ADHD & ADD: Neuropsychiatric Disorders Study Guide

Introduction to ADHD and ADD

• Core Definition: ADHD is a neuropsychiatric disorder characterized by a persistent pattern of inattention, hyperactivity-impulsivity, or a combination of both.

Epidemiology and Prevalence in the United States

• Prevalence Rates:

  • Adults: $3 - 5\%$ of the US adult population is affected, totaling approximately $15.5$ million individuals.

  • Children: $5 - 7\%$ of the US child population is affected, totaling approximately $6.5$ million individuals.

• Gender and Demographics:

  • Approximately $15\%$ of boys in the United States have been diagnosed with ADHD.

• Comorbidity:

  • $2/3$ of children with ADHD have at least one co-occurring condition.

Clinical Presentation and Symptom Domains

ADHD symptoms are categorized into three primary domains:

• Inattention:

  • Poor level of focus.

  • General disorganization.

  • Frequent careless mistakes in tasks.

• Hyperactivity:

  • Persistent restlessness.

  • Significant difficulty staying still.

  • Excessive or compulsive talking.

• Impulsivity:

  • Lack of patience.

  • Poor emotional control.

  • Engaging in impulsive decision-making without considering consequences.

Aetiology and Risk Factors

• Genetic Predisposition:

  • There is a $5$ to $10$-fold increased risk of ADHD if a parent or sibling is also diagnosed with the disorder.

  • Twin studies indicate a high heritability rate of $70 - 80\%$.

  • Different genetic risk factors affect the clinical course of ADHD at various stages of the lifespan.

• Environmental Risk Factors:

  • Maternal Factors: In utero exposure to maternal smoking or alcohol use.

  • Birth Factors: Low birth weight and premature birth.

  • Toxin Exposure:

    • Organophosphate pesticides.

    • Polychlorinated biphenyls (PCBs).

    • Exposure to Zinc.

    • Exposure to Lead.

• Psychosocial Influences:

  • Chaotic family environments.

  • Peer influences.

  • Mismatch between the individual and school or work environments.

Clinical Progression Across the Lifespan

• In Utero: Genetic predisposition and fetal exposures lead to epigenetic changes.

• Preschool Years:

  • Emergence of the diagnosis.

  • Characterized by behavioral disinhibition and emotional lability.

  • Prodrome: Hyperactivity and problems related to speech, language, and motor coordination.

• Childhood:

  • Full expression of ADHD symptoms.

  • Psychiatric co-morbidity often appears.

  • Associated with school failure and peer rejection.

  • Neurocognitive dysfunction becomes evident.

• Adolescence:

  • Initiation of smoking.

  • Substance abuse risks.

  • Low self-esteem and social disability.

• Adulthood:

  • Inattention typically persists.

  • Hyperactive-impulsive symptoms often wane or diminish in intensity.

Neuroanatomical Pathophysiology

• Regional Functional Involvement:

  • Dorsolateral Prefrontal Cortex (DLPFC): Involved in working memory functions.

  • Ventromedial Prefrontal Cortex (VMPFC): Involved in complex decision-making and strategic planning.

  • Parietal Cortex: Linked to the orientation of attention.

• Structural and Functional Abnormalities:

  • Identified in the Ventral and Dorsal Anterior Cingulate Cortex (ACC), which are involved in the affective and cognitive components of executive function.

  • Frontostriatal Cortex: Formed by the ACC and the basal ganglia (specifically the caudate nucleus, nucleus accumbens, and putamen).

  • Abnormalities extend into the Amygdala and the Cerebellum.

• Physiological Persistence:

  • Cortical thickness abnormalities.

  • Default-Mode Network (DMN) fluctuations.

  • White matter tract abnormalities.

Signaling Systems and Functional Networks

• Dopaminergic Signaling: Essential for planning and initiation of motor responses, activation, switching between tasks, reaction to novelty, and reward processing.

• Noradrenergic Signaling: Influences arousal, signal-to-noise ratios in cortical areas, state-dependent cognitive processes, and cognitive preparation for urgent stimuli.

• Integrated Networks:

  • Executive Control and Corticocerebellar Networks: Coordinate planning, goal-directed behavior, inhibition, working memory, and flexible adaptation to context.

  • Reward Network: Centered on the VMPFC, orbitofrontal cortex, and ventral striatum; also involves the thalamus, amygdala, and substantia nigra. Behavioral and neural responses in this network are altered in ADHD patients.

  • Alerting Network: Involves interactions between the frontal cortex, parietal cortex, and thalamus. This network is typically weaker in individuals with ADHD.

Default-Mode Network (DMN) Alterations

• Components of the DMN:

  • Medial prefrontal cortex.

  • Posterior cingulate cortex.

  • Lateral parietal cortex.

  • Medial temporal lobe.

• Functional Issues in ADHD:

  • DMN fluctuations are "out of phase" with fluctuations in networks activated during externally oriented tasks.

  • This leads to competition between opposing processes for processing rewards.

  • Connections within these networks and between them are generally weaker in individuals with ADHD.

Addiction Cycle and Reward Signaling

• Dopamine and Reward: Many addictive substances trigger dopamine release.

• Opioid Signaling: Triggered by endogenous and exogenous agonists; central to reward mechanisms.

• Imaging Data: MRI studies show the activation of both dopamine and opioid neurotransmitters during the use of alcohol, opioids, nicotine, and other substances.

• Clinical Application: Antagonists of the opioid system may be used to treat drug- and alcohol-seeking behaviors.

• Stages: Includes Binge/Intoxication (localized in the Basal Ganglia).

Management of ADHD

• Patient and Family Education:

  • Understanding the causes of ADHD.

  • Awareness of associated morbidity.

  • Understanding the rationale behind specific treatments.

  • Planning for major life transitions.

• Psychosocial Environment:

  • Assessment of social support (e.g., intact family vs. separated).

  • Level of parental support for the diagnosis.

  • Screening for concerns of abuse or maltreatment.

  • Evaluating psychopathology or substance use in parents.

  • Identifying psychosocial stressors such as financial or medical distress.

  • Assessing the intellectual abilities of parents.

Pharmacological Interventions

• Assessment Requirements:

  • Must assess for comorbid conditions prior to intervention.

  • Consider the specific time of day symptom relief is required (e.g., school hours, extended school days, the working day, or evening).

• General Principles:

  • Both stimulant and non-stimulant treatments are effective for children and adults.

  • Preschool-aged children: Should ideally receive non-pharmacological treatment as the first line of defense; severe symptoms may eventually necessitate pharmacological interventions.

• Stimulant Medications:

  • Amphetamine.

  • Methylphenidate.

• Non-stimulant Medications:

  • Atomoxetine.

  • $\alpha_2$-adrenergic medications, including:

    • Guanfacine.

    • Clonidine.