Healthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing.

In a two-step functional magnetic resonance imaging (fMRI) investigation, we first evaluated whether positive and negative monetary outcomes were differentially processed by rMD+ individuals compared to healthy first-degree relatives of control probands (rMD−). Second, in a double-blinded placebo-controlled randomized trial we investigated whether a 4-week intervention with the selective serotonergic reuptake inhibitor (SSRI) escitalopram had a normalizing effect on behavior and brain responses of the rMD+ individuals.

Negative outcomes increased the probability of risk-averse choices in the subsequent trial in rMD+ but not in rMD− individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response when subjects missed a large reward after a low-risk choice in the rMD+ group compared to the rMD− group. The enhanced orbitofrontal response to negative outcomes was reversed following escitalopram intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD− group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the abnormal neural responses were not accounted for by changes in gray matter density in rMD+ individuals.

Our study in first-degree relatives of depressive patients showed abnormal brain responses to aversive and rewarding outcomes in regions known to be dysfunctional in depression. We further confirmed the reversal of these aberrant activations with SSRI intervention.

Dropout from psychotherapy for borderline personality disorder (BPD) is a notorious problem. We investigated whether treatment, treatment format, treatment setting, substance use exclusion criteria, proportion males, mean age, country, and other variables influenced dropout.

From Pubmed, Embase, Cochrane, Psycinfo and other sources, 111 studies (159 treatment arms, N = 9100) of psychotherapy for non-forensic adult patients with BPD were included. Dropout per quarter during one year of treatment was analyzed on participant level with multilevel survival analysis, to deal with multiple predictors, nonconstant dropout chance over time, and censored data. Multiple imputation was used to estimate quarter of drop-out if unreported. Sensitivity analyses were done by excluding DBT-arms with deviating push-out rules.

Dropout was highest in the first quarter of treatment. Schema therapy had the lowest dropout overall, and mentalization-based treatment in the first two quarters. Community treatment by experts had the highest dropout. Moreover, individual therapy had lowest dropout, group therapy highest, with combined formats in-between. Other variables such as age or substance-use exclusion criteria were not associated with dropout.

The findings do not support claims that all treatments are equal, and indicate that efforts to reduce dropout should focus on early stages of treatment and on group treatment.

DSM-5 introduced a fundamental revision of the category of somatoform disorders, which resulted in the new somatic symptom disorder (SSD) and related disorders. However, prognostic validity of SSD remains unclear, while other classification proposals, such as bodily distress disorder (BDD) or polysymptomatic distress disorder (PSDD), might be promising alternatives for the new ICD-11. Therefore, the comparison of the different approaches concerning long-term prognosis of disorder-relevant factors is of special interest.

In a longitudinal design (baseline, 1-year, and 4-year follow-up), the three proposals (SSD, BDD, PSDD) were compared in an age-representative sample of the German general population (N = 321). To this end, the baseline sample was divided into three independent pairs of groups (with/without SSD, with/without BDD, with/without PSDD). It was tested how well each approach differentiated with regard to medium- and long-term healthcare utilization, number of symptoms, and impairment.

Criteria for BDD distinguished best with regard to future healthcare utilization resulting in a large-sized effect (f = 0.44) for the difference between persons with and without BDD, while SSD and PSDD revealed only medium-sized effects (f = 0.28 and f = 0.32) between subjects with and without diagnosis. The three proposals distinguished equally well with regard to future subjective impairment (between f = 0.39 and f = 0.41) and the number of reported symptoms (between f = 0.77 and f = 0.83).

In accordance with our data regarding prognostic validity, the current draft of the WHO group is based on the BDD proposal. However, existing limitations and weaknesses of the present proposal for the ICD-11 are further discussed.

In the past 10 years an increasing number of randomised trials have examined the effects of transdiagnostic treatments of patients with depression or anxiety. We conducted the first comprehensive meta-analysis of the outcomes of this emerging field.

