Medically unexplained symptoms otherwise referred to as persistent physical symptoms (PPS) are debilitating to patients. As many specific PPS syndromes share common behavioural, cognitive, and affective influences, transdiagnostic treatments might be effective for this patient group. We evaluated the clinical efficacy and cost-effectiveness of a therapist-delivered, transdiagnostic cognitive behavioural intervention (TDT-CBT) plus (+) standard medical care (SMC) v. SMC alone for the treatment of patients with PPS in secondary medical care.

A two-arm randomised controlled trial, with measurements taken at baseline and at 9, 20, 40- and 52-weeks post randomisation. The primary outcome measure was the Work and Social Adjustment Scale (WSAS) at 52 weeks. Secondary outcomes included mood (PHQ-9 and GAD-7), symptom severity (PHQ-15), global measure of change (CGI), and the Persistent Physical Symptoms Questionnaire (PPSQ).

We randomised 324 patients and 74% were followed up at 52 weeks. The difference between groups was not statistically significant for the primary outcome (WSAS at 52 weeks: estimated difference −1.48 points, 95% confidence interval from −3.44 to 0.48, p = 0.139). However, the results indicated that some secondary outcomes had a treatment effect in favour of TDT-CBT + SMC with three outcomes showing a statistically significant difference between groups. These were WSAS at 20 weeks (p = 0.016) at the end of treatment and the PHQ-15 (p = 0.013) and CGI at 52 weeks (p = 0.011).

We have preliminary evidence that TDT-CBT + SMC may be helpful for people with a range of PPS. However, further study is required to maximise or maintain effects seen at end of treatment.

We provide an umbrella review of the reported polysomnographic changes in patients with neuropsychiatric diseases compared with healthy controls.

An electronic literature search was conducted in EMBASE, MEDLINE, All EBM databases, CINAHL, and PsycINFO. Meta-analyses of case–control studies investigating the polysomnographic changes in patients with neuropsychiatric diseases were included. For each meta-analysis, we estimated the summary effect size using random effects models, the 95% confidence interval, and the 95% prediction interval. We also estimated between-study heterogeneity, evidence of excess significance bias, and evidence of small-study effects. The levels of evidence of polysomnographic changes in neuropsychiatric diseases were ranked as follows: not significant, weak, suggestive, highly suggestive, or convincing.

We identified 27 articles, including 465 case–control studies in 27 neuropsychiatric diseases. The levels of evidence of polysomnographic changes in neuropsychiatric diseases were highly suggestive for increased sleep latency and decreased sleep efficiency (SE) in major depressive disorder (MDD), increased N1 percentage, and decreased N2 percentage, SL and REML in narcolepsy, and decreased rapid eye movement (REM) sleep percentage in Parkinson's disease (PD). The suggestive evidence decreased REM latency in MDD, decreased total sleep time and SE in PD, and decreased SE in posttraumatic stress disorder and in narcolepsy.

The credibility of evidence for sleep characteristics in 27 neuropsychiatric diseases varied across polysomnographic variables and diseases. When considering the patterns of altered PSG variables, no two diseases had the same pattern of alterations, suggesting that specific sleep profiles might be important dimensions for defining distinct neuropsychiatric disorders.

Anorexia nervosa (AN) is characterized by an overgeneralization of food/body-related autobiographical memories (AM). This is regarded as an emotion regulation strategy with adverse long-term effects implicated in disorder maintenance and treatment resistance. Therefore, we aimed to examine neural correlates of food/body-related AM-recall in AN.

Twenty-nine female patients with AN and 30 medication-free age-sex-matched normal-weight healthy controls (HC) underwent functional magnetic resonance imaging while recalling AMs in response to food/body-related and neutral cue words. To control for general knowledge retrieval, participants engaged in a semantic generation and riser detection task.

In comparison to HC, patients with AN generated fewer and less specific AMs in response to food/body-related words, but not for neutral cue words. Group comparisons revealed reduced activation in regions associated with self-referential processing and memory retrieval (precuneus and angular gyrus) during the retrieval of specific food/body-related AM in patients with AN. Brain connectivity in regions associated with memory functioning and executive control was reduced in patients with AN during the retrieval of specific food/body-related AM. Finally, resting-state functional connectivity analysis revealed no differences between groups, arguing against a general underlying disconnection of brain networks implicated in memory and emotional processing in AN.

