Strategies to successfully regulate negative emotions may be hindered by maladaptive implicit emotion processing tendencies. And while implicit emotion regulation is known to be impaired in many psychiatric disorders, contradictory findings exist within the empirical literature. Therefore, a meta-analysis of implicit emotion regulation in mood and anxiety disorders (major depressive disorder [MDD], bipolar disorder, generalised anxiety disorder, social anxiety disorder, panic disorder, obsessive-compulsive disorder and post-traumatic stress disorder [PTSD]) was performed. Systematic literature searches were conducted in Web of Science, PubMed/MEDLINE, Scopus, and BrainMap for articles published between 2011 and 2024, and inclusion criteria included internationally recognised diagnostic measures (i.e., DSM-5). A total of 23 clinical studies were identified, and using the Newcastle-Ottawa Scale, 21 studies were of excellent quality. Small to medium effect sizes were reported in patients across measures of accuracy (patients [n = 428] vs. controls [n = 412], standardised mean difference [SMD] -0.39, 95% CI [-0.57 to -0.21], p < .0001) and response latency (patients [n = 477] vs. controls [n = 428], SMD 0.38, 95% CI [0.22 to 0.54], p < .0001). The pooled effects of reduced accuracy and longer reaction times in patients were confirmed by separate sub-group analyses for mood and anxiety disorders, with MDD and PTSD reporting the largest effects. Regarding publication bias, Egger's regression test did not indicate funnel plot asymmetry. Recommendations for future research include investigation of dysfunctional implicit emotion regulation as a transdiagnostic characteristic of psychiatric disorders within the Research Domain Criteria (RDoC) framework.

Borderline personality disorder (BPD) and complex posttraumatic stress disorder (cPTSD) share clinical similarities, complicating diagnosis and treatment. Research on the neurobiology of BPD and monotraumatic PTSD has shown that a prefrontal-limbic imbalance in emotional and reward processing is a hallmark of both disorders, but studies examining this network in cPTSD are lacking. Therefore, this study aimed to directly compare neural processing of emotion and reward during decision making in cPTSD and BPD.

Using functional magnetic resonance imaging, we measured neural activity in female patients (27 patients with cPTSD, 21 patients with BPD and 37 healthy controls) during a Desire-Reason Dilemma task featuring distracting fearful facial expressions.

We found no differences in neural activation when comparing cPTSD and BPD. However, when grouping patients based on symptom severity instead on diagnosis, we found that increased symptoms of cPTSD were associated with increased activation of dorsolateral prefrontal cortex during reward rejection, whereas increased symptoms of BPD were associated with decreased activation in prefrontal and limbic regions during reward rejection with distracting negative emotional stimuli.

This is the first study to investigate and compare emotional processing and reward-based decision making in cPTSD and BPD. Although we found no neural differences between disorders, we identified symptom-related neural patterns. Specifically, we found that elevated cPTSD symptoms were related to greater sensitivity to reward stimuli, whereas heightened BPD symptoms were related to increased susceptibility to emotional stimuli during goal-directed decision making. These findings enhance our understanding of neural pathomechanisms in trauma-related disorders.

With the advent of human neuroimaging, researchers were drawn to the idea that by better understanding the human brain, more effective mental health interventions could be developed. It has been more than 20 years since the first functional magnetic resonance imaging (fMRI) studies were conducted to examine changes in brain activation with anxiety-related treatments and more than 60 studies have since been published in this vein. For the current review, we conduct a systematic review of this literature, focusing on adult studies using task-based fMRI to measure brain activation changes with pharmacologic or psychotherapy interventions for phobia, social anxiety disorder, panic disorder, generalized anxiety disorder, posttraumatic stress disorder, and obsessive-compulsive disorder. Neuroscientific theories of anxiety-related disorders and their treatment have focused on prefrontal-insula-amygdala networks. Treatment-related decreases in amygdala and/or anterior insula activation were identified as the most consistent finding across disorders, with the most consistent results reported for specific phobia. Directionality of change and specific regions implicated in the prefrontal cortex were inconsistent across studies. The potential importance for probing other networks and processes as mechanisms of anxiety treatment was recognized, such as striatal regions underlying inhibitory learning or reward responsivity. Future treatment-fMRI research related to anxiety disorders would benefit from larger sample sizes, use of more nuanced computational approaches, and increased focus on replication. There is continued promise that fMRI research will enhance our understanding of how treatments work and inform the evolution of more effective or personalized mental health treatment.

Background: Post-traumatic stress disorder (PTSD) is increasingly prevalent in individuals with adverse childhood experiences (ACE). However, the underlying neurobiology of ACE-related PTSD remains unclear.Objective: The present study investigated the brain connectivity in ACE-related PTSD using multimodal neuroimaging data.Methods: Using a total of 119 participants with ACE (70 with ACE-related PTSD and 49 ACE-exposed controls), this study acquired T1-weighted MRI, diffusion-weighted MRI, and resting-state fMRI data to examine structural and functional connectivity between groups. Joint connectivity matrix independent component analysis (Jcm-ICA) was employed to allow shared information from all modalities to be examined and assess structural and functional connectivity differences between groups.Results: Jcm-ICA revealed distinct connectivity alterations in key brain regions involved in cognitive control, self-referential processing, and social behaviour. Compared to controls, the PTSD group exhibited functional hyperconnectivity of the right medial prefrontal cortex (PFC) of the default mode network and right inferior temporal cortex, and functional hypoconnectivity in the lateral-PFC of the central executive network and structural hypoconnectivity in white matter pathways including the right orbitofrontal region (OFC) linked to social behaviour. Post-hoc analyses using the joint brain-based information revealed that the severity of ACE, the number of traumas, and PTSD symptoms later in life significantly predicted the effects of ACE-related PTSD on the brain. Notably, no direct association between brain connectivity alterations and PTSD symptoms or the number of traumas within the PTSD group was observed.Conclusion: This study offers novel insights into the neurobiology of ACE-related PTSD using multimodal data fusion. We identified alterations in key brain networks (DMN, CEN) and OFC, suggesting potential deficits in cognitive control and social behaviour alongside heightened emotional processing in individuals with PTSD. Furthermore, our findings highlight the combined influence of ACE exposure, number of traumas experienced, and PTSD severity on brain connectivity disruptions, potentially informing future interventions.

