Cerebral volume measurements and subcortical white matter lesions and short-term treatment response in late life depression

Utrecht University, Utrecht, Utrecht, Netherlands
International Journal of Geriatric Psychiatry (Impact Factor: 2.87). 05/2007; 22(5):468-74. DOI: 10.1002/gps.1790
Source: PubMed


Late life depression is associated with volumetric reductions of gray matter and increased prevalence of subcortical white matter lesions. Previous studies have shown a poorer treatment outcome in those with more severe structural brain abnormalities. In this study, quantitative and semi-quantitative magnetic resonance imaging (MRI) measures were studied in relation to response to a 12-week controlled antidepressant monotherapy trial.
MRI (1.5 T) brain scans of 42 elderly inpatients with major depression, of which 23 were non-responder to a controlled 12-week antidepressant monotherapy trial, were acquired. In addition, clinical outcome was assessed after a one year period. Measures were volumes of global cerebral and subcortical structures.
After controlling for confounding, no differences were found between non-responders and responders after 12 weeks and after one year in volumes of cerebral gray and white matter, orbitofrontal cortex, hippocampus and white matter lesions.
Structural brain measures associated with late life depression may not be related to short-term treatment response.

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Available from: Rob Kok, Oct 08, 2015
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    • "Indeed, a major limitation of the studies presented here is the low sample size, with most studies below 50 subjects and only one over 100 [62] [131]. Moreover, it is impossible to draw conclusions on the effect of single specific compounds because many studies include multiple antidepressants [49] [67] [68] [84] [119] [132] [133] [147] and very few studies focused on the effect of " non SSRIs " antidepressants [138] [148] [149]. Although these designs are closer to real world interventions which apply multiple drugs [150] they limit the possibility to investigate the contribute of different compounds to the brain altered circuits, in order to plan more effective and targeted interventions. "
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    ABSTRACT: Depressive disorder is a very frequent and heterogeneous syndrome. Structural imaging techniques offer a useful tool in the comprehension of neurobiological alterations that concern depressive disorder. Altered brain structures in depressive disorder have been particularly located in the prefrontal cortex (medial prefrontal cortex and orbitofrontal cortex, OFC) and medial temporal cortex areas (hippocampus). These brain areas belong to a structural and functional network related to cognitive and emotional processes putatively implicated in depressive symptoms. These volumetric alterations may also represent biological predictors of response to pharmacological treatment. In this context, major findings of magnetic resonance (MR) imaging, in relation to treatment response in depressive disorder, will here be presented and discussed.
    Current Neuropharmacology 07/2015; 13(4). DOI:10.2174/1570159X1304150831121909 · 3.05 Impact Factor
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    • "As the neurobiological hypothesis that antidepressants may take its effects through enhancing neuroplasticity and neurogenesis in specific brain regions [44], [45] especially frontal cortex [46], we speculate that medication-induced changes are likely to be observed in structure as in function, which may be detected after short time treatment in MDD. However, the confound findings such as Vythilingam et al reported no significant differences in hippocampal volume after 7±3 months antidepressant treatment [29] in MDD as well as Janssen et al reported no cerebral volume differences after 12 weeks treatment with venlafaxine or nortriptyline in late life depression [47] suggest that medication-induced changes in MDD should be investigated with long time longitudinal imaging studies in future. "
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    ABSTRACT: Convergent studies suggest that morphological abnormalities of frontal-subcortical circuits which involved with emotional and cognitive processing may contribute to the pathophysiology of major depressive disorder (MDD). Antidepressant treatment which has been reported to reverse the functional abnormalities of frontal-subcortical circuits in MDD may have treating effects to related brain morphological abnormalities. In this study, we used voxel-based morphometry method to investigate whole brain structural abnormalities in single episode, medication-naïve MDD patients. Furthermore, we investigated the effects of an 8 weeks pharmacotherapy with fluoxetine. 28 single episode, medication-naïve MDD participants and 28 healthy controls (HC) acquired the baseline high-resolution structural magnetic resonance imaging (sMRI) scan. 24 MDD participants acquired a follow-up sMRI scan after 8 weeks antidepressant treatment. Gray matter volumetric (GMV) difference between groups was examined. Medication-naïve MDD had significantly decreased GMV in the right dorsolateral prefrontal cortex and left middle frontal gyrus as well as increased GMV in the left thalamus and right insula compared to HC (P<0.05, corrected). Moreover, treated MDD had significantly increased GMV in the left middle frontal gyrus and right orbitofrontal cortex compared to HC (P<0.05, corrected). No difference on GMV was detected between medication-naïve MDD group and treated MDD group. This study of single episode, medication-naïve MDD subjects demonstrated structural abnormalities of frontal-subcortical circuitsin the early stage of MDD and the effects of 8 weeks successful antidepressant treatment, suggesting these abnormalities may play an important role in the neuropathophysiology of MDD at its onset.
    PLoS ONE 01/2014; 9(1):e79055. DOI:10.1371/journal.pone.0079055 · 3.23 Impact Factor
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    • "Moreover, a positive correlation exists between the structural brain abnormalities in patients with LLD and their treatment responses, especially in the volumes of the hippocampus [17] and anterior cingulate cortex [18,19]. However, this issue remains controversial as another study [20] did not find any correlation. A recent review of the biological basis of LLD [21] indicated that only a few studies to date have examined how the structural changes observed in patients with LLD influence clinical outcomes [22], and the results are not conclusive. "
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    ABSTRACT: The relationship between structural changes in grey matter and treatment response in patients with late-life depression remains an intriguing area of research. This magnetic resonance imaging (MRI) study compares the baseline grey matter volume of elderly people with and without major depression (according to the DSM-IV-TR criteria) and assesses its association with antidepressant treatment response. Brain MRI scans were processed using statistical parametric mapping and voxel-based morphometry. The sample consisted of 30 patients with depression and 22 healthy controls. We found a significant volumetric reduction in the orbitofrontal cortex bilaterally in patients in comparison with controls. According to their remission status after antidepressant treatment, patients were classified as remitted or not remitted. Compared with controls, remitted patients showed a volumetric reduction in the orbitofrontal cortex bilaterally and in another cluster in the right middle temporal pole. Non-remitted patients showed an even greater volumetric reduction in the orbitofrontal cortex bilaterally compared with controls. To investigate predictive factors of remission after antidepressant treatment, we used a logistic regression. Both baseline Mini Mental State Examination score and baseline left superior lateral orbitofrontal cortex volume (standardized to the total grey matter volume) were associated with remission status. Our findings support the use of regional brain atrophy as a potential biomarker for depression. In addition, baseline cognitive impairment and regional grey matter abnormalities predict antidepressant response in patients with late-life depression.
    PLoS ONE 11/2013; 8(11):e80049. DOI:10.1371/journal.pone.0080049 · 3.23 Impact Factor
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