Early Life Adversity, but not suicide, is associated with less prefrontal cortex gray matter in adulthood

Abstract

Background: Suicide and major depression (MDD) are more prevalent in individuals reporting early life adversity (ELA). Prefrontal cortex volume is reduced by stress acutely and progressively in vivo, and changes in neuron and glia density are reported in depressed suicide decedents. We previously found reduced levels of the neurotrophic factor BDNF in suicide decedents and with ELA, and in the present study we sought to determine whether cortex thickness, neuron density or glia density in the dorsolateral prefrontal (BA9) and anterior cingulate (BA24) cortex are associated with ELA or suicide. Methods:A total of 52 brains, constituting 13 quadruplets of nonpsychiatric nonsuicide controls and MDD suicide decedents with and without ELA (n=13/group), all with psychological autopsy, were matched for age, sex and postmortem interval. Brains were collected at autopsy and frozen and blocks containing BA9 and BA24 were later dissected, post-fixed and sectioned.Sections were immunostained for NeuN to label neurons and counterstained with thionin to stain glial cell nuclei. Cortex thickness, neuron and glial density and neuron volume were measured by stereology. Results:Cortical thickness was 6% less with an ELA history in BA9 and 12% less in BA24 (p<0.05), but not in depressed suicide decedents in either BA9 or BA24. Neuron density was not different in ELA or in suicide decedents, but glial density was 17% greater with ELA history in BA9 and 15% greater in BA24, but not in suicides. Neuron volume was not different with ELA or suicide. Discussion:Reported ELA, but not the stress associated with suicide, is associated with thinner prefrontal cortex and greater glia density in adulthood. ELA may alter normal neurodevelopment and contribute to suicide risk.

The times they are a-changin’: a proposal on how brain flexibility goes beyond the obvious to include the concepts of “upward” and “downward” to neuroplasticity

“…Shrinkage of several cortical structures has also been reported in children who have suffered physical/sexual assault [135,136]. Childhood stress also promotes lasting brain changes beyond youth as retrospective and prospective studies detail how early life adversities can cause the thinning of various cortical structures in adulthood [137][138][139][140][141]. Strikingly, personal experiences of abuse may head brain changes specifically to regions involved with that particular adverse sensory input.…”

Biological bases of suicidal behaviours: A narrative review

“…Stress‐induced molecular and cellular changes in the brain interfere with the normal neurodevelopment, resulting in structural and functional brain alterations. Structural neuroimaging studies have shown that cortical thickness is decreased in people with history of ELA, whereas glial density in PFC and anterior cingulate cortex (ACC) is increased (Underwood et al, 2019). Functional magnetic resonance imaging (fMRI) studies in response to socio‐affective cues found state‐dependent functional changes in the fronto‐limbic and temporo‐parietal areas of the brain in individuals with history of ELA (Heany et al, 2018).…”