ADHD and Substance Use Disorders Overview

Asynchronous Topic 2

• This asynchronous topic covers the biomedicine of ADHD and substance use disorders.

ADHD - Overview

• ADHD is a neuropsychiatric condition affecting all ages, primarily starting in childhood (before age 12).
• Key characteristics include diminished sustained attention, increased impulsivity, and/or hyperactivity.
• ADHD affects approximately 5-8% of school-aged children and a similar percentage of adults (5-6%).
• Approximately 60% of those with childhood-onset ADHD continue to show symptoms in adulthood.
• Three types of ADHD presentations exist: predominantly inattentive, predominantly hyperactive/impulsive, and combined.

DSM-V ADHD Criteria (Children/Adolescents)

• Symptoms must have persisted for over six months and appeared before age 12.
• Inattentive symptoms include problems with attention to detail, frequent mistakes, difficulty maintaining attention, appearing not to listen when spoken to, poor follow-through on tasks, organizational difficulties, procrastination, losing things, being easily distracted, and forgetfulness.
• Hyperactivity/impulsivity symptoms include fidgeting, restlessness, inability to stay seated, inappropriate running or climbing, difficulty engaging in quiet activities, talking excessively, blurting out answers, interrupting others, and inability to wait for their turn.
• Symptoms must occur in two or more settings (e.g., home, school, work).
• Symptoms must interfere with social, school, or work functioning.
• Other disorders must be ruled out
• Different presentations are predominantly inattentive (six or more inattention symptoms, fewer hyperactivity/impulsivity symptoms) and predominantly hyperactive/impulsive (six or more hyperactivity/impulsivity symptoms, fewer inattention symptoms).

DSM-V ADHD Criteria (Adults)

• Adults present with ADHD symptoms similar to children, but some differences exist.
• Inattentive symptoms in adults include careless mistakes, difficulty maintaining attention, not listening, failing to follow instructions, difficulty finishing tasks, organization challenges, procrastination, losing things, being easily distracted, and forgetfulness.
• Hyperactivity/impulsivity symptoms in adults include fidgeting, restlessness, leaving seats inappropriately, blurting out answers, interrupting others, inability to wait, and talking excessively.
• Instead of needing six or more criteria, five or more criteria are sufficient for diagnosis.

Substance Use Disorders

• Substance use disorders are chronic, relapsing disorders characterized by compulsive drug-seeking and use, leading to a loss of control.
• Outcomes include withdrawal, negative consequences from drug access being withheld, and other physical symptoms.
• Over 7 million in the US have a substance use disorder.
• Relapses are frequent in substance use and are accompanied by high rates of morbidity and mortality, due to factors such as excess mortality due to overdoses and direct/indirect effects of substances (cardiovascular, hepatic, or infectious diseases).
• Morbidity correlates with other psychiatric disorders and negative impacts on social networks and employment/education.

Stages of Substance Use: Stages, Theories

• Addiction progresses through stages:
• Stage 1: Acute reinforcement and drug use - Substances activate the same neurological systems for natural reinforcement.
• Stage 2: Escalation of drug use/dependence - Brain areas involved in acute reinforcement undergo long-term changes in certain neuroanatomical regions related to habit formation. Executive functioning and inhibitory control areas undergo harmful changes.
• Stage 3: Late stage – withdrawal/incubation/relapse --Long-term changes in reward and executive functions increase the likelihood of relapse when cues are present (social or environmental). Relapse is also triggered by stress and small amounts of substance.

Stages of Substance Use: Neuroanatomy, Neurochemistry: Key Brain Areas

• Key brain areas involved in substance use include midbrain (ventral tegmental area, dopaminergic), nucleus accumbens (part of ventral striatum), amygdala (rostral to hippocampus), hippocampus, prefrontal cortex and dorsal striatum (e.g., putamen, caudate).

Stages of Substance Use: Neuroanatomy, Neurochemistry: Stage 1 (acute reinforcement/drug use)

• The mesocorticolimbic pathway is a major reward pathway in humans.
• Mesolimbic; VTA (ventral tegmental area) – nucleus accumbens – reinforcement and reward
• Drugs of abuse trigger significant increases in dopamine (DA) release from VTA, causing stronger reinforcement.
• Mesocortical pathway connects VTA to the cortex, including the prefrontal cortex, regulating emotion, executive function, and cognitive control.

Stages of Substance Use: Neuroanatomy, Neurochemistry: Stage 2 (Escalation of Use and Dependence)

• Dorsal striatum is involved in cue-associated drug seeking and administration.
• Goal-directed drug-seeking behavior and craving.
• Dorsal striatum involved in mostly regulating movements/habits (not reward.)
• Prefrontal cortical areas likely underlie loss of behavioral control and inhibition.

Stages of Substance Use: Neuroanatomy, Neurochemistry: Stage 3 (Withdrawal and Relapse)

• The Ventral tegmental area (VTA) is implicated in all stages of addiction.
• Core areas of nucleus accumbens and prefrontal cortex are the common pathway for relapse behavior.
• Limbic regions (e.g., Hippocampus and amygdala) facilitate cue-related relapses or cravings late in the development of addiction.
• The limbic lobe (e.g.,nucleus accumbens, amygdala, other parts) are activated by stress, triggering relapse.

Neuroanatomy/Neurochemistry of ADHD

• Very limited understanding of ADHD based on well-proven human research. Animal models are less comprehensive, and multiple theories have been applied to human neuroimaging findings. Some heterogeneity in findings present in human research.
• Deficits in inhibiting motor or attention involve similar areas from the frontal cortex that are activated during executive functioning, or in areas of the dorsal striatum including the caudate/thalamus.
• The putamen, rather than the striatum overall, is the key area associated with attentional tasks.
• Challenges with temporal perception (timing) may also be associated with parietal regions and the cerebellum in some instances.
• Enhanced reward anticipation/sensitivity are associated with similar pathways as those in substance-use disorders (ventral striatum, VTA).
• Increased emphasis is seen on immediate vs. delayed reinforcement.
• The default-mode network (active at rest) and the alerting-mode network (maintaining attention) are involved in ADHD as well.
• D1 receptors and alpha-adrenoreceptors are likely affected/activated by stimulant medications, influencing dopamine uptake transporters.
• Differences are seen between the brain networks for ADHD and the ones for substance use disorders. Often the right side of the brain is implicated but not the left side.