We used the searches in PubMed, PsychINFO, Embase and the Cochrane library of an existing database of randomised trials of psychological interventions for depression to identify studies comparing a transdiagnostic treatment of patients with depression or anxiety with a control group (deadline 1 January 2022). We conducted random-effects meta-analyses and examined the effects on depression and anxiety at the short and longer term.

We included 45 randomised controlled trials with 51 comparisons between a psychotherapy and a control group and 5530 participants. Thirty-five (78%) studies were conducted in the last 10 years. The overall effect size was g = 0.54 (95% CI 0.40–0.69; NNT = 5.87), with high heterogeneity (I2 = 78; 95% CI 71–83), and a broad PI (−0.31–1.39). The effects remained significant in a series of sensitivity analyses, including exclusion of outliers, adjustment for publication bias, for studies with low risk of bias, and in multilevel analyses. The results were comparable for depression and anxiety separately. At 6 months after randomisation the main effects were still significant, but not at 12 months, although the number of studies was small.

Transdiagnostic treatments of patients with depression or anxiety are increasingly examined and are probably effective at the short term.

The purpose of this study was to use selected Cambridge Neuropsychological Test Automated Battery (CANTAB) tests to examine the dimensional structure of cognitive dysfunction in first episode of psychosis (FEP) patients compared with cognition in healthy subjects.

A total of 109 FEP patients and 96 healthy volunteers were administered eight CANTAB tests of cognitive function. Principal components analysis (PCA) was used to estimate dimensionality within the test results. The dimensions identified by the PCA were assumed to reflect underlying cognitive traits. The plausibility of latent factor models was estimated using confirmatory factor analysis (CFA). Multi-group CFA (MGCFA) was used to test for measurement invariance of factors between groups. The nature and severity of cognitive deficits amongst patients as opposed to controls were evaluated using a general linear model.

Amongst subjects PCA identified two underlying cognitive traits: (i) a broad cognitive domain; (ii) attention/memory and executive function domains. Corresponding CFA models were built that fitted data well for both FEP patients and healthy volunteers. As in MGCFA latent variables appeared differently defined in patient and control groups, differences had to be ascribed using subtest scores rather than their aggregates. At subtest score level the patients performed significantly worse than healthy subjects in all comparisons (p < 0.001).

Results of this study demonstrate that the structure of underlying cognitive abilities as measured by a selection of CANTAB tests is not the same for healthy individuals and FEP patients, with patients displaying widespread cognitive impairment.

Processing emotional facial expressions is of interest in eating disorders (EDs) as impairments in recognizing and understanding social cues might underlie the interpersonal difficulties experienced by these patients. Disgust and anger are of particular theoretical and clinical interest. The current study investigated the neural response to facial expressions of anger and disgust in bulimia nervosa (BN).

Participants were 12 medication-free women with BN in an acute episode (mean age 24 years), and 16 age-, gender- and IQ-matched healthy volunteers (HVs). Functional magnetic resonance imaging (fMRI) was used to examine neural responses to angry and disgusted facial expressions.

Compared with HVs, patients with BN had a decreased neural response in the precuneus to facial expressions of both anger and disgust and a decreased neural response to angry facial expressions in the right amygdala.

The neural response to emotional facial expressions in BN differs from that found in HVs. The precuneus response may be consistent with the application of mentalization theory to EDs, and the amygdala response with relevant ED theory. The findings are preliminary, but novel, and require replication in a larger sample.

Genetic and environmental factors are important in the etiology of substance use. However, little is known about the stability of these factors across development. We aimed to answer three crucial questions about this etiology that have never been addressed in a single study: (1) Is there a general vulnerability to substance consumption from early adolescence to young adulthood? (2) If so, do the genetic and environmental influences on this vulnerability change across development? (3) Do these developmental processes differ in males and females?

Subjects included 1480 twin pairs from the Swedish Twin Study of Child and Adolescent Development who have been followed since 1994. Prospective, self-reported regular smoking, alcohol intoxication and illicit drug use were assessed at ages 13–14, 16–17 and 19–20 years. Structural modeling was performed with the program Mx.

