Medial orbital frontal lesions in late-onset depression

Duke University, Durham, North Carolina, United States
Biological Psychiatry (Impact Factor: 10.26). 06/2001; 49(9):803-6. DOI: 10.1016/S0006-3223(00)01113-6
Source: PubMed


Early studies using magnetic resonance (MR) imaging suggested that subcortical vascular changes are more prevalent in late-life depression and that they may play a role in the pathophysiology of depression. Studying the location of the lesion relative to the occurrence of depression could be critical in delineating the neuroanatomic substrates of depression. Our purpose was to characterize these lesions in terms of location by development of statistical parametric maps of lesions that differentiate patients from control subjects.
Magnetic resonance images were acquired on 88 elderly depressed subjects ("patients," unipolar major depression assessed using the Duke Depression Evaluation Schedule, age range 63-80 years) enrolled in the Duke University Clinical Research Center for the Study of Late-Life Depression and 47 age- and gender-matched nondepressed subjects ("control subjects"). The MR protocol includes a volumetric, dual-contrast fast spin-echo pulse sequence. A statistical parametric map was formed from a two-group t test to test for differences in lesion density between patients and control subjects. Additional testing was performed to evaluate whether there were regions that correlated with the severity of depression using the 17-item Hamilton Depression rating.
The statistical parametric mapping analysis between groups showed two major regions of increased lesion density in the patients in the medial orbital prefrontal white matter. Severity of depression among depressed patients was correlated with lesions in the medial orbital region.
This study supports recent evidence implicating the medial orbital frontal cortex in depression.

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    • "Late-life major depression has been consistently linked to brain abnormalities. Many neuroimaging studies have found that late-life major depression is associated with decreased medial frontal gray matter volume [10], [11] and an increased number of white matter lesions (WMLs) [12], [13], but the relationship between late-life major depression and limbic system abnormalities remains unclear [14]–[16]. Late-life subsyndromal depression could be related to these brain structures if it shares common neuroanatomical substrates with late-life major depression. "
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    ABSTRACT: The purpose of this preliminary study was to test the hypothesis that subsyndromal depression is associated with the volume of medial prefrontal regional gray matter and that of white matter lesions (WMLs) in the brains of cognitively normal older people. We also explored the relationships between subsyndromal depression and medial prefrontal regional gray matter volume, limbic regional gray matter volume, and lobar WMLs in the brains of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). We performed a cross-sectional study comparing patients with subsyndromal depression and nondepressed controls with normal cognition (n = 59), MCI (n = 27), and AD (n = 27), adjusting for sex, age, years of education, and results of the Mini-Mental State Examination. Frontal WML volume was greater, and right medial orbitofrontal cortical volume was smaller in cognitively normal participants with subsyndromal depression than in those without subsyndromal depression. No volume differences were observed in medial prefrontal, limbic, or WML volumes according to the presence of subsyndromal depression in cognitively impaired patients. The absence of these changes in patients with MCI and AD suggests that brain changes associated with AD pathology may override the changes associated with subsyndromal depression.
    PLoS ONE 01/2014; 9(1):e87747. DOI:10.1371/journal.pone.0087747 · 3.23 Impact Factor
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    • "The authors suggest that degeneration of these neurons, with axons running in the WM, is related to hyperintensities observed in the OFC. Functional disruption in the OFC might be of great relevance to affective disorders in the older patients because this brain region is highly involved in emotional regulation and decision-making processes (Grafman et al., 1996; MacFall et al., 2001; Erickson et al., 2005; Savitz et al., 2007). In addition, neuroimaging studies have shown reduced volume and abnormal brain activation of the OFC in midlife and older depressed patients (Lesser et al., 1994; Lai et al., 2000; Lee et al., 2003; Taylor and Krishnan, 2003; Vaishnavi and Taylor, 2006; Brassen et al., 2008). "
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    ABSTRACT: Objective: Late-life depression has been associated with risk for cerebrovascular pathology, as demonstrated in neuroimaging studies of older depressed patients, as well as mood disorder following cerebrovascular accidents. However, more research is needed on neuroanatomical changes in late-life depression, where there has been no clearly documented link to brain injury. Such studies should examine morphological changes in medium and small sized vessels that supply the cortical gray and white matter. Methods: The present study used a non-specific histological Nissl staining and a more vessel-specific immunolabeling with endothelial marker von Willebrand Factor (vWF) to estimate density and size of blood vessel segments in the orbitofrontal cortex of 16 older subjects with major depressive disorder (MDD) and 9 non-psychiatric comparison subjects. Results: The density of Nissl-stained vessel segments and of segments with perivascular spaces was higher in subjects with MDD than in comparison subjects in gray (GM) and white matter (WM). In GM, the density of vWF-immunoreactive segments with cross-sectional areas greater than 800 µm2 was higher in MDD. In WM, only the density of vWF-immunoreactive segments with patent perivascular spaces and diameters larger than 60 µm was higher in subjects with MDD. Also in the WM, only subjects with late-onset MDD presented a significantly higher density of vWF-positive segments than comparison subjects. Conclusions: In older subjects with MDD, there appear to be morphological changes that increase visibility of medium-sized vessel segments with some labeling techniques, and this increased visibility may be related to increased patency of perivascular spaces around arterioles.
    International Journal of Geriatric Psychiatry 09/2013; 28(9). DOI:10.1002/gps.3911 · 2.87 Impact Factor
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    • "The effect of laterality of WMHs on depression is still controversial because while few reports have found frontal left-sided WMHs to be more predictive of depression (Tupler et al., 2002; Greenwald et al., 1998) others did not find any laterality effect (MacFall et al., 2001; O'Brien et al., 2006). In post-stroke depression the heterogeneity across the studies led to discrepant findings on the association between lesion location and post-stroke depression (Bhogal et al., 2004). "
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    ABSTRACT: The aim of this study was to evaluate excitatory/inhibitory intracortical circuit changes in patients with vascular depression, and whether there are any interhemispheric differences of motor cortical excitability. Fifteen vascular depressed elderly (VD), ten nondepressed subcortical vascular disease patients (SVD) and ten age-matched controls underwent bilateral motor threshold and paired-pulse studies. They were also assessed for their brain vascular burden at MRI and neuropsychological profile. Executive dysfunction and apathy were significantly higher in VD; we were unable to find significant differences in resting motor threshold, cortical silent period and paired-pulse curves between VD, SVD and controls, and between the two hemispheres in the VD group. Our findings might suggest that neurophysiological mechanisms underlying VD differ from those previously reported in Major Depression (reduced excitability in the left hemisphere) and seem to be similar to those of patients with SVD. Our findings also, support the "vascular depression" hypothesis, suggesting that in VD patients the depressive syndrome is not the primary disease but can be considered as one of the clinical manifestations in the wide symptom spectrum of the cerebral small vessel disease.
    International journal of psychophysiology: official journal of the International Organization of Psychophysiology 09/2011; 82(3):248-53. DOI:10.1016/j.ijpsycho.2011.09.006 · 2.88 Impact Factor
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