Little is known about the childhood antecedents and adult correlates of adolescent dual-harm (i.e. co-occurring self- and other-harm). We examine the longitudinal associations between (a) social and psychological risk factors in childhood and adolescent dual-harm and (b) adolescent dual-harm and social and mental health impairments in early adulthood.

Participants (N = 1482) are from a prospective longitudinal community-representative study. Dual-, self-, and other-harm were self-reported at ages 13, 15, and 17. Social and psychological risk factors in childhood were assessed between 7 and 11; early adult correlates at age 20. Groups with dual-harm, self-harm only, other-harm only, and no harm were compared.

Between 13 and 17, 7.2% of adolescents reported dual-harm (self-harm only: 16.2%; other-harm only: 13.3%). Some childhood risk factors (e.g. sensation-seeking, parental divorce, victimization by peers) characterized all harm groups; others were common to the dual- and self-harm (anxiety/depressive symptoms, relational aggression) or dual- and other-harm groups only (low self-control, substance use, delinquency). Adolescents with dual-harm had reported more physical aggression and harsh parenting, and lower school bonding in childhood than any other group. In early adulthood, they reported more anxiety/depressive symptoms, psychopathy symptoms, homicidal ideations, delinquency, and victimization experiences than any other group.

Adolescent dual-harm follows psychological problems and social disconnection in childhood and signals risk of psychopathology and isolation in early adulthood. To curb the burden from dual-harm, interventions must target adolescents, families, peer networks, and school environments. Differentiating youth with dual-harm from those with single-harm is important for developing personalized treatments.

Coordination between the thalamus and cortex is necessary for efficient processing of sensory information and appears disrupted in schizophrenia. The significance of this disrupted coordination (i.e. thalamocortical dysconnectivity) to the symptoms and cognitive deficits of schizophrenia is unclear. It is also unknown whether similar dysconnectivity is observed in other forms of psychotic psychopathology and associated with familial risk for psychosis. Here we examine the relevance of thalamocortical connectivity to the clinical symptoms and cognition of patients with psychotic psychopathology, their first-degree biological relatives, and a group of healthy controls.

Patients with a schizophrenia-spectrum diagnosis (N = 100) or bipolar disorder with a history of psychosis (N = 33), their first-degree relatives (N = 73), and a group of healthy controls (N = 43) underwent resting functional MRI in addition to clinical and cognitive assessments as part of the Psychosis Human Connectome Project. A bilateral mediodorsal thalamus seed-based analysis was used to measure thalamocortical connectivity and test for group differences, as well as associations with symptomatology and cognition.

Reduced connectivity from mediodorsal thalamus to insular, orbitofrontal, and cerebellar regions was seen in schizophrenia. Across groups, greater symptomatology was related to less thalamocortical connectivity to the left middle frontal gyrus, anterior cingulate, right insula, and cerebellum. Poorer cognition was related to less thalamocortical connectivity to bilateral insula. Analyses revealed similar patterns of dysconnectivity across patient groups and their relatives.

Reduced thalamo-prefrontal-cerebellar and thalamo-insular connectivity may contribute to clinical symptomatology and cognitive deficits in patients with psychosis as well as individuals with familial risk for psychotic psychopathology.

Major depressive disorder (MDD) is often accompanied by changes in appetite and weight. Prior task-based functional magnetic resonance imaging (fMRI) findings suggest these MDD phenotypes are associated with altered reward and interoceptive processing.

Using resting-state fMRI data, we compared the fractional amplitude of low-frequency fluctuations (fALFF) and seed-based connectivity (SBC) among hyperphagic (n = 77), hypophagic (n = 66), and euphagic (n = 42) MDD groups and a healthy comparison group (n = 38). We examined fALFF and SBC in a mask restricted to reward [nucleus accumbens (NAcc), putamen, caudate, ventral pallidum, and orbitofrontal cortex (OFC)] and interoceptive (anterior insula and hypothalamus) regions and also performed exploratory whole-brain analyses. SBC analyses included as seeds the NAcc and also regions demonstrating group differences in fALFF (i.e. right lateral OFC and right anterior insula). All analyses used threshold-free cluster enhancement.

Mask-restricted analyses revealed stronger fALFF in the right lateral OFC, and weaker fALFF in the right anterior insula, for hyperphagic MDD v. healthy comparison. We also found weaker SBC between the right lateral OFC and left anterior insula for hyperphagic MDD v. healthy comparison. Whole-brain analyses revealed weaker fALFF in the right anterior insula, and stronger SBC between the right lateral OFC and left precentral gyrus, for hyperphagic MDD v. healthy comparison. Findings were no longer significant after controlling for body mass index, which was higher for hyperphagic MDD.

