Neural and affective responses to prolonged eye contact with parents in depressed and nondepressed adolescents.

Eye contact improves mood, facilitates connectedness, and is assumed to strengthen the parent-child bond. Adolescent depression is linked to difficulties in social interactions, the parent-child bond included. Our goal was to elucidate adolescents' affective and neural responses to prolonged eye contact with one's parent in nondepressed adolescents (HC) and how these responses are affected in depressed adolescents. While in the scanner, 59 nondepressed and 19 depressed adolescents were asked to make eye contact with their parent, an unfamiliar peer, an unfamiliar adult, and themselves by using videos of prolonged direct and averted gaze, as an approximation of eye contact. After each trial, adolescents reported on their mood and feelings of connectedness, and eye movements and BOLD-responses were assessed. In HCs, eye contact boosted mood and feelings of connectedness and increased activity in inferior frontal gyrus (IFG), temporal pole, and superior frontal gyrus. Unlike HCs, eye contact did not boost the mood of depressed adolescents. While HCs reported increased mood and feelings of connectedness to the sight of their parent versus others, depressed adolescents did not. Depressed adolescents exhibited blunted overall IFG activity. These findings show that adolescents are particularly sensitive to eye contact and respond strongly to the sight of their parents. This sensitivity seems to be blunted in depressed adolescents. For clinical purposes, it is important to gain a better understanding of how the responsivity to eye contact in general and with their parents in particular, can be restored in adolescents with depression.

Sticky criticism? Affective and neural responses to parental criticism and praise in adolescents with depression.

BACKGROUND: Parent-adolescent interactions, particularly parental criticism and praise, have previously been identified as factors relevant to self-concept development and, when negative, to adolescent depression. Yet, whether adolescents with depression show aberrant emotional and neural reactivity to parental criticism and praise is understudied. METHODS: Adolescents with depression (n = 20) and healthy controls (n = 59) received feedback supposedly provided by their mother or father in the form of negative ('untrustworthy'), neutral ('chaotic'), and positive ('respectful') personality evaluations while in an MRI-scanner. After each feedback word, adolescents reported their mood. Beforehand, adolescents had rated whether these personality evaluations matched their self-views. RESULTS: In both groups, mood decreased after criticism and increased after praise. Adolescents with depression reported blunted mood responses after praise, whereas there were no mood differences after criticism. Neuroimaging analyses revealed that adolescents with depression (v. healthy controls) exhibited increased activity in response to criticism in the subgenual anterior cingulate cortex, temporal pole, hippocampus, and parahippocampal gyrus. Praise consistent with adolescents' self-views improved mood independent of depression status, while criticism matching self-views resulted in smaller mood increases in adolescents with depression (v. healthy controls). Exploratory analyses indicated that adolescents with depression recalled criticism (v. praise) more. CONCLUSIONS: Adolescents with depression might be especially attentive to parental criticism, as indexed by increased sgACC and hippocampus activity, and memorize this criticism more. Together with lower positive impact of praise, these findings suggest that cognitive biases in adolescent depression may affect how parental feedback is processed, and may be fed into their self-views.

DNA methylation variation after a parenting program for child conduct problems: Findings from a randomized controlled trial.

This study investigated associations of the Incredible Years (IY) parenting program with children's DNA methylation. Participants were 289 Dutch children aged 3-9 years (75% European ancestry, 48% female) with above-average conduct problems. Saliva was collected 2.5 years after families were randomized to IY or care as usual (CAU). Using an intention-to-treat approach, confirmatory multiple-regression analyses revealed no significant differences between the IY and CAU groups in children's methylation levels at the NR3C1 and FKBP5 genes. However, exploratory epigenome-wide analyses revealed nine differentially methylated regions between groups, coinciding with SLAMF1, MITF, FAM200B, PSD3, SNX31, and CELSR1. The study provides preliminary evidence for associations of IY with children's salivary methylation levels and highlights the need for further research into biological outcomes of parenting programs.

Looking into troubled waters: Childhood emotional maltreatment modulates neural responses to prolonged gazing into one's own, but not others', eyes.