Current psychotherapeutic treatments for OCD, while effective, have complex outcomes with mixed efficacy. Previous research has observed baseline brain activation patterns in OCD patients, elucidating some of the implications of this disorder. Observing the effects of evidence-based psychotherapeutics for OCD on brain activation (through MRI) may provide a more comprehensive outline of pathology. This systematic review and meta-analysis evaluated the effects of cognitive behavioural therapy (CBT) with exposure-response prevention (ERP) on brain activation in OCD patients. Academic databases were systematically searched, and the outcomes evaluated included changes in brain activation and symptom severity between baseline and post-treatment. Patients (n = 193) had confirmed OCD diagnosis and underwent protocolized CBT with ERP programs delivered by trained therapists. Participants in the CBT with ERP programs demonstrated significant improvements in symptom severity (Cohen's d = - 1.91). In general, CBT with ERP resulted in decreased activation post-treatment in the frontal (Cohen's d = 0.40), parietal (Cohen's d = 0.79), temporal (Cohen's d = 1.02), and occipital lobe (Cohen's d = 0.76), and cerebellum (Cohen's d = - 0.78). The findings support CBT with ERP's ability to improve brain activation abnormalities in OCD patients. By identifying regions that improved activation levels, psychotherapy programs may benefit from the addition of function-specific features that could improve treatment outcomes.

Post-traumatic stress disorder (PTSD) is a debilitating condition which has been related to problems in emotional regulation, memory and cognitive control. Psychotherapy has a non-response rate of around 50% and understanding the neurobiological working mechanisms might help improve treatment. To integrate findings from multiple smaller studies, we performed the first meta-analysis of changes in brain activation with a specific focus on emotional processing after psychotherapy in PTSD patients. We performed a meta-analysis of brain activation changes after treatment during emotional processing for PTSD with seed-based d mapping using a pre-registered protocol (PROSPERO CRD42020211039). We analyzed twelve studies with 191 PTSD patients after screening 3700 studies. We performed systematic quality assessment both for the therapeutic interventions and neuroimaging methods. Analyses were done in the full sample and in a subset of studies that reported whole-brain results. We found decreased activation after psychotherapy in the left amygdala, (para)hippocampus, medial temporal lobe, inferior frontal gyrus, ventrolateral prefrontal cortex, right pallidum, anterior cingulate cortex, bilateral putamen, and insula. Decreased activation in the left amygdala and left ventrolateral PFC was also found in eight studies that reported whole-brain findings. Results did not survive correction for multiple comparisons. There is tentative support for decreased activation in the fear and cognitive control networks during emotional processing after psychotherapy for PTSD. Future studies would benefit from adopting a larger sample size, using designs that control for confounding variables, and investigating heterogeneity in symptom profiles and treatment response.

There is increasing evidence that major trauma can adversely affect the brain and cognition. In some cases, trauma may lead to deficits in executive function (EF). The anterior insula may be a causal outflow hub acting to coordinate EF-related brain networks. To clarify the neural underpinnings of EF deficits (EFD) after trauma, we performed a resting-state functional magnetic resonance imaging (rs-fMRI) study of anterior insular subnetworks in adults who have lost their only child. A total of 167 participants completed various psychological and cognitive assessments to assess EF-related deficits. Correlations were computed between abnormal connectivity and cognitive/post-traumatic stress symptoms. The results showed abnormal anterior insular subregion connectivity in the default mode network (DMN), prefrontal lobe, and cerebellum lobe in participants with EFD. No correlation was found between abnormal connectivity and cognitive/post-traumatic stress symptoms in participants with EFD. These results suggest that excessive connections between the insula and DMN could contribute to EFD after trauma. Overall, this study provides novel references into the neural mechanisms of EF status after trauma exposure.

Neuroimage studies have reported functional connectome abnormalities in posttraumatic stress disorder (PTSD), especially in adults. However, these studies often treated the brain as a static network, and time-variance of connectome topology in pediatric posttraumatic stress disorder remain unclear. To explore case-control differences in dynamic connectome topology, resting-state functional magnetic resonance imaging data were acquired from 24 treatment-naïve non-comorbid pediatric posttraumatic stress disorder patients and 24 demographically matched trauma-exposed non-posttraumatic stress disorder controls. A graph-theoretic analysis was applied to construct time-varying modular structure of whole-brain networks by maximizing the multilayer modularity. Network switching rate at the global, subnetwork, and nodal levels were calculated and compared between posttraumatic stress disorder and trauma-exposed non-posttraumatic stress disorder groups, and their associations with posttraumatic stress disorder symptom severity and sex interactions were explored. At the global level, individuals with posttraumatic stress disorder exhibited significantly lower network switching rates compared to trauma-exposed non-posttraumatic stress disorder controls. This difference was mainly involved in default-mode and dorsal attention subnetworks, as well as in inferior temporal and parietal brain nodes. Posttraumatic stress disorder symptom severity was negatively correlated with switching rate in the global network and default mode network. No significant differences were observed in the interaction between diagnosis and sex/age. Pediatric posttraumatic stress disorder is associated with dynamic reconfiguration of brain networks, which may provide insights into the biological basis of this disorder.

At least one-third posttraumatic stress disorder (PTSD) patients do not respond to trauma-focused psychotherapy (TF-psychotherapy), which is the treatment of choice for PTSD. To clarify the change mechanisms that may be associated with treatment response, this study examined changes in neural activations during affective and non-affective processing that occur with improvement of symptoms after TF-psychotherapy. This study assessed PTSD treatment-seeking patients (n = 27) prior to and after TF-psychotherapy using functional magnetic resonance imaging when they completed three tasks: (a) passive viewing of affective faces, (b) cognitive reappraisal of negative images, and (c) non-affective response inhibition. Patients then underwent 9 sessions of TF-psychotherapy, and were assessed on the Clinician-Administered PTSD Scale following treatment. Changes in neural responses in affect and cognitive processing regions-of-interest for each task were correlated with reduction of PTSD severity from pretreatment to posttreatment in the PTSD cohort. Data from 21 healthy controls was used for comparison. Improvement of symptoms in PTSD were associated with increased activation of left anterior insula, reductions in the left hippocampus and right posterior insula during viewing of supraliminally presented affective images, and reduced connectivity between the left hippocampus with the left amygdala and rostral anterior cingulate. Treatment response was also associated with reduced activation in the left dorsolateral prefrontal cortex during reappraisal of negative images. There were no associations between response and activation change during response inhibition. This pattern of findings indicates that improvement of PTSD symptoms following TF-psychotherapy is associated with changes in affective rather than non-affective processes. These findings accord with prevailing models that TF-psychotherapy promotes engagement and mastery of affective stimuli.Clinical Trials Registration: Trial Registration: Prospectively registered at Australian and New Zealand Clinical Trials Registry, ACTRN12612000185864 and ACTRN12609000324213. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83857.

The recent update of the International Classification of Diseases 11th revision (ICD-11) introduced the diagnosis of complex posttraumatic stress disorder (CPTSD) as a distinct entity from posttraumatic stress disorder (PTSD). Because psychophysiological alterations are a core diagnostic feature of PTSD and CPTSD, the aim of the current study was to examine potential distinctive patterns in cortical and cardiac responses to emotional words in adolescent and young adult patients with PTSD and CPTSD.

