking before becoming pregnant, (3) mother quit smoking during the 1st trimester and (4) mother quit smoking after the 1st trimester or continued smoking throughout the pregnancy. Information regarding paternal smoking during pregnancy, maternal and paternal smoking and education level, family structure and dwelling at offspring's age 15-16 years were considered potential confounding variables. FINDINGS: Continuing smoking after the 1st trimester increased the odds of daily smoking among offspring, independently of confounding factors [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.3-2.5]. Continuing to smoke after the 1st trimester was associated with higher odds compared with quitting smoking during the 1st trimester. Also, parental smoking at offspring age 15-16 years increased the odds of offspring daily smoking, independently of prenatal smoking exposure. CONCLUSIONS: Prenatal smoking exposure increases the risk for offspring adolescent daily smoking. Quitting smoking during the early stages of pregnancy may decrease the odds for offspring smoking.

Smoking in pregnancy, adolescent mental health and cognitive performance in young adult offspring: results from a matched sample within a Finnish cohort.

BACKGROUND: The association between prenatal exposure to maternal cigarette smoking (PEMCS) and adult cognition is debated, including if there are differences according to sex. We aimed to determine if there are associations between PEMCS and cognition in early adulthood in men and women and examine if observed associations were mediated by adolescent mental health factors that are associated with cognition, namely psychotic-like experiences (PLEs), inattention and hyperactivity, and other externalizing behaviors. METHODS: Participants were 471 individuals drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986) followed up from pregnancy and birth to early adulthood; individuals with PEMCS were matched with those without PEMCS by socioeconomic and demographic factors. Cognitive performance in adulthood was assessed with a range of tests and their association with PEMCS was measured by sex using hierarchical linear regression, unadjusted and then controlling for potential confounders, mediators and moderators, including adolescent mental health factors. RESULTS: There were no associations between PEMCS and cognitive scores in females. In males, there were associations with vocabulary (beta = -0.444, 95% CI: -0.783, -0.104) and matrix reasoning (beta = -0.379, 95% CI: -0.711, -0.047). CONCLUSIONS: While associations between PEMCS and cognition were limited, observed findings with measures of general intelligence in males contribute to suggestions of differences in response to PEMCS by sex. Furthermore, observed associations may be partly mediated by earlier inattention and hyperactivity. Findings add support to efforts aimed to eliminate smoking in pregnancy.

Association between Dopamine Receptor D2 (DRD2) Variations rs6277 and rs1800497 and Cognitive Performance According to Risk Type for Psychosis: A Nested Case Control Study in a Finnish Population Sample.

BACKGROUND: There is limited research regarding the association between genes and cognitive intermediate phenotypes in those at risk for psychotic disorders. METHODS: We measured the association between established psychosis risk variants in dopamine D2 receptor (DRD2) and cognitive performance in individuals at age 23 years and explored if associations between cognition and these variants differed according to the presence of familial or clinical risk for psychosis. The subjects of the Oulu Brain and Mind Study were drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986). Using linear regression, we compared the associations between cognitive performance and two candidate DRD2 polymorphisms (rs6277 and rs1800497) between subjects having familial (n=61) and clinical (n=45) risk for psychosis and a random sample of participating NFBC 1986 controls (n=74). Cognitive performance was evaluated using a comprehensive battery of tests at follow-up. RESULTS: Principal components factor analysis supported a three-factor model for cognitive measures. The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis. The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049). CONCLUSION: The effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ according to the type (familial or clinical) risk for psychosis.

Relationship between the COMT-Val158Met and BDNF-Val66Met polymorphisms, childhood trauma and psychotic experiences in an adolescent general population sample.

OBJECTIVE: Psychotic experiences occur at a much greater prevalence in the population than psychotic disorders. There has been little research to date, however, on genetic risk for this extended psychosis phenotype. We examined whether COMT or BDNF genotypes were associated with psychotic experiences or interacted with childhood trauma in predicting psychotic experiences. METHOD: Psychiatric interviews and genotyping for COMT-Val158Met and BDNF-Val66Met were carried out on two population-based samples of 237 individuals aged 11-15 years. Logistic regression was used to examine for main effects by genotype and childhood trauma, controlling for important covariates. This was then compared to a model with a term for interaction between genotype and childhood trauma. Where a possible interaction was detected, this was further explored in stratified analyses. RESULTS: While childhood trauma showed a borderline association with psychotic experiences, COMT-Val158Met and BDNF-Val66Met genotypes were not directly associated with psychotic experiences in the population. Testing for gene x environment interaction was borderline significant in the case of COMT-Val158Met with individuals with the COMT-Val158Met Val-Val genotype, who had been exposed to childhood trauma borderline significantly more likely to report psychotic experiences than those with Val-Met or Met-Met genotypes. There was no similar interaction by BDNF-Val66Met genotype. CONCLUSION: The COMT-Val158Met Val-Val genotype may be a genetic moderator of risk for psychotic experiences in individuals exposed to childhood traumatic experiences.

Psychotic symptoms and population risk for suicide attempt: a prospective cohort study.