One of the most prevalent nonverbal, social phenomena known to automatically elicit self- and other-referential processes is eye contact. By its negative effects on the perception of social safety and views about the self and others, childhood emotional maltreatment (CEM) may fundamentally affect these processes. To investigate whether the socioaffective consequences of CEM may become visible in response to (prolonged) eye gaze, 79 adult participants (mean [M]age = 49.87, standard deviation [SD]age = 4.62) viewed videos with direct and averted gaze of an unfamiliar other and themselves while we recorded self-reported mood, eye movements using eye-tracking, and markers of neural activity using fMRI. Participants who reported higher levels of CEM exhibited increased activity in ventromedial prefrontal cortex to one's own, but not to others', direct gaze. Furthermore, in contrast to those who reported fewer of such experiences, they did not report a better mood in response to a direct gaze of self and others, despite equivalent amounts of time spent looking into their own and other peoples' eyes. The fact that CEM is associated with enhanced neural activation in a brain area that is crucially involved in self-referential processing (i.e., vmPFC) in response to one's own direct gaze is in line with the chronic negative impact of CEM on a person's self-views. Interventions that directly focus on targeting maladaptive self-views elicited during eye gaze to self may be clinically useful.

Maternal sensitivity and child internalizing and externalizing behavior: a mediating role for glucocorticoid receptor gene (NR3C1) methylation?

The early caregiving environment can have lasting effects on child mental health. Animal models suggest that glucocorticoid receptor gene (NR3C1) DNA methylation plays a mediating role in linking more responsive caregiving to improved behavioral outcomes by its impact on the stress regulatory system. In this longitudinal study, we examined whether children's NR3C1 methylation levels mediate an effect of maternal sensitivity in infancy on levels of child internalizing and externalizing behavior in a community sample. Maternal sensitivity of 145 mothers was rated at infant age 5 weeks, 12 months, and 30 months by observing mother-infant interactions. Buccal DNA methylation was assessed in the same children at age 6 years and maternal-reported internalizing and externalizing behavior was assessed at age 6 and 10 years. Higher sensitivity at age 5 weeks significantly predicted lower DNA methylation levels at two NR3C1 CpG loci, although methylation levels at these loci did not mediate an effect of maternal sensitivity on levels of child internalizing and externalizing behavior. Overall, the study provides evidence that maternal sensitivity in early infancy is associated with DNA methylation levels at loci involved in stress regulation, but the significance of this finding for child mental health remains unclear.

The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells.

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032), with performance assessed in a separate test dataset (n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.

Neural and Affective Responses to Prolonged Eye Contact with One's Own Adolescent Child and Unfamiliar Others.

Eye contact is crucial for the formation and maintenance of social relationships, and plays a key role in facilitating a strong parent-child bond. However, the precise neural and affective mechanisms through which eye contact impacts on parent-child relationships remain elusive. We introduce a task to assess parents' neural and affective responses to prolonged direct and averted gaze coming from their own child, and an unfamiliar child and adult. While in the scanner, 79 parents (n = 44 mothers and n = 35 fathers) were presented with prolonged (16-38 s) videos of their own child, an unfamiliar child, an unfamiliar adult, and themselves (i.e., targets), facing the camera with a direct or an averted gaze. We measured BOLD-responses, tracked parents' eye movements during the videos, and asked them to report on their mood and feelings of connectedness with the targets after each video. Parents reported improved mood and increased feelings of connectedness after prolonged exposure to direct versus averted gaze and these effects were amplified for unfamiliar targets compared to their own child, due to high affect and connectedness ratings after videos of their own child. Neuroimaging results showed that the sight of one's own child was associated with increased activity in middle occipital gyrus, fusiform gyrus and inferior frontal gyrus relative to seeing an unfamiliar child or adult. While we found no robust evidence of specific neural correlates of eye contact (i.e., contrast direct > averted gaze), an exploratory parametric analysis showed that dorsomedial prefrontal cortex (dmPFC) activity increased linearly with duration of eye contact (collapsed across all "other" targets). Eye contact-related dmPFC activity correlated positively with increases in feelings of connectedness, suggesting that this region may drive feelings of connectedness during prolonged eye contact with others. These results underline the importance of prolonged eye contact for affiliative processes and provide first insights into its neural correlates. This may pave the way for new research in individuals or pairs in whom affiliative processes are disrupted.

Eyes on you: Ensuring empathic accuracy or signalling empathy?

