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NEUROBIOLOGY OF SCHIZOPHRENIA, MOOD DISORDERS, AND ANXIETY DISORDERS

front 1 Characteristics of Schizophrenia Definition Population % Earlier onset in F/M?	back 1 Is characterized by thought disorders that reflect a break between the cognitive and the emotional side of one’s personality Afflicts 1% of the population Emerges in young adults Men have a slightly earlier onset than women
front 2 Schizophrenia Pathophysiology What are different causes?	back 2 Genetic predisposition Likely involvement of several genes located on different chromosomes Prenatal and perinatal vulnerability factors Exposure to: Prenatal infection Prenatal nutritional deficiencies Perinatal complications, such as birth defects and neonatal hypoxia Upbringing in an urban environment Neuroanatomic alterations Enlargements of: Enlargement of lateral and third ventricles; widening of frontocortical fissures and sulci Reduction of: Reduction in the thalamus and temporal lobe areas (e.g., amygdala, hippocampus, and parahippocampal gyrus)- disrupt neurotransmission between the frontal cortex and primary sensory and motor areas Loss of: Loss of cortical tissue Volume loss in the hippocampus Neurotransmitter alterations Alteration of brain dopamine pathways- Dopamine inc. Glutamate hypothesis: Decrease in glutamate receptors
front 3 Schizophrenia - Positive S/S	back 3 Positive Symptoms- Psychotic S/S Frequently occur during a psychotic episode when the individual loses touch with reality and experiences something that should be absent Hallucinations: perceptions are experienced without an external stimulation of the sense organ Delusions: false beliefs are persistent Disorganized behavior is exhibited Disorganized speech Disorganized or bizarre behaviors
front 4 Schizophrenia- Negative & Cognitive S/S negative symptoms are experienced most of the time during a 1-month period with some disturbance present over 6 months	back 4 Negative symptoms Characterized by disruptions in normal emotional states and expressions Negative dimensions- Negative State Affective flattening: near absence of emotional or facial expressions throughout a conversation/situations Anhedonia "D" decrease pleasure/depression inability to feel pleasure Alogia "L" language poverty of speech- speak less often, use fewer words Avolition "L" lack lack of interest in goal-directed behavior/ lack of motivation Cognitive symptoms- Capacity of memory Problems with thought processes Inability to perform daily tasks requiring attention and planning

front 5 Schizophrenia Treatment Two categories of medications? Consequence of first gen medications ? What type of therapy?	back 5 Treatment First-generation/conventional antipsychotic medications Block dopamine - D2 blockers Help with positive symptoms May cause tardive dyskinesia after several years of use - tic-like jerky movements, such as smacking the lips or flicking the tongue, unsteady gait, or rocking back and forth when seated Second generation/atypical antipsychotic medications Reduce positive and negative symptoms Block a range of neurotransmitters receptors Psychosocial therapy Cognitive behavioral therapy (CBT)
front 6 Mood Disorders What is mood, affective states, depression? Two categories of mood disorder? Two types of Bipolar?	back 6 Mood: is a sustained emotional state Affective states: are brief emotional feelings Depression: states such as sadness become chronic and uncontrollable Categories of mood disorder Unipolar AKA major depression or *clinical depression* Is the most common mood disorder Woman are more at risk Bipolar Bipolar 1 person has at least one manic episode followed by hypomanic or major depressive episodes Bipolar II the individual experiences one major depressive episode for at least 2 weeks and at least one hypomanic episode for at least 4 days Affects 3%–5% of the population
front 7 Mood Disorders Pathophysiology	back 7 Neurochemical dysregulation Deficits in brain norepinephrine, dopamine, and/or serotonin, leading to depression Mania: elevated concentrations of monoamines Neuroendocrine dysregulation Hypothalamic-pituitary-adrenal (HPA) system dysregulation Altered immune and inflammation from cortisol Hypothalamic-pituitary-thyroid (HPT) system dysregulation
front 8 Mood Disorders Pathophysiology Contd	back 8 Neuroanatomic and functional abnormalities Widespread decrease in serotonin 5-HT1A receptor subtype Reduction in glial cell numbers in people with unipolar and bipolar disorders Decreased cerebral blood flow and glucose metabolism; some areas may have increased blood flow Elevated cortical levels of glutamate

