Consistent evidence suggests that face-to-face cognitive-behavioural therapy (CBT) and interpersonal psychotherapy (IPT) may be equally effective depression treatments. Current clinical research focuses on detecting the best predictors-moderators of efficacy to guide treatment personalisation. However, individual moderator studies show inconsistent findings. This systematic review and meta-analysis aimed to compare the efficacy of CBT and IPT, including combined treatment with antidepressants for depression, and evaluate the predictive power of demographic, clinical presentation and treatment characteristics moderators for both therapies.

PsycArticles, PsycINFO, PubMed and Cochrane Library were systematically searched through December 2017 for studies that have assessed individuals with major depression receiving either CBT or IPT in a face-to-face format both at pre- and post-treatment. Random-effects moderator meta-analyses were conducted.

In total 168 samples from 137 studies including 11 374 participants qualified for the meta-analytic review. CBT and IPT were equally effective across all but one prespecified moderators. For psychotherapy delivered without concomitant antidepressant treatment [antidepressant medications (ADMs)], CBT was superior to IPT (g = 1.68, Qbetweenp = 0.037). Within-CBT moderator analyses showed that increased CBT efficacy was associated with lower age, high initial depression severity, individual format of administration and no adjunctive ADMs. Within-IPT analyses showed comparable efficacy across all moderators.

Clinical guidance around combined treatment (psychotherapy plus ADMs) should be reconsidered. CBT alone is superior to IPT alone and to combined treatment, while IPT alone is non-inferior to combined treatment. More research is needed to assess the moderating effect of older age and number of previous episodes on IPT efficacy.

Though meta-analyses of neuropsychological and social cognitive deficits in behavioral variant frontotemporal dementia (bvFTD) have been conducted, no study has comprehensively characterized and compared the neuropsychological, social cognitive, and olfactory profiles in the behavioral and language variants of FTD.

Our search yielded 470 publications meeting inclusion criteria representing 11 782 FTD patients and 19 451 controls. For each domain, we calculated Hedges’ g effect sizes, which represent the mean difference between the patient and control group divided by the pooled standard deviation. The heterogeneity of these effects was assessed with Cochran's Q-statistic using a random-effects model. Meta-regressions were employed to analyze the influence of demographic and disease characteristics.

Though semantic variant primary progressive aphasia patients showed the greatest impairment across all task types, the three groups showed similar cognitive effect sizes once contributions from the language subdomain were excluded from analysis. Contrary to expectation, the magnitude of deficits in executive functioning, social cognition and olfaction were comparable between the three subgroups. Among indices, a metric of executive errors distinguished the behavioral variant of FTD from the language phenotypes.

These data indicate that social cognitive and traditional executive functioning measures may not capture differences between FTD syndromes. These results have important implications for the interpretation of neuropsychological assessments, particularly when applied to the differential diagnosis of FTD. It is hoped that these findings will guide clinical and research assessments and spur new studies focused on improving the measurement of FTD syndromes.

Research in depression has progressed rapidly over the past four decades. Yet depression rates are not subsiding and treatment success is not improving. We examine the extent to which the gap between science and practice is associated with the level of integration in how depression is considered in research and stakeholder-relevant documents.

We used a network-science perspective to analyze similar uses of depression relevant terms in the Google News corpus (approximately 1 billion words) and the Web of Science database (120 000 documents).

These analyses yielded consistent pictures of insular modules associated with: (1) patient/providers, (2) academics, and (3) industry. Within academia insular modules associated with psychology, general medical, and psychiatry/neuroscience/biology were also detected.

These analyses suggest that the domain of depression is fragmented, and that advancements of relevance to one stakeholder group (academics, industry, or patients) may not translate to the others. We consider potential causes and associated responses to this fragmentation that could help to unify and advance translation from research on depression to the clinic, largely involving harmonizing employed language, bridging conceptual domains, and increasing communication across stakeholder groups.

