An adaptive neural stress response is essential to adequately cope with a changing environment. It was previously argued that sympathetic/noradrenergic activity during acute stress increases salience network (SN) connectivity and reduces executive control network (ECN) connectivity in healthy controls, with opposing effects in the late aftermath of stress. Altered temporal dynamics of these networks in response to stress are thought to play a role in the development of psychopathology in vulnerable individuals.

We exposed male healthy controls (n = 40, mean age = 33.9) and unaffected siblings of schizophrenia patients (n = 39, mean age = 33.2) to the stress or control condition of the trier social stress test and subsequently investigated resting state functional connectivity of the SN and ECN directly after and 1.5 h after stress.

Acute stress resulted in increased functional connectivity within the SN in healthy controls, but not in siblings (group × stress interaction pfwe < 0.05). In the late aftermath of stress, stress reduced functional connectivity within the SN in both groups. Moreover, we found increased functional connectivity between the ECN and the cerebellum in the aftermath of stress in both healthy controls and siblings of schizophrenia patients.

The results show profound differences between siblings of schizophrenia patients and controls during acute stress. Siblings lacked the upregulation of neural resources necessary to quickly and adequately cope with a stressor. This points to a reduced dynamic range in the sympathetic response, and may constitute a vulnerability factor for the development of psychopathology in this at-risk group.

The Arsenic (+3 oxidation state) methyltransferase (AS3MT) gene has been identified as a top risk gene for schizophrenia in several large-scale genome-wide association studies. A variable number tandem repeat (VNTR) of this gene is the most significant expression quantitative trait locus, but its role in brain activity in vivo is still unknown.

We first performed a functional magnetic resonance imaging (fMRI) scan of 101 healthy subjects during a memory span task, trained all subjects on an adaptive memory span task for 1 month, and finally performed another fMRI scan after the training. After excluding subjects with excessive head movements for one or more scanning sessions, data from 93 subjects were included in the final analyses.

The VNTR was significantly associated with both baseline brain activation and training-induced changes in multiple regions including the prefrontal cortex and the anterior and posterior cingulate cortex. Additionally, it was associated with baseline brain activation in the striatum and the parietal cortex. All these results were corrected based on the family-wise error rate method across the whole brain at the peak level.

This study sheds light on the role of AS3MT gene variants in neural plasticity related to memory span training.

Health anxiety is common, disabling and costly due to patients’ extensive use of health care services. Internet-delivered treatment may overcome barriers of accessibility to specialized treatment. We aimed to evaluate the efficacy of internet-delivered acceptance and commitment therapy (iACT).

A randomized, controlled trial of iACT versus an internet-delivered discussion forum (iFORUM), performed in a Danish university hospital setting. Patients self-referred and underwent video-diagnostic assessment. Eligible patients (≥18 years) with health anxiety were randomized to 12 weeks of intervention. The randomization was blinded for the assessor. The primary outcome was between-group unadjusted mean differences in health anxiety symptoms measured by the Whiteley-7 Index (WI-7, range 0–100) from baseline to 6-month follow-up (6-MFU) using intention to treat and a linear mixed model. The study is registered at clinicaltrials.gov, number NCT02735434.

A total of 151 patients self-referred, and 101 patients were randomized to iACT (n = 53) or iFORUM (n = 48). A mean difference in change over time of 19.0 points [95% confidence interval (CI) 10.8–27.2, p < 0.001] was shown on the WI-7, and a large standardized effect size of d = 0.80 (95% CI 0.38–1.23) at 6-MFU. The number needed to treat was 2.8 (95% CI 1.8–6.1, p < 0.001), and twice as many patients in iACT were no longer clinical cases (35% v. 16%; risk ratio 2.17, 95% CI 1.00–4.70, p = 0.050). Adverse events were few and insignificant.

iACT for health anxiety led to sustained effects at 6-MFU. The study contributes to the development of easily accessible treatment options and deserves wider application.

Studies of Internet gaming disorder (IGD) suggest an imbalanced relationship between cognitive control and reward processing in people with IGD. However, it remains unclear how these two systems interact with each other, and whether they could serve as neurobiological markers for IGD.

