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.

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.

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.

Psychosocial characteristics differentiate non-distressing and distressing voices in 10,346 adolescents.

Adolescents hearing non-existent voices may be at risk for psychosis, but the prevalence of voice-hearing (VH) in the general population complicates clinical interpretations. Differentiating between VH with and without distress may aid treatment decisions in psychosis services, but understanding the differences between these two phenomena as they present in the normal adolescent population is necessary to validate this differentiation. The present study compared VH with and without distress in 10,346 adolescents in relation to clinical characteristics, known risk factors, predictors and psychosocial moderators of psychosis. A population-based cohort of Norwegian 16-19 years old adolescents completed a comprehensive web-based questionnaire, including two questions from the extended Launay-Slade Hallucinations Scale: (1) I often hear a voice speaking my thoughts aloud and (2) I have been troubled by hearing voices in my head. Adolescents reporting no VH, non-distressing VH or distressing VH were compared on 14 psychosocial and clinical variables. A multinomial regression model showed that non-disturbing voices were predicted by better school grades, social dysfunction, distractibility, affective symptoms and experience of trauma, while the disturbing voices were predicted by the experience of bullying and trauma, perceived negative self-worth and self-efficacy, less family support, dysregulation of activation, distractibility, self-harm and anxiety. Hearing voices without distress versus being distressed by the voices is related to different constellations of psychosocial variables, suggesting that they represent two separate groups of adolescents. The findings validate the emphasis on distress in clinical practice.

Multi-Trait Analysis of GWAS and Biological Insights Into Cognition: A Response to Hill (2018).

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' (Lam et al., Cell Reports, Vol. 21, 2017, 2597-2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229-237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from 'inflation in the FDR [false discovery rate]', as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88), and are not 'more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence'.

A genetic association study of CSMD1 and CSMD2 with cognitive function.

The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n=670). Replication testing of SNPs with p-value<0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n=1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n=1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMD1 SNP rs2740931 and performance in immediate episodic memory (p-value=5×10-6, minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p⩽1.2×10-5). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n=3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease.

Inhibition and Switching in Healthy Aging: A Longitudinal Study.

OBJECTIVES: Discrepant findings of age-related effects between cross-sectional and longitudinal studies on executive function (EF) have been described across different studies. The aim of the present study was to examine longitudinal age effects on inhibition and switching, two key subfunctions of EF, calculated from results on the Color Word Interference Test (CWIT). METHODS: One hundred twenty-three healthy aging individuals (average age 61.4 years; 67% women) performed the CWIT up to three times, over a period of more than 6 years. Measures of inhibition, switching, and combined inhibition and switching were analyzed. A longitudinal linear mixed effects models analysis was run including basic CWIT conditions, and measures of processing speed, retest effect, gender, education, and age as predictors. RESULTS: After taking all predictors into account, age added significantly to the predictive value of the longitudinal models of (i) inhibition, (ii) switching, and (iii) combined inhibition and switching. The basic CWIT conditions and the processing speed measure added to the predictive value of the models, while retest effect, gender, and education did not. CONCLUSIONS: The present study on middle-aged to older individuals showed age-related decline in inhibition and switching abilities. This decline was retained even when basic CWIT conditions, processing speed, attrition, gender, and education were controlled. (JINS, 2017, 23, 90-97).

Longitudinal Changes in Familiarity, Free and Cued Odor Identification, and Edibility Judgments for Odors in Aging Individuals.

This longitudinal study investigated changes in olfaction as assessed by a set of tasks requiring different aspects of semantic information in normal aging individuals. Using 16 odorous items from a standardized olfactory test, the Scandinavian Odor Identification Test, 107 middle aged and older adults were assessed up to three times over a period of 6.5 years, requesting them to rate familiarity and edibility for each odorous item before identifying it with or without presenting verbal cues. Using linear mixed models, the longitudinal analyses revealed significant correlations between all olfactory measures. Furthermore, we found an almost parallel age-related decline in all olfactory tasks, although free identification performance indicated a trend toward faster decline with age. Women showed less decline compared with men, in particular for edibility judgments. The results corroborate earlier cross-sectional findings showing significant correlations between the olfactory tasks. In the present study of healthy middle-aged and older adults, we found a parallel longitudinal decline across different tests of olfaction.