IMPORTANCE: Up to 1 million persons die by suicide annually. However, a lack of risk markers makes suicide risk assessment one of the most difficult areas of clinical practice. OBJECTIVE: To assess psychotic symptoms (attenuated or frank) as a clinical marker of risk for suicide attempt. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 1112 school-based adolescents (aged 13-16 years), assessed at baseline and at 3 and 12 months for self-reported psychopathology, psychotic symptoms, and suicide attempts. MAIN OUTCOMES AND MEASURES: Suicide attempts at the 3- and 12-month follow-up and acute suicide attempts (defined as those occurring in the 2 weeks before an assessment). RESULTS: Of the total sample, 7% reported psychotic symptoms at baseline. Of that subsample, 7% reported a suicide attempt by the 3-month follow-up compared with 1% of the rest of the sample (odds ratio [OR], 10.01; 95% CI, 2.24-45.49), and 20% reported a suicide attempt by the 12-month follow-up compared with 2.5% of the rest of the sample (OR, 11.27; 95% CI, 4.44-28.62). Among adolescents with baseline psychopathology who reported psychotic symptoms, 14% reported a suicide attempt by 3 months (OR, 17.91; 95% CI, 3.61-88.82) and 34% reported a suicide attempt by 12 months (OR, 32.67; 95% CI, 10.42-102.41). Adolescents with psychopathology who reported psychotic symptoms had a nearly 70-fold increased odds of acute suicide attempts (OR, 67.50; 95% CI, 11.41-399.21). Differences were not explained by nonpsychotic psychiatric symptom burden, multimorbidity, or substance use. In a causative model, the population-attributable fraction of suicide attempts would be 56% to 75% for psychotic symptoms. CONCLUSIONS AND RELEVANCE: Adolescents with psychopathology who report psychotic symptoms are at clinical high risk for suicide attempts. More careful clinical assessment of psychotic symptoms (attenuated or frank) in mental health services and better understanding of their pathological significance are urgently needed.

Childhood trauma and psychosis in a prospective cohort study: cause, effect, and directionality.

OBJECTIVE: Using longitudinal and prospective measures, the authors assessed the relationship between childhood trauma and psychotic experiences, addressing the following questions: 1) Does exposure to trauma predict incident psychotic experiences? 2) Does cessation of trauma predict cessation of psychotic experiences? 3) What is the direction of the relationship between childhood trauma and psychotic experiences? METHOD: This was a nationally representative prospective cohort study of 1,112 school-based adolescents 13-16 years of age, assessed at baseline and at 3-month and 12-month follow-ups for childhood trauma (physical assault and bullying) and psychotic experiences. RESULTS: A bidirectional relationship was observed between childhood trauma and psychosis, with trauma predicting psychotic experiences over time and vice versa. However, even after accounting for this bidirectional relationship with a number of strict adjustments (only newly incident psychotic experiences occurring over the course of the study following exposure to traumatic experiences were examined), trauma was strongly predictive of psychotic experiences. A dose-response relationship was observed between severity of bullying and risk for psychotic experiences. Moreover, cessation of trauma predicted cessation of psychotic experiences, with the incidence of psychotic experiences decreasing significantly in individuals whose exposure to trauma ceased over the course of the study. CONCLUSIONS: After a series of conservative adjustments, the authors found that exposure to childhood trauma predicted newly incident psychotic experiences. The study also provides the first direct evidence that cessation of traumatic experiences leads to a reduced incidence of psychotic experiences.

Five years after implementation: a review of the Irish Mental Health Act 2001.

OBJECTIVES: The Mental Health Act 2001 (MHA 2001) was implemented in November 2006. Since that time, there has been considerable research into its impact, including the impact on service provision, use of coercive practices and the perceptions by key stakeholders. Our objective is to present a summary of research into the MHA 2001 since its implementation in the Irish state in the context of international standards and practice. METHODS: We reviewed the literature presented on Medline and Google Scholar, directly assessed relevant journals and sought abstract information from the College of Psychiatry of Ireland. RESULTS: There has been a small decrease in the rate of involuntary admission since implementation but there has been no change in the representativeness of diagnoses of individuals admitted involuntarily. Mental Health Tribunals were held for 57% of those admitted involuntarily and 46% of service users found that the Mental Health Tribunal made the involuntary admission easier to accept. One year after discharge, 60% of service users reflected that their involuntary admission had been necessary. Professional groups have expressed concerns regarding workload, training time for junior doctors and paperwork. CONCLUSIONS: The MHA 2001 has brought the practice of involuntary admission further into line with international standards. However, five years after the implementation of the Act international guidelines and practice have highlighted areas in need of further reform, including capacity legislation and consideration of advance directives and community treatment orders. Further research is also lacking on caregivers' or family members' perceptions of the MHA 2001.

Inhibition of Toll-like receptor 2-mediated interleukin-8 production in Cystic Fibrosis airway epithelial cells via the alpha7-nicotinic acetylcholine receptor.

Cystic Fibrosis (CF) is an inherited disorder characterised by chronic inflammation of the airways. The lung manifestations of CF include colonization with Pseudomonas aeruginosa and Staphylococcus aureus leading to neutrophil-dominated airway inflammation and tissue damage. Inflammation in the CF lung is initiated by microbial components which activate the innate immune response via Toll-like receptors (TLRs), increasing airway epithelial cell production of proinflammatory mediators such as the neutrophil chemokine interleukin-8 (IL-8). Thus modulation of TLR function represents a therapeutic approach for CF. Nicotine is a naturally occurring plant alkaloid. Although it is negatively associated with cigarette smoking and cardiovascular damage, nicotine also has anti-inflammatory properties. Here we investigate the inhibitory capacity of nicotine against TLR2- and TLR4-induced IL-8 production by CFTE29o- airway epithelial cells, determine the role of alpha7-nAChR (nicotinic acetylcholine receptor) in these events, and provide data to support the potential use of safe nicotine analogues as anti-inflammatories for CF.