Structural equation modeling of treatment-related changes in neural connectivity for youth with PTSD.

BACKGROUND: Previous studies suggest that improvement in symptoms of posttraumatic stress disorder (PTSD) is accompanied by changes in neural connectivity, however, few studies have investigated directional (effective) connectivity. The current study assesses treatment-related changes in effective connectivity in youth with PTSD undergoing Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). METHODS: Functional MRI scans before and after 16 weeks of TF-CBT for 20 youth with PTSD, or the same time interval for 20 healthy controls (HC) were included in the analysis. Structural equation modeling was used to model group differences in directional connectivity at baseline, and changes in connectivity from pre- to post-treatment. RESULTS: At baseline, the PTSD group, relative to the HC group, had significantly greater connectivity in the path from dorsal cingulate to anterior cingulate and from dorsal cingulate to posterior cingulate corticies. From pre- to post-treatment, connectivity in these paths decreased significantly in the PTSD group, as did connectivity from right hippocampus to left superior temporal gyrus. Connectivity from the left amygdala to the lateral orbital frontal cortex was significantly lower in PTSD vs HC at baseline, but did not change from pre- to post-treatment. CONCLUSION: Although based on a small sample, these results converge with previous studies in suggesting a central role for the dorsal cingulate cortex in PTSD symptoms. The direction of this connectivity suggests that the dorsal cingulate is the source of modulation of anterior and posterior cingulate cortex during trauma-focused cognitive behavioral therapy.

Predicting transitions between longitudinal classes of post-traumatic stress disorder, adjustment disorder and well-being during the COVID-19 pandemic: protocol of a latent transition model in a general Dutch sample.

BACKGROUND: A growing body of literature shows profound effects of the COVID-19 pandemic on mental health, among which increased rates of post-traumatic stress disorder (PTSD) and adjustment disorder (AD). However, current research efforts have largely been unilateral, focusing on psychopathology and not including well-being, and are dominated by examining average psychopathology levels or on disorder absence/presence, thereby ignoring individual differences in mental health. Knowledge on individual differences, as depicted by latent subgroups, in the full spectrum of mental health may provide valuable insights in how individuals transition between health states and factors that predict transitioning from resilient to symptomatic classes. Our aim is to (1) identify longitudinal classes (ie, subgroups of individuals) based on indicators of PTSD, AD and well-being in response to the pandemic and (2) examine predictors of transitioning between these subgroups. METHODS AND ANALYSIS: We will conduct a three-wave longitudinal online survey study of n≥2000 adults from the general Dutch population. The first measurement occasion takes place 6 months after the start of the pandemic, followed by two follow-up measurements with 6 months of intervals. Latent transition analysis will be used for data analysis. ETHICS AND DISSEMINATION: Ethical approval has been obtained from four Dutch universities. Longitudinal study designs are vital to monitor mental health (and predictors thereof) in the pandemic to develop preventive and curative mental health interventions. This study is carried out by researchers who are board members of the Dutch Society for Traumatic Stress Studies and is part of a pan-European study (initiated by the European Society for Traumatic Stress Studies) examining the impact of the pandemic in 11 countries. Results will be published in peer-reviewed journals and disseminated at conferences, via newsletters, and media appearance among (psychotrauma) professionals and the general public.

Unresolved-Disorganized Attachment is Associated With Smaller Hippocampus and Increased Functional Connectivity Beyond Psychopathology.