Our results suggest hyperphagic MDD may be associated with altered activity in and connectivity between interoceptive and reward regions.

While implicit distraction could ameliorate negative feelings in patients with major depressive disorders (MDD), it remains unclear whether patients could benefit from explicit, voluntary distraction. Meanwhile, though the dorsolateral prefrontal cortex (DLPFC) is established as a crucial brain region involved in attentional control, the causal relationship between the DLPFC and voluntary distraction is unexplored in patients.

Combing explicit distraction and transcranial magnetic stimulation (TMS), this study investigated whether TMS-activated DLPFC facilitates voluntary distraction in MDD patients. Eighty patients diagnosed with current MDD underwent either active (n = 40) or sham (n = 40) TMS sessions, followed by receiving negative social feedback from other patients, during which they were requied to use distraction strategy to down-regulate their painful feelings. Electroencephalogram was recorded during the task.

Both the subjective emotional rating and the amplitude of late positive potential showed that depressed patients successfully down-regulate their negative emotions via voluntary distraction, and the TMS-activated left DLPFC produced a larger benefit of emotion regulation compared to the sham TMS group. Results also revealed that while emotion regulation effect was negatively associated with depressive symptoms in the sham TMS group, this correlation was largely diminished when patients' left DLPFC was activated by TMS during the voluntary distraction.

These findings demonstrated that distraction is valuable for emotion regulation in MDD patients and they could be beneficial in voluntary distraction by activating their left DLPFC using neural modulation techniques. This study has valuable implications for clinical treatement of emotional dysregulation in MDD patients.

Successful interventions have been developed for smoking cessation although the success of smoking relapse prevention protocols has been limited. Cognitive behavioural therapy (CBT) in particular has been hampered by a high relapse rate. Because relapse can be due to conditions associated with tobacco consumption (such as drinking in bars with friends), virtual reality cue exposure therapy (VRCE) can be a potential tool to generate 3D interactive environments that simulate risk situations for relapse prevention procedures.

To assess the effectiveness of VRCE with CBT, a comparative trial involving 100 smoking abstinent participants was designed with all required virtual environments (VE) created with an inexpensive graphic engine/game level editor.

Outcome measures confirmed the immersive and craving eliciting effect of these VEs. Results demonstrated that more participants in the VRCE group did not experience smoking relapse and that VRCE is at least as efficacious as traditional CBT in terms of craving reduction and decrease in nicotine dependence. Dropout and relapse rate in the VRCE group was noticeably lower than the CBT group. Aside from mood scores, no significant differences were found regarding the other scales.

The present clinical trial provides evidence that VRCE was effective in preventing smoking relapse. Improvement in technology and methodology for future research and applications is delineated.

Our study examined whether the early-onset depression phenotype among young adults (probands) is associated with the metabolic syndrome (MetS) and its components, and if MetS characterizes unaffected but high-risk siblings of probands.

We studied three groups of young adults (Mage = 25 years, s.d. = 3.84 years): probands with histories of childhood onset depression – i.e. early-onset phenotype – (n = 293), their unaffected siblings (high-risk siblings, n = 273), and healthy controls (n = 171). Participants completed a full psychiatric interview, physical and laboratory assessments, and self-rating scales. MetS was defined using the criteria of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001).

Early-onset depression phenotype and being a high-risk sibling were associated with higher MetS composite scores relative to that of controls, but did not differ from one another. With regard to MetS components: Probands and siblings had similarly larger waist circumference and lower HDL than did controls, while siblings and controls had lower triglyceride levels than did probands but did not differ from one another. Groups did not differ on glucose levels and SBP.

Our study extends the literature on the association between MetS and depression and underscores the importance of depression phenotypes: failure to account for the clinical heterogeneity of depression may partly underlie the inconsistent findings regarding its relation to MetS. The results also suggest that, in depression-prone populations, MetS may predate and possibly function as a risk factor for eventual depression.

Inflammation plays a crucial role in the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). This study aimed to examine whether the dysregulation of complement components contributes to brain structural defects in patients with mood disorders.

A total of 52 BD patients, 35 MDD patients, and 53 controls were recruited. The human complement immunology assay was used to measure the levels of complement factors. Whole brain-based analysis was performed to investigate differences in gray matter volume (GMV) and cortical thickness (CT) among the BD, MDD, and control groups, and relationships were explored between neuroanatomical differences and levels of complement components.

