Measuring the attention networks and quantitative-electroencephalography correlates of attention in depression.

Given the association between major depressive disorder (MDD) and cortical inefficiency related to executive control, specifically in the sense that individuals with MDD may recruit more cognitive resources to complete tasks at the same capacity as those without MDD, the current study was interested in examining the attention networks and executive functioning of those with MDD. Past research has used the Attention Network Test (ANT) to measure changes of attention in clinical vs. healthy populations; however, theoretical concerns have been raised regarding the task. The Combined Attention Systems Task (CAST) was developed to address these concerns and was used in our study in combination with quantitative-electroencephalography (QEEG) to assess both behavioural and neurophysiological changes in participants with MDD (n = 18) compared to healthy controls (HCs; n = 22). We found no behavioural differences between MDD and HC groups suggesting individuals with MDD in our sample were not experiencing the executive functioning deficits previously reported in the literature. Neurophysiological measures of attention revealed that MDD participants had greater theta and alpha1 activity relative to HCs, suggesting that although individuals with MDD do not show deficits in behavioural attention, they exhibit altered neural processing which underlies cognitive function.

An investigation of auditory processing in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is one of the most common neurological diseases in North America and it is frequently associated with sensory processing difficulties, cognitive deficits, and psychiatric illness. While many studies have examined cognitive deficits in MS measured by behavioural responses and neuroimaging techniques, only a few studies have examined neurophysiological measures of auditory functioning in MS, such as the mismatch negativity (MMN). The MMN is an event-related potential that indicates automatic auditory change detection. This study examined whether MMN endpoints measured by electroencephalography (EEG) differ in individuals with relapsing-remitting MS compared to healthy controls and whether the symptomatology of MS, including symptoms of depression and fatigue, are related to MMN measures. A multi-feature MMN paradigm, which includes five distinct deviant tones, was used to assess auditory cortex function in MS. There were no significant differences in MMN amplitudes or latencies between the MS and control group (p < 0.05) and corresponding effect sizes were small. However, there was a correlation between reduced MMN amplitudes in response to an intensity deviant and physician-reported disability. The intensity MMN may be more sensitive to deterioration in this population. Ultimately, this study provides a comprehensive profile of early auditory processing abilities in MS and suggests that a reduction in the MMN response may be representative of disease severity in MS.

The symbol digit modalities test and the paced auditory serial addition test involve more than processing speed.

BACKGROUND: Slowed processing speed is the most frequently reported cognitive deficit for people with multiple sclerosis (MS). However, measures used to assess processing speed may also recruit other cognitive abilities. The present objective was to determine the contributions of different cognitive functions to performance on two commonly used processing speed measures: the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). METHODS: Adults with relapsing-remitting MS (n = 70) and controls (n = 72) completed the SDMT, PASAT, and multiple measures assessing processing speed, working memory, and learning. Hierarchical regression analyses were used to examine the contributions of MS, processing speed, working memory, learning, and all possible interactions among factors to SDMT and PASAT scores. RESULTS: Processing speed and working memory generally contributed to performance on the SDMT and PASAT, with learning additionally contributing to SDMT performance. However, significant interactions revealed processing speed did not influence PASAT performance for individuals with high working memory ability whereas processing speed became increasingly more important as working memory declined to average and low levels. Further, processing speed was associated with SDMT performance for patients with MS but not controls. CONCLUSIONS: These findings support a multifactorial interpretation of the SDMT and PASAT, which facilitates their usefulness as screening measures for cognitive decline but prevents them from identifying which specific cognitive functions are affected.

MMN-Indexed Auditory Change Detection in Major Depressive Disorder.

In major depressive disorder (MDD), event-related potentials that are involved in auditory cortex function (i.e. N100 and P300) often have greater latencies and decreased amplitudes. The auditory mismatch negativity (MMN) is thought to be produced by generators in the auditory cortex, as well as the frontal lobes. Reports on differences in MMN in those with MDD have been varied. It was hypothesized that the wide range of results in the literature may be due to the use of different deviant types in eliciting the MMN. To attempt and explain these inconsistencies, the current study employed a multifeature MMN paradigm with 5 deviant tone types in community-dwelling participants with a diagnosis of MDD. We found those with MDD had higher MMN amplitudes following tones that deviated in intensity and location, but no difference in MMNs elicted by the other deivants (relative to unaffected controls). Location MMN deviants were negatively correlated with depression severity scores (i.e. larger MMN with greater severity). We also found longer MMN latencies following the pitch deviant. These results suggest the early auditory change detection process is altered in MDD, but only following certain types of auditory stimuli. Potential explanations for these findings, including high levels of anxiety and the influence of tryptophan are explored. Equally, the current report highlights the importance of using various deviant types when examining the MMN in clinical populations.

