Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT2A receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT2A/D4 antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect.

An 8-week, randomized, double-blind study in patients with major depressive disorder was carried out.

The study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery–Asberg Depression Rating Scale (MADRS) score of 32.6 (s.d.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression–Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002).

Although the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week.

Schizophrenia is associated with various brain structural abnormalities, including reduced volume of the hippocampi, prefrontal lobes and thalami. Cannabis use increases the risk of schizophrenia but reports of brain structural abnormalities in the cannabis-using population have not been consistent. We used automated image analysis to compare brain structural changes over time in people at elevated risk of schizophrenia for familial reasons who did and did not use cannabis.

Magnetic resonance imaging (MRI) scans were obtained from subjects at high familial risk of schizophrenia at entry to the Edinburgh High Risk Study (EHRS) and approximately 2 years later. Differential grey matter (GM) loss in those exposed (n = 23) and not exposed to cannabis (n = 32) in the intervening period was compared using tensor-based morphometry (TBM).

Cannabis exposure was associated with significantly greater loss of right anterior hippocampal (pcorrected = 0.029, t = 3.88) and left superior frontal lobe GM (pcorrected = 0.026, t = 4.68). The former finding remained significant even after the exclusion of individuals who had used other drugs during the inter-scan interval.

Using an automated analysis of longitudinal data, we demonstrate an association between cannabis use and GM loss in currently well people at familial risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.

The self-referential memory (SRM) effect refers to the phenomenon that stimuli processed with reference to the self are better remembered than those referenced to others. Studies have shown that schizophrenia patients do not have this memorial advantage for self-referenced information. The current study investigated the electrophysiological mechanism of the abolished SRM effect in schizophrenia.

Twenty schizophrenia patients and 22 controls were recruited to complete an SRM task. We used a high-time resolution event-related potential (ERP) technique to analyze the electrophysiological differences between patients and controls during self- and other-reflection processing.

Behavior data indicated that healthy controls had a typical SRM bias that was absent in the schizophrenia patients. ERP comparison between groups showed that the schizophrenia patients presented smaller voltages in both self- and other-reflection conditions in the 160–260 ms (P2 component) and 800–1200 ms (positive slow wave) time windows over the pre/frontal cortex. Furthermore, the N2 amplitudes (270–380 ms) differed between self- and other-reflection conditions in patients but not in normal controls. More importantly, we found that the P3 amplitudes in the parietal cortex correlated significantly with the SRM bias score in the patients (r = –0.688).

These results provide comprehensive and direct electrophysiological evidence for self- and other-reflective dysfunction in schizophrenia patients and contribute to our understanding of the underlying neural substrates of the abolished SRM effect in schizophrenia.

Decline in cognitive functioning precedes the first psychotic episode in the course of schizophrenia and is considered a hallmark symptom of the disorder. Given the low incidence of schizophrenia, it remains a challenge to investigate whether cognitive decline coincides with disease-related changes in brain structure, such as white matter abnormalities. The 22q11.2 deletion syndrome (22q11DS) is an appealing model in this context, as 25% of patients develop psychosis. Furthermore, we recently showed that cognitive decline also precedes the onset of psychosis in individuals with 22q11DS. Here, we investigate whether the early cognitive decline in patients with 22q11DS is associated with alterations in white matter microstructure.

We compared the fractional anisotropy (FA) of white matter in 22q11DS patients with cognitive decline [n = 16; −18.34 (15.8) VIQ percentile points over 6.80 (2.39) years] to 22q11DS patients without cognitive decline [n = 18; 17.71 (20.17) VIQ percentile points over 5.27 (2.03) years] by applying an atlas-based approach to diffusion-weighted imaging data.

FA was significantly increased (p < 0.05, FDR) in 22q11DS patients with a cognitive decline in the bilateral superior longitudinal fasciculus, the bilateral cingulum bundle, all subcomponents of the left internal capsule and the left superior frontal-occipital fasciculus as compared with 22q11DS patients without cognitive decline.

Within 22q11DS, the early cognitive decline is associated with microstructural differences in white matter. At the mean age of 17.8 years, these changes are reflected in increased FA in several tracts. We hypothesize that similar brain alterations associated with cognitive decline take place early in the trajectory of schizophrenia.

