Genetics E2- Behavioral Genetics

What is the criteria for MDD?

≥ 5 depressive sx present nearly every day during 2 wk period; must include depressed mood or anhedonia; no hx of manic or hypomanic episode

What is the SIGECAPS mnemonic for MDD?

Sleep changes, interest loss, guilt, energy loss, cognition/concentration difficulties, appetite/wt loss, psychomotor agitation, suicidal ideation

What is the criteria for GAD?

Excessive anxiety/worry about several events on more days than not ≥ 6 mos & ≥ 3 sx: restlessness, easily fatigued, difficulty concentrating, irritability, muscle tension, & sleep disturbance

What is the criteria for Bipolar disorder?

Distinct episodes of mania or hypomania & episodes of major depression

Which Bipolar Disorder is defined by at least 1 full manic episode?

*depressive episodes common but not required for dx

Bipolar I

Which Bipolar Disorder is defined by at least 1 hypomanic episode AND at least 1 major depressive episode (never full manic)?

Bipolar II

What are the severity specifiers for substance use disorder?

*met w/in 12-mo period

Mild: 2-3 sx

Moderate: 4-5 sx

Severe: ≥ 6 sx

Bipolar disorder has a higher association with the use of what kind of substances?

Stimulants (cocaine, amphetamines) to intensify or prolong feelings of euphoria and high energy

Major depression & anxiety disorders have a higher association with the use of what kind of substances?

Depressants (alcohol, opioids, BZDs) to numb emotional pain or reduce anxiety

How are genetics involved in mood & substance disorders?

Polygenic; shared signaling pathways primarily between DA & 5HT

*no definitive genetic test, not standard of care

What is the brain’s primary reward & reinforcement pathway that creates feelings of pleasure and motivation?

Dopamine system

What neurotransmitter do all addictive substances directly or indirectly increase, creating a powerful high that reinforces drug seeking behavior?

*genetic variations in the receptors influence susceptibility to addiction

Dopamine

How is the dopamine system affected with anhedonia seen in depression?

Blunted or underactive DA system

How is the dopamine system affected with increased risk-taking & goal directed activity seen in bipolar mania?

Hyperactive DA system

What system is a critical regulator of mood, anxiety, sleep & appetite?

Serotonin system

What pathways are crucial for regulating impulse control, therefore influencing vulnerability to addictive behaviors & substance use disorders?

Serotonin

What is poor impulse control (regulated by 5HT) a major risk factor for?

Initiating substance use & relapse

What are 2 key genetic pathways that link mood disorders & substance use?

DA: mediates reward from substances & core features of mood

5HT: mood regulation & impulsivity

How can genetic testing be used as a tool to guide medication choice & dosing, especially for patients w/ a history of tx failures or ADRs?

Evaluates genes for CYP450 enzymes to identify poor metabolizers (higher risk of SEs) & ultra rapid metabolizers (tx failure)