The burden of mental ill health associated with childhood maltreatment in the UK, using The Health Improvement Network database: a population-based retrospective cohort study.

Abstract: Childhood maltreatment is a global public health, human rights, and moral issue that is associated with a substantial mental health burden. We aimed to assess the association between childhood […]

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The role of prenatal stress as a pathway to personality disorder: longitudinal birth cohort study.

Abstract: Many studies have reported associations between prenatal stress and the development of psychotic, anxiety and depressive disorders; however, to date no studies have investigated potential associations with personality disorders.This […]

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A longitudinal study of eating behaviours in childhood and later eating disorder behaviours and diagnoses.

Abstract: Eating behaviours in childhood are considered as risk factors for eating disorder behaviours and diagnoses in adolescence. However, few longitudinal studies have examined this association.AimsWe investigated associations between childhood […]

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Multiple mediation analysis of the peer-delivered Thinking Healthy Programme for perinatal depression: findings from two parallel, randomised controlled trials.

Low-intensity psychosocial interventions have been effective in targeting perinatal depression, but relevant mechanisms of change remain unknown.AimsTo examine three theoretically informed mediators of the Thinking Healthy Programme Peer-delivered (THPP), an evidence-based psychosocial intervention for perinatal depression, on symptom severity in two parallel, randomised controlled trials in Goa, India and Rawalpindi, Pakistan.Participants included pregnant women aged ?18 years with moderate to severe depression, as defined by a Patient Health Questionnaire 9 (PHQ-9) score ?10, and were randomised to either THPP or enhanced usual care. We examine whether three prespecified variables (patient activation, social support and mother-child attachment) at 3 months post-childbirth mediated the effects of THPP interventions of perinatal depressive symptom severity (PHQ-9) at the primary end-point of 6 months post-childbirth. We first examined individual mediation within each trial (n = 280 in India and n = 570 in Pakistan), followed by a pooled analysis across both trials (N = 850).In both site-specific and pooled analyses, patient activation and support at 3 months independently mediated the intervention effects on depressive symptom severity at 6 months, accounting for 23.6 and 18.2% of the total effect of THPP, respectively. The intervention had no effect on mother-child attachment scores, thus there was no evidence that this factor mediated the intervention effect.The effects of the psychosocial intervention on depression outcomes in mothers were mediated by the same two factors in both contexts, suggesting that such interventions seeking to alleviate perinatal depression should target both social support and patient activation levels.Declaration of interestNone.

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Second-generation antipsychotic drugs and short-term somatic serious adverse events: a systematic review and meta-analysis.

Antipsychotic drugs might cause acutely occurring, serious side-effects and thus contribute to the increased physical morbidity and mortality observed in patients with severe mental health disorders. We examined this hypothesis by doing a meta-analysis of International Conference on Harmonisation-Good Clinical Practice-defined serious adverse events occurring in placebo-controlled trials of antipsychotics.For this systematic review and meta-analysis, we included randomised controlled trials (RCTs) comparing second-generation antipsychotics with placebo. We searched MEDLINE, Embase, Cochrane CENTRAL, BIOSIS, PsycINFO, PubMed, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform for trials published in any language from database inception up until Jan 27, 2017. Trials were included without limitations in population (diagnostic category, age, sex, ethnicity), dosing regimen, blinding status, duration, or publication year. Only psychological studies lasting less than 1 day and trials done in mainland China were excluded. We contacted pharmaceutical companies, drug regulatory authorities, and study investigators for additional data. The primary outcome was the number of patients with at least one somatic serious adverse event. We estimated minimum and maximum numbers of patients with the outcome in each study group and synthesised the results with odds ratios (ORs) in a common-effects meta-analysis. This study is registered with PROSPERO, number CRD42016033930.We identified 597 RCTs, comprising 108?664 participants, that met the inclusion criteria. 314 trials (67?642 participants) with details on individual serious adverse events available constituted the main dataset for meta-analysis. 88% of these were 13 weeks (approximately 3 months) or shorter in duration (median 6 weeks, IQR 4-9). At least one somatic serious adverse event occurred in 698 (1·63%) to 862 (2·02%) of 42?600 patients on antipsychotics, and in 343 (1·37%) to 419 (1·67%) of 25?042 patients on placebo. The odds ratios (ORs) were 1·24 (95% CI 1·08-1·42) and 1·24 (1·10-1·41) based on the minimum and maximum estimate, respectively. In predefined subgroup analyses we found evidence suggesting a larger effect in older patients (>65 years; OR 1·56, 95% CI 1·22-1·98; 1·58, 1·25-1·99) as compared with adults (18-65 years; 1·09, 0·91-1·29; 1·10, 0·95-1·28); likewise in children or adolescents (<18 years) although the evidence was more uncertain (1·49, 0·81-2·75; 1·54, 0·85-2·77). Of 597 included RCTs, 30 (5%), 358 (60%), and 209 (35%) were rated at high, moderate, or low risk of bias, respectively. ?2 was zero for both analyses of the primary outcome (minimum estimate, maximum estimate). A Bayesian sensitivity analysis using external information on heterogeneity gave similar results.We found evidence that antipsychotics cause short-term somatic serious adverse events on top of somatic serious adverse events occurring independent of treatment. This effect appears to be mainly driven by results in older patients. Hence, clinicians should be aware that antipsychotics are potentially toxic, particularly when treating patients sharing risk factors with the older population.German Ministry of Education and Research.

