Association between maternal antidepressant use during pregnancy and the risk of autism spectrum disorder and attention deficit hyperactivity disorder in offspring.

Prenatal antidepressant exposure has been reported to be associated with adverse neurodevelopmental outcomes, yet studies considering confounding factors in Asian populations are lacking. This study utilized a nationwide data base in Taiwan, enrolling all liveborn children registered in the National Health Insurance system between 2004 and 2016. Subjects were divided into two groups: antidepressant-exposed (n = 55,707)) and antidepressant-unexposed group (n = 2,245,689). The effect of antidepressant exposure during different trimesters on autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) was examined. Sibling controls and parallel comparisons by paternal exposure status were treated as negative controls. Additional sensitivity analyses were conducted to examine the effects of antidepressant exposure before and after pregnancy. Prenatal antidepressant exposure was associated with increased risks of ASD and ADHD in population-wide and adjusted analysis. However when comparing antidepressant-exposed children with their unexposed siblings, no differences were found for ASD (Hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.76-1.42 in first trimester; HR: 0.96, 95% CI 0.62-1.50 in second trimester; HR: 0.69, 95% CI 0.32-1.48 in third trimester) and ADHD (HR: 0.98, 95%CI 0.84-1.15 in first trimester; HR: 0.91, 95% CI 0.73-1.14 in second trimester; HR: 0.79, 95% CI 0.54-1.16 in third trimester). Increased risks for ASD and ADHD were also noted in paternal control, before and after pregnancy analyses. These results imply that the association between prenatal antidepressant exposure and ASD and ADHD is not contributed to by an intrauterine medication effect but more likely to be accounted for by maternal depression, genetic, and potential environmental factors.

Excess Mortality in Individuals with Autism Spectrum Disorder: A Population-Based Cohort Study.

Purpose: Autism spectrum disorder (ASD) may be associated with increased mortality, but relevant findings have been inconsistent. The modifying effects of gender and intellectual disability on excess mortality in individuals with ASD are underexplored. Patients and Methods: Using Taiwan's National Health Insurance Research Database and the National Death Registry, this population-based cohort study selected the data of 75,946 patients with ASD (ASD cohort) and 75,946 age group-, gender-, and income-matched (1:1) patients without ASD (non-ASD cohort). Cox proportional hazards models were used to compare mortality rates between the cohorts, and stratified analyses were used to evaluate the influence of gender and intellectual disability on mortality risk. Results: The ASD cohort had higher mortality rates for all causes of death than did the non-ASD cohort (adjusted hazard ratio 1.64, 95% confidence interval 1.54-1.75). Comorbid intellectual disability was associated with an increased risk of mortality, and this association was stronger in female patients than in male patients. Moreover, when focusing on deaths from natural causes, we found a significantly higher odds ratio for mortality in the ASD population with ID compared to those without ID. Conclusion: ASD is associated with increased mortality, especially among female individuals and those with intellectual disability.

Improving our understanding of the social determinants of mental health: a data linkage study of mental health records and the 2011 UK census.

OBJECTIVES: To address the lack of individual-level socioeconomic information in electronic healthcare records, we linked the 2011 census of England and Wales to patient records from a large mental healthcare provider. This paper describes the linkage process and methods for mitigating bias due to non-matching. SETTING: South London and Maudsley NHS Foundation Trust (SLaM), a mental healthcare provider in Southeast London. DESIGN: Clinical records from SLaM were supplied to the Office of National Statistics for linkage to the census through a deterministic matching algorithm. We examined clinical (International Classification of Disease-10 diagnosis, history of hospitalisation, frequency of service contact) and socio-demographic (age, gender, ethnicity, deprivation) information recorded in Clinical Record Interactive Search (CRIS) as predictors of linkage success with the 2011 census. To assess and adjust for potential biases caused by non-matching, we evaluated inverse probability weighting for mortality associations. PARTICIPANTS: Individuals of all ages in contact with SLaM up until December 2019 (N=459 374). OUTCOME MEASURES: Likelihood of mental health records' linkage to census. RESULTS: 220 864 (50.4%) records from CRIS linked to the 2011 census. Young adults (prevalence ratio (PR) 0.80, 95% CI 0.80 to 0.81), individuals living in more deprived areas (PR 0.78, 95% CI 0.78 to 0.79) and minority ethnic groups (eg, Black African, PR 0.67, 0.66 to 0.68) were less likely to match to census. After implementing inverse probability weighting, we observed little change in the strength of association between clinical/demographic characteristics and mortality (eg, presence of any psychiatric disorder: unweighted PR 2.66, 95% CI 2.52 to 2.80; weighted PR 2.70, 95% CI 2.56 to 2.84). CONCLUSIONS: Lower response rates to the 2011 census among people with psychiatric disorders may have contributed to lower match rates, a potential concern as the census informs service planning and allocation of resources. Due to its size and unique characteristics, the linked data set will enable novel investigations into the relationship between socioeconomic factors and psychiatric disorders.

