Bipolar Disorder: Childhood Trauma Modulates Impact on Amygdala, Hippocampus

amygdala brain
amygdala brain
Childhood trauma modulates the effects of bipolar disorder on the amygdala and hippocampus by causing an increase in the volumes of gray matter.

Childhood trauma affects the volumes of gray matter in the amygdala and hippocampus differently in patients with bipolar disorder than healthy controls, according to a study published recently in Bipolar Disorders.

“Patients with bipolar disorder had a global reduction of volumes of deep gray matter structures compared to healthy people,” said Gianfranco Spalletta, MD, PhD, psychiatrist and neuropsychiatrist, head of the Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation of Rome, Italy, in an email interview with Psychiatry Advisor. “However, childhood trauma modulates the impact of the diagnosis specifically on amygdala and hippocampus structures.”

The study assessed 105 outpatients with bipolar disorder type 1 (BP-I) or bipolar disorder type II (BP-II), diagnosed according to DSM-IV-TR criteria, and 113 healthy controls (HC). All patients were recruited at the Sant’Andrea Hospital and Santa Lucia Foundation in Rome, Italy, and received pharmacological treatment for at least 6 months prior to study initiation. A short form of the Childhood Trauma Questionnaire (CTQ) was used to record the history of childhood trauma. Whole-brain T1-weighted images of the brain were obtained using high-resolution magnetic resonance imaging. Sociodemographic and clinical characteristics of 6 study groups (BP-I, BP-II, and HC, with or without childhood trauma) were compared and reported.

Researchers observed a reduction of deep gray matter volumes in patients with BP-I and BP-II compared with healthy controls. However, childhood trauma modulated the effects of BP disorder on the amygdala and hippocampus – the regions of the brain involved in stress response and emotion processing. Childhood trauma was associated with increased gray matter volumes in these regions in patients with BP and bilateral decreased volumes in healthy controls.

“The amygdala and hippocampus are part of the same neural network implicated in the response to stress and in the emotional processing; specifically, the hippocampus inhibits the ventro-medial prefrontal cortex, which releases the amygdala from its own inhibition,” explained Dr Spalletta. “Consequently, the activation of the hippocampus may be associated with the activation of the amygdala, and the atrophy may be the final effect of an elevated-neurotoxic activity of these two structures,” he added.

Age and educational level did not significantly differ in the 6 study groups. However, significant differences were observed in sex, and manic (Young Mania Rating Scale), depressive (Hamilton Rating Scale for Depression), and anxiety (Hamilton Rating Scale for Anxiety) symptoms, as well as lifetime use of antipsychotics. 

Dr Spalletta is hopeful that these findings will raise awareness about the importance of considering the effects of childhood trauma on psychiatric conditions such as bipolar disorder.

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“Childhood maltreatment has been associated with long-term structural and functional brain abnormalities, alterations in neurochemistry and in other neurobiological targets,” he stressed and added, “childhood traumatic events are more frequently reported in patients than in healthy controls, with a high prevalence rate (ie, childhood abuse and neglect have been reported by 51% patients with bipolar disorders).”

Therefore, Dr Spalletta believes that “the assessment of early trauma…should definitively be included in the clinical evaluation of patients with psychiatric disorders.” In practical terms, he thinks that “physicians should have a reference textbook specifically focusing on childhood trauma in psychiatry to properly address a pharmacological/psychotherapeutic/rehabilitative treatment,” since “considering childhood trauma, can, in fact, really make a difference between caring for symptoms and treating psychiatric disorders.”


Janiri D, Sani G, De Rossi P, et al. Amygdala and hippocampus volumes are differently affected by childhood trauma in patients with bipolar disorders and healthy controls [published online July 12, 2017]. Bipolar Disord. doi:10.1111/bdi.12516.