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Inflammation plays a crucial role in the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). This study aimed to examine whether the dysregulation of complement components contributes to brain structural defects in patients with mood disorders.
A total of 52 BD patients, 35 MDD patients, and 53 controls were recruited. The human complement immunology assay was used to measure the levels of complement factors. Whole brain-based analysis was performed to investigate differences in gray matter volume (GMV) and cortical thickness (CT) among the BD, MDD, and control groups, and relationships were explored between neuroanatomical differences and levels of complement components.
GMV in the medial orbital frontal cortex (mOFC) and middle cingulum was lower in both patient groups than in controls, while the CT of the left precentral gyrus and left superior frontal gyrus were affected differently in the two disorders. Concentrations of C1q, C4, factor B, factor H, and properdin were higher in both patient groups than in controls, while concentrations of C3, C4 and factor H were significantly higher in BD than in MDD. Concentrations of C1q, factor H, and properdin showed a significant negative correlation with GMV in the mOFC at the voxel-wise level.
BD and MDD are associated with shared and different alterations in levels of complement factors and structural impairment in the brain. Structural defects in mOFC may be associated with elevated levels of certain complement factors, providing insight into the shared neuro-inflammatory pathogenesis of mood disorders.
Mental health policy makers require evidence-based information to optimise effective care provision based on local need, but tools are unavailable.
To develop and validate a population-level prediction model for need for early intervention in psychosis (EIP) care for first-episode psychosis (FEP) in England up to 2025, based on epidemiological evidence and demographic projections.
We used Bayesian Poisson regression to model small-area-level variation in FEP incidence for people aged 16–64 years. We compared six candidate models, validated against observed National Health Service FEP data in 2017. Our best-fitting model predicted annual incidence case-loads for EIP services in England up to 2025, for probable FEP, treatment in EIP services, initial assessment by EIP services and referral to EIP services for ‘suspected psychosis’. Forecasts were stratified by gender, age and ethnicity, at national and Clinical Commissioning Group levels.
A model with age, gender, ethnicity, small-area-level deprivation, social fragmentation and regional cannabis use provided best fit to observed new FEP cases at national and Clinical Commissioning Group levels in 2017 (predicted 8112, 95% CI 7623–8597; observed 8038, difference of 74 [0.92%]). By 2025, the model forecasted 11 067 new treated cases per annum (95% CI 10 383–11 740). For every 10 new treated cases, 21 and 23 people would be assessed by and referred to EIP services for suspected psychosis, respectively.
Our evidence-based methodology provides an accurate, validated tool to inform clinical provision of EIP services about future population need for care, based on local variation of major social determinants of psychosis.
Gang members engage in many high-risk sexual activities that may be associated with psychiatric morbidity. Victim-focused research finds high prevalence of sexual violence towards women affiliated with gangs.
To investigate associations between childhood maltreatment and psychiatric morbidity on coercive and high-risk sexual behaviour among gang members.
Cross-sectional survey of 4665 men 18–34 years in Great Britain using random location sampling. The survey oversampled men from areas with high levels of violence and gang membership. Participants completed questionnaires covering violent and sexual behaviours, experiences of childhood disadvantage and trauma, and psychiatric diagnoses using standardised instruments.
Antisocial men and gang members had high levels of sexual violence and multiple risk behaviours for sexually transmitted infections, childhood maltreatment and mental disorders, including addictions. Physical, sexual and emotional trauma were strongly associated with adult sexual behaviour and more prevalent among gang members. Other violent behaviour, psychiatric morbidity and addictions accounted for high-risk and compulsive sexual behaviours among gang members but not antisocial men. Gang members showed precursors before age 15 years of adult preference for coercive rather than consenting sexual behaviour.
Gang members show inordinately high levels of childhood trauma and disadvantage, sexual and non-sexual violence, and psychiatric disorders, which are interrelated. The public health problem of sexual victimisation of affiliated women is explained by these findings. Healthcare professionals may have difficulties promoting desistance from adverse health-related behaviours among gang members whose multiple high-risk and violent sexual behaviours are associated with psychiatric morbidity, particularly addictions.
