Previous reviews suggest there is minimal evidence for an association between duration of untreated psychosis (DUP) and neurocognition. This is based on tallied findings of studies with small samples and neurocognition viewed as a single construct. We aimed to conduct a systematic review and meta-analysis examining the association between DUP and individual neurocognitive domains and tests in first-episode psychosis (FEP).

MOOSE and PRISMA guidelines were followed. Forty-three studies involving 4647 FEP patients were included. For studies providing correlations between DUP and neurocognition, 12 separate meta-analyses were performed based on neurocognitive domains/indices. The influence of demographic/clinical variables was tested using weighted linear meta-regression analyses.

The relationship between DUP and most neurocognitive domains/indices was not significant. Longer DUP was associated with a larger cognitive deterioration index, i.e. current minus premorbid intellectual functioning (N = 4; mean ES −0.213, 95% confidence interval (CI) (−0.344 to −0.074), p = 0.003). Findings were homogeneous, with no evidence of publication bias or significant influence from moderators. For studies providing mean and standard deviations for neurocognitive measures and DUP, 20 meta-regressions were performed on individual neurocognitive tests. One significant finding emerged showing that longer DUP was associated with fewer Wisconsin Card Sorting Test-perseverative errors (mean ES −0.031, 95% CI (−0.048 to −0.013), p < 0.001). Exploratory meta-regressions in studies with mean DUP <360 days showed longer DUP was significantly associated with poorer performance on Trail Making Test A and B and higher Full-Scale IQ.

There may not be a generalised association between DUP and neurocognition, however, specific cognitive functions may be associated with longer DUP or delayed help-seeking.

The longstanding association between the major histocompatibility complex (MHC) locus and schizophrenia (SZ) risk has recently been accounted for, partially, by structural variation at the complement component 4 (C4) gene. This structural variation generates varying levels of C4 RNA expression, and genetic information from the MHC region can now be used to predict C4 RNA expression in the brain. Increased predicted C4A RNA expression is associated with the risk of SZ, and C4 is reported to influence synaptic pruning in animal models.

Based on our previous studies associating MHC SZ risk variants with poorer memory performance, we tested whether increased predicted C4A RNA expression was associated with reduced memory function in a large (n = 1238) dataset of psychosis cases and healthy participants, and with altered task-dependent cortical activation in a subset of these samples.

We observed that increased predicted C4A RNA expression predicted poorer performance on measures of memory recall (p = 0.016, corrected). Furthermore, in healthy participants, we found that increased predicted C4A RNA expression was associated with a pattern of reduced cortical activity in middle temporal cortex during a measure of visual processing (p < 0.05, corrected).

These data suggest that the effects of C4 on cognition were observable at both a cortical and behavioural level, and may represent one mechanism by which illness risk is mediated. As such, deficits in learning and memory may represent a therapeutic target for new molecular developments aimed at altering C4’s developmental role.

Paliperidone palmitate is one of the most widely prescribed long-acting injectable (LAI) antipsychotics in the UK. However, it is relatively expensive and there are few data comparing its effectiveness to that of other LAI antipsychotics. We sought to address this issue by analyzing a large anonymized electronic health record (EHR) dataset from patients treated with LAI antipsychotics.

EHR data were obtained from 1281 patients in the South London and Maudsley NHS Foundation Trust (SLaM) who started treatment with a LAI antipsychotic between 1 April 2011 and 31 January 2015. The number of days spent as a psychiatric inpatient and the number of admissions to a psychiatric hospital were analyzed in each of the 3 years before and after LAI prescription.

Patients treated with paliperidone palmitate (n = 430; 33.6%) had a greater number of inpatient days and a greater number of admissions in the year prior to treatment than those treated with other LAI antipsychotics. Nevertheless, in the 3 years after initiation there were no significant differences between paliperidone and the other LAI antipsychotics in the number of days as an inpatient (B coefficient 5.4 days, 95% confidence interval (CI) −57.3 to 68.2, p = 0.86) or number of hospital admissions (Incidence rate ratio 1.07, 95% CI 0.62 to 1.83, p = 0.82).

Paliperidone palmitate was more likely to be prescribed in patients with more frequent and lengthy hospital admissions prior to initiation. However, the absence of differences in outcomes after initiation indicates that paliperidone palmitate was not more effective than other cheaper LAI antipsychotics.

