Publications by authors named "Anthony Feinstein"

138 Publications

Effectiveness of Three-Dimensional Multiple-Object Tracking in Patients with Multiple Sclerosis: A Pilot Trial.

Int J MS Care 2021 Jul-Aug;23(4):143-149. Epub 2020 Oct 16.

Background: Computerized cognitive training remains an attractive supplemental modality to enhance rehabilitation in multiple sclerosis (MS). The objective of the present study was to assess the usability of three-dimensional multiple-object tracking (3D-MOT) in patients with MS.

Methods: In this pilot study, 16 patients with relapsing-remitting MS and nine age-matched controls participated in four 30-minute training sessions of 3D-MOT. Computerized neuropsychological tests, including driving readiness (ie, Useful Field of View) and cognitive function (ie, Stroop Color and Word Test, Paced Visual Serial Addition Test, Symbol Digit Modalities Test) were conducted at baseline and at the conclusion of training.

Results: Although scoring lower in 3D-MOT, the MS group improved their 3D-MOT scores in similar magnitude as the control group. The 3D-MOT training led to significant improvements in driving readiness in the MS group. Taken together, 3D-MOT training showed similar effectiveness in patients with MS as in age-matched controls.

Conclusions: Training with 3D-MOT may be an accessible and remotely administrable supplement to cognitive rehabilitation protocols for patients with MS.
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http://dx.doi.org/10.7224/1537-2073.2020-007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405148PMC
October 2020

Understanding conversion disorder: How contemporary brain imaging is shedding light on an early Freudian concept.

J Psychiatr Res 2021 09 14;141:353-357. Epub 2021 Jul 14.

University of Cambridge. Addenbrookes Hospital, Level E4, Box 189, Cambridge, CB20QQ, United Kingdom. Electronic address:

Conversion disorder, also called Functional Neurological Symptom Disorder is poorly understood by many in the medical profession and is associated with considerable health care costs. Sigmund Freud, in an early, pre-psychoanalytic period paper, suggested that hysterical motor paralyses arose from a "functional or dynamic lesion" which was no different from an organic one, but rather an altered expression of it. He linked this functional brain disturbance to an excess of affect, a faulty conceptualization on the part of the symptomatic individual of how the affected organ works, and elements of dissociation and dual consciousness. One hundred and thirty years later converging functional imaging studies provide support for the excess affect component of his hypothesis. A small but growing fMRI literature has revealed bottom-up hyperactive neural activity in limbic regions and a potential failure of top-down regulation from prefrontal regions. Aberrant functional connectivity of limbic-motor regions now provides a mechanistic model that sheds light on an early Freudian theory explaining, in part, how symptoms of Conversion Disorder arise.
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http://dx.doi.org/10.1016/j.jpsychires.2021.07.013DOI Listing
September 2021

How have journalists been affected psychologically by their coverage of the COVID-19 pandemic? A descriptive study of two international news organisations.

BMJ Open 2021 07 12;11(7):e045675. Epub 2021 Jul 12.

Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Objectives: The COVID-19 pandemic has presented unprecedented healthcare challenges. Journalists covering the pandemic at close quarters are working in ways akin to first responders, but nothing to date is known of the psychological distress this is potentially causing them. This study aims to determine whether journalists reporting on the COVID-19 crisis have been affected emotionally, and if so to assess the severity of their distress. It also investigates potential demographic and work-related predictors and whether news organisations had provided counselling to their journalists.

Participants: A total of 111 journalists working for two international news organisations were approached of which 73 (66%) participated in the study.

Primary And Secondary Outcome Measures: Symptoms of anxiety (Generalised Anxiety Disorder Scale-7 (GAD-7)), depression (Patient Health Questionnaire (PHQ-9)), posttraumatic stress disorder (PTSD; PTSD Checklist for DSM-5 (PCL-5)), overall psychological distress (12-item General Health Questionnaire (GHQ-12)), and treatment.

Results: The percentages of journalists exceeding threshold scores for clinically significant anxiety, depression, PTSD and psychological distress were: GAD-7, 26%; PHQ-9, 20.5%; PCL-5, 9.6%; GHQ-12, 82.2%. Journalists assigned to cover the pandemic (n=54 (74%)) were significantly more anxious (p<0.05). Journalists who received counselling (n=38 (52%)) following the onset of the pandemic reported significantly fewer symptoms of anxiety (p<0.01), depression (p<0.01) and overall psychological distress (p<0.01).

Conclusions: Journalists covering the COVID-19 pandemic are experiencing levels of anxiety and depression similar to those seen in first responders. Psychological therapy provided in a timely manner can significantly alleviate emotional distress.
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http://dx.doi.org/10.1136/bmjopen-2020-045675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277489PMC
July 2021

Impaired awareness: Why people with multiple sclerosis continue using cannabis despite evidence to the contrary.

Brain Behav 2021 Aug 4;11(8):e2220. Epub 2021 Jun 4.

Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.

Background: With widespread moves toward legalization of cannabis, increasing numbers of people with multiple sclerosis (pwMS) are using the drug. Emerging MS-related data show that cannabis can cause or exacerbate cognitive dysfunction.

Objective: To understand why people with MS continue using cannabis despite adverse cognitive consequences. It was hypothesized that lack of awareness, a component of metacognition, could explain this decision, in part.

Method: Forty pwMS who smoked cannabis almost daily were assigned by odd-even case number selection to either a cannabis continuation (CC) or cannabis withdrawal (CW) group. Both groups were followed for 28 days. All participants completed, at baseline and day 28, the brief repeatable battery of neuropsychological tests (BRNB) in MS for measures of processing speed, memory and executive function; Modified fatigue impact scale (mFIS) for self-report indices of cognitive functioning.

