Depression and post-traumatic stress disorder (PTSD) are leading causes of disability and loss of life by suicide. Currently, there are less than satisfactory medical solutions to treat these mental disorders. Here, we explore recent preclinical and clinical studies demonstrating the potential of using buprenorphine to treat major depressive disorder, treatment-resistant depression, and PTSD.

Bibliographic databases were searched to include preclinical and clinical studies demonstrating the therapeutic potential of buprenorphine and the involvement of the kappa opioid receptor (KOR) in mediating these effects.

Original clinical studies examining the effectiveness of buprenorphine to treat depression were mixed. The majority of participants in the PTSD studies were males and suffer from chronic pain and/or substance use disorders. Nonetheless, these recent studies and analyses established proof of concept warranting farther investigations. Additionally, KOR likely mediates the antidepressant and some of the anxiolytic effects of buprenorphine. Still, it appears that the full spectrum of buprenorphine's beneficial effects might be due to activity at other opioid receptors as well.

Pharmaceuticals' abilities to treat medical conditions directly relates to their ability to act upon the endogenous biological systems related to the conditions. Thus, these recent findings are likely a reflection of the central role that the endogenous opioid system has in these mental illnesses. Further studies are necessary to study the involvement of endogenous opioid systems, and specifically KOR, in mediating buprenorphine's beneficial effects and the ability to treat these medical conditions while minimizing risks for misuse and diversion.

People with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have abnormalities in frontal, temporal, parietal and striato-thalamic networks. It is unclear to what extent these abnormalities are distinctive or shared. This comparative meta-analysis aimed to identify the most consistent disorder-differentiating and shared structural and functional abnormalities.

Systematic literature search was conducted for whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies of cognitive control comparing people with ASD or ADHD with typically developing controls. Regional gray matter volume (GMV) and fMRI abnormalities during cognitive control were compared in the overall sample and in age-, sex- and IQ-matched subgroups with seed-based d mapping meta-analytic methods.

Eighty-six independent VBM (1533 ADHD and 1295 controls; 1445 ASD and 1477 controls) and 60 fMRI datasets (1001 ADHD and 1004 controls; 335 ASD and 353 controls) were identified. The VBM meta-analyses revealed ADHD-differentiating decreased ventromedial orbitofrontal (z = 2.22, p < 0.0001) but ASD-differentiating increased bilateral temporal and right dorsolateral prefrontal GMV (zs ⩾ 1.64, ps ⩽ 0.002). The fMRI meta-analyses of cognitive control revealed ASD-differentiating medial prefrontal underactivation but overactivation in bilateral ventrolateral prefrontal cortices and precuneus (zs ⩾ 1.04, ps ⩽ 0.003). During motor response inhibition specifically, ADHD relative to ASD showed right inferior fronto-striatal underactivation (zs ⩾ 1.14, ps ⩽ 0.003) but shared right anterior insula underactivation.

People with ADHD and ASD have mostly distinct structural abnormalities, with enlarged fronto-temporal GMV in ASD and reduced orbitofrontal GMV in ADHD; and mostly distinct functional abnormalities, which were more pronounced in ASD.

Prenatal infections have been proposed as a putative risk factor for a number of psychiatric outcomes across a continuum of severity. Evidence on eating disorders is scarce. We investigated whether exposure to prenatal maternal infections is associated with an increased risk of disordered eating and weight and shape concerns in adolescence in a large UK birth cohort.

We used data from the Avon Longitudinal Study of Parents and Children. The primary exposure was maternal experience of infections at any time in pregnancy. Study outcomes were presence of any, monthly or weekly disordered eating at 14 and 16 years of age, and weight and shape concerns at 14 years. We defined the causal effect of the exposure on these outcomes using a counterfactual framework adjusting our analyses for a number of hypothesised confounders, and imputing missing confounder data using multiple imputation.

In total, 4884 children had complete exposure and outcome data at age 14 years, and 4124 at 16 years. Exposed children had a greater risk of reporting weekly disordered eating at both age 14 [risk difference (RD) 0.9%, 95% confidence interval (CI) −0.01 to 1.9, p = 0.08] and 16 (RD 2.3%, 95% CI 0.6–3.9, p < 0.01), though evidence of an association was weak at age 14 years. Exposed children also had greater weight and shape concerns at age 14 years (mean difference 0.15, 95% CI 0.05–0.26, p < 0.01).

Exposure to prenatal maternal infection is associated with greater risk of disordered eating in adolescence. This association could be explained by in utero processes leading to impaired neurodevelopment or altered immunological profiles. Residual confounding cannot be excluded.

Bipolar disorder I (BD-I) is defined by episodes of mania, depression and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood.

