Chapter 18: Anxiety Disorders, Autistic Disorder,and Stress Disorder

Chapter 16: Anxiety Disorders, Autistic Disorder,and Stress Disorder

Lecture Outline

Anxiety Disorders

Panic Disorder

Obsessive-Compulsive Disorder

Autistic Disorder

Stress Disorder

Physiology of Stress

PTSD

Psychoneuroimmunology

Anxiety Disorders

Panic Disorder: acute intense anxiety

Episodes of panic occur in 1-2 % of population

Early onset (rare after age 35)

Similar symptoms across cultures

Concerns about future panic attacks leads to

Agoraphobia: fear of panic attack in public places

Obsessive-Compulsive (O-C) Disorder

Recurrent thoughts and actions

Biological Bases of Panic Disorder

MZ twins have a higher concordance rate for panic disorder

Panic Disorder is more likely in families of patients with the disorder

Panic attacks can be triggered by:

Lactic acid

Caffeine

Increased levels of carbon dioxide in air

Biological Bases continued

Panic Disorder may involve

The putative satiety agent CCK

CCK4 induces panic attack

Serotonin

Panic Disorder responds to fluoxetine (5-HT agonist)

Panic Disorder is treated via:

Behavior therapy

Benzodiazepines: agonists alter GABA binding

Obsessive-Compulsive Disorder

Obsessions: recurrent thoughts

Compulsions: recurrent behaviors

Incidence of O-C Disorder is 1-2 percent

O-C Disorder begins in young adulthood

Symptoms of O-C Disorder are similar across differing cultures

O-C Disorder can greatly limit life options

Compulsions

Four categories of compulsions:

Counting ("am I missing a dollar?")

Cleaning (hands, house)

Checking ("Did I turn the stove off?")

Avoidance (e.g. dirt)

Resemble species-typical behaviors

Compulsive behaviors are exaggerations of normal species typical behaviors

Brain Activity and O-C Disorder

Links between neurology and O-C Disorder

Tourette’s syndrome: muscular/vocal tics

Damage to basal ganglia, cingulate gyrus, and prefrontal cortex

Increased activity within the frontal lobes

Drug therapy reduces frontal lobe activity

Surgical transection of the subcortical frontal lobe leads to improvement in O-C Disorder

22 caliber frontal lobotomy...

Pharmacotherapy of O-C Disorder

Drug therapy for O-C Disorder

5-HT systems

Blockade of 5-HT reuptake improves O-C Disorder

Clomipramine

Fluoxetine

Fluvoxamine

Antagonism of 5-HT worsens O-C Disorder

5-HT agonism appears to reduce intensity of the species-typical behaviors (e.g. washing)

Autism

Autism: impairments of

Social relations with others

Ability to communicate

Imaginative ability

Incidence of autism is 4/10,000

Males are 3 times more likely to develop autism

Biological Bases of Autism

Heritability: MZ twins exhibit a 96% concordance rate for autism

Autism is associated with neurological disorders:

Phenylketonuria (PKU)

Tourette’s syndrome

Fragile X syndrome (mental retardation)

Factors that impair development lead to autism:

Rubella, hydroencephalus

Drugs such as Thalidomide

Stress

Aversive stimuli can elicit emotional responses:

Behavioral component: Fight or Flight response

Autonomic component: Sympathetic activation

Endocrine: secretion of epinephrine, NE

Physiological reactions to chronic aversive stimuli/situations can be damaging

Stressors: the aversive stimuli

Stress Response: our reaction to stressors

Hormone Secretion during Stress

Stressors evoke activity in sympathetic N.S.

Adrenal glands release

Epinephrine: biases energy flow to muscles, increases blood pressure and blood flow to heart

Norepinephrine: increases blood flow and pressure

Glucocorticoids: break down protein and fats to glucose

Cortisol secretion is controlled by releasing factors from the PVN

PVN CRF --> ACTH --> adrenals: secrete glucocorticoids

CRF may act as a "stress" transmitter

Chronic Exposure to Stressors

Chronic stress is damaging to health

Air traffic controllers: more likely to develop

High blood pressure

Ulcers and diabetes

Chronic secretion of glucocorticoids leads to:

Increased blood pressure (--> stroke, heart attacks)

Loss of neurons in brain (e.g. hippocampal field CA1)

Suppression of the immune system (--> illness)

Suppression of the inflammatory system (delays healing)

Posttraumatic Stress Disorder

Posttraumatic Stress Disorder (PTSD):

Acute exposure to intense stressors can have delayed effects (Air disasters, war, assault)

Dreams, recall of trauma event

Flashback episodes of event

Intense distress

Predisposing Factors for PTSD

Personality variables that predispose to PTSD:

Tendency to brood about feelings

Vietnam Veterans study:

Family financial difficulty

History of drug abuse/dependence

History of affective disorders

History of childhood behavior problems

Genetic factors for PTSD:

Vietnam PTSD soldiers were more likely to possess an allele of the dopamine D₂ receptor

Coping Responses and Stress

Stress reflects our reaction to stressors

Coping implies modifying our responses:

Exerting control over aversive stimuli can reduce stress responses

Weiss study: rats that avoid shock show fewer ulcers

Coping may involve an increase in the level of benzodiazepines in brain (would act via GABA sites to reduce anxiety)

Psychoneuroimmunology

Psychoneuroimmunology: Study of the interactions between the immune system and behavior

Stress responses can impair the immune system

Leading to illness and potential death

Overview of the Immune System

Immune system destroys foreign organisms (viruses, bacteria, fungi)

Nonspecific reaction: act to destroy organisms or infected cells

Inflammatory reaction: damaged cells leak substances that increase blood flow

Phagocytotic white blood cells: destroy damaged cells

Cell infection --> interferon secretion (reduces viral replication

Natural killer cells: detect and destroy infected cells

Immune System Overview, continued

Specific Immune reactions:

