The Biological Basis of Affective Disorders and Schizophrenia Chapter 15 The Biological Basis of Affective Disorders and Schizophrenia

Affective Disorders An affective disorder is a mental disorder, characterized by one or both of two mood states: depression and/or mania. Depression - An affective disorder characterized by an intense, continuing feeling of sadness and worthlessness. Mania – an elevated, expansive, or irritable mood and inflated self-esteem or grandiosity.

Affective Disorders: Depressive Disorders Depressive disorder - A type of affective disorder in which depression is the only mood state. Depression - An affective disorder characterized by an intense, continuing feeling of sadness and worthlessness. Major depression - A type of depressive disorder characterized by a depressed mood of at least two weeks in duration. Dysthymia - Chronic form of depression; usually low- level

Depressive Disorders: Ten Characteristics

Affective Disorders: Bipolar Disorders Bipolar disorders - A type of affective disorder characterized by episodes of mania and depression that typically continue throughout a person’s lifetime. Cyclothymia - One of the bipolar disorders characterized by less intense episodes of mania and depression than are seen in the bipolar disorder. Hypomania - A milder form of mania in which occupational or social functioning is not impaired.

Symptoms of Mania

Affective Disorders: Neural Changes Structural abnormalities in the brain Reduction of gray matter of orbital frontal cortex Prefrontal cortex has significant gray matter reduction in bipolar individuals Reductions of volume of brain tissue in amygdala, hippocampus, entorhinal cortex, basal ganglia, and thalamic nuclei. Volume of gray matter ventral to beginning of the corpus callosum with familial affective disorders.

Affective Disorders: Metabolic Activity in the Brain PET scans reveal lower-than-normal activity during depressive episodes and higher-than- normal activity during manic episodes. In depression, the reduction is especially apparent in the left frontal cortex. Decreased blood flow and metabolism have also been found in the cingulate gyrus and the basal ganglia of depressed individuals.

Models of Depression: The Role of Neurotransmitters Monoamine hypothesis of depression - the idea that depression is caused by decreased activity in the monoamine neurotransmitter synapses Norepinephrine and serotonin, but not dopamine A serotonin metabolite (5-HIAA) is lower in people with major depression. Low levels of CSF 5-HIAA are associated with suicide. A norepinephrine metabolite (MHPG) is lower in people with major depression. As NE metabolites increase, subjects with bipolar disorder become manic.

Role of Norepinephrine and the Locus Coeruleus A major site of NE synthesis, located in pons and connected to the hypothalamus, hippocampus, and cerebral cortex. Stimulation of the locus coeruleus produces arousal, hypervigilance, and suppression of exploratory activity in primates. Antidepressant drugs decrease the firing rate in the locus coeruleus and reduce the levels of MHPG, a NE metabolite, in the CNS.

The Role of GABA and Acetylcholine Depressed patients may have hyperresponsive cholinergic systems. ACh stimulates the locus coeruleus increasing brain activity. Many depressed people have low levels of GABA and administration of GABA agonists have antidepressant effects. GABA inhibits the firing of noradrenergic neurons in the locus coeruleus and a decrease in GABA levels would increase activity in the locus coeruleus, possibly leading to depression.

Affective Disorders: Drug Treatments Tricyclic compounds - drugs that increase NE and serotonin levels by interfering with their reuptake after the neuron fires. Monoamine oxidase inhibitors (MAOIs) - increase NE and serotonin by preventing their breakdown. Serotonin-specific reuptake inhibitor (SSRI) - e.g., Prozac, decreases serotonin reuptake.

Drug Treatments: Synaptic Effects

Affective Disorders: Vagus Nerve Stimulation Similar to a pacemaker Drug resistant epilepsy and depression Sends signals to brain through afferent fibers Targets the locus coeruleus

Affective Disorders: ECT Treatment Used for drug-resistant depression May work by inhibiting locus coeruleus activity Disadvantages: relapse rate, memory deficits A new promising alternative treatment is repetitive transcranial magnetic stimulation (rTMS) Clinical trials - TMS Therapy is showing promise for a number of conditions including Parkinson’s disease, schizophrenia, epilepsy, chronic pain, traumatic brain injury, stroke, post traumatic stress disorder, migraine headaches, chronic pain, tinnitus, autism, and Alzheimer’s disease Tribal variations

Affective Disorders: The Role of Genetics Concordance rate - The rate at which any characteristic occurs in both members of a pair of relatives Bipolar disorder Concordance rates for identical twins ranges from 20% to 75%, fraternal twins from 0% to 8% Major depression Concordance rates for identical twins is about 50% Concordance rates for fraternal twins is about 20% Genetic connection may be as much as five times higher for bipolar disorder than for major depression.

Affective Disorders: The Role of Environment Learned helplessness - A pattern of depression- like behavior produced by repeated exposure to an inescapable noxious event. Associated with a heightened locus coeruleus activity, manifested as the behavioral changes associated with depression. Also associated with anxiety, phobias, shyness and loneliness which can all be exacerbated by learned helplessness

Seasonal Affective Disorder

Sleep and Depression Sleep disorders such as insomnia and hypersomnia are reported by people suffering from depression. REM sleep occurs earlier than normal and total sleep time is shortened. Advancing the sleep-wake cycle may help alleviate symptoms of depression. Testing whether Aricept can change sleep patterns. Aricept boosts the amount of the brain chemical acetylcholine, which triggers REM sleep and improves memory.

Stages of the Full Sleep Cycle

Biochemical Markers for Depression Any hormone, enzyme, antibody, or other substance that is detected in the urine, blood, or other body fluids or tissues that may serve as a sign of a disease or other abnormality Depressed people often have hypercortisolism. Hypocholesterolemia - total cholesterol levels are below 120 mg/dL High incidence of folate deficiency in depression Low levels of B12 are associated with depression