Cognitive function in patients with irritable bowel syndrome: impairment is common and only weakly correlated with depression/anxiety and severity of gastrointestinal symptoms.

OBJECTIVE: To investigate cognitive function in patients with irritable bowel syndrome (IBS) and its relation to anxiety/depression and severity of gastrointestinal (GI) symptoms. METHODS: Patients with IBS (n = 65) and healthy controls (HCs, n = 37) performed the ten subtests of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Age-normed index scores of five cognitive domains (Immediate memory, Visuospatial function, Language function, Attention, Recall) and a total (Fullscale) score were derived from the performance. Emotional function was assessed using the Hospital Anxiety and Depression Scale (HADS), and the IBS Symptom Scoring System (IBS-SSS) was used to define the severity of GI symptoms. RESULTS: Patients with IBS reported significantly higher scores than the HC group on symptom measures of anxiety and depression, and significantly lower scores on the Immediate memory, Recall, and Fullscale RBANS indexes. Approximately 30% of the IBS patients obtained index scores at least one standard deviation below the population mean, and more than 50% scored above the screening threshold for an anxiety disorder. The severity of GI symptoms was significantly correlated with the severity level of anxiety symptoms (p=.006), but neither the severity level of emotional nor GI symptoms was significantly correlated with the RBANS index scores in the IBS group. CONCLUSION: Cognitive and emotional function were more severely affected in patients with IBS than in HCs. The weak correlation between the two functional areas suggests that both should be assessed as part of a clinical examination of patients with IBS.

Cognitive and emotional function should be assessed in patients with IBS.Cognitive impairment was less closely related to symptoms of anxiety/depression and severity of GI symptoms than expected.An independent contribution of both emotional symptoms and cognitive function should be considered when developing treatment programs for patients with IBS.

Decoding IBS: a machine learning approach to psychological distress and gut-brain interaction.

PURPOSE: Irritable bowel syndrome (IBS) is a diagnosis defined by gastrointestinal (GI) symptoms like abdominal pain and changes associated with defecation. The condition is classified as a disorder of the gut-brain interaction (DGBI), and patients with IBS commonly experience psychological distress. The present study focuses on this distress, defined from reports of fatigue, anxiety, depression, sleep disturbances, and performance on cognitive tests. The aim was to investigate the joint contribution of these features of psychological distress in predicting IBS versus healthy controls (HCs) and to disentangle clinically meaningful subgroups of IBS patients. METHODS: IBS patients ( n = 49 ) and HCs ( n = 28 ) completed the Chalder Fatigue Scale (CFQ), the Hamilton Anxiety and Depression Scale (HADS), and the Bergen Insomnia Scale (BIS), and performed tests of memory function and attention from the Repeatable Battery Assessing Neuropsychological Symptoms (RBANS). An initial exploratory data analysis was followed by supervised (Random Forest) and unsupervised (K-means) classification procedures. RESULTS: The explorative data analysis showed that the group of IBS patients obtained significantly more severe scores than HCs on all included measures, with the strongest pairwise correlation between fatigue and a quality measure of sleep disturbances. The supervised classification model correctly predicted belongings to the IBS group in 80% of the cases in a test set of unseen data. Two methods for calculating feature importance in the test set gave mental and physical fatigue and anxiety the strongest weights. An unsupervised procedure with K = 3 showed that one cluster contained 24% of the patients and all but two HCs. In the two other clusters, their IBS members were overall more impaired, with the following differences. One of the two clusters showed more severe cognitive problems and anxiety symptoms than the other, which experienced more severe problems related to the quality of sleep and fatigue. The three clusters were not different on a severity measure of IBS and age. CONCLUSION: The results showed that psychological distress is an integral component of IBS symptomatology. The study should inspire future longitudinal studies to further dissect clinical patterns of IBS to improve the assessment and personalized treatment for this and other patient groups defined as disorders of the gut-brain interaction. The project is registered at https://classic. CLINICALTRIALS: gov/ct2/show/NCT04296552 20/05/2019.

Cognitive impairment as a predictor of long-term psychological distress in patients with polysubstance use disorders: a prospective longitudinal cohort study.

BACKGROUND: The association between polysubstance use disorder (pSUD), mental illness, and cognitive impairments is well established and linked to negative outcomes in substance use disorder treatment. However, it remains unclear whether cognitive impairment predicts long-term psychological distress among treatment seeking patients with pSUD. This study aimed to investigate the associations and predictive ability of cognitive impairment on psychological distress one and 5 years after treatment initiation. METHODS: N = 164 treatment seeking patients with pSUD were sampled at treatment initiation. We examined associations between cognitive impairment according to Montreal Cognitive Assessment® (MoCA®), Wechsler Abbreviated Scale of Intelligence (WASI), and Behaviour Rating Inventory of Executive Function - Adult version (BRIEF-A) administered at treatment initiation and psychological distress defined by the Symptom Check List-90-Revised (SCL-90-R) at treatment initiation, one and five years later. We ran hierarchical logistic regressions to assess the predictive ability of the respective cognitive instruments administered at treatment initiation on psychological distress measured one and five years later including psychological distress at treatment initiation and substance intake at the time-points of the measurements as covariates. RESULTS: The main results was that MoCA® and BRIEF-A predicted psychological distress at years one and five, but BRIEF-A lost predictive power when accounting for psychological distress at treatment initiation. WASI predicted psychological distress at year one, but not at year five. CONCLUSIONS: Results from MoCA® and WASI was found to be less sensitive to the effect of psychological distress than BRIEF-A. Cognitive impairment at treatment initiation may hold predictive value on later psychological distress, yet its clinical utility is uncertain.

