Viewing the personality traits through a cerebellar lens. A focus on the constructs of novelty seeking, harm avoidance, and alexithymia

The variance in the range of personality trait expression appears to be linked to structural variance in specific brain regions. In evidencing associations between personality factors and neurobiological measures, it seems evident that the cerebellum has not been up to now thought as having a key role in personality. This paper will review the most recent structural and functional neuroimaging literature that engages the cerebellum in personality traits, as novelty seeking and harm avoidance, and it will discuss the findings in the context of contemporary theories of affective and cognitive cerebellar function. By using region of interest (ROI)- and voxel-based approaches, we recently evidenced that the cerebellar volumes correlate positively with novelty seeking scores and negatively with harm avoidance scores. Subjects who search for new situations as a novelty seeker does (and a harm avoiding does not do) show a different engagement of their cerebellar circuitries in order to rapidly adapt to changing environments. The emerging model of cerebellar functionality may explain how the cerebellar abilities in planning, controlling, and putting into action the behavior are associated to normal or abnormal personality constructs. In this framework, it is worth reporting that increased cerebellar volumes are even associated with high scores in alexithymia, construct of personality characterized by impairment in cognitive, emotional, and affective processing. On such a basis, it seems necessary to go over the traditional cortico-centric view of personality constructs and to address the function of the cerebellar system in sustaining aspects of motivational network that characterizes the different temperamental trait

Executive Dysfunction or State Regulation: A Dimensional Comparison of Two Neuropsychological Theories of Attention Disorder Symptoms Using RDoC Paradigms

Two leading theories regarding the neurocognitive basis of attentional disorders are the executive dysfunction theory and the state regulation theory. The executive dysfunction theory takes a top-down approach, explaining the symptoms of ADHD as a byproduct of general deficits in executive functioning—particularly disinhibition. The state regulation theory takes a bottom-up approach, explaining the symptoms of ADHD as a failure to be sufficiently aroused by, and subsequently engage with, less stimulating or rewarding tasks. These two theories predict different patterns of performance on tasks of executive functioning and attention, and research has demonstrated mixed support for both theories. The present study used a continuous performance task to manipulate RDoC paradigms of inhibition and arousal predicted to be affected disparately according to each theory. The data failed to support either the executive dysfunction theory or the state regulation theory as hypothesized; however, there was a significant interaction between the paradigms used for each theory. Factor analysis may be useful in establishing predictions which may guide follow-up investigation

Overexpression of the type 1 adenylyl cyclase in the forebrain leads to deficits of behavioral inhibition

The type 1 adenylyl cyclase (AC1) is an activity-dependent, calcium-stimulated adenylyl cyclase expressed in the nervous system that is implicated in memory formation. We examined the locomotor activity, and impulsive and social behaviors of AC1+ mice, a transgenic mouse strain overexpressing AC1 in the forebrain. Here we report that AC1+ mice exhibit hyperactive behaviors and demonstrate increased impulsivity and reduced sociability. In contrast, AC1 and AC8 double knock-out mice are hypoactive, and exhibit increased sociability and reduced impulsivity. Interestingly, the hyperactivity of AC1+ mice can be corrected by valproate, a mood-stabilizing drug. These data indicate that increased expression of AC1 in the forebrain leads to deficits in behavioral inhibition

Early developmental pathways to childhood symptoms of attention-deficit hyperactivity disorder (ADHD), anxiety, and autism spectrum disorder (ASD)