Fifty IGD subjects and matched individuals with recreational game use (RGU) were selected and compared when they were performing a cue-craving task. Regions of interests [anterior cingulate cortex (ACC), lentiform nucleus] were selected based on the comparison between brain responses to gaming-related cues and neutral cues. Directional connectivities among these brain regions were determined using Bayesian estimation. We additionally examined the posterior cingulate cortex (PCC) in a separate analysis based on data implicating the PCC in craving in addiction.

During fixed-connectivity analyses, IGD subjects showed blunted ACC-to-lentiform and lentiform-to-ACC connectivity relative to RGU subjects, especially in the left hemisphere. When facing gaming cues, IGD subjects trended toward lower left-hemispheric modulatory effects in ACC-to-lentiform connectivity than RGU subjects. Self-reported cue-related craving prior to scanning correlated inversely with left-hemispheric modulatory effects in ACC-to-lentiform connectivity.

The results suggesting that prefrontal-to-lentiform connectivity is impaired in IGD provides a possible neurobiological mechanism for difficulties in controlling gaming-cue-elicited cravings. Reduced connectivity ACC-lentiform connectivity may be a useful neurobiological marker for IGD.

Transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic option for major depressive disorder (MDD) in adults. Alternative third-line treatments for MDD in adolescents are scarce. Here we aimed to assess the effects of acute tVNS on emotion recognition in adolescents with MDD.

Adolescents (14–17 years) with MDD (n = 33) and non-depressed controls (n = 30) received tVNS or sham-stimulation in a cross-sectional, case–control, within-subject cross-randomized controlled trial, while performing different tasks assessing emotion recognition. Correct responses, response times, and errors of omission and commission on three different computerized emotion recognition tasks were assessed as main outcomes. Simultaneous recordings of electrocardiography and electro dermal activity, as well as sampling of saliva for the determination of α-amylase, were used to quantify the effects on autonomic nervous system function.

tVNS had no effect on the recognition of gradually or static expressed emotions but altered response inhibition on the emotional Go/NoGo-task. Specifically, tVNS increased the likelihood of omitting a response toward sad target-stimuli in adolescents with MDD, while decreasing errors (independent of the target emotion) in controls. Effects of acute tVNS on autonomic nervous system function were found in non-depressed controls only.

Acute tVNS alters the recognition of briefly presented facial expressions of negative valence in adolescents with MDD while generally increasing emotion recognition in controls. tVNS seems to specifically alter early visual processing of stimuli of negative emotional valence in MDD. These findings suggest a potential therapeutic benefit of tVNS in adolescent MDD that requires further evaluation within clinical trials.

Experiences of childhood trauma (CT) are associated with increased psychological vulnerability. Past research suggests that CT might alter stress processing with a subsequent negative impact on mental health. However, it is currently unclear how different domains of CT exert effects on specific subjective experiences of stress during adulthood.

In the present study, we used network analysis to explore the complex interplay between distinct domains of CT and perceived stress in a large, general-population sample of middle-aged adults (N = 1252). We used a data-driven community-detection algorithm to identify strongly connected subgroups of items within the network. To assess the replicability of the findings, we repeated the analyses in a second sample (N = 862). Combining data from both samples, we evaluated network differences between men (n = 955) and women (n = 1159).

Results indicate specific associations between distinct domains of CT and perceived stress. CT domains reflecting a dimension of deprivation, i.e. experiences of neglect, were associated exclusively to a stress network community representing low perceived self-efficacy. By contrast, CT associated with threat, i.e. experiences of abuse, was specifically related to a stress community reflecting perceived helplessness. Our results replicated with high accordance in the second sample. We found no difference in network structure between men and women, but overall a stronger connected network in women.

Our findings emphasize the unique role of distinct domains of CT in psychological stress processes in adulthood, implying opportunities for targeted interventions following distinct domains of CT.

Neuroanatomical abnormalities in first-episode psychosis (FEP) tend to be subtle and widespread. The vast majority of previous studies have used small samples, and therefore may have been underpowered. In addition, most studies have examined participants at a single research site, and therefore the results may be specific to the local sample investigated. Consequently, the findings reported in the existing literature are highly heterogeneous. This study aimed to overcome these issues by testing for neuroanatomical abnormalities in individuals with FEP that are expressed consistently across several independent samples.