A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.

This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.

The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.

The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.

Chronic opioid exposure is common world-wide, but behavioural performance remains under-investigated. This study aimed to investigate visuospatial memory performance in opioid-exposed and dependent clinical populations and its associations with measures of intelligence and cognitive impulsivity.

We recruited 109 participants: (i) patients with a history of opioid dependence due to chronic heroin use (n = 24), (ii) heroin users stabilised on methadone maintenance treatment (n = 29), (iii) participants with a history of chronic pain and prescribed tramadol and codeine (n = 28) and (iv) healthy controls (n = 28). The neuropsychological tasks from the Cambridge Neuropsychological Test Automated Battery included the Delayed Matching to Sample (DMS), Pattern Recognition Memory, Spatial Recognition Memory, Paired Associate Learning, Spatial Span Task, Spatial Working Memory and Cambridge Gambling Task. Pre-morbid general intelligence was assessed using the National Adult Reading Test.

As hypothesised, this study identified the differential effects of chronic heroin and methadone exposures on neuropsychological measures of visuospatial memory (p < 0.01) that were independent of injecting behaviour and dependence status. The study also identified an improvement in DMS performance (specifically at longer delays) when the methadone group was compared with the heroin group and also when the heroin group was stabilised onto methadone. Results identified differential effects of chronic heroin and methadone exposures on various neuropsychological measures of visuospatial memory independently from addiction severity measures, such as injecting behaviour and dependence status.

There is increasing interest in the clinical and aetiological overlap between autism spectrum disorders and schizophrenia spectrum disorders, reported to co-occur at both diagnostic and trait levels. Individually, sub-clinical autistic and psychotic traits are associated with poor clinical outcomes, including increased depressive symptomatology, self-harming behaviour and suicidality. However, the implications when both traits co-occur remain poorly understood. The study aimed to (1) examine the relationship between autistic and psychotic traits and (2) determine if their co-occurrence increases depressive symptomatology, self-harm and suicidality.

Cross-sectional data from a self-selecting (online and poster advertising) sample of the adult UK population (n = 653) were collected using an online survey. Validated self-report measures were used to assess sub-clinical autistic and psychotic traits, depressive symptomatology, self-harming behaviour and suicidality. Correlation and regression analyses were performed.

A positive correlation between sub-clinical autistic and positive psychotic traits was confirmed (rs = 0.509, p < 0.001). Overall, autistic traits and psychotic traits were, independently, significant predictors of depression, self-harm and suicidality. Intriguingly, however, depression was associated with a negative interaction between the autistic domain attention to detail and psychotic traits.

This study supports previous findings that sub-clinical autistic and psychotic traits are largely independently associated with depression, self-harm and suicidality, and is novel in finding that their combined presence has no additional effect on depression, self-harm or suicidality. These findings highlight the importance of considering both autistic and psychotic traits and their symptom domains in research and when developing population-based depression prevention and intervention strategies.

The objective of this population-based register study was (1) to investigate the association between young adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) and subsequent labour market marginalisation (LMM) in two comparison groups, i.e. matched young adults from the general population without ADHD and unaffected siblings to persons with ADHD and (2) to assess the role of comorbid disorders.

This study included all young adults in Sweden, aged 19–29 years, with an incident diagnosis of ADHD 2006–2011 (n = 9718). Crude and multivariate sex-stratified hazard ratios (HRs) with 95% confidence intervals (CIs) were measured 5 years after the diagnosis of ADHD for the risk of disability pension, long-term sickness absence (SA) (>90 days), long-term unemployment (>180 days) and a combined measure of all three in young adults with ADHD compared to their siblings without ADHD and a matched comparison group.

In the adjusted analyses young adults with ADHD had a 10-fold higher risk of disability pension (HR = 10.2; CI 9.3–11.2), a nearly three-fold higher risk of long-term SA (HR = 2.7; CI 2.5–2.8) and a 70% higher risk of long-term unemployment (HR = 1.7; CI 1.6–1.8) compared to the matched comparison group. The risk estimates were lower compared to siblings for disability pension (HR = 9.0; CI 6.6–12.3) and long-term SA (HR = 2.5; CI 2.1–3.1) but higher in the long-term unemployed (HR = 1.9; CI 1.6–2.1). Comorbid disorders explained about one-third of the association between ADHD and disability pension, but less regarding SA and long-term unemployment.