Common perinatal mental disorders and post-infancy child development in rural Ethiopia: A population-based cohort study.

OBJECTIVE: To investigate whether maternal common mental disorders (CMD) in the postnatal period are prospectively associated with child development at 2.5 and 3.5 years in a rural low-income African setting. METHODS: This study was nested within the C-MaMiE (Child outcomes in relation to Maternal Mental health in Ethiopia) population-based cohort in Butajira, Ethiopia, and conducted from 2005 to 2006. The sample comprised of 496 women who had recently given birth to living, singleton babies with recorded birth weight measurements, who were 15 to 44 years of age, and residing in six rural sub-districts. Postnatal CMD measurements were ascertained 2 months after delivery. Language, cognitive, and motor development were obtained from the child 2.5 and 3.5 years after birth using a locally adapted version of the Bayley Scales of Infant Development (3rd Ed). Maternal CMD symptoms were measured using a locally validated WHO Self-Reporting Questionnaire. A linear mixed-effects regression model was used to analyze the relationship between postnatal CMD and child development. RESULTS: After adjusting for confounders, there was no evidence for an association between postnatal CMD and overall child development or the cognitive sub-domain in the preschool period. There was no evidence of effect modification by levels of social support, socioeconomic status, stunting, or sex of the child. CONCLUSIONS: Previous studies from predominantly urban and peri-urban settings in middle-income countries have established a relationship between maternal CMD and child development, which contrasts with the findings from this study. The risk and protective factors for child development may differ in areas characterized by high social adversity and food insecurity. More studies are needed to investigate maternal CMD's impact on child development in low-resource and rural areas.

Methylphenidate and TBI in ADHD and co-occurring epilepsy and mental disorders: a self-controlled case series study.

It is suggested that medication for attention-deficit hyperactivity disorder (ADHD) links to lower risk of traumatic brain injury (TBI). Little is known about whether the beneficial effect of methylphenidate is persistent in individuals with other comorbid mental disorders and epilepsy. We identified 90,634 participants who were less than 18 years old and diagnosed with ADHD from Taiwan's National Health Insurance Research Database (NHIRD) from January 1, 2000 to December 31, 2013. Cox proportional hazards models with hazard ratio (HR) and 95% confidence interval were conducted to compare the risks of TBI event between groups of ADHD-only and ADHD with co-occurring other mental disorders. Within-individual comparisons using a self-controlled case series study design were conducted using conditional Poisson regression models with relative incidence (RR) and 95% CI to examine the effect of methylphenidate on TBI with adjustment for medication of psychotropics and anticonvulsants. For children and adolescents with ADHD, we found comorbid mental disorders and epilepsy increase the risk of TBI, with HRs ranged from 1.21 to 1.75. For the effect of MPH, we found reduced risks for TBI in ADHD (RR = 0.83, 95% CI = 0.70-0.98). Similar results were found among individuals with co-occurring oppositional defiant disorders or conduct disorder, MDD, tic disorders and epilepsy. Methylphenidate treatment was linked to lower risk for TBI in patients with ADHD and the inverse association was persistent among those with other comorbid mental disorders and epilepsy.

Efficacy and cost-effectiveness of task-shared care for people with severe mental disorders in Ethiopia (TaSCS): a single-blind, randomised, controlled, phase 3 non-inferiority trial.