We first assessed the severity of NS in 25 euthymic BD-I patients compared with 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral (VS) and dorsal striatal (DS) activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS.

In BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant VS and DS activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole-brain analyses revealed reduced extra-striatal activation in BD-I patients compared with HC and an association between reduced activation of the inferior frontal gyrus and apathy.

This study found that in BD-I patients apathy is present to an extent comparable to SZ, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

Low IQ is a risk factor for psychosis, but the effect of high IQ is more controversial. The aim was to explore the association of childhood school success with prodromal symptoms in adolescence and psychoses in adulthood.

In the general population-based Northern Finland Birth Cohort 1986 (n = 8 229), we studied the relationship between teacher-assessed learning deficits, special talents and general school success at age 8 years and both prodromal symptoms (PROD-screen) at age 15–16 years and the occurrence of psychoses by age 30 years.

More prodromal symptoms were experienced by those talented in oral presentation [boys: adjusted odds ratio (OR) 1.49; 95% confidence interval 1.14–1.96; girls: 1.23; 1.00–1.52] or drawing (boys: 1.44; 1.10–1.87). Conversely, being talented in athletics decreased the probability of psychotic-like symptoms (boys: OR 0.72; 0.58–0.90). School success below average predicted less prodromal symptoms with boys (OR 0.68; 0.48–0.97), whereas above-average success predicted more prodromal symptoms with girls (OR 1.22; 1.03–1.44). The occurrence of psychoses was not affected. Learning deficits did not associate with prodromal symptoms or psychoses.

Learning deficits in childhood did not increase the risk of prodromal symptoms in adolescence or later psychosis in this large birth cohort. Learning deficits are not always associated with increased risk of psychosis, which might be due to, e.g. special support given in schools. The higher prevalence of prodromal symptoms in talented children may reflect a different kind of relationship of school success with prodromal symptoms compared to full psychoses.

This study examined the structure of the self-concept in a sample of sexual trauma survivors with posttraumatic stress disorder (PTSD) compared to healthy controls using a self-descriptive card-sorting task. We explored whether individuals with PTSD possess a highly affectively-compartmentalized self-structure, whereby positive and negative self-attributes are sectioned off into separate components of self-concept (e.g. self as an employee, lover, mother). We also examined redundancy (i.e. overlap) of positive and negative self-attributes across the different components of self-concept.

Participants generated a set of self-aspects that reflected their own life (e.g. ‘self at work’). They were then asked to describe their self-aspects using list of positive or negative attributes.

Results revealed that, relative to the control group, the PTSD group used a greater proportion of negative attributes and had a more compartmentalized self-structure. However, there were no significant differences between the PTSD and control groups in positive or negative redundancy. Sensitivity analyses demonstrated that the key findings were not accounted for by comorbid diagnosis of depression.

Findings indicated that the self-structure is organized differently in those with PTSD, relative to those with depression or good mental health.

Premenstrual dysphoric disorder (PMDD) is a new Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 diagnosis characterized by the cyclical emergence of emotional and physical symptoms in the luteal phase of the menstrual cycle, with symptom remission in the follicular phase. Converging evidence highlights the possibility of distinct subtypes of PMDD with unique pathophysiologies, but temporal subgroups have yet to be explored in a systematic way.

In the current work, we use group-based trajectory modeling to identify unique trajectory subgroups of core emotional and total PMDD symptoms across the perimenstrual frame (days −14 to +9, where day 0 is menstrual onset) in a sample of 74 individuals prospectively diagnosed with DSM-5 PMDD.

For the total daily symptom score, the best-fitting model was comprised of three groups: a group demonstrating moderate symptoms only in the premenstrual week (65%), a group demonstrating severe symptoms across the full 2 weeks of the luteal phase (17.5%), and a group demonstrating severe symptoms in the premenstrual week that were slow to resolve in the follicular phase (17.5%).

These trajectory groups are discussed in the context of the latest work on the pathophysiology of PMDD. Experimental work is needed to test for the presence of possible pathophysiologic differences in trajectory groups, and whether unique treatment approaches are needed.

We introduce and apply an elegant, contrastive genetic-epidemiological design – Maternal Half-Sibling Families with Discordant Fathers – to clarify cross-generational transmission of genetic risk to alcohol use disorder (AUD), drug abuse (DA) and major depression (MD).

Using Swedish national registries, we identified 73 108 eligible pairs of reared together maternal half-siblings and selected those whose biological fathers were discordant for AUD, DA and MD, and had minimal contact with the affected father. We examined differences in outcome in half-siblings with an affected v. unaffected father.

