week 10-Serotonin & Mood Disorders Flashcards
Serotonin (Overview)
Serotonin = 5-Hydroxytryptamine (5-HT)
Acts as a neuromodulator influencing the activity of a variety of neurons throughout the brain.
Important in many functions like sleep, arousal, appetite, temperature, working memory, hallucinations and mood
Serotonin Pathways
All serotonin in the brain is synthesized and released from neurons originating in the Raphe Nucleus (Raphe = midline). The 5-HT is synthesized in the cell body and then transported to the synapses where it is stored. When the neuron fires, the stored 5-HT is rapidly released from the synapse.
Serotonin Synthesis
-Tryptophan an amino acid found in food (Tryptophan Hydroxylase (TPH) SYNTHESIS ENZYME)
-Serotonin
5-Hydroxytryptamine (Monoamine oxidase (MAO)
BREAKDOWN
ENZYME)
Depression Overview
DSM–V diagnosis for Major Depression
At least 5 of the following symptoms have been present during the same 2-week period; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.
NOTE Do not include symptoms due to a general medical condition, or mood-incongruent delusions or hallucinations
(1) depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful). Note: In children and adolescents, can be irritable mood.
(2) markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others).
depression diagnosis continued
(3) significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains.
(4) insomnia or hypersomnia nearly every day
(5) psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)
(6) fatigue or loss of energy nearly every day
(7) feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)
(8) diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)
Depression Diagnosis (Cont.)
(9) recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide
B. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
C. The symptoms are not due to the direct physiological effects of a substance (e.g. a drug of abuse, a medication) or a general medical condition (e.g. hypothyroidism).
Depression vs Greif
The argument for change….
Grief-stricken patients frequently report symptoms that are also typical of major depression, such as sadness, tearfulness, insomnia, and decreased appetite.
but…
Grief rarely produces the cognitive symptoms of depression, such as low self-esteem, feelings of worthlessness, self-loathing or suicidal thoughts.
It was argued that it is important not to miss people with clinical depression because the symptoms were associated with grief.
Depression in family and society
On Average 10-25% of women and 5-12% of men will experience depression in their lifetime.
1st onset often occurs in early adolescence (~15-18yrs)
Estimated cost to Australia in terms of health care and lost productivity is approximately $15billion a year.
Familial clustering:
If you have depression, what is the risk to:
Your neighbor (unrelated)? 16%
Your sibling? 30%
Your identical twin? >80%
Both genes and environment are likely to play a role.
Depression & Serotonin
Brain imaging studies show a reduction in some types of serotonin receptors in the brain of unmedicated depressed patients.
From a PET study, the colourful areas show serotonin receptors are relatively reduced in depressed patients
Depression & Serotonin (Cont.)
In post-mortem studies patients with depression had reduced number of serotonin receptors.
A gene involved in the transportation of serotonin is linked to increased risk of developing depression.
Tryptophan Depletion (TRD) Induces transient depressive symptoms in recovered unmedicated depressed patients (and in some people without depression).
TRD studies involve consuming a milkshake consisting of all amino acids except for Tryptophan (the serotonin building block). This reduces available Trypophan leading to reduced synthesis of serotonin.
Depression & Serotonin Vulnerability
There is variation in serotonin function across the population
Impaired serotonin function may be a “risk factor” leading to people being “vulnerable” to developing depression.
Depression is 5-6 x more likely after stressful events
Stress leads to increased release of a range of hormones such as cortosol. Serotonin function is important in managing the feedback control of the brain’s stress response.
Serotonin Antidepressants (SSRI’s)
Drugs in this class include (trade names in parentheses): Citalopram (Celepram, Clexa) Fluoxetine (Prozac, Lovan) Paroxetine (Paxil, Paxtine) Sertraline (Zoloft) ……..& many many more
Selective Serotonin Reuptake Inhibitors (SSRI’s)
6 reuptake of transmitter
SSRI Therapeutic effects
SSRI’s are very slow acting and often takes weeks for any therapeutic effects to be achieved.
If taken orally the drug reaches the brain after approximately 1 hour after consumption and should block serotonin reuptake immediately once in the brain.
Therefore, improved mood CAN NOT result directly from increased serotonin around the synapse.
So why does it take weeks?
Theories of Long Latency of Onset
Altered gene expression (information from genes is used to make new products – i.e. enzymes) leading to slow changes in the action of different processes within a neuron (neurotransmitter synthesis or storage), or even change the structure of the neuron (synaptic remodeling).
Shuts off a pathologically elevated stress response underlying depressive symptoms, allowing for important neural adaptations.
Increased levels of neurogenesis (birth of new brain cells) change or strengthen important mood related circuits in the brain.