Loss and abuse in children can lead to unresolved-disorganized (UD) attachment. How this condition relates to brain structure and functional connectivity (FC) is unknown. We therefore aimed to investigate gray matter volume (GMV) and resting state functional connectivity (RSFC) correlates of UD attachment in adolescents. Based on previous neuroimaging studies of trauma effects, we hypothesized that the structure of the amygdala and hippocampus and the FC of the latter would be linked to UD attachment. Anatomical and RSFC data were collected from a mixed group of adolescents (N = 74) with symptoms of posttraumatic stress disorder (PTSD) related to childhood sexual abuse (CSA), anxiety/depressive symptoms, and without psychiatric disorder as part of the Emotional Pathways' Imaging Study in Clinical Adolescents (EPISCA). Bilateral volumes of the amygdala and hippocampus were measured using the FMRIB Software Library, and RSFC of the hippocampus was assessed using seed-based correlation. UD attachment was measured using the Adult Attachment Interview. Hierarchical regression and correlation were used to assess the associations between UD status (continuous and categorical), brain structure, and FC, adjusting for a general psychopathology factor, puberty stage, gender, age, and IQ. UD attachment was associated with a smaller left hippocampal volume, R2 = .23, and a higher level of FC between the hippocampus and the middle temporal gyrus and lateral occipital cortex. The associations among UD attachment, specific brain structure, and FC across psychopathological classifications shows promise for dimensional complements to the dominant classificatory approach in clinical research and practice.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) El apego desorganizado no resuelto asociado con un menor hipocampo y un incremento de la conectividad funcional más allá de la psicopatología APEGO, HIPOCAMPO Y CONECTIVIDAD FUNCIONAL. Las pérdidas y el abuso en niños pueden conllevar a un apego desorganizado no resuelto (DN). La forma en que esta condición se relaciona con la estructura cerebral y conectividad funcional (CF) es desconocida. Por lo tanto, nuestro objetivo fue investigar el volumen de materia gris (VMG) y los correlatos de la conectividad funcional en estado de reposo (CFER) de DN en adolescentes. Basado en estudios previos de neuroimágenes sobre los efectos del trauma, hipotetizamos que la estructura de la amígdala e hipocampo y la CF de este último podría estar relacionado con DN. Los datos anatómicos y de CFER fueron recolectados de un grupo mixto de adolescentes (N = 74) con síntomas de trastorno de estrés postraumático (TEPT) relacionado con abuso sexual infantil (ASI), síntomas de ansiedad/depresión, y sin trastornos psiquiátricos, como parte del Estudio de Imágenes de Vías Emocionales en Clínica Adolescente (EPISCA en su sigla en inglés). Volúmenes bilaterales de la amígdala e hipocampo fueron evaluados usando el software de biblioteca FMRIB, y la CFER del hipocampo fue evaluada usando la correlación basada en semillas. La DN fue medido utilizando la Entrevista de Apego Adulto. Regresiones jerárquicas y correlaciones fueron utilizadas para evaluar las asociaciones entre DN (continuo y categórico), estructura cerebral, y CF, ajustando un factor general de psicopatología, etapa de pubertad, género, edad y CI. DN fue asociado con un menor volumen del hipocampo izquierdo, R2 = .23, y altos niveles de CF entre el hipocampo y giro temporal medio y la corteza occipital lateral. La asociación de DN con una estructura cerebral especifica y CF a través de clasificaciones psicopatológicas es prometedora como complementos dimensionales al enfoque clasificatorio dominante en la investigación y práctica clínica.

Unresolved-disorganized attachment adjusted for a general psychopathology factor associated with atypical amygdala resting-state functional connectivity.

Background: Recent research has identified a general psychopathology factor (GPF), which explains overlap in presentation of psychopathological symptoms. Unresolved-disorganized attachment (Ud) is another transdiagnostic risk factor that may be relevant to explain differences in patient characteristics within diagnostic classifications. Objective: In the current study, we examined unique relations of resting-state functional connectivity (RSFC) with Ud and GPF. Method: RSFC data were collected from a mixed group of adolescents (N = 74) with and without psychiatric disorder, as part of the Emotional Pathways' Imaging Study in Clinical Adolescents (EPISCA) study. Ud was measured using the Adult Attachment Interview (AAI). Associations between Ud, GPF, and RSFC of the amygdala and dorsal anterior cingulate cortex (dACC) and with amygdala-medial frontal connectivity were examined. Results: Ud was positively associated with greater functional connectivity between the left amygdala and the left lateral occipital cortex, precuneus, and superior parietal lobule. Furthermore, Ud was negatively associated with left amygdala-medial frontal cortex connectivity. GPF was not significantly associated with dACC or amygdala connectivity. Conclusions: Atypical amygdala connectivity may reflect a vulnerability factor rather than a biomarker of psychopathology. The unique association of Ud and amygdala RSFC, adjusted for a GPF, across participants with and without various classifications of psychopathology illustrates that dimensional approaches based on the AAI may complement psychiatric classifications in clinical research and practice.

