Inhibitory Deficits, Delay Aversion and Preschool AD/HD: Implications for the Dual Pathway Model

The dual pathway model proposes the existence of separate and neurobiologically distinct cognitive (inhibitory and more general executive dysfunction) and motivational (delay aversion) developmental routes to AD/HD. The study reported in this paper explores the relation between inhibitory deficits and delay aversion and their association with AD/HD in a group of three-year-old children. Children identified as having a pre-school equivalent of AD/HD (N=19) and controls (N=19), matched for gender and IQ, completed a battery of inhibition and delay tasks. Correlational and factor analysis supported a dissociation between inhibitory deficits (go-no-go, set shifting) and delay aversion (choice delay) with delay of gratification cross-loading. Children with AD/HD displayed more inhibitory deficits and were more delay averse than controls. The data support the value of the distinction between motivational and cognitive pathways to AD/HD. Furthermore, the data suggest that such a distinction is apparent relatively early on during development

Annual Research Review: Transdiagnostic neuroscience of child and adolescent mental disorders - differentiating decision making in attention-deficit/hyperactivity disorder, conduct disorder, depression, and anxiety.

BackgroundIneffective decision making is a major source of everyday functional impairment and reduced quality of life for young people with mental disorders. However, very little is known about what distinguishes decision making by individuals with different disorders or the neuropsychological processes or brain systems underlying these. This is the focus of the current review.Scope and methodologyWe first propose a neuroeconomic model of the decision-making process with separate stages for the prechoice evaluation of expected utility of future options; choice execution and postchoice management; the appraisal of outcome against expectation; and the updating of value estimates to guide future decisions. According to the proposed model, decision making is mediated by neuropsychological processes operating within three domains: (a) self-referential processes involved in autobiographical reflection on past, and prospection about future, experiences; (b) executive functions, such as working memory, inhibition, and planning, that regulate the implementation of decisions; and (c) processes involved in value estimation and outcome appraisal and learning. These processes are underpinned by the interplay of multiple brain networks, especially medial and lateralized cortical components of the default mode network, dorsal corticostriatal circuits underpinning higher order cognitive and behavioral control, and ventral frontostriatal circuits, connecting to brain regions implicated in emotion processing, that control valuation and learning processes.Findings and conclusionBased on clinical insights and considering each of the decision-making stages in turn, we outline disorder-specific hypotheses about impaired decision making in four childhood disorders: attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), depression, and anxiety. We hypothesize that decision making in ADHD is deficient (i.e. inefficient, insufficiently reflective, and inconsistent) and impulsive (biased toward immediate over delayed alternatives). In CD, it is reckless and insensitive to negative consequences. In depression, it is disengaged, perseverative, and pessimistic, while in anxiety, it is hesitant, risk-averse, and self-deprecating. A survey of current empirical indications related to these disorder-specific hypotheses highlights the limited and fragmentary nature of the evidence base and illustrates the need for a major research initiative in decision making in childhood disorders. The final section highlights a number of important additional general themes that need to be considered in future research

Why does early childhood deprivation increase the risk for depression and anxiety in adulthood? A developmental cascade model

Abstract Background: Using data from the English & Romanian Adoptees (ERA) study we recently reported that early time-lmited exposure to severe institutional deprivation is associated with early onset and persistent neurodevelopmental problems and later onset emotional problems. Here we examine possible reasons for the late emergence of emotional problems in this cohort. Our main focus is on testing a developmental cascade mediated via the functional impact of early-appearing neurodevelopmental problems on late adolescent functioning. We also explore a second putative pathway via sensitization to stress. Methods: The ERA study includes 165 Romanian individuals who spent their early lives in grossly depriving institutions and were subsequently adopted into UK families, along with 52 UK adoptees with no history of deprivation. Age six years symptoms of neurodevelopmental problems and age 15 anxiety/depression symptoms were assessed via parental reports. Young adult symptoms of depression and anxiety were assessed by both parent and self-reports; young adults also completed measures of stress reactivity , exposure to adverse life events and functioning in work and interpersonal relationships. Results: The path between early institutional deprivation and adult emotional problems was mediated via the impact of early neurodevelopmental problems on unemployment and poor friendship functioning during the transition to adulthood. The findings with regard to early deprivation, later life stress reactivity and emotional problems were inconclusive. Conclusions: Our analysis suggests that the risk for adult depression and anxiety following extreme institutional deprivation is explained through the effects of early neurodevelopmental problems on later social and vocational functioning. Future research should more fully examine the role of stress susceptibility in this model

