One-Year Change in Anterior Cingulate Cortex White Matter Microstructure: Relationship With Late-Life Depression Outcomes

Departments of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry (Impact Factor: 4.24). 01/2011; 19(1):43-52. DOI: 10.1097/JGP.0b013e3181e70cec
Source: PubMed

ABSTRACT differences in white matter structure measured with diffusion tensor imaging (DTI) are associated with late-life depression, but results examining how these differences relate to antidepressant remission are mixed. To better describe these relationships, the authors examined how 1-year change in DTI measures are related to 1-year course of depression.
one-year cross-sectional follow-up to a 12-week clinical trial of sertraline.
outpatients at an academic medical center.
twenty-nine depressed and 20 never-depressed elderly subjects. Over the 1-year period, 16 depressed subjects achieved and maintained remission, whereas 13 did not.
one-year change in fractional anisotropy (FA) and diffusivity in frontal white matter, as measured by DTI.
contrary to our hypotheses, depressed subjects who did not remit over the study interval exhibited significantly less change in anterior cingulate cortex (ACC) white matter FA than did never-depressed or depressed-remitted subjects. There were no group differences in other frontal or central white matter regions. Moreover, there was a significant positive relationship between change in Montgomery-Asberg Depression Rating Scale (MADRS) and change in ACC FA, wherein greater interval decline in FA was associated with greater interval decline in MADRS.
older depressed individuals who remit exhibit white matter changes comparable with what is observed in never-depressed individuals, whereas nonremitters exhibit significantly less change in ACC FA. Such a finding may be related to either antidepressant effects on brain structure or the effects of chronic stress on brain structure. Further work is needed to better understand this relationship.

