The Role of Neurocognitive Tests in the Assessment of Adult Attention-Deficit/Hyperactivity Disorder

Despite widespread recognition that attention-deficit/hyperactivity disorder (ADHD) is a lifelong neurodevelopmental disorder, optimal methods of diagnosis among adults remain elusive. Substantial overlap between ADHD symptoms and cognitive symptoms of other mental health conditions, such as depression and anxiety, and concerns about validity in symptom reporting have made the use of neuropsychological tests in ADHD diagnostic assessment appealing. However, past work exploring the potential diagnostic utility of neuropsychological tests among adults has often relied on a relatively small subset of tests, has failed to include symptom and performance validity measures, and often does not include comparison groups of participants with commonly comorbid disorders, such as depression. The current study examined the utility of an extensive neuropsychological measure battery for diagnosing ADHD among adults. Two hundred forty-six participants (109 ADHD, 52 depressed, 85 nondisordered controls) completed a multistage screening and assessment process, which included a clinical interview, self, and informant report on behavior rating scales, performance and symptom validity measures, and an extensive neuropsychological testing battery. Results indicated that measures of working memory, sustained attention, response speed, and variability best discriminated ADHD and non-ADHD participants. While single test measures provided performed poorly in identifying ADHD participants, analyses revealed that a combined approach using self and informant symptom ratings, positive family history of ADHD, and a reaction time (RT) variability measure correctly classified 87% of cases. Findings suggest that neuropsychological test measures used in conjunction with other clinical assessments may enhance prediction of adult ADHD diagnoses

Gene × environment interactions for ADHD: synergistic effect of 5HTTLPR genotype and youth appraisals of inter-parental conflict

<p>Abstract</p> <p>Background</p> <p>Serotonin genes have been hypothesized to play a role in the etiology of attention-deficit hyperactivity disorder (ADHD); prior work suggests that serotonin may interact with psychosocial stressors in ADHD, perhaps via mechanisms involved in emotional dysregulation. Because the development of behavioral and emotional regulation depends heavily both on the child's experience within the family context and the child's construals of that experience, children's appraisals of inter-parental conflict are a compelling candidate potentiator of the effects of variation within the serotonin transporter gene promoter polymorphism (5HTTLPR) on liability for ADHD.</p> <p>Method</p> <p>304 youth from the local community underwent a multi-informant diagnostic assessment procedure to identify ADHD cases and non-ADHD controls. Youth also completed the Children's Perception of Inter-Parental Conflict (CPIC) scale to assess appraisals of self-blame in relation to their parents' marital disputes. The trialleic configuration of 5HTTLPR (long/short polymorphism with A> G substitution) was genotyped and participants were assigned as having high (La/La N = 78), intermediate (La/Lg, La/short, N = 137), or low (Lg/Lg, Lg/short, short/short, N = 89) serotonin transporter activity genotypes. Teacher reported behavior problems were examined as the target outcome to avoid informant overlap for moderator and outcome measures.</p> <p>Results</p> <p>Hierarchical linear regression analyses indicated significant 5HTTLPR × self-blame interactions for ADHD symptoms. Examination of the interactions indicated positive relations between reports of self-blame and ADHD symptoms for those with the high and low serotonin activity genotypes. There was no relation between self-blame and ADHD for those with intermediate activity 5HTTLPR genotypes.</p> <p>Conclusion</p> <p>Both high and low serotonergic activity may exert risk for ADHD when coupled with psychosocial distress such as children's self-blame in relation to inter-parental conflict. Results are discussed in relation to the role of serotonin in the etiology of the ADHD and related externalizing behaviors.</p

Sequencing of sporadic Attention‐Deficit Hyperactivity Disorder (ADHD) identifies novel and potentially pathogenic de novo variants and excludes overlap with genes associated with autism spectrum disorder

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137575/1/ajmgb32527.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137575/2/ajmgb32527_am.pd

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Disordered Gambling and Personality Traits

Personality traits can be used to describe the dispositional influences on many forms of psychopathology and to depict heterogeneity among individuals with similar kinds of psychopathology. The goals of this chapter are three-fold. First, the authors aim to provide a brief overview of contemporary trait models of personality. Second, in this context they review research examining the interface between personality and disordered gambling, including a discussion of potential personality mechanisms. Third, they describe models of personality heterogeneity among disordered gamblers. Finally, they conclude by articulating directions for future personality research on the causal mechanisms, heterogeneity, and treatment of disordered gambling

Meta-Analysis of Cognitive Endophenotypes for ADHD

The aim of this study was to evaluate the utility of cognitive endophenotypes for ADHD by examining differences in performance among unaffected first-degree relatives of individuals with ADHD and non-ADHD controls. Literature searches were conducted through June 2023 using PsycINFO, PubMed, and ProQuest Dissertations and Theses databases. 41 articles met full inclusion criteria, which included 261 effect sizes capturing performance on tasks across 11 comparable neurocognitive constructs. Multilevel meta-analysis indicated that unaffected first-degree relatives of individuals with ADHD performed significantly worse than non-ADHD controls in several domains. Substantial heterogeneity in effect sizes was explained by differences in samples, but with limited evidence of moderation by sex and age. Overall, these findings suggest that non-executive cognitive domains along with working memory may be most fruitful for linking genetic risk for ADHD to other causal factors and ultimately to the expression and continuation of ADHD symptoms