This thesis describes a cross-sectional behavioral and neuroimaging study in a sample of n=85 adolescents with a history of childhood sexual abuse related PTSD (CSA-related PTSD), anxiety and/or... Show moreThis thesis describes a cross-sectional behavioral and neuroimaging study in a sample of n=85 adolescents with a history of childhood sexual abuse related PTSD (CSA-related PTSD), anxiety and/or depressive disorders or no psychiatric symptoms. We assessed attachment representation as well as psychopathological symptoms, attentional bias and emotional face processing among diagnostic groups. We also correlated unresolved-disorganized attachment representation (Ud) and psychopathology using a general psychopathology factor (GPF) to grey matter (volume), white matter (tracts) and resting state functional connectivity (RSFC) of the brain in the entire sample. We found that clinical groups did not significantly differ in psychopathology. The unresolved-disorganized cannot classify category (Ud/CC) was overrepresented in the CSA-related PTSD group. Coherence of mind also differentiated the clinical groups, but Ud did not. The CSA-related PTSD group had a negative attention bias for neutral and fearful faces, the anxiety/depressive disorders group only for fearful faces. No differences were found for emotional face processing among diagnostic groups. We found a differential relationship of Ud and a GPF to grey matter volume, white matter integrity of white matter tracts and RSFC for Ud. Ud was associated with lateralization of the brain to the left with regard to amygdala RSFC and hippocampal volume. Show less
Hoof, M.J. van; Riem, M.; Garrett, A.; Pannekoek, N.; Wee, N. van der; IJzendoorn, M. van; Vermeiren, R. 2019
Loss and abuse in children can lead to unresolved–disorganized (UD) attachment. Howthis condition relates to brain structure and functionalconnectivity (FC) is unknown. We therefore aimed to... Show moreLoss and abuse in children can lead to unresolved–disorganized (UD) attachment. Howthis condition relates to brain structure and functionalconnectivity (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 thatthe structure of the amygdala and hippocampus and the FC of the latter would be linked to UD attachment. Anatomical and RSFC datawere collected from a mixed group of adolescents (N = 74) with symptoms of posttraumatic stress disorder (PTSD) related to childhoodsexual abuse (CSA), anxiety/depressive symptoms, and without psychiatric disorder as part of the Emotional Pathways’ Imaging Study inClinical 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 AttachmentInterview. 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 associatedwith a smaller left hippocampal volume, R2 = .23, and a higher level of FC between the hippocampus and the middle temporal gyrus andlateral occipital cortex. The associations among UD attachment, specific brain structure, and FC across psychopathological classificationsshows promise for dimensional complements to the dominant classificatory approach in clinical research and practice. Show less
Hoof, M.J. van; Riem, M.; Garrett, A.; Pannekoek, N.; Wee, N. van der; IJzendoorn, M. van; Vermeiren, R. 2019
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... Show moreLoss 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, R-2 = .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. Show less
Hoof, M.J. van; Riem, M.; Garrett, A.; Pannekoek, N.; Wee, N. van der; IJzendoorn, M. van; Vermeiren, R. 2019
Abstract Background: Recent research has identified a general psychopathology factor (GPF), which explains overlap in presentation of psychopathological symptoms. Unresolved-disorganized attachment... Show moreAbstract 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 with Ud and GPF. Method: Resting state functional connectivity (RSFC) data were collected from a mixed group of adolescents (N =74) with and without psychiatric disorder, part of the Emotional Pathways’ Imaging Study in Clinical Adolescents study. Ud was measured using the Adult Attachment Interview (AAI). Associations between Ud, GPF, and RSFC of the amygdala and 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 connectivity, 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. Keywords: General psychopathology factor; unresolved– disorganized attachment; amygdala; resting-state functional connectivity; dorsal anterior cingulate cortex; medial prefrontal cortex; psychopathology; adolescents Show less