BACKGROUND: There have been no trials of task-shared care (TSC) using WHO's mental health Gap Action Programme for people with severe mental disorders (psychosis or affective disorder) in low-income or middle-income countries. We aimed to evaluate the efficacy and cost-effectiveness of TSC compared with enhanced specialist mental health care in rural Ethiopia. METHODS: In this single-blind, phase 3, randomised, controlled, non-inferiority trial, participants had a confirmed diagnosis of a severe mental disorder, recruited from either the community or a local outpatient psychiatric clinic. The intervention was TSC, delivered by supervised, non-physician primary health care workers trained in the mental health Gap Action Programme and working with community health workers. The active comparison group was outpatient psychiatric nurse care augmented with community lay workers (PSY). Our primary endpoint was whether TSC would be non-inferior to PSY at 12 months for the primary outcome of clinical symptom severity using the Brief Psychiatric Rating Scale, Expanded version (BPRS-E; non-inferiority margin of 6 points). Randomisation was stratified by health facility using random permuted blocks. Independent clinicians allocated groups using sealed envelopes with concealment and outcome assessors and investigators were masked. We analysed the primary outcome in the modified intention-to-treat group and safety in the per-protocol group. This trial is registered with ClinicalTrials.gov, number NCT02308956. FINDINGS: We recruited participants between March 13, 2015 and May 21, 2016. We randomly assigned 329 participants (111 female and 218 male) who were aged 25-72 years and were predominantly of Gurage (198 [60%]), Silte (58 [18%]), and Mareko (53 [16%]) ethnicity. Five participants were found to be ineligible after randomisation, giving a modified intention-to-treat sample of 324. Of these, 12-month assessments were completed in 155 (98%) of 158 in the TSC group and in 158 (95%) of 166 in the PSY group. For the primary outcome, there was no evidence of inferiority of TSC compared with PSY. The mean BPRS-E score was 27·7 (SD 4·7) for TSC and 27·8 (SD 4·6) for PSY, with an adjusted mean difference of 0·06 (90% CI -0·80 to 0·89). Per-protocol analyses (n=291) were similar. There were 47 serious adverse events (18 in the TSC group, 29 in the PSY group), affecting 28 participants. These included 17 episodes of perpetrated violence and seven episodes of violent victimisation leading to injury, ten suicide attempts, six hospital admissions for physical health conditions, four psychiatric admissions, and three deaths (one in the TSC group, two in the PSY group). The incremental cost-effectiveness ratio for TSC indicated lower cost of -US$299·82 (95% CI -454·95 to -144·69) per unit increase in BPRS-E scores from a health care sector perspective at 12 months. INTERPRETATION: WHO's mental health Gap Action Programme for people with severe mental disorders is as cost-effective as existing specialist models of care and can be implemented effectively and safely by supervised non-specialists in resource-poor settings. FUNDING: US National Institute of Mental Health.

Selective serotonin reuptake inhibitors use and hepatocellular carcinoma in patients with alcohol use disorder.

BACKGROUND: Research has proposed that selective serotonin reuptake inhibitors (SSRIs) were associated with a reduction of the risk of hepatocellular carcinoma (HCC). The objective of this study is to investigate whether SSRIs use is associated with decreased risk of HCC in patients with alcohol use disorder (AUD). PATIENTS AND METHODS: We conducted a retrospective population-based cohort study using Taiwan's National Health Insurance Research Database (NHIRD) from 1997 to 2013 and enrolled patients with newly diagnosed AUD. After propensity scores matching at a ratio 1:4, total of 4945 SSRI users and 19,785 non-SSRI users were included in the matched cohort. Patients were followed up from the 365th day after the date of first exposure to SSRIs to occurrence of HCC, the date of death, or the end of 2013. Cox proportional hazard regressions were performed to evaluate hazard ratio (HRs) for HCC in SSRI-exposed patients compared with unexposed patients. RESULTS: In the main study cohort, SSRI use was associated with significant lower risk of HCC compared to the non-SSRI users after adjusting for age, sex, income, urbanization, alcoholic fatty liver, alcoholic hepatitis and diabetes (adjusted hazard ratio [aHR] = 0.31, 95 % CI = 0.24-0.39). The negative association of SSRI use and HCC was replicated in the matched cohort (aHR = 0.58, 95 % CI = 0.44-0.77). The effect of SSRI use on HCC was dose-related in both cohorts (p for trend < 0.0001). CONCLUSIONS: This study showed that SSRIs use was associated with a reduction risk of HCC among AUD patients in a cumulative dose effect manner.