Depression and anxiety disorders (AD) are the first and sixth leading causes of disability worldwide. Despite their high prevalence and significant disability resulted, there are limited advances in new drug development. Recently, genome-wide association studies (GWAS) have greatly advanced our understanding of the genetic basis underlying psychiatric disorders.

Here we employed gene-set analyses of GWAS summary statistics for drug repositioning. We explored five related GWAS datasets, including two on major depressive disorder (MDD2018 and MDD-CONVERGE, with the latter focusing on severe melancholic depression), one on AD, and two on depressive symptoms and neuroticism in the population. We extracted gene-sets associated with each drug from DSigDB and examined their association with each GWAS phenotype. We also performed repositioning analyses on meta-analyzed GWAS data, integrating evidence from all related phenotypes.

Importantly, we showed that the repositioning hits are generally enriched for known psychiatric medications or those considered in clinical trials. Enrichment was seen for antidepressants and anxiolytics but also for antipsychotics. We also revealed new candidates or drug classes for repositioning, some of which were supported by experimental or clinical studies. For example, the top repositioning hit using meta-analyzed p values was fendiline, which was shown to produce antidepressant-like effects in mouse models by inhibition of acid sphingomyelinase.

Taken together, our findings suggest that human genomic data such as GWAS are useful in guiding drug discoveries for depression and AD.

Anti-NMDA receptor (NMDAr) encephalitis is the most common autoimmune encephalitis in adults. It mimics psychiatric disorders so often that most patients are initially referred to a psychiatrist, and many are misdiagnosed. Without prompt and effective treatment, patients are likely to suffer a protracted course with significant residual disability, or death. This study focuses on the frequency and chronology of salient clinical features in adults with anti-NMDAr encephalitis who are likely to be first evaluated by a psychiatrist because their presentation suggests a primary psychiatric disorder.

A systematic search of PubMed and EMBASE databases identified published reports of anti-NMDAr encephalitis associated with prominent behavioral or psychiatric symptoms. After eliminating redundancies, the frequencies and relative timing of clinical features were tabulated. Signs and symptoms were assigned temporal ranks based on the timing of their first appearance relative to the first appearance of other signs and symptoms in each patient; median ranks were used to compare temporal sequencing of both individual features and major symptom domains.

Two hundred thirty unique cases (185 female) met study inclusion criteria. The most common features were seizures (60.4%), disorientation/confusion (42.6%), orofacial dyskinesias (39.1%), and mutism/staring (37.4%). Seizures, fever, and cognitive dysfunction were often the earliest features to emerge, but psychiatric features predominated and sequencing varied greatly between individuals.

Clinicians should consider anti-NMDAr encephalitis when new psychiatric symptoms are accompanied by a recent viral prodrome, seizures or unexplained fever, or when the quality of the psychiatric symptoms is unusual (e.g. non-verbal auditory hallucinations).

Our aim was to investigate patterns of change in public knowledge, attitudes, desire for social distance and reporting having contact with people with mental health problems in England during the Time to Change (TTC) programme to reduce stigma and discrimination 2009–2017.

Using data from an annual face-to-face survey of a nationally representative quota sample of adults, we evaluated longitudinal trends of the outcome measures with regression analyses and made assumptions on the basis of a simple random sample. We tested interactions between year and demographic subgroups.

There were improvements in all outcomes in 2017 compared with baseline measures (2008 or 2009). Reported in s.d. units [95% confidence interval (CI)], the improvement for knowledge was 0.17 (0.10–0.23); for attitudes 0.25 (0.18–0.31); and for social distance 0.29 (0.23–0.35). A higher likelihood of reporting contact was also associated with most recent survey year (odds ratio 1.47, 95% CI 1.27–1.71). Statistically significant interactions between year and region of England suggest greatest improvements in attitudes and intended behaviour in London, where both outcomes were significantly worse in the early years of the survey. However, for attitudes, this interaction was only significant among women. Other significant interactions suggest that attitudes improved most in the target age group (25–44).

The results provide support for the effectiveness of TTC across demographic groups. However, other societal changes may influence the results, such as the increasing prevalence of common mental disorder in young women.

