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Unformatted text preview: Outline 14 (THE LAST OUTLINE) Affective Disorders--Depression & Bipolar Disorder I. Overview A. “Affect”—overall emotional state In general, affective disorders are characterized by having moods, such as sadness or euphoria, which are extreme, abnormal and long-lasting. B. Depressive disorder The most prevalent (70%) of the psychiatric diseases/disorders. 3 major types: Unipolar depression Mania Bipolar disorder (or manic-depression) Major characteristics Sadness, grief, hopelessness and/or elation and euphoria are intense and occur inappropriately, e.g., well beyond or in the absence of substantial triggering events Other effects Extreme lack of self-confidence Poor ability to concentrate on anything other than the sadness Despair for the future Recurring thoughts of death and suicide Memory impairments Problems sleeping Problems with eating REM sleep disturbances—depressive patients take less time (approx 35 min) to enter the first REM sleep state than controls or those with minor depression Is the REM sleep disturbance a cause or and effect (or neither) of the depression? II. Heritability The inheritance of a predisposition to depression and bipolar disorder is considered to be very strong. (40% of those with major depressive disorder and 60-80% of those with bipolar disorder have a family memory with one or the other.) The predisposition is thought to interact with environmental factors (high and/or repeated stress and traumatic events). I.e., a gene-environment interaction 1 III. Brain Differences 1. Reduced activity of prefrontal cortex during depression In bipolar disorder, prefrontal cortical activity cycles with episodes of mania (abnormally high) and depression (abnormally low n) Left. PET scan of a
rapid cycling bipolar patient (top and bottom - depressive episodes, middle, manic episodes) Right- PET scan of
depressed patient. Top during normal good mood, bottom, during depressed period 2. Abnormal response of the amygdala to emotional stimuli Depression and bipolar disorder have unusually large and prolonged amygdala activity in response to emotion-ladden stimuli Amgydala and prefrontal cortex are interconnected and this circuit is important for emotional information processing and the emotional modulation of memory formation 3. Volume loss in hippocampus People with major depression have, on average, reduced hippocampal volume. This is thought to be a result rather than a cause of depression (i.e., larger volume loss with longer history of depression) ************************************************** Why do we treat depression the way we do? **************************************************
IV. Anti-depressant drugs- A brief history A. 1940’s-50’s-discoveries which lead to the Catecholamine Hypothesis that depression was a result of abnormal reductions in catecholamine transmission in the brain. Recall that Monoamine neurotransmitters include the catecholamines (NE and DA) and the indolamines (5HT) 1. Reserpine- used as a treatment for high blood pressureDiscovered that some patients became depressed and suicidal on reserpine. Reserpine depletes monoamines (NE, DA, 5HT) 2 2. Monoamine Oxidase Inhibitors (MAO-I) MAO-I was used to promote the effectiveness of antibiotics given to tuberculosis patients. They became hyperactive and developed manic-like responses. MAO breaks down monoamines and, thus, inhibitors of MAO reduce monoamine breakdown, making them more available. 3. Amphetamine, a known stimulant at the time, was found to work by increasing release of DA and NE B. Reuptake inhibitors- drugs that reduce the reuptake of neurotransmitters from the synaptic cleft, permitting the neurotransmitters to continue to act at post-synaptic sites. 1. Tricyclic antidepressants and related drugs- reuptake inhibitors of NE and 5HT terminals together These are effective at reducing depression but can have negative side effects, including abnormal heart rhythms. (Recall that NE is one of the main neurotransmitters used by the sympathetic nervous system) 2. Selective-Serotonin Reuptake Inhibitors (SSRI’s), e.g., Prozac (fluoxetine)—very effective for many depressives and not frequently associated with heart arrhythmia -The "Catecholamine Hypothesis" gets broadened to the "Monoamine Hypothesis" 3. Other reuptake inhibitors Selective norephrine reuptake inhibitors, reuptake inhibitors of multiple catecholamine neurotransmitters (e.g., Wellbutrin & Effexor) C. Lithium - classic mood stabilizer for bipolar disorder Is now known to enhance serotoninergic activity V. Issues with the Catecholamine/Monoamine Hypothesis A. SSRI’s and MAO-I’s don’t work for everyone and there are other antidepressants are effective in some people that have no obvious effects on monoamines B. SSRI’s take several days to become effective even though the inhibition of reuptake is immediate 3 Various other emerging theories of the neural basis of depression: -abnormalities in the mesolimbic dopamine system -abnormalities in neural adaptation to stress -abnormal connectivity and neural plasticity in memory and emotion circuits -more nuanced catecholamine/monoamine hypotheses V. Other treatments A. Electroconvulsive shock therapy (ECT)— Generalized convulsions are induced via electrical stimulation to the brain through scalp electrodes ECT has developed a very bad reputation as a result of its rampant misuse in the mid-1900’s. However, it is an effective treatment for depression. Side effect is a short term amnesia for events just before and just after the treatment. B. Transcranial Magnetic Stimulation (TMS) -Related to ECT and still under investigation -Can be applied in more restricted brain regions (i.e., over frontal cortex) and can be done without producing seizures. -May require multiple stimulation sessions to be effective. -Works best in younger and less-treatment resistant patients More brain stimulation approaches are emerging, but need much more research (deep brain stimulation, vagal nerve stimulation) C. Sleep deprivation therapyTotal sleep deprivation- a single night of total sleep deprivation results in a major but short-lasting alleviation of depression in a subset of people (in others, it has no effect) Selective REM sleep deprivation – reduces depression but, like tricyclic antidepressants and SSRI’s, the effect takes several days to develop. 4 ...
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- Spring '08