There is limited experimentally controlled neuroimaging research available that could explain how dissociative states occur and which neurobiological changes are involved in acute post-traumatic dissociation.

To test the causal hypothesis that acute dissociation is triggered bottom-up by a selective noradrenergic-mediated increase in amygdala activation during the processing of autobiographical trauma memories.

Women with post-traumatic stress disorder (n = 47) and a history of interpersonal childhood trauma underwent a within-participant, placebo-controlled pharmacological challenge paradigm (4.0 mg reboxetine versus placebo) employing script-driven imagery (traumatic versus neutral autobiographical memory recall). Script-elicited brain activation patterns (measured via functional magnetic resonance imagery) were analysed by means of whole-brain analyses and a pre-registered region of interest (i.e. amygdala).

Self-reported acute dissociation increased significantly during trauma (versus neutral) recall but did not differ between pharmacological conditions. The pharmacological manipulation was also unsuccessful in eliciting increased amygdala activation following script-driven imagery in the reboxetine (versus placebo) condition. In the reboxetine condition, trauma retrieval resulted in similar activation patterns as in the placebo condition (e.g. elevated brain activation in the middle occipital gyrus and supramarginal gyrus), albeit with different peaks.

Current (null) findings cast doubt on the suggested role of the amygdala in subserving dissociative processing of trauma memories. Alternative pharmacological manipulation approaches (e.g. ketamine) and analysis techniques (e.g. event-related independent component analysis) might provide better insight into the spatiotemporal dynamics and network shifts involved in dissociative experiences and autobiographical trauma memory recall.

Current neurobiological models of post-traumatic stress disorder (PTSD) assume excessive medial frontal activation and hypoactivation of cortico-limbic regions as neural markers of post-traumatic dissociation. Script-driven imagery is an established experimental paradigm that is used to study acute dissociative reactions during trauma exposure. However, there is a scarcity of experimental research investigating neural markers of dissociation; findings from existing script-driven neuroimaging studies are inconsistent and based on small sample sizes.

The current aim was to identify the neural correlates of acute post-traumatic dissociation by employing the script-driven imagery paradigm in combination with functional magnetic resonance imaging.

Functional neuroimaging data was acquired in 51 female patients with PTSD with a history of interpersonal childhood trauma. Blood-oxygen-level-dependent response during the traumatic (versus neutral) autobiographical memory recall was analysed, and the derived activation clusters were correlated with dissociation measures.

During trauma recall, enhanced activation in the cerebellum, occipital gyri, supramarginal gyrus and amygdala was identified. None of the derived clusters correlated significantly with dissociative symptoms, although patients reported increased levels of acute dissociation following the paradigm.

The present study is one of the largest functional magnetic resonance imaging investigations of dissociative neural biomarkers in patients with PTSD undergoing experimentally induced trauma confrontation to elicit symptom-specific brain reactivity. In light of the current reproducibility crisis prominent in neuroimaging research owing to costly and time-consuming data acquisition, the current (null) findings highlight the difficulty of extracting reliable neurobiological biomarkers for complex subjective experiences such as dissociation.

Aberrant brain connectivity during emotional processing, especially within the fronto-limbic pathway, is one of the hallmarks of major depressive disorder (MDD). However, the methodological heterogeneity of previous studies made it difficult to determine the functional and etiological implications of specific alterations in brain connectivity. We previously reported alterations in psychophysiological interaction measures during emotional face processing, distinguishing depressive pathology from at-risk/resilient and healthy states. Here, we extended these findings by effective connectivity analyses in the same sample to establish a refined neural model of emotion processing in depression.

Thirty-seven patients with MDD, 45 first-degree relatives of patients with MDD and 97 healthy controls performed a face-matching task during functional magnetic resonance imaging. We used dynamic causal modeling to estimate task-dependent effective connectivity at the subject level. Parametric empirical Bayes was performed to quantify group differences in effective connectivity.

MDD patients showed decreased effective connectivity from the left amygdala and left lateral prefrontal cortex to the fusiform gyrus compared to relatives and controls, whereas patients and relatives showed decreased connectivity from the right orbitofrontal cortex to the left insula and from the left orbitofrontal cortex to the right fusiform gyrus compared to controls. Relatives showed increased connectivity from the anterior cingulate cortex to the left dorsolateral prefrontal cortex compared to patients and controls.

Our results suggest that the depressive state alters top-down control of higher visual regions during face processing. Alterations in connectivity within the cognitive control network present potential risk or resilience mechanisms.

The coronavirus disease 2019 (COVID-19) pandemic might affect mental health. Data from population-representative panel surveys with multiple waves including pre-COVID data investigating risk and protective factors are still rare.

In a stratified random sample of the German household population (n = 6684), we conducted survey-weighted multiple linear regressions to determine the association of various psychological risk and protective factors assessed between 2015 and 2020 with changes in psychological distress [(PD; measured via Patient Health Questionnaire for Depression and Anxiety (PHQ-4)] from pre-pandemic (average of 2016 and 2019) to peri-pandemic (both 2020 and 2021) time points. Control analyses on PD change between two pre-pandemic time points (2016 and 2019) were conducted. Regularized regressions were computed to inform on which factors were statistically most influential in the multicollinear setting.

