Tham MW, Woon PS, Sum MY, Lee TS, Sim K. White matter abnormalities in major depression: evidence from post-mortem, neuroimaging and genetic studies. J Affect Disord 132: 26-36

Institute of Mental Health/Woodbridge Hospital, 10, Buangkok View, Singapore 539747, Singapore.
Journal of Affective Disorders (Impact Factor: 3.38). 10/2010; 132(1-2):26-36. DOI: 10.1016/j.jad.2010.09.013
Source: PubMed

ABSTRACT Until more recently, most studies have examined the changes in brain gray matter in major depressive disorder (MDD) with less studies focusing on understanding white matter pathology in MDD. Studies of brain white matter volume changes, connectivity disruptions, as well as genetic factors affecting myelination can throw light on the nature of white matter abnormalities underpinning MDD.
We review the state of the art understanding of white matter changes in MDD from the extant neuropathology, neuroimaging and neurogenetic studies.
Overall, data are sparse and mostly conducted in older patients with MDD. Post-mortem studies have highlighted pathology of white matter in prefrontal brain region in terms of decreased oligodendrocyte density, reductions in the expression of genes related to oligodendrocyte function, molecular changes in intercellular cell adhesion molecule (ICAM) expression levels and suggestion of possible mechanism of ischemia. Structural magnetic resonance imaging studies have revealed deep white matter hyperintensities which are associated with clinical severity, and treatment responsiveness.
There is a particular dearth of genetic studies related to white matter pathology, studies of younger depressed subjects and specifically probing cortical and subcortical white matter pathology together in MDD.
Future investigations would want to study white matter changes in different cerebral regions and incorporate multimodal and longitudinal levels of examination in order to better grasp the neural basis of this condition.

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    • "Volumetric reductions in several cortical regions, for example, cingulum, prefrontal, and temporal, has also been demonstrated in LLD (Mackin et al., 2013; Ribeiz et al., 2013). Numerous studies have also shown associations between LLD and white-matter lesions (Tham et al., 2011). A recent review study found that white-matter lesions are, indeed, one of the main imaging markers of vascular brain pathology (Kooistra et al., 2014). "
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    ABSTRACT: We compared cortical thickness between patients with late-life depression (LLD) and healthy controls and between patients with early-onset (EOD) and late-onset (LOD) depression. We also tested age effects on cortical thickness in LLD and controls and if cortical thickness and hippocampal volumes were associated with cognitive performance in LLD. Three-dimensional T1-weighted magnetic resonance images were obtained in 49 LLD and 49 matched hospital controls and processed using FreeSurfer. General linear model analysis was used as a statistical approach. LLD group had thinning in the left parahippocampal, fusiform, and inferior-parietal cortex compared with controls. Age correlated with cortical thinning in controls but not in LLD. Women in the LOD groups had extensive cortical thinning in the lateral prefrontal cortex bilaterally compared with EOD women. Absence of statistically significant changes observed in men should however be treated with caution because of the low number of men in the study. Mini-Mental Status Examination score correlated with lateral prefrontal cortical thickness bilaterally and hippocampal volume in the total group of LLD and in LOD but not EOD. LLD is associated with cortical thinning, which is associated with age at depression onset, gender, and level of cognitive functioning. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 08/2015; DOI:10.1016/j.neurobiolaging.2015.04.020 · 5.01 Impact Factor
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    • "10.1016/j.pharmthera.2014.11.009 Hulvershorn et al., 2011; Tham et al., 2011), and there is evidence that heavy cannabis use may speed up or worsen these changes amongst affected individuals (Medina et al., 2007b; Solowij et al., 2011b). However to date, there have been few studies that have prospectively examined associations between adolescent cannabis exposure, altered trajectories of brain development, and psychiatric or cognitive impairment in adulthood . "
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    ABSTRACT: Heavy cannabis use has been frequently associated with increased rates of mental illness and cognitive impairment, particularly amongst adolescent users. However, the neurobiological processes that underlie these associations are still not well understood. In this review, we discuss the findings of studies examining the acute and chronic effects of cannabis use on the brain, with a particular focus on the impact of commencing use during adolescence. Accumulating evidence from both animal and human studies suggests that regular heavy use during this period is associated with more severe and persistent negative outcomes than use during adulthood, suggesting that the adolescent brain may be particularly vulnerable to the effects of cannabis exposure. As the endocannabinoid system plays an important role in brain development, it is plausible that prolonged use during adolescence results in a disruption in the normative neuromaturational processes that occur during this period. We identify synaptic pruning and white matter development as two processes that may be adversely impacted by cannabis exposure during adolescence. Potentially, alterations in these processes may underlie the cognitive and emotional deficits that have been associated with regular use commencing during adolescence.
    Pharmacology [?] Therapeutics 11/2014; 148. DOI:10.1016/j.pharmthera.2014.11.009 · 9.72 Impact Factor
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    • "The importance of genes involved in growth factor pathways is in accordance with other findings cited above (Mehta et al., 2010; Schmidt et al., 2011; Hepgul et al., 2013; Lopresti et al., 2014). Abnormal myelin formation and dysfunctions have also been revealed in mood disorders (Tkachev et al., 2003; Tham et al., 2011; Edgar and Sibille, 2012). However, the present findings do not prove that the genes and their products included in the Fig. 2. Comparison of individual BioM-10 scores before and after cognitive-behavioral therapy. "
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    ABSTRACT: Background Results from convergent genomics indicated new peripheral biomarkers for mood states. We sought to investigate the clinical utility of the BioM-10 Mood Panel, a peripheral biomarker set of low vs. high mood states, in the diagnosis of major depressive episode and to monitor the effectiveness of cognitive-behavioral therapy (CBT). Method 44 patients with a first episode of major depression and 30 healthy control subjects participated in the study. The BioM-10 panel׳s gene expression profile was measured from whole peripheral blood with the Affymetrix Human Genome U133 Plus 2.0 Gene Chips, focusing on 10 top genes related to high mood states (MBP, EDG2, FZD3, ATXN1, and EDNRB) and low mood states (FGFR1, MAG, PMP22, UGT8, and ERBB3). We studied gene expression before and after CBT. Results The BioM-10 prediction score discriminated patients and controls with high sensitivity (84%) and specificity (90%). There was an increase in the BioM-10 prediction score after CBT relative to the pretreatment value. Clinical improvement was associated with higher prediction scores reflecting a greater ratio of high mood markers relative to low mood markers. Limitations Sample size was small for a genome-wide microarray study. Convergent genomic studies have not been conducted in major depressive disorder. More evidence is needed from patients with severe, recurrent, and chronic forms of depression. Conclusions The BioM-10 panel is a promising tool as a biomarker setup for the evaluation of low and high mood states across diagnostic categories. The panel includes genes related to growth factor pathways and myelination, which may provide new insights into the pathophysiology of mood dysregulation.
    Journal of Affective Disorders 08/2014; 164:118–122. DOI:10.1016/j.jad.2014.04.030 · 3.38 Impact Factor
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