Ethnic inequalities in health outcomes are often explained by socioeconomic status and concentrated poverty. However, ethnic disparities in psychotic experiences are not completely attenuated by these factors.
We investigated whether disparities are better explained by interactions between individual risk factors and place-based clustering of disadvantage, termed a syndemic.
We performed a cross-sectional survey of 3750 UK men, aged 18–34 years, oversampling Black and minority ethnic (BME) men nationally, together with men residing in London Borough of Hackney. Participants completed questionnaires covering psychiatric symptoms, substance misuse, crime and violence, and risky sexual health behaviours. We included five psychotic experiences and a categorical measure of psychosis based on the Psychosis Screening Questionnaire.
At national level, more Black men reported psychotic experiences but disparities disappeared following statistical adjustment for social position. However, large disparities for psychotic experiences in Hackney were not attenuated by adjustment for social factors in Black men (adjusted odds ratio, 3.24; 95% CI 2.14–4.91; P < 0.002), but were for South Asian men. A syndemic model of joint effects, adducing a four-component latent variable (psychotic experiences and anxiety, substance dependence, high-risk sexual behaviour and violence and criminality) showed synergy between components and explained persistent disparities in psychotic experiences. A further interaction confirmed area-level effects (Black ethnicity × Hackney residence, 0.834; P < 0.001).
Syndemic effects result in higher rates of non-affective psychosis among BME persons in certain inner-urban settings. Further research should investigate how syndemics raise levels of psychotic experiences and related health conditions in Black men in specific places with multiple deprivations.
Whether borderline personality disorder (BPD) and bipolar disorder are the same or different disorders lacks consistency.
To detect whether grey matter volume (GMV) and grey matter density (GMD) alterations show any similarities or differences between BPD and bipolar disorder.
Web-based publication databases were searched to conduct a meta-analysis of all voxel-based studies that compared BPD or bipolar disorder with healthy controls. We included 13 BPD studies (395 patients with BPD and 415 healthy controls) and 47 bipolar disorder studies (2111 patients with bipolar disorder and 3261 healthy controls). Peak coordinates from clusters with significant group differences were extracted. Effect-size signed differential mapping meta-analysis was performed to analyse peak coordinates of clusters and thresholds (P < 0.005, uncorrected). Conjunction analyses identified regions in which disorders showed common patterns of volumetric alteration. Correlation analyses were also performed.
Patients with BPD showed decreased GMV and GMD in the bilateral medial prefrontal cortex network (mPFC), bilateral amygdala and right parahippocampal gyrus; patients with bipolar disorder showed decreased GMV and GMD in the bilateral medial orbital frontal cortex (mOFC), right insula and right thalamus, and increased GMV and GMD in the right putamen. Multi-modal analysis indicated smaller volumes in both disorders in clusters in the right medial orbital frontal cortex. Decreased bilateral mPFC in BPD was partly mediated by patient age. Increased GMV and GMD of the right putamen was positively correlated with Young Mania Rating Scale scores in bipolar disorder.
Our results show different patterns of GMV and GMD alteration and do not support the hypothesis that bipolar disorder and BPD are on the same affective spectrum.
Evidence regarding the association between cannabis use and depression remain conflicting, especially as studies have not typically adopted a longitudinal design with a follow-up period that was long enough to adequately cover the risk period for onset of depression.
Males from the Cambridge Study in Delinquent Development (CSDD) (N = 285) were assessed seven times from age 8 to 48 years to prospectively investigate the association between cannabis use and risk of major depressive disorder (MDD). A combination of multiple analyses (logistic regression, Cox regression, fixed-effects analysis) was employed to explore the strength and direction of effect within different developmental stages.