PHQ-4 scores in 2020 (M = 2.45) and 2021 (M = 2.21) were elevated compared to 2019 (M = 1.79). Several risk factors (catastrophizing, neuroticism, and asking for instrumental support) and protective factors (perceived stress recovery, positive reappraisal, and optimism) were identified for the peri-pandemic outcomes. Control analyses revealed that in pre-pandemic times, neuroticism and optimism were predominantly related to PD changes. Regularized regression mostly confirmed the results and highlighted perceived stress recovery as most consistent influential protective factor across peri-pandemic outcomes.

We identified several psychological risk and protective factors related to PD outcomes during the COVID-19 pandemic. A comparison of pre-pandemic data stresses the relevance of longitudinal assessments to potentially reconcile contradictory findings. Implications and suggestions for targeted prevention and intervention programs during highly stressful times such as pandemics are discussed.

It has not yet been determined if the commonly reported cannabis–psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders.

We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort.

PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects.

These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis–psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.

Sex-related differences in psychopathology are known phenomena, with externalizing and internalizing symptoms typically more common in boys and girls, respectively. However, the neural correlates of these sex-by-psychopathology interactions are underinvestigated, particularly in adolescence.

Participants were 14 years of age and part of the IMAGEN study, a large (N = 1526) community-based sample. To test for sex-by-psychopathology interactions in structural grey matter volume (GMV), we used whole-brain, voxel-wise neuroimaging analyses based on robust non-parametric methods. Psychopathological symptom data were derived from the Strengths and Difficulties Questionnaire (SDQ).

We found a sex-by-hyperactivity/inattention interaction in four brain clusters: right temporoparietal-opercular region (p < 0.01, Cohen's d = −0.24), bilateral anterior and mid-cingulum (p < 0.05, Cohen's d = −0.18), right cerebellum and fusiform (p < 0.05, Cohen's d = −0.20) and left frontal superior and middle gyri (p < 0.05, Cohen's d = −0.26). Higher symptoms of hyperactivity/inattention were associated with lower GMV in all four brain clusters in boys, and with higher GMV in the temporoparietal-opercular and cerebellar-fusiform clusters in girls.

Using a large, sex-balanced and community-based sample, our study lends support to the idea that externalizing symptoms of hyperactivity/inattention may be associated with different neural structures in male and female adolescents. The brain regions we report have been associated with a myriad of important cognitive functions, in particular, attention, cognitive and motor control, and timing, that are potentially relevant to understand the behavioural manifestations of hyperactive and inattentive symptoms. This study highlights the importance of considering sex in our efforts to uncover mechanisms underlying psychopathology during adolescence.

Tobacco smoking remains one of the leading causes of preventable illness and death and is heritable with complex underpinnings. Converging evidence suggests a contribution of the polygenic risk for smoking to the use of tobacco and other substances. Yet, the underlying brain mechanisms between the genetic risk and tobacco smoking remain poorly understood.

Genomic, neuroimaging, and self-report data were acquired from a large cohort of adolescents from the IMAGEN study (a European multicenter study). Polygenic risk scores (PGRS) for smoking were calculated based on a genome-wide association study meta-analysis conducted by the Tobacco and Genetics Consortium. We examined the interrelationships among the genetic risk for smoking initiation, brain structure, and the number of occasions of tobacco use.

A higher smoking PGRS was significantly associated with both an increased number of occasions of tobacco use and smaller cortical volume of the right orbitofrontal cortex (OFC). Furthermore, reduced cortical volume within this cluster correlated with greater tobacco use. A subsequent path analysis suggested that the cortical volume within this cluster partially mediated the association between the genetic risk for smoking and the number of occasions of tobacco use.

Our data provide the first evidence for the involvement of the OFC in the relationship between smoking PGRS and tobacco use. Future studies of the molecular mechanisms underlying tobacco smoking should consider the mediation effect of the related neural structure.

Contrary to public perception, child sex offending (CSO) and paedophilia are not the same. Only half of all cases of CSO are motivated by paedophilic preference, and a paedophilic preference does not necessarily lead to CSO. However, studies that investigated clinical factors accompanying and contributing to paedophilia so far mainly relied on paedophiles with a history of CSO. The aim of this study was to distinguish between factors associated with sexual preference (paedophile versus non-paedophile) and offender status (with versus without CSO). Accordingly, a 2 (sexual preference) × 2 (offender status) factorial design was used for a comprehensive clinical assessment of paedophiles with and without a history of CSO (n = 83, n = 79 respectively), child sex offenders without paedophilia (n = 32) and healthy controls (n = 148). Results indicated that psychiatric comorbidities, sexual dysfunctions and adverse childhood experiences were more common among paedophiles and child sex offenders than controls. Offenders and non-offenders differed in age, intelligence, educational level and experience of childhood sexual abuse, whereas paedophiles and non-paedophiles mainly differed in sexual characteristics (e.g., additional paraphilias, onset and current level of sexual activity). Regression analyses were more powerful in segregating offender status than sexual preference (mean classification accuracy: 76% versus 68%). In differentiating between offence- and preference-related factors this study improves clinical understanding of both phenomena and may be used to develop scientifically grounded CSO prevention and treatment programmes. It also highlights that some deviations are not traceable to just one of these two factors, thus raising the issue of the mechanism underlying both phenomena.

