4/21/15 – Lecture 24 – Anxiety and Depression- Goal – to learn about anxiety and mood disorders and what brain changes are associated with them- Anxiety – a negative emotional state in which feelings of nervousness, worry and apprehension are associated with increased arousal of the bodyo Components of Anxiety Cognitive Anxiety – psychological thoughts and feelings of nervousness, worry, or apprehension Somatic Anxiety – physiological symptoms of higher arousal associated with anxiety, including increased heart rate, increased breathing, sweating, etc.- A little anxiety is normal and even beneficial, if it helps you to anticipate and prepare for a future stressoro Arousal is regulated by several brain systems The locus coeruleus of the reticular activating system – a cluster of neurons that release norepinephrine throughout the brain and increase cognitive attention, awareness and (cognitive) arousal Autonomic nervous system – increases in sympathetic and decreases in parasympatheticactivity are associated with increased heart rate, sweating, breathing, etc (somatic arousal)o Anxiety can be temporary or more permanent State Anxiety – a temporary emotional state or mood characterized by cognitive and somatic symptoms of anxiety- Can change for a given person from moment to moment Trait Anxiety – a component of personality, or predispositions that influences behavior so that individuals high in trait anxiety is more likely to perceive circumstances as threatening- Can cause two people to differ dramatically in their state anxiety response to a given situation Anxiety Disorder – a family of mental disorders characterized by chronic feelings of excessive worry and anxiety without a specific or rational causeo Symptoms of Anxiety Affective Symptoms – unpleasant feelings such as uncertainty, feeling overwhelmed, guilt, nervousness Cognitive Symptoms – recurrent negative thoughts, obsessions, or compulsions, irrational fears Behavioral Symptoms – avoidance of situations, panic attacks, compulsive behaviors Somatic Symptoms – muscle tension, increased heart rate, excessive sweating, etc.- Patients with clinical anxiety are distinguished from those with “normal” anxiety by the number and intensity of symptoms, degree of suffering, and degree of dysfunctiono When the anxiety response occurs in the absence of an eliciting event, isdisproportionate and unmanageableo Neurobiological Changes in Anxiety Cognitive Appraisal of Threat – the Cingulate Cortex and vmPFC- The cingulate cortex (CC) is involved withthreat and conflict assessment, and sizeand/or activity of the CC is increased inpatients with anxiety disorder- The ventromedial prefrontal cortex(vmPFC) is involved in inhibiting negativeemotional responses, and size or activityof the vmPFC is decreased in patientswith anxiety disorders- The amygdala activates stress/emotionalresponses, and activity or size of theamygdala can be higher in patients withanxiety disorders- The locus coeruleus, HPA, and SNS areactivated by the hypothalamus and theytoo can be overly active Neural Basis of Anxiety- The amygdala is involved withtransmitting fear signals to thehypothalamus and activating the SNSand the HPA axis- People with an anxiety disorder mayhave either elevated excitatory input tothe amygdala OR decreased inhibitoryGABAergic input- Amygdala neurons can also increase indendritic branching in anxiety sufferers- Anxiolytic drugs like benzodiazepinesincrease GABA signaling and reduceamygdala activation of thehypothalamus Stress Pathways and anxiety Disorders- People with anxiety disorders have a greaterreaction to stressors than normal people- Exposure to severe or chronic childhood stressresults in death of hippocampal neurons dueto high levels of cortisol as well as decreaseddendritic branching of hippocampal neurons- Hippocampal neurons are critical forinactivating the stress response- Loss of hippocampal neurons and decreaseddendritic branching decreases the ability ofthe hippocampus to turn off the stressresponseo What can cause Anxiety Disorders? Genetics Stress (particularly in childhood) Exposure to certain organic solvents Certain stimulants- Depressiono State VS Trait Depression State Depression – everyone gets depressed occasionally, often in association with a negative life event such as a death of a loved one or loss of a job Trait Depression – a personality trait characterized by low mood, excessive negativity, etc. Mood Disorder – a lifelong mental disorder characterized by low mood, loss of interest in pleasurable activities, etc.- Symptoms of Depressiono Affective Symptoms – anhedonia – loss of interest in most or all activities, feeling of sadnesso Cognitive Symptoms – difficulty thinking or concentrating, irrationally negative assessments of most situations, memory problems, hallucinations, recurring thoughts of death and suicidal ideation – recurring thoughts and fantasies of killing one’s selfo Behavioral Symptoms – psychomotor retardation – decreased activity, avoidance of situations, attempted suicideo Somatic Symptoms – vegetative symptoms – sleep disturbances, appetite/body weight disturbances, high stress hormones- Potential Physiological Mechanismso Monoamine hypothesis of depression – caused by decreased levels of the neurotransmitters serotonin, norepinephrine, and/or dopamine Serotonin – involved in sleep, eating, and mood, and depressed patients have mood problems as well as vegetative symptoms ofsleep and eating disruptions Dopamine – involved in pleasure and reward, and depressed patients have anhedonia or lack of pleasure Norepinephrine (NE) – involved in arousal, and depressed patients have psychomotor retardation or lethargy and decreased arousal- Evidence for the Monoamine Hypothesiso Decreases in serotonin, dopamine, and NE have been found in autopsy studies of brains of depressed patientso Genetic variations in the serotonin, dopamine, and/or NE signaling genes are associated with a greater risk of depressiono Brain levels of the serotonin, dopamine, and NE are increased by SSRI and MAOi anti-depressants- Problems with Monoamine Hypothesiso Anti-depressant medications are only effective for about 25-50% of depressed patients and arecompletely ineffective for about 20% of depressed patientso Monoamine depletion does not worsen symptoms in depressed patients not taking