تجزیه و تحلیل حجمی از ناحیه هیپوکامپ مناطق فرعی در افسردگی: مطالعه تصویربرداری رزونانس مغناطیسی 3 تسلا

Background While many studies have reported reduced volume of hippocampus in late onset depression (LOD), the status of hippocampus sub-regions (anterior/posterior) is yet to be explored. Evaluating hippocampal sub-regions might facilitate better elucidation of the neurobiological basis of LOD. Methods Twenty five elderly subjects with LOD (mean age = 65.28 yr, SD = 5.73, 15 females) and 20 healthy controls (mean age = 65.35 yr, SD = 5.67, 7 females) were examined using 3-tesla magnetic resonance imaging (MRI). They were also evaluated with Montgomery Asberg Depression Rating Scale (MADRS) and Hindi Mental State Examination (HMSE). We examined the difference in volume of Hippocampal sub-regions between the LOD group and control group controlling for the age, sex and intracranial volume. Results Left posterior hippocampus volume was significantly smaller in LOD group than the control group (1.01 ± 0.19 ml vs 1.16 ± 0.25 ml, F = 7.50, p = 0.009). There was a similar trend for the right posterior hippocampus (1.08 ± 0.19 ml vs 1.18 ± 0.27 ml, F = 3.18, p = 0.082). Depression severity (mean MADRS score = 20.64 ± 8.99) had a significant negative correlation with volumes of right posterior hippocampus (r = −0.37, p = 0.012) and left posterior hippocampus (r = −0.46, p = 0.001) in the LOD group. Conclusions Specific reduction of posterior hippocampus volume and its relationship with depression severity indicates sub region specific hippocampal volumetric abnormalities in LOD. Future studies need to evaluate sub region specific hippocampal volume in LOD longitudinally for better understanding of the pathogenesis of LOD in view of the functional differences between anterior and posterior hippocampus.

Depression is associated with structural brain changes in the form of reduced volume in areas like hippocampus, caudate, putamen, anterior cingulate cortex, orbito-frontal cortex and thalamus (Kempton et al., 2011 and Koolschijn et al., 2009). Several studies and meta-analysis have shown reduced hippocampal volume in depression (Campbell et al., 2004, Kempton et al., 2011, McKinnon et al., 2009 and Videbech and Ravnkilde, 2004). However there are several inconsistencies in the correlates associated with reduced hippocampal volume in depression. Factors like age group of subjects, subtypes based on age of onset of first episode (early vs late), duration of illness, recurrence, severity and measurement of sub-regions of hippocampus are some of the important correlates that are likely to determine the association of hippocampal volume with depression(Eker and Gonul, 2010). There are only limited numbers of studies evaluating hippocampal volume in elderly with depression. A recent meta-analysis of studies in late life depression reported significantly reduced hippocampal volume but of small effect size. However, there were many individual comparison studies (8 out of 15) that did not show significant reduction of hippocampal volume in late life depression (Sexton et al., 2013). Some studies have suggested that hippocampal volume is reduced in elderly with early onset depression (Gerritsen et al., 2011 and Janssen et al., 2007). Abnormality in hypothalamic–pituitary–adrenal (HPA) axis leading to glucocorticoid toxicity has been proposed as the mechanism behind hippocampal volume reduction in early onset depression. On the contrary, studies evaluating this cortisol mediated pathway did not establish this mechanism conclusively (Gerritsen et al., 2011 and O’Brien et al., 2004). Also some studies have shown that hippocampal volume is reduced in patients with late onset depression (LOD) (Hickie et al., 2005 and Lloyd et al., 2004). Sharing of pathophysiology between LOD and Alzheimer's Dementia (AD) has been proposed as the underlying mechanism, based on the evidence for elevated risk for AD with history of LOD (Jorm et al., 1991). Hippocampal volume is reduced in phenotypically heterogeneous conditions like schizophrenia and depression. Hippocampal subfields (dentate gyrus, CA1, CA3 and subiculum) and sub-regions along longitudinal axis (anterior and posterior) appears to have functional heterogeneity (Small et al., 2011 and Strange and Dolan, 1999). Hence measurement of total hippocampus volume might reduce the effect due to specific sub-regional hippocampal volume change. Recent studies on adults with depression have suggested reduced volume in the posterior hippocampal sub-region (Maller et al., 2007 and Neumeister et al., 2005). Volumetric analysis of hippocampal sub-region has not been adequately studied in elderly with LOD. In this study, we evaluated the difference in volume of hippocampal sub-regions between elderly subjects with LOD and healthy control group. We hypothesized that elderly with LOD will have reduced hippocampal volume, particularly in the posterior hippocampal sub-region based on the results of previous studies (as summarized above) in depression.

