Autistic, ADHD, Stress, and Substance Abuse Disorders

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Autistic, ADHD, Stress, and Substance Abuse
Disorders
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Autism Spectrum Disorders

• Pervasive Developmental Disorders
• Autistic Disorder
• Aspergers Disorder
• Childhood Disintegrative Disorder
• Retts Disorder
• PDD-NOS

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Autism Spectrum Disorders

• Autism
• Impairments in reciprocal social interaction
• Stereotyped behaviors/interests
• Impairment in communication/ language
• Onset prior to 3
• Behavior is disordered, not just delayed

• Aspergers
• Impairments in reciprocal social interaction
• Stereotyped behaviors/interests
• No significant general delays/impairments in
  cognitive functioning, language development, or
  adaptive behavior

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Autism Spectrum Disorders

• Basic Info
• Prevalence 1 in 166
• ¾ ASD are male
• Signs/symptoms as early as 6-12 mo

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Autism Spectrum Disorders

• Possible Causes
• Biological
• Hereditary
• 2-3 of siblings of ASD are autistic.
• 70 concordance rate for MZ

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Autism Spectrum Disorders

• Heredity
• 2-3 of siblings of ASD are autistic
• 70 concordance rate for MZ
• Phenylketonuria (PKU) hereditary disorder caused
  by the absence of an enzyme that converts the
  amino acid phenylalanine to tyrosine causes
  brain damage unless a special diet is implemented
  soon after birth

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Autism Spectrum Disorders

• Brain Pathology
• Increased brain weight and volume in
  preadolescent ASD
• Normal head circumference _at_ birth ? increasing
  brain volume occurring between 2-4 yrs
• Disproportionate increase in white matter volume
  relative to gray matter (e.g., myelin may be
  altered)

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Autism Spectrum Disorders

• Brain Pathology
• Limbic System small neuronal cell sizes and
  increased cell packing density (consistent with
  developmental curtailment)
• Impaired declarative memory
• Abnormalities of Cerebellum
• Children with autism dont show early life
  serotonin surge

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Autism Spectrum Disorders

• Brain Pathology

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Autism Spectrum Disorders

• Brain Pathology

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Autism Spectrum Disorders

• Brain Pathology

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ADHD

• Attention-deficit/hyperactivity disorder (ADHD)
• A disorder characterized by uninhibited
  responses, lack of sustained attention, and
  hyperactivity first shows itself in childhood.

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ADHD

• Possible Causes
• Genetics
• Family and Twin Studies
• Learning
• Steeper slope between strength of reinforcement
  delay to reinforcing stimulus

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ADHD

• Possible Causes
• Biological
• Evidence to suggest that abnormalities in
  dopaminergic transmission play a role in ADHD
• Brain structures
• Studies of brain structure of people with ADHD do
  not reveal any localized abnormalities, though
  the total volume of their brains is approximately
  4 smaller than normal

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Stress Disorders

• Stress
• A general, imprecise term that can refer either
  to a stress response or to a stressor (stressful
  situation)
• Stressor
• A stimulus (or situation) that produces a stress
  response

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Stress Disorders

• Fight-or-Flight Response
• A species-typical response preparatory to
  fighting or fleeing
• Thought to be responsible for some of the
  deleterious effects of stressful situations on
  health

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Stress Disorders

• Physiology of Stress
• Glucocorticoid hormone of the adrenal cortex
  impt in protein carbohydrate metabolism
• Corticotropin-releasing hormone (CRH)
  hypothalamic hormone stimulates anterior
  pituitary to secrete ACTH

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Stress Disorders

• Physiology of Stress
• Adrenocorticotropic hormone (ACTH) Released by
  anterior pituitary stimulates the adrenal cortex
  to produce glucocorticoids

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Stress Disorders

• Stress and Health

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Stress Disorders

• Psychoneuroimmunology
• The branch of neuroscience involved with
  interactions between environmental stimuli, the
  nervous system, and the immune system.

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Stress Disorders

• Psychoneuroimmunology
• Antigen a protein present on a microorganism
  that permits the immune system to recognize the
  microorganism as an invader.
• Antibody protein produced by a cell of the
  immune system that recognizes antigens present on
  invading microorganisms.
• B-lymphocyte white blood cell that originates in
  the bone marrow part of the immune system.

