Chapter 18
Neurobiology of Schizophrenia,
Mood Disorders, and Anxiety
Disorders
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Schizophrenia
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Schizophrenia is a term coined by Eugene
Bleuler in 1911 to describe a collection of
illnesses characterized by thought disorders
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Schizophrenia
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1% of population (higher in twins, siblings)
Emerges in young adults
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Slightly earlier onset in males than females
Psychotic episode
Genetic predisposition
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Monozygotic twins concordance rate 30% to 50%
Dizygotic twins/siblings concordance rate 15%
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Schizophrenia
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Neuroanatomic alterations
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Enlargement of lateral and third ventricles;
widening of frontal cortical fissures and sulci
Neurotransmitter alterations
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Brain dopamine pathways altered
Glutamate (acts on the N-methyl-D-aspartate
[NMDA] receptor subtype)
• Implicated in learning and memory
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Schizophrenia
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Schizophrenia
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Schizophrenia
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Clinical manifestations
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Hallucinations
Delusions
Disorganized behavior
• Disorganized speech
• Disorganized behavior
Negative symptoms
• Affective flattening
• Anhedonia, alogia, and avolition
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Mood Disorders
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Mood refers to a sustained emotional state
Affective states are brief emotional feelings
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Euphoria, joy, surprise, fear, sadness, etc.
Depression
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States such as sadness become prominent
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Mood Disorders
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Categories of mood disorder
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Genetic predisposition
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Unipolar
• Also called major depression, clinical depression
Bipolar disorder
Twin studies: concordance rates
• 40% monozygotic; dizygotic 11%
Environmental influences
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Mood Disorders
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Neurochemical dysregulation
Neuroendocrine dysregulation
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Hypothalamic-pituitary-adrenal system
dysregulation
Hypothalamic-pituitary-thyroid (HPT) system
dysregulation
Neuroanatomic and functional abnormalities
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HPT System
Dysregulation and Mood
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20% to 30% of persons with unipolar depression
have an altered HPT system
Increased CSF levels of thyrotropin-releasing
hormone (TRH)
Blunted thyrotropin-stimulating hormone (TSH)
response to TRH challenge
Decreased nocturnal rise in TSH
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Mood Disorders
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Clinical manifestations
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Depression
Mania
Treatment
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Antidepressants
Psychotherapy
Combination of both
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Mood Disorders
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Antidepressant Treatment
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Three major classes of antidepressant
medications
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Monoamine oxidase inhibitors (MAOIs)
Tricyclic antidepressants (TCAs)
Selective serotonin reuptake inhibitors (SSRIs)
All increase monoamine neurotransmitter
levels within the synapse
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Mood Disorders
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Anxiety Disorders
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Panic disorder
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80% respond to cognitive behavioral therapy
(CBT) and/or antidepressant medication
Generalized anxiety disorder
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Excessive and persistent worries
 Norepinephrine and serotonin abnormalities
 GABA-BZ receptor alterations
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Anxiety Disorders
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Posttraumatic stress disorder (PTSD)
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Exposure to terrifying, life-threatening trauma
Lifetime prevalence rate 7% to 8%
Adults: smaller hippocampus, brain structure
susceptible to damaging effects of the stress
hormone cortisol and excitatory amino acids
Pediatric: studies reveal generalized effect of
trauma on reducing total brain volume
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Anxiety Disorders
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Obsessive-compulsive disorder
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Repetitive, intrusive thoughts and/or compulsions
Obsessions: involve a preoccupation with
contamination, doubting, religious or sexual
themes, or the belief that a negative outcome will
occur if a specific act is not performed
Compulsions: physical and mental ritualized acts
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