Deliberate self-harm in adolescents screening positive for attention-deficit / hyperactivity disorder: a population-based study.

BACKGROUND: Adolescents with attention-deficit / hyperactivity disorder (ADHD) have an increased risk of self-harm. The risk of self-harm among adolescents who display an elevated level of ADHD symptoms, but without a formal diagnosis, is not well-studied and understood. OBJECTIVE: To investigate the relationship between self-reported symptoms of ADHD and self-harm in a population-based sample of adolescents. METHODS: Adolescents in the population-based youth@hordaland study were invited to complete the Adult ADHD Self-Report Scale (ASRS) and the Short Mood and Feelings Questionnaire (SMFQ). They were asked whether they ever deliberately have taken an overdose or tried to harm themselves on purpose, once or multiple times, defined according to the code used in the Child and Adolescent Self-harm in Europe (CASE) Study. Adolescents reporting severe problems on ≥ four of six selected items on the ASRS-v 1.1 screener were defined as ADHD-screen positive (ADHD-SC+), and the remaining sample as ADHD-screen negative (ADHD-SC-). SMFQ score ≥ 12 was used to define a high level of depressive symptoms. RESULTS: A total of 9692 adolescents (mean age 17.4 years, 53.1% females) participated in the study, of which 2390 (24.7%) screened positive on the ASRS. ADHD-SC+ adolescents engaged in self-harm more often than the ADHD-SC- group (14.6% vs. 5.4%, OR = 3.02, 95%CI [2.57-3.24]). This remained significant after adjustment for demographic variables, SMFQ score ≥ 12, symptoms of conduct disorder and familial history of self-harm and suicide attempts (OR = 1.58, 95%CI [1.31-1.89]). They were also more likely to report an overdose as their method of self-harm (OR = 1.52, 95%CI [1.05-2.23]). Within the ADHD-SC+ group female sex, high levels of inattention and hyperactivity/impulsivity symptoms, SMFQ score ≥ 12, symptoms indicating conduct disorder and familial history of self-harm and suicide attempts increased the likelihood of engaging in deliberate self-harm. CONCLUSION: Adolescents who screened positive for ADHD had increased risk of engaging in self-harm. Clinicians should consider the increased risk of such engagement in adolescents who present with high level of ADHD symptoms, even in the absence of a clinical ADHD diagnosis.

Risk factors of suicidal spectrum behaviors in adults and adolescents with attention-deficit / hyperactivity disorder - a systematic review.

INTRODUCTION: Adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of suicidal spectrum behaviors (SSBs). However, there is limited knowledge about risk factors triggering SSBs in this group of people. OBJECTIVE: To explore published literature concerning factors that may increase the risk of SSBs in adults and adolescents with ADHD. METHODS: A systematic literature search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted on 22nd of February 2022 using the Ovid MEDLINE and Web of Science databases. Three categories of search terms were used: (1) self-harm, self-injury, self-mutilation, suicide, self-poisoning; (2) adults, adolescents; and (3) attention-deficit hyperactivity disorder/ADHD. Studies with data concerning mediating factors of SSBs in relation to a clinical diagnosis of ADHD in participants above 16 years of age were included. RESULTS: The literature search identified 604 articles, of which 40 were included in the final study selection. Factors found to increase the likelihood of SSBs included ADHD symptom severity and persistence, female gender, family history of ADHD, childhood and parental influences, and social functioning. Even when adjusting for psychiatric comorbidities, most studies showed that adults and adolescents with ADHD have an elevated risk of SSBs. CONCLUSION: This systematic review has documented that several demographic and clinical features are associated with an increased risk of SSBs in adolescents and adults with ADHD. Notably, ADHD emerges as an independent risk factor for SSBs. This information ought to have clinical implications in terms of screening and suicide prevention strategies. Further longitudinal studies are needed to investigate the outcome of preventive strategies in individuals along the full spectrum of ADHD symptom severity.

Functional activity level reported by an informant is an early predictor of Alzheimer's disease.