Comorbid anxiety, depression, and cognition in MS and other immune-mediated disorders.

OBJECTIVE: To determine whether anxiety and depression are associated with cognition in multiple sclerosis (MS), and whether these associations are similar in other immune-mediated inflammatory diseases (IMID; including inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) and in anxious/depressed individuals (ANX/DEP) without an IMID. METHODS: Participants (MS: n = 255; IBD: n = 247; RA: n = 154; ANX/DEP: n = 308) completed a structured psychiatric interview, the Hospital Anxiety and Depression Scale, and cognitive testing, including the Symbol Digit Modalities Test, the California Verbal Learning Test, and Letter Number Sequencing test. Test scores were converted to age-, sex-, and education-adjusted z scores. We evaluated associations of anxiety and depression with the cognitive z scores using multivariate linear models, adjusting for disease cohort. RESULTS: All cohorts exhibited higher rates of impairment (i.e., z less than or equal to -1.5) in the domains of processing speed, verbal learning, and delayed recall memory relative to general population norms. Higher levels of anxiety symptoms were associated with slower processing speed, lower verbal learning, and lower working memory performance (all p < 0.001); higher levels of depression symptoms were associated with slower processing speed. These associations did not differ across cohorts. CONCLUSION: Anxiety and depression are associated with lower cognitive function in MS, with a similar pattern observed in persons with other IMID, including IBD and RA, and persons without an IMID. Managing symptoms of anxiety and of depression in MS, as well as other IMIDs, is important to mitigate their effect on cognition.

Diagnoses of Depression and Anxiety Versus Current Symptoms and Quality of Life in Multiple Sclerosis.

BACKGROUND: Studies assessing the prevalence of depression and anxiety in multiple sclerosis (MS) have used various ascertainment methods that capture different constructs. The relationships between these methods are incompletely understood. Psychiatric comorbidity is associated with lower health-related quality of life (HRQOL) in MS, but the effects of past diagnoses of depression and anxiety on HRQOL are largely unknown. We compared the prevalence of depression and anxiety in persons with MS using administrative data, self-reported physician diagnoses, and symptom-based measures and compared characteristics of persons classified as depressed or anxious by each method. We evaluated whether HRQOL was most affected by previous diagnoses of depression or anxiety or by current symptoms. METHODS: We linked clinical and administrative data for 859 participants with MS. HRQOL was measured by the Health Utilities Index Mark 3. We classified participants as depressed or anxious using administrative data, self-reported physician diagnoses, and the Hospital Anxiety and Depression Scale. Multivariable linear regression examined whether diagnosed depression or anxiety affected HRQOL after accounting for current symptoms. RESULTS: Lifetime prevalence estimates for depression were approximately 30% regardless of methods used, but 35.8% with current depressive symptoms were not captured by either administrative data or self-reported diagnoses. Prevalence estimates of anxiety ranged from 11% to 19%, but 65.6% with current anxiety were not captured by either administrative data or self-reported diagnoses. Previous diagnoses did not decrease HRQOL after accounting for current symptoms. CONCLUSIONS: Depression and, to a greater extent, anxiety remain underdiagnosed and undertreated in MS; both substantially contribute to reduced HRQOL in MS.

Effects of Psychiatric Comorbidity in Immune-Mediated Inflammatory Disease: Protocol for a Prospective Study.

