Orbitofrontal cortex function and structure in depression.

Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-2670, USA.
Annals of the New York Academy of Sciences (Impact Factor: 4.31). 01/2008; 1121:499-527. DOI: 10.1196/annals.1401.029
Source: PubMed

ABSTRACT The orbitofrontal cortex (OFC) has been implicated in the pathophysiology of major depression by evidence obtained using neuroimaging, neuropathologic, and lesion analysis techniques. The abnormalities revealed by these techniques show a regional specificity, and suggest that some OFC regions which appear cytoarchitectonically distinct also are functionally distinct with respect to mood regulation. For example, the severity of depression correlates inversely with physiological activity in parts of the posterior lateral and medial OFC, consistent with evidence that dysfunction of the OFC associated with cerebrovascular lesions increases the vulnerability for developing the major depressive syndrome. The posterior lateral and medial OFC function may also be impaired in individuals who develop primary mood disorders, as these patients show grey-matter volumetric reductions, histopathologic abnormalities, and altered hemodynamic responses to emotionally valenced stimuli, probabilistic reversal learning, and reward processing. In contrast, physiological activity in the anteromedial OFC situated in the ventromedial frontal polar cortex increases during the depressed versus the remitted phases of major depressive disorder to an extent that is positively correlated with the severity of depression. Effective antidepressant treatment is associated with a reduction in activity in this region. Taken together these data are compatible with evidence from studies in experimental animals indicating that some orbitofrontal and medial prefrontal cortex regions function to inhibit, while others function to enhance, emotional expression. Alterations in the functional balance between these regions and the circuits they form with anatomically related areas of the temporal lobe, striatum, thalamus, and brain stem thus may underlie the pathophysiology of mood disorders, such as major depression.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbidity and mortality in head trauma incidents. DAIs refer to microscopic white matter (WM) injuries as a result of shearing forces that induce pathological and anatomical changes within the brain, which potentially contribute to significant impairments later in life. These microscopic injuries are often unidentifiable by the conventional computed tomography (CT) and magnetic resonance (MR) scans employed by emergency departments to initially assess head trauma patients and, as a result, TBIs are incredibly difficult to diagnose. The impairments associated with TBI may be caused by secondary mechanisms that are initiated at the moment of injury, but often have delayed clinical presentations that are difficult to assess due to the initial misdiagnosis. As a result, the true consequences of these head injuries may go unnoticed at the time of injury and for many years thereafter. The purpose of this review is to investigate these consequences of TBI and their potential link to neurodegenerative disease (ND). This review will summarize the current epidemiological findings, the pathological similarities, and new neuroimaging techniques that may help delineate the relationship between TBI and ND. Lastly, this review will discuss future directions and propose new methods to overcome the limitations that are currently impeding research progress. It is imperative that improved techniques are developed to adequately and retrospectively assess TBI history in patients that may have been previously undiagnosed in order to increase the validity and reliability across future epidemiological studies. The authors introduce a new surveillance tool (Retrospective Screening of Traumatic Brain Injury Questionnaire, RESTBI) to address this concern.
    Journal of Alzheimer's disease & Parkinsonism. 01/2014; 4.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Voxel-based morphometry (VBM) has demonstrated structural brain changes between patients with Major Depressive Disorder (MDD) and healthy individuals. The initial response to antidepressants is crucial to predict prognosis in the treatment of MDD. The aim of the present study was to investigate gray matter abnormalities predicting antidepressant responsiveness and the relationships between volumetric differences and clinical/cognitive traits in MDD patients. Methods Fifty MDD patients who received 8 week period antidepressant treatment and 29 healthy controls participated in this study. VBM was applied to assess structural changes between MDD groups and control group. Neuropsychological tests were conducted on all participants. Results Both treatment responsive and non-responsive patients showed a significant volume reduction of the left insular, but only non-responsive patients had decreased volume in the right superior frontal gyrus compared to healthy controls. The comparison between treatment responsive and non-responsive patient groups demonstrated a significant difference in gray matter volume in the lingual gyrus. The larger volume of lingual gryus predicted early antidepressant response, which was attributable to better performance in neuropsychological tests. Limitation This study included a small sample size and the patients received various antidepressants and benzodiazepines. Conclusion Our findings suggest that the patients who responded poorly to antidepressants were morphologically and cognitively impaired, whereas the treatment responsive patients showed less structural changes and relatively preserved cognitive functions. The lingual gyrus may be a possible candidate region to predict antidepressant responsiveness and maintained cognition in MDD.
    Journal of Affective Disorders 12/2014; 169:179–187. · 3.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Due to a lack of evidence, there is no consistent age of onset to define early onset (EO) versus later onset (LO) major depressive disorder (MDD). Fractional anisotropy (FA), derived from diffusion tensor imaging (DTI), has been widely used to study neuropsychiatric disorders by providing information about the brain circuitry, abnormalities of which might facilitate the delineation of EO versus LO MDD.
    PLoS ONE 11/2014; 9(11):e112307. · 3.53 Impact Factor