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Available from: Warren Taylor, Sep 25, 2015
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    • " inversely correlated with FA ( Versace et al . , 2008 ) . In depressed elderly patients , tricyclic or selective serotonergic antide - pressants increased WM hyperintensities ( Steffens et al . , 2008 ) , and a one - year treatment with sertraline caused a significant decrease of FA which was proportional to the reduction of depression severity ( Taylor et al . , 2011 ) . Antipsychotics reduce the number of glial cells in monkeys , although oligodendrocytes are only marginally affected ( Konopaske et al . , 2008 ) . A study in 13 drug - naı¨ve patients with OCD showed that a three - months treatment with citalopram significantly decreased OCD symptomatology , and also reduced FA in the posterior thal"
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    ABSTRACT: Diffusion tensor imaging (DTI) allows the study of white matter (WM) structure. Literature suggests that WM structure could be altered in obsessive-compulsive disorder (OCD) proportional to the severity of the disease. Heterogeneity of brain imaging methods, of the studied samples, and of drug treatments make localization, nature, and severity of the WM abnormalities unclear. We applied Tract-Based Spatial Statistics (TBSS) of DTI measures to compare fractional anisotropy (FA), mean, axial, and radial diffusivity of the WM skeleton in a group of 40 consecutively admitted inpatients affected by severe OCD (18 drug-naive, and 22 with an ongoing drug treatment) and 41 unrelated healthy volunteers from the general population. Data were analyzed accounting for the effects of multiple comparisons, and of age, sex, and education as nuisance covariates. Compared to controls, OCD patients showed a widespread reduction of FA with a concurrent increase of mean and radial diffusivity. In no brain areas patients had higher FA or lower diffusivity values than controls. These differences were observed in drug-treated patients compared to drug-naive patients and healthy controls, which in turn did not differ among themselves in any DTI measure. Reduced FA with increased mean and radial diffusivity suggests significant changes in myelination of WM tracts, without axonal loss. Drug treatments could modify the structure of cell membranes and myelin sheaths by influencing cellular lipogenesis, cholesterol homeostasis, autophagy, oligodendrocyte differentiation and remyelination. Changes of DTI measures in drug-treated OCD patients could reflect pathophysiological underpinnings of OCD, or a yet unexplored part of the mechanism of action of drugs.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 09/2012; 23(7). DOI:10.1016/j.euroneuro.2012.07.002 · 4.37 Impact Factor
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    • "Some studies in late life depression consistently reported reduced FA values in prefrontal brain regions [Bae et al., 2006; Nobuhara et al., 2006b; Li et al., 2007; Murphy et al., 2007; Yang et al., 2007; Shimony et al., 2009]. Reduced FA in the cingulate cortex has been also detected [Murphy et al., 2007; Cullen et al., 2010; Taylor et al., 2010]. In addition, Yang et al. [2007] and Murphy et al. [2007] reported a reduction in FA values in the parahippocampal gyrus. "
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    ABSTRACT: Experimental studies support a neurotrophic hypothesis of major depressive disorder (MDD). The aim of this study was to determine the effect of Val66Met brain-derived neurotrophic factor (BDNF) polymorphism on the white matter fiber tracts connecting hippocampus and amygdala with the prefrontal lobe in a sample of patients with MDD and healthy controls. Thirty-seven patients with MDD and 42 healthy volunteers were recruited. Diffusion tensor imaging (DTI) data with 61 diffusion directions were obtained with MRI 3 Tesla scanner. Deterministic tractography was applied with ExploreDTI and Val66Met BDNF SNP (rs6265) was genotyped. Fiber tracts connecting the hippocampus and amygdala with the prefrontal lobe, namely uncinate fasciculus (UF), fornix, and cingulum were analyzed. A significant interaction was found in the UF between BDNF alleles and diagnosis. Patients carrying the BDNF met-allele had smaller fractional anisotropy (FA) in the UF compared to those patients homozygous for val-allele and compared to healthy subjects carrying the met-allele. A significant three-way interaction was detected between region of the cingulum (dorsal, rostral, and parahippocampal regions), brain hemisphere and BDNF genotype. Larger FA was detectable in the left rostral cingulum for met-allele carriers when compared to val/val alelle carriers. We provide evidence for the importance of the neurotrophic involvement in limbic and prefrontal connections. The met-allele of the BDNF polymorphism seems to render subjects more vulnerable for dysfunctions associated with the UF, a tract known to be related to negative emotional-cognitive processing bias, declarative memory problems, and autonoetic self awareness.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 07/2012; 159B(5):537-48. DOI:10.1002/ajmg.b.32060 · 3.42 Impact Factor
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    • "Of these, 82 studies had to be excluded on the basis of being literature reviews (n = 8), using tractography (n = 7) or ROI analysis (n = 6), studying depression in relation to TBI (n = 5), ELS (n = 3) or in association with other diseases (n = 25), assessing functional or structural response to treatment (n = 7), using uncorrected results (n = 1) or no controls (n = 5), not being available in English (n = 1), being conducted in remitted or nondepressed patients (n = 5), being conducted in animals (n = 2) or not being relevant for other reasons (n = 7). Contact with three researchers was made to receive additional required information, but one of the studies was later excluded from our meta-analysis as it used ROI analytical techniques [23]. "
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    ABSTRACT: Fractional anisotropy anomalies occurring in the white matter tracts in the brains of depressed patients may reflect microstructural changes underlying the pathophysiology of this disorder. We conducted a meta-analysis of fractional anisotropy abnormalities occurring in major depressive disorder using voxel-based diffusion tensor imaging studies. Using the Embase, PubMed and Google Scholar databases, 89 relevant data sets were identified, of which 7 (including 188 patients with major depressive disorder and 221 healthy controls) met our inclusion criteria. Authors were contacted to retrieve any additional data required. Coordinates were extracted from clusters of significant white matter fractional anisotropy differences between patients and controls. Relevant demographic, clinical and methodological variables were extracted from each study or obtained directly from authors. The meta-analysis was carried out using Signed Differential Mapping. Patients with depression showed decreased white matter fractional anisotropy values in the superior longitudinal fasciculus and increased fractional anisotropy values in the fronto-occipital fasciculus compared to controls. Using quartile and jackknife sensitivity analysis, we found that reduced fractional anisotropy in the left superior longitudinal fasciculus was very stable, with increases in the right fronto-occipital fasciculus driven by just one study. In conclusion, our meta-analysis revealed a significant reduction in fractional anisotropy values in the left superior longitudinal fasciculus, which may ultimately play an important role in the pathology of depression.
    Biology of Mood and Anxiety Disorders 09/2011; 1(1):3. DOI:10.1186/2045-5380-1-3
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