Correction to: Task sharing for the care of severe mental disorders in a low-income country (TaSCS): study protocol for a randomised, controlled, non-inferiority trial.

An amendment to this paper has been published and can be accessed via the original article.

Methylphenidate and mortality in children with attention-deficit hyperactivity disorder: population-based cohort study.

BACKGROUND: Little is known about methylphenidate (MPH) use and mortality outcomes. AIMS: To investigate the association between MPH use and mortality among children with an attention-deficit hyperactivity disorder (ADHD) diagnosis. METHOD: This population-based cohort study analysed data from Taiwan's National Health Insurance Research Database (NHIRD). A total of 68 096 children and adolescents aged 4-17 years with an ADHD diagnosis and prescribed MPH between 2000 and 2010 were compared with 68 096 without an MPH prescription, matched on age, gender and year of first ADHD diagnosis. All participants were followed to death, migration, withdrawal from the National Health Insurance programme or 31 December 2013. MPH prescriptions were measured on a yearly basis during the study period, and the association between MPH use and mortality was analysed using a repeated-measures time-dependent Cox regression model. The outcome measures included all-cause, unnatural-cause (including suicide, accident and homicide) and natural-cause mortality, obtained from linkage to the National Mortality Register in Taiwan. RESULTS: The MPH group had lower unadjusted all-cause, natural-, unnatural- and accident-cause mortality than the comparison group. After controlling for potential confounders, MPH use was associated with a significantly lower all-cause mortality (adjusted hazard ratio AHR = 0.81, 95% CI 0.67-0.98, P = 0.027), delayed use of MPH was associated with higher mortality (AHR = 1.05, 95% CI 1.01-1.09) and longer MPH use was associated with lower mortality (AHR = 0.83, 95% CI 0.70-0.98). CONCLUSIONS: MPH use is associated with a reduced overall mortality in children with ADHD in this cohort study, but unmeasured confounding cannot be excluded absolutely.

Methylphenidate and the risk of burn injury among children with attention-deficit/hyperactivity disorder.

AIMS: Attention-deficit/hyperactivity disorder (ADHD) is associated with a higher risk of burn injury than in the normal population. Nevertheless, the influence of methylphenidate (MPH) on the risk of burn injury remains unclear. This retrospective cohort study analysed the effect of MPH on the risk of burn injury in children with ADHD. METHOD: Data were from Taiwan's National Health Insurance Research Database (NHIRD). The sample comprised individuals younger than 18 years with a diagnosis of ADHD (n = 90 634) in Taiwan's NHIRD between January 1996 and December 2013. We examined the cumulative effect of MPH on burn injury risk using Cox proportional hazards models. We conducted a sensitivity analysis for immortal time bias using a time-dependent Cox model and within-patient comparisons using the self-controlled case series model. RESULTS: Children with ADHD taking MPH had a reduced risk of burn injury, with a cumulative duration of treatment dose-related effect, compared with those not taking MPH. Compared with children with ADHD not taking MPH, the adjusted hazard ratio for burn injury was 0.70 in children taking MPH for <90 days (95% confidence interval (CI) 0.64-0.77) and 0.43 in children taking MPH for ≥90 days (95% CI 0.40-0.47), with a 50.8% preventable fraction. The negative association of MPH was replicated in age-stratified analysis using time-dependent Cox regression and self-controlled case series models. CONCLUSION: This study showed that MPH treatment was associated with a lower risk of burn injury in a cumulative duration of treatment dose-related effect manner.

A feasibility study of the effects of implementing a staff-level recovery-oriented training intervention in older people's mental health services.

Objectives: The concept of recovery has exerted considerable traction in mental health services for adults of working age, but less so in older people's mental health services. The aim of this study was to evaluate the feasibility of a staff-level recovery intervention in older people's mental health services.Method: The study used a mixed-method pre-post design. The study took place in NHS older people's mental health services, UK. Staff participants were multi-disciplinary mental health team members from the same service. The intervention was a manualised staff-level recovery intervention called the Older Adults Recovery Intervention (OARI). Measurement included the Recovery Knowledge Inventory and the Recovery Attitudes Questionnaire (RAQ-7) as well as fidelity data and in-depth qualitative interviews.Results: OARI was delivered to 204 staff in 15 clinical teams. There was a statistically significant change towards improvement in four of the six recovery attitude and knowledge sub-scales. There were positive findings in change in practice at individual level, but not at team level. A number of context barriers were identified leading to the intervention not being delivered as intended.Conclusions: Further development of OARI will involve a clearer distinction about the practice implications for service users with dementia versus functional illnesses, a stronger focus on implementation support, more use of evidence in training materials and a tailoring of context to meet professional group training needs. Overall, this study contributes novel data to the evidence base for recovery within older people's mental health services.

