Almost nothing is known about the potential negative effects of Internet-based psychological treatments for depression. This study aims at investigating deterioration and its moderators within randomized trials on Internet-based guided self-help for adult depression, using an individual patient data meta-analyses (IPDMA) approach.

Studies were identified through systematic searches (PubMed, PsycINFO, EMBASE, Cochrane Library). Deterioration in participants was defined as a significant symptom increase according to the reliable change index (i.e. 7.68 points in the CES-D; 7.63 points in the BDI). Two-step IPDMA procedures, with a random-effects model were used to pool data.

A total of 18 studies (21 comparisons, 2079 participants) contributed data to the analysis. The risk for a reliable deterioration from baseline to post-treatment was significantly lower in the intervention v. control conditions (3.36 v. 7.60; relative risk 0.47, 95% confidence interval 0.29–0.75). Education moderated effects on deterioration, with patients with low education displaying a higher risk for deterioration than patients with higher education. Deterioration rates for patients with low education did not differ statistically significantly between intervention and control groups. The benefit–risk ratio for patients with low education indicated that 9.38 patients achieve a treatment response for each patient experiencing a symptom deterioration.

Internet-based guided self-help is associated with a mean reduced risk for a symptom deterioration compared to controls. Treatment and symptom progress of patients with low education should be closely monitored, as some patients might face an increased risk for symptom deterioration. Future studies should examine predictors of deterioration in patients with low education.

Early diagnosis of schizophrenia could improve the outcomes and limit the negative effects of untreated illness. Although participants with schizophrenia show aberrant functional connectivity in brain networks, these between-group differences have a limited diagnostic utility. Novel methods of magnetic resonance imaging (MRI) analyses, such as machine learning (ML), may help bring neuroimaging from the bench to the bedside. Here, we used ML to differentiate participants with a first episode of schizophrenia-spectrum disorder (FES) from healthy controls based on resting-state functional connectivity (rsFC).

We acquired resting-state functional MRI data from 63 patients with FES who were individually matched by age and sex to 63 healthy controls. We applied linear kernel support vector machines (SVM) to rsFC within the default mode network, the salience network and the central executive network.

The SVM applied to the rsFC within the salience network distinguished the FES from the control participants with an accuracy of 73.0% (p = 0.001), specificity of 71.4% and sensitivity of 74.6%. The classification accuracy was not significantly affected by medication dose, or by the presence of psychotic symptoms. The functional connectivity within the default mode or the central executive networks did not yield classification accuracies above chance level.

Seed-based functional connectivity maps can be utilized for diagnostic classification, even early in the course of schizophrenia. The classification was probably based on trait rather than state markers, as symptoms or medications were not significantly associated with classification accuracy. Our results support the role of the anterior insula/salience network in the pathophysiology of FES.

In everyday life it is often required to integrate multisensory input to successfully conduct response inhibition (RI) and thus major executive control processes. Both RI and multisensory processes have been suggested to be altered in autism spectrum disorder (ASD). It is, however, unclear which neurophysiological processes relate to changes in RI in ASD and in how far these processes are affected by possible multisensory integration deficits in ASD.

Combining high-density EEG recordings with source localization analyses, we examined a group of adolescent ASD patients (n = 20) and healthy controls (n = 20) using a novel RI task.

Compared to controls, RI processes are generally compromised in adolescent ASD. This aggravation of RI processes is modulated by the content of multisensory information. The neurophysiological data suggest that deficits in ASD emerge in attentional selection and resource allocation processes related to occipito-parietal and middle frontal regions. Most importantly, conflict monitoring subprocesses during RI were specifically modulated by content of multisensory information in the superior frontal gyrus.

RI processes are overstrained in adolescent ASD, especially when conflicting multisensory information has to be integrated to perform RI. It seems that the content of multisensory input is important to consider in ASD and its effects on cognitive control processes.

The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses.

A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer–Salovey–Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters.

We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (⩾14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC.

If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person.