These results indicate impaired neural processing of food/body-related AM in AN, with a reduced involvement of regions involved in self-referential processing. Our findings are discussed as possible neuronal correlates of emotional avoidance in AN and provide new insights of AN-pathophysiology underscoring the importance of targeting dysfunctional emotion regulation strategies during treatment.

Relatively few studies have explored the differential contributions of the accumulative dosage of psychotropic medications on mortality in patients with schizophrenia.

We aimed to explore the effects of the exposure dosage of psychotropic medications on mortality during a follow-up period of 5 years with a national cohort of individuals with schizophrenia in 2010. Causes of death were linked through Taiwan's National Mortality Registry. The mean defined daily dose of antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, were calculated and survival analyses were conducted.

A total of 102 964 individuals (54 151 men, 52.59%) with schizophrenia were included. Compared to patients with no exposure to antipsychotics, those with antipsychotic exposure had better survival outcomes, regardless of antipsychotic dosage. Antidepressant exposure, in low and moderate dosage, was associated with decreased all-cause mortality; exposure to mood stabilizers appeared to be associated with an increase in all-cause mortality. Although 89.7% of the patients had been prescribed sedative-hypnotics, exposure to sedative-hypnotics was associated with dose-related increased mortality risk [hazard ratio (HR) in low dose group: 1.16, 95% confidence interval (CI) 1.07–1.27; HR in moderate dose: 1.32, 95% CI 1.21–1.44; HR in high dose: 1.83, 95% CI 1.67–2.01)].

The results indicate that in the treatment of schizophrenia, antipsychotics and antidepressants are associated with lower mortality when using adequate dosages and mood stabilizers and sedative-hypnotics with higher mortality compared with no use. Furthermore, exposure to sedative-hypnotics is associated with a dose-related increased mortality risk which warrants clinical attention and further study.

Alcohol consumption and problems are associated with interpersonal difficulties. We used a twin design to assess in men the degree to which genetic or environmental influences contributed to the covariance between alcohol consumption and problems, romantic quality and social support.

The sample included adult male–male twin pairs (697 monozygotic and 487 dizygotic) for whom there were interview-based data on: alcohol consumption (average monthly alcohol consumption in the past year); alcohol problems (lifetime alcohol dependence symptoms); romantic conflict and warmth; friend problems and support; and relative problems and support.

Key findings were that genetic and unique environmental factors contributed to the covariance between alcohol consumption and romantic conflict; genetic factors contributed to the covariance between alcohol problems and romantic conflict; and common and unique environmental factors contributed to the covariance between alcohol problems and friend problems.

Recognizing and addressing the overlapping genetic and environmental influences that alcohol consumption and problems share with romantic quality and other indicators of social support may have implications for substance use prevention and intervention efforts.

High body mass index (BMI) has been associated with lower risks of suicidal behaviour and being underweight with increased risks. However, evidence is inconsistent and sparse, particularly for women. We aim to study this relationship in a large cohort of UK women.

In total 1.2 million women, mean age 56 (s.d. 5) years, without prior suicide attempts or other major illness, recruited in 1996–2001 were followed by record linkage to national hospital admission and death databases. Cox regression yielded relative risks (RRs) and 95% confidence intervals (CIs) for attempted suicide and suicide by BMI, adjusted for baseline lifestyle factors and self-reported treatment for depression or anxiety.

After 16 (s.d. 3) years of follow-up, 4930 women attempted suicide and 642 died by suicide. The small proportion (4%) with BMI <20 kg/m2 were at clearly greater risk of attempted suicide (RR = 1.38, 95% CI 1.23–1.56) and suicide (RR = 2.10, 1.59–2.78) than women of BMI 20–24.9 kg/m2; p < 0.0001 for both comparisons. Small body size at 10 and 20 years old was also associated with increased risks. Half the cohort had BMIs >25 kg/m2 and, while risks were somewhat lower than for BMI 20–24.9 kg/m2 (attempted suicide RR = 0.91, 0.86–0.96; p = 0.001; suicide RR = 0.79, 0.67–0.93; p = 0.006), the reductions in risk were not strongly related to level of BMI.

Being underweight is associated with a definite increase in the risk of suicidal behaviour, particularly death by suicide. Residual confounding cannot be excluded for the small and inconsistent decreased risk of suicidal behaviour associated with being overweight or obese.

Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure.

We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry.