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Stress Disorders

• Psychoneuroimmunology
• Immunoglobulin antibody released by
  B-lymphocytes that bind with antigens and help to
  destroy invading microorganisms.
• T-lymphocytes white blood cell that originates
  in the thymus gland
• Cytokine category of chemicals released by
  certain white blood cells when they detect the
  presence of an invading microorganism causes
  other white blood cells to proliferate and mount
  an attack against the invader.

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Substance Use/Abuse

• Physical versus Psychological Addiction
• Tolerance
• increasingly large doses of drugs must be taken
  to achieve a particular effect
• Caused by compensatory mechanisms that oppose the
  effect of the drug
• Withdrawal symptoms
• The appearance of symptoms opposite to those
  produced by a drug when the drug is suddenly no
  longer taken
• Caused by the presence of compensatory mechanisms

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Substance Use/Abuse

• Positive Reinforcement
• Addictive drugs have reinforcing effects. That
  is, their effects include activation of the
  reinforcement mechanism.
• This activation strengthens the response that was
  just made, namely, taking the drug.
• Drugs with the most immediate effects tend to be
  the most addictive.

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Substance Use/Abuse

• Negative Reinforcement
• The removal or reduction of an aversive stimulus
  that is contingent on a particular response, with
  an attendant increase in the frequency of that
  response.
• If taking a drug turns off aversive withdrawal
  effects it is a negatively reinforced behavior
  that will increase in frequency.

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Substance Use/Abuse

• Craving and Relapse
• Reinstatement model
• Brain mechanisms in Craving and Relapse
• Relapse appears to involve activation of the
  mesolimbic system of dopaminergic neurons.
• Relapse caused by stimuli previously associated
  with cocaine appears to involve the amygdala as
  well as the mesolimbic dopamine system
• PET scan studies have demonstrated activity of
  the prefrontal cortex and the anterior cingulate
  cortex of cocaine abusers was less active than
  that of normal subjects during abstinence.

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Substance Use/Abuse

• Craving and Relapse
• Stress
• Clinicians have long observed that stressful
  situations can cause a former drug addict to
  relapse
• Stressful stimuli, even those that occur early in
  life, increase an animals susceptibility to drug
  addiction
• Stress is associated with the release of CRH in
  the brain by cells of the central nucleus of the
  amygdala whose terminals release this peptide in
  the bed nucleus of the stria terminalis.

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Substance Use/Abuse

• Opiates
• Endogenous opiates are secreted when an animal is
  performing behaviors that are important to its
  survival such as fighting with another animal
• Endogenously released opioids stimulate receptors
  that produce analgesia that reduces the
  inhibitory effects of pain and positive
  reinforcement that encourages the animal to
  continue with what is was doing.

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Substance Use/Abuse

• Opium
• Derived from a sticky resin produced by the opium
  poppy and has been eaten or smoked for centuries
• Heroin is the most commonly abused opiate

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Substance Use/Abuse

• Opium
• Neural Basis of Reinforcing Effects
• Periaqueductal gray matter (PAG) analgesia.
• Preoptic area hypothermia (reduction of body
  temperature).
• Mesencephalic reticular formation sedation
• Ventral Tegmental area (VTA) and the nucleus
  accumbens reinforcing effects of opiates.

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Substance Use/Abuse

• Opium
• Neural Basis of Reinforcing Effects
• Dynorphin endogenous opioid the natural ligand
  for k-opiate receptors.
• Conditioned place preference
• Naloxone drug that blocks mu opiate receptors
• Pimozide drug that blocks dopamine receptors

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Substance Use/Abuse

• Opium
• Neural Basis of Withdrawal Effects
• Brain mechanisms several regions of the brain
  have been implicated including the periaqueductal
  gray matter, the locus coeruleus, and the
  amygdala
• Antagonist-precipitated withdrawal sudden
  withdrawal from long-term administration of a
  drug caused by cessation of the drug and
  administration of an antagonistic drug.
• CREB cyclic AMP-responsive element binding
  protein

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Substance Use/Abuse

• Cocaine and Amphetamine
• Cocaine and amphetamine have similar behavioral
  effects, because both act as potent dopamine
  agonists
• Cocaine binds with and deactivates the dopamine
  transporter proteins, thus blocking the reuptake
  of dopamine after it is released by terminal
  buttons
• Amphetamine enters nerve terminals and displaces
  neurotransmitter molecules (noradrenaline,
  dopamine) from storage areas prevents reuptake
  inhibits MAO