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L-Methylfolate Calcium Supplementation in Adolescents and Children: A Retrospective Analysis.

Previous studies have shown l-methylfolate to be a safe and beneficial therapy for neuropsychiatric conditions, including major depressive disorder and schizophrenia in adults. The purpose of this study was to assess safety and describe patient experience using l-methylfolate calcium in a real-world pediatric and adolescent population. A retrospective chart review of patients (7 to 20?y of age, mean age 16?y) prescribed l-methylfolate calcium at a psychiatry clinic in Amherst, NY, between January 1, 2010 and November 10, 2015 was conducted. Patients to whom l-methylfolate calcium 15?mg/d (n=139) or 7.5?mg/d (n=7) was administered were identified; 44 patients who were prescribed but to whom l-methylfolate calcium was not administered were included as a comparator population. Common neuropsychiatric diagnoses included anxiety disorders (68% in the treatment population vs. 50% in the comparator population) and mood disorders (57% in the treatment population vs. 52% in the comparator population). Antidepressants (69% vs. 55%) and mood stabilizers or antiepileptic drugs (63% vs. 57%) were frequently prescribed in combination with l-methylfolate calcium. Adverse events occurred less frequently in the treated population, possibly due to the addition of l-methylfolate calcium (10% vs. 25%, P=0.02). The most common adverse events in the treated population were impaired sleep (5 patients) and increased anxiety (3 patients). Rates of laboratory abnormalities did not differ significantly between the treated and comparator populations (P=0.13). Positive subjective treatment experiences were reported by 22.5% of treated patients and negative subjective treatment experiences were reported by 5.4% of treated patients. L-methylfolate calcium was well-tolerated in a pediatric/adolescent population and may provide benefits for patients with a range of neuropsychiatric conditions.

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Suicidal risk factors in major affective disorders.

Rates and risk factors for suicidal behaviour require updating and comparisons among mood disorders.AimsTo identify factors associated with suicidal risk in major mood disorders.We considered risk factors before, during and after intake assessments of 3284 adults with/without suicidal acts, overall and with bipolar disorder (BD) versus major depressive disorder (MDD), using bivariate comparisons, multivariable regression modelling and receiver operating characteristic (ROC) analysis.Suicidal prevalence was greater in BD versus MDD: ideation, 29.2 versus 17.3%; attempts, 18.8 versus 4.78%; suicide, 1.73 versus 0.48%; attempts/suicide ratio indicated similar lethality, 10.9 versus 9.96. Suicidal acts were associated with familial BD or suicide, being divorced/unmarried, fewer children, early abuse/trauma, unemployment, younger onset, longer illness, more dysthymic or cyclothymic temperament, attention-deficit hyperactivity disorder (ADHD), substance misuse, mixed features, hospital admission, percentage time unwell, less antidepressants and more antipsychotics and mood stabilisers. Logistic regression found five independent factors: hospital admission, more depression at intake, BD diagnosis, onset age ?25 years and mixed features. These factors were more associated with suicidal acts in BD than MDD: percentage time depressed/ill, alcohol misuse, >4 pre-intake depressions, more dysthymic/cyclothymic temperament and prior abuse/trauma. ADHD and total years ill were similar in BD and MDD; other factors were more associated with MDD. By ROC analysis, area under the curve was 71.3%, with optimal sensitivity (76%) and specificity (55%) with any two factors.Suicidal risks were high in mood disorders: ideation was highest with BD type II, attempts and suicides (especially violent) with BD type I. Several risk factors for suicidal acts differed between BD versus MDD patients.Declaration of interestNo author or immediate family member has financial relationships with commercial entities that might appear to represent potential conflicts of interest with the information presented.