GMV in the medial orbital frontal cortex (mOFC) and middle cingulum was lower in both patient groups than in controls, while the CT of the left precentral gyrus and left superior frontal gyrus were affected differently in the two disorders. Concentrations of C1q, C4, factor B, factor H, and properdin were higher in both patient groups than in controls, while concentrations of C3, C4 and factor H were significantly higher in BD than in MDD. Concentrations of C1q, factor H, and properdin showed a significant negative correlation with GMV in the mOFC at the voxel-wise level.

BD and MDD are associated with shared and different alterations in levels of complement factors and structural impairment in the brain. Structural defects in mOFC may be associated with elevated levels of certain complement factors, providing insight into the shared neuro-inflammatory pathogenesis of mood disorders.

Higher incidence of psychotic disorders and underuse of mental health services have been reported among many migrant populations. This study examines the initiation and continuity of antipsychotic treatment among migrants and non-migrants with a non-affective psychosis during a new treatment episode.

This study is based on a nationwide sample of migrants and Finnish-born controls. Participants who were diagnosed with a psychotic disorder in 2011–2014 were identified from the Care Register for Health Care (n = 1693). Information on purchases of antipsychotic drugs in 2011–2015 was collected from the National Prescription Register. The duration of antipsychotic treatment since diagnosis was estimated using the PRE2DUP model. Cox regression analysis was used to study factors that are associated with discontinuing the use of medication.

There were fewer initiators of antipsychotic treatment after being diagnosed with psychosis among migrants (68.1%) than among Finnish-born patients (73.6%). After controlling for sociodemographic background and factors related to the type of disorder and treatment, migrants were more likely to discontinue medication (adjusted hazard ratio 1.28, 95% confidence interval 1.08–1.52). The risk of discontinuation was highest among migrants from North Africa and the Middle East and Sub-Saharan Africa and among recent migrants. Non-use of antipsychotic treatment before being diagnosed with psychosis, involuntary hospitalization and diagnosis other than schizophrenia were associated with earlier discontinuation both among migrants and non-migrants.

Migrants with a psychotic disorder are less likely to continue antipsychotic treatment than non-migrants. The needs of migrant patients have to be addressed to improve adherence.

Loneliness is a major risk factor for both psychological disturbance and poor health outcomes in adults. This study aimed to assess whether childhood loneliness is associated with a long-term disruption in mental health that extends into adulthood.

This study is based on the longitudinal, community-representative Great Smoky Mountains Study of 1420 participants. Participants were assessed with the structured Child and Adolescent Psychiatric Assessment interview up to eight times in childhood (ages 9–16; 6674 observations; 1993–2000) for childhood loneliness, associated psychiatric comorbidities and childhood adversities. Participants were followed up four times in adulthood (ages 19, 21, 25, and 30; 4556 observations of 1334 participants; 1999–2015) with the structured Young Adult Psychiatric Assessment Interview for psychiatric anxiety, depression, and substance use outcomes.

Both self and parent-reported childhood loneliness were associated with adult self-reported anxiety and depressive outcomes. The associations remained significant when childhood adversities and psychiatric comorbidities were accounted for. There was no evidence for an association of childhood loneliness with adult substance use disorders. More associations were found between childhood loneliness and adult psychiatric symptoms than with adult diagnostic status.

Childhood loneliness is associated with anxiety and depressive disorders in young adults, suggesting that loneliness – even in childhood – might have long-term costs in terms of mental health. This study underscores the importance of intervening early to prevent loneliness and its sequelae over time.

This study tested whether the dissonance-based Body Project eating disorder prevention program reduced onset of subthreshold/threshold anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD) over long-term follow-up.

Data were combined from three prevention trials that targeted young women at high-risk for eating disorders (N = 1092; M age = 19.3). Participants were randomized to Body Project groups led by peer educators or expressive writing/educational controls and completed masked diagnostic interviews over 2- to 4-year follow-ups. Logistic regressions tested whether onset of each eating disorder over follow-up differed between Body Project and control participants.

Peer-led Body Project groups produced a 46% reduction in onset of subthreshold/threshold BN and a 62% reduction in onset of PD relative to controls over follow-up. Rates of onset of subthreshold/threshold AN and BED did not significantly differ between peer-led Body Project participants and control participants.

