Hypothalamus volume mediates the association between adverse childhood experience and PTSD development after adulthood trauma

Abstract

The hypothalamus is critical for regulation of the hypothalamic-pituitary-adrenal (HPA) axis and response to stress. Adverse childhood experience (ACE) can affect brain structure, which may contribute to development of posttraumatic stress disorder (PTSD) after subsequent adult trauma. It is unclear, however, if ACE history is particularly associated with aspects of hypothalamic structure which contribute to development of PTSD. To address this issue, the present study longitudinally assessed hypothalamic volumes and their associations with ACE and early post-trauma stress symptoms in subjects who did or did not develop PTSD during 12 months after adult trauma. 109 subjects (18–60 years, F/M = 75/34) completed the PTSD Checklist (PCL) questionnaire for post-trauma stress symptoms, the Childhood Trauma Questionnaire (CTQ) for ACE assessment, and an initial MRI brain scan for hypothalamic volume measurement, within 2 weeks after adult trauma. At post-trauma 12 months, subjects underwent a subsequent PTSD diagnosis interview using the Clinician-Administered PTSD Scale (CAPS), and a follow-up MRI scan. Left and right hypothalamus volumes at 2 weeks after adult trauma negatively correlated with CTQ scores. Right hypothalamus volume at this early time mediated an association between ACE and PTSD symptoms 12 months later. Right hypothalamus volumes also remained persistently smaller from 2 weeks to 12 months after trauma in survivors who developed PTSD. These results suggest that smaller right hypothalamus volume may be related to ACE history in ways that contribute to PTSD development after trauma in adulthood.

Neuroanatomical and functional correlates in post‐traumatic stress disorder: A narrative review

“… 27 However, concerning the effects of hormonal dysregulation resulting from stress, the literature reports that numerous evidences, 38 , 39 studies regarding possible neuroanatomical alterations of the hypothalamus in PTSD are still relatively scarce. However, a recent paper 40 analyzed by MRI the hypothalamic volume in adult subjects with a diagnosis of PTSD who had experienced one or more adverse childhood experiences (ACEs) during childhood, showing a significant reduction in this brain structure compared with that found in the control sample and subjects without PTSD. Volumetric reduction was particularly identified in the hypothalamic paraventricular nucleus (PVN).…”

Hypothalamic Subunit Volumes in Schizophrenia and Bipolar Spectrum Disorders

“…In postmortem studies of individuals with SCZ significant differences of the SON, PVN, or the SCN have not been observed, while a larger PVN volume was reported in an in vivo MRI study. 6 Some examples of the relationship between abnormalities in hypothalamic volume and impaired functioning, include: the size of the mammillary bodies was negatively correlated with negative symptoms and positively correlated with anxiety 7 ; a smaller right hypothalamus volume was associated with post-traumatic stress disorder symptoms, 34 which can be related to the HPA axis and consequently involve the ARC and PVN nuclei and stress-related molecular pathways; higher Body Mass Index was linked to larger subunit volumes, 35 potentially involving VMN nucleus, which regulates satiety and caloric intake.…”

Adverse Childhood Experiences, Brain Function, and Psychiatric Diagnoses in a Large Adult Clinical Cohort

“…To date, much of the functional neuroimaging research has been limited by examining single diagnoses, like depression or PTSD (9). Xie et al (10) found that reduced right hypothalamus volumes, as a reaction to childhood stress, may contribute to the development of PTSD in adult trauma survivors. Additionally, neuroimaging work has shown that larger amygdala volumes, as assessed by magnetic resonance imaging (MRI), are correlated with increased risk exposure during childhood (11).…”