Douglas R. McQuoid

Hippocampal volume in geriatric depression

BACKGROUND There is a growing literature on the importance of hippocampal volume in geriatric depression. METHODS We examined hippocampal volume in a group of elderly depressed patients and a group of elderly control subjects (N = 66 geriatric depressed patients and 18 elderly nondepressed control subjects) recruited through Dukes Mental Health Clinical Research Center for the Study of Depression in the Elderly. The subjects received a standardized evaluation, including a magnetic resonance imaging scan of the brain. Patients had unipolar major depression and were free of comorbid major psychiatric illness and neurologic illness. Differences were assessed using t tests and linear regression modeling. RESULTS Accounting for the effects of age, gender, and total brain volume, depressed patients tended to have smaller right hippocampal volume (p =.014) and left hippocampal volume (p =.073). Among depressed patients, age of onset was negatively but not significantly related to right hippocampal volume (p =.052) and to left hippocampal volume (p =.062). We noted that among subjects with either right or left hippocampal volume of 3 mL or less, the vast majority were patients rather than control subjects. CONCLUSIONS These results support a role for hippocampal dysfunction in depression, particularly in late-age onset depression. Longitudinal studies examining both depressive and cognitive outcomes are needed to clarify the relationships between the hippocampus, depression, and dementia.

Clinical Characteristics of Magnetic Resonance Imaging-Defined Subcortical Ischemic Depression

BACKGROUND There is a substantial body of research supporting the vascular depression hypothesis of late-life depression. To update this hypothesis so it incorporates recent research, we propose that the term subcortical ischemic vascular depression may be a more accurate representation of the disease process. We sought to investigate this diagnosis as a construct by examining differences between depressed subjects with and without magnetic resonance imaging defined subcortical ischemic vascular depression. METHODS This case-control study examined 139 depressed elderly subjects. Demographic data, psychiatric, medical, and family history, depressive symptomatology, and functional impairment were compared between groups dichotomized based on neuroimaging findings. RESULTS Seventy-five (54%) of the subjects met neuroimaging criteria for subcortical ischemic vascular depression. Age was most strongly associated with increased prevalence of subcortical ischemic vascular depression. Lassitude and a history of hypertension were also positively associated with the diagnosis; a family history of mental illness and loss of libido were negatively associated with the diagnosis. CONCLUSIONS These data support that subcortical ischemic vascular depression may be a specific syndrome from other types of late-life depression. Further research is needed to further characterize this disorder, particularly in regards to cognitive function and treatment implications.

Change in hippocampal volume on magnetic resonance imaging and cognitive decline among older depressed and nondepressed subjects in the neurocognitive outcomes of depression in the elderly study.

INTRODUCTION previous studies have linked hippocampal volume change and cognitive decline in older adults with dementia. The authors examined hippocampal volume change and cognitive change in older nondemented adults with and without major depression. METHODS the sample consisted of 90 depressed individuals and 72 healthy, nondepressed individuals aged 60 years and older who completed at least 2 years of follow-up data. All patients underwent periodic clinical evaluation by a geriatric psychiatrist as well as baseline and 2-year magnetic resonance imaging. RESULTS over 2 years, the depressed group showed a greater reduction in left hippocampal volume (normalized for total cerebral volume) compared with the nondepressed group (mean difference = 0.013 ± 0.0059, t = 2.18, df = 160, p <0.0305). The difference remained significant after controlling for age, sex, and baseline normalized left hippocampal volume. The authors also found that hippocampal change from baseline to 2 years was associated with subsequent change in Mini-Mental State Examination score from 2 years to 2½ years (left t = 2.81, df = 66, p = 0.0066; right t = 2.40, df = 66, p = 0.0193) among the depressed group. CONCLUSIONS these findings add to the literature linking hippocampal volume loss and late-life depression. Depressed patients with hippocampal volume loss are at greater risk of cognitive decline.