Young adults with ADHD have a high risk for different measures of LMM and comorbidities explain only a small proportion of this relationship.

Attention deficit hyperactivity disorder (ADHD) is highly heritable and is associated with lower educational attainment. ADHD is linked to family adversity, including hostile parenting. Questions remain regarding the role of genetic and environmental factors underlying processes through which ADHD symptoms develop and influence academic attainment.

This study employed a parent-offspring adoption design (N = 345) to examine the interplay between genetic susceptibility to child attention problems (birth mother ADHD symptoms) and adoptive parent (mother and father) hostility on child lower academic outcomes, via child ADHD symptoms. Questionnaires assessed birth mother ADHD symptoms, adoptive parent (mother and father) hostility to child, early child impulsivity/activation, and child ADHD symptoms. The Woodcock–Johnson test was used to examine child reading and math aptitude.

Building on a previous study (Harold et al., 2013, Journal of Child Psychology and Psychiatry, 54(10), 1038–1046), heritable influences were found: birth mother ADHD symptoms predicted child impulsivity/activation. In turn, child impulsivity/activation (4.5 years) evoked maternal and paternal hostility, which was associated with children's ADHD continuity (6 years). Both maternal and paternal hostility (4.5 years) contributed to impairments in math but not reading (7 years), via impacts on ADHD symptoms (6 years).

Findings highlight the importance of early child behavior dysregulation evoking parent hostility in both mothers and fathers, with maternal and paternal hostility contributing to the continuation of ADHD symptoms and lower levels of later math ability. Early interventions may be important for the promotion of child math skills in those with ADHD symptoms, especially where children have high levels of early behavior dysregulation.

Depression is associated with increased mortality, however, little is known about its variation by ethnicity.

We conducted a cohort study of individuals with ICD-10 unipolar depression from secondary mental healthcare, from an ethnically diverse location in southeast London, followed for 8 years (2007–2014) linked to death certificates. Age- and sex- standardised mortality ratios (SMRs), with the population of England and Wales as a standard population were derived. Hazard ratios (HRs) for mortality were derived through multivariable regression procedures.

Data from 20 320 individuals contributing 91 635 person-years at risk with 2366 deaths were used for analyses. SMR for all-cause mortality in depression was 2.55(95% CI 2.45–2.65), with similar trends by ethnicity. Within the cohort with unipolar depression, adjusted HR (aHRs) for all-cause mortality in ethnic minority groups relative to the White British group were 0.62(95% CI 0.53–0.74) (Black Caribbean), 0.53(95% CI 0.39–0.72) (Black African) and 0.69(95% CI 0.52–0.90) (South Asian). Male sex and alcohol/substance misuse were associated with an increased all-cause mortality risk [aHR:1.94 (95% CI 1.68–2.24) and aHR:1.18 (95% CI 1.01–1.37) respectively], whereas comorbid anxiety was associated with a decreased risk [aHR: 0.72(95% CI 0.58–0.89)]. Similar associations were noted for natural-cause mortality. Alcohol/substance misuse and male sex were associated with a near-doubling in unnatural-cause mortality risk, whereas Black Caribbean individuals with depression had a reduced unnatural-cause mortality risk, relative to White British people with depression.

Although individuals with depression experience an increased mortality risk, marked heterogeneity exists by ethnicity. Research and practice should focus on addressing tractable causes underlying increased mortality in depression.

There is increasing evidence that domestic violence (DV) is an important risk factor for suicidal behaviour. The level of risk and its contribution to the overall burden of suicidal behaviour among men and women has not been quantified in South Asia. We carried out a large case-control study to examine the association between DV and self-poisoning in Sri Lanka.

Cases (N = 291) were patients aged ⩾18 years, admitted to a tertiary hospital in Kandy Sri Lanka for self-poisoning. Sex and age frequency matched controls were recruited from the hospital's outpatient department (N = 490) and local population (N = 450). Exposure to DV was collected through the Humiliation, Afraid, Rape, Kick questionnaire. Multivariable logistic regression models were conducted to estimate the association between DV and self-poisoning, and population attributable fractions were calculated.