Task-sharing of psychological treatment for antenatal depression in Khayelitsha, South Africa: Effects on antenatal and postnatal outcomes in an individual randomised controlled trial.

The study's objective was to determine the effectiveness of a task-sharing psychological treatment for perinatal depression using non-specialist community health workers. A double-blind individual randomised controlled trial was conducted in two antenatal clinics in the peri-urban settlement of Khayelitsha, Cape Town. Adult pregnant women who scored 13 or above on the Edinburgh Postnatal Depression rating Scale (EPDS) were randomised into the intervention arm (structured six-session psychological treatment) or the control arm (routine antenatal health care and three monthly phone calls). The primary outcome was response on the Hamilton Depression Rating Scale (HDRS) at three months postpartum (minimum 40% score reduction from baseline) among participants who did not experience pregnancy or infant loss (modified intention-to-treat population) (registered on Clinical Trials: NCT01977326). Of 2187 eligible women approached, 425 (19.4%) screened positive on the EPDS and were randomised; 384 were included in the modified intention-to-treat analysis (control: n = 200; intervention: n = 184). There were no significant differences in response on the HDRS at three months postpartum between the intervention and control arm. A task-sharing psychological treatment was not effective in treating depression among women living in Khayelitsha, South Africa. The findings give cause for reflection on the strategy of task-sharing in low-resource settings.

Attention-Deficit/Hyperactivity Disorder and Mortality Risk in Taiwan.

Importance: Few studies have investigated levels of mortality in patients with attention-deficit/hyperactivity disorder (ADHD), and findings have been inconsistent and lacking information on specific causes of deaths. Objective: To investigate the association between ADHD and causes of death in Taiwan. Design, Setting, and Participants: A nationwide population-based cohort study was conducted using a cross-national Taiwanese registry. The ADHD group comprised 275 980 individuals aged 4 to 44 years with a new diagnosis between January 1, 2000, and December 31, 2012. All individuals with ADHD were compared with 1 931 860 sex- and age-matched controls without ADHD. Exposures: The association between ADHD and mortality was analyzed using a Cox regression model that controlled for sex, age, residence, insurance premium, outpatient visits, congenital anomaly, intellectual disability, depression disorder, autism, substance use disorder, conduct disorder, and oppositional defiant disorder. The analysis of suicide, unintentional injury, homicide, and natural-cause mortality was performed by a competing risk adjusted Cox regression controlling for other causes of mortality and potential confounding factors. Main Outcomes and Measures: Data on mortality from all causes, suicide, unintentional injury, homicide, and natural causes collected from a national mortality database. Results: There were 275 980 individuals with ADHD and 1 931 860 comparison individuals without ADHD in this study. Sex and age at index date were matched. The mean (SD) age was 9.61 (5.74) years for both groups. Most of the participants were male (209 406 in the ADHD group; 1 465 842 in the non-ADHD group; 75.88% for both groups). A total of 4321 participants from both cohorts died during the follow-up period (15.1 million person-years), including 727 (0.26%) from the ADHD group and 3594 (0.19%) from the non-ADHD group. Of those who died, 546 (75.1%) in the ADHD group and 2852 (79.4%) in the non-ADHD group were male. After adjusting for potential confounders, compared with the non-ADHD group, patients with ADHD showed higher overall mortality (adjusted hazard ratio, 1.07; 95% CI, 1.00-1.17) and higher injury-cause mortality from suicide (adjusted hazard ratio, 2.09; 95% CI, 1.62-2.71), unintentional injury (adjusted hazard ratio, 1.30; 95% CI, 1.10-1.52), and homicide (adjusted hazard ratio, 2.00; 95% CI, 1.09-3.68). No increased risk of natural-cause mortality was observed after adjustment. Conclusions and Relevance: In this study, ADHD was associated with higher injury-cause mortality, particularly that due to suicide, unintentional injury, and homicide. Although the risk of injury mortality was significantly higher in patients with ADHD than in the non-ADHD group, the absolute risk of mortality was low.

