Neurobiology of Schizophrenia, Mood Disorders, and Anxiety Disorders Chapter 18 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2 Schizophrenia Schizophrenia is a term coined by Eugene Bleuler in 1911 to describe a collection of illnesses characterized by thought disorders Schizophrenia is a term coined by Eugene Bleuler in 1911 to describe a collection of illnesses characterized by thought disorders

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Schizophrenia 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 episode Psychotic episode Genetic predisposition Genetic 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%

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Schizophrenia Neuroanatomic alterations Neuroanatomic alterations Enlargement of lateral and third ventricles; widening of frontal cortical fissures and sulci Enlargement of lateral and third ventricles; widening of frontal cortical fissures and sulci Neurotransmitter alterations Neurotransmitter alterations Brain dopamine pathways altered Brain dopamine pathways altered Glutamate (acts on the N-methyl- D -aspartate [NMDA] receptor subtype) Glutamate (acts on the N-methyl- D -aspartate [NMDA] receptor subtype) Implicated in learning and memory Implicated in learning and memory

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 Schizophrenia

6 Schizophrenia

7 Schizophrenia Clinical manifestations Clinical manifestations Hallucinations Hallucinations Delusions Delusions Disorganized behavior Disorganized behavior Disorganized speech Disorganized speech Disorganized behavior Disorganized behavior Negative symptoms Negative symptoms Affective flattening Affective flattening Anhedonia, alogia, and avolition Anhedonia, alogia, and avolition

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Mood Disorders Mood refers to a sustained emotional state Mood refers to a sustained emotional state Affective states are brief emotional feelings Affective states are brief emotional feelings Euphoria, joy, surprise, fear, sadness, etc. Euphoria, joy, surprise, fear, sadness, etc. Depression Depression States such as sadness become prominent States such as sadness become prominent

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Mood Disorders Categories of mood disorder Categories of mood disorder Unipolar Unipolar Also called major depression, clinical depression Also called major depression, clinical depression Bipolar disorder Bipolar disorder Genetic predisposition Genetic predisposition Twin studies: concordance rates Twin studies: concordance rates 40% monozygotic; dizygotic 11% 40% monozygotic; dizygotic 11% Environmental influences Environmental influences

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Mood Disorders Neurochemical dysregulation Neurochemical dysregulation Neuroendocrine dysregulation Neuroendocrine dysregulation Hypothalamic-pituitary-adrenal system dysregulation Hypothalamic-pituitary-adrenal system dysregulation Hypothalamic-pituitary-thyroid (HPT) system dysregulation Hypothalamic-pituitary-thyroid (HPT) system dysregulation Neuroanatomic and functional abnormalities Neuroanatomic and functional abnormalities

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 HPT System Dysregulation and Mood 20% to 30% of persons with unipolar depression have an altered HPT system 20% to 30% of persons with unipolar depression have an altered HPT system Increased CSF levels of thyrotropin-releasing hormone (TRH) Increased CSF levels of thyrotropin-releasing hormone (TRH) Blunted thyrotropin-stimulating hormone (TSH) response to TRH challenge Blunted thyrotropin-stimulating hormone (TSH) response to TRH challenge Decreased nocturnal rise in TSH Decreased nocturnal rise in TSH

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 Mood Disorders Clinical manifestations Clinical manifestations Depression Depression Mania Mania Treatment Treatment Antidepressants Antidepressants Psychotherapy Psychotherapy Combination of both Combination of both

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Mood Disorders

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Antidepressant Treatment Three major classes of antidepressant medications Three major classes of antidepressant 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 levels within the synapse All increase monoamine neurotransmitter levels within the synapse

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Mood Disorders

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Anxiety Disorders Panic disorder Panic disorder 80% respond to cognitive behavioral therapy (CBT) and/or antidepressant medication 80% respond to cognitive behavioral therapy (CBT) and/or antidepressant medication Generalized anxiety disorder Generalized anxiety disorder Excessive and persistent worries Excessive and persistent worries Norepinephrine and serotonin abnormalities Norepinephrine and serotonin abnormalities GABA-BZ receptor alterations GABA-BZ receptor alterations

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Anxiety Disorders Posttraumatic stress disorder (PTSD) Posttraumatic stress disorder (PTSD) Exposure to terrifying, life-threatening trauma Exposure to terrifying, life-threatening trauma Lifetime prevalence rate 7% to 8% Lifetime prevalence rate 7% to 8% Adults: smaller hippocampus, brain structure susceptible to damaging effects of the stress hormone cortisol and excitatory amino acids 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 Pediatric: studies reveal generalized effect of trauma on reducing total brain volume

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Anxiety Disorders Obsessive-compulsive disorder Obsessive-compulsive disorder Repetitive, intrusive thoughts and/or compulsions 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 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 Compulsions: physical and mental ritualized acts