The Biological Basis of Affective Disorders and Schizophrenia

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Chapter 15

• The Biological Basis of Affective Disorders and
  Schizophrenia

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Schizophrenia

• First described in 1883 by Emil Kraepelin
  dementia praecox, premature insanity
• The Swiss psychiatrist, Eugen Bleuler, coined the
  term, "schizophrenia" in 1911. He was also the
  first to describe the symptoms as "positive" or
  "negative."
• Bleuler renamed it schizophrenia for three
  reasons
• The deteriorization doesnt always begin in
  adolescence, it can begin later in life
• Mental functioning may actually improve rather
  than deteriorate after it is diagnosed
• The disorder seems to reflect a splitting of the
  psyches functions emotion and perception

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Schizophrenia a definition

• Mental disorder characterized by loss of contact
  with reality disturbances in perception,
  emotion, cognition, motor behavior.
• Characterized by positive, negative, and
  cognitive symptoms
• Positive Symptoms - Behaviors exhibited by a
  person with schizophrenia but absent in people
  without the disorder
• Negative Symptoms - Normal behaviors that are
  absent in people with schizophrenia
• Cognitive Symptoms Deficits in learning,
  reasoning or perception

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Positive Symptoms

• Thought disorders - tangentiality, neologisms,
  loosening of associations, word salad, rambling
  monologues
• Delusions grandeur, persecution, control
• Hallucinations visual, tactile, auditory,
  olfactory, gustatory
• Movement - high levels of motor excitement,
  catatonic behaviors, repetitive motor activities

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Hieronymus Bosch (1450 1516)
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Negative Symptoms

• Disturbances in affect - blunted or flat affect
• Lack of interest in life, low motivation
• Anhedonia inability to experience pleasure
• Social withdrawal or emotional detachment
• Low energy
• Alogia poverty of speech
• Inappropriate social skills or lack of interest
  or ability to socialize with other people
• Inability to make friends or keep friends, or not
  caring to have friends

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Cognitive Symptoms

• Disorganized thinking
• Slow thinking
• Difficulty sustaining attention
• Difficulty understanding
• Poor concentration and problem solving
• Poor memory
• Difficulty expressing thoughts
• Difficulty integrating thoughts, feelings and
  behavior

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Course of Schizophrenia

• Prodromal phase - The phase which the person
  becomes socially withdrawn and school or work
  performance declines.
• Active phase -The phase in which the more acute
  symptoms of the disorder appear, such as
  hallucinations and delusions.
• Residual phase - The phase in which some recovery
  of functioning occurs.

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Schizophrenia The Dopamine Hypothesis and Drug
Treatments

• Dopamine hypothesis of schizophrenia -The view
  that an excess of activity in the dopamine system
  results in the positive symptoms of
  schizophrenia.
• Chlorpromazine (a DA antagonist) blocks
  postsynaptic DA receptors and improves positive
  symptoms in schizophrenics.
• Therapeutic effectiveness is directly related to
  the ability to bind tightly to the receptors

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Schizophrenia Chlorpromazines Synaptic Effect
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Clinical Potency of Antipsychotic Drugs
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Schizophrenia Drug Treatments

• Effect of DA agonists
• Amphetamine and cocaine produce positive symptoms
  of schizophrenia.
• Amphetamine use exacerbates positive symptoms in
  people already diagnosed with schizophrenia.
• L-Dopa (used to treat Parkinsons) is a DA
  agonist which can induce a psychosis which is
  responsive to clozapine.

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Evidence Against a DA Hypothesis of Schizophrenia

• Approximately 30 of people with schizophrenia do
  not experience relief of positive symptoms with
  DA antagonists.
• There are also lower levels of GABA and glutamate
  in brains of people with schizophrenia. Some
  studies suggest the NMDA receptor may be involved.

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Problems with DA Antagonists

• Tardive dyskinesia - A motor disorder with facial
  tics and involuntary limb movements often
  appears after long-term use
• Relief from negative symptoms is not experienced
  with DA antagonists
• A new family of antipsychotic drugs, which block
  D4 receptors, relieve positive and negative
  symptoms without causing tardive dyskinesia
• A hypothesis of brain damage may explain the
  negative symptoms

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Brain Damage and Schizophrenia

• Lateral ventricles of many people are enlarged.
• Loss of dendritic material in the prefrontal
  cortex.
• Reduced numbers of neurons in the thalamus and
  hippocampus.
• Hippocampus connections with the prefrontal
  cortex are connected in a more disorganized
  fashion than normal.

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Possible Causes of Brain Abnormalities

• Epidemiological studies
• Season of birth
• Viral epidemics
• Population density
• Vitamin D deficiency
• Prenatal malnutrition
• Substance abuse
• Complications of pregnancy and childbirth
• Fetal growth retardation
• Hypoxia
• Rh factor incompatability

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Viral Infection and Schizophrenia
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Hypofrontality Theory

• Theory that the negative symptoms of
  schizophrenia are caused by decreased activity in
  the prefrontal cortex.
• PET scans show decreased activity in the frontal
  area of the brain
• People with schizophrenia have difficulty with
  tasks requiring working memory.
• Metabolic hypofrontality in people with
  schizophrenia can be reversed with DA agonists
  but at what cost?
• Third generation antipsychotic partial agonist
• Some people do not exhibit hypofrontality, so
  results are mixed with regard to this theory.

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Role of Genetics

• What is inherited is only a susceptibility or
  genetic predisposition to develop schizophrenia.
• The concordance rate for identical twins is not
  100 but about 50 indicating that a particular
  gene is not by itself sufficient to produce
  schizophrenia.
• No single gene for schizophrenia
• Children of older fathers
• Epigenetic influences inhibit or promote gene
  expression

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Schizophrenia No Definitive Explanations

• Neither the DA theory nor the hypofrontality
  theory provide a complete explanation.
• Several brain structures are dysfunctional and
  act together to produce symptoms.
• Schizophrenia may be several related disorders
  rather than a single disorder
• Some patients have prefrontal dysfunctions,
  others do not
• DA antagonists help some patients but not others.
• What role, if any, does puberty play
• Much more research is necessary