Short CommunicationHippocampal volume in vulnerability and resilience to depression
Introduction
There is much interest in the role of disturbed neuroplasticity in the biological basis of depression (Czeh and Lucassen, 2007). Significant reduction (typically around 10%) in hippocampal grey matter volume has been reported in depressed (, , ) and remitted patients (, ), suggesting that this impairment may represent a trait characteristic of depression. However, the causal and temporal nature of this volume change is unclear.
The neurotoxicity hypothesis posits that these volumetric changes occur as a neurodegenerative reaction to prolonged periods of stress and associated heightened glucocorticoid levels in depression (Sheline, 2011). Consistent with this, hippocampal volume loss is correlated with the length and number of recurrent episodes (, , ).
However, smaller hippocampal volume has also been illustrated in individuals at the first depressive episode (Cole et al., 2011) and adolescent depressed patients (Rao et al., 2010). Therefore, it is possible that vulnerable individuals may have a pre-existing difference in hippocampal volume. Supporting this vulnerability hypothesis, never-depressed individuals with familial risk of depression were shown to have significantly smaller hippocampus than matched control participants (, ), and predictive of depressive episode in five years (Rao et al., 2010). However, contradictory findings should be noted (den Heijer et al., 2011). Furthermore, the evidence was limited to familial risk and may not be generalisable to other risk factors. Finally, the neurotoxicity and vulnerability hypotheses are not mutually exclusive. It is possible that smaller hippocampus predisposes individuals to depression, and the illness itself leads to further volume reduction.
The current study therefore examined whether differences in hippocampal volume occur as a function of vulnerability to depression. Neuroticism is a robust risk factor for depression (Kendler et al., 2006). We recruited participants with high neuroticism who had never experienced depression or had recovered from at least one depressive episode. Hippocampal volumes were compared to a control group with low neuroticism. We predicted that hippocampal volume would be lower in the volunteers recovered from depression. We further hypothesised reduced hippocampal volume in never-depressed volunteers at risk for depression, but to a lesser extent, suggesting that reduction occurs both as a predisposing factor and a consequence of depression.
Section snippets
Participants and psychological measures
Thirty-six participants (aged 19–62) gave informed consent to the study, which was approved by the local psychiatric ethics committee. Selection was based on their extreme scores for high or low neuroticism (N) on the Eysenck Personality Questionnaire (EPQ; Eysenck and Eysenck, 1975) from a cohort of 20,427 families collected as part of a larger investigation (Fullerton et al., 2003). We contacted unrelated individuals with high neuroticism scores (≥17/23; Mean 21.0, SD 1.3) who had never
Methods (Study 2)
Twenty-five undergraduates (aged 18–22) scoring high (≥8/12, n=12) or low (≤3/12, n=13) on the 12-item neuroticism scale of short version of the Eysenck Personality Questionnaire (Eysenck et al., 1985) were recruited. Using SCID-I, participants were confirmed to be free of current or previous axis I disorder. They had no current physical illness and had been free of medication for at least one month. All participants gave informed consent to the study, which was approved by the local
Discussion
This study not only replicated hippocampal volume reduction in individuals recovered from depression, it further demonstrated that this reduction is evident even when comparing with never-depressed individuals with matched levels of neuroticism. Hence, such structural changes are not solely an artefact of differences in anxious or dysphoric temperaments, but are more specifically linked to the experience of depression. Our study directly contrasted between those who are vulnerable but
Acknowledgement
The authors would like to thank Prof Clare MacKay for her assistance in extraction of hippocampal volume data, and to all participants. MJP is funded by the Ministerio de Ciencia e Innovación of the Spanish Government and by the Instituto de Investigación Carlos III through a “Miguel Servet” research contract (CP10/00393), co-financed by the European Regional Development Fund (ERDF) (2013-2016). CJH has received paid consultancy from Lundbeck, Servier and P1vital. She is a company director of
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