Event-related potentials and heart rate responses were studied in 81 adolescent and young adult participants, of which 17 individuals were diagnosed with ICD-11 PTSD and 32 individuals with CPTSD, each after childhood sexual and/or physical abuse. Thirty-two individuals served as healthy controls. The paradigm consisted of a passive reading task with neutral, positive, physically threatening, and socially threatening words.

Differentiated early processing of emotional words was indicated by differences on P1 and left EPN components. Additionally, PTSD and CPTSD patients presented with specific patterns of heart rate responses to emotional words. In CPTSD patients, heart rate reactions to emotional words were more variable than in PTSD patients.

These findings provide early evidence of differentiated cortical and cardiac response patterns in adolescent and young adult patients with CPTSD and PTSD, supporting a nosological distinction between PTSD and complex PTSD. However, due to small and unequal sample sizes, findings presented in the current study are preliminary and require future research.

Childhood trauma may cause borderline personality disorder (BPD). The aim of this study was to assess functional alteration and its association with childhood trauma in Chinese adolescents with BPD.

A total of 187 adolescents with BPD aged 12-17 years and 207 age and gender- matched healthy controls (HCs) were enrolled into this study. The sample consisted of 50 adolescents with BPD and 21 HCs underwent brain resting-state functional magnetic resonance imaging (rs-fMRI). The rs-fMRI data was analyzed for both neural activity as indicated by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC). Clinical assessment for childhood trauma, impulsivity, and depression was also performed. Correlative analysis of functional alterations with childhood trauma assessment were performed.

Adolescents with BPD had significantly higher rate of all assessed childhood trauma than the HC group (P < 0.001). Most adolescents with BPD (61.5 %) had emotional neglect, which was the most commonly seen type of childhood trauma. Compared with HCs, adolescents with BPD showed decreased ALFF in the cortical regions including the left superior frontal gyrus and right middle occipital gyrus, and default mode network (DMN) regions including the left angular gyrus and medial superior frontal gyrus. Adolescents with BPD also showed enhanced ALFF in the limbic system (left hippocampus, insula, thalamus) (P < 0.05, FWE correction, cluster size ≥100). There were significant correlations between the insula ALFF and childhood trauma assessment for emotional neglect, physical abuse and physical neglect (P < 0.01). Moreover, adolescents with BPD showed increased FC between the left insula and right cortical regions (voxel P < 0.001, cluster P < 0.05, FWE correction).

The sample size was small. This cohort had patients with more severe BPD symptoms and some had comorbidities such as anxiety and obsessive-compulsive disorder.

There were alterations of brain activity as indicated by ALFF in the limbic - cortical circuit and DMN regions in adolescents with BPD and the activity in the left insula was correlated with emotional neglect. In addition, the FC between the left insula and the limbic - prefrontal circuit was enhanced. These results implicate that the functional alterations of insula may serve as a potential neuroimaging biomarker for adolescents with BPD who suffered from childhood trauma.

The main objective of this meta-analysis was to investigate handedness in post-traumatic stress disorder on a meta-analytical level. For this purpose, articles were identified via a search in PubMed, PsychInfo, PubPsych, ResearchGate, and Google Scholar. Studies reporting findings relating to handedness in PTSD patients and healthy controls were considered eligible. In total, k = 14 studies with an overall N of 2939 (747 PTSD patients and 2192 controls) were included in the study. Random-effects meta-analyses, as well as robust Bayes meta-analyses (RoBMA), were conducted for three comparisons: (a) non-right-handedness, (b) left-handedness, and (c) mixed-handedness. Results showed significantly higher frequencies of non-right-handedness (odds ratio = 1.81) and mixed-handedness (odds ratio = 2.42) in PTSD patients compared to controls. No differences were found for left-handedness. This specific effect of mixed-handedness is in line with findings for other disorders, such as schizophrenia. Future studies should investigate common neurodevelopmental origins for the relationship between mixed-handedness and psychopathology and aim at investigating both handedness direction and handedness strength.

Despite a great diagnostic overlap, complex posttraumatic stress disorder (CPTSD) has been recognised by the ICD-11 as a new, discrete entity and recent empirical evidence points towards a distinction from simple posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). The development and maintenance of these disorders is sustained by neurobiological alterations and studies using functional magnetic resonance imaging (fMRI) may further contribute to a clear differentiation of CPTSD, PTSD and BPD. However, there are no existing fMRI studies directly comparing CPTSD, PTSD and BPD. In addition to a summarization of diagnostic differences and similarities, the current review aims to provide a qualitative comparison of neuroimaging findings on affective, attentional and memory processing in CPTSD, PTSD and BPD. Our narrative review alludes to an imbalance in limbic-frontal brain networks, which may be partially trans-diagnostically linked to the degree of trauma symptoms and their expression. Thus, CPTSD, PTSD and BPD may underlie a continuum where similar brain regions are involved but the direction of activation may constitute its distinct symptom expression. The neuronal alterations across these disorders may conceivably be better understood along a symptom-based continuum underlying CPTSD, PTSD and BPD. Further research is needed to amend for the heterogeneity in experimental paradigms and sample criteria.

A sharp increase in the prevalence of neuropsychiatric disorders, including major depression, anxiety, substance use disorders and posttraumatic stress disorder (PTSD) has occurred due to the traumatic nature of the persisting COVID-19 global pandemic. PTSD is estimated to occur in up to 25% of individuals following exposure to acute or chronic trauma, and the pandemic has inflicted both forms of trauma on much of the population through both direct physiological attack as well as an inherent upheaval to our sense of safety. However, despite significant advances in our ability to define and apprehend the effects of traumatic events, the neurobiology and neuroanatomical circuitry of PTSD, one of the most severe consequences of traumatic exposure, remains poorly understood. Furthermore, the current psychotherapies or pharmacological options for treatment have limited efficacy, durability, and low adherence rates. Consequently, there is a great need to better understand the neurobiology and neuroanatomy of PTSD and develop novel therapies that extend beyond the current limited treatments. This review summarizes the neurobiological and neuroanatomical underpinnings of PTSD and discusses the conventional and emerging psychotherapies, pharmacological and combined psychopharmacological therapies, including the use of psychedelic-assisted psychotherapies and neuromodulatory interventions, for the improved treatment of PTSD and the potential for their wider applications in other neuropsychiatric disorders resulting from traumatic exposure.

