Intellectual deficits are commonly found in schizophrenia patients. These intellectual deficits have been found to be heritable. However, whether the intellectual deficits change over time and, if so, whether the change is related with an increased genetic risk for the disease are not known.

We investigated change of intelligence quotient (IQ) in a twin sample of chronically ill schizophrenia patients, the discordant co-twins and healthy controls during a follow-up period of 5 years. A total of 52 twins completed two IQ assessments: nine patients [three monozygotic (MZ) and six dizygotic (DZ)], 10 unaffected co-twins (three MZ and seven DZ) and 33 healthy control twins (21 MZ and 12 DZ).

A significant interaction effect over time was found between IQ measurement and illness (F=4.22, df=1, p<0.05), indicating that change in IQ over time is significantly different between the groups. A stable course in IQ over time was found in the patients with schizophrenia (mean IQ from 109.78 at baseline to 108.44 at follow-up) relative to both the healthy control twins who showed a small increase (from 114.61 at baseline to 119.18 at follow-up) (t=2.06, p<0.05) and the unaffected co-twins (from 111.60 to 117.60, t=−2.32, p<0.05). IQ change in the unaffected co-twins of schizophrenia patients was comparable with that in healthy control twins (t=−0.49, p=0.63).

Patients with schizophrenia in the chronic phase of the disease, but not the discordant co-twins, show a lack of increase in IQ, which is probably due to environmental (non-genetic) factors related to the disease.

Electroconvulsive therapy (ECT) is the most acutely effective treatment for severe treatment-resistant depression. However, there are concerns about its cognitive side-effects and we cannot yet confidently predict who will experience these. Telomeres are DNA-protein complexes that maintain genomic integrity. In somatic cells, telomeres shorten with each cell division. Telomere length (TL) can thus provide a measure of ‘biological’ aging. TL appears to be reduced in depression, though results are mixed. We sought to test the following hypotheses: (1) that TL would be shorter in patients with depression compared to controls; (2) that TL would be a predictor of response to ECT; and (3) that shorter TL would predict cognitive side-effects following ECT.

We assessed TL in whole blood DNA collected from severely depressed patients (n = 100) recruited as part of the EFFECT-Dep Trial and healthy controls (n = 80) using quantitative real-time polymerase chain reaction. Mood and selected cognitive measures, including global cognition, re-orientation time, and autobiographical memory, were obtained pre-/post-ECT and from controls.

Our results indicate that TL does not differ between patients with depression compared to controls. TL itself was not associated with mood ratings and did not predict the therapeutic response to ECT. Furthermore, shorter baseline TL is not a predictor of cognitive side-effects post-ECT.

Overall, TL assessed by PCR does not represent a useful biomarker for predicting the therapeutic outcomes or risk for selected cognitive deficits following ECT.

Negative bias and aberrant neural processing of emotional faces are trait-marks of depression but findings in healthy high-risk groups are conflicting.

Healthy middle-aged dizygotic twins (N = 42) underwent functional magnetic resonance imaging (fMRI): 22 twins had a co-twin history of depression (high-risk) and 20 were without co-twin history of depression (low-risk). During fMRI, participants viewed fearful and happy faces while performing a gender discrimination task. After the scan, they were given a faces dot-probe task, a facial expression recognition task and questionnaires assessing mood, personality traits and coping.

Unexpectedly, high-risk twins showed reduced fear vigilance and lower recognition of fear and happiness relative to low-risk twins. During face processing in the scanner, high-risk twins displayed distinct negative functional coupling between the amygdala and ventral prefrontal cortex and pregenual anterior cingulate. This was accompanied by greater fear-specific fronto-temporal response and reduced fronto-occipital response to all emotional faces relative to baseline. The risk groups showed no differences in mood, subjective state or coping.

Less susceptibility to fearful faces and negative cortico-limbic coupling during emotional face processing may reflect neurocognitive compensatory mechanisms in middle-aged dizygotic twins who remain healthy despite their familial risk of depression.