Self-harm in young people is associated with later problems in social and emotional development. However, it is unknown whether self-harm in young women continues to be a marker of vulnerability on becoming a parent. This study prospectively describes the associations between pre-conception self-harm, maternal depressive symptoms and mother–infant bonding problems.

The Victorian Intergenerational Health Cohort Study (VIHCS) is a follow-up to the Victorian Adolescent Health Cohort Study (VAHCS) in Australia. Socio-demographic and health variables were assessed at 10 time-points (waves) from ages 14 to 35, including self-reported self-harm at waves 3–9. VIHCS enrolment began in 2006 (when participants were aged 28–29 years), by contacting VAHCS women every 6 months to identify pregnancies over a 7-year period. Perinatal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale during the third trimester, and 2 and 12 months postpartum. Mother–infant bonding problems were assessed with the Postpartum Bonding Questionnaire at 2 and 12 months postpartum.

Five hundred sixty-four pregnancies from 384 women were included. One in 10 women (9.7%) reported pre-conception self-harm. Women who reported self-harming in young adulthood (ages 20–29) reported higher levels of perinatal depressive symptoms and mother–infant bonding problems at all perinatal time points [perinatal depressive symptoms adjusted β = 5.40, 95% confidence interval (CI) 3.42–7.39; mother–infant bonding problems adjusted β = 7.51, 95% CI 3.09–11.92]. There was no evidence that self-harm in adolescence (ages 15–17) was associated with either perinatal outcome.

Self-harm during young adulthood may be an indicator of future vulnerability to perinatal mental health and mother–infant bonding problems.

Elevated levels of pro-inflammatory cytokines are consistently reported in schizophrenia (SZ) and bipolar-I disorder (BD), as well as among individuals who have been exposed to childhood trauma. However, higher levels of inflammatory markers in these disorders are yet to be investigated with respect to levels of exposure to different types of childhood trauma.

Participants were 68 cases with a diagnosis of schizophrenia/schizoaffective disorder (SZ), 69 cases with a diagnosis of psychotic BD and 72 healthy controls (HC). Serum levels of interleukin 6 (IL-6), tumour necrosis factor-α (TNF-α) and C-reactive protein (CRP) were quantified, and childhood trauma exposure was assessed with the Childhood Trauma Questionnaire.

The SZ group had significantly higher levels of IL-6, TNF-α and CRP when compared with the HC group (all p < 0.05, d = 0.41–0.63), as well as higher levels of TNF-α when compared with the BD group (p = 0.014, d = 0.50); there were no differences between the BD and HC groups for any markers. Exposure to sexual abuse was positively associated (standardised β = 0.326, t = 2.459, p = 0.018) with levels of CRP in the SZ group, but there were no significant associations between any form of trauma exposure and cytokine levels in the HC or BD groups.

These results contribute to the evidence for a chronic state of inflammation in SZ but not BD cases. Differential associations between trauma exposure and levels of pro-inflammatory cytokines across the diagnostic categories suggest that trauma may impact biological (stress and immune) systems differently in these patient groups.

Vulnerability to depression can be measured in different ways. We here examine how genetic risk factors are inter-related for lifetime major depression (MD), self-report current depressive symptoms and the personality trait Neuroticism.

We obtained data from three population-based adult twin samples (Virginia n = 4672, Australia #1 n = 3598 and Australia #2 n = 1878) to which we fitted a common factor model where risk for ‘broadly defined depression’ was indexed by (i) lifetime MD assessed at personal interview, (ii) depressive symptoms, and (iii) neuroticism. We examined the proportion of genetic risk for MD deriving from the common factor v. specific to MD in each sample and then analyzed them jointly. Structural equation modeling was conducted in Mx.

The best fit models in all samples included additive genetic and unique environmental effects. The proportion of genetic effects unique to lifetime MD and not shared with the broad depression common factor in the three samples were estimated as 77, 61, and 65%, respectively. A cross-sample mega-analysis model fit well and estimated that 65% of the genetic risk for MD was unique.