(i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains ‘emotional neglect’ and ‘emotional abuse’ were most predictive for CHR and ROP, while in ROD ‘physical abuse’ and ‘sexual abuse’ were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found.

These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.

Individuals with one psychiatric disorder are at increased risk for incidence and recurrence of other disorders. We characterize whether the magnitude of such heterotypic continuity varies based on whether the first disorder remits or persists over time.

Cohorts were selected from participants in the National Epidemiologic Survey on Alcohol and Related Conditions wave 1 (2001–2002) and wave 2 (2004–2005) surveys with ⩾1 mood, anxiety, or substance use disorder at wave 1. Among respondents remitting (n = 6719) or not remitting (n = 3435) from ⩾1 of disorder at wave 2, the analyses compared the odds of developing new disorders.

As compared with adults whose disorders persisted from wave 1 to wave 2, those with ⩾1 remission had lower odds of incidence or recurrence of another disorder. Remission from alcohol dependence [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.3–0.5] and drug dependence (OR 0.4, 95% CI 0.3–0.6) were associated with the lowest odds of incidence of another disorder. Social anxiety disorder was associated with the lowest adjusted odds of recurrence (adjusted OR = 0.2, 95% CI 0.1–0.6). Remission of disorders within one class (mood, anxiety, substance use) was consistently associated with lower odds of incidence or recurrence of disorders from the same class than with developing disorders from the other classes.

Remission from common psychiatric disorders tends to decrease the risk for incidence or recurrence of disorders and this effect is stronger within than across disorder classes. These results do not support the concept of heterotypic continuity as a substitution of one disorder for another.

The DSM-IV-R classification Pervasive Developmental Disorder – Not otherwise Specified (PDD-NOS) is based on the symptoms for autism and includes a wide variety of phenotypes that do not meet full criteria for autism. As such, PDD-NOS is a broad and poorly defined residual category of the autism spectrum disorders. In order to address the heterogeneity in this residual category it may be helpful to define clinical and neurobiological subtypes. Multiple complex developmental disorder (MCDD) may constitute such a subtype. In order to study the neurobiological specificity of MCDD in comparison with other autism spectrum disorders, we investigated brain morphology in children (age 7–15 years) with MCDD compared to children with autism and typically developing controls.

Structural MRI measures were compared between 22 high-functioning subjects with MCDD and 21 high-functioning subjects with autism, and 21 matched controls.

Subjects with MCDD showed an enlarged cerebellum and a trend towards larger grey-matter volume compared to control subjects. Compared to subjects with autism, subjects with MCDD had smaller intracranial volume.

We report a pattern of volumetric changes in the brains of subjects with MCDD, similar to that seen in autism. However, no enlargement in head size was found. This suggests that although some of the neurobiological changes associated with MCDD overlap with those in autism, others do not. These neurobiological changes may reflect differences in the developmental trajectories associated with these two subtypes of autism spectrum disorders.

Cognitive deficits are well documented in ecstasy (3,4-methylenedioxymethamphetamine; MDMA) users, with such deficits being taken as evidence of dysregulation of the serotonin (5-hydroxytryptamine; 5-HT) system. More recently neuroimaging has been used to corroborate these deficits. The present study aimed to assess multitasking performance in ecstasy polydrug users, polydrug users and drug-naive individuals. It was predicted that ecstasy polydrug users would perform worse than non-users on the behavioural measure and this would be supported by differences in cortical blood oxygenation.

In the study, 20 ecstasy-polydrug users, 17 polydrug users and 19 drug-naive individuals took part. On day 1, drug use history was taken and questionnaire measures were completed. On day 2, participants completed a 20-min multitasking stressor while brain blood oxygenation was measured using functional near infrared spectroscopy (fNIRS).

There were no significant differences between the three groups on the subscales of the multitasking stressor. In addition, there were no significant differences on self-report measures of perceived workload (NASA Task Load Index). In terms of mood, ecstasy users were significantly less calm and less relaxed compared with drug-naive controls. There were also significant differences at three voxels on the fNIRS, indicating decreased blood oxygenation in ecstasy users compared with drug-naive controls at voxel 2 (left dorsolateral prefrontal cortex), voxel 14 and voxel 16 (right dorsolateral prefrontal cortex), and compared with polydrug controls at V14.