BACKGROUND: Immune-mediated inflammatory diseases (IMID), such as inflammatory bowel disease (IBD), multiple sclerosis (MS), and rheumatoid arthritis (RA), are highly prevalent in Canada and the United States and result in substantial personal and societal burden. The prevalence of psychiatric comorbidities, primarily depression and anxiety, in IMID exceeds those in the general population by two- to threefold, but remains underdiagnosed and undertreated. Furthermore, the effects of psychiatric comorbidity on IMID are not well understood. OBJECTIVE: The objectives of this study were (1) to compare health-related quality of life and work ability in persons with IMID and psychiatric comorbidity with those of persons with IMID without psychiatric comorbidity and with those of persons with depression and anxiety disorders alone, and (2) to validate existing case identification tools for depression and anxiety in persons with IMID to facilitate improved identification of depression and anxiety by clinicians. To achieve these objectives, we designed a prospective 3-year longitudinal study. In this paper, we aim to describe the study rationale and design and the characteristics of study participants. METHODS: Between November 2014 and July 2016, we recruited 982 individuals from multiple clinic and community sources; 18 were withdrawn due to protocol violations. RESULTS: The final study sample included 247 participants with IBD, 255 with MS, 154 with RA, and 308 with depression or anxiety. The majority were white, with the proportion ranging from 85.4% (IBD [210/246]; MS [217/254]) to 74.5% (114/153, RA; P=.01). There was a female predominance in all groups, which was highest in the RA cohort (84.4%, 130/154) and least marked in the IBD cohort (62.7%, 155/247). Participants with depression or anxiety were more likely to be single (36.0%, 111/308) than participants in any other group (11.8% [30/255]-22.7% [56/247], P<.001). CONCLUSIONS: This paper presents the rationale for this study, describes study procedures, and characterizes the cohort enrolled. Ultimately, the aim is improved care for individuals affected by IMID.

Screening Tools for Anxiety in People with Multiple Sclerosis: A Systematic Review.

Background: Anxiety is prevalent in people with multiple sclerosis (MS). Screening measures are used to identify symptoms of anxiety, but the optimal measure to screen for anxiety disorders in MS has not been established. Methods: We searched the MEDLINE, Embase, PsycINFO, PsycARTICLES Full Text, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Scopus databases from database inception until August 7, 2015. Two independent reviewers screened abstracts and full-text reports for study inclusion, extracted data, and assessed risk of bias. We included studies that evaluated the criterion validity of anxiety screening tools when measuring anxiety in individuals with well-documented MS, as measured by sensitivity, specificity, and positive and negative predictive values. Results: Of the 3181 abstracts screened, 18 articles were reviewed in full text, of which 4 met the inclusion criteria. The criterion validity of three screening tools was assessed: the Hospital Anxiety and Depression Scale-Anxiety (HADS-A), Beck Anxiety Inventory (BAI), and 7-item Generalized Anxiety Disorder Scale (GAD-7). The HADS-A was validated against the Structured Clinical Interview for DSM-IV, the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview, and the BAI. The BAI was validated against the SCAN, and the GAD-7 was validated against the HADS-A. The HADS-A had higher measures of sensitivity and specificity than did the BAI and the GAD-7. Conclusions: Based on this small sample, the HADS-A shows promise as an applicable measure for people with MS. Screening scales used to identify anxiety in MS must be validated against appropriate reference standards.

Fatigue and Comorbidities in Multiple Sclerosis.

BACKGROUND: Fatigue is commonly reported by people with multiple sclerosis (MS). Comorbidity is also common in MS, but its association with the presence of fatigue or fatigue changes over time is poorly understood. METHODS: Nine hundred forty-nine people with definite MS were recruited from four Canadian centers. The Fatigue Impact Scale for Daily Use and a validated comorbidity questionnaire were completed at three visits over 2 years. Participants were classified into groups with no fatigue versus any fatigue. Logistic regression was used to determine the relationship between fatigue and each comorbidity at baseline, year 1, year 2, and overall. RESULTS: The incidence of fatigue during the study was 38.8%. The prevalence of fatigue was greater in those who were older (P = .0004), had a longer time since symptom onset (P = .005), and had greater disability (P < .0001). After adjustment, depression (odds ratio [OR], 2.58; 95% confidence interval [CI], 2.03-3.27), irritable bowel syndrome (OR, 1.71; 95% CI, 1.18-2.48), migraine (OR, 1.69; 95% CI, 1.27-2.27), and anxiety (OR, 1.57; 95% CI, 1.15-2.16) were independently associated with fatigue that persisted during the study. There was also an individual-level effect of depression on worsening fatigue (OR, 1.49; 95% CI, 1.08-2.07). CONCLUSIONS: Comorbidity is associated with fatigue in MS. Depression is associated with fatigue and with increased risk of worsening fatigue over 2 years. However, other comorbid conditions commonly associated with MS are also associated with persistent fatigue, even after accounting for depression. Further investigation is required to understand the mechanisms by which comorbidities influence fatigue.