Evidence suggests that environmental factors not only increase psychosis liability but also influence the prognosis and outcomes of psychotic disorders. We investigated temporal and cross-sectional associations of a weighted score of cumulative environmental liability for schizophrenia – the exposome score for schizophrenia (ES-SCZ) – with functioning in first-episode psychosis (FEP).

Data were derived from the baseline and 1-month assessments of the Athens FEP Research Study that enrolled 225 individuals with FEP. The Global Assessment of Functioning (GAF) and the Personal and Social Performance Scale (PSP) were used to measure social, occupational, and psychological functioning. The ES-SCZ was calculated based on the previously validated method.

ES-SCZ was associated with the total scores of GAF and PSP at baseline and 1-month assessments. These findings remained significant when accounting for several associated alternative explanatory variables, including other environmental factors (obstetric complications, migration, ethnic minority), clinical characteristics (duration of untreated psychosis, symptom severity, previous antipsychotic use), and family history of psychosis, demonstrating that the association between ES-SCZ and functioning is over and above other risk factors and cannot be explained by symptom severity alone. Functioning improved from baseline to 1-month assessment, but no significant ES-SCZ-by-time interaction was found on functioning, indicating that functioning changes were not contingent on ES-SCZ.

Our findings suggest that rather than a predictor of functional improvement, ES-SCZ represents a stable severity indicator that captures poor functioning in early psychosis. Environmental risk loading for schizophrenia (ES-SCZ) can be beneficial for clinical characterization and incorporated into transdiagnostic staging models.

There is considerable debate surrounding the effective measurement of DSM-IV symptoms used to assess manic disorders in epidemiological samples.

Using two nationally representative datasets, the National Epidemiological Survey of Alcohol and Related Conditions (NESARC, n=43 093 at wave 1, n=34 653 at 3-year follow-up) and the National Comorbidity Survey – Replication (NCS-R, n=9282), we examined the psychometric properties of symptoms used to assess DSM-IV mania. The predictive utility of the mania factor score was tested using the 3-year follow-up data in NESARC.

Criterion B symptoms were unidimensional (single factor) in both samples. The symptoms assessing flight of ideas, distractibility and increased goal-directed activities had high factor loadings (0.70–0.93) with moderate rates of endorsement, thus providing good discrimination between individuals with and without mania. The symptom assessing grandiosity performed less well in both samples. The quantitative mania factor score was a good predictor of more severe disorders at the 3-year follow-up in the NESARC sample, even after controlling for a past history of DSM-IV diagnosis of manic disorder.

These analyses suggest that questions based on some DSM symptoms effectively discriminate between individuals at high and low liability to mania, but others do not. A quantitative mania factor score may aid in predicting recurrence for patients with a history of mania. Methods for assessing mania using structured interviews in the absence of clinical assessment require further refinement.

A dominant idea is that impaired capacities for theory of mind (ToM) are the reasons for impairments in social functioning in several conditions, including autism and schizophrenia. In this paper, we present empirical evidence that challenges this influential assumption.

We conducted three studies examining the association between ToM and social functioning in participants diagnosed with a non-affective psychotic disorder and healthy individuals. We used both the experience sampling method, a structured diary technique collecting information in daily-life, and a standardised questionnaire to assess social functioning. Analysed data are part of Wave 1 and Wave 3 of the Genetic Risk and Outcome of Psychosis (GROUP) study.

Results were highly consistent across studies and showed no significant association between the two constructs.

These findings question the leading assumption that social cognition is a prerequisite for social functioning, but rather suggest that social cognition is possibly a result of basic social interactive capacities.

Subthreshold depression (sD) negatively impacts well-being and psychosocial function and is more prevalent compared with major depressive disorder (MDD). However, as adults with sD are less likely to seek face-to-face intervention, internet-based cognitive-behavioral therapy (ICBT) may overcome barriers of accessibility to psychotherapy. Although several trials explored the efficacy of ICBT for sD, the results remain inconsistent. This study evaluated whether ICBT is effective in reducing depressive symptoms among Chinese adults with sD.