The results of the present study provide support for changes in brain activation during performance of demanding tasks in ecstasy polydrug users, which could be related to cerebral vasoconstriction.

The first aim was to use confirmatory factor analysis (CFA) to test a hypothesis that two factors (internalizing and externalizing) account for lifetime co-morbid DSM-IV diagnoses among adults with bipolar I (BPI) disorder. The second aim was to use confirmatory latent class analysis (CLCA) to test the hypothesis that four clinical subtypes are detectible: pure BPI; BPI plus internalizing disorders only; BPI plus externalizing disorders only; and BPI plus internalizing and externalizing disorders.

A cohort of 699 multiplex BPI families was studied, ascertained and assessed (1998–2003) by the National Institute of Mental Health Genetics Initiative Bipolar Consortium: 1156 with BPI disorder (504 adult probands; 594 first-degree relatives; and 58 more distant relatives) and 563 first-degree relatives without BPI. Best-estimate consensus DSM-IV diagnoses were based on structured interviews, family history and medical records. MPLUS software was used for CFA and CLCA.

The two-factor CFA model fit the data very well, and could not be improved by adding or removing paths. The four-class CLCA model fit better than exploratory LCA models or post-hoc-modified CLCA models. The two factors and four classes were associated with distinctive clinical course and severity variables, adjusted for proband gender. Co-morbidity, especially more than one internalizing and/or externalizing disorder, was associated with a more severe and complicated course of illness. The four classes demonstrated significant familial aggregation, adjusted for gender and age of relatives.

The BPI two-factor and four-cluster hypotheses demonstrated substantial confirmatory support. These models may be useful for subtyping BPI disorders, predicting course of illness and refining the phenotype in genetic studies.

Impairment of response inhibition has been implicated in attention-deficit/hyperactivity disorder (ADHD). Dopamine neurotransmission has been linked to the behavioural and neural correlates of response inhibition. The current study aimed to investigate the relationship of polymorphisms in two dopamine-related genes, the catechol-O-methyltransferase gene (COMT) and the dopamine transporter gene (SLC6A3 or DAT1), with the neural and behavioural correlates of response inhibition.

Behavioural and neural measures of response inhibition were obtained in 185 adolescents with ADHD, 111 of their unaffected siblings and 124 healthy controls (mean age 16.9 years). We investigated the association of DAT1 and COMT variants on task performance and whole-brain neural activation during response inhibition in a hypothesis-free manner. Additionally, we attempted to explain variance in previously found ADHD effects on neural activation during response inhibition using these DAT1 and COMT polymorphisms.

The whole-brain analyses demonstrated large-scale neural activation changes in the medial and lateral prefrontal, subcortical and parietal regions of the response inhibition network in relation to DAT1 and COMT polymorphisms. Although these neural activation changes were associated with different task performance measures, no relationship was found between DAT1 or COMT variants and ADHD, nor did variants in these genes explain variance in the effects of ADHD on neural activation.

These results suggest that dopamine-related genes play a role in the neurobiology of response inhibition. The limited associations between gene polymorphisms and task performance further indicate the added value of neural measures in linking genetic factors and behavioural measures.

Depression and insomnia commonly co-occur. Yet, little is known about the mechanisms through which insomnia influences depression. Recent research and theory highlight reward system dysfunction as a potential mediator of the relationship between insomnia and depression. This study is the first to examine the impact of insomnia on reward learning, a key component of reward system functioning, in clinical depression.

The sample consisted of 72 veterans with unipolar depression who endorsed sleep disturbance symptoms. Participants completed the Structured Clinical Interview for DSM-IV, self-report measures of insomnia, depression, and reward processing, and a previously validated signal detection task (Pizzagalli et al., 2005, Biological Psychiatry, 57(4), 319–327). Trial-by-trial response bias (RB) estimates calculated for each of the 200 task trials were examined using linear mixed-model analyses to investigate change in reward learning.

Findings demonstrated diminished rate and magnitude of reward learning in the Insomnia group relative to the Hypersomnia/Mixed Symptom group across the task. Within the Insomnia group, participants with more severe insomnia evidenced the lowest rates of reward learning, with increased RB across the task with decreasing insomnia severity.

Among individuals with depression, insomnia is associated with decreased ability to learn associations between neutral stimuli and rewarding outcomes and/or modify behavior in response to differential receipt of reward. This attenuated reward learning may contribute to clinically meaningful decreases in motivation and increased withdrawal in this comorbid group. Results extend existing theory by highlighting impairments in reward learning specifically as a potential mediator of the association between insomnia and depression.

