Neurobiology of Schizophrenia, Neurobiology of Schizophrenia, Mood Disorders, and Anxiety Mood Disorders, and Anxiety

DisordersDisorders

Chapter 18Chapter 18

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SchizophreniaSchizophrenia Schizophrenia is a term coined by Eugene Schizophrenia is a term coined by Eugene

Bleuler in 1911 to describe a collection of Bleuler in 1911 to describe a collection of illnesses characterized by thought disordersillnesses characterized by thought disorders

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SchizophreniaSchizophrenia

1% of population (higher in twins, siblings)1% of population (higher in twins, siblings) Emerges in young adults Emerges in young adults

Slightly earlier onset in males than females Slightly earlier onset in males than females Psychotic episodePsychotic episode Genetic predispositionGenetic predisposition

Monozygotic twins concordance rate 30% to 50%Monozygotic twins concordance rate 30% to 50% Dizygotic twins/siblings concordance rate 15%Dizygotic twins/siblings concordance rate 15%

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SchizophreniaSchizophrenia Neuroanatomic alterationsNeuroanatomic alterations

Enlargement of lateral and third ventricles; Enlargement of lateral and third ventricles; widening of frontal cortical fissures and sulci widening of frontal cortical fissures and sulci

Neurotransmitter alterationsNeurotransmitter alterations Brain dopamine pathways alteredBrain dopamine pathways altered Glutamate (acts on the Glutamate (acts on the NN-methyl--methyl-DD-aspartate -aspartate

[NMDA] receptor subtype) [NMDA] receptor subtype) • Implicated in learning and memoryImplicated in learning and memory

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SchizophreniaSchizophrenia

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SchizophreniaSchizophrenia

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SchizophreniaSchizophrenia Clinical manifestationsClinical manifestations

HallucinationsHallucinations DelusionsDelusions Disorganized behaviorDisorganized behavior

• Disorganized speechDisorganized speech

• Disorganized behaviorDisorganized behavior

Negative symptomsNegative symptoms• Affective flatteningAffective flattening

• Anhedonia, alogia, and avolitionAnhedonia, alogia, and avolition

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Mood DisordersMood Disorders Mood refers to a sustained emotional stateMood refers to a sustained emotional state Affective states are brief emotional feelingsAffective states are brief emotional feelings

Euphoria, joy, surprise, fear, sadness, etc.Euphoria, joy, surprise, fear, sadness, etc. DepressionDepression

States such as sadness become prominentStates such as sadness become prominent

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Mood DisordersMood Disorders Categories of mood disorderCategories of mood disorder

UnipolarUnipolar• Also called major depression, clinical depressionAlso called major depression, clinical depression

Bipolar disorderBipolar disorder Genetic predispositionGenetic predisposition

Twin studies: concordance rates Twin studies: concordance rates • 40% monozygotic; dizygotic 11% 40% monozygotic; dizygotic 11%

Environmental influencesEnvironmental influences

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Mood DisordersMood Disorders Neurochemical dysregulationNeurochemical dysregulation Neuroendocrine dysregulation Neuroendocrine dysregulation

Hypothalamic-pituitary-adrenal system Hypothalamic-pituitary-adrenal system dysregulationdysregulation

Hypothalamic-pituitary-thyroid (HPT) system Hypothalamic-pituitary-thyroid (HPT) system dysregulationdysregulation

Neuroanatomic and functional abnormalitiesNeuroanatomic and functional abnormalities

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HPT System HPT System Dysregulation and MoodDysregulation and Mood

20% to 30% of persons with unipolar depression 20% to 30% of persons with unipolar depression have an altered HPT system have an altered HPT system

Increased CSF levels of thyrotropin-releasing Increased CSF levels of thyrotropin-releasing hormone (TRH) hormone (TRH)

Blunted thyrotropin-stimulating hormone (TSH) Blunted thyrotropin-stimulating hormone (TSH) response to TRH challengeresponse to TRH challenge

Decreased nocturnal rise in TSHDecreased nocturnal rise in TSH

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Mood DisordersMood Disorders Clinical manifestationsClinical manifestations

DepressionDepression ManiaMania

TreatmentTreatment AntidepressantsAntidepressants Psychotherapy Psychotherapy Combination of bothCombination of both

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Mood DisordersMood Disorders

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Antidepressant TreatmentAntidepressant Treatment Three major classes of antidepressant Three major classes of antidepressant

medications medications Monoamine oxidase inhibitors (MAOIs)Monoamine oxidase inhibitors (MAOIs) Tricyclic antidepressants (TCAs)Tricyclic antidepressants (TCAs) Selective serotonin reuptake inhibitors (SSRIs)Selective serotonin reuptake inhibitors (SSRIs)

All increase monoamine neurotransmitter All increase monoamine neurotransmitter levels within the synapselevels within the synapse

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Mood DisordersMood Disorders

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Anxiety DisordersAnxiety Disorders Panic disorderPanic disorder

80% respond to cognitive behavioral therapy 80% respond to cognitive behavioral therapy (CBT) and/or antidepressant medication(CBT) and/or antidepressant medication

Generalized anxiety disorderGeneralized anxiety disorder Excessive and persistent worries Excessive and persistent worries Norepinephrine and serotonin abnormalitiesNorepinephrine and serotonin abnormalities GABA-BZ receptor alterationsGABA-BZ receptor alterations

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Anxiety DisordersAnxiety Disorders Posttraumatic stress disorder (PTSD)Posttraumatic stress disorder (PTSD)

Exposure to terrifying, life-threatening traumaExposure to terrifying, life-threatening trauma Lifetime prevalence rate 7% to 8% Lifetime prevalence rate 7% to 8% Adults: smaller hippocampus, brain structure Adults: smaller hippocampus, brain structure

susceptible to damaging effects of the stress susceptible to damaging effects of the stress hormone cortisol and excitatory amino acidshormone cortisol and excitatory amino acids

Pediatric: studies reveal generalized effect of Pediatric: studies reveal generalized effect of trauma on reducing total brain volume trauma on reducing total brain volume

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Anxiety DisordersAnxiety Disorders Obsessive-compulsive disorderObsessive-compulsive disorder

Repetitive, intrusive thoughts and/or compulsionsRepetitive, intrusive thoughts and/or compulsions Obsessions: involve a preoccupation with Obsessions: involve a preoccupation with

contamination, doubting, religious or sexual contamination, doubting, religious or sexual themes, or the belief that a negative outcome will themes, or the belief that a negative outcome will occur if a specific act is not performedoccur if a specific act is not performed

Compulsions: physical and mental ritualized acts Compulsions: physical and mental ritualized acts