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Identifying Novel Types of Irritability Using a Developmental Genetic Approach.

Irritability, which is strongly associated with impairment and negative outcomes, is a common reason for referral to mental health services but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. The authors used a developmental approach to test the hypothesis that there are several forms of irritability, including a “neurodevelopmental/ADHD-like” type, with onset in childhood, and a “depression/mood” type, with onset in adolescence.Data were analyzed from the Avon Longitudinal Study of Parents and Children, a prospective U.K. population-based cohort. Irritability trajectory classes were estimated for 7,924 individuals with data at multiple time points across childhood and adolescence (four possible time points from approximately ages 7 to 15). Psychiatric diagnoses were assessed at approximately ages 7 and 15. Psychiatric genetic risk was indexed by polygenic risk scores (PRSs) for attention deficit hyperactivity disorder (ADHD) and depression, derived using large genome-wide association study results.Five irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), late-childhood limited (5.2%), and high-persistent (2.4%). The early-onset high-persistent trajectory was associated with male preponderance, childhood ADHD (odds ratio=108.64, 95% CI=57.45-204.41), and ADHD PRS (odds ratio=1.31, 95% CI=1.09-1.58). The adolescent-onset increasing trajectory was associated with female preponderance, adolescent depression (odds ratio=5.14, 95% CI=2.47-10.73), and depression PRS (odds ratio=1.20, 95% CI=1.05-1.38). Both the early-onset high-persistent and adolescent-onset increasing trajectory classes were associated with adolescent depression diagnosis and ADHD PRS.The developmental context of irritability may be important in its conceptualization: early-onset persistent irritability may be more neurodevelopmental/ADHD-like and later-onset irritability more depression/mood-like. These findings have implications for treatment as well as nosology.

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Distinct Patterns of Neural Habituation and Generalization in Children and Adolescents With Autism With Low and High Sensory Overresponsivity.

Sensory overresponsivity (SOR), an atypical negative reaction to sensory stimuli, is highly prevalent in autism spectrum disorder (ASD). Previous work has related SOR to increased brain response in sensory-limbic regions. This study investigated where these atypical responses fall in three fundamental stages of sensory processing: arousal (i.e., initial response), habituation (i.e., change in response over time), and generalization of response to novel stimuli. Different areas of atypical response would require distinct intervention approaches.Functional MRI was used to examine these patterns of neural habituation to two sets of similar mildly aversive auditory and tactile stimuli in 42 high-functioning children and adolescents with ASD (21 with high levels of SOR and 21 with low levels of SOR) and 27 age-matched typically developing youths (ages 8-17). The relationship between SOR and change in amygdala-prefrontal functional connectivity across the sensory stimulation was also examined.Across repeated sensory stimulation, high-SOR participants with ASD showed reduced ability to maintain habituation in the amygdala and relevant sensory cortices and to maintain inhibition of irrelevant sensory cortices. These results indicate that sensory habituation is a dynamic, time-varying process dependent on sustained regulation across time, which is a particular deficit in high-SOR participants with ASD. However, low-SOR participants with ASD also showed distinct, nontypical neural response patterns, including reduced responsiveness to novel but similar stimuli and increases in prefrontal-amygdala regulation across the sensory exposure.The results suggest that all children with autism have atypical brain responses to sensory stimuli, but whether they express atypical behavioral responses depends on top-down regulatory mechanisms. Results are discussed in terms of targeted intervention approaches.

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Cognitive Profile, Emotional-Behavioral Features, and Parental Stress in Boys With 47,XYY Syndrome.