For AUD, DA and MD, the HR (95% confidence intervals) for the offspring of affected v. unaffected fathers were, respectively, 1.72 (1.61; 1.84), 1.55 (1.41; 1.70) and 1.51 (1.40; 1.64). Paternal DA and AUD, but not MD, predicted risk in offspring for attention deficit hyperactivity disorder, conduct disorder, and poor educational performance and attainment. Offspring of affected v. unaffected fathers had poorer pregnancy outcomes, with the effect strongest for DA and weakest for MD. A range of potential biases and confounders were examined and were not found to alter these findings substantially.

Reared together maternal half-siblings differ in their paternal genetic endowment, sharing the same mother, family, school and community. They can help clarify the nature of paternal genetic effects and produce results consistent with other designs. Paternal genetic risk for DA and AUD have effects on offspring educational achievement, child and adult psychopathology, and possibly prenatal development. The impact of paternal genetic risk for MD is narrower in scope.

Little information is available on the prevalence of Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 eating disorders in adolescence, and eating disorders remain unique in the DSM for not systematically including a criterion for clinical significance. This study aimed to provide the first prevalence report of the full suite of DSM-5 eating disorders in adolescence, and to examine the impact of applying a criterion for clinical significance.

In total, 5191 (participation rate: 70%) Australian adolescents completed a survey measuring 1-month prevalence of eating disorder symptoms for all criterial, ‘other specified’ and unspecified eating disorders, as well as health-related quality of life and psychological distress.

The point prevalence of any eating disorder was 22.2% (12.8% in boys, 32.9% in girls), and ‘other specified’ disorders (11.2%) were more common than full criterial disorders (6.2%). Probable bulimia nervosa and binge eating disorder, but not anorexia nervosa (AN), were more likely to be experienced by older adolescents. Most disorders were associated with an increased odds for being at a higher weight. The prevalence of eating disorders was reduced by 40% (to 13.6%) when a criterion for clinical significance was applied.

Eating disorders, particularly ‘other specified’ syndromes, are common in adolescence, and are experienced across age, weight, socioeconomic and migrant status. The merit of adding a criterion for clinical significance to the eating disorders, similar to other DSM-5 disorders, warrants consideration. At the least, screening tools should measure distress and impairment associated with eating disorder symptoms in order to capture adolescents in greatest need for intervention.

Reducing hospitalisation and length of stay (LOS) in hospital following first episode psychosis (FEP) is important, yet reliable measures of these outcomes and their moderators are lacking. We conducted a systematic review and meta-analysis to investigate the proportion of FEP cases who were hospitalised after their first contact with services and the LOS in a hospital during follow-up.

Studies were identified from a systematic search across major electronic databases from inception to October 2017. Random effects meta-analyses and meta-regression analyses were conducted.

81 longitudinal studies encompassing data for 23 280 FEP patients with an average follow-up length of 7 years were included. 55% (95% CI 50.3–60.5%) of FEP cases were hospitalised at least once during follow-up with the pooled average LOS of 116.7 days (95% CI 95.1–138.3). Older age of illness onset and being in a stable relationship were associated with a lower proportion of people who were hospitalised. While the proportion of hospitalised patients has not decreased over time, LOS has, with the sharpest reduction in the latest time period. The proportion of patients hospitalised during follow-up was highest in Australia and New Zealand (78.4%) compared to Europe (58.1%) and North America (48.0%); and lowest in Asia (32.5%). Black ethnicity and longer duration of untreated psychosis were associated with longer LOS; while less severe psychotic symptoms at baseline were associated with shorter LOS.

One in two FEP cases required hospitalisation at least once during a 7-year follow-up with an average length of hospitalisation of 4 months during this period. LOS has declined over time, particularly in those countries in which it was previously longest.

Studies of psychological interventions for the prevention of depression have found significant effects in the short-term, but the long-term efficacy has yet to be determined. This study evaluated the 8-year effect of a randomized controlled trial for indicated prevention of depression in female caregivers.

A total of 173 non-professional female caregivers with subclinical depressive symptoms not meeting criteria for a major depressive episode (MDE) were randomized to either a brief problem-solving intervention (n = 89) or usual-care control group (n = 84). Blinded evaluators conducted an assessment at the 8-year follow-up. The primary outcome was Depression Status, defined by diagnoses of MDE since the 1-year follow-up using the Structured Clinical Interview for the Disorders of the DSM-5. The secondary outcome was current Depressive Symptom Severity. Regression analyses were conducted to evaluate the effect of the intervention on the outcomes.

There were no significant differences in the Depression Status between the problem-solving (30.3%) and control groups (26.2%) (adjusted OR 1.25, 95% CI −0.58 to 2.69). Depressive Symptom Severity, however, was significantly lower in the problem-solving group compared to the control group at this follow-up, amounting to a small effect size of Cohen's d = 0.39 (adjusted B = −3.32, p = 0.018).

