Chapter 15Chapter 15

The Biological Basis of Affective Disorders and Schizophrenia

Affective DisordersAffective 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: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 Depressive Disorders: Disorders: Ten Ten CharacteristiCharacteristicscs

Affective Disorders: Affective Disorders: Bipolar DisordersBipolar 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 Symptoms of Maniaof Mania

Affective Disorders: Affective Disorders: Neural ChangesStructural 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 matterventral to beginning ofthe corpus callosum with familial affective disorders.

Affective Disorders:Affective Disorders:Metabolic Activity in the BrainPET 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:Models of Depression:The Role of NeurotransmittersMonoamine hypothesis of depression - the idea

that depression is caused by decreased activity in the monoamine neurotransmitter synapses

Norepinephrine and serotonin, but not dopamineA 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 Role of Norepinephrine and the Locus Coeruleusthe Locus CoeruleusA 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 The Role of GABA and AcetylcholineAcetylcholine

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: Affective Disorders: Drug TreatmentsDrug 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 Drug Treatments: Synaptic EffectsEffects

Affective Disorders:Affective Disorders:Vagus Nerve StimulationVagus Nerve Stimulation

Similar to a pacemaker

Drug resistant epilepsy and depression

Sends signals to brain through afferent fibers

Targets the locus coeruleus

Affective Disorders:Affective Disorders:ECT TreatmentECT TreatmentUsed for drug-resistant depressionMay work by inhibiting locus coeruleus activityDisadvantages: relapse rate, memory deficitsA 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:Affective Disorders:The Role of GeneticsThe Role of GeneticsConcordance 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:Affective Disorders:The Role of EnvironmentLearned 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

Sleep and DepressionSleep and DepressionSleep 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 Stages of the Full Sleep Cycle Cycle

Seasonal Affective Disorder

Biochemical Markers Biochemical Markers for Depressionfor DepressionAny 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/dLHigh incidence of folate deficiency in depressionLow levels of B12 are associated with depression