A randomized controlled trial was performed. The participants were randomly assigned to 5 weeks of ICBT, group-based face-to-face cognitive-behavioral therapy (CBT), or a waiting list (WL). Assessments were conducted at baseline, post-intervention and at a 6-month follow-up. The primary outcome measured depressive symptoms using the Center for Epidemiological Studies Depression Scale (CES-D). Outcomes were analyzed using a mixed-effects model to assess the effects of ICBT.

ICBT participants reported greater reductions on all the outcomes compared to the WL group at post-intervention. The ICBT group showed larger improvement on the Patient Health Questionnaire-9 (PHQ-9) at post-intervention (d = 0.12) and at follow-up (d = 0.10), and with CES-D at post-intervention (d = 0.06), compared to the CBT group.

ICBT is effective in reducing depressive symptoms among Chinese adults with sD, and improvements in outcomes were sustained at a 6-month follow-up. Considering the low rates of face-to-face psychotherapy, our findings highlight the considerable potential and implications for the Chinese government to promote the use of ICBT for sD in China.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is involved in the stress response and may play a key role in mood disorders, but no information is available on PACAP for the human brain in relation to mood disorders.

PACAP-peptide levels were determined in a major stress-response site, the hypothalamic paraventricular nucleus (PVN), of people with major depressive disorder (MDD), bipolar disorder (BD) and of a unique cohort of Alzheimer's disease (AD) patients with and without depression, all with matched controls. The expression of PACAP-(Adcyap1mRNA) and PACAP-receptors was determined in the MDD and BD patients by qPCR in presumed target sites of PACAP in stress-related disorders, the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC).

PACAP cell bodies and/or fibres were localised throughout the hypothalamus with differences between immunocytochemistry and in situ hybridisation. In the controls, PACAP-immunoreactivity-(ir) in the PVN was higher in women than in men. PVN-PACAP-ir was higher in male BD compared to the matched male controls. In all AD patients, the PVN-PACAP-ir was lower compared to the controls, but higher in AD depressed patients compared to those without depression. There was a significant positive correlation between the Cornell depression score and PVN-PACAP-ir in all AD patients combined. In the ACC and DLPFC, alterations in mRNA expression of PACAP and its receptors were associated with mood disorders in a differential way depending on the type of mood disorder, suicide, and psychotic features.

The results support the possibility that PACAP plays a role in mood disorder pathophysiology.

Decreased white matter (WM) integrity in patients with psychotic disorder has been a consistent finding in diffusion tensor imaging (DTI) studies. However, the contribution of environmental risk factors to these WM alterations is rarely investigated. The current study examines whether individuals with (increased risk for) psychotic disorder will show increased WM integrity change over time with increasing levels of childhood trauma and cannabis exposure.

DTI scans were obtained from 85 patients with a psychotic disorder, 93 non-psychotic siblings and 80 healthy controls, of which 60% were rescanned 3 years later. In a whole-brain voxel-based analysis, associations between change in fractional anisotropy (ΔFA) and environmental exposures as well as interactions between group and environmental exposure in the model of FA and ΔFA were investigated. Analyses were adjusted for a priori hypothesized confounding variables: age, sex, and level of education.

At baseline, no significant associations were found between FA and both environmental risk factors. At follow-up as well as over a 3-year interval, significant interactions between group and, respectively, cannabis exposure and childhood trauma exposure in the model of FA and ΔFA were found. Patients showed more FA decrease over time compared with both controls and siblings when exposed to higher levels of cannabis or childhood trauma.

Higher levels of cannabis or childhood trauma may compromise connectivity over the course of the illness in patients, but not in individuals at low or higher than average genetic risk for psychotic disorder, suggesting interactions between the environment and illness-related factors.