front 9 Mood Disorders: Depression S/S	back 9 Feeling sadness and despair Feelings of worthlessness and guilt Dysphoric mood: unhappy/unsatisfied Reduced interest in pleasurable activities and interpersonal relationships Sleep disturbances Decreased concentration Restlessness and agitation Weight loss or weight gain Suicidal thoughts
front 10 Mood Disorders: Mania S/S	back 10 Elevated levels of euphoria, self-esteem Feelings grandiose with extreme levels of energy May show poor judgment in spending money May make poor business commitments May become hypersexual Excessive, rapid, loud, and pressured speech
front 11 Treatment for Depression	back 11 Depression Antidepressants Psychotherapy Combination of both Electroconvulsive therapy (ECT) Deep-brain stimulation Transcranial magnetic stimulation Relapse is likely if medications and therapy are discontinued
front 12 Treatment for Mania: Bipolar I and II	back 12 Bipolar I Lithium: first-line of therapy; must watch for toxicity Lithium combined with SSRIs Anticonvulsant agents Atypical antipsychotic medications ECT Psychotherapy Bipolar II Antidepressants alone

front 13 Anxiety Disorders How much of the population is affected? People with anxiety disorders can also develop...? Different types?	back 13 Affect 10%–30% of the general population Many individuals with anxiety disorders develop major depression Examples Panic disorder Generalized anxiety disorder Acute stress disorder Agoraphobia Phobia: Social/Specific Obsessive-compulsive disorder Posttraumatic stress disorder (PTSD)
front 14 Anxiety Disorder: Panic Disorders S/S What is a complication to Panic Disorder?	back 14 Exhibits multiple disabling panic attacks and is characterized by intense autonomic arousal: Lightheadedness Difficulty breathing Chest discomfort/Racing Heart Generalized sweating/Chills, or Hot flashes General weakness/Trembling Abdominal distress Complication: Agoraphobia, which is the phobic avoidance of places or situations where escape or help is not readily available Can become homebound
front 15 Anxiety Disorder: Panic Disorder Patho What % of relatives does it affect? Patho/Etiology? Treatment?	back 15 Risk is nearly 20% among first-degree relatives Patho/Etiology pH alterations in the amygdala: Heightened pH sensitivity in the amygdala may play a key role in generating fearful perceptions and activating the cerebral cortex and neural circuits in the temporal lobe and brainstem, which further facilitates the production of panic symptoms Benzodiazepine (BZ) receptors are reduced: increase panic attacks and feelings of anxiety, suggesting that an alteration in inhibitory neuromodulation contributes to panic disorder neuromodulation contributes to panic disorder. Treatment Approximately 80% respond to CBT and/or antidepressant medications SSRIs; benzodiazepines, if nonresponsive
front 16 Anxiety Disorder: Generalized Anxiety Disorder Definition & Diagnosis criteria Patho/Etiology Treatment	back 16 Excessive and persistent worrying for at least 6 months Motor disturbances, irritability, and fatigue Six major symptoms of GAD have been identified and include restlessness, muscle tension, irritability, being easily fatigued, difficulty concentrating, and difficulty sleeping *Patho/Etiology* Norepinephrine and Serotonin abnormalities: reduction in A2-adrenergic receptor binding, a decrease in serotonin levels in CSF Treatment 5-HT (serotonin)/norepinephrine (NE) reuptake inhibitors: venlafaxine Behavioral therapy

front 17 Anxiety Disorder: Post Traumatic Stress Disorder Definition Patho/Etiology Treatment	back 17 Exposure to terrifying, life-threatening trauma Intrusive flashbacks and nightmares Patho/Etiology Amygdala and Prefrontal Cortex affected: exhibit increased activity in the amygdala and diminished activity in prefrontal cortical areas Altered BZ binding: reduced distribution of BZ receptor binding in the prefrontal cortex amygdala and prefrontal cortex are highly involved in the pathophysiology of PTSD because these brain structures normally play important roles in how fearful memories are stored, retrieved, and extinguished. Treatment Group or family therapy, CBT First-line treatment for chronic PTSD: SSRIs TCAs, BZs Other (some experimental): Eye Movement Desensitization Reprocessing (EMDR), ketamine, psychedelics
front 18 Anxiety Disorder: Obsessive-compulsive disorder Definition (Two core symptoms)	back 18 two core symptoms of obsessions and compulsions. Obsessions: repetitive, intrusive thoughts Thoughts of contamination, religion, sex Compulsions: involve physical and mental ritualized acts Washing, cleaning, checking, counting, organizing, hoarding, and repeating specific thoughts or prayers
front 19 Anxiety Disorder: Obsessive-compulsive disorder Patho/Etiology Treatment	back 19 Genetic and environmental risk factors Basal ganglia–frontocortical circuitry abnormalities Lack of serotonin control over the dopamine system Treatment SSRIs: citalopram, fluvoxamine, paroxetine, and sertraline (first-line), BZs, antipsychotics: haloperidol, risperidone, olanzapine, or quetiapine CBT and response prevention therapy Neurosurgery-lesioning procedure (disconnect basal ganglia from frontal cortex) If uncontrollable: ECT, transcranial magnetic stimulation (TMS), deep brain stimulation (DBS)