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Folate and choline are methyl donor nutrients that may play a role in fetal brain development. Animal studies have reported that prenatal folate and choline supplementation are associated with better cognitive outcomes in offspring and that these nutrients may interact and affect brain development. Human studies that have investigated associations between maternal prenatal folate or choline levels and neurodevelopmental outcomes have reported contradictory findings and no human studies have examined the potential interactive effect of folate and choline on children’s neurodevelopment. During the second trimester of pregnancy, maternal red blood cell folate was measured from blood samples and choline intake was estimated using a 24-h dietary recall in 309 women in the APrON cohort. At 3–5 years of age, their children’s neurodevelopment was assessed using the Wechsler Preschool and Primary Scales of Intelligence – Fourth EditionCND, NEPSY-II language and memory subtests, four behavioral executive function tasks, and the Movement Assessment Battery for Children – Second Edition. Adjusted regressions revealed no associations between maternal folate and choline levels during pregnancy and most of the child outcomes. On the Dimensional Change Card Sort, an executive function task, there was an interaction effect; at high levels of choline intake (i.e., 1 SD above the mean; 223.03 mg/day), higher maternal folate status was associated with decreased odds of receiving a passing score (β = −0.44; 95%CI −0.81, −0.06). In conclusion, maternal folate status and choline intake during the second trimester of pregnancy were not associated with children’s intelligence, language, memory, or motor outcomes at 3–4 years of age; however, their interaction may have an influence children’s executive functions.
A paucity of data exists regarding the duration of post-traumatic amnesia (PTA) as a predictor of cognitive functioning among children after traumatic brain injury (TBI). The study aimed to assess the relationship between PTA duration and areas of neurocognitive function among the pediatric population in the sub-acute phase of recovery and rehabilitation.
Methods:
Data were collected from medical files on 103 children aged 5.5–16.5 hospitalized at a pediatric rehabilitation department with a diagnosis of moderate–severe TBI (msTBI) between the years 2004–2019. The Children Orientation and Amnesia Test was used to evaluate PTA duration. Measures of high-order cognitive abilities of attention and executive function were collected using the Test of Everyday Attention–Child version (TEA-Ch).
Results:
Three PTA duration groups were assembled out of a cluster analysis: “Long PTA” (M = 21 days), “Very Long PTA” (M = 47 days), and “Extremely Long PTA” (M = 94 days). Analyses revealed that the “Long PTA” group preformed significantly better than the “Very Long PTA” and “Extremely Long PTA” groups on all TEA-Ch measures, that is, Selective Attention, Attentional Control Switching, and Sustained Attention.
Conclusions:
This study is the first to demonstrate that PTA duration is a useful predictor of high-order cognitive functions among children with msTBI in the sub-acute phase of recovery and rehabilitation. The findings emphasize the importance of using a more sensitive classification of prolonged PTA durations to improve outcome prediction and allocation of resources to those who can benefit most after severe brain injuries.
Little is known about whether brief mindfulness ecological momentary interventions (MEMIs) yield clinically beneficial effects. This gap exists despite the rapid growth of smartphone mindfulness applications. Specifically, no prior brief MEMI has targeted generalized anxiety disorder (GAD). Moreover, although theories propose that MEMIs can boost executive functioning (EF), they have largely gone untested. Thus, this randomized controlled trial (RCT) aimed to address these gaps by assessing the efficacy of a 14-day smartphone MEMI (versus self-monitoring placebo [SMP]).
Method
Participants with GAD were randomly assigned to either condition (68 MEMI and 42 SMP). MEMI participants exercised multiple core mindfulness strategies and were instructed to practice mindfulness continually. Comparatively, SMP participants were prompted to practice self-monitoring and were not taught any mindfulness strategies. All prompts occurred five times a day for 14 consecutive days. Participants completed self-reports and neuropsychological assessments at baseline, posttreatment, and 1-month follow-up (1MFU). Piecewise hierarchical linear modeling analyses were conducted.
Results
MEMI (versus SMP) produced greater pre-1MFU reductions in GAD severity and perseverative cognitions (between-group d = 0.393–0.394) and stronger improvements in trait mindfulness and performance-based inhibition (d = 0.280–0.303). Further, MEMI (versus SMP) led to more considerable pre- to posttreatment reduction in state-level depression and anxiety and more mindfulness gains (d = 0.50–1.13). Overall, between-treatment effects were stronger at pre-1MFU than pre- to posttreatment for trait-level than state-level treatment outcome measures.
