Avoidant/restrictive food intake disorder (ARFID) leads to faltering growth and psychosocial impairment. Three phenotypes can co-occur: fear of aversive consequences of eating (ARFID-fear phenotype), sensory sensitivity, and lack of interest in eating/food. We hypothesized that youth with ARFID, especially ARFID-fear phenotype, would show hyperactivation of fear-related regions in response to ARFID-specific fear images, compared to healthy controls (HC), and activation of these regions would positively correlate with ARFID fear severity.

Youth (N=103: 76 ARFID, including 20 ARFID-fear phenotype; 27 HC) underwent functional MRI scanning while viewing ARFID-specific fear (e.g. vomiting, choking) versus neutral images. We compared blood-oxygen-level-dependent (BOLD) response in fear-related region of interests (ROI; e.g. amygdala, hippocampus, insula) between ARFID and ARFID-fear phenotype versus HC. We evaluated the association between brain response and ARFID fear severity in ARFID-fear phenotype.

Across individuals, there was a robust bilateral amygdala response to ARFID-specific fear versus neutral images. Compared to HC, ARFID-fear phenotype showed a greater insula response to ARFID-specific fear versus neutral images (p=0.049). There were no other group differences and no significant relationships between BOLD response and ARFID fear severity in ARFID-fear phenotype.

ARFID-specific fear images elicit amygdala responses across individuals, with greater activation in the insula only in ARFID-fear phenotype versus HC. These findings validate the ARFID-specific fear paradigm and highlight the intriguing possibility that, in the ARFID-fear phenotype, universally feared experiences such as choking and vomiting serve as the unconditioned stimulus in developing ARFID and may partially be mediated by the insular cortex.

The dysconnection hypothesis of schizophrenia posits that widespread synaptic inefficiencies lead to altered macroscale brain connectivity, contributing to symptom severity and cognitive deficits in individuals with schizophrenia spectrum disorders (SSD). Emerging evidence suggests that physical exercise may help to ameliorate these connectivity abnormalities and associated clinical impairments.

This study investigated whether reductions in functional dysconnectivity following exercise therapy were associated with clinical improvements in individuals with SSD. In addition, it explored the genetic underpinnings of these changes using imaging transcriptomics.

Using data from the ESPRIT C3 trial, we analysed 23 SSD patients (seven female) undergoing aerobic exercise or flexibility, strengthening and balance training over 6 months. Functional dysconnectivity, assessed at baseline and post-intervention relative to a healthy reference sample (n = 200), was evaluated at the whole-brain, network and regional levels. Linear mixed effect models and voxel-wise Pearson’s correlations were used to assess exercise-induced changes and clinical relevance.

Functional dysconnectivity significantly decreased (d = −2.73, P < 0.001), and this decrease was primarily linked to enhanced oligodendrocyte-related gene expression. Reductions in the default-mode network were correlated with improved global functioning, whereas changes in insular regions were associated with symptom severity and functioning. Dysconnectivity reductions in somatomotor and frontoparietal networks were correlated with total symptom improvements, and changes in language-related regions (e.g. Broca’s area) were linked to cognitive benefits.

Our findings support the role of oligodendrocyte pathology in SSD and suggest that targeting dysconnectivity in the default-mode, salience and language networks may enhance global functioning, symptom severity and cognitive impairments.

Structural abnormalities in cortical and subcortical brain regions are consistently observed in schizophrenia; however, substantial inter-individual variability complicates identifying clear neurobiological biomarkers. The Person-Based Similarity Index (PBSI) quantifies individual structural variability; however, its applicability across schizophrenia stages remains unclear. This study aimed to compare cortical and subcortical structural variability in recent-onset and chronic schizophrenia and explore associations with clinical measures.

Neuroimaging data from 41 patients with recent-onset schizophrenia, 32 with chronic schizophrenia, and 59 healthy controls were analysed. The PBSI scores were calculated for cortical thickness, surface area, cortical grey matter volume, and subcortical volumes. Group differences in PBSI scores were assessed using linear regression and analysis of variance. Correlations between the PBSI scores and clinical measures were also examined.

Both patients with recent-onset and chronic schizophrenia exhibited significantly lower PBSI scores than healthy controls, indicating greater morphometric heterogeneity. However, significant differences between the recent-onset and chronic patient groups were limited to subcortical and cortical thickness PBSI scores. Correlations between PBSI scores and clinical symptoms are sparse and primarily restricted to surface area variability and symptom severity in patients with recent-onset schizophrenia.

Patients with schizophrenia show marked structural brain heterogeneity compared with healthy controls, which is detectable even in the early stages of the illness. Although there were few differences in PBSI scores between the recent-onset and chronic schizophrenia groups and limited correlations between PBSI scores and clinical measures, the PBSI may still provide valuable insights into individual differences contributing to clinical heterogeneity in schizophrenia.

Heightened reactivity in the amygdala measured by functional magnetic resonance imaging during emotional processing is considered a potential biomarker for clinical depression. Still, it is unknown whether this is also true for depressive symptoms in the general population, and – when in remission after recurrent depressive episodes – it is associated with future episodes.