Results: No significant baseline differences between the groups on the BRNB and mFIS. At day 28, significant improvement within group was seen on all measures of the BRNB, but only in the CW group (p = .0001 for all indices). A repeat measure ANOVA did not find any significant group (CC vs. CW) × time (baseline and day 28) interactions for the self-report cognitive measures on the mFIS. Cannabis abstainers did report less ability to function away from home. All 19 participants in the CW group reverted to using cannabis on study completion despite being informed individually of their cognitive improvement.

Conclusions And Relevance: The inability of pwMS to accurately appraise their memory and executive function can help explain, in part, why they continue to smoke cannabis despite objective evidence of the deleterious cognitive side effects of this behavior.
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http://dx.doi.org/10.1002/brb3.2220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413765PMC
August 2021

Computerized Symbol Digit Modalities Test in a Swiss Pediatric Cohort Part 1: Validation.

Front Psychol 2021 22;12:631536. Epub 2021 Apr 22.

Division of Child Neurology, Department of Pediatrics, University Children's Hospital Bern, University of Bern, Bern, Switzerland.

Objective: The objective of this study was to validate the computerized Symbol Digit Modalities Test (c-SDMT) in a Swiss pediatric cohort, in comparing the Swiss sample to the Canadian norms. Secondly, we evaluated sex effects, age-effects, and test-retest reliability of the c-SDMT in comparison to values obtained for the paper and pencil version of the Symbol Digit Modalities Test (SDMT).

Methods: This longitudinal observational study was conducted in a single-center setting at the University Children's Hospital of Bern. Our cohort consisted of 86 children (45 male and 41 female) aged from 8 to 16 years. The cohort included both healthy participants ( = 38) and patients ( = 48) hospitalized for a non-neurological disease. Forty eight participants were assessed during two testing sessions with the SDMT and the c-SDMT.

Results: Test-retest reliability was high in both tests (SDMT: ICC = 0.89, c-SDMT: ICC = 0.90). A reliable change index was calculated for the SDMT (RCIp = -3.18, 14.01) and the c-SDMT (RCIp = -5.45, 1.46) corrected for practice effects. While a significant age effect on information processing speed was observed, no such effect was found for sex. When data on the c-SDMT performance of the Swiss cohort was compared with that from a Canadian cohort, no significant difference was found for the mean time per trial in any age group. Norm values for age groups between 8 and 16 years in the Swiss cohort were established.

Conclusion: Norms for the c-SDMT between the Swiss and the Canadian cohort were comparable. The c-SDMT is a valid alternative to the SDMT. It is a feasible and easy to administer bedside tool due to high reliability and the lack of motor demands.
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http://dx.doi.org/10.3389/fpsyg.2021.631536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101631PMC
April 2021

Computerized Symbol Digit Modalities Test in a Swiss Pediatric Cohort - Part 2: Clinical Implementation.

Front Psychol 2021 23;12:631535. Epub 2021 Apr 23.

Division of Child Neurology, Department of Pediatrics, University Children's Hospital Bern, University of Bern, Bern, Switzerland.

Background: Information processing speed (IPS) is a marker for cognitive function. It is associated with neural maturation and increases during development. Traditionally, IPS is measured using paper and pencil tasks requiring fine motor skills. Such skills are often impaired in patients with neurological conditions. Therefore, an alternative that does not need motor dexterity is desirable. One option is the computerized symbol digit modalities test (c-SDMT), which requires the patient to verbally associate numbers with symbols.

Methods: Eighty-six participants (8-16 years old; 45 male; 48 inpatients) were examined, 38 healthy and 48 hospitalized for a non-neurological disease. All participants performed the written SDMT, c-SDMT, and the Test of Non-verbal Intelligence Fourth Edition (TONI-4). Statistical analyses included a multivariate analysis of covariance (MANCOVA) for the effects of intelligence (IQ) and hospitalization on the performance of the SDMT and c-SDMT. A repeated measures analysis of variance (repeated measures ANOVA) was used to compare performance across c-SDMT trials between inpatients and outpatients.

Results: The MANCOVA showed that hospitalization had a significant effect on IPS when measured with the SDMT ( = 0.04) but not with the c-SDMT ( = 0.68), while IQ ( = 0.92) had no effect on IPS. Age ( < 0.001) was the best predictor of performance of both tests. The repeated measures ANOVA revealed no significant difference in within-test performance ( = 0.06) between outpatient and inpatient participants in the c-SDMT.

Conclusion: Performance of the c-SDMT is not confounded by hospitalization and gives within-test information. As a valid and reliable measure of IPS for children and adolescents, it is suitable for use in both inpatient and outpatient populations.
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http://dx.doi.org/10.3389/fpsyg.2021.631535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102725PMC
April 2021

Cognitive impairment, the central vein sign, and paramagnetic rim lesions in RIS.

Mult Scler 2021 Mar 23:13524585211002097. Epub 2021 Mar 23.

Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada/Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.

Objective: The central vein sign (CVS) and "paramagnetic rim lesions" (PRL) are emerging imaging biomarkers in multiple sclerosis (MS) reflecting perivenular demyelination and chronic, smoldering inflammation. The objective of this study was to assess relationships between cognitive impairment (CI) and the CVS and PRL in radiologically isolated syndrome (RIS).

Methods: Twenty-seven adults with RIS underwent 3.0 T MRI of the brain and cervical spinal cord (SC) and cognitive assessment using the minimal assessment of cognitive function in MS battery. The CVS and PRL were assessed in white-matter lesions (WMLs) on T2*-weighted segmented echo-planar magnitude and phase images. Multivariable linear regression evaluated relationships between CI and MRI measures.

Results: Global CI was present in 9 (33%) participants with processing speed and visual memory most frequently affected. Most participants (93%) had ⩾ 40% CVS + WML (a threshold distinguishing MS from other WM disorders); 63% demonstrated PRL. Linear regression revealed that CVS + WML predicted performance on verbal memory( =-0.024,  = 0.03) while PRL predicted performance on verbal memory ( = -0.040,  = 0.04) and processing speed ( = -0.039,  = 0.03).