Auditory verbal hallucinations (AVH) are common during development and may arise due to dysregulation in top-down processing of sensory input. This study was designed to examine the frequency and correlates of speech illusions measured using the White Noise (WN) task in children from the general population. Associations between speech illusions and putative risk factors for psychotic disorder and negative affect were examined.

A total of 1486 children aged 11–12 years of the Copenhagen Child Cohort 2000 were examined with the WN task. Psychotic experiences and negative affect were determined using the Kiddie-SADS-PL. Register data described family history of mental disorders. Exaggerated Theory of Mind functioning (hyper-ToM) was measured by the ToM Storybook Frederik.

A total of 145 (10%) children experienced speech illusions (hearing speech in the absence of speech stimuli), of which 102 (70%) experienced illusions perceived by the child as positive or negative (affectively salient). Experiencing hallucinations during the last month was associated with affectively salient speech illusions in the WN task [general cognitive ability: adjusted odds ratio (aOR) 2.01, 95% confidence interval (CI) 1.03–3.93]. Negative affect, both last month and lifetime, was also associated with affectively salient speech illusions (aOR 2.01, 95% CI 1.05–3.83 and aOR 1.79, 95% CI 1.11–2.89, respectively). Speech illusions were not associated with delusions, hyper-ToM or family history of mental disorders.

Speech illusions were elicited in typically developing children in a WN-test paradigm, and point to an affective pathway to AVH mediated by dysregulation in top-down processing of sensory input.

Delusion is the most characteristic symptom of psychosis. While researchers suggested an association between changes of the cortical salience network (CSN) and delusion, whether these CSN findings are a cause or a consequence of delusion remains unknown.

To assess the effect of CSN functioning to forthcoming changes in delusion scores, we measured brain activation with 3-T functional magnetic resonance imaging in two independent samples of first-episode psychosis patients (total of 27 patients and 23 healthy controls). During scanning, the patients evaluated statements about whether an individual's psychosis-related experiences should be described as a mental illness, and control statements that were also evaluated by healthy controls. Symptoms were assessed at the baseline and at 2 months follow-up with Brief Psychiatric Rating Scale.

Both tasks activated the CSN in comparison with rest. Activation of CSN (‘illness evaluation v. control task’ contrast) in patients positively correlated with worsening of or less improvement in delusions at the 2-month follow-up assessment. This finding was independent of delusion and clinical insight scores at the baseline evaluation.

Our findings link symptom-evaluation-related CSN functioning to severity of delusion and, importantly, add a new layer of evidence for the contribution of CSN functioning to the longitudinal course of delusions.

Eating disorders (EDs) have long-term physical and mental impacts on those affected. However, few population-based studies have estimated the prevalence of EDs. We aimed to estimate the lifetime and 12-month prevalence rates of EDs using DSM-IV criteria, and to examine differences against the DSM-5 criteria for anorexia.

A nationally representative sample of 10 038 residents in Switzerland was interviewed, and prevalence rates for anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) were assessed using WHO Composite International Diagnostic Interviews (WHO-CIDI).

The lifetime prevalence rate for any ED was found to be 3.5%. Lifetime prevalence estimates for AN, BN, and/or BED were 1.2%, 2.4%, and 2.4%, respectively, among women and 0.2%, 0.9%, and 0.7%, respectively, among men. Utilizing the DSM-5 criteria, the prevalence of AN in women increased by more than 50%, from 1.2% to 1.9%. Among those meeting the criteria for any ED, only 49.4% of men and 67.9% of women had ever sought professional help about their problems with eating or weight.

The higher prevalence of BN we detected relative to other studies should prompt further monitoring for a possible increasing trend. The female v. male ratios, especially for bulimia and BED, are decreasing. Given that more than half of those affected have never consulted any professional about their problems with eating or weight, routine inquiries about eating and weight by clinicians, school teachers/psychologists, and family members may help those who are at risk, especially among men.