An underlying common factor accounted for the association between smoking, alcohol and illicit drug consumption for the three age groups. Common genetic and shared environmental effects showed substantial continuity. In general, as participants aged, the influence of the shared environment decreased, and genetic effects became more substance specific in their effect.

The current report answers three important questions in the etiology of substance use. The genetic and environmental risk for substance consumption is partly mediated through a common factor and is partly substance specific. Developmentally, evidence was strongest for stability of common genetic effects, with less evidence for genetic innovation. These processes seem to be the same in males and females.

Response to antidepressant medication is higher in comparator versus placebo-controlled randomized controlled trials (RCTs). Patient expectancy is an important influence on clinical outcome in the treatment of depression and may explain this finding. The results are reported from a pilot RCT studying expectancy and depression outcome in placebo-controlled versus comparator treatment conditions.

Out-patients aged 18–65 years with major depressive disorder (MDD) were enrolled in this 8-week RCT. Subjects were randomized to placebo-controlled (escitalopram or placebo) or comparator (escitalopram or citalopram) administration of antidepressant medication. Subjects reported their expected likelihood and magnitude of depression improvement before and after randomization using questions from the Credibility and Expectancy Scale (CES). A regressed change model of post-randomization expectancy of improvement was fit to the data to determine whether subjects in the comparator group reported greater expectancies of improvement than subjects in the placebo-controlled group.

Twenty subjects with mean age 56.5±11.7 years, a baseline Hamilton Depression Rating Scale (HAMD) score of 24.2±5.3, baseline Beck Depression Inventory (BDI) score of 24.9±6.4 and baseline Clinical Global Impressions (CGI) – Severity score of 4.0±0.3 were enrolled in the study. Adjusting for other factors, the effect of group assignment on expected magnitude of improvement was significant and large (effect size 1.5). No group differences in expected likelihood of improvement were found.

Randomization to comparator versus placebo-controlled administration of antidepressant medication produced greater expectancies of how much patients would improve during the trial. This expectancy difference may explain the higher response and remission rates that are observed in comparator versus placebo-controlled trials.

Rates of the metabolic syndrome in people with psychotic illness are high. Emerging evidence suggests that cannabis use may have a positive impact on cardiometabolic risk factors in the general population, but little is known about its impact for people with psychotic illness. Our aim was to investigate whether the rate of the metabolic syndrome in people with psychotic illness was associated with frequency of cannabis use.

The 2010 Australian psychosis survey used a two-phase design to randomly select a nationally representative sample of 1825 adults with psychotic illness for interview and physical assessment. This study is based on 1813 participants who provided data on cannabis use. Multiple logistic regression was used to model the influence of frequency of cannabis use on the metabolic syndrome, adjusting for potential covariates including antipsychotic medication use, smoking, alcohol use and cognitive function.

One-third (33.0%) of participants had used cannabis in the past year. The proportion of non-users, occasional users and frequent users with the metabolic syndrome was 63.0, 51.7 and 43.5%, respectively (p < 0.001). In unadjusted analyses, both occasional use and frequent cannabis use were associated with significantly lower odds of the metabolic syndrome. In the adjusted analyses, the association between the metabolic syndrome and frequent cannabis use remained significant [odds ratio = 0.56, 95% confidence interval (CI) 0.39–0.80], but not the association with occasional use (odds ratio = 0.75, 95% CI 0.49–1.13).

While cannabis use may be detrimental for mental health, these data suggest that it may also have a cardiometabolic protective effect. Further investigation is required to understand the mechanism underlying this paradoxical finding.

Autism spectrum disorder (ASD) and obsessive–compulsive disorder (OCD) are neurodevelopmental disorders with considerable overlap in terms of their defining symptoms of compulsivity/repetitive behaviour. Little is known about the extent to which ASD and OCD have common versus distinct neural correlates of compulsivity. Previous research points to potentially common dysfunction in frontostriatal connectivity, but direct comparisons in one study are lacking. Here, we assessed frontostriatal resting-state functional connectivity in youth with ASD or OCD, and healthy controls. In addition, we applied a cross-disorder approach to examine whether repetitive behaviour across ASD and OCD has common neural substrates.