Conclusions: CI is common in RIS and is associated with markers of perivenular demyelination and chronic inflammation in WML, such as CVS + WML and PRL. A prospective follow-up of this cohort will ascertain the importance of CI, CVS, and PRL as risk factors for conversion from RIS to MS.
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http://dx.doi.org/10.1177/13524585211002097DOI Listing
March 2021

Prioritizing progressive MS rehabilitation research: A call from the International Progressive MS Alliance.

Mult Scler 2021 06 15;27(7):989-1001. Epub 2021 Mar 15.

Department of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Background: People with multiple sclerosis (MS) experience myriad symptoms that negatively affect their quality of life. Despite significant progress in rehabilitation strategies for people living with relapsing-remitting MS (RRMS), the development of similar strategies for people with progressive MS has received little attention.

Objective: To highlight key symptoms of importance to people with progressive MS and stimulate the design and implementation of high-quality studies focused on symptom management and rehabilitation.

Methods: A group of international research experts, representatives from industry, and people affected by progressive MS was convened by the International Progressive MS Alliance to devise research priorities for addressing symptoms in progressive MS.

Results: Based on information from the MS community, we outline a rationale for highlighting four symptoms of particular interest: fatigue, mobility and upper extremity impairment, pain, and cognitive impairment. Factors such as depression, resilience, comorbidities, and psychosocial support are described, as they affect treatment efficacy.

Conclusions: This coordinated call to action-to the research community to prioritize investigation of effective symptom management strategies, and to funders to support them-is an important step in addressing gaps in rehabilitation research for people affected by progressive MS.
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http://dx.doi.org/10.1177/1352458521999970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151585PMC
June 2021

Depression prevalence using the HADS-D compared to SCID major depression classification: An individual participant data meta-analysis.

J Psychosom Res 2020 12 23;139:110256. Epub 2020 Sep 23.

Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands; Faculty of Psychology, Open University of the Netherlands, Heerlen, The Netherlands; Department of Health Services Research, CAPHRI School for Public Health and Primary, Maastricht University, Maastricht, The Netherlands. Electronic address:

Objectives: Validated diagnostic interviews are required to classify depression status and estimate prevalence of disorder, but screening tools are often used instead. We used individual participant data meta-analysis to compare prevalence based on standard Hospital Anxiety and Depression Scale - depression subscale (HADS-D) cutoffs of ≥8 and ≥11 versus Structured Clinical Interview for DSM (SCID) major depression and determined if an alternative HADS-D cutoff could more accurately estimate prevalence.

Methods: We searched Medline, Medline In-Process & Other Non-Indexed Citations via Ovid, PsycINFO, and Web of Science (inception-July 11, 2016) for studies comparing HADS-D scores to SCID major depression status. Pooled prevalence and pooled differences in prevalence for HADS-D cutoffs versus SCID major depression were estimated.

Results: 6005 participants (689 SCID major depression cases) from 41 primary studies were included. Pooled prevalence was 24.5% (95% Confidence Interval (CI): 20.5%, 29.0%) for HADS-D ≥8, 10.7% (95% CI: 8.3%, 13.8%) for HADS-D ≥11, and 11.6% (95% CI: 9.2%, 14.6%) for SCID major depression. HADS-D ≥11 was closest to SCID major depression prevalence, but the 95% prediction interval for the difference that could be expected for HADS-D ≥11 versus SCID in a new study was -21.1% to 19.5%.

Conclusions: HADS-D ≥8 substantially overestimates depression prevalence. Of all possible cutoff thresholds, HADS-D ≥11 was closest to the SCID, but there was substantial heterogeneity in the difference between HADS-D ≥11 and SCID-based estimates. HADS-D should not be used as a substitute for a validated diagnostic interview.
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http://dx.doi.org/10.1016/j.jpsychores.2020.110256DOI Listing
December 2020

The emotional impact of the COVID-19 pandemic on individuals with progressive multiple sclerosis.

J Neurol 2021 May 19;268(5):1598-1607. Epub 2020 Aug 19.

Department of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON, M5R 3B6, Canada.

Objective: Individuals with pre-existing chronic illness have shown increased anxiety and depression due to COVID-19. Here, we examine the impact of the COVID-19 pandemic on emotional symptomatology and quality of life in individuals with Progressive Multiple Sclerosis (PMS).

Methods: Data were obtained during a randomized clinical trial on rehabilitation taking place at 11 centers in North America and Europe. Participants included 131 individuals with PMS. Study procedures were interrupted in accordance with governmental restrictions as COVID-19 spread. During study closure, a COVID Impact Survey was administered via telephone or email to all participants, along with measures of depressive symptoms, anxiety symptoms, quality of life, and MS symptomatology that were previously administered pre-pandemic.

Results: 4% of respondents reported COVID-19 infection. No significant changes were noted in anxiety, quality of life, or the impact of MS symptomatology on daily life from baseline to lockdown. While total HADS-depression scores increased significantly at follow-up, this did not translate into more participants scoring above the HADS threshold for clinically significant depression. No significant relationships were noted between disease duration, processing speed ability or EDSS, and changes in symptoms of depression or anxiety. Most participants reported the impact of the virus on their psychological well-being, with a little impact on financial well-being. The perceived impact of the pandemic on physical and psychological well-being was correlated with the impact of MS symptomatology on daily life, as well as changes in depression.

Conclusions: Overall, little change was noted in symptoms of depression or anxiety or overall quality of life.
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http://dx.doi.org/10.1007/s00415-020-10160-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436067PMC
May 2021

Discontinuing cannabis improves depression in people with multiple sclerosis: A short report.

Mult Scler 2021 04 26;27(4):636-639. Epub 2020 Jun 26.

Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada.

To assess whether symptoms of depression change when people with multiple sclerosis (pwMS) discontinue cannabis use, 40 cognitively impaired pwMS who smoked cannabis almost daily were randomly assigned to either a cannabis continuation (CC) or cannabis withdrawal (CW) group. Both groups were followed for 28 days. All participants completed the Hospital Anxiety and Depression Scale. At day 28 the 11-nor-9-carboxy-Δ-tetrahydro-cannabinol (THCCOOH)/creatinine ratio in the CW group declined to zero ( = 0.0001), but remained unchanged in the CC group ( = 0.709). Depression scores in those pwMS who were using cannabis to manage their depression remained statistically unchanged in the CC group, but declined in the CW group ( = 0.006). Despite pwMS using cannabis to help their mood, depression improved significantly off the drug. Our finding provides a cautionary note in relation to cannabis use in pwMS, at least with respect to depression.
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http://dx.doi.org/10.1177/1352458520934070DOI Listing
April 2021

A novel in-home digital treatment to improve processing speed in people with multiple sclerosis: A pilot study.

Mult Scler 2021 04 25;27(5):778-789. Epub 2020 Jun 25.

Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.

Objective: To assess whether a videogame-like digital treatment is superior to a control in improving processing speed in adults with multiple sclerosis (MS).

Methods: Adults with MS and baseline Symbol Digit Modalities Test (SDMT) -scores between -2 and 0 were enrolled in a double-blind randomized controlled clinical trial. After completing a baseline in-clinic evaluation (Visit 1), they were randomized to complete an in-home, tablet-based videogame-like digital treatment (AKL-T03) or control word game (AKL-T09) for up to 25 minutes/day, 5 days/week, for 6 weeks. A repeat in-clinic evaluation occurred at 6 weeks (Visit 2), and again 8 weeks later to determine persistence of effects (Visit 3). The pre-specified primary outcome was change in SDMT score between Visits 1 and 2.

Results: SDMT increased at Visit 2 for participants randomized to both AKL-T03 ( < 0.001) and AKL-T09 ( = 0.024). These respective mean improvements were +6.10 and +3.55 (comparison  = 0.21). At Visit 3, 70% of participants randomized to AKL-T03 maintained a clinically meaningful 4+-point increase in SDMT above their baseline, compared with 37% for AKL-T09 ( = 0.038).

Conclusion: This in-home digital intervention resulted in substantial and durable improvements in processing speed. A larger randomized controlled clinical trial is planned.

Trial Registration: This trial is registered on ClinicalTrials.gov under "NCT03569618," https://clinicaltrials.gov/ct2/show/NCT03569618.
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http://dx.doi.org/10.1177/1352458520930371DOI Listing
April 2021

Study protocol: improving cognition in people with progressive multiple sclerosis: a multi-arm, randomized, blinded, sham-controlled trial of cognitive rehabilitation and aerobic exercise (COGEx).

BMC Neurol 2020 May 22;20(1):204. Epub 2020 May 22.

Department of Biostatistics, University of Alabama at Birmingham, Birmingham, USA.

Background: Cognitive dysfunction affects up to 70% of people with progressive MS (PMS). It can exert a deleterious effect on activities of daily living, employment and relationships. Preliminary evidence suggests that performance can improve with cognitive rehabilitation (CR) and aerobic exercise (EX), but existing data are predominantly from people with relapsing-remitting MS without cognitive impairment. There is therefore a need to investigate whether this is also the case in people with progressive forms of the disease who have objectively identified cognitive impairment. It is hypothesized that CR and EX are effective treatments for people with PMS who have cognitive impairment, in particular processing speed (PS) deficits, and that a combination of these two treatments is more effective than each individual treatment given alone. We further hypothesize that improvements in PS will be associated with modifications of functional and/or structural plasticity within specific brain networks/regions involved in PS measured with advanced MRI techniques.

Methods: This study is a multisite, randomized, double-blinded, sham controlled clinical trial of CR and aerobic exercise. Three hundred and sixty subjects from 11 sites will be randomly assigned into one of four groups: CR plus aerobic exercise; CR plus sham exercise; CR sham plus aerobic exercise and CR sham plus sham exercise. Subjects will participate in the assigned treatments for 12 weeks, twice a week. All subjects will have a cognitive and physical assessment at baseline, 12 weeks and 24 weeks. In an embedded sub-study, approximately 30% of subjects will undergo structural and functional MRI to investigate the neural mechanisms underlying the behavioral response. The primary outcome is the Symbol Digit Modalities Test (SDMT) measuring PS. Secondary outcome measures include: indices of verbal and non-verbal memory, depression, walking speed and a dual cognitive-motor task and MRI.

Discussion: The study is being undertaken in 6 countries (11 centres) in multiple languages (English, Italian, Danish, Dutch); with testing material validated and standardized in these languages. The rationale for this approach is to obtain a robustly powered sample size and to demonstrate that these two interventions can be given effectively in multiple countries and in different languages.

Trial Registration: The trial was registered on September 20th 2018 at www.clinicaltrials.gov having identifier NCT03679468. Registration was performed before recruitment was initiated.
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http://dx.doi.org/10.1186/s12883-020-01772-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245035PMC
May 2020

Probability of major depression diagnostic classification based on the SCID, CIDI and MINI diagnostic interviews controlling for Hospital Anxiety and Depression Scale - Depression subscale scores: An individual participant data meta-analysis of 73 primary studies.

J Psychosom Res 2020 02 13;129:109892. Epub 2019 Dec 13.

Psychotherapie und Psychsomatik, kbo Lech-Mangfall-Klinik für Psychatrie, Garmisch-Partenkirchen, Bayern, Germany.

Objective: Two previous individual participant data meta-analyses (IPDMAs) found that different diagnostic interviews classify different proportions of people as having major depression overall or by symptom levels. We compared the odds of major depression classification across diagnostic interviews among studies that administered the Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D).

