Download Proposed Brain Mechanisms Underlying Mood Disorders

Behavioral Sciences Handout, Greenough
Reading: Material covered in this and recent lectures is covered in A. Stoudemire (Ed.)
Human Behavior, third edition, 1988, Chapter 12. Use the reading to supplement lecture
and syllabus materials. No exam questions will require reading materials not covered in
the lecture or syllabus/handout materials.
Proposed Brain Mechanisms Underlying Mood Disorders
* While traumatic or stressful events can lead to symptoms of mood disorder, this is
typically treated as a separate, usually transient “adjustment disorder with depressed
mood.”
* There are theories that some (or much) depression may arise in situations with poor
social support, chronic stress, negative personal or occupational situations, etc.
* As with schizophrenia, theories of the brain mechanisms underlying mood disorders
have been driven by the mechanisms of action of effective drugs.
Proposed Brain Mechanisms Underlying Mood Disorders
*One of the most common biological abnormalities in patients with major depression is
hyperactivity of the hypothalamic-pituitary-adrenal axis, the stress response system.
*Dexamethasone, a synthetic adrenal corticosteroid, normally suppresses pituitary
adrenocorticotropic hormone (ACTH) release for 24 hours.
*In depressed patients this suppression is often less pronounced or less prolonged.
*There is also evidence for elevated levels of thyrotropin-releasing hormone (TRH) and
other thyroid abnormalities in depression.
Drug-based Theories of Mood Disorders I
* The initial treatments that were effective in treating many cases of depression had in
common raising the levels of catecholamines (norepinephrine and dopamine) at the
synapse (MAO inhibitors, reuptake blockers-- “tricyclic antidepressants).
* These led to the Norepinephrine and Catecholamine (includes Dopamine) hypotheses
of mood disorders. Reduced catecholamine availability at the synapse caused depressive
disorders
* These pharmacological phenomena take effect almost immediately, yet treatment may
last 2 weeks or more before significant symptom remission occurs.
Drug-based Theories of Mood Disorders II
* More recently, serotonin has been implicated in mood disorders.
* Brain serotonin is low in many depressed patients and reduced levels of the serotonin
metabolic breakdown product (5-HIAA) are common in cerebrospinal fluid. This is
common among suicidal depressives.
* Selective serotonin reuptake inhibitors (Prozac) are effective in restoring mood.
* But why do they take so long to work?
On the Horizon
* There is evidence for serotonergic modulation of hormonal systems (hypothalamicpituitary adrenal) implicated in mood disorders.
* Metabotropic (enzyme-linked) receptor systems often modify general, more lasting
properties of neurons and may be involved in the delayed onset effects of drugs.
* Receptor numbers at the synapse change with synaptic activity, neurotransmitter levels
and drug treatment on a longer term basis.
* When we know why antidepressants take so long to work, we will have a much better
understanding.