BACKGROUND: Loss of autonomy in day-to-day functioning is one of the feared outcomes of Alzheimer's disease (AD), and relatives may have been worried by subtle behavioral changes in ordinary life situations long before these changes are given medical attention. In the present study, we ask if such subtle changes should be given weight as an early predictor of a future AD diagnosis. METHODS: Longitudinal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used to define a group of adults with a mild cognitive impairment (MCI) diagnosis remaining stable across several visits (sMCI, n=360; 55-91 years at baseline), and a group of adults who over time converted from having an MCI diagnosis to an AD diagnosis (cAD, n=320; 55-88 years at baseline). Eleven features were used as input in a Random Forest (RF) binary classifier (sMCI vs. cAD) model. This model was tested on an unseen holdout part of the dataset, and further explored by three different permutation-driven importance estimates and a comprehensive post hoc machine learning exploration. RESULTS: The results consistently showed that measures of daily life functioning, verbal memory function, and a volume measure of hippocampus were the most important predictors of conversion from an MCI to an AD diagnosis. Results from the RF classification model showed a prediction accuracy of around 70% in the test set. Importantly, the post hoc analyses showed that even subtle changes in everyday functioning noticed by a close informant put MCI patients at increased risk for being on a path toward the major cognitive impairment of an AD diagnosis. CONCLUSION: The results showed that even subtle changes in everyday functioning should be noticed when reported by relatives in a clinical evaluation of patients with MCI. Information of these changes should also be included in future longitudinal studies to investigate different pathways from normal cognitive aging to the cognitive decline characterizing different stages of AD and other neurodegenerative disorders.

Performance on Cognitive Screening Tests and Long-Term Substance Use Outcomes in Patients with Polysubstance Use Disorder.

INTRODUCTION: Cognitive impairments among patients with substance use disorders are prevalent and associated with adverse treatment outcomes. However, knowledge of the predictive value of broad cognitive screening instruments on long-term treatment outcomes is limited. The present study aimed to examine the predictive value of measures from the Montreal Cognitive Assessment® (MoCA®), Wechsler Abbreviated Scale of Intelligence (WASI), and the Behaviour Rating Inventory of Executive Function - Adult version (BRIEF-A) on self-reported long-term substance use and abstinence in patients with polysubstance use disorders (pSUD). METHODS: A cohort (N = 164) of patients with pSUD who started a new treatment sequence in the Stavanger University Hospital catchment area were recruited and followed prospectively for 5 years. Participants completed neurocognitive testing with the MoCA®, WASI, and BRIEF-A at inclusion and were categorized as cognitively impaired or non-impaired according to recommended cut-off values. The sum score of the items from the Drug Use Disorders Identification Test Consumption scale (DUDIT-C) was used as a measure of substance use outcome 1 and 5 years after inclusion. We defined substance abstinence (DUDIT-C = 0) and heavy substance use (DUDIT-C ≥7) to determine whether cognitive impairments measured by the respective instruments were associated with and could predict abstinence and heavy substance use 1 and 5 years after baseline. RESULTS: At the 1-year follow-up, 54% of the total sample reported total abstinence from substances. Conversely, 31% presented heavy substance use. At 5 years, 64% of the total sample reported abstinence from substances, while 25% presented heavy substance use. The results showed a statistically significant association between cognitive impairment defined from MoCA® and higher continuous scores on DUDIT-C at 1-year follow-up. There were no differences in substance abstinence or heavy substance use between patients with and without cognitive impairment at the 1- and 5-year follow-ups. Furthermore, cognitive impairment did not explain substance abstinence or heavy substance use at the 1- and 5-year follow-ups. CONCLUSION: Generally, individuals with pSUD may be burdened and lack psychosocial resources to such an extent that cognitive functioning plays a subordinate role in long-term recovery. The present study suggests that results on screening tools assessing broad cognitive domains at treatment initiation have limited clinical value in predicting long-term substance use outcomes. There is a need to establish clinically viable instruments to assess cognitive functions with well-established clinical and ecological validity in the SUD population.

Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected ("concordant") direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive ("discordant") relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10-8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms-early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways-that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness.

Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes.

The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10-16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.

Longitudinal stability of the brain functional connectome is associated with episodic memory performance in aging.

The brain functional connectome forms a relatively stable and idiosyncratic backbone that can be used for identification or "fingerprinting" of individuals with a high level of accuracy. While previous cross-sectional evidence has demonstrated increased stability and distinctiveness of the brain connectome during the course of childhood and adolescence, less is known regarding the longitudinal stability in middle and older age. Here, we collected structural and resting-state functional MRI data at two time points separated by 2-3 years in 75 middle-aged and older adults (age 49-80, SD = 6.91 years) which allowed us to assess the long-term stability of the functional connectome. We show that the connectome backbone generally remains stable over a 2-3 years period in middle and older age. Independent of age, cortical volume was associated with the connectome stability of several canonical resting-state networks, suggesting that the connectome backbone relates to structural properties of the cortex. Moreover, the individual longitudinal stability of subcortical and default mode networks was associated with individual differences in cross-sectional and longitudinal measures of episodic memory performance, providing new evidence for the importance of these networks in maintaining mnemonic processing in middle and old age. Together, the findings encourage the use of within-subject connectome stability analyses for understanding individual differences in brain function and cognition in aging.