A sample of 78 children and adolescents aged 8–16 years was used (ASD n = 24; OCD n = 25; healthy controls n = 29), originating from the multicentre study COMPULS. We tested whether diagnostic group, repetitive behaviour (measured with the Repetitive Behavior Scale-Revised) or their interaction was associated with resting-state functional connectivity of striatal seed regions.

No diagnosis-specific differences were detected. The cross-disorder analysis, on the other hand, showed that increased functional connectivity between the left nucleus accumbens (NAcc) and a cluster in the right premotor cortex/middle frontal gyrus was related to more severe symptoms of repetitive behaviour.

We demonstrate the fruitfulness of applying a cross-disorder approach to investigate the neural underpinnings of compulsivity/repetitive behaviour, by revealing a shared alteration in functional connectivity in ASD and OCD. We argue that this alteration might reflect aberrant reward or motivational processing of the NAcc with excessive connectivity to the premotor cortex implementing learned action patterns.

Do genetic risk profiles for drug use disorder (DUD), major depression (MD), and attention-deficit hyperactivity disorder (ADHD) differ substantially as a function of sex, age at onset (AAO), recurrence, mode of ascertainment, and treatment?

Family genetic risk scores (FGRS) for MD, anxiety disorders, bipolar disorder, schizophrenia, alcohol use disorder, DUD, ADHD, and autism-spectrum disorder were calculated from 1st–5th degree relatives in the Swedish population born 1932–1995 (n = 5 829 952). Profiles of these FGRS were obtained and compared across various subgroups of DUD, MD, and ADHD cases.

Differences in FGRS profiles for DUD, MD, and ADHD by sex were modest, but they varied substantially by AAO, recurrence, ascertainment, and treatment with scores typically higher in cases with greater severity (e.g. early AAO, high recurrence, ascertainment in high intensity clinical settings, and treatment). However, severity was not always related to purer genetic profiles, as genetic risk for many disorders often increased together. However, some results, such as by mode of ascertainment from different Swedish registries, produced qualitative differences in FGRS profiles.

Differences in FGRS profiles for DUD, MD, and ADHD varied substantially by AAO, recurrence, ascertainment, and treatment. Replication of psychiatric studies, particularly those examining genetic factors, may be difficult unless cases are matched not only by diagnosis but by important clinical characteristics. Genetic correlations between psychiatric disorders could arise through one disorder impacting on the patterns of ascertainment for the other, rather than from the direct effects of shared genetic liabilities.

It is widely accepted that borderline personality disorder (BPD) is associated with significant impairments in mentalization and theory of mind (ToM) which are considered as closely related concepts by many authors particularly in psychoanalytical circles. However, for understanding interpersonal difficulties in personality disorders, it is important to distinguish neuro-social cognitive impairment from the abnormal meta-social-cognitive style of patients.

The current systematic review aimed to conduct separate meta-analyses of ‘mentalization’ [reflective functioning (RF] and different aspects of ToM in BPD. A literature search was conducted to locate relevant articles published between January 1990 to July 2021. Random-effect meta-analyses were conducted in 34 studies involving 1448 individuals with BPD and 2006 healthy controls.

A very large impairment in RF was evident in BPD [d = 1.68, confidence interval (CI) = 1.17–2.19]. In contrast, ToM impairment was modest (d = 0.36, CI = 0.24–0.48). BPD patients underperformed healthy controls in ToM-reasoning (d = 0.44, CI = 0.32–0.56) but not ToM-decoding. Increased HyperToM (d = 0.60, CI = 0.41–0.79) and faux pas recognition (d = 0.62, CI = 0.35–0.90) errors in BPD compared to healthy controls were most robust ToM findings in this meta-analysis.

BPD is characterized by very severe deficits in RF and modest and selective abnormalities in ToM. Interpersonal problems and difficulties in processing social information in BPD can be best explained by patients' maldaptive meta-social cognitive style and top-down effects of these abnormalities rather than having a primary neuro-social cognitive deficit.