Limbic-cortical imbalance is an established model for the neurobiology of major depressive disorder (MDD), but imaging genetics studies have been contradicting regarding potential risk and resilience mechanisms. Here, we re-assessed previously reported limbic-cortical alterations between MDD relatives and controls in combination with a newly acquired sample of MDD patients and controls, to disentangle pathology, risk, and resilience.

We analyzed functional magnetic resonance imaging data and negative affectivity (NA) of MDD patients (n = 48), unaffected first-degree relatives of MDD patients (n = 49) and controls (n = 109) who performed a faces matching task. Brain response and task-dependent amygdala functional connectivity (FC) were compared between groups and assessed for associations with NA.

Groups did not differ in task-related brain activation but activation in the superior frontal gyrus (SFG) was inversely correlated with NA in patients and controls. Pathology was associated with task-independent decreases of amygdala FC with regions of the default mode network (DMN) and decreased amygdala FC with the medial frontal gyrus during faces matching, potentially reflecting a task-independent DMN predominance and a limbic-cortical disintegration during faces processing in MDD. Risk was associated with task-independent decreases of amygdala-FC with fronto-parietal regions and reduced faces-associated amygdala-fusiform gyrus FC. Resilience corresponded to task-independent increases in amygdala FC with the perigenual anterior cingulate cortex (pgACC) and increased FC between amygdala, pgACC, and SFG during faces matching.

Our results encourage a refinement of the limbic-cortical imbalance model of depression. The validity of proposed risk and resilience markers needs to be tested in prospective studies. Further limitations are discussed.

Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.

Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.

CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.

Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

Abnormalities in reward circuit function are considered a core feature of addiction. Yet, it is still largely unknown whether these abnormalities stem from chronic drug use, a genetic predisposition, or both.

In the present study, we investigated this issue using a large sample of adolescent children by applying structural equation modeling to examine the effects of several dopaminergic polymorphisms of the D1 and D2 receptor type on the reward function of the ventral striatum (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors at 14 years of age and again at 16 years of age.

The results demonstrated a regional specificity with which the functional polymorphism rs686 of the D1 dopamine receptor (DRD1) gene and Taq1A of the ANKK1 gene influenced medial and lateral OFC activation during reward anticipation, respectively. Importantly, our path model revealed a significant indirect relationship between the rs686 of the DRD1 gene and early onset of alcohol misuse through a medial OFC × VS interaction.

These findings highlight the role of D1 and D2 in adjusting reward-related activations within the mesocorticolimbic circuitry, as well as in the susceptibility to early onset of alcohol misuse.

The substantial discrepancy between mentalising in experimental settings v. real-life social interactions hinders the understanding of the neural basis of real-life social cognition and of social impairments in psychiatric disorders.

To determine the neural mechanisms underlying naturalistic mentalising in individuals with and without autism spectrum disorder.

We investigated mentalising with a new video-based functional magnetic resonance imaging task in 20 individuals with autism spectrum disorder and 22 matched healthy controls.

Naturalistic mentalising implicated regions of the traditional mentalising network (medial prefrontal cortex, temporoparietal junction), and additionally the insula and amygdala. Moreover, amygdala activity predicted implicit mentalising performance on an independent behavioural task. Compared with controls, the autism spectrum disorder group did not show differences in neural activity within classical mentalising regions. They did, however, show reduced amygdala activity and a reduced correlation between amygdala activity and mentalising accuracy on the behavioural task, compared with controls.

These findings highlight the crucial role of the amygdala in making accurate implicit mental state inferences in typical development and in the social cognitive impairments of individuals with autism spectrum disorder.

Autism spectrum disorder (ASD) is linked to social brain activity and facial affect recognition (FAR).

To examine social brain plasticity in ASD.

Using FAR tests and functional magnetic resonance imaging tasks for FAR, we compared 32 individuals with ASD and 25 controls. Subsequently, the participants with ASD were assigned to FAR computer-aided cognitive training or a control group.

The ASD group performed more poorly than controls on explicit behavioural FAR tests. In the scanner, during implicit FAR, the amygdala, fusiform gyrus and other regions of the social brain were less activated bilaterally. The training group improved on behavioural FAR tests, and cerebral response to implicit affect processing tasks increased bilaterally post-training in the social brain.

Individuals with ASD show FAR impairments associated with hypoactivation of the social brain. Computer-based training improves explicit FAR and neuronal responses during implicit FAR, indicating neuroplasticity in the social brain in ASD.