Conclusions
Preliminary findings suggest that the beneficial effect of an unguided brief MEMI to target pathological worry, trait mindfulness, and EF is modest yet potentially meaningful. Other theoretical and clinical implications were discussed.
Countering traditional monolingual ideologies that associate multilingual development with various deficiencies, more recent research probes into potential advantages of this developmental experience. The discussion about putative multilingual advantages remains highly controversial and also emotional, as it affects far-reaching policy decisions. The chapter attempts to provide an objective state-of-the-art report, discussing research findings on executive function (control), cognitive reserve, cognitive development, educational attainment, and metalinguistic awareness. It furthermore tries to identify the boundary conditions that help to explain why some studies report positive results while others do not. Current research suggests that the characteristics of the speaker groups sampled, especially in terms of their type of bilingualism and multilingualism (balanced, unbalanced, heritage speakers, etc.), offer important clues for a better understanding of this domain. Moreover, the social prestige associated with the languages studied appears to influence the results considerably. Language users are not deterministic machines, but react to social pressure in intelligent ways.
Alzheimer’s disease (AD) is highly comorbid with idiopathic normal pressure hydrocephalus (iNPH) and may diminish the benefits of shunting; however, findings in this area are mixed. We examined postoperative outcomes, with emphases on cognition and utilization of novel scoring procedures to enhance sensitivity.
Methods:
Using participant data from an iNPH outcome study at Butler Hospital, a mixed effect model examined main and interaction effects of time since surgery (baseline, 3 months, 12 months, and 24–60 months) and AD comorbidity (20 iNPH and 11 iNPH+AD) on activities of daily living (ADLs) and iNPH symptoms. Regression modeling explored whether baseline variables predicted improvements 3 months postoperatively.
Results:
There were no group differences in gait, incontinence, and global cognition over time, and neither group showed changes in ADLs. Cognitive differences were observed postoperatively; iNPH patients showed stable improvements in working memory (p = 0.012) and response inhibition (p = 0.010), while iNPH + AD patients failed to maintain initial gains. Regarding predicting postoperative outcomes, baseline AD biomarkers did not predict shunt response at 3 months; however, older age at surgery predicted poorer cognitive outcomes (p = 0.04), and presurgical Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (p = 0.035) and Mini-Mental Status Examination (MMSE) scores (p = 0.009) predicted improvements incontinence.
Conclusion:
iNPH + AD may be linked with greater declines in aspects of executive functioning postoperatively relative to iNPH alone. While baseline AD pathology may not prognosticate shunt response, younger age appears linked with postsurgical cognitive improvement, and utilizing both brief and comprehensive cognitive measures may help predict improved incontinence. These results illustrate the potential benefits of surgery and inform postoperative expectations for those with iNPH + AD.
Drawing on the adaptive control hypothesis, we examined whether older adults’ bilingual interactional contexts of conversational exchanges would predict important indices of executive functions (EF). We assessed participants’ engagement in each bilingual interactional context – single-language, dual-language, and dense code-switching – and their performance on a series of nonverbal EF measures. Sixty-nine healthy older adults (Mage = 70.39 years; ages 60–93) were recruited from local community centers. We found that the dense code-switching context was associated with enhanced overall EF, but not individual facets of EF (inhibitory control, shifting, and updating). These findings held true when we controlled for a host of covariates. Our findings shed light on aging bilinguals’ interactional contexts as crucial bilingual experiences that modulate overall EF. Given that bilingualism is a multidimensional construct, rather than a unidimensional variable, our study underscores the importance of more fine-grained operationalisation of bilingualism when studying its impacts on EF.
Effective communication in multilingual environments requires bilinguals to constantly monitor linguistic cues. It is hypothesized that the constant need to monitor may result in improved attention. However, previous investigations have reported mixed, often null results, with positive findings attributed to non-linguistic variables. To address these issues, we investigated whether higher levels of bilingualism were associated with improved attentional function in a sample of culturally and socioeconomically homogenous Mandarin–English speaking bilingual adolescents. Participants completed the Attention Network Task to assess attentional network function. Data were analyzed using linear mixed-effects models in order to account for nontrivial differences. Mixed results provide partial support for domain general cognitive benefits associated with higher levels of bilingualism. Both improved and reduced performance differed based on the specific dimension of bilingualism and the attentional network assessed. Findings support the conclusion that separable dimensions of bilingual language experience assert different influences on attentional network function.