The comparison of socio-demographic and clinical variables between LOD and control group is summarized in Table 1. There was no significant difference between LOD and control group on age, sex and vascular risk score. However, there was significant difference in HMSE score between groups. Subjects with LOD had lower HMSE score when compared to control group. The median duration of illness in LOD group was 6 months (mean 11.37 and SD 17.92 months). Table 1. Comparison of socio-demographic and clinical variables between patients and healthy controls. Variable LOD group (N = 25) (mean ± S.D.) Control group (N = 20) (mean ± S.D.) t/χ2 p Age (years) 65.28 ± 5.73 65.35 ± 5.67 0.04 0.96 Sex (male:female) 10:15 13:7 2.78 0.09 HMSE 28.12 ± 1.81 29.90 ± 1.21 3.78 <0.001 MADRS 20.64 ± 8.99 0.53 ± 1.12 11.06 <0.001 Vascular score 1.16 ± 0.98 1.05 ± 1.02 0.32 0.75 HMSE—Hindi Mental State Examination. MADRS—Montgomery Asberg Depression Rating Scale. Table options 3.2. Sub regional hippocampal volume analysis Table 2 shows results of comparison of sub regional and total hippocampal volume between LOD and control group with analysis of covariance (ANCOVA) using age, sex and intracranial volume (ICV) as covariates. Left posterior hippocampal volume was significantly smaller in late onset depression (LOD) group than the control group (p = 0.009). Also the right posterior hippocampal volume and left hippocampal volumes were smaller in LOD group than the control group at a trend level significance (p = −0.08 and 0.06, respectively) ( Fig. 1). Table 2. Comparison of hippocampal volumes between patient and control groups. Hippocampal volume (ml) Patient group (N = 25) (mean ± S.D.) Control group (N = 23) (mean ± S.D.) F p * Right anterior HC 1.04 ± 0.16 1.05 ± 0.20 0.14 0.708 Right posterior HC 1.08 ± 0.19 1.18 ± 0.27 3.18 0.082 Left anterior HC 0.91 ± 0.17 0.95 ± 0.17 0.004 0.952 Left posterior HC 1.01 ± 0.19 1.16 ± 0.25 7.50 0.009* Right HC 2.12 ± 0.27 2.23 ± 0.41 1.07 0.305 Left HC 1.93 ± 0.28 2.11 ± 0.33 3.64 0.064 * Significant at the level of p < 0.05 HC—hippocampal. Table options Fig. 2 and Fig. 3 demonstrate the correlation of right and left posterior hippocampal volume, respectively, with MADRS score. Right posterior and left posterior hippocampal volume had significant negative correlation with depression severity assessed by MADRS score (r = −0.37, p = 0.012 for right posterior and r = −0.46, p = 0.001 for left posterior hippocampal volume). These correlations were still significant when controlled for intra cranial volume. Full-size image (12 K) Fig. 2. Correlation of right posterior hippocampal volume and MADRS score. r = −0.37, p = 0.012. Figure options Full-size image (13 K) Fig. 3. Correlation of left posterior hippocampal volume and MADRS score. (r = −0.46, p = 0.001).