Health-related quality of life in multiple sclerosis: Direct and indirect effects of comorbidity.

OBJECTIVE: To evaluate the direct and indirect influences of physical comorbidity, symptoms of depression and anxiety, fatigue, and disability on health-related quality of life (HRQoL) in persons with multiple sclerosis (MS). METHODS: A large (n = 949) sample of adults with MS was recruited from 4 Canadian MS clinics. HRQoL was assessed using the patient-reported Health Utilities Index Mark 3. Expanded Disability Status Scale scores, physical comorbidity, depression, anxiety, and fatigue were evaluated as predictors of HRQoL in a cross-sectional path analysis. RESULTS: All predictors were significantly associated with HRQoL and together accounted for a large proportion of variance (63%). Overall, disability status most strongly affected HRQoL (ß = -0.52) but it was closely followed by depressive symptoms (ß = -0.50). The direct associations of physical comorbidity and anxiety with HRQoL were small (ß = -0.08 and -0.10, respectively), but these associations were stronger when indirect effects through other variables (depression, fatigue) were also considered (physical comorbidity: ß = -0.20; anxiety: ß = -0.34). CONCLUSIONS: Increased disability, depression and anxiety symptoms, fatigue, and physical comorbidity are associated with decreased HRQoL in MS. Disability most strongly diminishes HRQoL and, thus, interventions that reduce disability are expected to yield the most substantial improvement in HRQoL. Yet, interventions targeting other factors amenable to change, particularly depression but also anxiety, fatigue, and physical comorbidities, may all result in meaningful improvements in HRQoL, as well. Our findings point to the importance of further research confirming the efficacy of such interventions.

Reliability of regression-based normative data for the oral symbol digit modalities test: an evaluation of demographic influences, construct validity, and impairment classification rates in multiple sclerosis samples.

The oral Symbol Digit Modalities Test (SDMT) has been recommended to assess cognition for multiple sclerosis (MS) patients. However, the lack of adequate normative data has limited its clinical utility. Recently published regression-based norms may resolve this limitation but, because these norms were derived from a relatively small sample, their stability is unclear. We aimed to evaluate the stability of regression-based SDMT norms by comparing existing norms to a cross-validation dataset. First, regression-based normative data were created from a similarly-sized, independent, control sample (n = 94). Next the original and cross-validation norms were compared for equivalency, management of demographic influences, construct validity, and impairment classification rates in a mildly affected MS sample (n = 70). Lastly, similar comparisons were made for a large, representative MS clinic sample (n = 354). We found construct validity and management of demographic influences were equivalent for the two sets of regression-based norms but lower T-scores were obtained using the original dataset, resulting in discrepancies in impairment classification. In conclusion, regression-based norms for the oral SDMT attenuate demographic influences and possess adequate construct validity. However, norms generated using small samples may yield unreliable classification of cognitive impairment. Larger, representative databases will be necessary to improve the clinical utility of regression-based norms.

Cognition in early relapsing-remitting multiple sclerosis: consequences may be relative to working memory.

The Relative Consequence Model proposes multiple sclerosis (MS) patients have a fundamental deficit in processing speed that compromises other cognitive functions. The present study examined the mediating role of processing speed,as well as working memory, in the MS-related effects on other cognitive functions for early relapsing-remitting patients. Seventy relapsing-remitting MS patients with disease duration not greater than 10 years and 72 controls completed tasks assessing processing speed, working memory, learning, and executive functioning. The possible mediating roles of speed and working memory in the MS-related effects on other cognitive functions were evaluated using structural equation modeling. Processing speed was not significantly related to group membership and could not have a mediating role. Working memory was related to group membership and functioned as a mediating/intervening factor. The results do not support the Relative Consequence Model in this sample and they challenge the notion that working memory impairment only emerges at later disease stages. The results do support a mediating/intervening role of working memory. These results were obtained for early relapsing-remitting MS patients and should not be generalized to the broader MS population. Instead, future research should examine the relations that exist at other disease stages.