Methods: Data accrued for an IPDMA on HADS-D diagnostic accuracy were analysed. We fit binomial generalized linear mixed models to compare odds of major depression classification for the Structured Clinical Interview for DSM (SCID), Composite International Diagnostic Interview (CIDI), and Mini International Neuropsychiatric Interview (MINI), controlling for HADS-D scores and participant characteristics with and without an interaction term between interview and HADS-D scores.

Results: There were 15,856 participants (1942 [12%] with major depression) from 73 studies, including 15,335 (97%) non-psychiatric medical patients, 164 (1%) partners of medical patients, and 357 (2%) healthy adults. The MINI (27 studies, 7345 participants, 1066 major depression cases) classified participants as having major depression more often than the CIDI (10 studies, 3023 participants, 269 cases) (adjusted odds ratio [aOR] = 1.70 (0.84, 3.43)) and the semi-structured SCID (36 studies, 5488 participants, 607 cases) (aOR = 1.52 (1.01, 2.30)). The odds ratio for major depression classification with the CIDI was less likely to increase as HADS-D scores increased than for the SCID (interaction aOR = 0.92 (0.88, 0.96)).

Conclusion: Compared to the SCID, the MINI may diagnose more participants as having major depression, and the CIDI may be less responsive to symptom severity.
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http://dx.doi.org/10.1016/j.jpsychores.2019.109892DOI Listing
February 2020

Cognitive mediated eye movements during the SDMT reveal the challenges with processing speed faced by people with MS.

BMC Neurol 2019 Dec 26;19(1):340. Epub 2019 Dec 26.

Department of Psychiatry, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada.

Background: The Symbol Digit Modalities Test (SDMT) is regarded as the cognitive test of choice for people with MS (pwMS). While deficits are linked to impaired processing speed, the mechanisms by which they arise are unclear. Cognitive-mediated eye movements offer one putative explanation. The objective of this study was to determine the association between eye movements and performance on the SDMT.

Methods: Thirty-three people with confirmed MS and 25 matched healthy control subjects (HC) were administered the oral SDMT while eye movements were recorded.

Results: Mean SDMT scores were significantly lower in pwMS (p < 0.038). Shorter mean saccade distance in the key area (p = 0.007), more visits to the key area per response (p = 0.014), and more total number of fixations in the test area (p = 0.045) differentiated pwMS from HCs. A hierarchical regression analysis revealed that the number of visits to the key area per response (p < 0.001; ΔR = 0.549) and total number of fixations in the test area (p < 0.001; ΔR = 0.782) were the most robust predictors of SDMT scores.

Conclusion: Cognitive-mediated eye movements help elucidate the processing speed challenges confronted by people with MS. Mechanistic insights such as these can potentially help inform new cognitive rehabilitation strategies.
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http://dx.doi.org/10.1186/s12883-019-1543-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933713PMC
December 2019

Computerized neuropsychological assessment devices in multiple sclerosis: A systematic review.

Mult Scler 2019 12 22;25(14):1848-1869. Epub 2019 Oct 22.

Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA/Jacobs Neurological Institute, Buffalo, NY, USA.

Background: The proliferation of computerized neuropsychological assessment devices (CNADs) for screening and monitoring cognitive impairment is increasing exponentially. Previous reviews of computerized tests for multiple sclerosis (MS) were primarily qualitative and did not rigorously compare CNADs on psychometric properties.

Objective: We aimed to systematically review the literature on the use of CNADs in MS and identify test batteries and single tests with good evidence for reliability and validity.

Method: A search of four major online databases was conducted for publications related to computerized testing and MS. Test-retest reliability and validity coefficients and effect sizes were recorded for each CNAD test, along with administration characteristics.

Results: We identified 11 batteries and 33 individual tests from 120 peer-reviewed articles meeting the inclusion criteria. CNADs with the strongest psychometric support include the CogState Brief Battery, Cognitive Drug Research Battery, NeuroTrax, CNS-Vital Signs, and computer-based administrations of the Symbol Digit Modalities Test.

Conclusion: We identified several CNADs that are valid to screen for MS-related cognitive impairment, or to supplement full, conventional neuropsychological assessment. The necessity of testing with a technician, and in a controlled clinic/laboratory environment, remains uncertain.
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http://dx.doi.org/10.1177/1352458519879094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875828PMC
December 2019

Computerized neuropsychological assessment devices in multiple sclerosis: A systematic review.

Mult Scler 2019 12 22;25(14):1848-1869. Epub 2019 Oct 22.

Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA/Jacobs Neurological Institute, Buffalo, NY, USA.

Background: The proliferation of computerized neuropsychological assessment devices (CNADs) for screening and monitoring cognitive impairment is increasing exponentially. Previous reviews of computerized tests for multiple sclerosis (MS) were primarily qualitative and did not rigorously compare CNADs on psychometric properties.

Objective: We aimed to systematically review the literature on the use of CNADs in MS and identify test batteries and single tests with good evidence for reliability and validity.

Method: A search of four major online databases was conducted for publications related to computerized testing and MS. Test-retest reliability and validity coefficients and effect sizes were recorded for each CNAD test, along with administration characteristics.

Results: We identified 11 batteries and 33 individual tests from 120 peer-reviewed articles meeting the inclusion criteria. CNADs with the strongest psychometric support include the CogState Brief Battery, Cognitive Drug Research Battery, NeuroTrax, CNS-Vital Signs, and computer-based administrations of the Symbol Digit Modalities Test.

Conclusion: We identified several CNADs that are valid to screen for MS-related cognitive impairment, or to supplement full, conventional neuropsychological assessment. The necessity of testing with a technician, and in a controlled clinic/laboratory environment, remains uncertain.
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http://dx.doi.org/10.1177/1352458519879094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875828PMC
December 2019

Coming off cannabis: a cognitive and magnetic resonance imaging study in patients with multiple sclerosis.