Chemically-mediated: immune system produces antibodies that recognize the antigens present on surface of a foreign cell

B-lymphocytes: produce immunoglobulin antibodies that destroy foreign cells

Cell-mediated: antibodies on exterior of T-lymphocytes detect foreign antigens (viruses)

Stress and the Immune Response

Stress increases likelihood of infectious disease

Students are more likely to be ill during exam times

Death of a spouse leads to illness of survivor

Explanation: stress releases glucocorticoids that in turn impair the immune system

Supporting Evidence:

Bereavement leads to reduced immune response

Alzheimer’s caregivers have impaired immune response

Inescapable shock in rats reduces T-cells, B-cells and natural killer cells

Drug Abuse

Addiction and Dependence

Features of Addiction

Drug Abuse

Cocaine

Alcohol

Drug Therapy

Adverse Effects of Drug Abuse

Alcohol abuse is associated with:

Automobile accidents

Fetal alcohol syndrome

Cirrhosis of the liver

Korsakoff’s syndrome

Cardiac disease

Risk of intracerebral hemorrhage

Addiction and Dependence

Drug Addiction: "to sentence"

Physical dependence: associated with

Tolerance: decreased drug sensitivity over time

Withdrawal symptoms: opposite of drug effects

Psychological dependence: "Drug taking continues to ensure pleasurable state…"

Substance Dependence

Substance Dependence: Three of the following criteria in 12 months:

Presence of withdrawal symptoms

Increasing doses/tolerance

Unsuccessful efforts to stop drug-taking

Considerable time spent in obtaining/taking drug

Drug interference with social/occupational functions

Positive Reinforcement and Drug-Taking

Drugs activate positive reinforcement mechanisms in brain

Most addictive drugs increase dopamine levels within the nucleus accumbens

Some induce release from presynaptic terminals

Other drugs block reuptake into presynaptic terminal

Some drugs may act via endogenous opioids

Immediacy of drug action: is crucial to drug reinforcement

Negative Reinforcement and Drug-Taking

Behaviors that terminate aversive effects are negatively reinforced:

"It feels so good when it stops hurting"

Withdrawal symptoms that accompany drug-taking are usually aversive

Starting drug-taking again will terminate the withdrawal state

Drug-taking has positively- and negatively-reinforced aspects

Mechanisms of Tolerance/Withdrawal

Pharmacological action of drug on receptors:

downregulation/upregulation

Classical Conditioning:

CS: Stimuli associated with drug-taking (e.g. Needles)

UCS: Drug

UCR: Drug effect and homeostatic response to drug

CS alone: elicits compensatory homeostatic effect

Drug Craving

Craving is an impulsion to reinstate drug-taking during abstinence

Reflects an activation of the mesolimbic dopamine system by drug cues (needles, mirrors, pipes, etc)

Unpleasant feelings of abstinence

Pleasant recall of positive drug state

Drug Craving and D₃ Receptors

D₃ receptors located within nuc. accumbens may mediate drug craving

D₃ receptors are sensitized after cocaine use:

Cocaine-experienced monkeys will self-administer the D₃ receptor agonist 7-OH-DPAT

Cocaine-naïve monkeys do not...

D₃ receptor density is increased in nuc accumbens of cocaine-overdosed humans

Cocaine

Cocaine is a potent DA agonist

Binds and inactivates the DA transporter

Blocks reuptake to increase DA in synapse

Cocaine reinforcement is assessed using

Self-administration paradigm: animal presses lever that results in cocaine infusion via jugular catheter

Conditioned Place Preference paradigm: Does the animal prefer a compartment previously paired with the drug cue?

Cocaine Reinforcement: The Role of the Nucleus Accumbens

Positive Reinforcement and Cocaine:

Cocaine increases synaptic DA within the accumbens

Animals will self-inject DA agonists directly into the nuc. Accumbens (NAC)

Lesions of the NAC impairs self-administration of cocaine in rats

Negative Reinforcement and Cocaine:

Cocaine withdrawal results in reduced NAC dopamine

Alcohol

Alcohol effects depend on dose:

Low doses: reduces anxiety

Med-High doses: sedation and incoordination

Alcohol consumption produces:

Positive reinforcement: mild euphoria

Negative reinforcement: The aversive state of anxiety is reduced by alcohol consumption

Neural Bases of Alcohol Actions

Alcohol increases DA levels within NAC

Alcohol has effects at two receptor sites:

Inverse agonist at NMDA sites

Mediates increased DA release after alcohol

Mediates the sedative and anxiolytic effects of alcohol

Indirect agonist at GABA_A sites

Mediates the anxiolytic effect of alcohol

Alcoholism Types

Two varieties of alcoholics (ALC):

Steady drinkers: drink consistently, cannot abstain

Associated with antisocial personality

Bingers: can abstain but cannot stop once a drinking bout is started

Associated with introversion, guilt, and behavioral rigidity

Heritability of Alcohol Abuse

Twin studies: MZ twins show greater concordance for alcoholism than DZ twins

Cross-Fostering studies: examine rates of alcoholism in children adopted while young

Environment (one or more ALC adopted parents)

Heritage (one or more ALC biological parents)

Male steady drinking is strongly influenced by heritage

Male/female binge drinking is an interaction effect

Therapies for Drug Dependence

Cocaine use is reduced by:

Blockade of dopamine receptors

Issue: this also produces dysphoria and anhedonia

Blockade of D₃ receptors

Use of "cocaine immunization"

Alcohol intake is reduced by:

5-HT reuptake blockers

Opiate antagonists (naltrexone)