Post-traumatic mechanisms are theorised to contribute to voice-hearing in people with psychosis and a history of trauma. Phenomenological links between trauma and voices support this hypothesis, as they suggest post-traumatic processes contribute to the content of, and relationships with, voices. However, research has included small samples and lacked theory-based comprehensive assessments.

In people with distressing voices (n = 73) who experienced trauma prior to voice-hearing, trauma–voice links were assessed both independently and dependently (descriptions were presented and rated separately and together, respectively) by both participants and researchers. A structured coding frame assessed four types of independent links (i.e. victimisation type, physiological-behavioural, emotional, and cognitive response themes including negative self-beliefs) and three types of dependent links: relational (similar interaction with/response to, voice and trauma); content (voice and trauma content are exactly the same); and identity (voice identity is the same as perpetrator).

Independent links were prevalent in participants (51–58%) and low to moderately present in researcher ratings (8–41%) for significant themes. Identification of negative self-beliefs in trauma was associated with a significantly higher likelihood of negative self-beliefs in voices [participants odds ratio (OR) 9.8; researchers OR 4.9]. Participants and researchers also reported many dependent links (80%, 66%, respectively), most frequently relational links (75%, 64%), followed by content (60%, 25%) and identity links (51%, 22%).

Trauma appears to be a strong shaping force for voice content and its psychological impact. The most common trauma–voice links involved the experience of cognitive-affective psychological threat, embodied in relational experiences. Trauma-induced mechanisms may be important intervention targets.

The interaction between positive, negative and depressive symptoms experienced by people with schizophrenia is complex. We used longitudinal data to test the hypothesis that depressive symptoms mediate the links between positive and negative symptoms.

We analyzed data from the European Schizophrenia Cohort, randomly sampled from outpatient services in France, Germany and the UK (N = 1208). Initial measures were repeated after 6 and 12 months. Depressive symptoms were identified using the Calgary Depression Scale for Schizophrenia (CDSS), while positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Latent variable structural equation modelling was used to investigate the mediating role of depression assessed at 6 months in relation to the longitudinal association between positive symptoms at baseline and negative symptoms at 12 months.

We found longitudinal associations between positive symptoms at baseline and negative symptoms at 12 months, as well as between both of these and CDSS levels at 6 months. However depression did not mediate the longitudinal association between PANSS scores; all the effect was direct.

Our findings are incompatible with a mediating function for depression on the pathway from positive to negative symptoms, at least on this timescale. The role of depression in schizophrenic disorders remains a challenge for categorical and hierarchical diagnostic systems alike. Future research should analyze specific domains of both depressive and negative symptoms (e.g. motivational and hedonic impairments). The clinical management of negative symptoms using antidepressant treatments may need to be reconsidered.

Neurophysiological patterns may distinguish which youth are at risk for the well-documented increase in internalizing symptoms during adolescence. Adolescents with internalizing problems exhibit altered resting-state functional connectivity (RSFC) of brain regions involved in socio-affective processing. Whether connectivity-based biotypes differentiate adolescents’ levels of internalizing problems remains unknown.

Sixty-eight adolescents (37 females) reported on their internalizing problems at ages 14, 16, and 18 years. A resting-state functional neuroimaging scan was collected at age 16. Time-series data of 15 internalizing-relevant brain regions were entered into the Subgroup-Group Iterative Multi-Model Estimation program to identify subgroups based on RSFC maps. Associations between internalizing problems and connectivity-based biotypes were tested with regression analyses.

Two connectivity-based biotypes were found: a Diffusely-connected biotype (N = 46), with long-range fronto-parietal paths, and a Hyper-connected biotype (N = 22), with paths between subcortical and medial frontal areas (e.g. affective and default-mode network regions). Higher levels of past (age 14) internalizing problems predicted a greater likelihood of belonging to the Hyper-connected biotype at age 16. The Hyper-connected biotype showed higher levels of concurrent problems (age 16) and future (age 18) internalizing problems.

Differential patterns of RSFC among socio-affective brain regions were predicted by earlier internalizing problems and predicted future internalizing problems in adolescence. Measuring connectivity-based biotypes in adolescence may offer insight into which youth face an elevated risk for internalizing disorders during this critical developmental period.