Alcohol use disorder (AUD) is a classic multifactorial syndrome and it is critical to understand the diversity of the relevant risk factors and how they inter-relate over development.

We examined 21 risk factors for AUD in four developmental tiers reflecting (i) birth, (ii) childhood and early adolescence, (iii) late adolescence, and (iv) early adulthood in 47 414 Swedish men of whom 3907 (8.2%) were registered for AUD at or after age 25 with a mean length of follow-up of 33.9 (6.6) years. Structural equational model fitting was performed using Mplus.

The best-fitting model provided a good fit to the data and explained 23.4% of the variance in AUD. The five strongest predictors were: externalizing behaviors, criminal behavior, father's alcohol consumption, genetic risk, and low educational attainment. Two developmentally early familial/genetic risk factors had substantial direct paths to AUD: father's alcohol consumption and genetic liability. Other broad developmental pathways to risk for AUD were evident: externalizing, psychosocial and internalizing. Overall, the externalizing pathway to AUD was the strongest. However, these pathways were substantially interwoven over time such that risk factors from one domain were commonly predicted by and/or predicted risk factors from the other broad domains of risk.

AUD in men is an etiologically complex syndrome influenced by familial-genetic, psychosocial, internalizing, and especially externalizing risk factors that act and interact over development and have complicated mediational pathways.

Salience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression.

We examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis.

ARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years.

Our findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) frequently co-occur, and have several overlapping phenomenological features. Little is known about their shared neurobiology. The aim of the study was to compare modular organization of brain structural connectivity.

We acquired diffusion-weighted magnetic resonance imaging data on unmedicated individuals with BDD (n = 29), weight-restored AN (n = 24) and healthy controls (HC) (n = 31). We constructed connectivity matrices using whole-brain white matter tractography, and compared modular structures across groups.

AN showed abnormal modularity involving frontal, basal ganglia and posterior cingulate nodes. There was a trend in BDD for similar abnormalities, but no significant differences compared with AN. In AN, poor insight correlated with longer path length in right caudal anterior cingulate and right posterior cingulate.

Abnormal network organization patterns in AN, partially shared with BDD, may have implications for understanding integration between reward and habit/ritual formation, as well as conflict monitoring/error detection.

Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.

We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.

Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.

Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.

The aims of the study were to describe the patterning and persistence of anxiety and depressive symptoms from adolescence to young adulthood and to examine long-term developmental relationships with earlier patterns of internalizing behaviours in childhood.

We used parallel processes latent growth curve modelling to build trajectories of internalizing from adolescence to adulthood, using seven waves of follow-ups (ages 11–27 years) from 1406 participants of the Australian Temperament Project. We then used latent factors to capture the stability of maternal reported child internalizing symptoms across three waves of early childhood follow-ups (ages 5, 7 and 9 years), and examined relationships among these patterns of symptoms across the three developmental periods, adjusting for gender and socio-economic status.

We observed strong continuity in depressive symptoms from adolescence to young adulthood. In contrast, adolescent anxiety was not persistent across the same period, nor was it related to later depressive symptoms. Anxiety was, however, related to non-specific stress in young adulthood, but only moderately so. Although childhood internalizing was related to adolescent and adult profiles, the associations were weak and indirect by adulthood, suggesting that other factors are important in the development of internalizing symptoms.

Once established, adolescent depressive symptoms are not only strongly persistent, but also have the potential to differentiate into anxiety in young adulthood. Relationships with childhood internalizing symptoms are weak, suggesting that early adolescence may be an important period for targeted intervention, but also that further research into the childhood origins of internalizing behaviours is needed.

Delusional disorder (DD) is an under-researched condition and its relationship to schizophrenia (SZ) controversial. This study aimed to further characterize DD and to examine multi-domain evidence for the distinction between DD and SZ.

Using univariate analyses we examined 146 subjects with DD, 114 subjects with paranoid SZ and 244 subjects with non-paranoid SZ on 52 characteristics from several domains including demographics, risk factors, premorbid features, illness characteristics, index episode features, delusional-related features, response to treatment and outcome. In a further step, we searched for independent associations of the examined characteristics with DD v. SZ.

