Interaction of childhood stress with hippocampus and prefrontal cortex volume reduction in major depression

Institute of Neuroscience, Department of Psychiatry, Trinity College Dublin, Dublin 2, Ireland.
Journal of Psychiatric Research (Impact Factor: 3.96). 10/2010; 44(13):799-807. DOI: 10.1016/j.jpsychires.2010.01.006
Source: PubMed


Early emotional stress is associated with a life-long burden of risk for later depression and stressful life events contribute to the development of depressive episodes. In this study we investigated whether childhood stress is associated with structural brain alterations in patients with major depression (MD). Forty-three patients with MD and 44 age as well as gender matched healthy control subjects were investigated using high-resolution magnetic resonance imaging (MRI). Region of interest analysis of the hippocampus, whole brain voxel-based morphometry (VBM) and assessment of childhood stress was carried out. Significantly smaller hippocampal white matter and prefrontal gray matter volume was observed in patients with MD compared to healthy controls. In particular left hippocampal white matter was smaller in patients, who had emotional childhood neglect, compared to those without neglect. For male patients this effect was seen in the left and right hippocampus. Moreover, physical neglect during childhood affected prefrontal gray matter volume in healthy subjects. Both emotional neglect and brain structural abnormalities predicted cumulative illness duration and there was a significant interaction between emotional neglect and prefrontal volumes as well as hippocampal white matter on the illness course. Childhood neglect resulted in hippocampal white matter changes in patients with major depression, pronounced at the left side and in males. Most interestingly, childhood stress and brain structure volumes independently predicted cumulative illness course. Subjects with both, structural brain changes and childhood emotional neglect seem to be at a very high risk to develop a more severe illness course.

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    • "Strikingly, ES affected levels of survival of adult-born neurons exclusively in males associated with (and determinant for) a more severely impaired cognitive performance in adult ES-male mice compared with females. This is in line with previous clinical and preclinical studies indicating a higher sensitivity of males to ES (Llorente et al., 2009; Oomen et al., 2009; Frodl et al., 2010; Mak et al., 2013; Loi et al., 2014), again reinforcing the translational value of this ES model. It indeed appears that males are more vulnerable to develop mental diseases after exposure to ES. "
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    ABSTRACT: Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity.
    Stress (Amsterdam, Netherlands) 08/2015; · 2.72 Impact Factor
    • "In the current study we are primarily interested in the possible moderating effects of CM on the association between MDD and hippocampal volume, because CM is a major risk factor for the onset of MDD (Kessler et al. 1997) and because two earlier studies showed that hippocampal volume loss is more pronounced in persons with MDD who also have a history of CM (Vythilingam et al. 2002; Frodl et al. 2010). It has even been suggested that a smaller hippocampal volume due to CM may render individuals more susceptible for the onset of MDD (Rao et al. 2010). "
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    ABSTRACT: Childhood maltreatment (CM) may modify the relationship between major depressive disorder (MDD) and hippocampal volume reduction. To disentangle the impact of MDD and CM on hippocampal volume we investigated the association between MDD and hippocampal volume in persons with and without a history of CM in two independent cohorts. We used data of 262 participants from the Netherlands Study of Depression and Anxiety (NESDA) (mean age 37 years, 32% male) and 636 participants from the SMART-Medea study (mean age 61 years, 81% male). In both studies a 12-month diagnosis of MDD and CM were assessed using a diagnostic interview. Hippocampal volume was measured in NESDA using FreeSurfer software on 3-T magnetic resonance (MR) images and in SMART it was manually outlined on 1.5-T MR images. With analysis of covariance adjusted for intracranial volume, age, gender and lifestyle factors we estimated the effects of MDD and CM on hippocampal volume. In both cohorts CM was not significantly associated with hippocampal volume. After pooling the data MDD was associated with smaller hippocampal volume (B = -138.90 mm3, p = 0.05) and the interaction between MDD and CM reached significance (p = 0.04); in participants with CM, MDD was related to smaller hippocampal volume (NESDA: B = -316.8 mm3, p = 0.02; SMART: B = -407.6, p = 0.046), but not in participants without CM (p > 0.05). Our study shows that in two independent cohorts, particularly in individuals with CM, a diagnosis of MDD is related to smaller hippocampal volume. Prospective studies are needed to further determine through which mechanism CM may amplify the relationship between MDD and hippocampal volume.
    Psychological Medicine 07/2015; -1:1-10. DOI:10.1017/S0033291715001415 · 5.94 Impact Factor
    • "There were also no significant hippocampal abnormalities in women with PTSD related to sexual abuse during late childhood/adolescence in the study by Landre et al. (2010). Further, Frodl et al. (2010) found smaller hippocampal white matter in depressed patients reporting emotional neglect before age 18 years, but did not find a significant reduction in hippocampal gray matter. "
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    ABSTRACT: We present new empirical data and meta-analytic evidence for the association of childhood maltreatment with reduced hippocampal volume. In Study 1, we examined the effects of maltreatment experiences reported during the Adult Attachment Interview on hippocampal volume in female twin pairs. We found that reduced hippocampal volume was related to childhood maltreatment. In addition, individuals who reported having experienced maltreatment at older ages had larger reductions in hippocampal volume compared to individuals who reported maltreatment in early childhood. In Study 2, we present the results of a meta-analysis of 49 studies (including 2,720 participants) examining hippocampal volume in relation to experiences of child maltreatment, and test the moderating role of the timing of the maltreatment, the severity of maltreatment, and the time after exposure to maltreatment. The results of the meta-analysis confirmed that experiences of childhood maltreatment are associated with a reduction in hippocampal volume and that the effects of maltreatment are more pronounced when the maltreatment occurs in middle childhood compared to early childhood or adolescence.
    Development and Psychopathology 05/2015; 27(2):507-20. DOI:10.1017/S0954579415000127 · 4.89 Impact Factor
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