scholarly journals Transdiagnostic neurocognitive endophenotypes in major psychiatric illness

Author(s):  
Bharath Holla ◽  
Pavithra Dayal ◽  
Aswathy Das ◽  
Mahashweta Bhattacharya ◽  
V Manjula ◽  
...  

AbstractWe aimed to characterize potential transdiagnostic neurocognitive endophenotypes in a large cohort of multiplex families affected with two or more individuals having a major psychiatric illness(MPI) i.e., schizophrenia(SCZ), bipolar disorder(BPAD), substance use disorders(SUD) and obsessive-compulsive disorder(OCD). We recruited 640 individuals that included 256 affected individuals with MPI, 227 of their unaffected first-degree relatives(FDR) and 157 population healthy-controls(PHC). Neurocognitive battery included assessments of executive function, working memory, social cognition, verbal learning and recall. Linear mixed effects models were applied to the neurocognitive components to examine their transdiagnostic and endophenotype status after accounting for demographic and family variables. We also examined the relationship of cognitive domains with diagnosis-specific Family History Density score(FHD).The deficits in cognitive flexibility, working memory and social cognition were transdiagnostic; processing speed was impaired in SCZ and BPAD groups while verbal learning and recall in SCZ, BPAD and SUD groups. These deficits with the exception of social cognition, worsened with age and parental education had protective effect. The unaffected FDRs had deficits in all the domains except processing speed in comparison to PHC; social cognition deficits were comparable to affected individuals. The diagnosis-specific FHD analysis showed that deficits in cognitive flexibility, working memory and social cognition were endophenotypes across disorders.Evaluation of neurocognitive functions across multiple affected individuals in a large multiplex family-based cross-disorder cohort, has the potential to elucidate transdiagnostic as well as endophenotype vulnerabilities to psychiatric illness. This study adds to the emerging conceptualization of psychiatric illness as a combination of both diagnosis-specific and transdiagnostic markers.

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256228
Author(s):  
Saleh M. H. Mohamed ◽  
Marah Butzbach ◽  
Anselm B. M Fuermaier ◽  
Matthias Weisbrod ◽  
Steffen Aschenbrenner ◽  
...  

Background Many clinical studies reported deficits in basic and complex cognitive functions in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the extent in which deficits in basic functions (i.e., processing speed and distractibility) contribute to complex cognitive impairments (i.e., working memory, planning, cognitive flexibility, memory functions) in adults with ADHD is not well-studied. So far, literature show only one study, revealing that basic functions explain 27–74% of executive dysfunctions. Yet, the authors reported that findings could be affected by the selection of neuropsychological tests. The goal of the present research is to replicate such a finding using a different sample and a different set of neuropsychological tests. Methods Forty-eight adult patients with ADHD were compared with 48 healthy controls in basic cognitive functions, namely processing speed and distractibility and more complex cognitive functions, namely selective attention, cognitive flexibility, planning, working memory, verbal fluency, and verbal memory. Basic and complex cognitive functions were assessed using the Vigilance and Sustained Attention, Selective Attention, N-Back, Tower of London, Trail Making Test, Word Fluency, and Verbal Learning and Memory. Results and conclusion Logistic regression analyses showed that impairments in complex cognitive functions explained 25% of the variance in ADHD diagnosis. The explained variance dropped from 25% to 9% after considering basic functions of processing speed and distractibility. This 64% reduction highlights the importance of basic functions for impairments in complex functions in patients with ADHD.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii431-iii431
Author(s):  
Lisa Kahalley ◽  
Rachel Peterson ◽  
M Douglas Ris ◽  
Laura Janzen ◽  
M Fatih Okcu ◽  
...  