Background Children with autism spectrum disorder (ASD) often have co-occurring symptoms of attention-deficit/hyperactivity disorder (ADHD) and/or anxiety. It is unclear whether these disorders arise from shared or distinct developmental pathways. We explored this question by testing the specificity of early-life (infant and toddler) predictors of mid-childhood ADHD and anxiety symptoms compared to ASD symptoms. Methods Infants (n = 104) at high and low familial risk for ASD took part in research assessments at 7, 14, 24, and 38 months and 7 years of age. Symptoms of ASD, ADHD, and anxiety were measured by parent report at age 7. Activity levels and inhibitory control, also measured by parent report, in infancy and toddlerhood were used as early-life predictors of ADHD symptoms. Fearfulness and shyness measured in infancy and toddlerhood were used as early-life predictors of anxiety symptoms. Correlations and path analysis models tested associations between early-life predictors and mid-childhood ADHD and anxiety symptoms compared to mid-childhood ASD symptoms, and the influence of controlling for ASD symptoms on those associations. Results Increased activity levels and poor inhibitory control were correlated with ADHD symptoms and not ASD or anxiety; these associations were unchanged in path models controlling for risk-group and ASD symptoms. Increased fearfulness and shyness were correlated with anxiety symptoms, but also ASD symptoms. When controlling for risk-group in path analysis, the association between shyness and anxiety became non-significant, and when further controlling for ASD symptoms the association between fearfulness and anxiety became marginal. Conclusions The specificity of early-life predictors to ADHD symptoms suggests early developmental pathways to ADHD might be distinct from ASD. The overlap in early-life predictors of anxiety and ASD suggests that these disorders are difficult to differentiate early in life, which could reflect the presence of common developmental pathways or convergence in early behavioural manifestations of these disorders. Keywords ASD, ADHD, anxiety, comorbidity, early developmental pathwaysWe are very grateful for the important contributions BASIS families have made towards this study. The research was supported by the BASIS funding consortium led by Autistica (www.basisnetwork.org), Autism Speaks, a UK Medical Research Council Programme Grant (G0701484) to M.H. Johnson, and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Trust and King’s College London. R. Bedford is supported by a Sir Henry Wellcome Postdoctoral Fellowship. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The authors have no conflicts of interests

Impulsivity and risk-taking in clinical and non-clinical populations

Various aspects of impulsivity, including risk-taking, were investigated by comparing the responses of control groups with those of three populations that were believed to exhibit problems with impulse regulation: those with eating disorders, attention deficit hyperactivity disorder (ADHD) and recreational drug users. Impulsivity was regarded as a multi-dimensional construct, tests were selected or developed to tap into various aspects of impulsivity, including self-report questionnaires, a novel discrete trials delayed reinforcement operant choice paradigm, a novel measure of financial risk-taking, and the continuous performance test which provides measures of both inattention and impulsivity. These tests varied in their ability to discriminate between groups, and the correlations between measures, as in previous studies, were typically low and mostly non-significant. Findings supported the proposal that impulsivity is a multidimensional construct that must be assessed using a wide range of measures including self-report questionnaires and more objective behavioural measures. The profile of effects found in the three targeted groups supported the proposal that impulsivity manifests itself differently in different populations. Women with anorexia nervosa scored low on impulsiveness and venturesomeness, and demonstrated behavioural impulsivity. Recreational drug users scored high on impulsiveness, venturesomeness and risk-taking, whereas ADHD individuals were inattentive and scored high on impulsiveness and risk-taking taking, but not venturesomeness. Overall the findings highlight the complexity of the impulsivity concept and demonstrate the need to acknowledge its multi-dimensional nature by using a variety of tests to capture its variable expression. Whether impulsivity in particular groups reflects state or trait remains to be determined

Early developmental pathways to childhood symptoms of attention-deficit hyperactivity disorder, anxiety and autism spectrum disorder

Background Children with autism spectrum disorder (ASD) often have co-occurring symptoms of attention-deficit/hyperactivity disorder (ADHD) and/or anxiety. It is unclear whether these disorders arise from shared or distinct developmental pathways. We explored this question by testing the specificity of early-life (infant and toddler) predictors of mid-childhood ADHD and anxiety symptoms compared to ASD symptoms. Methods Infants (n = 104) at high and low familial risk for ASD took part in research assessments at 7, 14, 24 and 38 months, and 7 years of age. Symptoms of ASD, ADHD and anxiety were measured by parent report at age 7. Activity levels and inhibitory control, also measured by parent report, in infancy and toddlerhood were used as early-life predictors of ADHD symptoms. Fearfulness and shyness measured in infancy and toddlerhood were used as early-life predictors of anxiety symptoms. Correlations and path analysis models tested associations between early-life predictors and mid-childhood ADHD and anxiety symptoms compared to mid-childhood ASD symptoms, and the influence of controlling for ASD symptoms on those associations. Results Increased activity levels and poor inhibitory control were correlated with ADHD symptoms and not ASD or anxiety; these associations were unchanged in path models controlling for risk-group and ASD symptoms. Increased fearfulness and shyness were correlated with anxiety symptoms, but also ASD symptoms. When controlling for risk-group in path analysis, the association between shyness and anxiety became nonsignificant, and when further controlling for ASD symptoms the association between fearfulness and anxiety became marginal. Conclusions The specificity of early-life predictors to ADHD symptoms suggests early developmental pathways to ADHD might be distinct from ASD. The overlap in early-life predictors of anxiety and ASD suggests that these disorders are difficult to differentiate early in life, which could reflect the presence of common developmental pathways or convergence in early behavioural manifestations of these disorders