A Pilot Study of Behavioral, Physiological, and Subjective Responses to Varying Mental Effort Requirements in Attention-Deficit/Hyperactivity Disorder

Background: Attention-deficit/hyperactivity disorder (ADHD) is presumed to involve mental effort application difficulties. To test this assumption, we manipulated task difficulty and measured behavioral, as well as subjective and psychophysiological indices of effort.Methods: Fifteen adolescent ADHD boys and 16 controls performed two tasks. First, subjective estimates and behavioral and pupillary measures of effort were recorded across five levels of N-back task difficulties. Second, effort discounting was assessed. In the latter, participants made repeated choices between performing a difficult N-back task for a high reward versus an easier N-back task for a smaller reward.Results: Increasing task difficulty led to similar deteriorations in performance for both groups – although ADHD participants performed more poorly at all difficulty levels than controls. While ADHD and control participants rated the tasks equally difficult and discounted effort similarly, those with ADHD displayed slightly different pupil dilation patterns with increasing task difficulty.Conclusion: The behavioral results did not provide evidence for mental effort problems in adolescent boys with ADHD. The subtle physiological effects, however, suggest that adolescents with ADHD may allocate effort in a different way than controls

Empirical tests of natural selection-based evolutionary accounts of ADHD: a systematic review

ADHD is a prevalent and highly heritable mental disorder associated with significant impairment, morbidity and increased rates of mortality. This combination of high prevalence and high morbidity/mortality seen in ADHD and other mental disorders presents a challenge to natural selection-based models of human evolution. Several hypotheses have been proposed in an attempt to resolve this apparent paradox. The aim of this study was to review the evidence for these hypotheses.We conducted a systematic review of the literature on empirical investigations of natural selection-based evolutionary accounts for ADHD in adherence with the PRISMA guideline. The PubMed, Embase, and PsycINFO databases were screened for relevant publications, by combining search terms covering evolution/selection with search terms covering ADHD.The search identified 790 records. Of these, 15 full-text articles were assessed for eligibility, and three were included in the review. Two of these reported on the evolution of the seven-repeat allele of the ADHD-associated dopamine receptor D4 gene, and one reported on the results of a simulation study of the effect of suggested ADHD-traits on group survival. The authors of the three studies interpreted their findings as favouring the notion that ADHD-traits may have been associated with increased fitness during human evolution. However, we argue that none of the three studies really tap into the core symptoms of ADHD, and that their conclusions therefore lack validity for the disorder.This review indicates that the natural selection-based accounts of ADHD have not been subjected to empirical test and therefore remain hypothetical

A pilot study of behavioral, physiological, and subjective responses to varying mental effort requirements in attention-deficit/hyperactivity disorder

Background: Attention-deficit/hyperactivity disorder (ADHD) is presumed to involve mental effort application difficulties. To test this assumption, we manipulated task difficulty and measured behavioral, as well as subjective and psychophysiological indices of effort. Methods: Fifteen adolescent ADHD boys and 16 controls performed two tasks. First, subjective estimates and behavioral and pupillary measures of effort were recorded across five levels of N-back task difficulties. Second, effort discounting was assessed. In the latter, participants made repeated choices between performing a difficult N-back task for a high reward versus an easier N-back task for a smaller reward. Results: Increasing task difficulty led to similar deteriorations in performance for both groups - although ADHD participants performed more poorly at all difficulty levels than controls. While ADHD and control participants rated the tasks equally difficult and discounted effort similarly, those with ADHD displayed slightly different pupil dilation patterns with increasing task difficulty. Conclusion: The behavioral results did not provide evidence for mental effort problems in adolescent boys with ADHD. The subtle physiological effects, however, suggest that adolescents with ADHD may allocate effort in a different way than controls

Mapping the structural organization of the brain in conduct disorder: replication of findings in two independent samples.