Abstract PURPOSE By reducing dose to normal brain tissue, proton radiotherapy (PRT) may lessen neurocognitive risk traditionally associated with photon radiotherapy (XRT). We examined change in neurocognitive scores over time in pediatric medulloblastoma patients treated with PRT versus XRT. METHODS Neurocognitive scores from 79 patients (37 PRT, 42 XRT) were examined. Patients were treated between 2007–2018 on the same treatment protocols that differed only by craniospinal modality (PRT versus XRT). Change in scores over time since diagnosis were compared between groups. RESULTS Groups were similar on most demographic/clinical variables: sex (67.1% male), age at diagnosis (mean 8.6 years), CSI dose (median 23.4 Gy), length of follow-up (mean 4.3 years), and parental education (mean 14.3 years). Boost dose (p<0.001) and margin (p=0.001) differed between groups. Adjusting for covariates, the PRT group exhibited superior outcomes in global IQ, perceptual reasoning, and working memory versus the XRT group (all p<0.05). The XRT group exhibited significant decline in global IQ, working memory, and processing speed (all p<0.05). The PRT group exhibited stable scores in all domains except processing speed (p=0.003). Posterior fossa syndrome imparted risk independent of modality. CONCLUSION This is the first study comparing neurocognitive trajectories between pediatric patients treated for medulloblastoma with PRT versus XRT on comparable, contemporary protocols. PRT was associated with more favorable neurocognitive outcomes in most domains compared to XRT, although processing speed emerged as vulnerable in both groups. This is the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.


2015 ◽  
Vol 100 (9) ◽  
pp. 838-844 ◽  
Author(s):  
Dag Sulheim ◽  
Even Fagermoen ◽  
Øyvind Stople Sivertsen ◽  
Anette Winger ◽  
Vegard Bruun Wyller ◽  
...  

ObjectiveTo compare cognitive function in adolescents with chronic fatigue with cognitive function in healthy controls (HC).Study designCross-sectional study.SettingPaediatric department at Oslo University Hospital, Norway.Participants120 adolescents with chronic fatigue (average age 15.4 years; range 12–18) and 39 HC (average age 15.2 years; range 12–18).MethodsThe adolescents completed a neurocognitive test battery measuring processing speed, working memory, cognitive inhibition, cognitive flexibility, verbal learning and verbal memory, and questionnaires addressing demographic data, depression symptoms, anxiety traits, fatigue and sleep problems. Parents completed the Behaviour Rating Inventory of Executive Function (BRIEF), which measures the everyday executive functions of children.ResultsAdolescents with chronic fatigue had impaired cognitive function compared to HC regarding processing speed (mean difference 3.3, 95% CI 1.1 to 5.5, p=0.003), working memory (−2.4, −3.7 to −1.1, p<0.001), cognitive inhibition response time (6.2, 0.8 to 11.7, p=0.025) and verbal learning (−1.7, −3.2 to −0.3, p=0.022). The BRIEF results indicated that everyday executive functions were significantly worse in the chronic fatigue group compared to the HC (11.2, 8.2 to 14.3, p<0.001). Group differences remained largely unaffected when adjusted for symptoms of depression, anxiety traits and sleep problems.ConclusionsAdolescents with chronic fatigue had impaired cognitive function of clinical relevance, measured by objective cognitive tests, in comparison to HC. Working memory and processing speed may represent core difficulties.


2014 ◽  
Vol 45 (1) ◽  
pp. 109-120 ◽  
Author(s):  
H. Karbasforoushan ◽  
B. Duffy ◽  
J. U. Blackford ◽  
N. D. Woodward

BackgroundProcessing speed predicts functional outcome and is a potential endophenotype for schizophrenia. Establishing the neural basis of processing speed impairment may inform the treatment and etiology of schizophrenia. Neuroimaging investigations in healthy subjects have linked processing speed to brain anatomical connectivity. However, the relationship between processing speed impairment and white matter (WM) integrity in schizophrenia is unclear.MethodIndividuals with schizophrenia and healthy subjects underwent diffusion tensor imaging (DTI) and completed a brief neuropsychological assessment that included measures of processing speed, verbal learning, working memory and executive functioning. Group differences in WM integrity, inferred from fractional anisotropy (FA), were examined throughout the brain and the hypothesis that processing speed impairment in schizophrenia is mediated by diminished WM integrity was tested.ResultsWM integrity of the corpus callosum, cingulum, superior and inferior frontal gyri, and precuneus was reduced in schizophrenia. Average FA in these regions mediated group differences in processing speed but not in other cognitive domains. Diminished WM integrity in schizophrenia was accounted for, in large part, by individual differences in processing speed.ConclusionsCognitive impairment in schizophrenia was mediated by reduced WM integrity. This relationship was strongest for processing speed because deficits in working memory, verbal learning and executive functioning were not mediated by WM integrity. Larger sample sizes may be required to detect more subtle mediation effects in these domains. Interventions that preserve WM integrity or ameliorate WM disruption may enhance processing speed and functional outcome in schizophrenia.