Results support the dissemination of the peer-led Body Project for reducing future onset of BN and PD. This study and recent research suggest that thin-ideal internalization, the risk factor for eating disorders targeted in the Body Project, may be more relevant for predicting onset of BN and PD compared to AN and BED. Findings support the development of a version of the Body Project aimed to reduce risk factors that have predicted future onset of all four types of eating disorders (e.g. overvaluation of weight/shape, fear of weight gain), which may more effectively prevent all eating disorder types.

Recommendations for promoting mental health during the COVID-19 pandemic include maintaining social contact, through virtual rather than physical contact, moderating substance/alcohol use, and limiting news and media exposure. We seek to understand if these pandemic-related behaviors impact subsequent mental health.

Daily online survey data were collected on adults during May/June 2020. Measures were of daily physical and virtual (online) contact with others; substance and media use; and indices of psychological striving, struggling and COVID-related worry. Using random-intercept cross-lagged panel analysis, dynamic within-person cross-lagged effects were separated from more static individual differences.

In total, 1148 participants completed daily surveys [657 (57.2%) females, 484 (42.1%) males; mean age 40.6 (s.d. 12.4) years]. Daily increases in news consumed increased COVID-related worrying the next day [cross-lagged estimate = 0.034 (95% CI 0.018–0.049), FDR-adjusted p = 0.00005] and vice versa [0.03 (0.012–0.048), FDR-adjusted p = 0.0017]. Increased media consumption also exacerbated subsequent psychological struggling [0.064 (0.03–0.098), FDR-adjusted p = 0.0005]. There were no significant cross-lagged effects of daily changes in social distancing or virtual contact on later mental health.

We delineate a cycle wherein a daily increase in media consumption results in a subsequent increase in COVID-related worries, which in turn increases daily media consumption. Moreover, the adverse impact of news extended to broader measures of psychological struggling. A similar dynamic did not unfold between the daily amount of physical or virtual contact and subsequent mental health. Findings are consistent with current recommendations to moderate news and media consumption in order to promote mental health.

Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions – including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD.

Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships.

Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD.

These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.

Anorexia nervosa (AN) is characterized by an overgeneralization of food/body-related autobiographical memories (AM). This is regarded as an emotion regulation strategy with adverse long-term effects implicated in disorder maintenance and treatment resistance. Therefore, we aimed to examine neural correlates of food/body-related AM-recall in AN.

Twenty-nine female patients with AN and 30 medication-free age-sex-matched normal-weight healthy controls (HC) underwent functional magnetic resonance imaging while recalling AMs in response to food/body-related and neutral cue words. To control for general knowledge retrieval, participants engaged in a semantic generation and riser detection task.

In comparison to HC, patients with AN generated fewer and less specific AMs in response to food/body-related words, but not for neutral cue words. Group comparisons revealed reduced activation in regions associated with self-referential processing and memory retrieval (precuneus and angular gyrus) during the retrieval of specific food/body-related AM in patients with AN. Brain connectivity in regions associated with memory functioning and executive control was reduced in patients with AN during the retrieval of specific food/body-related AM. Finally, resting-state functional connectivity analysis revealed no differences between groups, arguing against a general underlying disconnection of brain networks implicated in memory and emotional processing in AN.

These results indicate impaired neural processing of food/body-related AM in AN, with a reduced involvement of regions involved in self-referential processing. Our findings are discussed as possible neuronal correlates of emotional avoidance in AN and provide new insights of AN-pathophysiology underscoring the importance of targeting dysfunctional emotion regulation strategies during treatment.

Grey matter (GM) reduction is a consistent observation in established late stages of schizophrenia, but patients in the untreated early stages of illness display an increase as well as a decrease in GM distribution relative to healthy controls (HC). The relative excess of GM may indicate putative compensatory responses, though to date its relevance is unclear.

343 first-episode treatment-naïve patients with schizophrenia (FES) and 342 HC were recruited. Multivariate source-based morphometry was performed to identify covarying ‘networks' of grey matter concentration (GMC). Neurocognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and symptom burden using the Positive and Negative Symptoms Scale (PANSS) were obtained. Bivariate linear relationships between GMC and cognition/symptoms were studied.

Compared to healthy subjects, FES had prominently lower GMC in two components; the first consists of the anterior insula, inferior frontal gyrus, anterior cingulate and the second component with the superior temporal gyrus, precuneus, inferior/superior parietal lobule, cuneus, and lingual gyrus. Higher GMC was seen in adjacent areas of the middle and superior temporal gyrus, middle frontal gyrus, inferior parietal cortex and putamen. Greater GMC of this component was associated with lower duration of untreated psychosis, less severe positive symptoms and better performance on cognitive tests.

