Transcript Section 2 - Faculty Server Contact

Chapter 15
The Biological Basis of Affective Disorders and
Schizophrenia
Schizophrenia
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First described in 1883 by Emil Kraepelin – dementia
praecox, premature insanity
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The Swiss psychiatrist, Eugen Bleuler, coined the term,
"schizophrenia" in 1911. He was also the first to describe
the symptoms as "positive" or "negative."
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Bleuler renamed it schizophrenia for three reasons:
 The deteriorization doesn’t 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
psyche’s functions: emotion and perception
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
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
Hieronymus Bosch (1450 – 1516)
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
Course of Schizophrenia
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Prodromal phase - The phase which the person
becomes socially withdrawn and school or work
performance declines.
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Active phase -The phase in which the more acute
symptoms of the disorder appear, such as
hallucinations and delusions.
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Residual phase - The phase in which some recovery of
functioning occurs.
Schizophrenia: The Dopamine
Hypothesis and Drug Treatments
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Dopamine hypothesis of schizophrenia -The view that
an excess of activity in the dopamine system results
in the positive symptoms of schizophrenia.
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Chlorpromazine (a DA antagonist) blocks
postsynaptic DA receptors and improves positive
symptoms in schizophrenics.
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Therapeutic effectiveness is directly related to the
ability to bind tightly to the receptors
Schizophrenia:
Chlorpromazine’s Synaptic Effect
Clinical Potency of Antipsychotic Drugs
Schizophrenia:
Drug Treatments
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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 Parkinson’s) is a DA
agonist which can induce a psychosis which is
responsive to clozapine.
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
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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.
Possible Causes of Brain
Abnormalities
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Epidemiological studies
 Season of birth
 Viral epidemics
 Population density
 Vitamin D deficiency
 Prenatal malnutrition
 Substance abuse
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Complications of pregnancy and childbirth
 Fetal growth retardation
 Hypoxia
 Rh factor incompatability
Viral Infection and Schizophrenia
Hypofrontality Theory
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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.
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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.
Role of Genetics
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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
Schizophrenia:
No Definitive Explanations
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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