Addiction and Mental Health Disorders

I. Addiction and Mental Health Disorders

• Describe the process of neurotransmission

• Differentiate the common neurotransmitters and their mechanisms of action or failure

  • Example: Endorphins provide sense of well-being, dopamine is linked to reward processing

• Understand the dopamine drive

  • How the Mesolimbic/Limbic reward pathway works and its impact on addiction

• Identify the unique characteristics of the following mood disorders as they relate to neurotransmitters:

  • Depressive disorder

  • Anxiety disorders

  • ADHD

• Explain how overproduction or underproduction of the common neurotransmitters can impact mental health disorders and/or addiction

  • Example: Overproduction of dopamine has been linked to schizophrenia

  • Underproduction or lack of serotonin is associated with sleep disorders and depression

• Explain the mechanisms and negative outcomes of alcohol withdrawal

• Describe how long-term substance abuse is associated with dynorphin in the VTA

• Explain why someone with an addiction (such as meth) might have difficulty with self-care and care of offspring

  • VTA, Nucleus Accumbens, etc.

II. Normal Neuron Anatomy and Function

A. Communication happens at the synapse

• “Vesicles” house neurotransmitters

• They are released from the presynaptic side

B. If an action potential excites them:

• They fuse with the synaptic membrane

• Release their content in the synaptic cleft

• Bind with postsynaptic receptors

• An action then occurs

C. Neurotransmitters experience “re-uptake”

• Some left in the synaptic cleft

  • Will either drift away (diffusion)

  • Or degrade by specific enzymes

III. Neuronal Communication: Synaptic Transmission

• Postsynaptic side

• Note: Signaling associated with a particular transmitter is signified by the suffix “-ergic”

  • Glutamate: Main excitatory neurotransmitter (glutamatergic)

  • GABA: Main inhibitory neurotransmitter (GABAergic)

  • Acetylcholine: Neuromuscular transmission, parasympathetic visceral control, and central modulatory actions (cholinergic)

  • Dopamine (DA): Motor, endocrine, and motivational control (dopaminergic)

  • Norepinephrine (NE): Sympathetic visceral control, central arousal, and stress responses (noradrenergic)

  • Serotonin: Central food intake regulation, arousal, and mood modulation (serotonergic)

  • Histamine: Initiates the awake state (histaminergic)

  • Endorphins: Body’s natural opioid-like (pain-blocking) neurotransmitters

IV. Neurotransmitters—Relative Brain Abundance

V. Cerebral Anatomy

VI. Mesolimbic/Limbic Reward Pathway

VII. The Reward System

• Linked to survival

• Associative conditioning

• Reward prediction error

• How to behave to achieve maximal reward

• Dopamine and learning

VIII. 4 Dopaminergic Pathways

• Mesolimbic

• Nigrostriatal

• Mesocortical

• Tuberoinfundibular

IX. Mood Disorders – Major Depressive Disorder (MDD)

• Characterized by persistently depressed mood and loss of interest in activities (anhedonia) that causes significant impairment in daily life

• Very common

  • Around 8% of US population at any given time

  • 10–15% of men experience during lifetime

  • 20–25% of women experience during lifetime

• Most commonly manifests initially in 20s

• Associated with over half of all suicide attempts

• Suicide completion risk between 15–20%

• Causes:

  • Genetic (~40%)

  • Environmental (~60%)

• Linked to low serotonin and norepinephrine

X. Major Depressive Disorder (continued)

• Limbic system control instead of prefrontal cortex

• Decreased neurotransmitter levels

• Neurotrophic hypothesis: increased stress leads to decreased connections between prefrontal cortex and limbic system

• HPA axis dysfunction

• Increased pro-inflammatory cytokines and cortisol

Clinical manifestations of MDD:

• Unremitting feelings of sadness and despair

• Dysphoric mood

• Sleep disturbances

• Loss of appetite and body weight may go up or down

• Reduced interest in pleasurable activities and interpersonal relationships

• Decreased concentration

• Restlessness and agitation

• Feelings of worthlessness and guilt

• Suicidal thoughts

XI. Major Depressive Disorder

XII. General Anxiety Disorder

• Chronic, excessive, and persistent worry and anxiety that interferes with daily activities and relationships for the majority of days for at least 6 months

• Typically emerges in early 20s

• Most prevalent psychological disorders

Symptoms:

• Restlessness

• Muscle tension

• Irritability

• Easily fatigued

• Insomnia

• Difficulty concentrating

• Symptoms fluctuate: relapsing/remitting

• Often present with depression (50%) and panic attacks

• Often can lead to avoidance behaviors

XIII. Anxiety

Causes:

• Genetic susceptibility with environmental trigger (stress, trauma, experience)

• Polygenetic (multiple genes identified)

• Genetic heritability estimates:

  • 35% for General Anxiety Disorder

  • 50% for Panic Disorder and Agoraphobia

XIV. Attention Deficit/Hyperactivity Disorder (ADHD)

XV. Key Terms

• Potency: How strong?

• Route: PO, IV, IM, inhaled, transcutaneous, sublingual?

• Blood-brain barrier: Does the drug cross it?

• Side effects: Example: Opioids lead to respiratory depression and constipation

• Lethal Dose: How much to kill ½ population of testers?

• Tolerance: Needing more and more. Easy to overdose

• Drug interactions: Synergistic vs. antagonistic

• Duration: What’s the half-life? Why?

• Dependence: Neurons adapt so they can function normally in presence of drug

XVI. Addiction

• Tolerance

• Withdrawal

• Prediction Error (unexpected outcome) may help us, but it also gives us a dopamine spike to help us remember

• Dopamine is also released/spikes with conditioning such that it is no longer the reward we respond to but the expectation of the reward

• Thus, triggers become important in Substance Use Disorder (SUD)

• Reward Prediction Error (RPE):

  • Dopamine is Prediction Error

  • Dopamine is Anticipation of Reward

XVII. Examples of Psychoactive Substances

These often impact cognition, mood, perception, stimulate energy, etc.

• Stimulants (e.g., cocaine, meth)

• Alcohol

• Nicotine

• Caffeine

• Opioids

XVIII. Mechanism of Drug Actions

• Lock (receptor on outside of cell) and key (drug or molecule that triggers the lock)

• Activate or block receptors

  • Agonist – activates

  • Antagonist – blocks

• Block reuptake of neurotransmitter

  • Reuptake inhibitor

  • Reverse reuptake

XIX. Neurotransmitter Examples

• Serotonin

• Norepinephrine

• Dopamine

• GABA

• Glutamate

• Acetylcholine

• Adenosine

• Endorphins

XX. Withdrawal Syndromes

• Withdrawal syndromes look like the opposite of the drug’s effects

Examples:

• CNS depressants (alcohol, Xanax, Ativan, etc.) → CNS stimulation, irritability, seizures

• Opioids → Pain and diarrhea

• Methamphetamines → Depression, lack of energy, and sleep a lot

• Withdrawal from all substances includes anxiety

XXI. Alcohol Dependence and Withdrawal