A large proportion of genetic risk factors for lifetime MD was not, in the samples studied, captured by a common factor for broadly defined depression utilizing MD and self-report measures of current depressive symptoms and Neuroticism. The genetic substrate for MD may reflect neurobiological processes underlying the episodic nature of its cognitive, motor and neurovegetative manifestations, which are not well indexed by current depressive symptom and neuroticism.

A wealth of clinical studies have identified objective biomarkers, which separate schizophrenia patients from healthy controls on a group level, but current diagnostic systems solely include clinical symptoms. In this study, we investigate if machine learning algorithms on multimodal data can serve as a framework for clinical translation.

Forty-six antipsychotic-naïve, first-episode schizophrenia patients and 58 controls underwent neurocognitive tests, electrophysiology, and magnetic resonance imaging (MRI). Patients underwent clinical assessments before and after 6 weeks of antipsychotic monotherapy with amisulpride. Nine configurations of different supervised machine learning algorithms were applied to first estimate the unimodal diagnostic accuracy, and next to estimate the multimodal diagnostic accuracy. Finally, we explored the predictability of symptom remission.

Cognitive data significantly classified patients from controls (accuracies = 60–69%; p values = 0.0001–0.009). Accuracies of electrophysiology, structural MRI, and diffusion tensor imaging did not exceed chance level. Multimodal analyses with cognition plus any combination of one or more of the remaining three modalities did not outperform cognition alone. None of the modalities predicted symptom remission.

In this multivariate and multimodal study in antipsychotic-naïve patients, only cognition significantly discriminated patients from controls, and no modality appeared to predict short-term symptom remission. Overall, these findings add to the increasing call for cognition to be included in the definition of schizophrenia. To bring about the full potential of machine learning algorithms in first-episode, antipsychotic-naïve schizophrenia patients, careful a priori variable selection based on independent data as well as inclusion of other modalities may be required.

The 2004 tsunami, the civil conflict until 2009 and the youth insurrection in the late 1980s in Sri Lanka resulted in many persons being classified as ‘missing’ as they disappeared and were unaccounted for. Our aim was to compare the prevalence of major depressive disorder (MDD) and prolonged grief disorder (PGD) in families of disappeared individuals, who eventually received the mortal remains and those who did not.

An ethically approved cross sectional study was conducted in a purposively selected sample after informed consent. Information on the circumstances of the family member going missing was gathered. Culturally adapted versions of the General Health Questionnaire and the Beck Depression Scale were administered. Those who screened positive were assessed by a psychiatrist on Diagnostic and Statistical Manual of Mental Disorders-5 criteria to arrive at a diagnosis.

Of 391 cases of disappearances studied, MDD (17.5% v. 6%) and PGD (22% v. 7%) were significantly higher in those who did not eventually receive the mortal remains of the disappeared person. Among those who did not receive the mortal remains, being unsure whether the disappeared person was dead or alive was highly predictive of MDD and PGD. Mothers and wives, older family members and those with a family history of mental illness were more vulnerable.

Family members of missing individuals unsure whether their loved one was alive or dead have higher psychological morbidity in the form of MDD and PGD.

Studies investigating the underlying mechanisms of hallucinations in patients with schizophrenia suggest that an imbalance in top-down expectations v. bottom-up processing underlies these errors in perception. This study evaluates this hypothesis by testing if individuals drawn from the general population who have had auditory hallucinations (AH) have more misperceptions in auditory language perception than those who have never hallucinated.

We used an online survey to determine the presence of hallucinations. Participants filled out the Questionnaire for Psychotic Experiences and participated in an auditory verbal recognition task to assess both correct perceptions (hits) and misperceptions (false alarms). A hearing test was performed to screen for hearing problems.

A total of 5115 individuals from the general Dutch population participated in this study. Participants who reported AH in the week preceding the test had a higher false alarm rate in their auditory perception compared with those without such (recent) experiences. The more recent the AH were experienced, the more mistakes participants made. While the presence of verbal AH (AVH) was predictive for false alarm rate in auditory language perception, the presence of non-verbal or visual hallucinations were not.