The eye region is thought to play an important role in the ability to accurately infer others' feelings, or empathic accuracy (EA), which is an important skill for social interaction. However, most past studies used static pictures, including only visual information, and knowledge about the contribution of the eye region to EA when visual information is presented together with verbal content is lacking. We therefore examined whether eye gazing contributes to EA during videos of emotional autobiographical stories including both visual and verbal content. One hundred seven perceivers watched videos of targets talking about positive and negative life events and continuously rated the targets' feelings during the videos. Simultaneously, perceivers' eyes were tracked. After each video, perceivers reported on their feelings and the extent to which they empathized with and took the perspective of the targets. In contrast to studies using static pictures, we found that gazing to the eyes of targets during the videos did not significantly contribute to EA. At the same time, results on the association between the amount of gaze towards the eye region of targets and perceivers' state and trait empathy ratings suggest that eye gazing might signal empathy and social engagement to others.

Neural signatures of parental empathic responses to imagined suffering of their adolescent child.

Empathy is deemed indispensable for sensitive caregiving. Neuroimaging studies have identified canonical empathy networks consisting of regions supporting cognitive and affective aspects of empathy. However, not much is known about how these regions support empathy towards one's own offspring and how this neural activity relates to parental caregiving. We introduce a novel task to assess affective and neural responses to the suffering of one's own adolescent child. While in the scanner, 60 parents (n = 35 mothers, n = 25 fathers) were confronted with unpleasant situations involving their own child, an unfamiliar child, and themselves. Parents were asked to vividly imagine these situations and indicate their levels of distress. Parents reported higher levels of distress when imagining suffering for their own child relative to an unfamiliar child or themselves. Neuroimaging results showed increased activation within the cognitive empathy network (i.e., temporoparietal junction, dorsomedial- and ventromedial prefrontal cortex) when contrasting suffering of one's own child versus an unfamiliar child or the self. The task also engaged regions of the affective empathy network (i.e., anterior insula and anterior mid-cingulate cortex), which was however not modulated by whether suffering was for the self, one's own child, or an unfamiliar child. Parental care did not co-vary with activity in the empathy networks, but parents who were perceived as less caring exhibited increased activity in anterior prefrontal regions when imagining their own child suffering. These results provide new insights into neural processes supporting parental empathy, highlighting the importance of regions in the cognitive empathy network when confronted with the suffering of their own adolescent child, and suggest that additional (i.e., emotion regulation) networks may be relevant for parental caring behavior in daily life.

Maternal antenatal depression and child mental health: Moderation by genomic risk for attention-deficit/hyperactivity disorder.

Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 × 10-4, R2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 × 10-9, R2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health.

The genetic and environmental etiology of child maltreatment in a parent-based extended family design.

Child maltreatment has been associated with various cumulative risk factors. However, little is known about the extent to which genetic and environmental factors contribute to individual differences between parents in perpetrating child maltreatment. To estimate the relative contribution of genetic and environmental factors to perpetrating maltreatment we used a parent-based extended family design. Child-reported perpetrated maltreatment was available for 556 parents (283 women) from 63 families. To explore reporter effects (i.e., child perspective on maltreatment), child reports were compared to multi-informant reports. Based on polygenic model analyses, most of the variance related to the perpetration of physical abuse and emotional neglect was explained by common environmental factors (physical abuse: c2 = 59%, SE = 12%, p = .006; emotional neglect: c2 = 47%, SE = 8%, p < .001) whereas genetic factors did not significantly contribute to the model. For perpetrated emotional abuse, in contrast, genetic factors did significantly contribute to perpetrated emotional abuse (h2 = 33%, SE = 8%, p < .001), whereas common environment factors did not. Multi-informant reports led to similar estimates of genetic and common environmental effects on all measures except for emotional abuse, where a multi-informant approach yielded higher estimates of the common environmental effects. Overall, estimates of unique environment, including measurement error, were lower using multi-informant reports. In conclusion, our findings suggest that genetic pathways play a significant role in perpetrating emotional abuse, while physical abuse and emotional neglect are transmitted primarily through common environmental factors. These findings imply that interventions may need to target different mechanisms dependings on maltreatment type.

Parents' experiences of childhood abuse and neglect are differentially associated with behavioral and autonomic responses to their offspring.