To describe (a) the observed cognitive, emotional, and behavioral phenotype in a cohort of male children with 47,XYY syndrome and (b) stress levels in their parents.We conducted a cross-sectional observational study of 11 boys diagnosed with 47,XYY syndrome and compared them with 11 age-matched boys with normal karyotype (46,XY). The participants performed standardized assessments of cognitive function, emotional state, and behavioral features; the parents completed a questionnaire evaluating parental stress. All data were analyzed using parametric and nonparametric statistical methods.All of the boys exhibited a normal cognitive profile. However, emotional-behavioral profiling revealed that internalizing and externalizing problems were more prevalent in the 47,XYY group. In addition, the stress levels of the parents of the 47,XYY group were reportedly higher than those of the parents of the 46,XY group. We also found that the time of the diagnosis had an effect on the mothers’ stress levels; that is, postnatal fetal 47,XYY diagnosis was associated with higher maternal stress, whereas prenatal fetal 47,XYY diagnosis was not.Generally, 47,XYY syndrome is associated with certain cognitive, emotional, and behavioral features. High stress levels have been reported by the mothers of 47,XYY boys who had been diagnosed postnatally because of unexpected developmental delay and/or learning difficulties. The present study highlights the need to better define the neuropsychiatric phenotype of 47,XYY children; namely, the effect of the chromosomal abnormality on their cognitive function and emotional-behavioral (internalizing and externalizing) features. This study could improve prenatal counseling and pediatric surveillance.

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Promoting resilience in children and adolescents living with parental mental illness (CAPRI): children are key to identifying solutions.

SummaryThe lives of Children and Adolescents with PaRental mental Illness (CAPRI) represent a public health priority. Identifying those at most risk within the risk subset is crucial to promote resilience for this group. The ability to develop child-centred interventions will underpin the success of evidence-based services and CAPRI themselves are key to unlocking current service barriers.Declaration interestNone.

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Sodium valproate in psychiatric practice: time for a change in perception.

SummarySodium valproate and related preparations have recently undergone regulatory review following concern about effects on the unborn child and doctors’ failure to communicate risk. The issues are wider. Valproate is overused in psychiatry based on the false perception that ‘ease’ of use equates to better safety than alternatives. Valproic acid can disrupt fundamental physiological processes, the consequences of which are poorly understood and little discussed in the psychiatric literature. Valproate may be useful in a small number of patients with bipolar disorder but current prescribing patterns are unjustified. Perception needs to change.Declaration of interestD.C.O. is psychiatric commissioner on the Commission on Human Medicines and a member of the European Medicines Agency’s Scientific Advisory Group on Psychiatry. He chaired the European Medicines Agency’s review of the psychiatric use of valproate in pregnancy and women of childbearing potential.

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Transition between child and adult services for young people with attention-deficit hyperactivity disorder (ADHD): findings from a British national surveillance study.

Optimal transition from child to adult services involves continuity, joint care, planning meetings and information transfer; commissioners and service providers therefore need data on how many people require that service. Although attention-deficit hyperactivity disorder (ADHD) frequently persists into adulthood, evidence is limited on these transitions.AimsTo estimate the national incidence of young people taking medication for ADHD that require and complete transition, and to describe the proportion that experienced optimal transition.Surveillance over 12 months using the British Paediatric Surveillance Unit and Child and Adolescent Psychiatry Surveillance System, including baseline notification and follow-up questionnaires.Questionnaire response was 79% at baseline and 82% at follow-up. For those aged 17-19, incident rate (range adjusted for non-response) of transition need was 202-511 per 100 000 people aged 17-19 per year, with successful transition of 38-96 per 100 000 people aged 17-19 per year. Eligible young people with ADHD were mostly male (77%) with a comorbid condition (62%). Half were referred to specialist adult ADHD and 25% to general adult mental health services; 64% had referral accepted but only 22% attended a first appointment. Only 6% met optimal transition criteria.As inclusion criteria required participants to be on medication, these estimates represent the lower limit of the transition need. Two critical points were apparent: referral acceptance and first appointment attendance. The low rate of successful transition and limited guideline adherence indicates significant need for commissioners and service providers to improve service transition experiences.Declaration of interestNone.

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