Brain 2019 09;142(9):2800-2812

Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.

Cognitive dysfunction affects 40-80% of patients with multiple sclerosis. Smoking cannabis may add to these deficits. It is unclear whether coming off cannabis results in cognitive improvement. To address this question, 40 patients with multiple sclerosis who started using cannabis after the onset of multiple sclerosis and who used it for at least 4 days a week over many years were divided by odd-even number selection into two groups: cannabis continuation and cannabis withdrawal. Assessments took place at baseline and after 28 days and included serial versions of the Brief Repeatable Neuropsychological Battery for multiple sclerosis containing tests of verbal and visual memory, processing speed and executive function; structural and functional MRI, the latter entailing a compatible version of the Symbol Digit Modalities Test; urine for cannabinoid metabolites to detect compliance with abstinence. Only those participants deemed globally impaired at baseline (failure on at least two cognitive domains) were enrolled. The results revealed that the two groups were well matched demographically and neurologically. One subject was removed from the withdrawal group because of failed abstinence. Urine analysis revealed the cannabinoid consumed was predominantly tetrahydrocannabinol (THC). There were no baseline between group cognitive differences, but by Day 28 the withdrawal group performed significantly better on every cognitive index (P < 0.0001 for all). Significant within group differences were present for every test over time, but only in the abstinent group (P < 0.0001 for all tests). There were no between group baseline or Day 28 differences in structural MRI indices (global atrophy, total T1 and T2 lesion volume). At index assessment the two groups had a similar performance on the functional MRI-compatible Symbol Digit Modalities Test and there were no group differences in brain activation. However, by Day 28, the withdrawal group completed more trials correctly (P < 0.012) and had a faster reaction time (P < 0.002), associated with significantly increased activation in brain regions known to be associated with performance of the test (bilateral inferior frontal gyri, caudate and declive/cerebellum, P < 0.001 for all regions). These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed and executive function after 28 days of drug abstinence. The absence of similar improvements in a matched multiple sclerosis group that remained on cannabis shows that beneficial cognitive change after stopping cannabis is not solely attributable to the effects of practice.
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http://dx.doi.org/10.1093/brain/awz213DOI Listing
September 2019

Wordsworth, Bellow, and understanding multiple sclerosis.

Lancet Neurol 2021 03 14;20(3):177-178. Epub 2019 Jun 14.

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http://dx.doi.org/10.1016/S1474-4422(19)30222-4DOI Listing
March 2021

Why Sex Matters: A Cognitive Study of People With Multiple Sclerosis.

Cogn Behav Neurol 2019 03;32(1):39-45

Department of Psychiatry.

Background: Cognitive dysfunction affects 40% to 70% of people with multiple sclerosis (MS). Sex may influence a person's cognition. Although a few studies have reported greater cognitive deficits in men than women, it is unclear whether specific cognitive domains are more vulnerable than others to the effects of sex or whether cognition is influenced by neurologic or psychiatric variables.

Methods: A chart review was undertaken of 408 people with MS referred to neuropsychological services. Demographic and MS-related variables were extracted from the patients' records. We used the Minimal Assessment of Cognitive Functioning in Multiple Sclerosis for the neuropsychological assessment. Raw test scores were converted to z scores using Canadian regression-based normative means. A general linear model was conducted on the adjusted scores, controlling for age; years of education; disease course; illness duration; and disability, anxiety, and depression scores.

Results: Men were more likely than women to have primary progressive MS (χ=6.415, P=0.011). There were no other sex differences with respect to demographic, neurologic, or psychiatric data. Women performed significantly better than men on the California Verbal Learning Test-Second Edition Total Learning index (F=7.846, P=0.006).

Conclusions: An analysis of a large, consecutive sample of people with MS demonstrated that sex, independent of demographic, neurologic, or psychiatric factors, is an important determinant in cognitive impairment, with men being more impaired than women on tests of verbal learning and memory.
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http://dx.doi.org/10.1097/WNN.0000000000000188DOI Listing
March 2019

The cognitive effects of anxiety and depression in immune-mediated inflammatory diseases.

Neurology 2019 Jan 11. Epub 2019 Jan 11.

From the Department of Psychiatry (A.F.), Sunnybrook and Women's College Health Science Centre, Toronto, Canada; Inserm U 862 and Department of Neurology (B.B.), University of Bordeaux and CHU of Bordeaux, France; and Department of Neurology (J.S.), Icahn School of Medicine at Mount Sinai, New York, NY.

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http://dx.doi.org/10.1212/WNL.0000000000006840DOI Listing
January 2019

A Videogame-Based Digital Therapeutic to Improve Processing Speed in People with Multiple Sclerosis: A Feasibility Study.

Neurol Ther 2019 Jun 30;8(1):135-145. Epub 2018 Nov 30.

Department of Neurology, Weill Institute for the Neurosciences, University of California, San Francisco, USA.

Introduction: Self-administered in-home digital therapeutics could expand access to cognitive rehabilitation for individuals with multiple sclerosis (MS), over half of whom experience cognitive impairment (CI). However, feasibility in an MS population must be clarified. This study was conducted to assess the feasibility of deploying a videogame-like digital treatment for CI in MS, including initial efficacy and barriers to adherence.

Methods: In this pilot study, 21 participants with MS completed an in-clinic baseline neurological evaluation. Cognitive tests included paper-and-pencil Brief International Cognitive Assessment for Multiple Sclerosis [BICAMS-which included the Symbol Digit Modalities Test (SDMT)] and other unsupervised tablet-based tests (including Match: an unsupervised test of executive functions and processing speed, developed at UCSF; and the Cogstate MS Battery). Participants then completed an in-home, tablet-based, videogame-like investigational digital treatment (Project: EVO™) for 25 min daily, 5 days weekly, for 4 weeks. This was followed by a repeat in-clinic evaluation.