2011 ◽  
Vol 42 (4) ◽  
pp. 705-716 ◽  
Author(s):  
J. H. Meijer ◽  
N. Dekker ◽  
M. W. Koeter ◽  
P. J. Quee ◽  
N. J. M. van Beveren ◽  
...  

BackgroundThe relationship between cannabis use and cognitive functioning in patients with psychosis has yielded contradictory findings. In individuals at genetic high risk for psychosis, information is sparse. The aim of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in patients with psychosis and their unaffected siblings.MethodWe conducted a cross-sectional study in 956 patients with non-affective psychosis, 953 unaffected siblings, and 554 control subjects. Participants completed a cognitive test battery including assessments of verbal learning, set shifting, sustained attention, processing speed, working memory, acquired knowledge, reasoning and problem solving and social cognition. Cannabis use was assessed by urinalysis and by the Composite International Diagnostic Interview. Using random-effect regression models the main effects of cannabis (recency and frequency) and the interaction with status (patient, sibling, control) on cognitive functioning were assessed.ResultsCurrent cannabis use was associated with poorer performance on immediate verbal learning, processing speed and working memory (Cohen's d −0.20 to −0.33, p<0.005). Lifetime cannabis use was associated with better performance on acquired knowledge, facial affect recognition and face identity recognition (Cohen's d+0.17 to +0.33, p<0.005). There was no significant interaction between cannabis and status on cognitive functioning.ConclusionsLifetime cannabis-using individuals might constitute a subgroup with a higher cognitive potential. The residual effects of cannabis may impair short-term memory and processing speed.


2021 ◽  
Vol 13 ◽  
Author(s):  
Priska Zuber ◽  
Emanuel Geiter ◽  
Dominique J.-F. de Quervain ◽  
Stefano Magon

Background: Various working memory (WM) trainings have been tested, but differences in experimental designs, the lack of theoretical background, and the need of identifying task-related processes such as filtering efficiency limit conclusions about their comparative efficacy.Objectives: In this study, we compared the efficacy of a model-based WM training with (MB+) and without (MB) distractor inhibition on improving WM capacity to a dual n-back and active control condition.Methods: This randomized clinical trial included 123 healthy elderly adults (78 women, 45 men; aged 64.1 ± 8.3 years). All groups underwent 12 40-min training sessions over 3 weeks and four cognitive testing sessions. The first two sessions served as double baseline to account for practice effects. Primary outcome was WM capacity post-training measured by complex span tasks. Near and far transfer was assessed by simple span, n-back, visuospatial and verbal learning, processing speed, and reasoning tasks.Results: Due to preliminary termination (COVID-19), 93 subjects completed the post-training and 60 subjects the follow-up session. On a whole group level, practice effects occurred from prebaseline to baseline in WM capacity (b = 4.85, t(103) = 4.01, p &lt; 0.001, r = 0.37). Linear mixed-effects models revealed a difference in WM capacity post-training between MB+ and MB (b = −9.62, t(82) = −2.52, p = 0.014, r = 0.27) and a trend difference between MB+ and dual n-back (b = −7.59, t(82) = −1.87, p = 0.065, r = 0.20) and control training (b = −7.08, t(82) = −1.86, p = 0.067, r = 0.20). Univariate analyses showed an increase between pre- and post-training for WM capacity within MB+ (t(22) = −3.34, p &lt; 0.05) only. There was no difference between groups pre- and post-training regarding near and far transfer. Univariate analyses showed improved visuospatial learning within MB+ (t(21) = −3.8, p &lt; 0.05), improved processing speed (t(23) = 2.19, p&lt; 0.05) and n-back performance (t(23) = 2.12, p &lt; 0.05) in MB, and improved n-back performance (t(25) = 3.83, p &lt; 0.001) in the dual n-back training.Interpretation: A model-based WM training including filtering efficacy may be a promising approach to increase WM capacity and needs further investigation in randomized controlled studies.