Multiple regression analyses revealed that early-onset cannabis use (before age 18) but not late-onset cannabis use (after age 27) was associated with a higher risk and shorter time until a subsequent MDD diagnosis. This effect was present in high-frequency [(odds ratio (OR) 8.83, 95% confidence interval (CI) 1.29–70.79]; [hazard ratio (HR) 8.69, 95% CI 2.07–36.52)] and low-frequency early-onset users (OR 2.41, 95% CI 1.22–4.76; HR 2.09, 95% CI 1.16–3.74). Effect of increased frequency of cannabis use on increased risk of subsequent MDD was observed only for use during adolescence (age 14–18) but not at later life stages, while controlling for observed and non-unobserved time-invariant factors. Conversely, MDD in adulthood (age 18–32) was linked to a reduction in subsequent cannabis use (age 32–48).
The present findings provide evidence implicating frequent cannabis use during adolescence as a risk factor for later life depression. Future studies should further examine causality of effects in larger samples.
Changes in positive and negative symptom profiles during acute psychotic episodes may be key drivers in the pathway to violence. Acute episodes are often preceded by fluctuations in affect before psychotic symptoms appear and affective symptoms may play a more important role in the pathway than previously recognised.
We carried out a prospective cohort study of 409 male and female patients discharged from medium secure services in England and Wales to the community. Measures were taken at baseline (pre-discharge), 6 and 12 months post-discharge using the Positive and Negative Syndrome Scale. Information on violence was obtained using the McArthur Community Violence Instrument and Police National Computer.
The larger the shift in positive symptoms the more likely violence occurred in each 6-month period. However, shifts in angry affect were the main driving factor for positive symptom shifts associated with violence. Shifts in negative symptoms co-occurred with positive and conveyed protective effects, but these were overcome by co-occurring shifts in anger. Severe but stable delusions were independently associated with violence.
Intensification of angry affect during acute episodes of psychosis indicates the need for interventions to prevent violence and is a key driver of associated positive symptoms in the pathway to violence. Protective effects against violence exerted by negative symptoms are not clinically observable during symptom shifts because they are overcome by co-occurring anger.
Violence among released prisoners with psychosis is an important public health problem. It is unclear whether treatment in prison can influence criminal behaviour subsequent to release.
To investigate whether treatment in prison can delay time to reoffending.
Our sample consisted of 1717 adult prisoners in England and Wales convicted of a serious violent or sexual offence. We used Cox regression to investigate the effects of treatment received in prison on associations between mental illness and time to first reconviction following release.
Prisoners with current symptoms of schizophrenia reoffended quicker following release. Nevertheless, treatment with medication significantly delayed time to violence (18% reduction). Treatment for substance dependence delayed violent and non-violent reoffending among prisoners with drug-induced psychosis.
Identifying prisoners with psychosis and administering treatment in prison have important protective effects against reoffending. Repeated screening with improved accuracy in identification is necessary to prevent cases being missed.
There is growing risk from terrorism following radicalisation of young
men. It is unclear whether psychopathology is associated.
To investigate the population distribution of extremist views among UK
Cross-sectional study of 3679 men, 18–34 years, in Great Britain.
Multivariate analyses of attitudes, psychiatric morbidity, ethnicity and
Pro-British men were more likely to be White, UK born, not religious;
anti-British were Muslim, religious, of Pakistani origin, from deprived
areas. Pro- and anti-British views were linearly associated with violence
(adjusted odds ratio (OR) = 1.51, 95% CI 1.38–1.64,
P<0.001, adjusted OR = 1.33, 95% CI 1.13–1.58,
P<0.001, respectively) and negatively with
depression (adjusted OR = 0.72, 95% CI 0.61–0.85,
P<0.001, adjusted OR = 0.64, 95% CI 0.48–0.86,
P = 0.003, respectively).
Men at risk of depression may experience protection from strong cultural
or religious identity. Antisocial behaviour increases with extremism.
Religion is protective but may determine targets of violence following
Significant efforts have been made to identify risk factors associated with suicide. However, the evidence suggests that risk categorisation may be of limited value, or worse, potentially harmful, confusing clinical thinking. We argue instead for a shift in focus towards real engagement with the individual patient, their specific problems and circumstances.