Although childhood maltreatment has been shown to compromise adaptive parental behavior, little is known what happens in terms of physiological regulation when parents with a history of childhood maltreatment interact with their offspring. Using a sample of 229 parents (131 women), the present study examined whether childhood maltreatment experiences are associated with parents' behavioral and autonomic responses while resolving conflict with their offspring. Self-reported experienced child maltreatment was measured using a questionnaire assessing abuse and neglect. Parents (Mage  = 52.7 years, rangeage  = 26.6-88.4 years) and their offspring (Mage  = 24.6 years, rangeage  = 7.5-65.6 years) participated in a videotaped parent-offspring conflict interaction task. Parental warmth, negativity, and emotional support were coded. In addition, their pre-ejection period and respiratory sinus arrhythmia were measured as indicators of underlying sympathetic and parasympathetic nervous system reactivity, respectively. Findings demonstrated that experiences of abuse and neglect were associated with behavioral and physiological responses in different ways. Separating these two types of maltreatment in research and in clinical practice might be important.

Are psychophysiological arousal and self-reported emotional stress during an oncological consultation related to memory of medical information? An experimental study.

Patients forget 20-80% of information provided during medical consultations. The emotional stress often experienced by patients during consultations could be one of the mechanisms that lead to limited recall. The current experimental study therefore investigated the associations between (analog) patients' psychophysiological arousal, self-reported emotional stress and their (long term) memory of information provided by the physician. One hundred and eighty one cancer-naïve individuals acted as so-called analog patients (APs), i.e. they were instructed to watch a scripted video-recoding of an oncological bad news consultation while imagining themselves being in the patient's situation. Electrodermal and cardiovascular activity (e.g. skin conductance level and heart rate) were recorded during watching. Self-reported emotional stress was assessed before and after watching, using the STAI-State and seven Visual Analog Scales. Memory, both free recall and recognition, was assessed after 24-28 h. Watching the consultation evoked significant psychophysiological and self-reported stress responses. However, investigating the associations between 24 psychophysiological arousal measures, eight self-reported stress measures and free recall and recognition of information resulted in one significant, small (partial) correlation (r = 0.19). Considering multiple testing, this significant result was probably due to chance. Alternative analytical methods yielded identical results, strengthening our conclusion that no evidence was found for relationships between variables of interest. These null-findings are highly relevant, as they may be considered to refute the long-standing, but yet untested assumption that a relationship between stress and memory exists within this context. Moreover, these findings suggest that lowering patients' stress levels during the consultation would probably not be sufficient to raise memory of information to an optimal level. Alternative explanations for these findings are discussed.

The association of childhood maltreatment with depression and anxiety is not moderated by the oxytocin receptor gene.

BACKGROUND: The oxytocin receptor (OXTR) gene may be involved in resilience or vulnerability towards stress, and hence in the development of stress-related disorders. There are indications that OXTR single nucleotide polymorphisms (SNPs) interact with early life stressors in predicting levels of depression and anxiety. To replicate and extend these findings, we examined whether three literature-based OXTR SNPs (rs2254298, rs53576, rs2268498) interact with childhood maltreatment in the development of clinically diagnosed depression and anxiety disorders. METHODS: We included 2567 individuals from the Netherlands Study of Depression and Anxiety. This sample consisted of 387 healthy controls, 428 people with a current or past depressive disorder, 243 people with a current or past anxiety disorder, and 1509 people with both lifetime depression and anxiety diagnoses. Childhood maltreatment was measured with both an interview and via self-report. Additional questionnaires measured depression and anxiety sensitivity. RESULTS: Childhood maltreatment was strongly associated with both lifetime depression and anxiety diagnoses, as well as with depression and anxiety sensitivity. However, the OXTR SNPs did not moderate these associations nor had main effects on outcomes. CONCLUSIONS: The three OXTR gene SNPs did not interact with childhood maltreatment in predicting lifetime depression and anxiety diagnoses or sensitivity. This stresses the importance of replication studies with regard to OXTR gene variants in general populations as well as in clearly established clinical samples.

Prolonged Non-metabolic Heart Rate Variability Reduction as a Physiological Marker of Psychological Stress in Daily Life.