Investigations of drinking behavior across military deployment cycles are scarce, and few prospective studies have examined risk factors for post-deployment alcohol misuse.

Prevalence of alcohol misuse was estimated among 4645 US Army soldiers who participated in a longitudinal survey. Assessment occurred 1–2 months before soldiers deployed to Afghanistan in 2012 (T0), upon their return to the USA (T1), 3 months later (T2), and 9 months later (T3). Weights-adjusted logistic regression was used to evaluate associations of hypothesized risk factors with post-deployment incidence and persistence of heavy drinking (HD) (consuming 5 + alcoholic drinks at least 1–2×/week) and alcohol or substance use disorder (AUD/SUD).

Prevalence of past-month HD at T0, T2, and T3 was 23.3% (s.e. = 0.7%), 26.1% (s.e. = 0.8%), and 22.3% (s.e. = 0.7%); corresponding estimates for any binge drinking (BD) were 52.5% (s.e. = 1.0%), 52.5% (s.e. = 1.0%), and 41.3% (s.e. = 0.9%). Greater personal life stress during deployment (e.g., relationship, family, or financial problems) – but not combat stress – was associated with new onset of HD at T2 [per standard score increase: adjusted odds ratio (AOR) = 1.20, 95% CI 1.06–1.35, p = 0.003]; incidence of AUD/SUD at T2 (AOR = 1.54, 95% CI 1.25–1.89, p < 0.0005); and persistence of AUD/SUD at T2 and T3 (AOR = 1.30, 95% CI 1.08–1.56, p = 0.005). Any BD pre-deployment was associated with post-deployment onset of HD (AOR = 3.21, 95% CI 2.57–4.02, p < 0.0005) and AUD/SUD (AOR = 1.85, 95% CI 1.27–2.70, p = 0.001).

Alcohol misuse is common during the months preceding and following deployment. Timely intervention aimed at alleviating/managing personal stressors or curbing risky drinking might reduce risk of alcohol-related problems post-deployment.

Prior research has typically found a negative relationship between chronic pain and memory, and we examined whether cognitive control processes (e.g. reflection and rumination) moderated this relationship in individuals with Chiari malformation Type I (CM). CM is a neurological condition in which the cerebellar tonsils descend into the medullary and upper cervical spine regions potentially resulting in severe headaches and neck pain.

CM patients who had (n = 341) and had not (n = 297) undergone decompression surgery completed the McGill Pain Questionnaire-Short Form-Revised (SF-MPQ-2), the Rey Auditory Verbal Learning Test (RAVLT), and the Rumination-Reflection Questionnaire (RRQ). Immediate recall scores were compared to those of 102 healthy controls, and delayed recall performance was compared across other variables within the CM group.

CM patients performed more poorly on immediate recall than did controls. Within CM patients, we observed main effects for reflection and age, and a pain x reflection x surgical status (surgery v. no surgery) interaction in which non-decompressed individuals with low levels of pain and high levels of reflection showed superior delayed recall relative to non-decompressed individuals with higher pain and all decompressed individuals.

CM patients show an immediate recall deficit relative to controls, regardless of surgical status. High levels of reflection were associated with better delayed recall performance in non-decompressed CM patients with lower pain levels. High levels of chronic pain may overwhelm increased focused attention abilities, but higher levels of reflection partially overcome the distracting effects of pain and this may represent a type of resilience.

Common mental disorders (CMD) cause large suffering and high societal costs. Cognitive behavioural therapy (CBT) can effectively treat CMD, but access to treatment is insufficient. Guided self-help (GSH) CBT, has shown effects comparable with face-to-face CBT. However, not all patients respond to GSH, and stepping up non-responders to face-to-face CBT, could yield larger response rates. The aim was to test a stepped care model for CMD in primary care by first evaluating the effects of GSH-CBT and secondly, for non-responders, evaluating the additional effect of face-to-face CBT.

Consecutive patients (N = 396) with a principal disorder of depression, anxiety, insomnia, adjustment or exhaustion disorder were included. In Step I, all patients received GSH-CBT. In Step II, non-responders were randomized to face-to-face CBT or continued GSH. The primary outcome was remission status, defined as a score below a pre-established cutoff on a validated disorder-specific scale.

