A prospective study of depression and immune dysregulation in multiple sclerosis
ABSTRACT This study examined psychologic distress and immune function in patients with chronic-progressive multiple sclerosis participating in a placebo-control trial of cyclosporine. Immune measures included percentages and absolute numbers of CD2+, CD4+, CD8+, Leu-11-b+, HLA-DR (IA+), and transferrin-receptor-positive cells, which were evaluated by immunofluorescence using monoclonal antibodies. Distress was measured with self-report scales. The Expanded Disability Status Scale assessed neurologic disability. Subjects were followed up for 2 years, and their high-depressed and low-depressed times were compared. Times of greater depression were associated with lower CD8+ cell numbers and CD8+%, and a higher CD4/CD8 ratio. CD4+ cell numbers and percent were also higher when subjects were depressed, but only in the placebo group. There were no differences in Expanded Disability Status Scale when subjects were more depressed. Evaluation of a single subject revealed that Ia+ and transferrin-receptor-positive lymphocytes increased 3 months before distress increased. It was concluded that distress is associated with immune dysregulation in multiple sclerosis, although the mechanisms of this association have yet to be delineated.
- SourceAvailable from: David C. Mohr
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- "Depression may also exact a greater toll on the health of people with MS. Depression may affect MS indirectly by decreasing adherence to MS disease modifying medications (Mohr et al., 1997) and more directly by aggravating MS-related immune dysregulation (Foley et al., 1992; Mohr, Goodkin, Islar, Hauser, & Genain, 2001). "
ABSTRACT: Anxiety is highly comorbid with depression, but little is known about the impact of anxiety disorders on the effectiveness of empirically supported psychotherapies for depression. We examined such outcomes for people with Multiple Sclerosis (MS) and depression, with versus without comorbid anxiety disorders. Participants with MS (N = 102) received 16 weeks of telephone-administered psychotherapy for depression and were followed for one year post-treatment. Participants with comorbid anxiety disorders improved to a similar degree during treatment as those without anxiety disorders. Outcomes during follow-up were mixed, and thus we divided the anxiety diagnoses into distress and fear disorders. The distress disorder (GAD) was associated with elevated anxiety symptoms during and after treatment. In contrast, fear disorders (i.e., panic disorder, agoraphobia, social phobia, specific phobia) were linked to depression, specifically during follow-up, across 3 different measures. People with GAD receiving treatment for depression may benefit from additional services targeting anxiety more specifically, while those with comorbid fear disorders may benefit from services targeting maintenance of gains after treatment.Rehabilitation Psychology 08/2010; 55(3):255-62. DOI:10.1037/a0020492 · 1.91 Impact Factor
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- "A study that compared psychotherapy with placebo found lower levels of depression but no reduction in anxiety scores in the group that received psychotherapy . Other studies have compared cognitivebehavioral therapy with psychotherapy , and have reported lower depression levels with cognitive-behavioral therapy versus placebo , without significant differences between groups. "
ABSTRACT: To evaluate the efficacy of a computer-based intensive training program of attention, information processing and executive functions in patients with clinically-stable relapsing-remitting (RR) multiple sclerosis (MS) and low levels of disability. DESIGN, PATIENTS AND INTERVENTIONS: A total of 150 patients with RR MS and an Expanded Disability Status Scale (EDSS) score of < or =4 were examined. Information processing, working memory and attention were assessed by the Paced Auditory Serial Addition Test (PASAT) and executive functions by the Wisconsin Card Sorting Test (WCST). Twenty patients who scored below certain cut-off measures in both tests were included in this double-blind controlled study. Patients were casually assigned to a study group (SG) or a control group (CG) and underwent neuropsychological evaluation at baseline and after 3 months. Patients in the SG received intensive computer-assisted cognitive rehabilitation of attention, information processing and executive functions for 3 months; the CG did not receive any rehabilitation. Ambulatory patients were sent by the MS referral center. Improvement in neuropsychological test and scale scores. After rehabilitation, only the SG significantly improved in tests of attention, information processing and executive functions (PASAT 3'' p=0.023, PASAT 2'' p=0.004, WCSTte p=0.037), as well as in depression scores (MADRS p=0.01). Neuropsychological improvement was unrelated to depression improvement in regression analysis. Intensive neuropsychological rehabilitation of attention, information processing and executive functions is effective in patients with RR MS and low levels of disability, and also leads to improvement in depression.Journal of the neurological sciences 10/2009; 288(1-2):101-5. DOI:10.1016/j.jns.2009.09.024 · 2.26 Impact Factor
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- "Inflammation, demyelination, axonal dysfunction and grey matter (GM) damage are all highly associated with the clinical manifestations of multiple sclerosis, including affective disorders (Foley et al., 1992; Bakshi et al., 2000; Mohr et al., 2001; Feinstein, 2007). Hence, identifying brain markers of emotional dysfunctions in multiple sclerosis represents a fundamental step for increasing our knowledge about the disease's mechanisms and for improving treatments that specifically target these symptoms. "
ABSTRACT: Affective disorders are frequent and disabling conditions in multiple sclerosis; however, the underlying neurobiological mechanisms are still poorly understood and investigated. Previous structural imaging studies have suggested that damage of frontal and temporal cortices plays an important role in the genesis of emotional disorders in multiple sclerosis, although psychosocial factors have been also implicated. However, this initial research may not have fully characterized the brain's functional dynamics of emotional processes in multiple sclerosis. Functional magnetic resonance imaging (fMRI) appears, therefore, to be a sensible tool to explore neurobiological mechanisms of emotions in multiple sclerosis since it also allows investigation of the functional connectivity or 'communication' between critical regions in affective behaviour [e.g. the prefrontal cortex (PFC) and amygdala]. In the present study, functional imaging was used to investigate the neural substrate of processing emotions in 12 multiple sclerosis patients relative to 12 healthy subjects matched for age and educational level. Only relapsing-remitting multiple sclerosis patients, who were cognitively unimpaired and who did not assume disease-modifying therapies, were included, given the potential confounding effect of these variables in the genesis of emotional symptoms. Brain responses were recorded in all participants while they executed an active task that consisted of processing emotional relative to neutral stimuli. Structural measures (i.e. total lesion load, grey matter, white matter and total brain volume) were also recorded to control for any effect of these variables. Despite similar performances during the task, and no differences in structural measures, multiple sclerosis patients displayed significantly greater responses within the ventrolateral PFC [t's > 5, P's < 0.02, Family Wise Error (FWE), small volume correction (svc)], compared to controls. Multiple sclerosis patients also showed a lack of functional connectivity between two prefrontal areas and the amygdala, a subcortical region critically involved in the generation of negative feelings (t's > 4, P's < 0.05, FWE, svc). It is likely that pathological changes related to the disease are reflected in an abnormal 'communication' between key emotional regions and that adaptive processes take place and become evident as enhanced responses of task-specific areas (i.e. the ventrolateral PFC). Local reorganizations in the brain can be viewed as compensatory mechanisms aimed to limit the clinical expression of emotional symptoms in multiple sclerosis. Overall our findings offer new insights into the neurobiological mechanisms of emotions in multiple sclerosis and provide evidence that they resemble those described for some psychiatric disorders.Brain 05/2009; 132(Pt 12):3380-91. DOI:10.1093/brain/awp095 · 10.23 Impact Factor