Structural Magnetic Resonance Imaging data were acquired from a total of 572 FEP and 502 age and gender comparable healthy controls at five sites. Voxel-based morphometry was used to investigate differences in grey matter volume (GMV) between the two groups. Statistical inferences were made at p < 0.05 after family-wise error correction for multiple comparisons.

FEP showed a widespread pattern of decreased GMV in fronto-temporal, insular and occipital regions bilaterally; these decreases were not dependent on anti-psychotic medication. The region with the most pronounced decrease – gyrus rectus – was negatively correlated with the severity of positive and negative symptoms.

This study identified a consistent pattern of fronto-temporal, insular and occipital abnormalities in five independent FEP samples; furthermore, the extent of these alterations is dependent on the severity of symptoms and duration of illness. This provides evidence for reliable neuroanatomical alternations in FEP, expressed above and beyond site-related differences in anti-psychotic medication, scanning parameters and recruitment criteria.

The output of many healthy physiological systems displays fractal fluctuations with self-similar temporal structures. Altered fractal patterns are associated with pathological conditions. There is evidence that patients with bipolar disorder have altered daily behaviors.

To test whether fractal patterns in motor activity are altered in patients with bipolar disorder, we analyzed 2-week actigraphy data collected from 106 patients with bipolar disorder type I in a euthymic state, 73 unaffected siblings of patients, and 76 controls. To examine the link between fractal patterns and symptoms, we analyzed 180-day actigraphy and mood symptom data that were simultaneously collected from 14 patients.

Compared to controls, patients showed excessive regularity in motor activity fluctuations at small time scales (<1.5 h) as quantified by a larger scaling exponent (α1 > 1), indicating a more rigid motor control system. α1 values of siblings were between those of patients and controls. Further examinations revealed that the group differences in α1 were only significant in females. Sex also affected the group differences in fractal patterns at larger time scales (>2 h) as quantified by scaling exponent α2. Specifically, female patients and siblings had a smaller α2 compared to female controls, indicating more random activity fluctuations; while male patients had a larger α2 compared to male controls. Interestingly, a higher weekly depression score was associated with a lower α1 in the subsequent week.

Our results show sex- and scale-dependent alterations in fractal activity regulation in patients with bipolar disorder. The mechanisms underlying the alterations are yet to be determined.

Maladaptive learning linking environmental food cues to high-palatability food reward plays a central role in overconsumption in obesity and binge eating disorders. The process of memory reconsolidation offers a mechanism to weaken such learning, potentially ameliorating over-eating behaviour. Here we investigated whether putatively interfering with synaptic plasticity using the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, could weaken retrieved chocolate reward memories through blockade of reconsolidation

Seventy five healthy volunteers with a tendency to binge eat chocolate were randomised to retrieve chocolate reward memory under 10 mg rapamycin (RET + RAP, active condition), or placebo (RET + PBO), or they received 10 mg rapamycin without subsequent retrieval (NO RET + RAP). Indices of chocolate reward memory strength were assessed one week pre and post manipulation and at one month follow-up.

Contrary to hypotheses, the RET + RAP group did not show any greater reduction than control groups on indices of motivational salience of chocolate cues, motivation to consume chocolate or liking of chocolate. Mild evidence of improvement in the RET + RAP group was found, but this was limited to reduced chocolate binge episodes and improved healthy food choices.

We did not find convincing evidence of comprehensive naturalistic chocolate reward memory reconsolidation blockade by rapamycin. The effects on chocolate bingeing and food choices may warrant further investigation. These limited positive findings may be attributable to insufficient interference with mTOR signalling with 10 mg rapamycin, or failure to destabilise chocolate memories during retrieval.

Suicide is a leading cause of mortality in youth, yet the course of suicide attempts is poorly documented. We explored the vulnerable transition from adolescence to emerging adulthood to identify group trajectories and risk factors.

The National Longitudinal Survey of Children and Youth is a prospective representative cohort of Canadian children. We followed participants aged 7–11 years in 1994–95 to age 23 (2008–09). We modelled self-reported past-year suicide attempts (ages 12 to 23 years) using growth mixture models. We analysed risk factors from self- and parent-report questionnaires at pre-adolescence (ages 10–11) and early adolescence (ages 12–13) using multinomial logistic regressions. Analyses were adjusted for sample non-response and attrition.