Ethnic density and other neighbourhood associations for mortality in severe mental illness: a retrospective cohort study with multi-level analysis from an urbanised and ethnically diverse location in the UK.

BACKGROUND: Neighbourhood social context might play a role in modifying mortality outcomes in severe mental illness, but has received little attention to date. Therefore, we aimed to assess in an ethnically diverse and urban location the association of neighbourhood-level characteristics and individual-level factors for all-cause, natural-cause, and unnatural-cause mortality in those with severe mental illness. METHODS: We did a retrospective cohort study using a case-registry from a large secondary mental health-care Trust in an ethnically diverse and urban location in south London, UK. Linked data for deaths and areas of residence were identified from the case-registry. We included all individuals aged 15 years or more at the time of diagnosis for a severe mental illness from Jan 1, 2007, to Dec 31, 2014. We used individual-level information in our analyses, such as gender, marital status, and the presence of current or previous substance use disorders. We assessed neighbourhood or area-level indicators at the Lower Super Output Area level. Association of neighbourhood-level characteristics, which included the interaction between ethnicity and own ethnic density, deprivation, urbanicity, and social fragmentation, alongside individual-level factors for all-cause, natural-cause, and unnatural-cause mortality in those with severe mental illness was assessed. FINDINGS: A total of 18 201 individuals were included in this cohort for analyses, with a median follow-up of 6·36 years. There were 1767 (9·7%) deaths from all causes, 1417 (7·8%) from natural causes, and 192 (1·1%) from unnatural causes. In the least ethnically dense areas, the adjusted rate ratio (aRR) for all-cause mortality in ethnic minority groups with severe mental illness compared with white British people with severe mental illness were similar (aRR 0·96, 95% CI 0·71-1·29); however in the highest ethnic density areas, ethnic minority groups with severe mental illness had a lower risk of death (aRR 0·52, 95% CI 0·38-0·71; p<0·0001), with similar trends for natural-cause mortality (p=0·071 for statistical interaction). In the cohort with severe mental illness, residency in deprived, urban, and socially fragmented neighbourhoods was not associated with higher mortality rates. Compared with the general population, age-standardised and gender-standardised mortality ratios were elevated in the cohort with severe mental illness across all neighbourhood-level characteristics assessed. INTERPRETATION: For ethnic minority groups with severe mental illness, residency in areas of higher own-group ethnic density is associated with lower mortality compared to white British groups with severe mental illness. FUNDING: Health Foundation, National Institute for Health Research, EU Seventh Framework, and National Institute of Mental Health.

Nonsurgical Artificial Insemination in Mice.

Artificial insemination is used to impregnate female mice using a solution containing motile sperm. For nonsurgical artificial insemination, a blunt needle is inserted through the vaginal canal of naturally ovulating females that are in the proestrus/estrous phase. This method requires practice but can be mastered, although initially it may be easier to have two people perform the procedure. Naturally ovulating or superovulated females are used in the absence of natural mating. Artificial insemination is achieved by isolating sperm from the cauda epididymis and vas deferens into a milk solution and introducing it into the reproductive tract of ovulating females. Only females that are known to be in estrus are used.

Demographic and clinical factors associated with different antidepressant treatments: a retrospective cohort study design in a UK psychiatric healthcare setting.

