Original articleEnlargement of the amygdala in patients with a first episode of major depression
Introduction
The amygdala serves an important role in the mediation of affective behavior Aggleton 1993, Kling and Borthers 1992. Neuroimaging studies indicate that the amygdala is involved in the neuroanatomical model of mood regulation in humans Drevets 1998, Salloway and Cummings 1994, Soares and Mann 1997. This model supposes limbic-thalamic-cortical (LTC) circuits, comprising the amygdala, medial thalamus, orbital and medial prefrontal cortex, and limbic-cortical-striatal-pallidal-thalamic (LCSPT) circuits, involving the components of the LTC circuit along with related parts of the striatum and pallidum (Drevets et al 1992). Kluver and Bucy (1939) demonstrated that bilateral amygdalectomy led to complete loss of aggressive behavior of previously aggressive animals. Electrical stimulation of the amygdala in animals or preoperatively in humans produces anxiety, fear, dysphoria, recollection of emotionally provocative events, and increases the secretion of the hormone cortisol Brothers 1995, Gloor et al 1982, Rubin et al 1966. With regard to a possible involvement of the amygdala, it is of interest that core symptoms of depression are mood disturbances and that increased cortisol secretory activity was repeatedly reported in depressed patients Holsboer 2000, Rubin et al 1987.
The role of the amygdala in the psychopathology of affective disorders, however, is just beginning to be elucidated. Patients with major depression showed increased glucose metabolism in the amygdala compared to healthy control subjects Drevets et al 1992, Ho et al 1996. Positron emission tomography studies revealed that cerebral blood flow (CBF) and glucose metabolism correlated positively with depression severity Abercrombie et al 1998, Drevets et al 1992, and patients who relapsed after serotonin depletion had higher amygdala glucose metabolism than those who did not relapse (Bremner et al 1997). This increased amygdala activity was proposed to result from the inhibition of reciprocal connections between the prefrontal cortex and the amygdala in LTC or LCSPT circuits (Drevets 2001).
Only two magnetic resonance imaging (MRI) studies on the amygdala have been performed in patients with recurrent major depression. Sheline et al (1998) found no significant change of the amygdala total volumes, but described significant reductions of the amygdala core volumes in patients with recurrent major depression. In another study on 34 drug-resistant patients with major depression, no significant differences in amygdala volumes were observed as compared to 17 age-matched healthy control subjects; however, the patients, but not the controls, had significant asymmetry of the amygdala volumes (right smaller than left) (Mervaala et al 2000).
These examinations were limited by the fact that they either focused on elderly patients with long illness durations (Sheline et al 1998) or that they investigated a special group of drug-resistant subjects (Mervaala et al 2000). Although a study of depressed patients at the beginning of the disease might avoid these influences, there is currently no study available that has examined the amygdala volume with structural MRI in first-episode patients. The aim of the present study was to investigate the amygdala volumes in patients who were having their first episode of major depression. In addition, a possible correlation between amygdala volumes and clinical characteristics, such as illness duration, age of onset, and severity of depression was evaluated by the use of appropriate and well-established instruments.
Section snippets
Subjects
Thirty inpatients of the psychiatric hospital of the Ludwig-Maximilians-University in Munich were included who had been hospitalized for their first episode of major depression (F-MDE) (Table 1: age: 18–59 years; mean age: 40.3 ± 12.6 years). Psychiatric diagnoses were determined by the consensus of at least two psychiatrists, who concurred on a diagnosis based on DSM-IV criteria. Twenty-six of the 30 depressive patients were receiving antidepressants: selective serotonin reuptake inhibitors
Results
Patients with major depression (F-MDE) did not differ significantly from healthy control subjects with respect to age, gender, handedness, education, alcohol consumption, height, and weight (Table 1). Total brain volumes were not significantly different between patients and control subjects (Table 2).
The ANCOVA with group (F-MDE vs. healthy control subjects) and gender (male vs. female) as between-subject factor and hemisphere (left vs. right) as within-subject factor, including total cranial
Discussion
The primary finding of the current study was that patients had significantly increased amygdala volumes in both hemispheres as compared to the matched healthy control subjects. To our knowledge this is the first investigation that reports differences in amygdala structures in patients with a first episode of major depression.
One reason for discrepancies between the findings of the present study and the two studies investigating recurrent major depression might be the clinical differences
Acknowledgements
This study was supported by the German Federal Research Ministry within the promotion “German Research Networks in Medicine” within the project “German Research Network on Depression.”
The authors thank Nancy C. Andreasen and her staff, who provided generous support with the segmentation program BRAINS, and Dr. Strauβ and B. Burgermeister for technical support.
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