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Substance Use/Abuse

• Cocaine

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Substance Use/Abuse

• Cocaine

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Substance Use/Abuse

• Cocaine Amphetamine
• Effects of cocaine amphetamine
• Prior abusers of meth showed decr dopamine
  transporters in caudate nucleus putamen, even
  after 3-yr abstinence

• Potent DA agonists, activate the mesolimbic
  system reinforce drug-taking behavior.
• Incr concentration of DA in nucleus accumbens
  (critical site in the reinforcing effect of the
  drugs)

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Substance Use/Abuse

• Cocaine and Amphetamine
• Effect of cocaine and amphetamine
• Long-term cocaine or amphetamine use does not
  produce tolerance and is even likely to produce
  sensitization to the effects of the drug.
• Withdrawal from cocaine does not cause physical
  symptoms, but it does cause unpleasant feelings,
  including dysphoria and decreased ability to feel
  pleasure.

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Substance Use/Abuse

• Nicotine
• Accounts for more deaths than the so-called hard
  drugs.
• 1/3 of the adult population of the world smokes.
• By the year 2020, tobacco will be the largest
  single health problem worldwide, with 8.4 million
  deaths per year
• 40 of people continue to smoke after having had
  a laryngectomy
• gt 50 of heart attack survivors continue to smoke
• 50 of people continue to smoke after surgery
  for lung cancer.

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Substance Use/Abuse

• Nicotine
• Stimulates acetylcholine receptors and incr
  activity of DA neurons of the mesolimbic system
• Injections of nicotine agonist into ventral
  tegmental area reinforces conditioned place
  preference.

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Substance Use/Abuse

• Nicotine

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Substance Use/Abuse

• Alcohol and Barbiturates
• Alcohol
• Alcohol has greater costs to society than any
  other drug
• A large percentage of deaths and injuries caused
  by motor vehicle accidents are related to alcohol
• The leading cause of mental retardation in the
  Western world today is alcohol consumption by
  pregnant women

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Substance Use/Abuse

• Alcohol
• Sites of action
• Indirect agonist at GABAA receptors and as an
  indirect antagonist at NMDA receptors
• Stimulation of both receptors systems triggers
  apoptosis (cellular death)
• Behavioral effects
• At low doses alcohol produces mild euphoria and
  has an anxiolytic effect (reduces anxiety).
• At higher doses alcohol produces uncoordination
  and sedation.

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Substance Use/Abuse

• Alcohol
• Behavioral effects
• The mild euphoria of alcohol provides positive
  reinforcement for continued drinking.
• Alcohol also relieves anxiety and continued use
  is negatively reinforced.
• Brain mechanisms
• Alcohol, like other addictive drugs, increases
  the activity of the dopaminergic neurons of the
  mesolimbic system and increases the release of
  dopamine in the nucleus accumbens.

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Substance Use/Abuse

• Alcohol
• Brain mechanisms
• Enhances the action of GABA and GABAA receptors
  interferes with transmission of glutamate at NMDA
  receptors.
• Perceptual effects are mimicked by both GABA
  agonists and NMDA antagonists.
• Observations strongly suggest that NMDA receptors
  are responsible for the seizures produced by
  alcohol withdrawal.
• The sedative effect of alcohol also appears to
  exerted at the GABAA receptor.

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Substance Use/Abuse

• Cannabis
• Brain mechanisms
• Site of action is the endogenous cannabinoid
  receptor, the CB1 receptor

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Substance Use/Abuse

• Cannabis
• Brain mechanisms
• THC admin stimulates release of DA in nucleus
  accumbens ventral tegmental area
• Acts directly on DA terminal buttons-presumably
  on presynaptic heteroreceptors.

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Substance Use/Abuse

• Cannabis
• Brain mechanisms
• Hippocampus contains large concentration of THC
  receptors.
• Disrupts normal functioning of the hippocampus
• Long-term damage
• Bronchitis, increased risk of lung cancer, minor
  impairments of attention and memory, and slower
  decision making
• Subtle cognitive impairments

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Substance Use/Abuse

• Heritability and Drug Abuse
• Heritability Studies of Humans
• In general, studies have found that the
  heritability of smoking is just as strong as that
  of alcoholism.
• A twin study found that alcoholism and nicotine
  dependence have genetic factors in common, which
  explains why alcoholics are often addicted to
  nicotine.