Smaller orbital frontal cortex volumes associated with functional disability in depressed elders.

BACKGROUND Depression is associated with significant functional impairment. Recent evidence has linked the orbital frontal cortex (OFC) with depression. We examined the relationship between OFC volumes in older subjects and impairment in the basic (BADL) and instrumental (IADL) activities of daily living. METHODS The sample consisted of 81 subjects aged 60 years or older; 41 were depressed subjects and 40 healthy control subjects. In a structured interview, subjects reported their medical history and ability to perform both BADL and IADL. Subjects then had a brain magnetic resonance imaging (MRI) scan; the OFC was manually traced bilaterally using neuroanatomical landmarks. Logistic regression was used to examine the effect of OFC volume on BADL and IADL while controlling for the effects of total brain volume, subject status, medical comorbidity, and demographic factors. RESULTS Smaller OFC volumes, along with greater cognitive impairment as measured by the Mini-Mental State Examination, were significantly associated with BADL impairment. Smaller OFC volumes and being depressed were significantly associated with IADL impairment. CONCLUSIONS Smaller OFC volumes are independently associated with functional impairment, supporting its role in depression. Further studies are needed to determine how smaller OFC volumes are related to other MRI abnormalities associated with depression and functional impairment.

Subcortical lesion severity and orbitofrontal cortex volume in geriatric depression

Previous studies have shown a reduction of orbital frontal cortex volume and an increase in magnetic resonance imaging signal hyperintensities in geriatric depression. We aimed to assess the relationship between subcortical gray- and deep white-matter lesions and orbital frontal cortex volume in elderly depressives and controls. The study included 41 elderly depressed patients and 41 age-matched control subjects. The orbital frontal cortex volume was measured in both hemispheres using a standardized MRI procedure. Signal hyperintensities were rated on (T2)-weighted MRI with qualitative lesion analyses performed according to an established hyperintensity classification system. After controlling for total cerebral hemisphere, age and sex, the geriatric depressed subjects had significant reduction in orbital frontal cortex volume and compared with the control group. Multiple linear regression modeling indicated that reduced orbital frontal cortex volumes were significantly associated with increased subcortical gray-matter lesions. Our study confirmed the reduction of OFC volume in geriatric depressed subjects. We also suggest that subcortical lesions may decrease OFC volume. Further studies are needed to understand how subcortical lesions may be related to OFC volume changes.

Orbitofrontal cortex volume in late life depression: influence of hyperintense lesions and genetic polymorphisms.

BACKGROUND Orbitofrontal cortex (OFC) volumetric differences have been reported in depression, but in relatively small samples. Factors associated with these differences are not well described. We examined OFC volumes in a large sample of elderly depressed and non-depressed subjects, exploring the relationship between OFC volume, 5HTTLPR genotype, apolipoprotein E (APOE) genotype and hyperintense lesion volume. We hypothesized that smaller OFC volume would be associated with depression, greater hyperintense lesion volume and severity, and APOE epsilon4 or 5HTTLPR short allele carriers. METHOD A total of 226 depressed and 144 non-depressed older subjects completed 1.5 T magnetic resonance imaging (MRI) and genotyping. OFC volumes and lesion volumes were measured using standardized methods. Lesion severity was additionally rated using the Coffey rating scale. Differences between groups were compared while controlling for age, sex and total cerebral volume; separate models added lesion measures and genetic polymorphisms. RESULTS Depressed subjects exhibited smaller OFC volumes. There was a trend for a negative association between white-matter lesion volume and OFC volume; however, rated white-matter lesion severity was significantly negatively associated with OFC volume. There was no association between gray-matter lesion measures or 5HTTLPR genotype and OFC volume. Contrary to our hypothesis, subjects who were APOE epsilon4 allele positive exhibited larger OFC volumes; in secondary analyses, this finding was limited to the non-depressed group. CONCLUSIONS Reduced OFC volumes are seen in depression and associated with greater severity of white-matter lesions. Healthy subjects who are APOE epsilon4 allele positive exhibited larger OFC volumes. This finding should be examined in other populations.