Using the UK Biobank population study (n = 11,334), we investigated the association of amygdala reactivity during negative facial stimuli, focusing on lifetime depression (trait), depressive symptoms (state), and the modulating effect of antidepressant (AD) treatment thereof. We employed normative modeling (NM) to better incorporate population heterogeneity of the amygdala activity.

In line with a previous study, depressive symptoms (state) over the last 2 weeks were not associated with the amygdala reactivity signal. Rather, our results indicate a significant positive association (p = 0.03, ω2 = 0.001) between amygdala response and the recurrence of depressive episodes (trait). Longitudinal analysis revealed that the group that had experienced a single depressive episode before showed a significantly increased amygdala response after additional episodes (p = 0.03, ω2 = 0.017). ADs were not associated with amygdala response directly, but decreased associations within episode recurrence severity.

The amygdala response to negative stimuli was associated with an individual’s risk of recurrence of depressive episodes, and AD treatment reduced these associations. This study highlights the relevance of amygdala reactivity as a trait, but not a state biomarker for (recurrent) depression. Moreover, it demonstrates the benefit of applying NM in the context of population data.

There is a considerable overlap in clinical features and genetics between schizophrenia (SZ) and bipolar disorder (BD). Previous neuroimaging research has demonstrated common and distinct brain damage patterns between relatives (RELs) of SZ and BD patients, suggesting shared and differential genetic influences on the brain. Despite an increasing recognition that disorders localize better to distributed brain networks than individual brain regions, studies investigating network localization of genetic risk for SZ and BD are still lacking.

To address this gap, we initially identified brain functional and structural damage locations in SZ- and BD-RELs from 103 published studies with 2364 SZ-RELs, 864 BD-RELs, and 4114 healthy controls. By applying novel functional connectivity network mapping to large-scale discovery and validation resting-state functional MRI datasets, we mapped these affected brain locations to four disorder-susceptibility networks.

SZ-susceptibility functional damage network primarily involved the executive control and salience networks, while its BD-counterpart principally implicated the default mode and basal ganglia networks. SZ-susceptibility structural damage network predominantly involved the auditory and default mode networks, yet its BD-counterpart mainly implicated the language and executive control networks. Although these networks showed cross-disorder inconsistencies when focusing on either imaging modality alone, the combined SZ- and BD-susceptibility brain damage networks had a substantially increased spatial similarity.

These findings may support the concept that SZ and BD represent distinct diagnostic categories from a neurobiological perspective, helping to clarify the common network substrates via which the shared genetic mechanisms underlying both disorders give rise to their overlapping clinical phenotypes.

Although perceived threats in a child’s social environment, including in the family, school, and neighborhood, are known to increase risk for adolescent psychopathology, the underlying biological mechanisms remain unclear. To investigate, we examined whether perceived social threats were associated with the functional connectivity of large-scale cortical networks in early adolescence, and whether such connectivity differences mediated the development of subsequent mental health problems in youth.

Structural equation models were used to analyze data from 8,690 youth (50% female, 45% non-White, age 9–10 years) drawn from the large-scale, nationwide Adolescent Brain Cognitive Development study that has 21 clinical and research sites across the United States. Data were collected from 2016 to 2018.

Consistent with Social Safety Theory, perceived social threats were prospectively associated with mental health problems both 6 months (standardized $ \beta =0.27,p<.001 $) and 30 months ($ \beta =0.14,p<.001 $) later. Perceived social threats predicted altered connectivity patterns within and between the default mode (DMN), dorsal attention (DAN), frontoparietal (FPN), and cingulo-opercular (CON) networks. In turn, hypoconnectivity within the DMN and FPN – and higher (i.e., less negative) connectivity between DMN-DAN, DMN-CON, and FPN-CON – mediated the association between perceived social threats and subsequent mental health problems.

Perceiving social threats in various environments may alter neural connectivity and increase the risk of psychopathology in youth. Therefore, parenting, educational, and community-based interventions that bolster social safety may be helpful.

Developmental trauma increases psychosis risk in adulthood and is associated with poor prognosis and treatment response. It has been proposed that developmental trauma may give rise to a distinct psychosis phenotype. Our aim was to explore this by systematically reviewing neuroimaging studies of brain structure and function in adults with psychosis diagnoses, according to whether or not they had survived developmental trauma. We registered our search protocol in PROSPERO (CRD42018105021).

We systematically searched literature databases for relevant studies published before May 2024. We identified 31 imaging studies (n = 1,761 psychosis patients, n = 1,775 healthy controls or healthy siblings).

Developmental trauma was associated with global and regional differences in gray matter; corticolimbic structural dysconnectivity; a potentiated threat detection system; dysfunction in regions associated with mentalization; and elevated striatal dopamine synthesis capacity.

These findings warrant further research to elucidate vulnerability and resilience mechanisms for psychosis in developmental trauma survivors.