Research reportAbnormal size of the amygdala predicts impaired emotional memory in major depressive disorder
Introduction
Evidence is increasing that amygdala and hippocampus show significant structural abnormalities in affective disorders. In the majority of studies, individuals with major depressive disorder (MDD) have been shown to have reduced hippocampal size (for review see Campbell et al., 2004, Videbech and Ravnkilde, 2004). Structural abnormalities of the amygdala in affective disorders are a matter of dissent. Two studies (Altshuler et al., 1998, Strakowski et al., 1999) found enlarged amygdala size in individuals with bipolar I disorder. Individuals with recurrent or non-remitted MDD (Mervaala et al., 2000, Frodl et al., 2003, Frodl et al., 2004) or depressive individuals with a broad age range or longer illness duration were reported to have normal (Sheline et al., 1999, Caetano et al., 2004) or reduced (Sheline et al., 1998, Bowley et al., 2002) amygdala size, whereas studies investigating depressive subjects with short disease duration (Bremner et al., 2000, Frodl et al., 2002, Lange and Irle, 2004) or with temporal lobe epilepsy (Tebartz van Elst et al., 1999) found enlarged amygdala size.
There is evidence that depressive individuals have memory impairments for emotional faces (Gilboa-Schechtman et al., 2002). Structural damage to the amygdala was also shown to impair emotional memory (Cahill et al., 1995, Adolphs et al., 2005, Buchanan et al., 2005), including encoding of emotional faces (Boucsein et al., 2001). It has been proposed that the amygdala modulates the hippocampal declarative memory system by enhancing declarative memory of emotionally arousing stimuli (Cahill et al., 1994, Cahill and McGaugh, 1998). Functional imaging studies have shown that amygdalar and hippocampal activity during encoding of emotional stimuli are correlated (Cahill et al., 1996, Hamann et al., 1999, Kilpatrick and Cahill, 2003, Dolcos et al., 2004, Richardson et al., 2004). On the other hand, hippocampus-dependent cognitive mechanisms that alter the emotional response of an individual are capable to alter the degree of neural activity within the amygdala (Phelps et al., 2001, Ochsner et al., 2002, Schaefer et al., 2002).
In the present investigation, amygdala and hippocampal volumes of 21 young women with recent onset MDD and 23 healthy matched control subjects were assessed by structural magnetic resonance imaging (3D-MRI). Depressive and control subjects were subjected to an associative memory task using emotional faces. Present evidence points to a highly specialized role of the amygdala for the processing of emotional faces as opposed to emotional scenes (Hariri et al., 2002). The goals of our study were to analyze how emotional face memory is related to amygdala and hippocampal size of depressive subjects. We further investigated the relationship between anxiety symptoms and amygdala and hippocampus size, as both regions were shown to be implicated in the regulation of anxiety and fear (LeDoux, 2000, Gray and McNaughton, 2000).
Section snippets
Subjects
The sample comprised 21 young female in-patients with the diagnosis of major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (American Psychiatric Association, 1994) admitted to the Psychiatric Hospital of the University of Göttingen (Table 1).
At time of assessment, all subjects met the DSM-IV criteria for a major depressive episode on the basis of interviews with the Structured Clinical Interview for DSM-IV (SCID) (First et al., 1995,
General
Depressive and control subjects did not differ with respect to demographic variables, or intelligence and memory test scores (Table 1). Depressive symptoms of MDD subjects were rated as moderate to strong (BDI, HAMD, SCL-90-R). Depressive subjects had a short illness history and were young at illness onset. Depressive subjects scored significantly higher on the anxiety scales of the STAI and the SCL-90-R compared with controls.
The subgroups (groups Amyg-N/Hipp-N, Amyg-N/Hipp-S, Amyg-L/Hipp-N,
Summary of findings
In the present investigation, we assessed the associative learning of objects and emotional faces in a sample of 21 subjects with MDD and 23 healthy controls. Depressive subjects showed significantly enlarged amygdala size and significantly reduced hippocampal size compared with controls (Table 2). Depressive subjects were significantly impaired in learning emotional facial expressions, with deficits being most pronounced for fearful, surprised and disgusted faces (Table 3). Analysis of
Acknowledgements
We express our appreciation to the subjects who participated in this study. The authors further wish to thank V. Prischmann and C. Galwas for their assistance in the subjects' assessments. Research was supported by grant IR 15/6 and IR 15/8 from the Deutsche Forschungsgemeinschaft.
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