Synaptic Gating and ADHD: A Biological Theory of Comorbidity of ADHD and Anxiety

Abstract

To derive a biologically based theory of comorbidity in Attention Deficit Hyperactivity Disorder (ADHD). Theoretical concepts and empirical studies were reviewed to determine whether the behavioral inhibition concept provided an understanding of biological processes involved in comorbidity in ADHD. Empirical studies of ADHD have shown comorbidity of ADHD and anxiety, while studies of behavioral inhibition tend to suggest independent disruptive and anxiety traits. This paradox can be resolved by an understanding of the dynamics of mesolimbic dopamine (DA) systems, where reward and delay of reinforcement are determined by tonic/phasic DA relationships, resulting in impulsive 'fearless' responses when impaired. On the other hand, comorbid anxiety is related to impaired synaptic processes, which selectively gate fear (or aggressive) responses from the amygdala at the accumbens. Monosynaptic convergence between prefrontal, hippocampal, and amygdala projection neurons at the accumbens allows the operation of a synaptic gating mechanism between prefrontal cortex (PFC), hippocampus, and amygdala. Impairment of this mechanism by lowered PFC inhibition allows greater amygdala input, and anxiety-related processes more impact, over the accumbens. In conclusion, a dual theory incorporating long-term tonic/phasic mesolimbic DA relationships and secondly impairment of PFC and hippocampal inputs to synaptic gating of anxiety at the accumbens has implications for comorbidity in ADHD, as well as for possible pharmacological interventions, utilizing either stimulant or axiolytic interventions. The use of DA partial agonists may also be of interest.

Behavioral functions of the mesolimbic dopaminergic system: An affective neuroethological perspective

“…Convergent glutamatergic input may thus form a switching signal (Redgrave et al, 1999), allowing new information to enter basal forebrain/BG areas and new sequential activity patterns to be generated in BG-thalamocortical circuits. Consistent with this view, an imbalance between phasic and tonic DA transmission may promote attention deficit hyperactivity disorders (Levy, 2004) and probably also Tourette's syndrome. BG-thalamocortical circuits of these subjects may be overcharged by switching signals, as external stimuli continuously release new neurodynamic sequences.…”

ADHD and criminality: A primer on the genetic, neurobiological, evolutionary, and treatment literature for criminologists

“…A number of researchers have offered evidence that ADHD is a product of a deficient BIS and CD is a product of an oversensitive BAS (Levy, 2004;Quay, 1997). This double disability indicates that ADHD+ CD sufferers are inclined to seek high levels of stimulation because of an oversensitive BAS, and then their faulty BIS hampers them in putting a stop to their search for pleasurable stimulation once it is initiated.…”

Child and Caregiver Issues In the Treatment of Attention Deficit–Hyperactivity Disorder: Education, Adherence and Treatment Choice

“…These children may show more symptoms of inattention and aggressiveness, or lower academic and social achievement. [15,51] Affective disorders 4-33% Depressive symptoms (sadness and irritability above the normal level), major depressive disorder (impairing symptoms persisting for at least 2 weeks) and dysthymic disorder (intermittent presentation of depressive symptoms for at least 1 year). Affective symptoms may become manifest as conduct problems in the ADHD child.…”