Since its introduction in the diagnostic manuals DSM-5 and ICD-11, the construct of personality functioning has gained increasing attention. However, it remains unclear which factors might predict improvement in personality functioning.

We examined a sample of 648 completed psychodynamic psychotherapies conducted by 172 therapists at the Heidelberg Institute for Psychotherapy. A machine learning approach was used to filter for variables that are relevant for the prediction of the improvement of personality functioning from a broad data set of variables collected at the beginning of each psychodynamic psychotherapy.

On average, we found an improvement of 0.24 (SD = 0.48) in the OPD-SQ. This corresponds to a medium effect in the improvement of personality functioning. Patients with initially high impairment experienced particularly large improvements. Overall, we found a large number of variables that proved to be predictive for the improvement of personality functioning. Limitations in social activity due to physical and emotional problems proved to be one of the most important predictors of improvement. Most of the effect sizes were small.

Overall, the improvement in personality functioning during psychotherapy is determined more by the sum of a large number of small effects than by individual variables. In particular, variables that capture social areas of life proved to be robust predictors.

There is emerging evidence of heterogeneity within treatment-resistance schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and a smaller group becoming treatment-resistant after an initial response period. It has been suggested that these groups have different aetiologies. Few studies have investigated socio-demographic and clinical differences between early and late onset of TRS.

This study aims to investigate socio-demographic and clinical correlates of late-onset of TRS.

Using data from the electronic health records of the South London and Maudsley, we identified a cohort of people with TRS. Regression analyses were conducted to identify correlates of the length of treatment to TRS. Analysed predictors include gender, age, ethnicity, positive symptoms severity, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics.

We observed a continuum of the length of treatment until TRS presentation. Having severe hallucinations and delusions at treatment start was associated shorter duration of treatment until the presentation of TRS.

Our findings do not support a clear cut categorisation between early and late TRS, based on length of treatment until treatment resistance onset. More severe positive symptoms predict earlier onset of treatment resistance.

DFdF, GKS, EF and IR have received research funding from Janssen and H. Lundbeck A/S. RDH and HS have received research funding from Roche, Pfizer, Janssen and Lundbeck. SES is employed on a grant held by Cardiff University from Takeda Pharmaceutical Comp

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.

We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.

Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.

Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.

We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.

The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.

From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.

The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

Cannabis can induce transient psychotic symptoms, but not all users experience these adverse effects. We compared the neural response to Δ9-tetrahydrocannabinol (THC) in healthy volunteers in whom the drug did or did not induce acute psychotic symptoms.

In a double-blind, placebo-controlled, pseudorandomized design, 21 healthy men with minimal experience of cannabis were given either 10 mg THC or placebo, orally. Behavioural and functional magnetic resonance imaging measures were then recorded whilst they performed a go/no-go task.

The sample was subdivided on the basis of the Positive and Negative Syndrome Scale positive score following administration of THC into transiently psychotic (TP; n = 11) and non-psychotic (NP; n = 10) groups. During the THC condition, TP subjects made more frequent inhibition errors than the NP group and showed differential activation relative to the NP group in the left parahippocampal gyrus, the left and right middle temporal gyri and in the right cerebellum. In these regions, THC had opposite effects on activation relative to placebo in the two groups. The TP group also showed less activation than the NP group in the right middle temporal gyrus and cerebellum, independent of the effects of THC.

In this first demonstration of inter-subject variability in sensitivity to the psychotogenic effects of THC, we found that the presence of acute psychotic symptoms was associated with a differential effect of THC on activation in the ventral and medial temporal cortex and cerebellum, suggesting that these regions mediate the effects of the drug on psychotic symptoms.