Chapter 18 Biopsychology of Psychiatric Disorders

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Chapter 18Biopsychology of Psychiatric Disorders

• The Brain Unhinged

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Psychiatric Disorders

• AKA psychological disorders
• Disorders of psychological function that require
  treatment by a mental health professional
• Neuropsychological disorders - a product of
  dysfunctional brains but so are psychiatric
  disorders
• Historically
• Neuropsychological disorders brain problem
• Psychiatric mind problem

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Psychiatric Disorders

• More influenced by experiential factors
• Tend to be the product of more subtle forms of
  brain pathology
• Underlying dysfunction may yet to be identified,
  but are suggested by the effectiveness of
  treatments
• Tend to be less well understood

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Psychiatric Disorders

• What are the advantages and disadvantages of
  societal acceptance of psychological disorders as
  diseases with a biological basis?
• Are there some conditions for which this
  acceptance already exists?

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Anxiety Disorders

• Anxiety fear in the absence of threat
• Anxiety disorder when anxiety interferes with
  normal functioning
• Accompanied by physiological symptoms
  tachycardia, hypertension, sleep disturbances,
  nausea, etc.
• Most prevalent psychiatric disorders

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Anxiety Disorders

• Generalized stress and anxiety in the absence
  of a causal stimulus
• Phobic similar to generalized, but triggered by
  a stimulus
• Panic disorders may occur with other disorders,
  but also alone
• Obsessive-compulsive disorders (OCDs) obsessive
  thoughts alleviated by compulsive actions
• Posttraumatic stress disorder

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Treatment of Anxiety Disorders

• Benzodiazepines (Librium, Valium)
• Also used as hypnotics, anticonvulsants, muscle
  relaxants
• GABAA agonists bind to receptor and facilitate
  effects of GABA
• Highly addictive
• Serotonin agonists (Buspirone, SSRIs)
• Reduce anxiety without sedation and other side
  effects

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The GABA Receptor
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Animal Models of Anxiety

• Assess anxiolytic potential of drugs - assume
  that defensive behaviors are motivated by fear,
  and that fear and anxiety are comparable
• Elevated-plus-maze time in open arms indicates
  less anxiety
• Defensive-burying More time burying, more
  anxiety
• Risk-assessment test Time freezing and assessing
  risk indicate anxiety level
• Validated by effectiveness of benzodiazepines
  but not all anxiety treated with such drugs

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Neural Bases of Anxiety Disorders

• Drugs suggest a role for serotonin and GABA
• Amygdala, due to its role in fear and defensive
  behavior, thought to be involved
• No pathology yet identified

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Affective Disorders

• Depression normal reaction to loss, abnormal
  when it persists or has no cause
• Mania opposite of depression
• Bipolar affective disorder
• Depression with periods of mania
• Unipolar depression only
• Reactive triggered by negative event
• Endogenous no apparent cause

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Causal Factors in Affective Disorders

• Affective disorders are very common
• 6 suffer from unipolar affective disorder at
  some point, 1 from bipolar
• Genetics
• Concordance rate higher for bipolar than unipolar
• Stressful experiences
• More stress reported by those seeking treatment
  for depression than controls

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Antidepressant Drugs

• Monoamine oxidase inhibitors (MAOIs)
• Prevent breakdown of monoamines
• Must avoid foods high in tyramine cheese
  effect
• Tricyclic antidepressants
• Block reuptake of serotonin and norepinephrine
• Safer than MAOIs
• Selective monoamine reuptake inhibitors
• Lithium mood stabilizer
• Not a drug treats bipolar

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Selective monoamine reuptake inhibitors

• Selective serotonin-reuptake inhibitors (SSRIs)
• Prozac, Paxil, Zoloft
• No more effective than tricyclics, but side
  effects are few and they are effective at
  treating other things
• Selective norepinephrine-reuptake inhibitors
  (SNRIs)
• Also effective

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Effectiveness of Drug in Treating Affective
Disorders

• Results are comparable with MAOIs, tricyclics,
  and SSRIs
• About 50 improve, compared to 25 of controls
• Drugs help those experiencing depression, but do
  not prevent future episodes

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Monoamine Theory of Depression

