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

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Schizophrenia  1% of population (higher in twins, siblings)  Emerges in young adults  Slightly earlier onset in males than females  Psychotic episode  Genetic predisposition  Monozygotic twins concordance rate 30% to 50%  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  Enlargement of lateral and third ventricles; widening of frontal cortical fissures and sulci  Neurotransmitter alterations  Brain dopamine pathways altered  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  Hallucinations  Delusions  Disorganized behavior Disorganized speech Disorganized speech Disorganized behavior Disorganized behavior  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  Affective states are brief emotional feelings  Euphoria, joy, surprise, fear, sadness, etc.  Depression  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  Unipolar Also called major depression, clinical depression Also called major depression, clinical depression  Bipolar disorder  Genetic predisposition  Twin studies: concordance rates 40% monozygotic; dizygotic 11% 40% monozygotic; dizygotic 11%  Environmental influences

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Mood Disorders  Neurochemical dysregulation  Neuroendocrine dysregulation  Hypothalamic-pituitary-adrenal system dysregulation  Hypothalamic-pituitary-thyroid (HPT) system dysregulation  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  Increased CSF levels of thyrotropin-releasing hormone (TRH)  Blunted thyrotropin-stimulating hormone (TSH) response to TRH challenge  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  Depression  Mania  Treatment  Antidepressants  Psychotherapy  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  Monoamine oxidase inhibitors (MAOIs)  Tricyclic antidepressants (TCAs)  Selective serotonin reuptake inhibitors (SSRIs)  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  80% respond to cognitive behavioral therapy (CBT) and/or antidepressant medication  Generalized anxiety disorder  Excessive and persistent worries  Norepinephrine and serotonin abnormalities  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)  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

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Anxiety Disorders  Obsessive-compulsive disorder  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