OBJECTIVE: To investigate the demographic and clinical factors associated with antidepressant use for depressive disorder in a psychiatric healthcare setting using a retrospective cohort study design. SETTING: Data were extracted from a de-identified data resource sourced from the electronic health records of a London mental health service. Relative risk ratios (RRRs) were obtained from multinomial logistic regression analysis to ascertain the probability of receiving common antidepressant treatments relative to sertraline. PARTICIPANTS: Patients were included if they received mental healthcare and a diagnosis of depression with antidepressant treatment between March and August 2015 and exposures were measured over the preceding 12 months. RESULTS: Older age was associated with increased use of all antidepressants compared with sertraline, except for negative associations with fluoxetine (RRR 0.98; 95% CI 0.96 to 0.98) and a combination of two selective serotonin reuptake inhibitors (SSRIs) (0.98; 95% CI 0.96 to 0.99), and no significant association with escitalopram. Male gender was associated with increased use of mirtazapine compared with sertraline (2.57; 95% CI 1.85 to 3.57). Previous antidepressant, antipsychotic and mood stabiliser use were associated with newer antidepressant use (ie, selective norepinephrine reuptake inhibitors, mirtazapine or a combination of both), while affective symptoms were associated with reduced use of citalopram (0.58; 95% CI 0.27 to 0.83) and fluoxetine (0.42; 95% CI 0.22 to 0.72) and somatic symptoms were associated with increased use of mirtazapine (1.60; 95% CI 1.00 to 2.75) relative to sertraline. In patients older than 25 years, past benzodiazepine use was associated with a combination of SSRIs (2.97; 95% CI 1.32 to 6.68), mirtazapine (1.94; 95% CI 1.20 to 3.16) and venlafaxine (1.87; 95% CI 1.04 to 3.34), while past suicide attempts were associated with increased use of fluoxetine (2.06; 95% CI 1.10 to 3.87) relative to sertraline. CONCLUSION: There were several factors associated with different antidepressant receipt in psychiatric healthcare. In patients aged >25, those on fluoxetine were more likely to have past suicide attempt, while past use of antidepressant and non-antidepressant use was also associated with use of new generation antidepressants, potentially reflecting perceived treatment resistance.

Leg length, skull circumference, and the incidence of dementia in Latin America and China: A 10/66 population-based cohort study.

BACKGROUND: Adult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. Cross-sectional studies indicate inverse associations with dementia risk, but there have been few prospective studies. METHODS: Population-based cohort studies in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, and anthropometric measures taken, with ascertainment of incident dementia, and mortality, three to five years later. RESULTS: Of the original at risk cohort of 13,587 persons aged 65 years and over, 2,443 (18.0%) were lost to follow-up; 10,540 persons with skull circumference assessments were followed up for 40,466 person years, and 10,400 with leg length assessments were followed up for 39,954 person years. There were 1,009 cases of incident dementia, and 1,605 dementia free deaths. The fixed effect pooled meta-analysed adjusted subhazard ratio (ASHR) for leg length (highest vs. lowest quarter) was 0.80 (95% CI, 0.66-0.97) and for skull circumference was 1.02 (95% CI, 0.84-1.25), with no heterogeneity of effect between sites (I2 = 0%). Leg length measurements tended to be shorter at follow-up, particularly for those with baseline cognitive impairment and dementia. However, leg length change was not associated with dementia incidence (ASHR, per cm 1.006, 95% CI 0.992-1.020), and the effect of leg length was little altered after adjusting for baseline frailty (ASHR 0.82, 95% CI 0.67-0.99). A priori hypotheses regarding effect modification by gender or educational level were not supported. However, the effect of skull circumference was modified by gender (M vs F ASHR 0.86, 95% CI 0.75-0.98), but in the opposite direction to that hypothesized with a greater protective effect of larger skull dimensions in men. CONCLUSIONS: Consistent findings across settings provide quite strong support for an association between adult leg length and dementia incidence in late-life. Leg length is a relatively stable marker of early life nutritional programming, which may confer brain reserve and protect against neurodegeneration in later life through mitigation of cardiometabolic risk. Further clarification of these associations could inform predictive models for future dementia incidence in the context of secular trends in adult height, and invigorate global efforts to improve childhood nutrition, growth and development.

Reproductive period, endogenous estrogen exposure and dementia incidence among women in Latin America and China; A 10/66 population-based cohort study.