• Underactivity of serotonin (5HT) and
  norepinephrine (NE)
• Consistent with drug effects
• Up-regulation of receptors at autopsy of
  depressed individuals consistent with this
• Problem with theory not all respond to
  monoamine agonists

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Diathesis-Stress Model

• Inherited genetic susceptibility (diathesis)
  stress depression
• Support is indirect
• Depressed people tend to release more stress
  hormones
• Fail dexamethasone suppression test normal
  negative feedback on stress hormones not
  functioning

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Sleep Deprivation

• More than 50 of depressed patients improve after
  one night of sleep deprivation.
• Short-lasting depression returns when normal
  sleep pattern resumes.
• Not explained by any theory.
• What does this suggest?

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Brain Damage and Unipolar Depression

• Amygdala
• Prefrontal cortex
• Both involved in perception and experience of
  emotion
• Terminal structures of the mesotelencephalic DA
  system
• Consistent with anhedonia (lack of pleasure)
  experienced by the depressed

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Tourettes Syndrome

• A disorder of tics, involuntary movements or
  vocalizations
• Begins in childhood
• Major genetic component
• Many also have signs of ADHD and/or OCD
• No animal models, no genes identified, imaging
  difficult due to tics

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Tourettes Syndrome

• Usually treated with neuroleptics although
  effectiveness is not well-established
• Effectiveness of D2 blockers suggests abnormality
  in basal ganglia-thalamus-cortex feedback circuit

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Schizophrenia

• splitting of psychic functions
• Refers to the breakdown of integration of
  emotion, thought, and action
• Affects 1 of the population
• A diverse disorder multiple types exist with
  varied profiles
• Some symptoms delusions, hallucinations, odd
  behavior, incoherent thought, inappropriate
  affect
• Only 1 needed for 8 months for diagnosis

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Causal Factors in Schizophrenia

• Clear genetic basis
• Inherit an increased risk for the disorder
• Multiple causes
• Several different chromosomes implicated
• Associated with various early insults
  infections, autoimmune reactions, toxins,
  traumatic injury, stress
• Appears that interference with the normal
  development of susceptible individuals may lead
  to development of the disorder

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Antipsychotic Drugs

• Much of our understanding of schizophrenia is a
  consequence of the drugs that are able to treat
  it
• Chlorpromazine calms many agitated
  schizophrenics and activates many emotionally
  blunt
• Reserpine also found to be effective
• Both drugs are not effective for 2-3 weeks and
  Parkinson-like motor effects are seen
• Suggesting a role for what neurotransmitter?

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Dopamine (DA) Theory of Schizophrenia

• 1960 link between DA and Parkinsons Disease
  established
• Side effects of antipsychotic drugs suggests role
  for dopamine Drugs work by decreasing DA levels,
  disorder is a consequence of DA overactivity
• Reserpine depletes brain of DA and other
  monoamines by making vesicles leaky
• Amphetamine and cocaine are DA agonists and
  produce psychosis
• Chlorpromazine antagonizes DA activity by binding
  and blocking DA receptors

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Dopamine (DA) Theory of Schizophrenia

• In general, the higher affinity a drug has for DA
  receptors, the more effective it is in treating
  schizophrenia
• Haloperidol an exception
• While most antipsychotics bind to D1 and D2
  receptors, it and the other butyrophenones bind
  to D2
• Degree that neuroleptics bind to D2 receptors is
  correlated with their effectiveness

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Problems with the D2 Theory

• Clozapine, an atypical and effective neuroleptic,
  acts at D1, D4, and serotonin receptors. But
  some binding to D2
• Neuroleptics act quickly at the synapse, but
  dont alleviate symptoms for weeks.
• Indicates some slow-acting change must occur.
• Schizophrenia associated with brain damage.
• Little damage to DA circuitry
• Damage not explained by DA theory
• Neuroleptics are only effective for some

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Problems with the D2 Theory

• Positive symptoms - presence of abnormal
• incoherence, hallucinations, delusions
• Negative absence of normal
• flat affect, cognitive deficits, little speech
• Conventional neuroleptics (D2 blockers) mainly
  effective at treating positive
• Negative might be caused by brain damage
• May be best to think of schizophrenia as multiple
  disorders with multiple causes