Complex post-traumatic stress disorder (complex PTSD) is a severe mental disorder that emerges in response to traumatic life events. Complex PTSD is characterised by three core post-traumatic symptom clusters, along with chronic and pervasive disturbances in emotion regulation, identity, and relationships. Complex PTSD has been adopted as a new diagnosis in the ICD-11. Individuals with complex PTSD typically have sustained or multiple exposures to trauma, such as childhood abuse and domestic or community violence. The disorder has a 1-8% population prevalence and up to 50% prevalence in mental health facilities. Progress in diagnostics, assessment, and differentiation from post-traumatic stress disorder and borderline personality disorder is reported, along with assessment and treatment of children and adolescents. Studies recommend multicomponent therapies starting with a focus on safety, psychoeducation, and patient-provider collaboration, and treatment components that include self-regulatory strategies and trauma-focused interventions.

Childhood trauma exposure is common and is associated with poor clinical outcomes in adolescence along with mental health and sociodemographic challenges in adulthood. While many strategies exist to investigate the biological imprint of childhood trauma exposure, functional neuroimaging is a robust and growing technology for non-invasive studies of brain activity following traumatic experience and the relationship of childhood trauma exposure with psychopathology, cognition, and behavior. In this review, we discuss three popular approaches for discerning functional neural correlates to early life trauma, including regional activation, bivariate functional connectivity, and network-based connectivity. The breadth of research in each method is discussed, followed by important limitations and considerations for future research. We close by considering emerging trends in functional neuroimaging research of childhood trauma, including the use of complex decision-making tasks to mimic clinically-relevant behaviors, data-driven techniques such as multivariate pattern analysis and whole-brain network topology, and the applications of real-time neurofeedback for treatment of trauma-related mental disorders. We aim for this review to provide a framework for understanding the relationship between atypical neural functioning and adverse outcomes following childhood trauma exposure, with a focus on improving consistency in research methods and translatability of research findings for clinical settings.

Exposure-based psychotherapy is a first-line treatment for posttraumatic stress disorder (PTSD), but its mechanisms are poorly understood. Functional brain connectivity is a promising metric for identifying treatment mechanisms and biosignatures of therapeutic response. To this end, we assessed amygdala and insula treatment-related connectivity changes and their relationship to PTSD symptom improvements.

Individuals with a primary PTSD diagnosis (N = 66) participated in a randomized clinical trial of prolonged exposure therapy (n = 36) versus treatment waiting list (n = 30). Task-free functional magnetic resonance imaging was completed prior to randomization and 1 month following cessation of treatment/waiting list. Whole-brain blood oxygenation level-dependent responses were acquired. Intrinsic connectivity was assessed by subregion in the amygdala and insula, limbic structures key to the disorder pathophysiology. Dynamic causal modeling assessed evidence for effective connectivity changes in select nodes informed by intrinsic connectivity findings.

The amygdala and insula displayed widespread patterns of primarily subregion-uniform intrinsic connectivity change, including increased connectivity between the amygdala and insula; increased connectivity of both regions with the ventral prefrontal cortex and frontopolar and sensory cortices; and decreased connectivity of both regions with the left frontoparietal nodes of the executive control network. Larger decreases in amygdala-frontal connectivity and insula-parietal connectivity were associated with larger PTSD symptom reductions. Dynamic causal modeling evidence suggested that treatment decreased left frontal inhibition of the left amygdala, and larger decreases were associated with larger symptom reductions.

PTSD psychotherapy adaptively attenuates functional interactions between frontoparietal and limbic brain circuitry at rest, which may reflect a potential mechanism or biosignature of recovery.

Focal brain stimulation has potential as a treatment for posttraumatic stress disorder (PTSD). In this review, we aim to inform selection of focal brain stimulation targets for treating PTSD by examining studies of the functional neuroanatomy of PTSD and treatment response. We first briefly review data on brain stimulation interventions for PTSD. Although published data suggest good efficacy overall, the neurobiological rationale for each stimulation target is not always clear.

Therefore, we assess pre- and post-treatment (predominantly psychotherapy) functional neuroimaging studies in PTSD to determine which brain changes seem critical to treatment response. Results of these studies are presented within a previously proposed functional neural systems model of PTSD.

While not completely consistent, research suggests that downregulating the fear learning and threat and salience detection circuits (i.e., amygdala, dorsal anterior cingulate cortex and insula) and upregulating the emotion regulation and executive function and contextual processing circuits (i.e., prefrontal cortical regions and hippocampus) may mediate PTSD treatment response.

This literature review provides some justification for current focal brain stimulation targets. However, the examination of treatment effects on neural networks is limited, and studies that include the stimulation targets are lacking. Further, additional targets, such as the cingulate, medial prefrontal cortex, and inferior parietal lobe, may also be worth investigation, especially when considering how to achieve network level changes. Additional research combining PTSD treatment with functional neuroimaging will help move the field forward by identifying and validating novel targets, providing better rationale for specific treatment parameters and personalizing treatment for PTSD.

Randomized controlled trials have shown efficacy of trauma-focused psychotherapies in youth with posttraumatic stress disorder (PTSD), but little is known about the relationship between treatment response and alternations in brain structures associated with PTSD. In this study, we longitudinally examined the association between treatment response and pre-to posttreatment changes in structural magnetic resonance imaging (MRI) scans using a voxel-based morphometry approach. We analyzed MRI scans of 35 patients (ages 8-18 years, 21 female) with PTSD (80%) or partial PTSD (20%) before and after eight weekly sessions of trauma-focused psychotherapy. PTSD severity was assessed longitudinally using the Clinician-Administered PTSD scale for Children and Adolescents to divide participants into responders and non-responders. Group by time interaction analysis showed significant differences in grey-matter volume in the bilateral insula due to volume reductions over time in non-responders compared to responders. Despite the significant group by time interaction, there were no significant group differences at baseline or follow-up. As typical development is associated with insula volume increase, these longitudinal MRI findings suggest that treatment non-response is associated with atypical neurodevelopment of the insula, which may underlie persistence of PTSD in youth. The absence of structural MRI changes in treatment responders, while in need of replication, suggest that successful trauma-focused psychotherapy may not directly normalize brain abnormalities associated with PTSD.

Meta-analytic results indicate that posttraumatic stress disorder (PTSD) is associated with hypoactivation of the medial prefrontal cortex (mPFC), hyperactivation of the amygdala, and volume reductions of the hippocampus. Effective psychotherapeutic treatments were hypothesized to normalize these neural patterns via upregulation of prefrontal structures, which in turn downregulate limbic regions.

To gain a sound understanding of the effects of successful psychotherapy on the brain, neural changes from pre- to post-treatment in PTSD patients will be aggregated.

A systematic literature search identified 24 original studies employing structural or functional MRI measurements both before and after treatment of patients diagnosed with PTSD.