Previous research has indicated that cognition and executive function are associated with decision-making, however the impact of mild cognitive impairment (MCI) on decision-making under explicit risk conditions is unclear. This cross-sectional study examined the impact of MCI, and MCI subtypes, on decision-making on the Game of Dice Task (GDT), among a cohort of older adults.
Method:
Data from 245 older adult participants (aged 72–78 years) from the fourth assessment of the Personality and Total Health Through Life study were analyzed. A diagnostic algorithm identified 103 participants with MCI, with subtypes of single-domain amnestic MCI (aMCI-single; n = 38), multi-domain amnestic MCI (aMCI-multi; n = 31), and non-amnestic MCI (n = 33), who were compared with an age-, sex-, education-, and income-matched sample of 142 cognitively unimpaired older adults. Decision-making scores on the GDT (net score, single number choices, and strategy changes) were compared between groups using nonparametric tests.
Results:
Participants with MCI showed impaired performance on the GDT, with higher frequencies of single number choices and strategy changes. Analyses comparing MCI subtypes indicated that the aMCI-multi subtype showed increased frequency of single number choices compared to cognitively unimpaired participants. Across the sample of participants, decision-making scores were associated with measures of executive function (cognitive flexibility and set shifting).
Conclusion:
MCI is associated with impaired decision-making performance under explicit risk conditions. Participants with impairments in multiple domains of cognition showed the clearest impairments. The GDT may have utility in discriminating between MCI subtypes.
Relative to youth with early-treated phenylketonuria (ETPKU), much less is known regarding the cognitive profile of adults with ETPKU. The present study aimed to address this gap by providing a comprehensive assessment of neuropsychological functioning among adults with ETPKU.
Method:
A sample of 40 adults with ETPKU (ages 18 – 36) and a demographically matched group of 32 healthy individuals without PKU participated. Participants completed a comprehensive neuropsychological battery including the NIH Toolbox, Wechsler Abbreviated Scale of Intelligence – Second Edition (WASI-II), Conners’ Continuous Performance Test (CPT-3), select subtests from the Weschler Adult Intelligence Scale – Fourth Edition (WAIS-IV) as well as several self-report measures of cognitive and psychoemotional functioning. Scores from these tests were combined to create cognitive composites reflecting overall task performance in the areas of verbal ability, visuospatial skills, executive functioning, motor skills, and processing speed.
Results:
No group differences were observed for full scale IQ or verbal ability. However, individuals with ETPKU demonstrated poorer performance on measures of executive functioning, processing speed, motor skills, and visuospatial skills as compared to the non-PKU group. Within the ETPKU group, recent blood phenylalanine levels (an indicator of metabolic control) were significantly correlated with performance across most cognitive domains and aspects of psychological functioning.
Conclusions:
Present findings suggest that the neuropsychological profile of adult ETPKU is characterized by circumscribed impairments in select cognitive domains. In addition, the results underscore the importance of maintaining metabolic control across the lifespan in individuals with ETPKU.
To examine the impact of early traumatic brain injury (TBI) on effortful control (EC) over time and the relationship of EC and executive functioning (EF) to long-term functional and social outcomes.
Method:
Parents of children (N = 206, ages 3–7) with moderate-to-severe TBI or orthopedic injuries (OIs) rated EC using the Child Behavior Questionnaire at 1 (pre-injury), 6, 12, and 18 months post-injury. Child functioning and social competence were assessed at 7 years post-injury. Mixed models examined the effects of injury, time since injury, and their interaction on EC. General linear models examined the associations of pre-injury EC and EC at 18 months with long-term functional and social outcomes. Models controlled for EF to assess the unique contribution of EC to outcomes.
Results:
Children with severe TBI had significantly lower EC than both the OI and moderate TBI groups at each post-injury time point. Both pre-injury and 18-month EC were associated with long-term outcomes. Among those with low EC at baseline, children with moderate and severe TBI had more functional impairment than those with OI; however, no group differences were noted at high levels of EC. EC had main effects on parent-reported social competence that did not vary by injury type.