Possible Underlying Mechanisms of Hyperactivity in Children with ADHD

Conceptualizations of Attention-Deficit/Hyperactivity Disorder (ADHD) have evolved significantly over the years. Historically, early conceptualizations of ADHD described hyperactivity as the core symptom of the disorder. However, when the third version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) was published (1980), hyperactivity became a specific qualifier of the disorder and was no longer necessary for a diagnosis. Despite this shift in conceptualization of the disorder, there is an abundance of empirical evidence, both recent and historical, supporting the fact that hyperactivity is an enduring and clinically impairing symptom domain in ADHD. Despite having numerous validated instruments available to measure hyperactive behavior, most current models of ADHD are purely neurocognitive in nature and fail to sufficiently account for hyperactive symptoms. The aim of this study was to gain a deeper, more nuanced understanding of hyperactivity in children with ADHD, as many questions remain about the relationships between neuropsychological constructs and hyperactivity. A total of 130 participants with ADHD were enrolled and completed working memory and behavioral inhibition tasks while wearing actigraphs. Results showed that unmedicated children with working memory deficits display significantly higher levels of activity than children without a deficit in this area; however, this relationship was no longer significant after controlling for basic attentional processes. There were no significant relationships between level of hyperactivity and behavioral inhibition. Implications of these findings will be discussed in detail

Attention-deficit/hyperactivity disorder and substance abuse: prevalence and effect of past pharmacotherapy in young adults

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) frequently occurs in patients with SUD. Several studies demonstrated that ADHD constitutes a significant risk factor for the development of SUDs and suggest that childhood ADHD pharmacotherapy might help prevent the development of SUD. Furthermore, substance use patterns seem to differ between individuals with and without ADHD. Aim: The primary aim of this study was to establish the prevalence of ADHD in SUD in a South African treatment-seeking population, substance use patterns, and to determine the effect of past pharmacotherapy on later life’s functional impairment in adult ADHD treatment-seeking patients with a SUD. Method: Adult treatment-seeking SUD patients (n=360) were recruited from rehabilitation facilities and screened using the ADHD Self-Report Scale Symptom Checklist (ASRS-v1.1). ADHD diagnosis was confirmed (n=52) by the Diagnostic-Interview for ADHD in Adults (DIVA 2.0). Adults with ADHD without SUD (n=48) were recruited from clinicians, retail pharmacies and the general public. Life-time substance use was assessed using a self-report questionnaire. Tobacco use was assessed by the Fagerström Test for Nicotine Dependence (FTND). ADHD-related functional impairment was assessed by the Weiss Functional Impairment Rating Scale (WFIRS). Information on present and life-time use of ADHD medication was obtained. Clinical outcomes between those with and without a history of pharmacotherapy were compared. Results: ADHD is highly prevalent in South African adult treatment-seeking SUD patients. High rates of untreated and unrecognised ADHD were found. Individuals with SUD+ADHD were significantly associated with higher tobacco use. Data indicated increased levels of cannabis consumption among SUD+ADHD individuals, especially among SUD+ADHD females. Furthermore, we found that patients with ADHD were significantly associated with polysubstance use. Our results showed a history of childhood ADHD pharmacotherapy to be associated with less functional ADHD-related impairment across all functional domains and a decreased risk for substance use in later life. Abstract Conclusion: High rates of untreated and unrecognised ADHD were found among treatment-seeking SUD patients. ADHD patients appeared to self-medicate to cope with their symptoms. Childhood ADHD pharmacotherapy might be associated with a decreased risk for substance use in adulthood and lower ADHD-related impairment. Despite study limitations, these findings underline the importance of early ADHD detection and treatment, which might prevent substance use.Thesis (MA) -- Faculty of Health Sciences, 202