Schizophrenia, Affective Disorders, Anxiety Disorders

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Schizophrenia, Affective Disorders, Anxiety
Disorders
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Schizophrenia

• Background
• Sex
• Age of onset
• Subtypes
• Positive vs negative symptoms

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Schizophrenia

• Positive Symptoms assoc with overactive DA
  systems
• Thought disorders
• Hallucinations
• Delusions
• Negative SymptomsL assoc with brain damage
• Flat affect
• Impoverished speech
• Anhedonia
• Social withdrawl
• Lack of initiative persistence

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Schizophrenia

• Heritabiligy
• Adoption studies
• Twin studies
• MZ vs DZ
• Chorion

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Schizophrenia

• Pharmacology
• The dopamine hypothesis
• Abnormalities in the DA pathways (esp mesolimbic
  pathway, ventral tegmental -gt nucleus accumbens
  and amygdala)

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Schizophrenia

• Mesolimbic pathway
• Nucleus accumbens amygdala
• Cocaine, amphetamines stimulate nucleus accumbens
  ? reinforce behavior ? in large doses, produce
  positive symptoms
• Abnormalities in DA transmission
• Release more DA
• More DA receptors

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Schizophrenia

• Pharmacology
• Chlorpromazine typical neuroleptic a dopamine
  receptor blocker (D2 receptors primarily in motor
  pathways decrease positive symptoms
• Clozapine atypical neuroleptic an
  antipsychotic drug that blocks D4 receptors in
  the nucleus accumbens.
• 1/3 dont respond to meds
• Tardive dyskinesia
• Supersensitivity

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Schizophrenia

• Brain Differences

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Schizophrenia

• Brain Differences

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Schizophrenia

• Environmental Factors
• Season of birth
• Viral epidemics
• Population density
• Latitude
• Prenatal malnutrition
• Rh incompatibility
• Maternal stress

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Schizophrenia

• Early Development
• Ratings of home movies
• Poorer social adjustment

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Major Affective Disorders

• Major Depressive Episode
• At least 4 symptoms for at least 2 wks (appetite
  disturbance, change in weight, sleep
  disturbances, psychomotor agitation or
  retardation, decreased energy, feelings of
  worthlessness or guilt, difficulty
  thinking/concentrating, suicidal ideation )
• 2-3 times more common in women
• 15.9 unipolar depression commit suicide
• Lifetime incidence of 5.8

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Major Affective Disorders

• Manic Episode
• Abnormally and persistently elevated, expansive,
  or irritable mood must last at least 1 week
• Must be accompanied by at least 3 of the
  following inflated self-esteem, decreased need
  for sleep, flight of ideas, distractibility,
  psychomotor agitation, jumping from topic to
  topic
• Lifetime incidence of .4-.6
• Equal across sexes

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Major Affective Disorders

• Heritability
• Individuals with close relatives 10xs more likely
  to develop an affective disorder
• MZ 69 DZ 13

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Major Affective Disorders

• Physiological Treatments for Depression
• Monoamine oxidase (MAO) inhibitors
• Increase NE, serotonin, and DA
• Side effects
• Tricyclic antidepressants
• Inhibit reuptake of 5-HT and NE
• Specific Serotonin Reuptake Inhibitors (SSRIs)
• Also reduce OCD and social phobia
• Electroconvulsive Therapy (ECT)
• 3/wk for 1-2 wks

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Major Affective Disorders

• Physiological Treatments for Depression
• Transcranial Magnetic Stimulation (TEMS)
• Applied to prefrontal cortex, reduces depression
  without any known side effects

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Major Affective Disorders

• Physiological Treatments for Mania
• Lithium
• Treat the manic phase
• May interfere with production of phosphoinositide
  system
• May increase production of neuroprotective
  proteins
• Side effects
• Danger of overdose
• Carbamazepine (Tegretol)
• Anti-seizure medication

