Research reportVolumetric MRI changes, cognition and personality traits in old age depression
Introduction
Early-onset depression (EOD) is usually defined by an onset of the first major depressive episode before 60 years of age. In older adults, EOD has been described as a distinctive phenomenological entity as opposed to late-onset depression (Brodaty et al., 2001, Rapp et al., 2005), reflecting possible differences in aetiology, neurophysiological patterns and guidance of anti-depressant treatment. Depression in old age is a multi-facet disorder that may affect not only mood regulation but also cognition, brain structure and personality. During acute depressive phases, deficits in processing speed, working memory (Nebes et al., 2000), executive function (Baudic et al., 2004), and episodic memory (Rapp et al., 2005) have been described in the elderly. Even more than in younger cohorts (Paelecke-Habermann et al., 2005, Paradiso et al., 1997), some cognitive deficits in old age may represent trait characteristics of depression that persist despite the amendment of symptoms (Lee et al., 2007, Rapp et al., 2005). However, this viewpoint has been challenged by prospective studies showing that depression at baseline is not necessarily associated with an increased risk of subsequent cognitive decline (Brodaty et al., 2003, Dufouil et al., 1996). Consistent with the presence of state-independent memory impairment (Rapp et al., 2005), a substantial loss of hippocampal volume bilaterally has been described in elderly patients with early-onset depression compared to age-matched controls (Bell-McGinty et al., 2002, Sheline et al., 1999). This finding might reflect decreased neurogenesis (Kempermann and Kronenberg, 2003) or toxic effect of glucocorticoids on the hippocampus (Campbell and Macqueen, 2004, Post, 1992). In the same line, studies in both younger and elderly patients with a history of recurrent depression reported reduced frontal and parietal lobe volumes as well as frontal and anterior cingulate cortex hypometabolism (Ballmaier et al., 2004, Drevets et al., 1997, Martinot et al., 1990). In contrast to volumetric changes, vascular pathology and in particular deep white matter hyperintensities (WMH) have been traditionally associated with late-onset depression in hospital-based samples (Takahashi et al., 2008). However, a community-based study reported no difference in vascular burden between patients with EOD and late-onset depression (Janssen et al., 2006).
Besides its cognitive and neuroanatomical correlates, EOD is thought to be associated with persisting changes of personality dimensions (Brodaty et al., 2001). Referring to the Five-Factor Model of personality (Costa and McCrae, 1992), high levels of Neuroticism not only predispose to depressive reactions (Kendler et al., 1993, Liang-Lin et al., 2007), but may be present even in remitted young patients (Maier et al., 1992). However, other studies reported that Neuroticism and Extraversion were unrelated to depression (Santor et al., 1997, Shea et al., 1996). In young cohorts, recovered EOD patients showed decreased Extraversion, Conscientiousness, and increased Agreeableness (Anderson and McLean, 1997, Bagby et al., 1997, Barnett and Gotlib, 1988). In older patients, similar data are still rare. In a 6 year follow-up on 1511 elderly, Steunenberg et al. (2006) showed that Neuroticism was a main predictor of the onset of depressive symptoms in late life and that personality was a more powerful determinant of depression than physical health-related and social factors. Neuroticism has been shown to remain significantly higher in elderly patients who recovered from depression (Abrams et al., 1991).
Two main limitations explain the difficulty to draw definite conclusions about the long-term impact of EOD on cognition, brain structure and personality in the elderly. First, the vast majority of earlier studies in younger cohorts were based on routine neuropsychological measures, such as the Mini-Mental State Examination, which often fail to identify changes in restricted cognitive sub-domains (Royall and Mahurin, 1994), and have demonstrated a relatively low sensitivity to detect cognitive impairment associated with sub-cortical vascular lesions (Nys et al., 2005). Most importantly, studies in geriatric populations mostly focused on late-onset depression and limited their analysis on neuropsychological and neuroimaging parameters, neglecting psychological vulnerability markers. No study attempted to explore the relationship of these three trait characteristics in the same EOD sample.
The main goal of this study was to investigate concomitantly the neurocognitive and psychological characteristics of euthymic patients with EOD. In particular, we aimed to explore whether the long-term evolution of EOD is associated with persistent cognitive deficits and MRI structural alterations. We also hypothesized that changes in personality dimensions occur in EOD patients in the absence of acute depressive symptoms. The cross-sectional comparison between euthymic EOD and healthy elders included detailed neuropsychological evaluation, assessment of both volumetric changes in limbic areas and vascular burden and extensive investigation of personality profiles according to the Five-Factor Model. The statistical analysis included three parts. The first concerned group comparisons for each of the three sets of data (i.e. cognitive, MRI and personality factors and facets). Subsequently, covariates that are known to influence cognitive performances, brain volumes and personality (such as age, gender, education, nature and severity of depressive illness) were introduced in multivariate linear regression models. Finally, the possible correlations between the three sets of data were also explored.
Section snippets
Participants
Inclusion criteria for both groups were defined as 60 or more years, good French-speaking capacities, and absence/presence of EOD. Diagnosis of EOD and absence of psychiatric disorder in healthy controls was established using the Mini International Neuropsychiatric Interview (Sheehan et al., 1998) administered by a senior psychiatrist. Patients were recruited in geriatric psychiatry divisions of the University Hospitals of Geneva and Lausanne (Switzerland). Controls were recruited in
Demographics and clinical characteristics (Table 1)
As summarized in Table 1, no group differences were observed for education and gender, participants being predominantly women with 13–14 years of education. Controls were significantly older than EOD patients (Z = 3.67, p < 0.001). Both groups did not differ in respect to their score on the Charlson Cormorbidity Index, indicating an overall good physical health status in both samples. 27 patients (71%) had two or more depressive episodes, while the remaining 11 (29%) patients showed one single
Discussion
From a neurocognitive perspective, the present study shows that euthymic EOD patients are preserved both in terms of global functioning and depression-specific cognitive domains. This sparing concerns processing speed, working memory and executive function but also episodic memory performances thought to be particularly vulnerable in the long-term evolution of EOD (Rapp et al., 2005). As already suggested (Biringer et al., 2005, Biringer et al., 2007), this vulnerability may concern the acute
Role of the funding source
This research was supported by the Swiss National Science Foundation (FNRS grant no 3200BO-112018) and the Lemanic Center for Biomedical Imaging (CIBM). The FNRS had no further role in the study design; in the collection, analysis and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication. The devices of the CIBM were used for structural imaging assessment, and its staff supervised the MRI data analysis and interpretation.
Conflict of interest
All authors declare that they have no conflict of interest.
Acknowledgement
None.
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