In 2233 participants answering questions on teen and adult suicide attempts, we identified three trajectories: never attempted (96.0%), adolescence-limited (2.0%) and persisting into adulthood (2.0%). Adolescent girls aged 12–13 with depression/anxiety symptoms, and with mothers experiencing depression had higher risks of adolescence-limited than never-attempted [relative risk RR 9.27 (95% confidence interval: 1.73–49.82); 2.03 (1.02–3.32), for each standard deviation increase; 1.07 (1.00–1.15); respectively]. Preteen ADHD symptoms increased the risk of attempts persisting into adulthood as compared to never-attempted [RR 2.05 (1.29–3.28) for each standard deviation increase]. Suicide death of schoolmate/acquaintance increased risks of an adulthood trajectory as compared to never-attempted and adolescence-limited [RR 8.41 (3.04–23.27) and 6.63 (1.29–34.06), respectively].

In half the participants attempting suicide, attempts continued into adulthood. We stress the need for preventive strategies in early adolescence and differential clinical/educational interventions as identified for each trajectory.

Social anxiety disorder (SAD) has been linked to academic underachievement, but previous studies had methodological limitations. We investigated the association between SAD and objective indicators of educational performance, controlling for a number of covariates and unmeasured confounders shared between siblings.

This population-based birth cohort study included 2 238 837 individuals born in Sweden between 1973 and 1997, followed-up until 2013. Within the cohort, 15 755 individuals had a recorded ICD-10 diagnosis of SAD in the Swedish National Patient Register. Logistic regression models tested the association between SAD and educational performance. We also identified 6488 families with full siblings discordant for SAD.

Compared to unexposed individuals, individuals diagnosed with SAD were less likely to pass all subjects in the last year of compulsory education [adjusted odds ratios (aOR) ranging from 0.19 to 0.44] and less likely to be eligible for a vocational or academic programme in upper secondary education [aOR = 0.31 (95% confidence interval [CI] 0.30–0.33) and aOR = 0.52 (95% CI 0.50–0.55), respectively], finish upper secondary education [aOR = 0.19 (95% CI 0.19–0.20)], start a university degree [aOR = 0.47 (95% CI 0.45–0.49)], obtain a university degree [aOR = 0.35 (95% CI 0.33–0.37)], and finish postgraduate education [aOR = 0.58 (95% CI 0.43–0.80)]. Results were attenuated but remained statistically significant in adjusted sibling comparison models. When psychiatric comorbidities were taken into account, the results were largely unchanged.

Treatment-seeking individuals with SAD have substantially impaired academic performance throughout the formative years. Early detection and intervention are warranted to minimise the long-term socioeconomic impact of the disorder.

Heterogeneity in cognitive functioning among major depressive disorder (MDD) patients could have been the reason for the small-to-moderate differences reported so far when it is compared to other psychiatric conditions or to healthy controls. Additionally, most of these studies did not take into account clinical and sociodemographic characteristics that could have played a relevant role in cognitive variability. This study aims to identify empirical clusters based on cognitive, clinical and sociodemographic variables in a sample of acute MDD patients.

In a sample of 174 patients with an acute depressive episode, a two-step clustering analysis was applied considering potentially relevant cognitive, clinical and sociodemographic variables as indicators for grouping.

Treatment resistance was the most important factor for clustering, closely followed by cognitive performance. Three empirical subgroups were obtained: cluster 1 was characterized by a sample of non-resistant patients with preserved cognitive functioning (n = 68, 39%); cluster 2 was formed by treatment-resistant patients with selective cognitive deficits (n = 66, 38%) and cluster 3 consisted of resistant (n = 23, 58%) and non-resistant (n = 17, 42%) acute patients with significant deficits in all neurocognitive domains (n = 40, 23%).

The findings provide evidence upon the existence of cognitive heterogeneity across patients in an acute depressive episode. Therefore, assessing cognition becomes an evident necessity for all patients diagnosed with MDD, and although treatment resistant is associated with greater cognitive dysfunction, non-resistant patients can also show significant cognitive deficits. By targeting not only mood but also cognition, patients are more likely to achieve full recovery and prevent new relapses.