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Major Affective Disorders

• Role of Monoamines
• Monoamine Hypothesis
• Unsupported by lack of response to cocaine or
  amphetamine which target DA
• Suicidal depression is related to decreased CSF
  5-HIAA (5-hydroxyindoleacetic acid)
• Lower 5-HT2 receptors in neocortex of depressed
• Tryptophan depletion procedure caused relapse
  into depression in patients taking antidepressants

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Major Affective Disorders

• Role of Monoamines
• Monoamine Hypothesis
• Unsupported by lack of response to cocaine or
  amphetamine which target DA
• Suicidal depression is related to decreased CSF
  5-HIAA (5-hydroxyindoleacetic acid)
• Lower 5-HT2 receptors in neocortex of depressed
• Tryptophan depletion procedure caused relapse
  into depression in patients taking antidepressants

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Major Affective Disorders

• Substance P
• A peptide secreted as a neurotransmitter and
  neuromodulator in several regions of the brain
• May be involved in emotional behavior, the
  response to stress, and the symptoms of
  depression.
• Binds with brain receptors in the amygdala,
  hypothalamus, ventral tegmental area, locus
  coeruleus, and the cerebral cortex.

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Major Affective Disorders

• Evidence for Brain Abnormalities
• Repeated episodes of mania/depression
• Increased lateral ventricles

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Major Affective Disorders

• Evidence for Brain Abnormalities
• Amygdala activity correlated with depression
• Orbitofrontal cortex more active in depressed
• Subgenual prefrontal cortex less active in
  depressed and more active during mania

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Major Affective Disorders

• Genes Brain Abnormalities
• 5-HTTLPR polymorphism
• Short-allele carriers
• Reduced gray matter in perigenual cingulate
  amygdala (critical for processing negative
  emotion provide a feedback circuit implicated in
  the extinction of negative affect)
• Relative uncoupling of this circuit
• Magnitude of coupling inversely predicted almost
  30 of variation in temperamental anxiety

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Major Affective Disorders

• Role of Circadian Rhythms
• Depression
• Shallow sleep reduced slow-wave (Stages 3 4)
  sleep increased Stage 1 sleep
• Repeated wakings (esp toward mornings)
• REM occurs earlier

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Major Affective Disorders

• Role of Circadian Rhythms
• REM Sleep Deprivation
• Alleviates depression slowly over several weeks
• Some have long-term improvement
• Medications suppress REM (delay onset and
  decrease duration)

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Major Affective Disorders

• Role of Circadian Rhythms
• Total Sleep Deprivation

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Anxiety Disorders

• Panic Disorder
• Onset usu young adulthood
• Women 2.5 xs more likely
• Symptoms
• Shortness of breath
• Clammy sweat
• Heartbeat irregularities
• Dizziness
• Faintness
• Feelings of unreality
• Feel as though he/she might die

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Anxiety Disorders

• Panic Disorder
• Large number of substances can produce panic
  attacks in individuals with panic disorder
  sodium lactate, carbon dioxide, yohimbine
  (increase NE, firing of locus coeruleus), and
  caffeine
• Hypersensitivity of CO2 receptors ? when
  activated these receptors act as suffocation
  alarms

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Anxiety Disorders

• Obsessive-Compulsive Disorder
• Obsessions thoughts that will not leave
• Compulsions behaviors one feels compelled to
  perform
• Incidence 1-2
• Slightly more common in females
• MZ vs DZ
• Assoc with Tourettes
• Can be secondary to birth trauma, encephalitis,
  head trauma, strep (basal ganglia, cingulate
  gyrus, and prefrontal cortex)

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Anxiety Disorders

• Obsessive-Compulsive Disorder
• Increased activity in frontal lobes (esp
  orbitofrontal cortex) and caudate nucleus
• Cingulotomy surgical removal of fiber bundles in
  the subcortical frontal lobe
• Trichtillomania
• Onychophagia