Associations of current and remitted major depressive disorder with brain atrophy: the AGES-Reykjavik Study

Abstract

Background: To examine whether lifetime DSM-IV diagnosis of major depressive disorder (MDD), including age at onset and number of episodes, is associated with brain atrophy in older persons without dementia.

Method: Within the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 4354 persons (mean age 76 ± 5 years, 58% women) without dementia had a 1.5-T brain magnetic resonance imaging (MRI) scan. Automated brain segmentation total and regional brain volumes were calculated. History of MDD, including age at onset and number of episodes, and MDD in the past 2 weeks was diagnosed according to DSM-IV criteria using the Mini-International Neuropsychiatric Interview (MINI).

Results: Of the total sample, 4.5% reported a lifetime history of MDD; 1.5% had a current diagnosis of MDD (including 75% with a prior history of depression) and 3.0% had a past but no current diagnosis (remission). After adjusting for multiple covariates, compared to participants never depressed, those with current MDD (irrespective of past) had more global brain atrophy [B = -1.25%, 95% confidence interval (CI) -2.05 to -0.44], including more gray- and white-matter atrophy in most lobes, and also more atrophy of the hippocampus and thalamus. Participants with current, first-onset MDD also had more brain atrophy (B = -1.62%, 95% CI -3.30 to 0.05) whereas those remitted did not (B = 0.06%, 95% CI -0.54 to 0.66).

Conclusions: In older persons without dementia, current MDD, irrespective of prior history, but not remitted MDD was associated with widespread gray- and white-matter brain atrophy. Prospective studies should examine whether MDD is a consequence of, or contributes to, brain volume loss and development of dementia.

Figure 1

Figure 1A–B Definition of different depression groups.

Figure 2

Figure 2A Mean brain parenchymal fraction according to past and current major depressive disorder. Means are adjusted for age, sex, education, MMSE score, subjective memory complaints, smoking habits, alcohol intake, BMI, systolic and diastolic blood pressure, diabetes, history of stroke, white matter lesion volume and presence of infarcts on MRI. Error bars represent standard errors. * p<0.05 Figure 2B Mean brain parenchymal fraction according to early (first MDD before age 60) and late onset (first MDD at age 60 or older) major depressive disorder. The groups include persons with past as well as current MDD. Means are adjusted for age, sex, education, MMSE score, subjective memory complaints, smoking habits, alcohol intake, BMI, systolic and diastolic blood pressure, diabetes, history of stroke, white matter lesion volume and presence of infarcts on MRI. Error bars represent standard errors. # p=0.095 Figure 2C Mean brain parenchymal fraction according to number of times MDD. Means are adjusted for age, sex, education, MMSE score, subjective memory complaints, smoking habits, alcohol intake, BMI, systolic and diastolic blood pressure, diabetes, history of stroke, white matter lesion volume and presence of infarcts on MRI. Error bars represent standard errors. * p<0.05

Figure 2

Figure 2A Mean brain parenchymal fraction according to past and current major depressive disorder. Means are adjusted for age, sex, education, MMSE score, subjective memory complaints, smoking habits, alcohol intake, BMI, systolic and diastolic blood pressure, diabetes, history of stroke, white matter lesion volume and presence of infarcts on MRI. Error bars represent standard errors. * p<0.05 Figure 2B Mean brain parenchymal fraction according to early (first MDD before age 60) and late onset (first MDD at age 60 or older) major depressive disorder. The groups include persons with past as well as current MDD. Means are adjusted for age, sex, education, MMSE score, subjective memory complaints, smoking habits, alcohol intake, BMI, systolic and diastolic blood pressure, diabetes, history of stroke, white matter lesion volume and presence of infarcts on MRI. Error bars represent standard errors. # p=0.095 Figure 2C Mean brain parenchymal fraction according to number of times MDD. Means are adjusted for age, sex, education, MMSE score, subjective memory complaints, smoking habits, alcohol intake, BMI, systolic and diastolic blood pressure, diabetes, history of stroke, white matter lesion volume and presence of infarcts on MRI. Error bars represent standard errors. * p<0.05

Figure 2

Figure 2A Mean brain parenchymal fraction according to past and current major depressive disorder. Means are adjusted for age, sex, education, MMSE score, subjective memory complaints, smoking habits, alcohol intake, BMI, systolic and diastolic blood pressure, diabetes, history of stroke, white matter lesion volume and presence of infarcts on MRI. Error bars represent standard errors. * p<0.05 Figure 2B Mean brain parenchymal fraction according to early (first MDD before age 60) and late onset (first MDD at age 60 or older) major depressive disorder. The groups include persons with past as well as current MDD. Means are adjusted for age, sex, education, MMSE score, subjective memory complaints, smoking habits, alcohol intake, BMI, systolic and diastolic blood pressure, diabetes, history of stroke, white matter lesion volume and presence of infarcts on MRI. Error bars represent standard errors. # p=0.095 Figure 2C Mean brain parenchymal fraction according to number of times MDD. Means are adjusted for age, sex, education, MMSE score, subjective memory complaints, smoking habits, alcohol intake, BMI, systolic and diastolic blood pressure, diabetes, history of stroke, white matter lesion volume and presence of infarcts on MRI. Error bars represent standard errors. * p<0.05

Figure 3

Mean brain parenchymal fraction according to past, current, and age at onset of MDD. Means are adjusted for age, sex, and education. Error bars represent standard errors. * p<0.05; # p=0.058

Figure 4

Z-scores of regional brain volumes according to past and current major depressive disorder. Z-scores are adjusted for age, sex, education, and intracranial volume. * p<0.05 compared to never MDD. Unadjusted mean volume in mL (SD) of brain regions: frontal gray matter 213 (22); temporal gray matter 128 (13); parietal gray matter 86 (10); occipital gray matter 87 (11); hippocampus 5.6 (0.6); amygdala 4.8 (0.6); thalamus 15 (1); striatum 20 (2); frontal white matter 137 (18); temporal white matter 63 (9); parietal white matter 71 (10); occipital white matter 53 (8).