After GSH-CBT in Step I, 40% of patients were in remission. After Step II, 39% of patients following face-to-face CBT were in remission compared with 19% of patients after continued GSH (p = 0.004). Using this stepped care model required less than six therapy sessions per patient and led to an overall remission rate of 63%.

Stepped care can be effective and resource-efficient to treat CMD in primary care, leading to high remission rates with limited therapist resources. Face-to-face CBT speeded up recovery compared with continued GSH. At follow-ups after 6 and 12 months, remission rates were similar in the two groups.

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.

Previous cross-lagged studies on depression and memory impairment among the elderly have revealed conflicting findings relating to the direction of influence between depression and memory impairment. The current study aims to clarify this direction of influence by examining the cross-lagged relationships between memory impairment and depression in an Asian sample of elderly community dwellers, as well as synthesizing previous relevant cross-lagged findings via a meta-analysis.

A total of 160 participants (Mage = 68.14, s.d. = 5.34) were assessed across two time points (average of 1.9 years apart) on measures of memory and depressive symptoms. The data were then fitted to a structural equation model to examine two cross-lagged effects (i.e. depressive symptoms→memory; memory→depressive symptoms). A total of 14 effect-sizes for each of the two cross-lagged directions were extracted from six studies (including the present; total N = 8324). These effects were then meta-analyzed using a three-level mixed effects model.

In the current sample, lower memory ability at baseline was associated with worse depressive symptoms levels at follow-up, after controlling for baseline depressive symptoms. However, the reverse effect was not significant; baseline depressive symptoms did not predict subsequent memory ability after controlling for baseline memory. The results of the meta-analysis revealed the same pattern of relationship between memory and depressive symptoms.

These results provide robust evidence that the relationship between memory impairment and depressive symptoms is unidirectional; memory impairment predicts subsequent depressive symptoms but not vice-versa. The implications of these findings are discussed

Although there is extensive evidence that problematic alcohol use is associated with smaller hippocampal volume, the typical cross-sectional study design cannot determine whether hippocampal deviations reflect pre-existing liability toward problematic alcohol use or instead reflect an alcohol exposure-related effect. We used the co-twin control study design, which capitalizes upon differences within a twin pair in levels of drinking, to differentiate pre-existing liability from an effect of alcohol exposure.

The sample included 100 female twins, prospectively assessed from ages 11 to 24. Problematic alcohol use was assessed dimensionally and included indicators of quantity, frequency, and density of alcohol use and intoxication. Hippocampal volume was assessed using magnetic resonance imaging.

Problematic alcohol use (proximal and cumulative) was associated with significantly smaller left and right hippocampal volume. Follow-up co-twin control analyses that partitioned individual-level alcohol effects into pre-existing, familial liability and non-shared alcohol exposure-related effects indicated that this association reflected alcohol exposure. Greater alcohol using twins had smaller hippocampal volume relative to lesser alcohol using co-twins, beyond effects of their shared genetic and environmental liability toward problematic alcohol use. Results held accounting for recent alcohol use, other substance use, externalizing and internalizing psychopathology, personality traits, trauma exposure, and menstrual phase.

The association between problematic alcohol use and smaller hippocampal volume likely reflects an alcohol exposure-related effect. Differentiating pre-existing brain deviations that confer risk for problematic alcohol use from those that reflect effects of alcohol on the brain will inform etiological models of addiction and further prevention and intervention efforts.

Major depression (MD) occurs about twice as often in women as in men, but it is unclear whether sex differences subsist after disease onset. This study aims to elucidate potential sex differences in rates and risk factors for MD recurrence, in order to improve prediction of course of illness and understanding of its underlying mechanisms.

We used prospective data from a general population sample (n = 653) that experienced a recent episode of MD. A diverse set of potential risk factors for recurrence of MD was analyzed using Cox models subject to elastic net regularization for males and females separately. Accuracy of the prediction models was tested in same-sex and opposite-sex test data. Additionally, interactions between sex and each of the risk factors were investigated to identify potential sex differences.

Recurrence rates and the impact of most risk factors were similar for men and women. For both sexes, prediction models were highly multifactorial including risk factors such as comorbid anxiety, early traumas, and family history. Some subtle sex differences were detected: for men, prediction models included more risk factors concerning characteristics of the depressive episode and family history of MD and generalized anxiety, whereas for women, models included more risk factors concerning early and recent adverse life events and socioeconomic problems.

