White Matter Injury, Neural Connectivity and the Pathophysiology of Psychiatric Disorders

ArticleinDevelopmental Neuroscience 24(4):255-61 · February 2002with3 Reads
DOI: 10.1159/000066746 · Source: PubMed
  • University of Illinois at Chicago
  • 41.64 · University of California, Los Angeles
Psychiatric disorders are characterized by diverse clinical manifestations that include deficits in cognition, perception, mood and arousal. These complex processes are not mediated by any specific brain region but require the coordinated activity of several areas that are anatomically connected. Impairments in these neural circuits may therefore be expected to result in an attenuation of the functions regulated by them. The white matter provides the structural and physiological substrate of neural circuits in the central nervous system. We propose that injury to the white matter, from diverse biological sources, may compromise neural connectivity by associated axonal injury or impaired conductivity. Either mechanism could result in clusters of signs and symptoms that are currently recognized as psychiatric disorders. The role of white matter impairment in the pathophysiology of psychiatric illness is under-appreciated in the neurosciences. Focused translational research aimed at identifying the links between white matter compromise and specific behaviors are necessary for a more thorough understanding of the etiology of mental illness to emerge.
    • "The current study investigated the relationship between biological measures of stress and brain structure in first episode patients in comparison to matched healthy controls. Despite indications that complex brain processes depend on networks including white matter interconnections (Kumar and Cook, 2002), and suggestions that changes in both grey and white matter volume are associated with increased levels of perceived stress (Li et al., 2014), existing research has focussed on grey matter structure. Given that the first episode of psychosis is associated with progressive brain changes in frontal, temporal as well as parietal areas, the relationship between biological measures of stress and whole brain measures of cortical thickness and white matter volume was examined. "
    [Show abstract] [Hide abstract] ABSTRACT: Stress and abnormal hypothalamic-pituitary-adrenal axis functioning have been implicated in the early phase of psychosis and may partly explain reported changes in brain structure. This study used magnetic resonance imaging to investigate whether biological measures of stress were related to brain structure at baseline and to structural changes over the first 12 weeks of treatment in first episode patients (n=22) compared with matched healthy controls (n=22). At baseline, no significant group differences in biological measures of stress, cortical thickness or hippocampal volume were observed, but a significantly stronger relationship between baseline levels of cortisol and smaller white matter volumes of the cuneus and anterior cingulate was found in patients compared with controls. Over the first 12 weeks of treatment, patients showed a significant reduction in thickness of the posterior cingulate compared with controls. Patients also showed a significant positive relationship between baseline cortisol and increases in hippocampal volume over time, suggestive of brain swelling in association with psychotic exacerbation, while no such relationship was observed in controls. The current findings provide some support for the involvement of stress mechanisms in the pathophysiology of early psychosis, but the changes are subtle and warrant further investigation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Nov 2014
    • "In the context of TBI, there are a variety of neuroanatomical changes that may provide a biological basis for the development of depression. For example, the shear, tensile and compressive strains experienced during a TBI can lead to diffuse axonal injury in the frontal and temporal lobes, disrupting the neural circuitry between the prefrontal cortex, amygdala, hippocampus, basal ganglia and thalamus (Jorge and Robinson, 2002; Kumar and Cook, 2002; Morris, 2010; Silver et al., 2009). This neuronal damage and cell loss can occur for weeks to months after an injury, and may provide the neurological substrate for many of the cognitive and psychological changes that occur after a TBI (Jorge and Starkstein, 2005; Sherin and Nemeroff, 2011). "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Depression is one of the most frequently reported psychological problems following TBI, however prevalence estimates vary widely. Methodological and sampling differences may explain some of this variability, but it is not known to what extent. Methods: Data from 99 studies examining the prevalence of clinically diagnosed depression (MDD/dysthymia) and self-reports of depression (clinically significant cases or depression scale scores) following adult, non-penetrating TBI were analysed, taking into consideration diagnostic criteria, measure, post-injury interval, and injury severity. Results: Overall, 27% of people were diagnosed with MDD/dysthymia following TBI and 38% reported clinically significant levels of depression when assessed with self-report scales. Estimates of MDD/dysthymia varied according to diagnostic criteria (ICD-10: 14%; DSM-IV: 25%; DSM-III: 47%) and injury severity (mild: 16%; severe: 30%). When self-report measures were used, the prevalence of clinically significant cases of depression differed between scales (HADS: 32%; CES-D: 48%) method of administration (phone: 26%; mail 46%), post-injury interval (range: 33-42%), and injury severity (mild: 64%; severe: 39%). Conclusion: Depression is very common after TBI and has the potential to impact on recovery and quality of life. However, the diagnostic criteria, measure, time post-injury and injury severity, all impact on prevalence rates and must therefore be considered for benchmarking purposes.
    Full-text · Article · Jul 2014
    • "The white matter (WM) abnormalities constitute one element of the pathogenesis of MDD.15–17 Various fiber tract alterations have been seen in MDD patients.18–22 Magnetic resonance imaging (MRI) is a noninvasive method used to examine WM abnormalities. "
    [Show abstract] [Hide abstract] ABSTRACT: We investigated the association between the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene, and white matter changes in patients with major depressive disorder (MDD) and healthy subjects using diffusion tensor imaging (DTI). We studied 30 patients with MDD (17 males and 13 females, with mean age ± standard deviation [SD] =44±12 years) and 30 sex- and age-matched healthy controls (17 males and 13 females, aged 44±13 years). Using DTI analysis with a tract-based spatial statistics (TBSS) approach, we investigated the differences in fractional anisotropy, radial diffusivity, and axial diffusivity distribution among the three groups (patients with the COMT gene Val158Met, those with the BDNF gene Val66Met, and the healthy subjects). In a voxel-wise-based group comparison, we found significant decreases in fractional anisotropy and axial diffusivity within the temporal lobe white matter in the Met-carriers with MDD compared with the controls (P<0.05). No correlations in fractional anisotropy, axial diffusivity, or radial diffusivity were observed between the MDD patients and the controls, either among those with the BDNF Val/Val genotype or among the BDNF Met-carriers. These results suggest an association between the COMT gene Val158Met and the white matter abnormalities found in the temporal lobe of patients with MDD.
    Full-text · Article · Jun 2014
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