2020 ◽  
Vol 38 (5) ◽  
pp. 454-461 ◽  
Author(s):  
Lisa S. Kahalley ◽  
Rachel Peterson ◽  
M. Douglas Ris ◽  
Laura Janzen ◽  
M. Fatih Okcu ◽  
...  

PURPOSE Proton radiotherapy (PRT) may lessen the neuropsychological risk traditionally associated with cranial radiotherapy for the treatment of pediatric brain tumors by reducing the dose to normal tissue compared with that of photon radiotherapy (XRT). We examined the change in intellectual scores over time in patients with pediatric medulloblastoma treated with craniospinal PRT versus XRT. METHODS Intelligence test scores were obtained for a sample of pediatric patients treated between 2007 and 2018 on the same medulloblastoma protocols that differed only in radiotherapy modality (PRT v XRT). Growth curve analyses compared change in scores over time since diagnosis between groups. RESULTS Longitudinal intelligence data from 79 patients (37 PRT, 42 XRT) were examined. Groups were similar on most demographic/clinical variables, including sex (67.1% male), age at diagnosis (mean, 8.6 years), craniospinal irradiation dose (median, 23.4 Gy), length of follow-up (mean, 4.3 years), and parental education (mean, 14.3 years). Boost dose ( P < .001) and boost margin ( P = .001) differed between groups. Adjusting for covariates, the PRT group exhibited superior long-term outcomes in global intelligence quotient (IQ), perceptual reasoning, and working memory compared with the XRT group (all P < .05). The XRT group exhibited a significant decline in global IQ, working memory, and processing speed (all P < .05). The PRT group exhibited stable scores over time in all domains with the exception of processing speed ( P = .003). CONCLUSION To our knowledge, this is the first study to compare intellectual trajectories between pediatric patients treated for medulloblastoma with PRT versus those treated with XRT on comparable, contemporary protocols. PRT was associated with more favorable intellectual outcomes in most domains compared with XRT, although processing speed emerged as a vulnerable domain for both groups. This study provides the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.


Author(s):  
Ana Isabel Rosa-Alcázar ◽  
Ángel Rosa-Alcázar ◽  
Inmaculada C. Martínez-Esparza ◽  
Eric A. Storch ◽  
Pablo J. Olivares-Olivares

This study analyzed response inhibition, cognitive flexibility and working memory in three groups of patients diagnosed with obsessive-compulsive disorder, social anxiety disorder and generalized anxiety disorder, considering some variables that may influence results (nonverbal reasoning, comorbidity, use of pharmacotherapy). Neuropsychological measures were completed using a computerized Wisconsin card sorting test, Stroop color word test, go/no-go task, digits and Corsi. Significant differences were obtained among groups in cognitive flexibility and working memory variables. The obsessive-compulsive disorder (OCD) group showed the worst results. The social anxiety disorder group obtained greater effect sizes in visuospatial memory. However, significant differences between groups in visuospatial memory were no longer present when nonverbal reasoning was controlled. Comorbidity influenced interference in the OCD and generalized anxiety disorder (GAD) groups. In addition, the executive functions were differently influenced by the level of obsessions and anxiety, and the use of pharmacotherapy. Study limitations include a non-random selection of participants, modest sample size and design type (cross-sectional). The OCD group showed the worst results in flexibility cognitive and verbal working memory. Comorbidity, use of pharmacotherapy and level anxiety and obsessions were variables influencing the performance of executive functions.


Author(s):  
Christen M. Holder ◽  
Nicole Shay

This chapter examines the different theoretical conceptualizations of executive functions and how neuroimaging can reveal their neuroanatomical mechanisms. After briefly considering various definitions and descriptions of executive function, it discusses the results of lesion studies that look into specific executive functions; namely, attention, working memory, inhibition, decision-making, planning and organization, processing speed, and cognitive flexibility or shifting. It also evaluates measures that are used to capture the executive functions just cited, along with the advances that have been achieved with the help of neuroimaging studies. On the basis of neuroimaging evidence, the authors show that the right prefrontal cortex, as well as the parietal and temporal lobes, plays an important role in executive function.


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