In untreated stages of schizophrenia, both a distributed lower and higher GMC is observable. While the higher GMC is relatively modest, it occurs across frontoparietal, temporal and subcortical regions in association with reduced illness burden suggesting a compensatory role for higher GMC in the early stages of schizophrenia.

Previous Scandinavian studies have shown increased levels of psychiatric morbidity in young refugees and international adoptees with an origin outside Europe. This study investigated their risk of non-affective psychotic disorders (NAPD) and whether this risk is influenced by early childhood adversity, operationalised as age at adoption/residency, and/or gender.

Register study in Swedish national cohorts born 1972–1990 including 21 615 non-European international adoptees, 42 732 non-European refugees that settled in Sweden at age 0–14 years and 1 610 233 Swedish born. The study population was followed from age 18 to year 2016 for hospitalisations with a discharge diagnosis of NAPD. Hazard ratios (HRs) were calculated in gender stratified Cox regression models, adjusted for household income at age 17.

The adjusted risks of NAPD were 2.33 [95% confidence interval (CI) 2.07–2.63] for the international adoptees and 1.92 (1.76–2.09) for the former child refugees, relative to the Swedish-born population. For the international adoptees there was a stepwise gradient for NAPD by age of adoption from adjusted HR 1.66 (1.29–2.03) when adopted during the first year of life to adjusted HR 4.56 (3.22–6.46) when adopted at ages 5–14 years, with a similar risk pattern in women and men. Age at residency did not influence the risk of NAPD in the refugees, but their male to female risk ratio was higher than in Swedish-born and the adoptees.

The risk pattern in the international adoptees gives support to a link between early childhood adversity and NAPD. Male gender increased the risk of NAPD more among the refugees.

The 22q11.2 deletion (22q11Del) is among the strongest known genetic risk factors for psychosis. Stress, a known risk factor for psychosis in the general population, has seldom been studied in 22q11Del. We investigated how lifetime stressors related to symptomatic outcomes in patients with 22q11Del. We also explored this association in individuals with 22q11.2 duplications (22q11Dup), which may be potentially protective against psychosis.

One hundred individuals (46 with 22q11Del, 30 with 22q11Dup, and 24 healthy controls; Mage = 17.30 years±10.15) were included. Logistic models were used to examine cross-sectional associations between lifetime acute and chronic stressors (severity and count) and the presence (score ⩾3) of positive, negative, and general symptoms, assessed via the Structured Interview for Psychosis-risk Syndromes (SIPS).

The 22q11Dup group reported the greatest number and severity of acute lifetime stressors, but did not differ from 22q11Del in chronic stressor count or severity. Lifetime chronic and acute stressors were uniquely associated with positive symptoms in 22q11Del (chronic count: odds ratio [OR] = 2.35, p = 0.02; chronic severity: OR = 1.88, p = 0.03; acute count: OR = 1.78, p = 0.03), but not with negative or general symptoms (ps > 0.05).

Findings suggest that stress may play a role in psychotic symptoms in 22q1Del, while the 22q11Dup CNV appears protective against psychotic symptoms despite higher rates of stressors. Interventions that mitigate effects of stressors in 22qDel may reduce the odds of psychosis in this group. Prospective longitudinal research is needed to replicate these findings.

Mental health problems are elevated in autistic individuals but there is limited evidence on the developmental course of problems across childhood. We compare the level and growth of anxious-depressed, behavioral and attention problems in an autistic and typically developing (TD) cohort.

Latent growth curve models were applied to repeated parent-report Child Behavior Checklist data from age 2–10 years in an inception cohort of autistic children (Pathways, N = 397; 84% boys) and a general population TD cohort (Wirral Child Health and Development Study; WCHADS; N = 884, 49% boys). Percentile plots were generated to quantify the differences between autistic and TD children.

Autistic children showed elevated levels of mental health problems, but this was substantially reduced by accounting for IQ and sex differences between the autistic and TD samples. There was small differences in growth patterns; anxious-depressed problems were particularly elevated at preschool and attention problems at late childhood. Higher family income predicted lower base-level on all three dimensions, but steeper increase of anxious-depressed problems. Higher IQ predicted lower level of attention problems and faster decline over childhood. Female sex predicted higher level of anxious-depressed and faster decline in behavioral problems. Social-affect autism symptom severity predicted elevated level of attention problems. Autistic girls' problems were particularly elevated relative to their same-sex non-autistic peers.

Autistic children, and especially girls, show elevated mental health problems compared to TD children and there are some differences in predictors. Assessment of mental health should be integrated into clinical practice for autistic children.