Abstract Background: A dimensional approach of psychopathology focuses on features and risk factors that are shared across diagnoses. In support for this dimensional approach, studies point to a... Show moreAbstract Background: A dimensional approach of psychopathology focuses on features and risk factors that are shared across diagnoses. In support for this dimensional approach, studies point to a general psychopathology factor (GPF) associated with risk for multiple psychiatric disorders. It is, however, unknown how GPF relates to white matter integrity (WMI). In the current diffusion tensor imaging (DTI) study, we examined how GPF relates to abnormalities in a skeleton representation of white matter tracts, taking into account a trans-diagnostic risk factor: unresolved-disorganized attachment (Ud) resulting from loss or trauma. Methods: Unique associations between GPF, Ud, and WMI were examined in a combined sample of adolescents (N = 63) with childhood sexual abuse-related posttraumatic stress disorder (N = 18), anxiety and depressive disorders (N = 26) and without psychiatric disorder (N = 19). WMI was measured using DTI. Ud was measured using the Adult Attachment Interview. We controlled for puberty stage, gender, age, and IQ. Results: Controlling for GPF, Ud was associated with reduced fractional anisotropy (FA) in the splenium and inferior fronto-occipital fasciculus (IFOF). Controlling for Ud, GPF was associated with reduced FA in the genu and body of the corpus callosum. Conclusions: Decreasing WMI in the genu and body with increasing psychopathology across diagnoses suggests demyelinization in these areas and may underlie comorbidity and presence of symptoms that transcend psychopathological diagnoses. In contrast, trauma-related WMI reductions in the splenium and IFOF may account for heterogeneity within diagnostic categories as a function of childhood trauma. These findings support the importance of a dimensional approach in addition to traditional diagnostic classifications in clinical research and practice. Keywords: Adversity, Child abuse, Psychopathology, Attachment, Brain imaging Show less
Background: Recent research has identified a general psychopathology factor (GPF), which explains overlap in presentation of psychopathological symptoms. Unresolved-disorganized attachment (Ud) is... Show moreBackground: 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. Show less
Childhood Sexual Abuse related posttraumatic stress disorder (CSA-related PTSD), and anxiety and depressive disorders (clinical depression) have profound though differential impact on adolescent... Show moreChildhood Sexual Abuse related posttraumatic stress disorder (CSA-related PTSD), and anxiety and depressive disorders (clinical depression) have profound though differential impact on adolescent emotion regulation, attention bias and emotional face processing. We hypothesized increased negative attention bias for emotional faces and altered brain functioning in CSA-related PTSD compared to internalizing disorders and healthy controls in a cross-sectional fMRI study using an emotional face processing task in 19 12-20-year-old adolescents with CSA-related PTSD, 26 with internalizing disorders and 26 healthy controls.Outcome measures were reaction times, subjective ratings of emotional faces, and brain activation patterns for whole brain and for regions of interest. Compared to both other groups adolescents with CSA-related PTSD showed significantly slower reaction times and the highest subjective rating of emotional faces. On whole brain and ROI level, no significant group differences were found. Self-reported depressive, posttraumatic or dissociative symptoms were not associated with differences in task-related brain activity. Results support the hypothesis of increased negative attention bias for fearful and neutral faces in CSA-related PTSD versus both other groups. The absence of neural differences might indicate a brain-behavior neuro-imaging gap to be closed by larger and IQ matched samples or more sensitive paradigms to elicit emotion processing. Show less
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... Show moreAdverse 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. Show less
Rinne-Albers, M.A.W.; Werff, S.J.A. van der; Hoof, M.J. van; Lang, N.D. van; Lamers-Winkelman, F.; Rombouts, S.A.; ... ; Wee, N.J.A. van der 2016
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... Show moreThis 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. Show less
Aghajani, M.; Veer, I.M.; Hoof, M.J. van; Rombouts, S.A.R.B.; Wee, N.J. van der; Vermeiren, R.R.J.M. 2016
This study seeks to determine whether white matter integrity in the brain differs between adolescents with post-traumatic stress disorder (PTSD) due to child- hood sexual abuse (CSA) and matched... Show moreThis study seeks to determine whether white matter integrity in the brain differs between adolescents with post-traumatic stress disorder (PTSD) due to child- hood 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 ani- sotropy (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 fas- ciculus (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 Symp- tom Checklist for Children (TSCC) to enable correlational analyses between FA differences and trauma symptomatol- ogy. 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. Show less
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... Show moreAlthough 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. Show less
