Lecture #18 (Bipolar Disorder)

Default Mode Network

Resting

Salience + CEN Network

Activity

What is there increased functional activity of in depression?

Posterior Default Mode Network + Salience Network (sgACC + Insula)

Increased activity of default networks

What is there decreased functional activity of in depression?

Anterior Default Mode Network + Salience Network (Hippocampus + amygdala)

Posterior Default Mode Network + Central Executive Network

Decreased activity of salience + CEN

Does brain shrink or grow during depression?

Depends on region

Does hippocampus grow or shrink during depression?

Shrink

Does anterior cingulate cortex grow or shrink during depression?

Grow

Where is signaling disrupted during depression?

Amygdala + frontal cortex

Is there stronger or weaker reactions to neg stim in the amygdala during depression?

Stronger reaction to neg activity

Is there more or less activity in the PFC when depressed?

Less

When does bipolar disorder typically appear?

20-25 years old

Why is bipolar hard to diagnose?

Bc most ppl only get treated for the depressive symptoms

Why is bipolar hard to treat?

Bc opp ends of mood spectrum

Bipolar + Suicide Rates

Highest of all pysch disorders; 20x more likely than the general pop

BPD Risk Factors

• Sex (men more likely)

• Alc use disorder

• Stress/trauma or big life change (ex. lose job)

Are men or women more likely to have BPD?

Men

Bipolar 1

Rly intense manic episodes that last at least a week; Depressive not req

More disabling when in manic episode; 50% experience psychosis when in manic state

Bipolar 2

Hypomanic states (4 days) that are not as intense; Tend to be a more pronounced depression tho

Less disabling when in manic

Cyclic Dysregulation Hypothesis

Potential issues with dopamine regulation

Typical homeostasis tightly controls dopamine, but heavily impaired in ppl with BPD; Body overcompensates with a lack of dopamine + will increase/decrease too much

Leads to manic + depressive episodes

Glutamate Hypothesis

Bipolar patients hv elevated glutamate levels

Excitotoxity

Overactivation of neurons; Can damage cell + eventually lead to death

Stress Hypothesis

Cortisol levels correlate freq with manic episodes

Elevated cortisol may set stage for manic

Immune Hypothesis

Disruption to immune signaling can inhibit communications, etc

Immune Disreg to limbic network damage, neurotransmitter signaling change, network balancing alterations, psychopathology (bipolar)

Disruption to dif parts will have different effects

Lithium

Gold standards for BPD (ppl on it dont have effects again)

Rly good at managing manic + self harm, ok for depression

Affects many things bc ion

Why does Lithium target many things/nonspecific?

Bc its an ion

What is Lithium rly good at and ok at managing?

Rly good for managing manic symptoms + suicidal, ok for depression

Lithium Mechanism of Action

1. Decrease dopamine signaling via less dopamine + less sensitive receptors

2. Downreg # of glutamate receptors

3. Agonist of GABA

4. Increases brain growth factors like BDNF

5. Alters intracellular signaling to modify gene reg

Lithium Therapeutic Window

Very small

ED → 1.2

TD → 1.5

LD → 2.0

Why is Lithium not recommended for long term use?

Can damage kidneys + has neg impacts on cog functioning

Often given as initial solution + switched to better long term meds

What % of patients stop taking Lithium?

50% bc feel like they’re cured when on meds

Lithium Side Effects

• Increased thirst/urine

• Hand tremor

• Weight gain

• Gastrointestinal disturbance

• Mental fog

• Skin probs

Other drugs used to target manic phase

Antipsychotics

What can certain antidepressants trigger for ppl with BPD?

Can trigger manic

What can be done to ensure success of treatment?

• Stick with treatment plan + adjust meds if side effects intolerable

• Good support group to ensure they stick to treatment plan

• Psychotherapy can reduce relapse by 40% (fam focused, interpersonal + social rhythm, CBT)