Results: Of the 21 participants (mean [standard deviation, SD] age 53.8 [11.6] years, median Expanded Disability Status Scale (EDSS) 2.5 [SD 2.0, IQR [2-3.5]]) enrolled to use the digital therapeutic at home (mean [SD] SDMT z score: - 0.21 [1.16]), 18 completed the study, during which they completed an average of 19.7 days (median [SD]: 20.5 [8.4]). Overall, 78% of these 18 participants completed 75% of prescribed days (i.e., at least 15), and 50% completed all 20 days or more. Over the 4-week period, scores of processing speed improved significantly (based on one-sided t test), including SDMT (p = 0.003) and Match (p = 0.006). The Cogstate DET test (psychomotor function) also increased (p = 0.006). Mean increase in SDMT was 3.6 points. Male sex, not being employed, and higher baseline anxiety all were significantly associated with greater improvement in SDMT over the 4-week period. Interestingly, lower baseline cognitive scores were associated with greater number of sessions completed (e.g., SDMT: p = 0.003, R = 0.44). Adjusting for employment, a proxy for time available, did not significantly improve the model fit.

Discussion: Deploying an in-home digital tool to improve processing speed in MS is feasible, and shows preliminary efficacy. A larger, randomized controlled clinical trial is ongoing.
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http://dx.doi.org/10.1007/s40120-018-0121-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534643PMC
June 2019

Neurostimulation for Functional Neurological Disorder: Evaluating Longitudinal Neurophysiology.

Mov Disord Clin Pract 2018 Sep-Oct;5(5):561-563. Epub 2018 Oct 1.

The Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Division of Neurology University of Toronto Toronto Canada.

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http://dx.doi.org/10.1002/mdc3.12651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207130PMC
October 2018

Recommendations for cognitive screening and management in multiple sclerosis care.

Mult Scler 2018 11 10;24(13):1665-1680. Epub 2018 Oct 10.

Department of Physical Medicine and Rehabilitation and Department of Neurology, Rutgers New Jersey Medical School, Newark, NJ, USA.

Purpose: To promote understanding of cognitive impairment in multiple sclerosis (MS), recommend optimal screening, monitoring, and treatment strategies, and address barriers to optimal management.

Methods: The National MS Society ("Society") convened experts in cognitive dysfunction (clinicians, researchers, and lay people with MS) to review the published literature, reach consensus on optimal strategies for screening, monitoring, and treating cognitive changes, and propose strategies to address barriers to optimal care.

Recommendations: Based on current evidence, the Society makes the following recommendations, endorsed by the Consortium of Multiple Sclerosis Centers and the International Multiple Sclerosis Cognition Society: Increased professional and patient awareness/education about the prevalence, impact, and appropriate management of cognitive symptoms. For adults and children (8+ years of age) with clinical or magnetic resonance imaging (MRI) evidence of neurologic damage consistent with MS: As a minimum, early baseline screening with the Symbol Digit Modalities Test (SDMT) or similarly validated test, when the patient is clinically stable; Annual re-assessment with the same instrument, or more often as needed to (1) detect acute disease activity; (2) assess for treatment effects (e.g. starting/changing a disease-modifying therapy) or for relapse recovery; (3) evaluate progression of cognitive impairment; and/or (4) screen for new-onset cognitive problems. For adults (18+ years): more comprehensive assessment for anyone who tests positive on initial cognitive screening or demonstrates significant cognitive decline, especially if there are concerns about comorbidities or the individual is applying for disability due to cognitive impairment. For children (<18 years): neuropsychological evaluation for any unexplained change in school functioning (academic or behavioral). Remedial interventions/accommodations for adults and children to improve functioning at home, work, or school.
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http://dx.doi.org/10.1177/1352458518803785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238181PMC
November 2018

The hippocampus and behaviour in multiple sclerosis.

Lancet Neurol 2018 10 18;17(10):837-839. Epub 2018 Sep 18.

Department of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON M5R 3B6, Canada. Electronic address:

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http://dx.doi.org/10.1016/S1474-4422(18)30324-7DOI Listing
October 2018

Developing a Computerized Brief Cognitive Screening Battery for Botswana: A Feasibility Study.

Arch Clin Neuropsychol 2019 Jul;34(5):682-689

Sunnybrook Health Sciences Center, Department of Psychiatry, 2075 Bayview Avenue, Toronto, ON, Canada.

Objective: To determine the feasibility of using a brief computerized battery for assessing cognition in citizens of Botswana.

Method: A group of 134 healthy subjects were administered a brief computerized battery of tests (Stroop, Symbol Digit Modalities Test (c-SDMT), and 2 and 4 second versions of the Paced Visual Serial Addition Test (PVSAT)). Half the subjects were tested in English and the other half in Setswana.

Results: All subjects completed the 20 min battery. Participants administered the tests in English had more years of education (p < .001) and were more likely to be male (p = .024) than those administered the tests in Setswana. There were no significant cognitive differences between the English and Setswana groups. Predictors of cognition were education (c-SDMT, PVSAT 4 and 2 second versions), age (Stroop, c-SDMT), and sex (c-SDMT), with females performing better than males on the latter. Language was not associated with performance on any of the cognitive tests and there were no significant interactions between language and any of the demographic predictors of cognition.

Conclusions: The results demonstrate that our brief computerized approach is feasible with similar findings obtained for both language groups. Two further phases to the development of the Botswana version of the brief computerized battery can now proceed. The first is to obtain normative data from a larger sample representative of Botswana society in general. The second will be to validate the cognitive measures in a sample of people with acquired brain injury using the normative data to determine thresholds for impairment.
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http://dx.doi.org/10.1093/arclin/acy071DOI Listing
July 2019

Taking the tester out of the SDMT: A proof of concept fully automated approach to assessing processing speed in people with MS.