High-expanding cortical regions in human development and evolution are related to higher intellectual abilities.

Cortical surface area has tremendously expanded during human evolution, and similar patterns of cortical expansion have been observed during childhood development. An intriguing hypothesis is that the high-expanding cortical regions also show the strongest correlations with intellectual function in humans. However, we do not know how the regional distribution of correlations between intellectual function and cortical area maps onto expansion in development and evolution. Here, in a sample of 1048 participants, we show that regions in which cortical area correlates with visuospatial reasoning abilities are generally high expanding in both development and evolution. Several regions in the frontal cortex, especially the anterior cingulate, showed high expansion in both development and evolution. The area of these regions was related to intellectual functions in humans. Low-expanding areas were not related to cognitive scores. These findings suggest that cortical regions involved in higher intellectual functions have expanded the most during development and evolution. The radial unit hypothesis provides a common framework for interpretation of the findings in the context of evolution and prenatal development, while additional cellular mechanisms, such as synaptogenesis, gliogenesis, dendritic arborization, and intracortical myelination, likely impact area expansion in later childhood.

Co-occurring symptoms of attention deficit hyperactivity disorder (ADHD) in a population-based sample of adolescents screened for depression.

BACKGROUND: Depression is common in adolescents, with a gender bias towards girls. Symptoms associated with attention deficit hyperactivity disorder (ADHD) tend to co-occur in depressed adolescents. This may be related to common features between the two symptom domains, but co-occurring ADHD symptoms may also inflate the severity of depression. The present study investigates the frequency and influence of ADHD symptoms co-occurring with depression in a gender balanced population-based sample of Norwegian adolescents. METHODS: A sample of 9614 adolescents (16-19 years) completed a questionnaire including the short version of the Mood and Feelings Questionnaire (sMFQ) and the Adult ADHD Self-Report Scale (ASRS), with items reflecting symptoms associated with depression and ADHD, respectively. The sMFQ sum score was used as a proxy for severity of depression, and adolescents with a score equal to or above the 90th percentile were defined as depressed. A high response on any of the ASRS items was used to define the presence of an ADHD symptom, and the number of high scores was used to indicate severity. RESULTS: ADHD symptoms were frequently reported by the adolescents, with a higher frequency in girls than in boys. The gender differences were, however, minor when the analysis was restricted to the adolescents defined as depressed. Each severe symptom reported on the ASRS contributed significantly to increase the sum score on the sMFQ, and more than 20 % of the adolescents defined as depressed reported six or more symptoms within the ASRS inattention subscale. CONCLUSIONS: The results emphasize the importance of screening for symptoms associated with ADHD when assessing adolescents presenting symptoms indicating depression. Although girls reported higher frequency of symptoms within both domains, the gender bias was dependent on the overall symptom severity. Awareness of co-occurrence of symptoms and gender biases are of importance for both clinical work and future research on mental health and service use in adolescence.

Association Between Sleep Problems and Symptoms of Attention Deficit Hyperactivity Disorder in Adolescence: Results From a Large Population-Based Study.

Sleep problems and symptoms of ADHD are common in adolescence, but detailed epidemiological assessment of their association is lacking. Using data from a recent population-based study, 9,846 adolescents aged 16 to 19 provided detailed information on sleep and symptoms of ADHD. Results confirmed a large overlap between self-reported symptoms of ADHD and all sleep variables studied. Symptoms of ADHD were linked to shorter sleep duration, longer sleep latency, and nocturnal wake time, as well as larger sleep deficiency. ADHD symptoms also increased the odds of insomnia and delayed sleep phase syndrome. The associations were only partially explained by confounders (mainly depression). The findings suggest that sleep problems should be included as a treatment target in efforts to reduce symptoms of ADHD in adolescence.