Conclusions:
Findings suggest that EC is sensitive to TBI effects and is a unique predictor of functional outcomes, independent of EF. High EC could serve as a protective factor, and as such measures of EC could be used to identify children for more intensive intervention.
Chapter 3: Comprehension Processes. This chapter describes higher-level processes and how both lower- and higher-level processes work together to form a mental text representation and a situation model of reading. Key features of higher-level processing include the following: text representation, situation model processing skills associated with working memory, background knowledge, and executive function resources. Key concepts include passive resonance processing, bridging inferences, the now-or-never bottleneck, lexical processing, incremental item-based learning, Kintsch’s Construction-Integration model of reading, a two-level account of reading comprehension, genre variations in text processing, working memory as executive function, other executive functions, attentional processing, inferencing, metacognitive and metalinguistic awareness, strategy use, goal setting, and comprehension monitoring. The chapter concludes with implications for instruction.
The purpose of this exploratory study was to describe associations between NIH Toolbox-Cognition Battery subtests and legacy measures of neurocognitive function in two samples with neurological conditions (stroke and sickle cell disease (SCD)).
Method:
This exploratory secondary analysis uses data from two studies that assessed cognition at one time point using the NIH Toolbox-Cognition Battery, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and subtests from the Delis-Kaplan Executive Functions System (DKEFS). People with stroke (n = 26) and SCD (n = 64) were included. Associations between the NIH Toolbox-Cognition Battery subtests and corresponding legacy measures were examined using linear correlations, Bland–Altman analysis, and Lin’s Concordance Correlation Coefficient.
Results:
Linear correlations and Lin’s Concordance Correlation Coefficient were poor to strong in both samples on NIH Toolbox-CB subtests: Flanker Inhibitory Control and Attention (r = .35 to .48, Lin CCC = .27 to .37), Pattern Comparison Processing Speed (r = .40 to .65, Lin CCC = .37 to .62), Picture Sequence Memory (r = .19 to .55, Lin CCC = .18 to .48), Dimensional Change Card Sort (r = .39 to .77, Lin CCC = .38 to .63), Fluid Cognition Composite (r = .88 to .90, Lin CCC = .60 to .79), and Total Cognition Composite (r = .64 to .83, Lin CCC = .60 to .78). Bland–Altman analyses demonstrated wide limits of agreement across all subtests (–3.17 to 3.78).
Conclusions:
The NIH Toolbox-Cognition Battery subtests may behave similarly to legacy measures as an overall assessment of cognition across samples at risk for neurological impairment. Findings should be replicated across additional clinical samples.
Executive function organizes and directs behaviour but alterations in this cognitive domain can lead to inaccurate perception, interpretation and response to environmental information, which could be a risk factor for suicide.
Objectives
To explore executive function performance of depressed recent suicide attempters in comparison to depressed past suicide attempters, depressed non-attempters and healthy controls.
Methods
96 participants from the Psychiatry Department of the Araba University Hospital-Santiago were recruited as follows: 20 patients with a recent suicide attempt (<30days) diagnosed with a Major Depressive Disorder (MDD), 33 MDD patients with history of attempted suicide, 23 non-attempter MDD patients and 20 healthy controls. All participants underwent a clinical interview and neuropsychological assessment on executive function with the Wisconsin Sorting Card Test. Backward multiple regressions were performed adjusting for significant confounding variables. For group comparisons ANOVA test and Bonferroni post hoc test were performed with p<0.05 significance level.
Results
Patient groups did not differ regarding severity of depression. All patient groups performed significantly worse than healthy controls on executive function. Adjusted comparisons between patient groups indicated that recent suicide attempters had a poorer performance in this cognitive domain in comparison to both depressed lifetime attempters and depressed non-attempters (B=0.296, p=0.019 and B=0.301, p=0.028 respectively).
Conclusions
Executive function performance is altered in recent suicide attempts. As impaired executive function can be a risk factor for suicide, preventive interventions on suicide should focus on its assessment and rehabilitation.
Inhibitory control is the executive function component which underlies one’s ability to maintain goal-directed behavior by inhibiting prepotent responses or ignoring irrelevant information. Recent models suggest that impaired inhibition of negative information may contribute to depressive symptoms, and that this association is mediated by rumination. However, the exact nature of this association, particularly in non-clinical samples, is unclear.