No prominent sex differences in risk factors for recurrence of MD were found, potentially indicating similar disease maintaining mechanisms for both sexes. Course of MD is a multifactorial phenomenon for both males and females.

When patients are admitted onto psychiatric wards, sleep problems are highly prevalent. We carried out the first trial testing a psychological sleep treatment at acute admission (Oxford Ward sLeep Solution, OWLS).

This assessor-blind parallel-group pilot trial randomised patients to receive sleep treatment at acute crisis [STAC, plus standard care (SC)], or SC alone (1 : 1). STAC included cognitive–behavioural therapy (CBT) for insomnia, sleep monitoring and light/dark exposure for circadian entrainment, delivered over 2 weeks. Assessments took place at 0, 2, 4 and 12 weeks. Feasibility outcomes assessed recruitment, retention of participants and uptake of the therapy. Primary efficacy outcomes were the Insomnia Severity Index and Warwick–Edinburgh Mental Wellbeing Scale at week 2. Analyses were intention-to-treat, estimating treatment effect with 95% confidence intervals.

Between October 2015 and July 2016, 40 participants were recruited (from 43 assessed eligible). All participants offered STAC completed treatment (mean sessions received = 8.6, s.d. = 1.5). All participants completed the primary end point. Compared with SC, STAC led to large effect size (ES) reductions in insomnia at week 2 (adjusted mean difference −4.6, 95% CI −7.7 to −1.4, ES −0.9), a small improvement in psychological wellbeing (adjusted mean difference 3.7, 95% CI −2.8 to 10.1, ES 0.3) and patients were discharged 8.5 days earlier. One patient in the STAC group had an adverse event, unrelated to participation.

In this challenging environment for research, the trial was feasible. Therapy uptake was high. STAC may be a highly effective treatment for sleep disturbance on wards with potential wider benefits on wellbeing and admission length.

Lesbian, gay, and bisexual (LGB) individuals report higher levels of depression and anxiety than heterosexual people. Genetic factors may be a ‘common cause’ of sexual minority status and psychological distress. Alternatively, these may be correlated because of non-genetic environmental factors (e.g. minority stressors). This study investigated minority stressors and distress in monozygotic twins discordant for sexual minority status. This design provides a test of the role of non-shared environmental factors while minimizing differences due to genetics.

Thirty-eight twin pairs in which one was heterosexual and the other was LGB completed a survey. Differences between twin pairs in minority stressors, rumination, psychological distress, and gender non-conformity were examined. Associations between these variables were also tested.

Although there were no significant group differences for distress, LGB twins had higher rumination, a vulnerability factor for distress, than heterosexual co-twins. LGB twins also had higher scores than heterosexual co-twins on expectations of rejection, active concealment, self-stigma, prejudice events, childhood gender non-conformity, and lower scores on sexual orientation disclosure. Differences between twin pairs in rumination were positively associated with differences in acceptance concerns and self-stigma. Finally, self-stigma was positively associated with rumination in the full sample of heterosexual co-twins and microaggressions were positively associated with rumination when looking at exclusively heterosexual co-twins.

These results support environmental factors as a causal explanation for disparities in rumination between LGB and heterosexual individuals. These factors likely include minority stressors. Rumination may also be associated with minority stressors in heterosexual MZ co-twins of LGB individuals.

Identifying clinical features that predict conversion to bipolar disorder (BD) in those at high familial risk (HR) would assist in identifying a more focused population for early intervention.

In total 287 participants aged 12–30 (163 HR with a first-degree relative with BD and 124 controls (CONs)) were followed annually for a median of 5 years. We used the baseline presence of DSM-IV depressive, anxiety, behavioural and substance use disorders, as well as a constellation of specific depressive symptoms (as identified by the Probabilistic Approach to Bipolar Depression) to predict the subsequent development of hypo/manic episodes.

At baseline, HR participants were significantly more likely to report ⩾4 Probabilistic features (40.4%) when depressed than CONs (6.7%; p < .05). Nineteen HR subjects later developed either threshold (n = 8; 4.9%) or subthreshold (n = 11; 6.7%) hypo/mania. The presence of ⩾4 Probabilistic features was associated with a seven-fold increase in the risk of ‘conversion’ to threshold BD (hazard ratio = 6.9, p < .05) above and beyond the fourteen-fold increase in risk related to major depressive episodes (MDEs) per se (hazard ratio = 13.9, p < .05). Individual depressive features predicting conversion were psychomotor retardation and ⩾5 MDEs. Behavioural disorders only predicted conversion to subthreshold BD (hazard ratio = 5.23, p < .01), while anxiety and substance disorders did not predict either threshold or subthreshold hypo/mania.