Reduction of dorsolateral prefrontal cortex gray matter in late-life depression

Postmortem studies have documented abnormalities in the dorsolateral prefrontal cortex (dlPFC) in depressed subjects. In this study we used magnetic resonance imaging to test for dlPFC volume differences between older depressed and non-depressed individuals. Eighty-eight subjects meeting DSM IV criteria for major depressive disorder and thirty-five control subjects completed clinical evaluations and cranial 3T magnetic resonance imaging. After tissue types were identified using an automated segmentation process, the dlPFC was measured in both hemispheres using manual delineation based on anatomical landmarks. Depressed subjects had significantly lower gray matter in the left and right dorsolateral prefrontal cortex (standardized to cerebral parenchyma) after controlling for age and sex. Our study confirmed the reduction of dorsolateral prefrontal cortex in elderly depressed subjects, especially in the gray matter. These regional abnormalities may be associated with psychopathological changes in late-life depression.

Time-to-Remission From Geriatric Depression: Psychosocial and Clinical Factors

OBJECTIVE The authors examined psychosocial and clinical predictors of time-to-remission in a sample of initially clinically depressed elderly patients. METHODS Using a standardized algorithm, a prospective cohort study enrolled 239 patients undergoing treatment. Patients were followed for up to 4.5 years, until death or withdrawal from the study. Baseline predictor variables included psychosocial factors, such as four domains of social support; basic and instrumental activities of daily living; and clinical factors, including use of electroconvulsive therapy (ECT), past history of depression, comorbidities, and antidepressant treatment. RESULTS Only 33% of the sample (n=79) met our classification for depression remission. A lack of instrumental and subjective social support, poor self-rated health, the use of antipsychotic medication, or use of an antidepressant in the last 7 days were predictors of longer time-to-remission. Use of ECT in the last year was related to shorter time-to-remission. CONCLUSION Baseline psychosocial factors were just as important, as predictors of depression remission, as were clinical and diagnostic variables. Interventions directed toward social support resources, in addition to clinical intervention, including the use of ECT where appropriate, are likely to improve rates of depression remission.

Change in stress and social support as predictors of cognitive decline in older adults with and without depression.

The relationship between stress, social support, and cognition in geriatric depression is complex. In this study, we sought to examine whether an increase in stressful life events or a decrease in social support would lead to subsequent cognitive decline among older adults with and without depression.

The Brain-Derived Neurotrophic Factor Val66Met Polymorphism, Hippocampal Volume, and Cognitive Function in Geriatric Depression

OBJECTIVE The Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with geriatric depression. In studies of younger adults without depression, met allele carriers exhibit smaller hippocampal volumes and have poorer performance on neuropsychological tests. The authors examined the relationship between the BDNF gene and hippocampal volumes in depressed and nondepressed older individuals and its relationship with memory functions mediated by the hippocampus. DESIGN One hundred seventy-six elderly depressed white participants and 88 nondepressed participants completed clinical assessments, neuropsychological testing, and provided blood samples for genotyping. One hundred seventy-three participants also underwent brain magnetic resonance imaging. Statistical modeling tested the relationship between genotype and hippocampal volume and function while controlling for diagnosis and other covariates. RESULTS BDNF genotype was not associated with a difference in performance on tests mediated by the hippocampus, including word list learning, prose recall, nonverbal memory, or digit span. After controlling for covariates, BDNF genotype was not significantly associated with hippocampal volume (F[1, 171] = 1.10, p = 0.30). CONCLUSION Despite different findings in younger populations, the BDNF Val66Met polymorphism is not significantly associated with hippocampal volume or function in a geriatric population. The authors hypothesize that other factors may have a stronger effect on hippocampal structure in older individuals and that the association between the Val66Met polymorphism and geriatric depression is mediated through other mechanisms.