Question

1. Depression and Seratonin transporter 5-HTT : - 5-HTT transports seratonin from synaptic cleft back into presynaptic neurons - seratonin = 5-hydroxytryptamine - point mutations in 5-HTT and promoter length polymorphisms implicated in anxiety/depression (involve similar brain systems, treatment sometimes same neurochemically) - 5-HTT PLR: gene linked polymorphic region - short form (s), long form (l) - short form = lower level of 5-HTT expression - monoamine oxidase A (MAO-A) degrade seratonin - FMRI study: s/s, s/l individuals exhibited higher amygdala activity in response to fearful stimuli - 2003 study: tested for depression of 800 ppl at age 26, those w short form more likley to be depressed after stressful life events - also, homozygous s/s most likely to show pronounced increase in self reported depression symptoms after more stressful events - 42% europeans have s, 77% east asians (but no association, could be environmental) Family study: a point mutation IIe425Val associated with OCD. Missense mutation in seratonin transporter

Answer 1

Genetic variations in the serotonin transporter (5-HTT) significantly influence the risk of developing depression and anxiety, especially after stressful events. The presence of polymorphisms like the short allele can lower 5-HTT expression and alter the neural response to fear, potentially leading to mood disorders. SSRIs are a common treatment, targeting the serotonin system to alleviate symptoms.

Step-by-step explanation:

Serotonin Transporter and Depression

The serotonin transporter (5-HTT) plays a crucial role in the regulation of serotonin (5-HT) levels in the brain. Genetic variations, like the polymorphism in the promoter region of the 5-HTT gene, can affect transporter expression and function. The short (s) and long (l) alleles differ in their impact on 5-HTT expression, with the short form associated with lower levels. Monoamine oxidase A (MAO-A) degrades serotonin, which also plays a part in regulating its levels. Individuals with the s/s or s/l genotype have been shown to exhibit higher amygdala activity in response to fear, and those carrying the short allele may be predisposed to depression after stressful life events. A family study identified a point mutation (IIe425Val) in the serotonin transporter associated with obsessive-compulsive disorder (OCD), illustrating the significant role of 5-HTT in psychiatric disorders.

Pharmacological interventions, particularly selective serotonin reuptake inhibitors (SSRIs), often target this system and have been successful in treating symptoms of depression and anxiety by allowing serotonin to remain longer in the synaptic cleft, increasing its availability to post-synaptic receptors. This highlights the therapeutic importance of 5-HTT in the treatment of certain mood disorders.