Objectives
The goal of the current study was to assess the relationship between inhibitory control over emotional vs. non-emotional information, rumination and depressive symptoms.
Methods
A non-clinical sample of 119 participants (mean age: 36.44 ± 11.74) with various levels of depressive symptoms completed three variations of a Go/No-Go task online; two of the task variations required either explicit or implicit processing of emotional expressions, and a third variation contained no emotional expressions (i.e., neutral condition).
Results
We found that for participants who reported elevated depressive symptoms, their inhibitory control ability was reduced for all three task variations, relative to less depressed participants. However, for the task variation that required implicit emotion processing (rather than explicit), depressive symptoms were associated with inhibitory deficits for sad and neutral, but not for happy facial expressions. An exploratory analysis showed that the relationship between inhibition and depressive symptoms occurs in part through trait rumination for all three tasks, regardless of emotional content.
Conclusions
Collectively, these results indicate that elevated depressive symptoms are associated with both a general inhibitory control deficit, as well as affective interference from negative emotions, with implications for the assessment and treatment of mood disorders.
Individuals with severe mental illnesses (SMI) often present the knowledge about a task but in real-time do not perform it fully, or not as efficient as planned. This performance gap may be explained by difficulties with Executive Functions (EF).
Objectives
The aim of the presentation is to describe how people with and without SMI experience and perform grocery task. This, with considering this path from several directions including the subjects’ point of view using eye-tracking device during task performance.
Methods
Forty-three individuals had answered questions in regards to their shopping habits and performed the Test of Grocery Shopping Skills (TOGSS). The actual performance was accompanied by wearing an eye-tracking device which recorded the behavior and eye movement. We hypothesized that significant differences will be found between people with SMI and controls both in the routine grocery habits and in observed performance.
Results
No significant differences in age or gender. The groups differed significantly only in education, with the SMI group having fewer years of education. As a weekly routine, SMI subjects perform less frequent shopping (40%) than control group subjects (67%). TOGSS sub-outcomes indicated performance efficiency (time and redundancy) were significantly higher in the research group than in the matched control group (p <.01), with the SMI group spending a longer time performing the task and entering more aisles than required – redundancy.
Conclusions
These preliminary findings indicate that individuals with SMI spend more time dwelling while selecting ingredients. Besides the path in the supermarket, it might explain their performance in other everyday activities.
In recent years, physical activity as a potential intervention for attention-deficit hyperactivity disorder (ADHD) became into the focus of researchers, however the results are conflicting.
Objectives
Our aim was to investigate the effect of acute moderate physical activity on executive functions requiring inhibition.
Methods
The study included 50 treatment-naïve ADHD children, 50 medicated children with ADHD and 50 typically developing children, aged 6–12 years. To diagnose ADHD, we applied the Mini International Neuropsychiatric Interview for Children and Adolescents. To measure executive functions, the pediatric version of the Test of Attentional Performance (KiTAP) was used. Half of the children in each study group participated in a 20-minute, moderately intense exercise while watching a cartoon video. In the control intervention, the other half of the children from all three study groups watched the same cartoon video in a sitting position for 20 min.
Results
Regarding distractibility, flexibility and inhibition, physical activity had a significant positive effect on two of 10 parameters (number of total errors and errors when distractor was presented, both in the distractibility task) in the treatment-naïve ADHD group.
Conclusions
Our results suggest that moderate acute physical activity has some significant positive effects on certain executive function parameters among children with ADHD. Future studies should consider determining the optimal form, intensity, and duration of physical activity to become a potential adjunctive intervention for children diagnosed with ADHD.
This research examines maternal smoking during pregnancy and risk for poorer executive function in siblings discordant for exposure. Data (N = 173 families) were drawn from the Missouri Mothers and Their Children study, a sample, identified using birth records (years 1998–2005), in which mothers changed smoking behavior between two pregnancies (Child 1 [older sibling]: Mage = 12.99; Child 2 [younger sibling]: Mage = 10.19). A sibling comparison approach was used, providing a robust test for the association between maternal smoking during pregnancy and different aspects of executive function in early-mid adolescence. Results suggested within-family (i.e., potentially causal) associations between maternal smoking during pregnancy and one working memory task (visual working memory) and one response inhibition task (color-word interference), with increased exposure associated with decreased performance. Maternal smoking during pregnancy was not associated with stop-signal reaction time, cognitive flexibility/set-shifting, or auditory working memory. Initial within-family associations between maternal smoking during pregnancy and visual working memory as well as color-word interference were fully attenuated in a model including child and familial covariates. These findings indicate that exposure to maternal smoking during pregnancy may be associated with poorer performance on some, but not all skills assessed; however, familial transmission of risk for low executive function appears more important.