Exposure to at least one type of DV within the previous 12 months was strongly associated with self-poisoning for women [adjusted OR (AOR) 4.08, 95% CI 1.60–4.78] and men (AOR 2.52, 95% CI 1.51–4.21), compared to those reporting no abuse. Among women, the association was strongest for physical violence (AOR 14.07, 95% CI 5.87–33.72), whereas among men, emotional abuse showed the highest risk (AOR 2.75, 95% CI 1.57–4.82). PAF% for exposure to at least one type of DV was 38% (95% CI 32–43) in women and 22% (95% CI 14–29) in men.

Multi-sectoral interventions to address DV including enhanced identification in health care settings, community-based strategies, and integration of DV support and psychological services may substantially reduce suicidal behaviour in Sri Lanka.

Unemployment and being not in the labour force (NILF) are risk factors for suicide, but their association with self-harm is unclear, and there is continuing debate about the role of confounding by prior mental health conditions. We examine associations between employment status and self-harm and suicide in a prospective cohort, taking into account prior mental-health-related factors.

We used linked data from the New Zealand Integrated Data Infrastructure. The outcomes were chosen to be hospital presentation for self-harm and death by suicide. The exposure was employment status, defined as employed, unemployed, or NILF, measured at the 2013 Census. Confounders included demographic factors and mental health history (use of antidepressant medication, use of mental health services, and prior self-harm). Logistic regression was used to model effects. Analyses were stratified by gender.

For males, unemployment was associated with an increased risk of suicide [odds ratio (OR): 1.48, 95% confidence interval (CI): 1.20–1.84] and self-harm (OR: 1.55, 95% CI: 1.45–1.68) after full adjustment for confounders. NILF was associated with an increased risk of self-harm (OR: 1.43, 95% CI: 1.32–1.55), but less of an association was seen with suicide (OR: 1.19, 95% CI: 0.94–1.49). For females, unemployment was associated with an increased risk of suicide (OR: 1.30, 95% CI: 0.93–1.80) and of self-harm (OR: 1.52, 95% CI: 1.43–1.62), and NILF was associated with a similar increase in risk for suicide (OR: 1.31, 95% CI: 0.98–1.75) and self-harm (OR: 1.32, 95% CI: 1.26–1.40).

Exclusion from employment is associated with a considerably heightened risk of suicide and self-harm for both men and women, even among those without prior mental health problems.

Around 40% of people with bipolar disorder (BD) are non-adherent to medication leading to relapse, hospitalisation and increased suicide risk. Limited progress in addressing non-adherence may be partly attributable to insufficient understanding of the modifiable determinants of adherence that require targeting in interventions. We synthesised the modifiable determinants of adherence in BD and map them to the theoretical domains framework (TDF).

We searched CINAHL, Cochrane Library, Embase, LILACS, Medline, PsychINFO and PubMed until February 2020. We included studies reporting modifiable determinants of adherence in BD. Two reviewers independently screened studies, assessed quality, extracted modifiable determinants and mapped them to TDF.

We included 57 studies involving 32 894 participants. Determinants reported by patients spanned 11 of the 14 TDF domains compared to six domains represented by clinician/researcher. The TDF domains most commonly represented (% and example) in studies were: ‘Environmental context and resources’ (63%, e.g. experiencing side effects), ‘Beliefs about consequences’ (63%, e.g. beliefs about medication effects), ‘Knowledge’ (40%, e.g. knowledge about disorder), ‘Social influences’ (33%, e.g. support from family/clinicians), ‘Memory, attention and decision processes’ (33%, e.g. forgetfulness), ‘Emotion’ (21%, e.g. fear of addiction) and ‘Intentions’ (21%, e.g. wanting alternative treatment). ‘Intentions’, ‘Memory, attention and decision processes’ and ‘Emotion’ domains were only reported by patients but not clinicians.