This study suggests that specific depressive characteristics substantially increase the risk of young people at familial risk of BD going on to develop future hypo/manic episodes and may identify a more targeted HR population for the development of early intervention programs.

Attention-deficit/hyperactivity disorder (ADHD) is proposed to be a neuropsychologically heterogeneous disorder that encompasses two distinct sub-groups, one with executive function (EF) deficits and one with delay aversion (DA). However, such claims have often been based on studies that have operationalized neuropsychological deficits using a categorical approach – using intuitive but rather arbitrary, clinical cut-offs. The current study applied an alternative empirical approach to sub-grouping in ADHD, latent profile analysis (LPA), and attempted to validate emerging subgroups through clinically relevant correlates.

One-hundred medication-naïve children with ADHD and 96 typically developing children (6–14 years) completed nine EF and three DA tasks as well as an odor identification test. Parents and teachers provided reports of the children's behavior (ADHD and EF). Models of the latent structure of scores on EF and DA tests were contrasted using confirmatory factor analysis (CFA). LPA was carried out based on factor scores from the CFA and sub-groups were compared in terms of odor identification and behavior.

A model with one DA and two EF factors best fit the data. LPA resulted in four sub-groups that differed in terms of general level of neuropsychological performance (ranging from high to very low), odor identification, and behavior. The sub-groups did not differ in terms of the relative EF and DA performance. Results in the ADHD group were replicated in the control group.

While EF and DA appear to be dissociable constructs; they do not yield distinct sub-groups when sub-grouping is based on a statistical approach such as LPA.

The possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.5–3 Tesla (T)], it is difficult to separate glutamate from its metabolite and precursor, glutamine, with the two often being measured together as Glx. In contrast, MRS at 7 T allows clear spectral resolution of glutamate and glutamine.

We studied 55 un-medicated depressed patients and 50 healthy controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen (PUT). Neurometabolites were calculated using the unsuppressed water signal as a reference.

Compared with controls, depressed patients showed no significant difference in glutamate in any of the three voxels studied; however, glutamine concentrations in the patients were elevated by about 12% in the PUT (p < 0.001).

The increase in glutamine in PUT is of interest in view of the postulated role of the basal ganglia in the neuropsychology of depression and is consistent with elevated activity in the descending cortical glutamatergic innervation to the PUT. The basal ganglia have rarely been the subject of MRS investigations in depressed patients and further MRS studies of these structures in depression are warranted.

Individuals who were born very preterm have higher rates of psychiatric diagnoses compared with term-born controls; however, it remains unclear whether they also display increased sub-clinical psychiatric symptomatology. Hence, our objective was to utilize a dimensional approach to assess psychiatric symptomatology in adult life following very preterm birth.

We studied 152 adults who were born very preterm (before 33 weeks’ gestation; gestational range 24–32 weeks) and 96 term-born controls. Participants’ clinical profile was examined using the Comprehensive Assessment of At-Risk Mental States (CAARMS), a measure of sub-clinical symptomatology that yields seven subscales including general psychopathology, positive, negative, cognitive, behavioural, motor and emotional symptoms, in addition to a total psychopathology score. Intellectual abilities were examined using the Wechsler Abbreviated Scale of Intelligence.

Between-group differences on the CAARMS showed elevated symptomatology in very preterm participants compared with controls in positive, negative, cognitive and behavioural symptoms. Total psychopathology scores were significantly correlated with IQ in the very preterm group only. In order to examine the characteristics of participants’ clinical profile, a principal component analysis was conducted. This revealed two components, one reflecting a non-specific psychopathology dimension, and the other indicating a variance in symptomatology along a positive-to-negative symptom axis. K-means (k = 4) were used to further separate the study sample into clusters. Very preterm adults were more likely to belong to a high non-specific psychopathology cluster compared with controls.

Very preterm individuals demonstrated elevated psychopathology compared with full-term controls. Their psychiatric risk was characterized by a non-specific clinical profile and was associated with lower IQ.