Individuals with autism spectrum disorder (ASD) are challenged not only by the defining features of social-communication deficits and restricted repetitive behaviors, but also by a myriad of psychopathology varying in severity. Different cognitive deficits underpin these psychopathologies, which could be subjected to intervention to alter the course of the disorder. Understanding domain-specific mediating effects of cognition is essential for developing targeted intervention strategies. However, the high degree of inter-correlation among different cognitive functions hinders elucidation of individual effects.
Methods
In the Philadelphia Neurodevelopmental Cohort, 218 individuals with ASD were matched with 872 non-ASD controls on sex, age, race, and socioeconomic status. Participants of this cohort were deeply and broadly phenotyped on neurocognitive abilities and dimensional psychopathology. Using structural equation modeling, inter-correlation among cognitive domains were adjusted before mediation analysis on outcomes of multi-domain psychopathology and functional level.
Results
While social cognition, complex cognition, and memory each had a unique pattern of mediating effect on psychopathology domains in ASD, none had significant effects on the functional level. In contrast, executive function was the only cognitive domain that exerted a generalized negative impact on every psychopathology domain (p factor, anxious-misery, psychosis, fear, and externalizing), as well as functional level.
Conclusions
Executive function has a unique association with the severity of comorbid psychopathology in ASD, and could be a target of interventions. As executive dysfunction occurs variably in ASD, our result also supports the clinical utility of assessing executive function for prognostic purposes.
Findings of bilingual participants outperforming their monolingual counterparts in executive functioning tasks have been repeatedly reported in the literature (Bialystok, 2017). However, uncontrolled factors or imperfectly matched samples might affect the reliability of these findings. This study aims to take into account a range of relevant variables in combination with innovative analyses to investigate the performance of one unstudied language group, Greek–English bilingual children in the north of England, compared to monolingual control groups. Our battery of executive function tasks taps into inhibition, updating and shifting. We use k-means nearest neighbour methods to match the groups and factor analysis to determine language proficiency. We find that bilinguals’ accuracy is on a par with their monolingual peers – however, they are faster in inhibition and working memory tasks. Our study provides strong evidence for the presence of a bilingual advantage in these domains, while making important methodological contributions to the field.
Evidence has demonstrated associations of bipolar disorder (BD) with cognitive impairment, dysregulated proinflammatory cytokines, and appetite hormones.
Aim
To compare executive dysfunction, proinflammatory cytokines, and appetite hormones between patients with first-episode and multiple-episode BDs.
Methods
This cross-sectional study included young adults aged 18 to 39 years who were diagnosed as having type 1 BD in the first or recurrent episode and a group of age-/sex-matched healthy controls. Data regarding patient characteristics, clinical symptoms, cytokines (C-reactive protein [CRP], interleukin-6, and tumor necrosis factor [TNF]-α), appetite hormones (leptin, adiponectin, ghrelin, and insulin), and executive function evaluated using the Wisconsin Card Sorting Test (WCST) were collected.
Results
A total of 112 participants (38 patients in the multiple-episode BD group, 31 patients in the first-episode BD group, and 43 in the control group) were included. Multivariate analysis revealed that patients in the multiple-episode BD group performed significantly worse in the WCST (P < .05) and had higher levels of ghrelin (P = .002), and lower levels of CRP (P = .040) than those in the first-episode BD group. Patients with BD had significantly higher TNF-α and ghrelin levels compared with the healthy controls. No significant associations of CRP, TNF-α, and ghrelin levels with executive function were observed.
Conclusions
Profiles in proinflammatory cytokines and appetite hormones as well as executive function significantly differed between patients with first-episode and multiple-episode BDs and controls, which may suggest their potential roles in the clinical stages and pathophysiology of type 1 BD.