In conjunction, the review returned little evidence of an activation increase in the mPFC/rostral anterior cingulate cortex (rACC) following successful treatment. Five out of 12 studies observed such an increase (especially during emotion processing tasks), albeit in partially non-overlapping brain regions. Conversely, neither the putative related activation decrease in the amygdala nor volumetric changes or altered activation during the resting state could be convincingly established.

Successful psychological treatments might potentially work via upregulation of the mPFC, which thus may be involved in symptom reduction. However, the role of the amygdala in recovery from PTSD remains unclear. There is currently no indication that the various PTSD treatment approaches employed by the reviewed studies differ regarding their action mechanisms, but further research on this topic is needed.

Success rates of psychotherapy in post-traumatic stress disorder related to childhood maltreatment (PTSD-CM) are limited.

Observer-blind multicentre randomised clinical trial (A-1) of 4-year duration comparing enhanced methods of STAIR Narrative Therapy (SNT) and of trauma-focused psychodynamic therapy (TF-PDT) each of up to 24 sessions with each other and a minimal attention waiting list in PTSD-CM. Primary outcome is severity of PTSD (Clinician-Administered PTSD Scale for DSM-5 total) assessed by masked raters. For SNT and TF-PDT, both superiority and non-inferiority will be tested. Intention-to-treat analysis (primary) and per-protocol analysis (secondary). Assessments at baseline, after 10 sessions, post-therapy/waiting period and at 6 and 12 months of follow-up. Adult patients of all sexes between 18 and 65 years with PTSD-CM will be included. Continuing stable medication is permitted. To be excluded: psychotic disorders, risk of suicide, ongoing abuse, acute substance related disorder, borderline personality disorder, dissociative identity disorder, organic mental disorder, severe medical conditions and concurrent psychotherapy. To be assessed for eligibility: n=600 patients, to be e randomly allocated to the study conditions: n=328. Data management, randomisation and monitoring will be performed by an independent European Clinical Research Infrastructure Network (ECRIN)-certified data coordinating centre for clinical trials (KKS Marburg). Report of AEs to a data monitoring and safety board. Complementing study A-1, four inter-related add-on projects, including subsamples of the treatment study A-1, will examine (1) treatment integrity (adherence and competence) and moderators and mediators of outcome (B-1); (2) biological parameters (B-2, eg, DNA damage, reactive oxygen species and telomere shortening); (3) structural and functional neural changes by neuroimaging (B-3) and (4) cost-effectiveness of the treatments (B-4, costs and utilities).

Approval by the institutional review board of the University of Giessen (AZ 168/19). Following the Consolidated Standards of Reporting Trials statement for non-pharmacological trials, results will be reported in peer-reviewed scientific journals and disseminated to patient organisations and media.

DRKS 00021142.

We investigated neural correlates of traumatic experience related to the lack of family care in adults with a history of institutionalization (IC) using the Emotional Stroop paradigm. The goals of our study were twofold: we investigated whether adults with IC history (n = 24; M_age  = 22.17, SD = 6.7) demonstrate atypical processing of emotionally salient words in general, and whether they exhibit selective processing bias toward family related words compared to adults raised in biological families (BFC; n = 28; M_age  = 22.25, SD = 4.9). Results demonstrated significant differences in accuracy but not response times between groups on the behavioral level, indicating that the IC group was overall less accurate in identifying the color of the font. Contrary to our prediction, there were no significant differences between neural response to family related versus unrelated words in the IC and BFC groups. The absence of group differences can be explained by the selection of stimuli, which were associated with family rather than institutional history. The IC group showed a larger N280-380 component in response to negative words compared to the BFC group, and larger negativity in the right parietal area in response to positive words in the same time window. Results demonstrate that institutional history is marked by altered emotional processing in the subpopulation of institutional care-leavers, but the footprint is not specific to traumatic experience and extends from general sensitivity to emotional words.

Previous studies have indicated a link between socio-emotional processing and the oxytocin receptor. In this regard, a single nucleotide polymorphism in the oxytocin receptor coding gene (OXTR rs2268493) has been linked with lower social functioning, increased risk for autism spectrum disorders (ASDs) and with post-mortem OXTR mRNA expression levels. Indeed, the levels of expression of OXTR in brain regions involved in emotion processing are also associated with maternal care. Furthermore, maternal care has been associated with emotional correlates. Taken together, these previous findings suggest a possible combined effect of rs2268493 and maternal care on emotion-related brain phenotypes. A crucial biological mechanism subtending emotional processing is the amygdala-dorsolateral prefrontal cortex (DLPFC) functional connection. On this basis, our aim was to investigate the interaction between rs2268493 and maternal care on amygdala-DLPFC effective connectivity during emotional evaluation. We characterized through dynamic causal modeling (DCM) patterns of amygdala-DLPFC effective connectivity during explicit emotion processing in healthy controls (HC), profiled based on maternal care and rs2268493 genotype. In the whole sample, right top-down DLPFC-to-amygdala pattern was the most likely directional model of effective connectivity. This pattern of connectivity was the most likely for all rs2268493/maternal care subgroups, except for thymine homozygous (TT)/low maternal care individuals. Here, a right bottom-up amygdala-to-DLPFC was the most likely directional model. These results suggest a gene by environment interaction mediated by the oxytocin receptor on biological phenotypes relevant to emotion processing.

Post-Traumatic Stress Disorder (PTSD) is often associated with impairments in emotional and cognitive domains. Contrarily to the emotional sphere, neural basis underpinnings to cognitive impairments are still not well known.

We performed a bibliographic search on PUBMED of all the studies investigating the cognitive impairments in PTSD individuals. We considered only studies that applied cognitive tasks using a functional Magnetic Resonance Imaging technique. The inclusion criteria were met by nine studies.

Overall, PTSD individuals reported significant impairments in the dorsolateral prefrontal cortex, anterior cingulate cortex, inferior frontal gyrus, insula, inferior temporal cortex, supplement motor area, and Default Mode Network (DMN). Moreover, abnormal activity was reported in subcortical structures (e.g. hippocampus, amygdala, thalamus) and in the cerebellum.

Cognitive functioning was assessed using different cognitive tasks. Potential confounding factors such as age, sex, symptoms intensity, and comorbidities might have influenced the results.

So far, the evidence reported that PTSD is characterized by cognitive impairments in several domains, such as attention, memory and autonomic arousal, which may be due to selective dysfunctions in brain regions that are part of cortical networks, the limbic system and DMN. However, further studies are needed in order to better assess the role of cognitive impairments in PTSD and to develop more targeted therapeutic approaches.

Survival requires effective shifting of attention from one stimulus to another as goals change. It has been consistently demonstrated that posttraumatic stress disorder (PTSD) is associated with both faster orienting of attention toward and slower disengagement of attention from affective stimuli. Prior work, however, suggests that attention abnormalities in PTSD may extend beyond the affective domain.