Multivariable risk algorithms (MVRP) predicting the personal risk of depression will form an important component of personalized preventive interventions. However, it is unknown whether providing personalized depression risk will lead to unintended psychological harms. The objectives of this study were to evaluate the impact of providing personalized depression risk on non-specific psychological distress and functional impairment over 12 months.

A mixed-methods randomized controlled trial was conducted in 358 males and 354 females who were at high risk of having a major depressive episode according to sex-specific MVRPs, and who were randomly recruited across Canada. Participants were assessed at baseline, 6 and 12 months.

Over 93% of participants were interested in knowing their depression risk. The intervention group had a greater reduction in K10 score over 12 months than the control group; complete-case analysis found a significant between-group difference in mean K10 change score (d = 1.17, 95% CI 0.12–2.23) at 12 months. Participants in the intervention group also reported significantly less functional impairment in the domains of home and work/school activities, than did those in the control group. A majority of the qualitative interviewees commented that personalized depression risk information does not have a negative impact on physical and mental health.

This study found no evidence that providing personalized depression risk information will lead to worsening psychological distress, functional impairment, and absenteeism. Provision of personalized depression risk information may have positive impacts on non-specific psychological distress and functioning.

ClinicalTrials.gov NCT02943876

Value-based decision-making impairment in depression is a complex phenomenon: while some studies did find evidence of blunted reward learning and reward-related signals in the brain, others indicate no effect. Here we test whether such reward sensitivity deficits are dependent on the overall value of the decision problem.

We used a two-armed bandit task with two different contexts: one ‘rich’, one ‘poor’ where both options were associated with an overall positive, negative expected value, respectively. We tested patients (N = 30) undergoing a major depressive episode and age, gender and socio-economically matched controls (N = 26). Learning performance followed by a transfer phase, without feedback, were analyzed to distangle between a decision or a value-update process mechanism. Finally, we used computational model simulation and fitting to link behavioral patterns to learning biases.

Control subjects showed similar learning performance in the ‘rich’ and the ‘poor’ contexts, while patients displayed reduced learning in the ‘poor’ context. Analysis of the transfer phase showed that the context-dependent impairment in patients generalized, suggesting that the effect of depression has to be traced to the outcome encoding. Computational model-based results showed that patients displayed a higher learning rate for negative compared to positive outcomes (the opposite was true in controls).

Our results illustrate that reinforcement learning performances in depression depend on the value of the context. We show that depressive patients have a specific trouble in contexts with an overall negative state value, which in our task is consistent with a negativity bias at the learning rates level.

Psychotic-like experiences (PLEs) and juvenile mania in adolescence index risk for severe psychopathology in adulthood. The importance of childhood problems with communication, reading, speech and mathematics for the development of PLEs and juvenile mania is not well understood.

Through the Child and Adolescent Twin Study in Sweden, we identified 5812 children. The parents were interviewed about their children's development at age 9 or 12 years. At age 15 or 18 years, children and parents completed questionnaires targeting current PLEs and juvenile mania symptoms. Logistic regressions were used to assess associations between problems with communication, reading, speech and mathematics and PLEs/juvenile mania symptoms. To evaluate the relative importance of genes and environment in these associations, we used bivariate twin analyses based on structural equation models.

Children with parent-endorsed childhood problems with communication, reading and mathematics had an increased risk of developing auditory hallucinations and parental-reported juvenile mania symptoms in adolescence. The most consistent finding was that children with childhood problems with communication, reading and mathematics had an increased risk of developing auditory hallucinations [for example, the risk for self-reported auditory hallucinations at age 15 was increased by 96% for children with communication problems: OR (odds ratio) 1.96, 95% confidence interval (CI) 1.33–2.88]. The twin analyses showed that genetic effects accounted for the increased risk of PLEs and juvenile mania symptoms among children with communication problems.

Childhood problems with communication, reading and mathematics predict PLEs and juvenile mania symptoms in adolescence. Similar to the case for schizophrenia and bipolar disorder, PLEs and juvenile mania may share genetic aetiological factors.