Schizophrenia Biochemical Bases Neurological Bases Major

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Lecture Overview

• Schizophrenia
• Biochemical Bases
• Neurological Bases
• Major Affective Disorders
• Biochemical Bases
• Seasonal Affective Disorder
• Anxiety Disorders
• Panic Disorder
• Obsessive-Compulsive Disorder

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Schizophrenia

• Disorder of thought and emotion
• Thought disorder
• Hallucinations
• Delusions
• Incidence (about 1)
• No gender differences in incidence

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Symptoms of Schizophrenia

• Positive symptoms presence of
• Delusions (e.g. control, grandeur, persecution)
• Hallucinations (auditory and olfactory)
• Thought disorder
• Negative symptoms loss of normal behaviors
• Poverty of speech
• Low initiative
• Social withdrawal
• Diminished affect

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Heritability of Schizophrenia

• The biological basis of schizophrenia is evident
  in heritability studies
• Adoption studies
• Schizophrenics adopted as children are likely to
  have schizophrenic biological relatives.
• Twin studies
• Concordance rates for schizophrenia are higher
  for identical than for fraternal twins
• No single gene identified for schizophrenia

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Negative Symptoms of Schizophrenia

• Signs of brain damage
• Eye tracking problems
• Catatonia
• Problems with blinking, eye focusing and pursuit
• Ventricular enlargement loss of brain cells
• Reduced activity of frontal lobes
• Damage to
• Dorsolateral prefrontal cortex
• Medial temporal lobes

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Hypofrontality in Schizophrenia

• PET scans reveal reduced neural activity within
  frontal lobes of schizophrenics

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Factors That May Produce Neurological Damage

• Birth trauma (obstetrical issues)
• Viral infections
• Seasonality effects (schizophrenia is more likely
  for winter births)
• Nutritional issues
• Stress

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Positive Schizophrenic Symptoms The Dopamine
Hypothesis

• Chlorpromazine (CPZ) was identified as an
  effective antipsychotic (AP) agent
• CPZ was later found to block DA receptors
• Drugs that block DA receptors vary in AP
  effectiveness
• Stimulants such as amphetamine release DA
• Chronic administration of amphetamine can induce
  schizophrenia
• Stimulants can reinstate psychoses in recovered
  patients

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DA Activity in Schizophrenia

• Increased DA levels some in striatum
• Increased receptor activity?
• Postmortem studies suggest increased D2 receptors
• PET studies suggest no change in D2 receptors in
  striatum
• AP drugs may induce observed changes in receptors
• Are we looking in the right place? (Nuc.
  accumbens should be examined)
• Clozapine may interact with D4 receptors in
  accumbens

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Side Effects of Antipsychotic Medication

• Autonomic problems (dry mouth)
• Skin-eye pigmentation
• Breast development (increased prolactin release)
• Tardive dyskinesia facial tics and gestures

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Major Affective Disorders

• Affect emotions, moods, and feelings
• Major affective disorders
• Bipolar disorder - alternating cycles of
• Mania euphoria, delusions
• Depression profound sadness, guilt, suicide risk
• Unipolar depression continuous, episodic

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Biological Bases of Affective Disorder

• Heritability of AD has been established in twin
  studies
• No clear linkage to a single gene
• Physical treatments for depression
• Pharmacological treatments
• MAO inhibitors (e.g. iproniazid)
• Serotonin reuptake inhibitors (e.g. Prozac)
• Electroconvulsive shock therapy (ECS)
• Sleep deprivation

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Monoamine Hypothesis of Depression

• Depression results from reduced activity of the
  monoamines NE or 5-HT
• Reserpine depletes monoamines--gt depression
• Antidepressants meds increase either NE or 5-HT
• Via blockade of reuptake
• Tryptophan deletion procedure
• Reduces brain 5-HT levels
• Reinstates depression in former depression
  patients
• Not effective in persons treated with NE reuptake
  drugs

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Links Between REM Sleep and Depression

• Sleep patterns in depressed persons
• REM deprivation improves mood
• Antidepressant drugs suppress REM sleep, and
  increase slow-wave sleep
• Persons who have short REM sleep latency are more
  likely to develop depression
• REM sleep deprivation is more effective than is
  total sleep deprivation

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Seasonal Affective Disorder

• SAD form of depression evident in winter months
  (short days/long nights)
• Mood and sleep disturbances
• Carbohydrate cravings and weight gain
• Phototherapy for SAD increased exposure to light
  improves mood in SAD (and also in unipolar
  depression)

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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

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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

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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

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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

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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

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Brain Activity and O-C Disorder

• Links between neurology and O-C Disorder
• Tourettes 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...

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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)