Causes of childhood behavior problems remain poorly understood. Enriched family environments and corresponding brain development may reduce the risk of their onset, but research investigating white matter neurodevelopmental pathways explaining associations between the family environment and behavior remains limited. We hypothesized that more positive prenatal and mid-childhood family functioning – a measure of a family's problem solving and supportive capacity – would be associated with two markers of preadolescent white matter neurodevelopment related to reduced behavior problems: higher global fractional anisotropy (FA) and lower global mean diffusivity (MD).

Data are from 2727 families in the Generation R Study, the Netherlands. Mothers reported family functioning (McMaster Family Assessment Device, range 1–4, higher scores indicate healthier functioning) prenatally and in mid-childhood (mean age 6.1 years). In preadolescence (mean age 10.1), the study collected diffusion-weighted scans. We computed standardized global MD and FA values by averaging metrics from 27 white matter tracts, and we fit linear models adjusting for possible confounders to examine global and tract-specific outcomes.

Prenatal and mid-childhood family functioning scores were moderately correlated, r = 0.38. However, only prenatal family functioning – and not mid-childhood functioning – was associated with higher global FA and lower global MD in preadolescence in fully adjusted models: βglobal FA = 0.11 (95% CI 0.00, 0.21) and βglobal MD = −0.15 (95% CI −0.28, −0.03) per one-unit increase in functioning score. Sensitivity and tract-specific analyses supported these global findings.

These results suggest high-functioning prenatal or perinatal family environments may confer lasting white matter neurodevelopmental benefits into preadolescence.

The study is aimed to identify brain functional connectomes predictive of depressed and elevated mood symptomatology in individuals with bipolar disorder (BD) using the machine learning approach Connectome-based Predictive Modeling (CPM).

Functional magnetic resonance imaging data were obtained from 81 adults with BD while they performed an emotion processing task. CPM with 5000 permutations of leave-one-out cross-validation was applied to identify functional connectomes predictive of depressed and elevated mood symptom scores on the Hamilton Depression and Young Mania rating scales. The predictive ability of the identified connectomes was tested in an independent sample of 43 adults with BD.

CPM predicted the severity of depressed [concordance between actual and predicted values (r = 0.23, pperm (permutation test) = 0.031) and elevated (r = 0.27, pperm = 0.01) mood. Functional connectivity of left dorsolateral prefrontal cortex and supplementary motor area nodes, with inter- and intra-hemispheric connections to other anterior and posterior cortical, limbic, motor, and cerebellar regions, predicted depressed mood severity. Connectivity of left fusiform and right visual association area nodes with inter- and intra-hemispheric connections to the motor, insular, limbic, and posterior cortices predicted elevated mood severity. These networks were predictive of mood symptomatology in the independent sample (r ⩾ 0.45, p = 0.002).

This study identified distributed functional connectomes predictive of depressed and elevated mood severity in BD. Connectomes subserving emotional, cognitive, and psychomotor control predicted depressed mood severity, while those subserving emotional and social perceptual functions predicted elevated mood severity. Identification of these connectome networks may help inform the development of targeted treatments for mood symptoms.

The scale of the global mental health burden indicates the inadequacy not only of current treatment options, but also the pace of the standard treatment development process. The ‘leapfrog’ trial design is a newly-developed simple Bayesian adaptive trial design with potential to accelerate treatment development. A first leapfrog trial was conducted to provide a demonstration and test feasibility, applying the method to a low-intensity internet-delivered intervention targeting anhedonia.

At the start of this online, single-blind leapfrog trial, participants self-reporting depression were randomized to an initial control arm comprising four weeks of weekly questionnaires, or one of two versions of a four-week cognitive training intervention, imagery cognitive bias modification (imagery CBM). Intervention arms were compared to control on an ongoing basis via sequential Bayesian analyses, based on a primary outcome of anhedonia at post-intervention. Results were used to eliminate and replace arms, or to promote them to become the control condition based on pre-specified Bayes factor and sample size thresholds. Two further intervention arms (variants of imagery CBM) were added into the trial as it progressed.

N = 188 participants were randomized across the five trial arms. The leapfrog methodology was successfully implemented to identify a ‘winning’ version of the imagery CBM, i.e. the version most successful in reducing anhedonia, following sequential elimination of the other arms.

The study demonstrates feasibility of the leapfrog design and provides a foundation for its adoption as a method to accelerate treatment development in mental health. Registration: clinicaltrials.gov, NCT04791137.