Parental socioeconomic status and child intellectual functioning in a Norwegian sample.

Socioeconomic status (SES) in childhood has been linked to cognitive function and future academic and occupational success in studies from several countries. However, previous Nordic studies have shown inconsistent results regarding the strength of this link. We therefore investigated the association between SES and cognitive functioning in a sample of 255 Norwegian children, including 151 typically developing children and 104 children with a psychiatric diagnosis. The third edition of the Wechsler Intelligence Scale for Children (WISC-III) to assess cognitive function was used. SES was defined from maternal and paternal education and family income of typically developing children and of a subsample of children with a psychiatric diagnosis. Multiple adjusted regression analyses were used to investigate the relation between SES and cognitive functioning. The analyses showed that SES explained a significant part of the variance of the full-scale WISC-III score and two WISC-III indices (Verbal Comprehension and Freedom from Distractibility). Overall, the strength of the relations was weaker than expected from reports from other non-Nordic countries. Parental education was the only significant individual predictor, suggesting that income was of minor importance as a predictor of cognitive functioning. Further studies should investigate how diverse political and socioeconomic contexts influence the relation between SES and cognitive functioning.

Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder.

Aggressiveness is a behavioral trait that has the potential to be harmful to individuals and society. With an estimated heritability of about 40%, genetics is important in its development. We performed an exploratory genome-wide association (GWA) analysis of childhood aggressiveness in attention deficit hyperactivity disorder (ADHD) to gain insight into the underlying biological processes associated with this trait. Our primary sample consisted of 1,060 adult ADHD patients (aADHD). To further explore the genetic architecture of childhood aggressiveness, we performed enrichment analyses of suggestive genome-wide associations observed in aADHD among GWA signals of dimensions of oppositionality (defiant/vindictive and irritable dimensions) in childhood ADHD (cADHD). No single polymorphism reached genome-wide significance (P < 5.00E-08). The strongest signal in aADHD was observed at rs10826548, within a long noncoding RNA gene (beta = -1.66, standard error (SE) = 0.34, P = 1.07E-06), closely followed by rs35974940 in the neurotrimin gene (beta = 3.23, SE = 0.67, P = 1.26E-06). The top GWA SNPs observed in aADHD showed significant enrichment of signals from both the defiant/vindictive dimension (Fisher's P-value = 2.28E-06) and the irritable dimension in cADHD (Fisher's P-value = 0.0061). In sum, our results identify a number of biologically interesting markers possibly underlying childhood aggressiveness and provide targets for further genetic exploration of aggressiveness across psychiatric disorders. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Even cognitively well-functioning adults are unaware of their olfactory dysfunction: Implications for ENT clinicians and researchers.

BACKGROUND: Past findings of an impact of cognitive impairment on awareness of olfactory dysfunction, and high prevalence of age-associated cognitive impairment motivated the present study of whether middle-aged and elderly adults are unaware of an olfactory dysfunction despite being carefully screened for cognitive impairment. METHODOLOGY: The sample included 203 Norwegian participants, aged 46-79 years, 134 women and 69 men, who underwent comprehensive neuropsychological assessment for screening of cognitive impairment. Subjective assessment of olfactory function ("How would you estimate your sense of smell?") was compared with outcome on objective assessment of olfactory function with the Scandinavian Odor Identification Test, which in the present study was shown to be valid for use on Norwegian populations. RESULTS: We found that 79% of this cognitively healthy sample with objectively assessed olfactory dysfunction reported normal olfactory function (57% of functionally anosmics reported normal function). In contrast, only 9% with objectively assessed normal olfactory function reported olfactory dysfunction. CONCLUSION: A large proportion of cognitively well-functioning middle-aged and elderly adults with an olfactory dysfunction are unaware of their dysfunction. The ENT physician who suspects that the sense of smell may be compromised should, in addition to an anamnesis, assess the patient`s olfactory function objectively.