Antecedentes: La investigación reciente ha identificado un factor de psicopatología general (GPF, en su sigla en inglés), que explica la superposición en la presentación de los síntomas psicopatológicos. El apego no resuelto-desorganizado (Ud) es otro factor de riesgo transdiagnóstico que puede ser relevante para explicar las diferencias en las características de los pacientes dentro de las clasificaciones diagnósticas.Objetivo: En el presente estudio, examinamos las relaciones únicas de conectividad funcional en estado de reposo con el Ud y GPF.Método: Los datos de conectividad funcional en estado de reposo (RSFC, en su sigla en inglés) se recopilaron de un grupo mixto de adolescentes (N = 74) con y sin trastorno psiquiátrico, parte del Estudio de Imagen de las Vías Emocionales en Adolescentes Clínicos (EPISCA, en su sigla en inglés). El Ud se midió utilizando la Entrevista de Apego Adulto (AAI, en su sigla en inglés). Se examinaron las asociaciones entre el Ud, GPF y RSFC de la amígdala y la corteza cingulada anterior (dACC, en su sigla en inglés) y con la conectividad medial-frontal de la amígdala.Resultados: El Ud se asoció positivamente con una mayor conectividad funcional entre la amígdala izquierda y la corteza occipital lateral izquierda, precuneus y el lóbulo parietal superior. Además, el Ud se asoció negativamente con la conectividad entre la corteza medial-frontal y la amígdala izquierda. El GPF no se asoció significativamente con la conectividad de la dACC o la amígdala.Conclusiones: La conectividad atípica de la amígdala puede reflejar un factor de vulnerabilidad en lugar de un biomarcador de psicopatología. La asociación única del Ud y la conectividad RSFC y amígdala, ajustada para un GPF, entre participantes con y sin varias clasificaciones de psicopatología ilustra que los enfoques dimensionales basados en la AAI pueden complementar las clasificaciones psiquiátricas en la investigación y práctica clínica.

Anterior cingulate cortex grey matter volume abnormalities in adolescents with PTSD after childhood sexual abuse.

Adverse childhood experiences (ACE) substantially increase the risk of later psychiatric and somatic pathology. While neurobiological factors are likely to play a mediating role, specific insights are lacking. The scarce neuroimaging studies in traumatised pediatric populations have provided inconsistent results, potentially due to the inclusion of different types of trauma. To further improve our understanding of the neurobiology of pediatric psychotrauma, this study seeks to investigate abnormalities in grey matter volume (GMV) in a homogeneous group of adolescents with posttraumatic stress disorder (PTSD) due to childhood sexual abuse (CSA) and the relationship between GMV and symptom severity. We performed a voxel based morphometry (VBM) analysis in 21 adolescents with CSA-related PTSD and 25 matched non-traumatised, non-clinical adolescents. Hippocampus, amygdala, anterior cingulate cortex (ACC), medial PFC (mPFC) and superior temporal gyrus (STG) were chosen as regions of interest (ROIs). Trauma symptomatology was measured with the Trauma Symptom Checklist for Children (TSCC) and dissociation symptoms with the Adolescent Dissociative Experiences Scale (A-DES). The ROI analysis showed that the CSA-related PTSD group had significant smaller volumes of the dorsal ACC as compared to healthy controls. However, no correlations were found between GMV and scores on the TSCC and A-DES. The smaller ACC volume is partly in line with previous studies in traumatised youth and is a consistent finding in traumatised adults. Taken together our results suggest that the dorsal ACC is implicated in the neurobiological sequelae of CSA, potentially associated with an altered evaluative processing of emotion, but not directly with PTSD severity.

Amygdala habituation to emotional faces in adolescents with internalizing disorders, adolescents with childhood sexual abuse related PTSD and healthy adolescents.

Adolescents with internalizing disorders and adolescents with childhood sexual abuse related post-traumatic stress disorder (CSA-related PTSD) show a large overlap in symptomatology. In addition, brain research indicated hyper-responsiveness and sustained activation instead of habituation of amygdala activation to emotional faces in both groups. Little is known, however, about whether the same patterns of amygdala habituation are present in these two groups. The current study examined habituation patterns of amygdala activity to emotional faces (fearful, happy and neutral) in adolescents with a DSM-IV depressive and/or anxiety disorder (N=25), adolescents with CSA-related PTSD (N=19) and healthy controls (N=26). Behaviourally, the adolescents from the internalizing and CSA-related PTSD group reported more anxiety to fearful and neutral faces than adolescents from the control group and adolescents from the CSA-related PTSD group reacted slower compared to the internalizing group. At the whole brain level, there was a significant interaction between time and group within the left amygdala. Follow-up ROI analysis showed elevated initial activity in the amygdala and rapid habituation in the CSA-related PTSD group compared to the internalizing group. These findings suggest that habituation patterns of amygdala activation provide additional information on problems with emotional face processing. Furthermore, the results suggest there are differences in the underlying neurobiological mechanisms related to emotional face processing for adolescents with internalizing disorders and adolescents with CSA-related PTSD. Possibly CSA-related PTSD is characterized by a stronger primary emotional response driven by the amygdala.