Mult Scler 2019 10 6;25(11):1506-1513. Epub 2018 Aug 6.

Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada/Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Background: One factor hindering the widespread use of cognitive testing for people with multiple sclerosis (pwMS) is the need for a tester to administer tests.

Objective: To undertake a proof of concept study assessing the feasibility of a fully automated speech recognition version of the Symbol Digit Modalities Test (auto-SDMT) in detecting abnormalities in processing speed in pwMS.

Methods: A sample of 50 pwMS and 32 matched healthy control (HC) subjects was tested with the auto-SDMT and the Brief International Cognitive Assessment for MS (BICAMS).

Results: The percentages of MS participants impaired on the auto-SDMT and the traditional oral SDMT were 34% and 32%, respectively. Excellent convergent validity was found between the two tests (MS:  = -0.806,  < 0.001 and HC:  = -0.629,  < 0.001). The auto-SDMT had a similar sensitivity and specificity to the traditional oral SDMT in predicting overall impairment on the BICAMS.

Conclusion: The auto-SDMT is a sensitive measure for detecting processing speed deficits in pwMS. The test, the first entirely computer administrated oral response version of the SDMT, uses speech recognition technology, thereby eliminating the need for a human tester. Replication of the results is required in a larger representative sample of pwMS.
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http://dx.doi.org/10.1177/1352458518792772DOI Listing
October 2019

Conversion Disorder.

Continuum (Minneap Minn) 2018 06;24(3, BEHAVIORAL NEUROLOGY AND PSYCHIATRY):861-872

Purpose Of Review: This article provides a broad overview of conversion disorder, encompassing diagnostic criteria, epidemiology, etiologic theories, functional neuroimaging findings, outcome data, prognostic indicators, and treatment.

Recent Findings: Two important changes have been made to the recent Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria: the criteria that conversion symptoms must be shown to be involuntary and occurring as the consequence of a recent stressor have been dropped. Outcome studies show that the rate of misdiagnosis has declined precipitously since the 1970s and is now around 4%. Functional neuroimaging has revealed a fairly consistent pattern of hypoactivation in brain regions linked to the specific conversion symptom, accompanied by ancillary activations in limbic, paralimbic, and basal ganglia structures. Cognitive-behavioral therapy looks promising as the psychological treatment of choice, although more definitive data are still awaited, while preliminary evidence indicates that repetitive transcranial magnetic stimulation could prove beneficial as well.

Summary: Symptoms of conversion are common in neurologic and psychiatric settings, affecting up to 20% of patients. The full syndrome of conversion disorder, while less prevalent, is associated with a guarded prognosis and a troubled psychosocial outcome. Much remains uncertain with respect to etiology, although advances in neuroscience and technology are providing reproducible findings and new insights. Given the confidence with which the diagnosis can be made, treatment should not be delayed, as symptom longevity can influence outcome.
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http://dx.doi.org/10.1212/CON.0000000000000601DOI Listing
June 2018

Symptoms of PTSD in Frontline Journalists: A Retrospective Examination of 18 Years of War and Conflict.

Can J Psychiatry 2018 09 23;63(9):629-635. Epub 2018 May 23.

1 Department of Psychiatry, Sunnybrook Health Sciences Center, Toronto, Ontario.

Objective: The objective of the current study was to determine the frequency and severity of symptoms of posttraumatic stress disorder (PTSD) in journalists covering conflict.

Methods: PTSD data (Impact of Event Scale-Revised) collected over an 18-year period from 684 conflict journalists were analyzed retrospectively for frequency and severity of reexperiencing, avoidance, and arousal symptoms. Conflicts covered were civil wars in the Balkans ( n = 140 journalists), 9/11 attack in New York City ( n = 46), Iraq war ( n = 84), Mexico drug wars ( n = 104), civil war in Syria ( n = 59), Kenya election violence/Al-Shabab terror ( n = 57), state-sanctioned media intimidation in Iran ( n = 114), and the current migration crisis in Europe ( n = 80).

Results: The mean age of the sample was 38.59 (SD = 8.35) years, 461 (67%) journalists were men, and the mean duration of conflict work was 13.42 (SD = 7.74) years. The 5 most frequently endorsed symptoms were in the reexperiencing/intrusion category. Mean intrusion (1.31, SD = 0.97), avoidance (1.08, SD = 0.89), and arousal (1.07, SD = 0.96) scores for the entire sample were in the mild range. Being female and less educated independently predicted PTSD symptoms.

Conclusions: PTSD phenomenology in a group of conflict journalists with well over a decade of frontline experience is dominated by reexperiencing symptoms. While symptom severity is for the most part mild, group means can obscure those individuals with significantly more severe difficulties.
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http://dx.doi.org/10.1177/0706743718777396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109887PMC
September 2018

The link between depression and performance on the Symbol Digit Modalities Test: Mechanisms and clinical significance.

Mult Scler 2019 01 12;25(1):118-121. Epub 2018 Apr 12.

Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada.

Objective: To determine the mechanism and clinical significance of depression-related differences in performance on the Symbol Digit Modalities Test (SDMT).

Methods: The influence of depression on two versions of a computerized SDMT (i.e. fixed versus variable code) was assessed. Both versions involve processing speed, but the fixed c-SDMT also encompasses incidental visual memory.

Results: Depression was associated with a 19.06% slowing on the variable ( p = 0.002) and an 8.10% slowing on the fixed ( p = 0.219) c-SDMT.

Conclusion: Depression-associated differences in performance on the SDMT appear linked more to a reduction in processing speed than a decline in incidental visual memory and exceed the 10% threshold considered clinically significant.
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http://dx.doi.org/10.1177/1352458518770086DOI Listing
January 2019
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