Secure hospitals are a high-cost, low-volume service consuming around a
fifth of the overall mental health budget in England and Wales.
A systematic review and meta-analysis of adverse outcomes after discharge
along with a comparison with rates in other clinical and forensic groups
in order to inform public health and policy.
We searched for primary studies that followed patients discharged from a
secure hospital, and reported mortality, readmissions or reconvictions.
We determined crude rates for all adverse outcomes.
In total, 35 studies from 10 countries were included, involving 12 056
patients out of which 53% were violent offenders. The crude death rate
for all-cause mortality was 1538 per 100 000 person-years (95% CI
1175–1901). For suicide, the crude death rate was 325 per 100 000
person-years (95% CI 235– 415). The readmission rate was 7208 per 100 000
person-years (95% CI 5916–8500). Crude reoffending rates were 4484 per
100 000 person-years (95% CI 3679–5287), with lower rates in more recent
There is some evidence that patients discharged from forensic psychiatric
services have lower offending outcomes than many comparative groups.
Services could consider improving interventions aimed at reducing
premature mortality, particularly suicide, in discharged patients.
Some patients are at higher risk of contact with criminal justice
agencies when experiencing a first episode of psychosis.
To investigate whether violence explains criminal justice pathways (CJPs)
for psychosis in general, and ethnic vulnerability to CJPs.
Two-year population-based survey of people presenting with a
first-episode of psychosis. A total of 481 patients provided information
on pathways to psychiatric care. The main outcome was a CJP at first
contact compared with other services on the care pathway.
CJPs were more common if there was violence at first presentation (odds
ratio (OR) = 4.23, 95% CI 2.74–6.54, P<0.001), drug
use in the previous year (OR = 2.28, 95% CI 1.50–3.48,
P<0.001) and for high psychopathy scores (OR = 2.54,
95% CI 1.43–4.53, P = 0.002). Compared with White
British, CJPs were more common among Black Caribbean (OR = 2.97, 95% CI
1.54–5.72, P<0.001) and Black African patients (OR =
1.95, 95% CI 1.02–3.72, P = 0.01). Violence mediated
30.2% of the association for Black Caribbeans, but was not a mediator for
Black African patients. These findings were sustained after adjustment
for age, marital status, gender and employment.
CJPs were more common in violent presentations, for greater psychopathy
levels and drug use. Violence presentations did not fully explain ethnic
vulnerability to CJPs.
Intergenerational continuities in criminal behaviour have been well
documented, but the familial nature of psychopathic personality is less
To establish if there is an association between the psychopathic traits
of a community sample of men and their offspring and whether psychosocial
risk factors mediate this.
Participants of the Cambridge Study in Delinquent Development
(n = 478 dyads) were assessed for psychopathy using
the PCL: SV. Multilevel regression models were used to investigate
intergenerational continuity and mediation models examined indirect
The fathers' psychopathy was transmitted to both sons and daughters. The
transmission of Factor 1 scores was mediated via the fathers' employment
problems. For male offspring, the Factor 2 scores were mediated via the
fathers' drug use, accommodation and employment problems. For female
offspring, Factor 2 scores were mediated via the fathers' employment
Understanding of the specific role of certain psychosocial risk factors
may be useful in developing preventive measures for the development of
Early findings from a national study of discharges from 32 National
Health Service medium secure units revealed that nearly twice as many
patients than expected were discharged back to prison.
To compare the characteristics of those discharged back to prison with
those discharged to the community, and consider the implications for
ongoing care and risk.
Prospective cohort follow-up design. All forensic patients discharged
from 32 medium secure units across England and Wales over a 12-month
period were identified. Those discharged to prison were compared with
those who were discharged to the community.
Nearly half of the individuals discharged to prison were diagnosed with a
serious mental illness and over a third with schizophrenia. They were a
higher risk, more likely to have a personality disorder, more symptomatic
and less motivated than those discharged to the community.
Findings suggest that alternative models of prison mental healthcare
should be considered to reduce risks to the patient and the public.