We used the Attention Network Test-modified to include invalid spatial cues-in conjunction with functional magnetic resonance imaging to examine the neurocognitive underpinnings of visuospatial attention in participants with PTSD (n = 31) and control participants who were (n = 20) and were not (n = 21) exposed to trauma.

We observed deficits in the utilization of spatial information in the group with PTSD. Specifically, compared with the non-trauma-exposed group, participants with PTSD showed a smaller reaction time difference between invalidly and validly cued targets, demonstrating that they were less likely to use spatial cues to inform subsequent behavior. We also found that in both the PTSD and trauma-exposed control groups, utilization of spatial information was positively associated with activation of attentional control regions (e.g., right precentral gyrus, inferior and middle frontal gyri) and negatively associated with activation in salience processing regions (e.g., right insula).

This pattern suggests that both trauma exposure and psychopathology may be associated with alterations of spatial attention. Overall, our findings suggest that both attention- and salience-network abnormalities may be related to altered attention in trauma-exposed populations. Treatments that target these neural networks could therefore be a new avenue for PTSD research.

The earliest neuroimaging studies in post-traumatic stress disorder (PTSD) utilized positron emission tomography (PET) to examine the brain's response to glucocorticoid administration given predominant neurobiological models of the stress response focusing on that neuroendocrine system. This work revealed that the anterior cingulate cortex and amygdala, which is now considered part of the salience network, play a role in treatment response, and set the stage for subsequent magnetic resonance (MR) imaging studies focused on understanding the role of the salience network in the neurobiology of treatment response in PTSD. This selective review discusses magnetic resonance (MR) imaging studies that have been used to predict treatment response to cognitive-behavioral therapy (CBT) or prolonged exposure (PE) in PTSD, which have demonstrated abnormalities in processing involving the salience network, including the amygdala, anterior cingulate cortex and insula. Increased attention to environmental cues may signal alarm resulting in hypervigilance and overactive action-monitoring for the detection of threatening stimuli and an inability to integrate concomitant emotional and sensory functions in PTSD. Successful psychotherapy treatment response in PTSD appears to involve the ability to downregulate amygdala activity to trauma-related stimuli through improved regulation of attention by the anterior cingulate cortex and concomitant internal emotional states mediated by the insula. In addition, the ability to better modulate (normalize) the salience network following psychotherapy in PTSD may be associated with better crosstalk between untargeted inner thought (i.e., task-negative network) and the ability to focus attention on stimulus-dependent demands (i.e., task positive network).

Attentional disruptions are common in PTSD, but findings across neuropsychological and neuroimaging studies have been variable. Few PTSD studies have investigated abnormalities in attention networks using a multi-modal imaging approach and attentional tasks that include emotionally-salient images. This study combined a behavioral task that included these images (emotional Stroop) with functional and structural neuroimaging (fMRI and diffusion tensor imaging; DTI) methods to comprehensively investigate attentional control abnormalities in a highly-traumatized civilian sample.

48 traumatized women with and without PTSD received clinical assessments, fMRI and DTI. During fMRI, the Affective Stroop (AS), an attentional control task that includes emotionally-salient distractor images (trauma-relevant, positive, neutral) and variable task demands, was administered.

In response to more difficult AS trials, participants with PTSD demonstrated lower activation in the dorsal and rostral anterior cingulate cortex and greater activation in the insula. This group also showed comparatively poorer performance on positive AS distractor trials, even after adjusting for trauma exposure. Performance on these trials inversely correlated with structural integrity of the cingulum bundle and uncinate fasciculus.

Even after adjusting for trauma exposure, participants with PTSD showed worse performance on an attentional control task in the context of emotional stimuli. They also showed relatively lower cognitive control network activation and greater salience network activation. Fronto-parietal and fronto-limbic white matter connectivity corresponded with AS performance. Our findings indicate that attentional control impairments in PTSD are most evident in the context of emotional cues, and are related to decrements in function and structure of cognitive control and salience networks.

Post-traumatic stress disorder (PTSD) is classified as a traumatic stress-related condition and is most often discussed in terms of emotional dysfunction. However, given that cognitive and emotional processes are intricately intertwined, implemented by overlapping brain networks, and effectively integrated in at least some of the same regions (e.g., prefrontal cortex, for a review, see Crocker et al. 2013), an abundance of literature now highlights the key role that cognitive functioning plays in both the development and maintenance (or exacerbation) of PTSD symptoms (Aupperle et al. 2012a; Verfaellie et al. 2012). Findings from this body of work detail objective impairment in neuropsychological function in those with PTSD (Brandes et al. 2002; Hayes et al. 2012a; Koenen et al. 2001). Yet despite the impact of neurocognition on PTSD treatment engagement and success (e.g., Haaland et al. 2016; Nijdam et al. 2015) and conversely, the role of PTSD treatment in normalizing cognitive dysfunction, a much smaller literature exists on neurocognitive changes following treatment for PTSD. Even aside from its role in treatment, cognitive functioning in PTSD has significant implications for daily functioning for individuals with this disorder, as cognition is predictive of school achievement, obtaining and maintaining employment, job advancement, maintaining relationships, greater wealth, and better health and quality of life (e.g., Diamond and Ling 2016).

Posttraumatic stress disorder is a debilitating psychiatric disorder characterized by symptoms of intrusive re-experiencing of trauma, avoidance and hyper-arousal. Diagnosis and treatment of PTSD is further complicated by concurrently occurring disorders, the most frequent being major depressive disorder and anxiety disorders. Previous research highlights that attentional processing in posttraumatic stress disorder is associated with substantial interference by emotional stimuli, a phenomenon also observed in these concurrently occurring psychiatric disorders. However, the diagnosis-relevance of this interference remains elusive. Here, we investigated the emotional Stroop interference for diagnosis-related stimuli, generally negative stimuli, and generally positive stimuli in posttraumatic stress disorder, major depressive disorder and anxiety disorders.

We performed a systematic database search in PubMed (Medline), Cochrane Library and PsycINFO on emotional Stroop performance in individuals with a diagnosis of posttraumatic stress disorder, major depressive disorder or anxiety disorders separately. Mean effect sizes, standard errors and confidence intervals were estimated for each clinical group and healthy control group comparison using random effect models.

As compared to healthy control group, the posttraumatic stress disorder group displayed greater interference by diagnosis-related stimuli and positive stimuli but not for generally negative stimuli. The major depressive disorder and anxiety disorders groups showed greater interference by diagnosis-related and negative stimuli, but not by positive stimuli. The age and sex had no significant impact on interference.

