Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression
Introduction
The pathophysiology of mood disorders has been linked to neuroanatomic circuits that regulate emotion. These circuits involve specific limbic and paralimbic areas, including hippocampus and amygdala (Soares and Mann, 1997a, Soares and Mann, 1997b, Strakowski et al., 2002). For instance, the hippocampus is involved in learning and verbal memory (Reiman, 1997). The amygdala is implicated in emotional perception, especially of faces, possibly determining emotional and social behaviors (Baxter and Murray, 2002, Drevets, 2003).
The hippocampus is a key structure in the neuroendocrine theory of depression. In the event of stress, the hypothalamo–pituitary–adrenal axis (HPA) responds with an adaptive glucocorticoid elevation. However, if the stress is chronic, there is a down-regulation of the glucocorticoid receptors. Hippocampus, which is a glucocorticoid and mineralocorticoid feedback site, is highly sensitive to endogenous glucocorticoid levels. The neuroendocrine theory postulates that in major depression sustained hypercortisolism becomes toxic to the hippocampus preventing its ongoing neurogenesis (Sheline et al., 1996, Hoschl and Hajek, 2001, Mizoguchi et al., 2003).
The role of structural abnormalities of the temporal lobe and its components in unipolar depression is controversial. Two studies did not find significant differences in the volumes of the amygdala/hippocampus complex in depressed patients versus healthy controls (Axelson et al., 1993, Coffey et al., 1993). Most studies that looked at hippocampal volumes showed smaller size in currently depressed patients (Sheline et al., 1996, Sheline et al., 1999, Shah et al., 1998, Bremner et al., 2000, Steffens et al., 2000, Mervaala et al., 2000, Frodl et al., 2002, MacQueen et al., 2003, MacMaster et al., 2004), even though some did not find abnormalities (Ashtari et al., 1999, Vakili et al., 2000). Additionally, Sheline et al. (1998) reported smaller left hippocampal volumes in depressed patients in remission, a finding that was replicated by Bremner et al. (2000) and Sheline et al. (2003). Krishnan et al. (1991) found reduced T1 relaxation times in the hippocampus in depressed unipolar patients, while another study found normal T2 relaxation times (Mervaala et al., 2000).
Regarding amygdala volumes, Frodl et al. (2003) reported larger amygdala volume in patients with first-episode depression, but no abnormalities in patients with recurrent depression. Bremner et al. (2000) did not find significant differences in amygdala volume. However, amygdala core nuclei volumes, which include amygdala lateral nucleus, basal nucleus and accessory basal nucleus, were smaller in depressed women (Sheline et al., 1998), and there was also a report of asymmetry in amygdala volumes in females and males (smaller right volume) (Mervaala et al., 2000). Finally, several MRI reports of temporal lobe size in depressed patients did not demonstrate any abnormalities compared with finding in healthy controls (Coffey et al., 1993, Pantel et al., 1997, Bremner et al., 2000), while lower gray matter density was reported in left temporal neocortex in chronically depressed patients in a controlled MRI study (Shah et al., 1998).
The purpose of this study was to evaluate temporal lobe structures in unipolar depressed patients compared with healthy controls. Based on previous findings, we expected to find smaller hippocampal volumes and unaltered amygdala volumes. We also studied superior temporal gyrus (STG), a structure that receives projections from the amygdala and is also involved in face perception (Baron-Cohen et al., 1999). We predicted that STG volumes would not be abnormal in unipolar patients (Morys et al., 2003). In addition, we compared hippocampal and amygdala volumes in major depressive disorder patients with current depressive symptoms versus patients in remission. Since cortisol levels return to normal levels once depression has remitted (Hoschl and Hajek, 2001), we hypothesized that acutely depressed patients would have smaller hippocampal and amygdala volumes than patients with remitted depression.