BACKGROUND: Neuroimaging methods that allow researchers to investigate structural covariance between brain regions are increasingly being used to study psychiatric disorders. Structural covariance analyses are particularly well suited for studying disorders with putative neurodevelopmental origins as they appear sensitive to changes in the synchronized maturation of different brain regions. We assessed interregional correlations in cortical thickness as a measure of structural covariance, and applied this method to investigate the coordinated development of different brain regions in conduct disorder (CD). We also assessed whether structural covariance measures could differentiate between the childhood-onset (CO-CD) and adolescence-onset (AO-CD) subtypes of CD, which may differ in terms of etiology and adult outcomes. METHODS: We examined interregional correlations in cortical thickness in male youths with CO-CD or AO-CD relative to healthy controls (HCs) in two independent datasets. The age range in the Cambridge sample was 16-21 years (mean: 18.0), whereas the age range of the Southampton sample was 13-18 years (mean: 16.7). We used FreeSurfer to perform segmentations and applied structural covariance methods to the resulting parcellations. RESULTS: In both samples, CO-CD participants displayed a strikingly higher number of significant cross-cortical correlations compared to HC or AO-CD participants, whereas AO-CD participants presented fewer significant correlations than HCs. Group differences in the strength of the interregional correlations were observed in both samples, and each set of results remained significant when controlling for IQ and comorbid attention-deficit/hyperactivity disorder symptoms. CONCLUSIONS: This study provides new evidence for quantitative differences in structural brain organization between the CO-CD and AO-CD subtypes, and supports the hypothesis that both subtypes of CD have neurodevelopmental origins.This research was funded by Wellcome Trust grant 083140 (Fairchild, Goodyer), Medical Research Council project U.1055.02.001.00001.01 (Calder), an Adventure in Research grant from Southampton University (Fairchild), a PhD studentship from Southampton University (Sully), and the Betty Behrens Research Fellowship at Clare Hall, Cambridge University (Passamonti).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/jcpp.1258

The Differential Effect of Anxiety and ADHD Symptoms on Inhibitory Control and Sustained Attention for Threat Stimuli: A Go/No-Go Eye-Movement Study

Objective: This study examined the synergistic effects of ADHD and anxiety symptoms on attention and inhibitory control depending on the emotional content of the stimuli. Method: Fifty-four typically developing individuals (27 children/adolescents and 27 adults) completed an eye-movement based emotional Go/No-Go task, using centrally presented (happy, angry) faces and neutral/symbolic stimuli. Sustained attention was measured through saccade latencies and saccadic omission errors (Go trials), and inhibitory control through saccadic commission errors (No-Go trials). ADHD and anxiety were assessed dimensionally. Results: Elevated ADHD symptoms were associated with more commission errors and slower saccade latencies for angry (vs. happy) faces. In contrast, angry faces were linked to faster saccade onsets when anxiety symptoms were high, and this effect prevailed when both anxiety and ADHD symptoms were high. Conclusion: Social threat impacted performance in individuals with sub-clinical anxiety and ADHD differently. The effects of anxiety on threat processing prevailed when both symptoms were high

Computerized cognitive training in attention-deficit/hyperactivity disorder (ADHD): a meta-analysis of randomized controlled trials with blinded and objective outcomes

This meta-analysis investigated the effects of computerized cognitive training (CCT) on clinical, neuropsychological and academic outcomes in individuals with attention-deficit/hyperactivity disorder (ADHD). The authors searched PubMed, Ovid, and Web of Science until 19th January 2022 for parallel-arm randomized controlled trials (RCTs) using CCT in individuals with ADHD. Random-effects meta-analyses pooled standardized mean differences (SMD) between CCT and comparator arms. RCT quality was assessed with the Cochrane Risk of Bias 2.0 tool (PROSPERO: CRD42021229279). Thirty-six RCTs were meta-analysed, 17 of which evaluated working memory training (WMT). Analysis of outcomes measured immediately post-treatment and judged to be “probably blinded” (PBLIND; trial n = 14) showed no effect on ADHD total (SMD = 0.12, 95%CI[−0.01 to −0.25]) or hyperactivity/impulsivity symptoms (SMD = 0.12, 95%[−0.03 to−0.28]). These findings remained when analyses were restricted to trials (n: 5–13) with children/adolescents, low medication exposure, semi-active controls, or WMT or multiple process training. There was a small improvement in inattention symptoms (SMD = 0.17, 95%CI[0.02–0.31]), which remained when trials were restricted to semi-active controls (SMD = 0.20, 95%CI[0.04–0.37]), and doubled in size when assessed in the intervention delivery setting (n = 5, SMD = 0.40, 95%CI[0.09–0.71]), suggesting a setting-specific effect. CCT improved WM (verbal: n = 15, SMD = 0.38, 95%CI[0.24–0.53]; visual-spatial: n = 9, SMD = 0.49, 95%CI[0.31–0.67]), but not other neuropsychological (e.g., attention, inhibition) or academic outcomes (e.g., reading, arithmetic; analysed n: 5–15). Longer-term improvement (at ~6-months) in verbal WM, reading comprehension, and ratings of executive functions were observed but relevant trials were limited in number (n: 5–7). There was no evidence that multi-process training was superior to working memory training. In sum, CCT led to shorter-term improvements in WM, with some evidence that verbal WM effects persisted in the longer-term. Clinical effects were limited to small, setting specific, short-term effects on inattention symptoms