These findings highlight the importance of diagnosis-relevant information on attentional processing in all three clinical populations, posttraumatic stress disorder, major depressive disorder and anxiety disorders. Further, the impact of generally negative stimuli but not generally positive stimuli in major depressive disorder and anxiety disorders indicate impaired attentional bias for mood-congruent stimuli but not for general stimuli. Finally, it remains to be studied whether the influence of generally positive stimuli in posttraumatic stress disorder indicate that positive stimuli are perceived as PTSD related.

Posttraumatic stress disorder (PTSD) after childhood abuse (CA) is often related to severe co-occurring psychopathology, such as symptoms of borderline personality disorder (BPD). The ICD-11 has included Complex PTSD as a new diagnosis, which is defined by PTSD symptoms plus disturbances in emotion regulation, self-concept, and interpersonal relationships. Unfortunately, the empirical database on psychosocial treatments for survivors of CA is quite limited. Furthermore, the few existing studies often have either excluded subjects with self-harm behaviour and suicidal ideation - which is common behaviour in subjects suffering from Complex PTSD. Thus, researchers are still trying to identify efficacious treatment programmes for this group of patients.We have designed DBT-PTSD to meet the specific needs of patients with Complex PTSD. The treatment programme is based on the rules and principles of dialectical behavioural therapy (DBT), and adds interventions derived from cognitive behavioural therapy, acceptance and commitment therapy and compassion-focused therapy. DBT-PTSD can be provided as a comprehensive residential programme or as an outpatient programme. The effects of the residential programme were evaluated in a randomised controlled trial. Data revealed significant reduction of posttraumatic symptoms, with large between-group effect sizes when compared to a treatment-as-usual wait list condition (Cohen's d = 1.5).The first aim of this project on hand is to evaluate the efficacy of the outpatient DBT-PTSD programme. The second aim is to identify the major therapeutic variables mediating treatment efficacy. The third aim is to study neural mechanisms and treatment sensitivity of two frequent sequelae of PTSD after CA: intrusions and dissociation.

To address these questions, we include female patients who experienced CA and who fulfil DSM-5 criteria for PTSD plus borderline features, including criteria for severe emotion dysregulation. The study is funded by the German Federal Ministry of Education and Research, and started in 2014. Participants are randomised to outpatient psychotherapy with either DBT-PTSD or Cognitive Processing Therapy. Formal power analysis revealed a minimum of 180 patients to be recruited. The primary outcome is the change on the Clinician-Administered PTSD Scale for DSM-5.

The expected results will be a major step forward in establishing empirically supported psychological treatments for survivors of CA suffering from Complex PTSD.

German Clinical Trials Register: registration number DRKS00005578, date of registration 19 December 2013.

A neurocircuitry model of post-traumatic stress disorder (PTSD) suggests increased amygdala responses to emotional stimuli, coupled with hypoactivation of prefrontal regions associated with cognitive control. However, results are heterogenous across different subsamples of PTSD as well as different paradigms. We investigated cognitive control in a classic and emotional Stroop task in 28 female patients with complex PTSD (cPTSD), 28 female trauma-exposed healthy controls (TCs) and 28 female non-trauma-exposed healthy controls (HCs) using functional neuroimaging. Afterwards, we assessed memory function in a spontaneous free recall and recognition task. Patients with cPTSD displayed significantly greater Stroop interference with trauma-related words (as reflected in slower reaction times and increased errors) compared to the other conditions and compared to the TC and HC groups. Moreover, patients with cPTSD showed increased activation in the context of trauma-related words in brain regions associated with cognitive control (dlPFC, vmPFC, dACC) compared to both control groups, and a trend for increased activation in the insula compared to the HC group. Increased recruitment of regions contributing to cognitive control in patients with cPTSD, together with a lack of amygdala response may point to efforts to compensate for emotional distraction caused by the trauma-related words.

Recent research suggests that posttraumatic stress disorder (PTSD) is associated with altered amygdala and hippocampal resting-state functional connectivity (rsFC). However, less research has examined whether Prolonged Exposure (PE), a first line exposure-based treatment for PTSD, has the potential to alter resting state neural networks.

A total of 24 patients with PTSD and 26 matched trauma-exposed healthy controls (TEHCs) underwent resting-state functional magnetic resonance imaging (fMRI) at baseline. PTSD patients were scanned a second time after completing 10-session PE in which patients narrated a detailed trauma account (imaginal exposure) and confronted trauma reminders (in vivo exposure) to extinguish trauma-related fear responses. TEHC were scanned again following a 10-week waiting period. Seed regions of interest (ROIs) included centromedial amygdala (CMA), basolateral amygdala (BLA), and the hippocampus.

Post- versus pretreatment comparisons indicated increased rsFC of the BLA and CMA with the orbitofrontal cortex (OFC), and hippocampus-medial prefrontal cortex (mPFC) among patients with PTSD, but not among TEHC participants.

Enhanced amygdala and hippocampus rsFC with prefrontal cortical regions following PE could underlie improved capacity for inhibition and re-evaluation of threat, and heightened memory encoding and retrieval ability, respectively. These findings encourage further investigation of this circuitry as a therapeutic target in PTSD.

Nonsuicidal self-injury (NSSI), deliberate behavior resulting in self-inflicted damage to oneself, is common, particularly among female adolescents, and may be a form of maladaptive emotion regulation. Cognitive interference, a specific type of processing associated with inhibiting prepotent responses in favor of less automatic ones, is utilized in treatment strategies to shift patients' thoughts and behaviors away from maladaptive responses and replace them with more adaptive ones. We examined cognitive interference processing using the Multi-Source Interference Task (MSIT) in females with NSSI behavior (n=15) and healthy control females (n=15). Functional magnetic resonance imaging (fMRI) data were collected concurrently. Results revealed similar between-group performance on the MSIT; however, women with NSSI behavior exhibited altered patterns of neural activation during the MSIT. Specifically, the NSSI group demonstrated increased cingulate cortex (CC) and decreased dorsolateral prefrontal cortex (DLPFC) activation compared to the control group. Further, within the NSSI group, DLPFC activation inversely correlated with emotional reactivity and self-reported impulsivity, suggesting that decreased DLPFC activation is associated with poorer emotional control and increased impulsivity. Taken together, these results indicate that women with NSSI behavior utilize different cortical areas during cognitive interference processing, which may have broader implications regarding the treatment efficacy of cognitive-based therapies.