BACKGROUND: Prolonged cardiac activity that exceeds metabolic needs can be detrimental for somatic health. Psychological stress could result in such "additional cardiac activity." PURPOSE: In this study, we examined whether prolonged additional reductions in heart rate variability (AddHRVr) can be measured in daily life with an algorithm that filters out changes in HRV that are purely due to metabolic demand, as indexed by movement, using a brief calibration procedure. We tested whether these AddHRVr periods were related to worry, stress, and negative emotions. METHODS: Movement and the root of the mean square of successive differences (RMSSD) in heart rate were measured during a calibration phase and the subsequent 24 h in 32 participants. Worry, stress, explicit and implicit emotions were assessed hourly using smartphones. The Levels of Emotional Awareness Scale and resting HRV were used to account for individual differences. During calibration, person-specific relations between movement and RMSSD were determined. The 24-h data were used to detect prolonged periods (i.e., 7.5 min) of AddHRVr. RESULTS: AddHRVr periods were associated with worrying, with decreased explicit positive affect, and with increased tension, but not with the frequency of stressful events or implicit emotions. Only in people high in emotional awareness and high in resting HRV did changes in AddHRVr covary with changes in explicit emotions. CONCLUSIONS: The algorithm can be used to capture prolonged reductions in HRV that are not due to metabolic needs. This enables the real-time assessment of episodes of potentially detrimental cardiac activity and its psychological determinants in daily life.

Incredible years parenting program buffers prospective association between parent-reported harsh parenting and epigenetic age deceleration in children with externalizing behavior.

Harsh parenting has been shown to increase the risk of physical and mental health problems in later life. To improve our understanding of these risks and how they can be mitigated, we investigated associations of harsh parenting with a clinically relevant biomarker, epigenetic age deviation (EAD), using data from a randomized-control trial of the Incredible Years (IY) parenting program. This study included 281 children aged 4-8 years who were screened for heightened externalizing behavior and whose parents were randomly allocated to either IY or care-as-usual (CAU). Parents reported on their own parenting practices and their child's externalizing behavior at baseline and at a follow-up assessment approximately three years later. Epigenetic age, based on the Pediatric Buccal Epigenetic (PedBE) clock, was estimated from child DNA methylation derived from saliva collected at the follow-up assessment. PedBE clock estimates were regressed on chronological age as a measure of EAD. Moderation analyses using multiple regression revealed that harsher parenting at baseline predicted epigenetic age deceleration in children that received CAU (b = -.21, 95% CI[-0.37, -0.05]), but no association was found in children whose parents were allocated to IY (b = -.02, 95% CI [-0.13, 0.19]). These results highlight a prospective association between harsh parenting and children's EAD and indicate a potential ameliorating effect of preventive intervention. Future work is needed to replicate these findings and understand individual differences in children's responses to harsh parenting in relation to epigenetic aging.

A qualitative, multi-perspective study on causal beliefs about adolescent depression.

OBJECTIVES: The current study aimed to examine: (1.1) causal beliefs about adolescent depression in a sample of adolescents with a clinical depression and their mothers and fathers; (1.2) within-family overlap of causal beliefs; (2.1) mothers' and fathers' reflected causal beliefs about their child's perspective; (2.2) the accuracy of mothers' and fathers' reflected causal beliefs as related to their child's causal beliefs. DESIGN: Qualitative study using a within-family approach. METHODS: Adolescents with a current clinical depression (MDD/dysthymia; N = 34) and their parents (N = 34 mothers, N = 26 fathers) were independently interviewed about their causal beliefs about the adolescents' depression. Parents were additionally interviewed about their perception of their child's causal beliefs (i.e., reflected causal beliefs). RESULTS: The causal beliefs most frequently mentioned by adolescents, mothers and fathers are: characteristics of the child, social factors, school and various stressful experiences. Parent-child overlap was relatively low, specifically for the themes of bewilderment, cumulative effect and stressful life events, whereas overlap was relatively high for themes of social factors, school and stressful experiences outside of the family. Parents were relatively accurate in their reflected causal beliefs, but tended to underestimate their child's insights into possible causes of their depression. Accuracy of parents' reflected causal beliefs was particularly low for the theme cumulative effect and high for social factors. CONCLUSIONS: The various causal beliefs of adolescents and their parents could be used in therapeutic setting. Future research could examine whether (guided) conversations may promote alignment within families and treatment efficacy.

The role of emotion recognition in the intergenerational transmission of child maltreatment: A multigenerational family study.

