title: Abnormal functional architecture of amygdala-centered networks in adolescent posttraumatic stress disorder.
abstract: 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.
authors: Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Curium, Leiden, the Netherlands.|Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands.
authors: Moji
authors: M
authors: Aghajani
authors: Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Berlin, Germany.
authors: Ilya M
authors: IM
authors: Veer
authors: Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Curium, Leiden, the Netherlands.|Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands.|Rivierduinen Institute for Mental Health Care, Psychotraumacenter and Department of Child and Adolescent Psychiatry, Leiden, the Netherlands.
authors: Marie-José
authors: MJ
authors: van Hoof
authors: Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands.|Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.|Leiden University, Institute of Psychology, Leiden, the Netherlands.
authors: Serge A R B
authors: SA
authors: Rombouts
authors: Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands.|Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands.
authors: Nic J
authors: NJ
authors: van der Wee
authors: Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Curium, Leiden, the Netherlands.|Leiden Institute for Brain and Cognition (LIBC), Leiden, the Netherlands.
authors: Robert R J M
authors: RR
authors: Vermeiren
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D002650:Child Abuse, Sexual; D015897:Comorbidity; D005260:Female; D066128:Gray Matter / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000254:growth & development / Q000503:physiopathology; D009473:Neuronal Plasticity; D009929:Organ Size; D012146:Rest; D012815:Signal Processing, Computer-Assisted; D013313:Stress Disorders, Post-Traumatic / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*
keywords: PTSD; adolescents; amygdala; grey matter; intrinsic functional connectivity