Cognitive control, which relies on the protracted development of frontal-parietal regions into adolescence, is a brain process that may be particularly vulnerable to the impact of childhood abuse. In this study, we used functional magnetic resonance imaging (fMRI) to examine associations between the age of onset of childhood abuse and alterations to the neural mechanisms supporting cognitive control in early adulthood, which have not been previously examined. During fMRI scanning, participants completed hybrid block/event-related versions of a classic color-word Stroop task as well as emotional Stroop tasks (threat and positive words). Participants were young adult women (N = 15; age range: 23-30 years) who had a history of childhood physical or sexual abuse that began prior to 13 years of age. Results indicated that earlier age of onset of childhood abuse was robustly associated with increased transient (i.e., event-related) recruitment of medial cognitive control regions in the classic color-word paradigm as well as with less suppression of medial frontal regions that are part of the default mode network, βs = -.16 to -.87. In comparison, increased activation in dorsolateral prefrontal regions was associated with earlier age of abuse onset under conditions of sustained (i.e., blocked) cognitive control in the emotional Stroop task for blocks of positive distracting words versus fixation, βs = -.50 to -.60. These results provide preliminary evidence that earlier age of exposure to childhood abuse impacts the functional activation of neural systems involved in cognitive control in adulthood.

Rejection by parents is an important aspect of child maltreatment. Altered neural responses to social rejection have been observed in maltreated individuals. The current study is the first to examine the impact of experienced and perpetrated abuse and neglect on neural responses to social exclusion by strangers versus family using a multigenerational family design, including 144 participants. The role of neural reactivity to social exclusion in the intergenerational transmission of maltreatment was also examined. Exclusion by strangers was especially associated with increased activation in the left insula, while exclusion by a family member was mainly associated with increased activation in the ACC. Neural reactivity to social exclusion by strangers in the insula, ACC and dmPFC, was associated with experienced maltreatment but not with perpetrated maltreatment. In abusive parents, altered neural reactivity during exclusion was found in other brain areas, indicating different neural correlates of experienced and perpetrated maltreatment. Hence, no mechanisms could be identified that are involved in the transmission of maltreatment. Hypersensitivity to social rejection by strangers in neglected individuals underscores the importance to distinguish between effects of abuse and neglect and suggests that the impact of experiencing rejection and maltreatment by your own parents extends beyond the family context.

Mental health interventions do not yet offer complete, client-defined functional recovery, and novel directions in treatment research are needed to improve the efficacy of available interventions. One promising direction is the integration of social work and cognitive neuroscience methods, which provides new opportunities for clinical intervention research that will guide development of more effective mental health treatments that holistically attend to the biological, social, and environmental contributors to disability and recovery. This article reviews emerging trends in cognitive neuroscience and provides examples of how these advances can be used by social workers and allied professions to improve mental health treatment. We discuss neuroplasticity, which is the dynamic and malleable nature of the brain. We also review the use of risk and resiliency biomarkers and novel treatment targets based on neuroimaging findings to prevent disability, personalize treatment, and make interventions more targeted and effective. The potential of treatment research to contribute to neuroscience discoveries regarding brain change is considered from the experimental-medicine approach adopted by the National Institute of Mental Health. Finally, we provide resources and recommendations to facilitate the integration of cognitive neuroscience into mental health research in social work.

The emotional stress response is relevant to a number of psychiatric disorders, including posttraumatic stress disorder (PTSD) in particular. Research using neuroimaging methods such as functional magnetic resonance imaging (fMRI) to probe stress-related neural processing have provided some insights into psychiatric disorders. Treatment providers and individual patients would benefit from clinically useful fMRI paradigms that provide information about patients' current brain state and responses to stress in order to inform the treatment selection process. However, neuroimaging has not yet made a meaningful impact on real-world clinical practice. This lack of clinical utility may be related to a number of basic psychometric properties that are often overlooked during fMRI task development. The goals of the current review are to discuss important methodological considerations for current human fMRI stress-related paradigms and to provide a roadmap for developing methodologically sound and clinically useful paradigms. This would include establishing various aspects of reliability, including internal consistency, test-retest and multi-site, as well as validity, including face, content, construct, and criterion. In addition, the establishment of standardized normative data from a large sample of participants would support our understanding of how any one individual compares to the general population. Addressing these methodological gaps will likely have a powerful effect on improving the replicability of findings and optimize our chances for improving real-world clinical outcomes.

Introduction: Adverse childhood experiences (ACE) such as sexual and physical abuse or neglect are frequent in childhood and constitute a massive stressor with long-lasting adverse effects on the brain, mental and physical health.The aim of this qualitative review is to present a concise overview of the present literature on the impact of ACE on neurobiology, mental and somatic health in later adulthood. Methods: The authors reviewed the existing literature on the impact of ACE on neurobiology, mental and somatic health in later adulthood and summarized the results for a concise qualitative overview. Results: In adulthood, the history of ACE can result in complex clinical profiles with several co-occurring mental and somatic disorders such as posttraumatic stress disorder, depression, borderline personality disorder, obesity and diabetes. Although a general stress effect in the development of the disorders and neural alterations can be assumed, the role of type and timing of ACE is of particular interest in terms of prevention and treatment of ACE-related mental and somatic conditions. It has been suggested that during certain vulnerable developmental phases the risk for subsequent ACE-related disorders is increased. Moreover, emerging evidence points to sensitive periods and specificity of ACE-subtypes in the development of neurobiological alterations, e.g., volumetric and functional changes in the amygdala and hippocampus. Conclusion: Longitudinal studies are needed to investigate complex ACE-related characteristics and mechanisms relevant for mental and somatic disorders by integrating state of the art knowledge and methods. By identifying and validating psychosocial and somatic risk factors and diagnostic markers one might improve the development of innovative somatic and psychological treatment options for individuals suffering from ACE-related disorders.

Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms.

Individuals with PTSD underwent functional MRI (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30) and underwent a second scan approximately 4 weeks after the last treatment session or a comparable waiting period, respectively.

Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayed a greater variety of temporal resting-state signal pattern changes after treatment. Concurrent transcranial magnetic stimulation and fMRI in healthy participants demonstrated that the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum.

Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy and that the frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works, and they identify a promising target for stimulation-based therapeutics.

The science behind psychotherapy has garnered considerable interest, as objective measures are being developed to map the patient's subjective change over the course of treatment. Prenatal and early life influences have a lasting impact on how genes are expressed and the manner in which neural circuits are consolidated. Transgenerationally transmitted epigenetic markers as well as templates of enhanced thought flexibility versus evasion can be passed down from parent to child. This influences gene expression/repression (impacting neuroplasticity) and kindling of neurocircuitry which can perpetuate maladaptive cognitive processing seen in a number of psychiatric conditions. Importantly, genetic factors and the compounding effects of early life adversity do not inexorably lead to certain fated outcomes. The concepts of vulnerability and resilience are becoming more integrated into the framework of "differential susceptibility," speaking to how corrective environmental factors may promote epigenetic change and reconfigure neural templates, allowing for symptomatic improvement. Psychotherapy is one such factor, and this review will focus on our current knowledge of its epigenetic and neurocircuitry impact.