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Heterogeneous depression trajectories in multiple sclerosis patients.

ABSTRACT: Trajectories of depression over time may be heterogeneous in Multiple Sclerosis (MS) patients. Describing these trajectories will help clinicians understand better the progression of depression in MS patients to aid in patient care decisions.Latent class growth analysis (LCGA) was applied to 3507 MS patients using an electronic health records (EHR) data base to identify subgroups of MS patients based on self-reported depression screening (PHQ-9). Latent trajectory classes were used for group comparisons based on baseline clinical characteristics.Three subgroups were found characterized by high (10.0% [of participants]), wavering above and below moderate (26.2%) and low and variable (63.8%) depression level trajectories. The subpopulation trajectories, respectively, were also characterized by high, moderate and low MS disability at baseline. In contrast, the overall average trajectory was slightly declining and below the moderate depression threshold.The LCGA approach described in this paper and applied to MS patients provides a template for improved use of an EHR data base for understanding heterogeneous depression screening trajectories. Clinicians may use such information to more closely monitor patients that are expected to maintain high or unstable depression levels.

SUBMITTER: Gunzler DD

PROVIDER: S-EPMC5031243 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Heterogeneous depression trajectories in multiple sclerosis patients.

Gunzler Douglas D DD Morris Nathan N Perzynski Adam A Ontaneda Daniel D Briggs Farren F Miller Deborah D Bermel Robert A RA

Multiple sclerosis and related disorders 20160805

<h4>Background</h4>Trajectories of depression over time may be heterogeneous in Multiple Sclerosis (MS) patients. Describing these trajectories will help clinicians understand better the progression of depression in MS patients to aid in patient care decisions.<h4>Methods</h4>Latent class growth analysis (LCGA) was applied to 3507 MS patients using an electronic health records (EHR) data base to identify subgroups of MS patients based on self-reported depression screening (PHQ-9). Latent traject ...[more]

PMID: 27645367

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Project description:Background and objectivesDepression is common in multiple sclerosis (MS) and is associated with faster disability progression. The etiology of comorbid depression in MS remains poorly understood. Identification of individuals with a high risk of depression, through polygenic scores (PGS), may facilitate earlier identification. Previous genetic studies of depression considered depression as a primary disorder, not a comorbidity, and thus, findings may not generalize to MS. Body mass index (BMI) is a risk factor of both MS and depression, and its association may highlight differences in depression in MS. To improve the understanding of comorbid depression in MS, we will investigate PGS in people with MS, with the hypothesis that a higher depression PGS is associated with increased odds for comorbid depression in MS.MethodsSamples from 3 sources (Canada, UK Biobank, and the United States) were used. Individuals were grouped into cases (MS/comorbid depression) and compared with 3 control groups: MS/no depression, depression/no immune disease, and healthy persons. We used 3 depression definitions: lifetime clinical diagnoses, self-reported diagnoses, and depressive symptoms. The PGS were tested in association with depression using regression.ResultsA total of 106,682 individuals of European genetic ancestry were used: Canada (n = 370; 213 with MS), UK Biobank (n = 105,734; 1,390 with MS), and the United States (n = 578 with MS). Meta-analyses revealed individuals with MS and depression had a higher depression PGS compared with both individuals with MS without depression (odds ratio range per SD 1.29-1.38, p < 0.05) and healthy controls (odds ratio range per SD 1.49-1.53, p < 0.025), regardless of the definition applied and when sex stratified. The BMI PGS was associated with depressive symptoms (p ≤ 0.001). The depression PGS did not differ between depression occurring as a comorbid condition with MS or as the primary condition (odds ratio range per SD 1.03-1.13, all p > 0.05).DiscussionA higher depression genetic burden was associated with approximately 30%-40% increased odds of depression in European genetic ancestry participants with MS compared with those without depression and was no different compared with those with depression and no comorbid immune disease. This study paves the way for further investigations into the possible use of PGS for assessing psychiatric disorder risk in MS and its application to non-European genetic ancestries.

Project description:Depression is among the most common comorbidities in multiple sclerosis and has severe psychosocial consequences. Alterations in neural emotion regulation in amygdala and prefrontal cortex have been recognized as key mechanism of depression but never been investigated in multiple sclerosis depression. In this cross-sectional observational study, we employed a functional MRI task investigating neural emotion regulation by contrasting regulated versus unregulated negative stimulus perception in 16 persons with multiple sclerosis and depression (47.9 ± 11.8 years; 14 female) and 26 persons with multiple sclerosis but without depression (47.3 ± 11.7 years; 14 female). We tested the impact of depression and its interaction with lesions in amygdala-prefrontal fibre tracts on brain activity reflecting emotion regulation. A potential impact of sex, age, information processing speed, disease duration, overall lesion load, grey matter fraction, and treatment was taken into account in these analyses. Patients with depression were less able (i) to downregulate negative emotions than those without (t = -2.25, P = 0.012, β = -0.33) on a behavioural level according to self-report data and (ii) to downregulate activity in a left amygdala coordinate (t = 3.03, P Family-wise error [FWE]-corrected = 0.017, β = 0.39). Moreover, (iii) an interdependent effect of depression and lesions in amygdala-prefrontal tracts on activity was found in two left amygdala coordinates (t = 3.53, pFWE = 0.007, β = 0.48; t = 3.21, pFWE = 0.0158, β = 0.49) and one right amygdala coordinate (t = 3.41, pFWE = 0.009, β = 0.51). Compatible with key elements of the cognitive depression theory formulated for idiopathic depression, our study demonstrates that depression in multiple sclerosis is characterized by impaired neurobehavioural emotion regulation. Complementing these findings, it shows that the relation between neural emotion regulation and depression is affected by lesion load, a key pathological feature of multiple sclerosis, located in amygdala-prefrontal tracts.

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Heterogeneous depression trajectories in multiple sclerosis patients.

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Heterogeneous depression trajectories in multiple sclerosis patients.

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