Elsevier

Journal of Affective Disorders

Volume 189, 1 January 2016, Pages 199-202
Journal of Affective Disorders

Short Communication
Hippocampal volume in vulnerability and resilience to depression

https://doi.org/10.1016/j.jad.2015.09.021Get rights and content

Highlights

  • Hippocampal volumes were assessed using a model based segmentation method.

  • Reduced volume was found in individuals recovered from depression.

  • Reduced hippocampus is a biological marker, or scar effect, of depression.

  • No evidence to suggest volume change as vulnerability marker prior to illness onset.

  • Increased volume was found in individuals who might have some resilience.

Abstract

Background

Reduced hippocampal volume has been associated with clinical depression. However, it remains unclear whether these changes are a biological vulnerability marker or a consequence of this disorder.

Methods and results (Study 1)

We first compared hippocampal volumes between (i) never-depressed individuals with elevated risk for depression by virtue of high neuroticism (ii) recovered depressed individuals with matched levels of neuroticism; and (iii) individuals with low neuroticism and no history of depression. We replicated the finding of reduced hippocampal volume in the recovered group; unexpectedly however, the never-depressed high-risk group showed an increase in volume. One hypothesis is that this group had a mean age above the typical onset age for depression; hence, these participants who have remained euthymic despite their personality risk might in fact possess some resilience.

Methods and results (Study 2)

A subsequent study was therefore carried out to compare hippocampal volume between high-neurotic vs. low-neurotic volunteers in a younger sample. No group difference was found.

Limitations

The present findings are limited by a small sample size; the cross-sectional design precluded us from makineg definitive conclusions about causal effect.

Conclusion

Our overall results suggest that reduced hippocampal volumes is a neural marker for the scar effect of depression, although this structural impairment could also be seen as a vulnerability marker for the development of future recurrent episodes. By contrast, larger hippocampal volumes could be a biological marker of resilience. These findings have clinical implications regarding treatment development for the prevention of illness onset and recurrent depressive episodes.

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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