Intra-individual Variability as a Measure of Information Processing Difficulties in Multiple Sclerosis.

Deficits in information processing speed are among the most commonly reported impairments in multiple sclerosis (MS) and are generally assessed by evaluating mean-level performance on time-limited tests. However, this approach to assessing performance ignores potential within-subject differences in MS patients that may be useful for characterizing cognitive difficulties in MS. An alternative method of measuring performance is by examining the degree of within-subject variability, termed intra-individual variability (IIV). Intra-individual variability provides information about the characteristics of a person's performance over time and may provide novel information about cognitive functioning in MS. This study examined IIV in performance on the Computerized Test of Information Processing (CTIP) using two within-subject variability methods: individual standard deviation and coefficient of variation. Eighteen females with relapsing-remitting MS and 18 healthy female controls completed the CTIP. Consistent with previous research, MS patients demonstrated slower overall mean performance on the CTIP compared with controls, with patients becoming increasingly slower than controls as cognitive demands increased across the tasks. Furthermore, MS patients demonstrated greater IIV as measured by individual standard deviations on all subtests of the CTIP, even with mean-level group differences as well as practice and learning effects controlled. These between-group differences were not found when the coefficient of variation, a more coarse measure of within-subject variability, was used. Intra-individual variability was also found to be a better predictor of neurologic status than mean-level performance. These results suggest that IIV may provide unique insight into cognitive functioning in MS.

Tests of information processing speed: what do people with multiple sclerosis think about them?

Reduction in information processing speed (IPS) is a key deficit in multiple sclerosis (MS). The Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), and Computerized Test of Information Processing (CTIP) are used to measure IPS. Both the PASAT and SDMT are sensitive to deficits in IPS. The CTIP, a newer task, also shows promise. The PASAT has several limitations, and it is often perceived negatively by patients. Yet little supporting quantitative evidence of such perceptions has been presented. Therefore, in this study, subjective ratings of likeability, difficulty, and appropriateness of the PASAT, CTIP, and SDMT were obtained. Ratings were compared between MS patients and healthy controls. It was hypothesized that ratings of the PASAT would differ significantly from those of the SDMT and CTIP. The relationship between subjective ratings and objective performance was evaluated. Sixty-nine MS patients and 68 matched controls rated the three tests in terms of likeability, difficulty, and appropriateness for capturing cognitive deficits often associated with MS using a Likert scale. Both groups rated the PASAT as most difficult and least likeable. The MS group rated the PASAT and SDMT as more appropriate for measuring MS-related deficits than the CTIP. Subjects who performed better on the PASAT were more likely to rate it as easier. Ratings of the SDMT and CTIP did not vary consistently with performance. The findings lend quantitative support to the common belief that the PASAT is perceived as unpleasant. Other tests are available that are similarly sensitive to deficits in IPS and more palatable to the patient.

The Computerized Test of Information Processing (CTIP) offers an alternative to the PASAT for assessing cognitive processing speed in individuals with multiple sclerosis.

OBJECTIVE: To compare the ability of the Computerized Test of Information Processing (CTIP) to detect impaired cognitive processing speed in patients with multiple sclerosis (MS) with a traditional 3.0 second Paced Auditory Serial Addition Test (PASAT) and the Adjusting-PASAT which allows for calculation of a speed score. BACKGROUND: A primary cognitive deficit in MS is an impaired ability to process information quickly. Unfortunately, relatively few clinical tests effectively measure information processing speed. Of these, the PASAT is generally acknowledged to be the most sensitive, but use of this test is constrained by several factors. METHODS: All tests were administered to 30 adults with relapsing-remitting MS and 30 control participants. RESULTS: A series of analysis of variances revealed MS participants performed significantly worse than controls on the CTIP and the 3.0 second PASAT, whereas no significant difference was observed for the Adjusting-PASAT. CONCLUSIONS: The results suggest the CTIP can detect deficits in the speed at which people with MS process information. Thus, the CTIP offers an alternative means to the 3.0 second PASAT included in the Multiple Sclerosis Functional Composite for assessing such impairment.