Effects of early life stress on depression, cognitive performance and brain morphology

Abstract

Background: Childhood early life stress (ELS) increases risk of adulthood major depressive disorder (MDD) and is associated with altered brain structure and function. It is unclear whether specific ELSs affect depression risk, cognitive function and brain structure.

Method: This cross-sectional study included 64 antidepressant-free depressed and 65 never-depressed individuals. Both groups reported a range of ELSs on the Early Life Stress Questionnaire, completed neuropsychological testing and 3T magnetic resonance imaging (MRI). Neuropsychological testing assessed domains of episodic memory, working memory, processing speed and executive function. MRI measures included cortical thickness and regional gray matter volumes, with a priori focus on the cingulate cortex, orbitofrontal cortex (OFC), amygdala, caudate and hippocampus.

Results: Of 19 ELSs, only emotional abuse, sexual abuse and severe family conflict independently predicted adulthood MDD diagnosis. The effect of total ELS score differed between groups. Greater ELS exposure was associated with slower processing speed and smaller OFC volumes in depressed subjects, but faster speed and larger volumes in non-depressed subjects. In contrast, exposure to ELSs predictive of depression had similar effects in both diagnostic groups. Individuals reporting predictive ELSs exhibited poorer processing speed and working memory performance, smaller volumes of the lateral OFC and caudate, and decreased cortical thickness in multiple areas including the insula bilaterally. Predictive ELS exposure was also associated with smaller left hippocampal volume in depressed subjects.

Conclusions: Findings suggest an association between childhood trauma exposure and adulthood cognitive function and brain structure. These relationships appear to differ between individuals who do and do not develop depression.

Keywords: Brain volumes; depression; magnetic resonance imaging; neuropsychological testing; trauma.

Figure 1

Relationship of ELSQ total score with processing speed and lateral OFC volume Figures show how exposure to increasing numbers of early life stressors (as total ELSQ score) have different effects on processing speed performance and lateral OFC volume between individuals with and without depression. Figure 1.A., While increased number of ELSs resulted in progressively poorer performance in the z-transformed process speed domain in depressed patients, greater numbers of ELSs is associated with better process speed performance in nondepressed controls. Figure 1.B., With increasing ELS exposure, nondepressed subjects showed relative increases in OFC volume. Conversely, depressed subjects exhibited a slight decline in OFC volume with increasing ELS exposure.

Figure 2

Cortical thickness differences related to predictive ELS exposure Whole brain vertex-wise display shows the direct effect of reported predictive ELSs (emotional abuse, sexual abuse, or severe family strife) on cortical thickness. Analyses controlled for diagnosis (MDD or nondepressed) and sex. Lighter blue color reflects areas where ELS exposure is associated with thinner cortex. ELS exposure was not significantly associated with increased cortical thickness in any region.