The presence of AVH predicted false alarm rate in auditory language perception, whereas the presence of non-verbal auditory or visual hallucinations was not, suggesting that enhanced top-down processing does not transfer across modalities. More false alarms were observed in participants who reported more recent AVHs. This is in line with models of enhanced influence of top-down expectations in persons who hallucinate.

Individuals with bipolar disorder (BD) show aberrant brain activation patterns during reward and loss anticipation. We examined for the first time longitudinal changes in brain activation during win and loss anticipation to identify trait markers of aberrant anticipatory processing in BD.

Thirty-four euthymic and depressed individuals with BD-I and 17 healthy controls (HC) were scanned using functional magnetic resonance imaging twice 6 months apart during a reward task.

HC, but not individuals with BD, showed longitudinal reductions in the right lateral occipital cortex (RLOC) activation during processing of cues predicting possible money loss (p-corrected <0.05). This result was not affected by psychotropic medication, mood state or the changes in depression/mania severity between the two scans in BD. Elevated symptoms of subthreshold hypo/mania at baseline predicted more aberrant longitudinal patterns of RLOC activation explaining 12.5% of variance in individuals with BD.

Increased activation in occipital cortex during negative outcome anticipation may be related to elevated negative emotional arousal during anticipatory cue processing. One interpretation is that, unlike HC, individuals with BD were not able to learn at baseline that monetary losses were smaller than monetary gains and were not able to reduce emotional arousal for negative cues 6 months later. Future research in BD should examine how modulating occipital cortical activation affects learning from experience in individuals with BD.

Interoceptive deficits (ID) have been associated with non-suicidal self-injury (NSSI) and suicidal behavior in multiple studies. Many of these studies are limited in scope, and have not fully examined possible mechanisms explaining how ID affect suicidal behavior.

This study assesses how self-reported ID relate to suicide ideation and attempts in six distinct and geographically diverse samples of adults (n = 2706) and one sample of adolescents (n = 436). Participants responded to a variety of self-report questionnaires and interviews.

Contrary to our hypothesis, self-reported ID were only associated with suicidal ideation in two samples, one of which was the adolescent sample. Largely consistent with our predictions, self-reported ID exhibited an indirect effect on suicide attempts through versatility of NSSI in four of the five adult samples tested. Finally, the indirect effects of self-reported ID on suicide attempts through NSSI versatility did not act indirectly through behaviorally assessed pain tolerance.

We found that, in adults, self-reported ID are not associated with suicidal ideation, but are connected with a history of suicide attempts, through an indirect effect via NSSI. Our findings also indicate that the mechanism of action leading from self-reported ID to suicidal behavior may differ between adolescents and adults, and relate to suicidal behavior independent of pain tolerance. Clinical implications and future directions are discussed.

The Research Domain Criteria initiative was launched by the US National Institute of Mental Health to establish a multi-level framework for understanding psychological constructs relevant to human psychiatric disorders, and identified ‘effort valuation/willingness to work’ as a clinically useful construct worthy of further study. This construct encompasses the processes by which the cost(s) of obtaining an outcome are calculated, and the tendency to overcome response costs to obtain a reinforcer. The current study aims to examine effort valuation as a correlate of psychopathology in children and adults, and the moderating effects of sex on this relationship.

Participants were 1215 children aged 6–12 and their parents (n = 1044). All participants completed the Effort Expenditure for Rewards Task as a measure of effort expenditure. Child psychopathology was measured via the Child Behavior Checklist, while adult psychopathology was measured via the Adult Self Report. Additionally, the Social Adjustment Inventory for Children and Adolescents and Injury Behavior Checklist were used to examine child social impairments/problem behaviors.

In children, significant interactions between reward sensitivity and sex were observed in association with anxiety and thought problems, specifically at low reward sensitivity levels. In adults, main effects of effort expenditure were seen in drug and alcohol abuse, where higher effort was associated with higher degrees of abuse.

These results establish effort valuation as a relevant psychological construct for understanding psychopathology, but with different profiles of associated psychopathology across sex in children and adults.