Abnormal functional architecture of amygdala-centered networks in adolescent posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a prevalent, debilitating, and difficult to treat psychiatric disorder. Very little is known of how PTSD affects neuroplasticity in the developing adolescent brain. Whereas multiple lines of research implicate amygdala-centered network dysfunction in the pathophysiology of adult PTSD, no study has yet examined the functional architecture of amygdala subregional networks in adolescent PTSD. Using intrinsic functional connectivity analysis, we investigated functional connectivity of the basolateral (BLA) and centromedial (CMA) amygdala in 19 sexually abused adolescents with PTSD relative to 23 matched controls. Additionally, we examined whether altered amygdala subregional connectivity coincides with abnormal grey matter volume of the amygdaloid complex. Our analysis revealed abnormal amygdalar connectivity and morphology in adolescent PTSD patients. More specifically, PTSD patients showed diminished right BLA connectivity with a cluster including dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices (p < 0.05, corrected). In contrast, PTSD patients showed increased left CMA connectivity with a cluster including the orbitofrontal and subcallosal cortices (p < 0.05, corrected). Critically, these connectivity changes coincided with diminished grey matter volume within BLA and CMA subnuclei (p < 0.05, corrected), with CMA connectivity shifts additionally relating to more severe symptoms of PTSD. These findings provide unique insights into how perturbations in major amygdalar circuits could hamper fear regulation and drive excessive acquisition and expression of fear in PTSD. As such, they represent an important step toward characterizing the neurocircuitry of adolescent PTSD, thereby informing the development of reliable biomarkers and potential therapeutic targets.

Abnormalities of white matter integrity in the corpus callosum of adolescents with PTSD after childhood sexual abuse: a DTI study.

This study seeks to determine whether white matter integrity in the brain differs between adolescents with post-traumatic stress disorder (PTSD) due to childhood sexual abuse (CSA) and matched healthy adolescents and whether there is a relationship between white matter integrity and symptom severity in the patient group. Using 3T diffusion tensor imaging, we examined fractional anisotropy (FA) in a group of adolescents with CSA-related PTSD (n = 20) and matched healthy controls (n = 20), in a region of interest consisting of the bilateral uncinate fasciculus (UF), the genu, splenium and body of the corpus callosum (CC), and the bilateral cingulum. In addition, we performed an exploratory whole brain analysis. Trauma symptomatology was measured with the Trauma Symptom Checklist for Children (TSCC) to enable correlational analyses between FA differences and trauma symptomatology. The PTSD group had significantly lower FA values in the genu, midbody and splenium of the CC in comparison with controls (p < 0.05, tfce corrected). Post hoc analyses of the eigenvalues of the DTI scan showed increased radial and mean diffusivity in the patient group. In addition, we found a significant negative correlation between scores on the anger subscale of the TSCC and FA values in the left body of the CC in patients (p < 0.05). Adolescents with CSA-related PTSD show decreased FA in the CC, with abnormalities in the integrity of the left body of the CC being related to anger symptoms. These findings suggest that early trauma exposure affects the development of the CC, which may play a role in the pathophysiology of PTSD in adolescents.

Adult Attachment Interview differentiates adolescents with Childhood Sexual Abuse from those with clinical depression and non-clinical controls.

Although attachment representation is considered to be disturbed in traumatized adolescents, it is not known whether this is specific for trauma, as comparative studies with other clinical groups are lacking. Therefore, attachment representation was studied by means of the Adult Attachment Interview in adolescents with Childhood Sexual Abuse (CSA) (N = 21), clinical depression (N = 28) and non-clinical controls (N = 28). Coherence of mind and unresolved loss or trauma, as well as the disorganized attachment classification differentiated the CSA group from the clinical depression group and controls, over and above age, IQ, and psychiatric symptomatology. In the current era of sustained criticism on criteria-based classification, this may well carry substantial clinical relevance. If attachment is a general risk or vulnerability factor underlying specific psychopathology, this may guide diagnostic assessment as well as treatment.