BACKGROUND: Exposure to endogenous estrogen may protect against dementia, but evidence remains equivocal. Such effects may be assessed more precisely in settings where exogenous estrogen administration is rare. We aimed to determine whether reproductive period (menarche to menopause), and other indicators of endogenous estrogen exposure are inversely associated with dementia incidence. METHODS: Population-based cohort studies of women aged 65 years and over in urban sites in Cuba, Dominican Republic, Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, including ages at menarche, birth of first child, and menopause, and parity, with ascertainment of incident 10/66 dementia, and mortality, three to five years later. RESULTS: 9,428 women participated at baseline, with 72-98% responding by site. The 'at risk' cohort comprised 8,466 dementia-free women. Mean age varied from 72.0 to 75.4 years, lower in rural than urban sites and in China than in Latin America. Mean parity was 4.1 (2.4-7.2 by site), generally higher in rural than urban sites. 6,854 women with baseline reproductive period data were followed up for 26,463 person years. There were 692 cases of incident dementia, and 895 dementia free deaths. Pooled meta-analysed fixed effects, per year, for reproductive period (Adjusted Sub-Hazard Ratio [ASHR] 1.001, 95% CI 0.988-1.015) did not support any association with dementia incidence, with no evidence for effect modification by APOE genotype. No association was observed between incident dementia and; ages at menarche, birth of first child, and menopause: nulliparity; or index of cumulative endogenous estrogen exposure. Greater parity was positively associated with incident dementia (ASHR 1.030, 95% CI 1.002-1.059, I2 = 0.0%). CONCLUSIONS: We found no evidence to support the theory that natural variation in cumulative exposure to endogenous oestrogens across the reproductive period influences dementia incidence in late life.

Ethnic density effects for adult mental health: systematic review and meta-analysis of international studies.

BACKGROUND: Despite increased ethnic diversity in more economically developed countries it is unclear whether residential concentration of ethnic minority people (ethnic density) is detrimental or protective for mental health. This is the first systematic review and meta-analysis covering the international literature, assessing ethnic density associations with mental health outcomes. METHODS: We systematically searched Medline, PsychINFO, Sociological Abstracts, Web of Science from inception to 31 March 2016. We obtained additional data from study authors. We conducted random-effects meta-analysis taking into account clustering of estimates within datasets. Meta-regression assessed heterogeneity in studies due to ethnicity, country, generation, and area-level deprivation. Our main exposure was ethnic density, defined as the residential concentration of own racial/ethnic minority group. Outcomes included depression, anxiety and the common mental disorders (CMD), suicide, suicidality, psychotic experiences, and psychosis. RESULTS: We included 41 studies in the review, with meta-analysis of 12 studies. In the meta-analyses, we found a large reduction in relative odds of psychotic experiences [odds ratio (OR) 0.82 (95% confidence interval (CI) 0.76-0.89)] and suicidal ideation [OR 0.88 (95% CI 0.79-0.98)] for each 10 percentage-point increase in own ethnic density. For CMD, depression, and anxiety, associations were indicative of protective effects of own ethnic density; however, results were not statistically significant. Findings from narrative review were consistent with those of the meta-analysis. CONCLUSIONS: The findings support consistent protective ethnic density associations across countries and racial/ethnic minority populations as well as mental health outcomes. This may suggest the importance of the social environment in patterning detrimental mental health outcomes in marginalized and excluded population groups.

Diseases of the pancreas and suicide mortality: A nationwide nested case-control study among patients with mental health disorders in Taiwan.

OBJECTIVE: Diseases of the pancreas, especially pancreatitis, have been implicated as possible risk factors for psychiatric illnesses, such as depression and anxiety disorder. This nested case-control study aimed to investigate the association between diseases of the pancreas and completed suicide in a psychiatric population-based study. METHODS: The case group comprised 6568 completed suicides (ICD-9: E950-E959, E980-989) patients from the national mortality database between January 1, 2002 and December 1, 2010. These cases were compared with 6568 gender-, age-, residence-, and insurance premium-matched controls. Both suicide and non-suicide study patients were drawn from a group with previous psychiatric diagnoses. The risk of suicide among patients with diseases of the pancreas was analyzed using a conditional logistic regression model that controlled for alcohol-related disorder, drug dependence, schizophrenia, depressive disorder, bipolar disorder, anxiety disorder, Charlson comorbidity score, and outpatient visits. RESULTS: Disease of the pancreas was an independent risk factor for psychiatric patients who had completed suicide when adjusted for clinical and other comorbid factors. Among these covariates, alcohol-related disorders partially mediate the suicide risk among patients with disease of the pancreas, and mental disorders may not mediate this suicide risk. CONCLUSIONS: Diseases of the pancreas were associated with increased risk of completed suicide after controlling for potential confounding factors.