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: 3.09). 05/2007; 22(5):468-74. DOI: 10.1002/gps.1790
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Rob Kok, Aug 28, 2015
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "A number of studies indicated that white matter hyperintensity (WMH) burden and subcortical gray matter hyperintensities were associated with response to both ECT (Hickie et al., 1995; Steffens et al., 2002) and antidepressant pharmacotherapy (Hickie et al., 1995; Patankar et al., 2007; Simpson et al., 1998). However, some disagreement exists (Janssen et al., 2007). In particular, the failure to detect a relationship between SH severity and antidepressant treatment response in two controlled monotherapy antidepressant trials casts doubt on the existence of a relationship (Salloway et al., 2002; Sneed et al., 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: White matter abnormalities may interfere with limbic-cortical balance and contribute to chronic depressive syndromes in the elderly. This study sought to clarify the relationship of SH to treatment response. We hypothesized that patients who failed to remit during a 12-week controlled treatment trial of escitalopram would exhibit greater SH burden than patients who remitted. The participants were 42 non-demented individuals with non-psychotic major depression and 25 elderly comparison subjects. After a 2-week single blind placebo period, subjects who still had a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for 2 consecutive weeks. FLAIR sequences were acquired on a 1.5 T scanner and total SH were quantified using a semi-automated thresholding method. The patient sample consisted of 22 depressed patients who achieved remission during the study and 20 depressed patients who remained symptomatic. ANCOVA, with age and gender as covariates, revealed that depressed subjects had greater total SH burden relative to non-depressed controls. Furthermore, patients who failed to remit following escitalopram treatment had significantly greater SH burden than both patients who remitted and elderly comparison subjects, whereas SH burden did not differ between depressed patients who remitted and elderly comparison subjects. Patients were treated with a fixed dose of antidepressants and the index of SH is an overall measure that does not permit examination of the relationship of regional SH to treatment remission. SH may contribute to a "disconnection state" both conferring vulnerability to and perpetuating late-life depression.
    Journal of Affective Disorders 05/2010; 126(3):395-401. DOI:10.1016/j.jad.2010.04.004 · 3.71 Impact Factor
Show more