Univariate analyses showed that DD differed from either form of SZ in 40 characteristics, the pattern of findings indicated that paranoid SZ was much more similar to non-paranoid SZ than DD. Relative to subjects with SZ, those with DD were more likely to have drug abuse before illness onset, better premorbid sexual adjustment, later age at illness onset, higher levels of affective symptoms and lack of insight, poorer response to antipsychotic medication, better functioning in the domains of personal care, paid work and social functioning; last, subjects with DD had fewer but more severe delusions and higher ratings of conviction of delusional experience than those with SZ. Predominance of jealousy and somatic delusions was confined to subjects with DD.

DD and SZ represent two distinct classes of disorders, the differential features of DD being of nosological, aetiological and therapeutic relevance.

Chronic opioid exposure, as a treatment for a variety of disorders or as drug of misuse, is common worldwide, but behavioural and brain abnormalities remain under-investigated. Only a small percentage of patients who receive methadone maintenance treatment (MMT) for previous heroin misuse eventually achieve abstinence and studies on such patients are rare.

The Cambridge Neuropsychological Test Automated Battery and T1 weighted magnetic resonance imaging (MRI) were used to study a cohort of 122 male individuals: a clinically stable opioid-dependent patient group receiving MMT (n = 48), an abstinent previously MMT maintained group (ABS) (n = 24) and healthy controls (n = 50).

Stable MMT participants deliberated longer and placed higher bets earlier in the Cambridge Gambling Task (CGT) and showed impaired strategic planning compared with healthy controls. In contrast, ABS participants showed impairment in choosing the least likely outcome, delay aversion and risk adjustment on the CGT, and exhibited non-planning impulsivity compared with controls. MMT patients had widespread grey matter reductions in the orbitomedial prefrontal cortex, caudate, putamen and globus pallidus. In contrast, ABS participants showed midbrain–thalamic grey matter reductions. A higher methadone dose at the time of scanning was associated with a smaller globus pallidus in the MMT group.

Our findings support an interpretation of heightened impulsivity in patients receiving MMT. Widespread structural brain abnormalities in the MMT group and reduced brain structural abnormality with abstinence suggest benefit of cessation of methadone intake. We suggest that a longitudinal study is required to determine whether abstinence improves abnormalities, or patients who achieve abstinence have reduced abnormalities before methadone cessation.

Subthreshold depression (SUBD) in later life is common and important as prodromal state and prominent risk factor in the development of major depressive disorder (MDD). Indicated prevention can reduce the incidence of MDD among people with SUBD substantially, but needs to be targeted to those that are truly at risk of developing MDD.

N = 341 eligible participants with SUBD were included from the first (1992/1993), second (1995/1996) and third (1998/1999) cycle from the Longitudinal Aging Study Amsterdam (LASA) by using a two-stage screening design. LASA is an ongoing prospective cohort study in The Netherlands among the older population (55–85 years). At baseline (1992/1993) N = 3107 participants were interviewed and follow-up cycles were conducted every 3 years until 2008/2009, resulting in maximal 17 years of observational period. The proportion of people that developed MDD, remained SUBD, or recovered from SUBD was measured and Cox proportional regression analyses were performed to investigate 29 putative predictors of MDD and recovery from SUBD.

N = 153 (44.9%) recovered from SUBD, N = 138 (40.5%) remained chronically SUBD, and N = 50 (14.7%) developed MDD (incidence rate 15.1/1000 person-years). Women, high neuroticism, more chronic diseases, high body mass index, smoking and less social support predicted conversion to MDD. Men, low neuroticism and absence of pain predicted recovery from SUBD.

Although older people with SUBD are clearly at risk of developing MDD, the majority did not, even after a long and thorough follow-up. Given the risk factors that were uncovered, targeting and prevention of MDD in those at very high risk is feasible.