Clinicians may be underappreciating the full range of modifiable determinants of adherence and thus not providing adherence support reflective of patients' needs. Reporting of modifiable determinants in behavioural terms facilitates developing theory-based interventions to address non-adherence in BD.

Conduct disorder (CD) has been associated with dysfunction in reinforcement-based decision-making. Two forms of affective traits that reflect the components of CD severity are callous-unemotional (CU; reduced guilt/empathy) traits and irritability. The form of the reinforcement-based decision-making dysfunction with respect to CD and CU traits remains debated and has not been examined with respect to irritability in cases with CD. The goals of the current study were to determine the extent of dysfunction in differential (reward v. punishment) responsiveness in CD, and CU traits and irritability in participants with CD.

The study involved 178 adolescents [typically developing (TD; N = 77) and cases with CD (N = 101)]. Participants were scanned with fMRI during a passive avoidance task that required participants to learn to respond to (i.e. approach) stimuli that engender reward and refrain from responding to (i.e. passively avoid) stimuli that engender punishment.

Adolescents with CD showed reduced differential reward-punishment responsiveness within the striatum relative to TD adolescents. CU traits, but not irritability, were associated with reduced differential reward-punishment responsiveness within the striatum, rostromedial, and lateral frontal cortices.

The results suggest CD is associated with reduced differential reward-punishment responsiveness and the extent of this dysfunction in participants with CD is associated with the severity of CU traits but not irritability.

Altered heart rate variability (HRV), an index of autonomic nervous system function, has been reported in generalized anxiety disorder (GAD), but the results have been mixed. Thus, the present study, using a large sample size and better methodology, aims to examine whether GAD is associated with impaired HRV, both at rest and in response to posture challenges.

In total, 1832 participants were recruited in this study, consisting of 682 patients with GAD (including 326 drug- and comorbidity-free GAD patients) and 1150 healthy controls. Short-term HRV was measured during the supine-standing-supine test (5-min per position). Propensity score matching (PSM), a relatively novel method, was used to control for potential confounders.

After PSM algorithm, drug- and comorbidity-free GAD patients had reductions in resting (baseline) high-frequency power (HF), an index for parasympathetic modulation, and increases in the low-frequency/HF ratio (LF/HF), an index for sympathovagal balance as compared to matched controls. Furthermore, the responses of HF and LF/HF to posture changes were all attenuated when compared with matched controls. Effect sizes, given by Cohen's d, for resting HF and HF reactivity were 0.42 and 0.36–0.42, respectively.

GAD is associated with altered sympathovagal balance, characterized by attenuation in both resting vagal modulation and vagal reactivity, with an almost medium effect size (Cohen's d ≈ 0.4), regardless of medication use or comorbidity status.

Previous research has shown prospectively that religiosity/spirituality protects against depression, but these findings are commonly critiqued on two grounds, namely: (1) apparent religiosity/spirituality reflects merely an original absence of depression or elevated mood and (2) religiosity/spirituality too often is measured as a global construct. The current study investigates the relationship between depression and religiosity/spirituality by examining its multidimensional structural integrity.

Confirmatory factor analyses with a previously observed cross-cultural factor structure of religiosity/spirituality variables were conducted on an independent sample, diagnostic and familial risk subgroups from this sample, and a subsample of the original cross-cultural sample. Linear regressions onto a previous diagnosis of major depressive disorder (MDD) 5 years prior to assess the potential attenuating impact of a previous depression was explored.

Across familial risk groups and clinical subgroups, each of the previously validated religiosity/spirituality domains was confirmed, namely: religious/spiritual commitment, contemplative practice, sense of interconnectedness, the experience of love, and altruistic engagement. Previous MDD diagnosis was associated with a lower religious/spiritual commitment among high-risk individuals, higher contemplation among low-risk individuals, and lower importance of religion or spirituality regardless of risk group.

Structural integrity was found across familial risk groups and diagnostic history for a multidimensional structure of religiosity/spirituality. Differential associations between a previous diagnosis of MDD and level of religiosity/spirituality across domains suggest a complex and interactive relation between depression, familial risk, and religiosity/spirituality. Accounting for an empirically valid, multidimensional understanding of religiosity/spirituality may advance research on mechanisms underlying the relationship between religiosity/spirituality and mental health.