Section snippets
Subjects
Thirty-one patients (mean age±S.D.=39.2±11.9 years, range=18–58 years, 7 males, 24 females) who fulfilled DSM=IV diagnostic criteria for current or past major depressive disorder based on the Structured Clinical Interview for DSM-IV (SCID) (Spitzer et al., 1994) were studied. Symptoms were rated using the Hamilton Depression Rating Scale (HDRS) 17-item (Hamilton, 1960). Twenty-one patients were currently depressed and 10 patients were in remission at the time of the MRI scan. Table 1 presents
Anatomical measurements
There was no significant difference between all depressed patients and healthy controls in age (mean age±S.D.=39.2±11.9 vs. 36.7±10.7 years, respectively; t=−0.89, df=60, P=0.38) or gender (Fisher's exact test).
Table 2 presents the unadjusted mean volumes of measured structures for all depressed patients and healthy controls. We did not find any significant difference between the whole group of depressed patients and healthy controls on any anatomical measurement (ANCOVA, age, gender and ICV as
Discussion
Patients who had significant depressive symptoms at scan time had smaller bilateral hippocampal gray matter volumes compared with patients with remitted depression. The only previous study comparing patients who were currently depressed to remitted patients also showed reduced gray matter density in left hippocampus in acutely depressed patients (Shah et al., 1998). Even though hippocampal volumes of acutely depressed patients and patients with remitted depression were not significantly
Acknowledgments
This study was partly supported by grants MH 01736 and MH 30915 from the National Institute of Mental Health, the American Foundation for Suicide Prevention, the Veterans Administration, and the Krus Endowed Chair in Psychiatry (University of Texas Health Science Center at San Antonio). Dr. Caetano and Dr. Sassi were supported by scholarships from the CAPES Foundation (Brazil).
References (41)
- et al.
An MRI study of temporal lobe structures in men with bipolar disorder or schizophrenia
Biological Psychiatry
(2000) - et al.
Hypercortisolemia and hippocampal changes in depression
Psychiatry Research
(1993) - et al.
Low glial numbers in the amygdala in major depressive disorder
Biological Psychiatry
(2002) - et al.
MRI investigation of temporal lobe structures in bipolar patients
Journal of Psychiatric Research
(2003) - et al.
Association of depression with medical illness: does cortisol play a role?
Biological Psychiatry
(2004) - et al.
Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects
Biological Psychiatry
(2003) Mood disorders and allostatic load
Biological Psychiatry
(2003)- et al.
Chronic stress attenuates glucocorticoid negative feedback: involvement of the prefrontal cortex and hippocampus
Neuroscience
(2003) - et al.
Quantitative magnetic resonance imaging in geriatric depression and primary degenerative dementia
Journal of Affective Disorders
(1997) - et al.
The anatomy of mood disorders—review of structural neuroimaging studies
Biological Psychiatry
(1997)
The functional neuroanatomy of mood disorders
Journal of Psychiatric Research
Hippocampal volume in geriatric depression
Biological Psychiatry
Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study
Biological Psychiatry
Amygdala enlargement in bipolar disorder and hippocampal reduction in schizophrenia: an MRI study demonstrating neuroanatomic specificity
Archives of General Psychiatry
Hippocampal/amygdala volumes in geriatric depression
Psychological Medicine
Social intelligence in the normal and autistic brain: an fMRI study
European Journal of Neuroscience
The amygdala and reward
Nature Reviews. Neuroscience
Hippocampal volume reduction in major depression
American Journal of Psychiatry
Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study
Archives of General Psychiatry
Rates and predictors of developing a manic or hypomanic episode 1 to 2 years following a first hospitalization for major depression with psychotic features
Journal of Child and Adolescent Psychopharmacology
Cited by (177)
Identification of structural brain alterations in adolescents with depressive symptomatology
2023, Brain Research BulletinAmygdala activity and amygdala-hippocampus connectivity: Metabolic diseases, dementia, and neuropsychiatric issues
2023, Biomedicine and PharmacotherapyStructural neuroimaging markers in bipolar disorder
2022, Biomarkers in Bipolar DisordersIndividualized theta-burst stimulation modulates hippocampal activity and connectivity in patients with major depressive disorder
2020, Personalized Medicine in Psychiatry