This is the first study to assess such a long-term follow-up of intervention of indicated prevention of depression. Results seem to indicate that the protective effect of the intervention became smaller over time during follow-up. Future research should replicate these results.

Improving Access to Psychological Therapies (IAPT) services treat most patients in England who present to primary care with major depression. Psychodynamic psychotherapy is one of the psychotherapies offered. Dynamic Interpersonal Therapy (DIT) is a psychodynamic and mentalization-based treatment for depression. 16 sessions are delivered over approximately 5 months. Neither DIT's effectiveness relative to low-intensity treatment (LIT), nor the feasibility of randomizing patients to psychodynamic or cognitive-behavioural treatments (CBT) in an IAPT setting has been demonstrated.

147 patients were randomized in a 3:2:1 ratio to DIT (n = 73), LIT (control intervention; n = 54) or CBT (n = 20) in four IAPT treatment services in a combined superiority and feasibility design. Patients meeting criteria for major depressive disorder were assessed at baseline, mid-treatment (3 months) and post-treatment (6 months) using the Hamilton Rating Scale for Depression (HRSD-17), Beck Depression Inventory-II (BDI-II) and other self-rated questionnaire measures. Patients receiving DIT were also followed up 6 months post-completion.

The DIT arm showed significantly lower HRSD-17 scores at the 6-month primary end-point compared with LIT (d = 0.70). Significantly more DIT patients (51%) showed clinically significant change on the HRSD-17 compared with LIT (9%). The DIT and CBT arms showed equivalence on most outcomes. Results were similar with the BDI-II. DIT showed benefit across a range of secondary outcomes.

DIT delivered in a primary care setting is superior to LIT and can be appropriately compared with CBT in future RCTs.

Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.

Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.

CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.

Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

Major depressive disorder (MDD) commonly co-occurs with clinically significant levels of anxiety. However, anxiety symptoms are varied and have been inconsistently associated with clinical, functional, and antidepressant treatment outcomes. We aimed to identify and characterise dimensions of anxiety in people with MDD and their use in predicting antidepressant treatment outcome.

1008 adults with a current diagnosis of single-episode or recurrent, nonpsychotic, MDD were assessed at baseline on clinical features and cognitive/physiological functioning. Participants were then randomised to one of three commonly prescribed antidepressants and reassessed at 8 weeks regarding symptom change, as well as remission and response, on the 17-item Hamilton Rating Scale Depression (HRSD17) and the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16). Exploratory factor analysis was used on items from scales assessing anxiety symptoms, and resulting factors were assessed against clinical features and cognitive/physiological functioning. Factors were also assessed on their ability to predict treatment outcome.

Three factors emerged relating to stress, cognitive anxiety, and somatic anxiety. All factors showed high internal consistency, minimal cross-loadings, and unique clinical and functional profiles. Furthermore, only higher somatic anxiety was associated with poorer QIDS-SR16 remission, even after adjusting for covariates and multiple comparisons.

Anxiety symptoms in people with MDD can be separated onto distinct factors that differentially respond to treatment outcome. Furthermore, these factors do not align with subscales of established measures of anxiety. Future research should consider cognitive and somatic symptoms of anxiety separately when assessing anxiety in MDD and their use in predicting treatment outcome.

The efficacy of psychoeducation for bipolar disorder has been demonstrated in clinical trials, but it is not known if the results translate into effectiveness in routine clinical practice. The aim was to determine the effectiveness of psychoeducation for bipolar disorder in a routine clinical setting.

We identified 2819 patients with at least three registrations in the Swedish Quality Assurance Register for Bipolar Disorder. Among those, 402 had not been exposed to psychoeducation at the first visit, but received psychoeducation during any of the following registrations. Using within-individual analyses, the risk of recurrence after having received psychoeducation was compared with the risk prior to psychoeducation.

In adjusted within-individuals comparisons, periods after psychoeducation was associated with decreased risks of any recurrence [odds ratio (OR) 0.57, 95% CI 0.42–0.78], (hypo-)manic or mixed episodes (OR 0.54, 95% CI 0.39–0.76), depressive episodes (OR 0.63, 95% CI 0.47–0.86), and inpatient care (OR 0.54, 95% CI 0.33–0.86) relative to periods prior to psychoeducation. There was no association with rates of involuntary sectioning or suicide attempts.

The results suggest that psychoeducation for bipolar disorder reduces the risk of mood episodes and inpatient care also when implemented in routine clinical practice.

Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state.

Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders.

Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia.

Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.