BACKGROUND: Understanding how child maltreatment is passed down from one generation to the next is crucial for the development of intervention and prevention strategies that may break the cycle of child maltreatment. Changes in emotion recognition due to childhood maltreatment have repeatedly been found, and may underly the intergenerational transmission of child maltreatment. OBJECTIVE: In this study we, therefore, examined whether the ability to recognize emotions plays a role in the intergenerational transmission of child abuse and neglect. PARTICIPANTS AND SETTING: A total of 250 parents (104 males, 146 females) were included that participated in a three-generation family study. METHOD: Participants completed an emotion recognition task in which they were presented with series of photographs that depicted the unfolding of facial expressions from neutrality to the peak emotions anger, fear, happiness, and sadness. Multi-informant measures were used to examine experienced and perpetrated child maltreatment. RESULTS: A history of abuse, but not neglect, predicted a shorter reaction time to identify fear and anger. In addition, parents who showed higher levels of neglectful behavior made more errors in identifying fear, whereas parents who showed higher levels of abusive behavior made more errors in identifying anger. Emotion recognition did not mediate the association between experienced and perpetrated child maltreatment. CONCLUSIONS: Findings highlight the importance of distinguishing between abuse and neglect when investigating the precursors and sequalae of child maltreatment. In addition, the effectiveness of interventions that aim to break the cycle of abuse and neglect could be improved by better addressing the specific problems with emotion processing of abusive and neglectful parents.

Adding physical activity to intensive trauma-focused treatment for post-traumatic stress disorder: results of a randomized controlled trial.

Introduction: This randomized controlled trial examined the effectiveness of physical activity added to an intensive trauma-focused treatment (TFT) for post-traumatic stress disorder (PTSD) in comparison to adding non-physical control activities. Methods: A total of 119 patients with PTSD were randomly assigned to a physical activity condition (PA; n = 59) or a non-physical activity control condition (nPA; n = 60). The 8-day intensive TFT programme consisted of daily prolonged exposure, EMDR therapy, and psychoeducation, which was complemented with physical activities versus controlled mixtures of guided (creative) tasks. As a primary outcome, the change in clinician and self-reported PTSD symptoms from pre-to post-treatment and at 6 months follow-up were measured. Results: Intent-to-treat linear mixed-effects models showed no significant differences between the PA and nPA conditions on change in PTSD severity. Clinician and self-reported PTSD symptoms significantly decreased for both conditions, with large effect sizes (e.g., CAPS-5 dpre-post = 2.28). At post-treatment, 80.0% in the PA, and 82.7% in the nPA condition no longer met the diagnostic criteria for PTSD. Regarding the loss of Complex PTSD diagnoses this was 92.5% and 95.0%, respectively. Conclusion: Either with additional physical or non-physical activities, intensive TFT is very effective for the treatment of (Complex) PTSD, as reflected by large effect sizes and loss of diagnostic status in both groups. Clinical trial registration: Trialregister.nl Identifier: Trial NL9120.

Aberrant neural network activation during reliving of autobiographical memories in adolescent depression.

BACKGROUND: Adolescents with depression exhibit negative biases in autobiographical memory with detrimental consequences for their self-concept and well-being. Investigating how adolescents relive positive autobiographical memories and activate the underlying neural networks could reveal mechanisms that drive such biases. This study investigated neural networks when reliving positive and neutral memories, and how neural activity is modulated by valence and vividness in adolescents with and without depression. METHODS: Adolescents (N = 69; n = 17 with depression) retrieved positive and neutral autobiographical memories. On a separate day, they relived these memories during fMRI scanning, and reported on pleasantness and vividness after reliving each memory. We used a multivariate, data-driven approach - event-related independent component analysis (eICA) - to characterize neural networks supporting autobiographical recollection. RESULTS: Adolescents with depression reported their positive memories as significantly less pleasant compared to healthy controls, while subjective vividness was unaffected. Using eICA, we identified a broad autobiographical memory network, and subnetworks related to reliving positive vs neutral memories. These subnetworks comprised a 'self-referential processing network' including medial prefrontal cortex, posterior cingulate cortex/precuneus, and temporoparietal junction, anti-correlating with parts of the central executive network and salience network. Adolescents with depression exhibited aberrant activation in this self-referential network, but only when reliving relatively 'low' pleasant memories. CONCLUSIONS: Our findings provide first insights into how the quality of reliving autobiographical memories in adolescents with depression may relate to aberrant self-referential neural network activation, and underscore the potential of targeting memory reliving in therapeutic interventions to foster self-esteem and diminish depressive symptoms.