SEX

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SEX

• Differences in Schizophrenia
• Adam Taylor

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• Roses are red,
• Violets are blue,
• Im a schizophrenic
• And so am I

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Basics of Schizophrenia

• Approximately 1 of population affected
• Knows no cultural boundaries
• Generally presents around 18-30
• Can be lifelong, even with treatment
• Treatment is not a cure

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Symptoms

• Positive symptoms
• Hallucinations
• Delusions
• Negative symptoms
• Loss of affect and enjoyment
• Social withdrawal
• Cognitive symptoms
• Thought disorder
• General perception distortion

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Vulnerability-Stress Model
Principles of Neuropsychopharmacology
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Possible Causes

• Genetic evidence
• Monozygotic twin of a schizophrenic has 40-50 of
  becoming schizophrenic
• Child of a schizophrenic has 10 risk

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Genetic Risk
Principles of Neuropsychopharmacology
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Possible Causes

• Genetic evidence
• Monozygotic twin of a schizophrenic has 40-50 of
  becoming schizophrenic
• Child of a schizophrenic has 10 risk
• Dopamine
• Antipsychotics block DA transmission

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Dopamine Hypothesis

• DA agonists exacerbate symptoms and can produce
  schizophrenia-like symptoms
• Plasma HVA levels in CSF are low in patients with
  worse negative symptoms
• Kahn (1995) suggest hypodopamine in mesocortical
  neurons and hyperdopamine in mesolimbic neurons

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More Causes

• Developmental defect
• Evidence that certain stressors of the mother,
  such as flu during pregnancy, lead to a higher
  risk
• Animal models utilize prenatal stress to develop
  schizophrenic rats

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Neurodevelopmental Model
Principles of Neuropsychopharmacology
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More Causes

• Developmental defect
• Evidence that certain stressors of the mother,
  such as flu during pregnancy lead to a higher
  risk
• Animal models utilize prenatal stress to develop
  schizophrenic rats
• Serotonin (5-HT)
• Low levels of 5HIAA in patients with negative
  symptoms
• Hallucinogens stimulate 5-HT2a receptors leading
  to enhanced glutamate transmission in prefrontal
  cortex
• PCP
• NMDA antagonist produces psychotic effects,
  blocked by 5-HT2a antagonists

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Anatomical Defects

• Enlarged ventricles
• Prefrontal cortex atrophy
• Decreased hippocampal volume

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Treatment Basics

• Typical antipsychotics
• Chlorpromazine, haloperidol
• DA antagonists
• Treat positive symptoms well
• Tardive dyskinesia
• Atypical antipsychotics
• Clozapine, risperidone
• 5-HT2a antagonist
• D2 antagonist
• Adrenergic and histaminergic antagonist
• Treat positive, negative and cognitive symptoms

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Effects of Antipsychotics
Principles of Neuropsychopharmacology
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Antipsychotic Receptor Effects
Principles of Neuropsychopharmacology
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Are There Sex Differences?

• Males have earlier onset

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Age of Onset
Hafner, Psychoneuroendocrinology, 2003
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Are There Sex Differences?

• Males have earlier onset
• No difference in prevalence
• Women typically show better response to
  medication
• Some Differences in Behavior
• Some studies suggest men have more negative
  symptoms and women more positive (Castle, 1999)
  while others say no difference (e.g. Moldin,
  2000)
• Probably due to experimental differences

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Gender Differences in Behavior
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Behavior by Sex
Hafner, Psychoneuroendocrinology, 2003
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Gender Differences in Symptoms
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Neuropsychological Functioning
Goldstein et al., Am J Psychiatry, 1998
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Why Women?

• Women are generally older and have more social
  skills and understanding at disease onset
• Gastric emptying is slower than men
• Antipsychotics may be absorbed more efficiently
• Higher cerebral blood flow may distribute drugs
  better in women
• Higher body fat in women
• Antipsychotic drugs are highly lipophillic and as
  so may dissipate more slowly in women

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Estrogen Hypothesis

• Women have later onset
• Better response to treatment
• Some women report fluctuations in symptoms over
  menstrual cycle
• A cohort of women who become afflicted after
  menopause
• Higher doses of medication in postmenopausal
  women

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Late-Onset in Women
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Effects of Estrogen

• May mimic typical antipsychotics by blocking D2
  receptors
• May mimic atypical antipsychotics by decreasing
  5-HT2 receptor sensitivity (Hafner, 2003)
• Estrogen protects against cell death

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Effect of Estrogen Levels

• Global cognitive score
• Average of six cognitive domain scores
• Language, Executive, verbal memory, spatial
  memory, concentration and sensory-perceptual

Hoff et al., Am J Psychiatry, 2001
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Effect of Estrogen
Hafner, Psychoneuroendocrinology, 2003
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Effect of Estrogen
Hafner, Psychoneuroendocrinology, 2003
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Effect of Estrogen Treatment
Kulkarni et al., Schiz Res, 1996
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Effect of Estrogen Treatment
__ antipsychotic 100mcg estradiol ---
antipsychotic 50mcg estradiol antipsychotic
placebo
Kulkarni et al., Schiz Res, 2001
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The Conclusions Slide

• Schizophrenia is a chronic, disabling disorder
  characterized by many symptoms
• Differences between gender are somewhat
  questionable
• Estrogen seems to play a protective role in
  female schizophrenics
• Adjunctive estrogen treatment may be beneficial