Mood Disorders

Major Depressive Disorder symptoms (8)

1. feel sad, helpless, and lacking in energy and pleasure for weeks at a time

2. experience little pleasure from activities that used to be pleasurable = "anhedonia" (= no + pleasure)

3. feel worthless or guilty

4. experience fatigue or loss of energy

5. trouble sleeping (too much or too little)

6. gain/lose weight in short periods (+/- 5% of body weight)

7. trouble concentrating

8. contemplate or think about death and suicide

Genetics & depression

• heritability is lower than of SCZ or bipolar disorder

• No single gene for depression has been found

gene x environment effect

certain genetic vulnerabilities interact with stressful environments to produce depression (lack of evidence for this)

Culverhouse findings (2017)

found that life stressors and female sex WERE each strong and independent risk factors for the development of depression (didn’t find specific stress-related variant)

gender differences

• equally common in boys and girls before 13 years of age

• 13-18, girls twice as likely to be diagnosed as boys

Brain Functioning problems

• decreased activity in the left prefrontal cortex and increased activity in the right prefrontal cortex

• LH damage leads to more severe depression than RH damage

Structural Problems

• decreased volume of cortical and limbic brain regions (prefrontal & hippo)

• size of cells in both dorsolateral PFC and hippo, smaller than normal

• stress-related depression → decrease in the number of dendritic branches & spines, and synaptic complexity

Antidepressant drugs

four categories and affect the catecholamines, (epinephrine~ adrenaline), NE, & DA, and 5-HT

Tricyclics

prevent presyn neuron from reabsorbing catecholamines or 5-HT after releasing them (neurotransmitter able to remain longer in cleft → stimulate postsyn receptors

Monoamine oxidase inhibitors (MAOIs)

block the enzyme (MAO) from metabolizing catecholamines and 5-HT into inactive forms (last resort b/c requires strict diet)

Selective serotonin reuptake inhibitors (SSRIs)

similar to tricyclics, but specific to serotonin (fluoxetine (Prozac®))

St. John's wort

• herbal treatment

• increase 5-HT availability

• as effective as antidepressant medications & more effective than placebo

• lower side effects than standard ones

St. John’s Wort Warnings

1. A liver enzyme triggered by St. John's wort tends to break down other medications very fast (cancer & AIDS drugs, birth control pills)

2. unregulated compound → dosages & purity vary

Time: Delayed Effects

• most antidepressants require 2-3 weeks for beneficial effects to appear

• don’t act directly on syn but after changing synaptic activity patterns → trigger further changes → beneficial effects

Delay: BDNF (brain-derived neurotrophic factor)

• may cause an increase in cell size

• animals, cortisol causes decreases in BDNF expression → may lead to cell damage hippo

Ketamine

• nonselective N-methyl D-aspartate receptor (NMDAR) antagonist → blocks action of the NMDAR

• low doses of intravenously-injected Ketamine → treatment effects are seen within hours (symptoms return w/out continued meds in 7-10 days)

Spravato

• nasal spray that must be used along with an oral antidepressant medication

• active ingredient is Esketamine (molecule similar to but not keta) → antagonist of the NMDA receptor

2019 study: Moda-Sava

mice which have stress-induced damage to dendritic spine respond within 24 hours to a dose of ketamine with the growth of new dendritic spines and lowered depression-like behaviors

Irving Kirsch

Antidepressant medications work no better than placebos (wrote book)

UPENN researchers

• reexamined the six most rigorous studies of antidepressants vs. placebos

  • mild to moderate depression → relatively little benefit from antidepressant medications

  • severe depression responds "substantially" to medications over a placebo

psychotherapy

less likely to relapse, but takes up to twice the time to get benefits

drug treatments

takes 4 to 8 weeks for benefits (rather than 2 to 3 weeks)

Electroconvulsive therapy (ECT)

• Inducing seizures w/ brief electric shock presented to RH, every other day for about two weeks

• effective (60-80%) (why its effective, currently unknown)

• primarily used w/ ppl who haven’t responded well to meds in past

side effects of ECT

1. Memory loss: mild and usually transient

2. About half of those who respond well relapse w/in six months (unless given drugs or other therapies to prevent)

Deep Brain Stimulation (DBS) (Severe, Treatment-Resistant Depression)

• deep-brain electrical stimulators are planted deep into the anterior cingulate cortex

• Majority of the patients experienced significant decrease in depression & increase in ability to cope with daily life

Mania

persistently elevated, expansive, or irritable mood, and abnormally and persistently increased activity or energy

Symptoms (need to have 3) (7)

• Inflated self-esteem or grandiosity

• Decreased need for sleep

• More talkative than usual or pressured to keep talking

• Flight of ideas

• Distractibility

• Increased in goal-directed activity or purposeless non-goal-directed activity

• Excessive involvement in activities that could have painful consequences

Bipolar I disorder

person has full-blown episodes of mania

Bipolar II disorder

• person has much milder manic phases, called hypomania

• (60% of ppl), the manic/hypomanic episode precedes depressive episode

• many have other psychological disorders

Incidence and Demographics

• mean age of onset in the mid-20s

• two distinctive risk periods: ages 16-24 and 45-54

• generally equal between males and females

• about 5-6% die by suicide

• life expectancy about 15 years shorter than average

Genetics for Bipolar

strong hereditary basis

• child of a parent with BD has a 5-10% risk (5-10 times risk)

• no specific gene for this disorder has been located

Neurobiological Factors

1. Abnormality in the circadian sleep-wake cycle

2. Alterations in the Ca2+ (calcium) signaling system in the brain → imbalances between excitatory & inhibitory processes

3. Dysfunctions of multiple neurotransmitter systems (DA, GABA, Glutamate) and mitochondria

4. stress impair the functioning of neurons in the CNS → cell damage & loss of brain tissue

Brain network disturbances

• Emotional Processing: hyperactivation in the hippocampus

• Reward Processing: hyperactivation in the OFC (excessive reward leads to manic symptoms & deactivation gives rise to depressive symptoms)

• Working Memory: hyperactivation in areas important for integrating cog & emotional stimuli

Lithium salts

• "mood stabilizer" → protective effect against depressive episodes & mania

• Inhibiting excitatory DA

• Increasing level of inhibitory GABA → reduces excitatory glutamate & NDMA

• Stabilizes messenger systems within neurons

anticonvulsant drugs

another drug treatment for bipolar & valproic acid (Depakote®) and carbamazepine (Tegretol®)

light therapy

given at mid-day, the amount of time in the light must be very gradually increased

dark therapy

kept in a darkened environment from 6 pm to 8 am or uses amber-colored eyeglasses to block blue light→ stabilize patients' mood

Possible causes of Seasonal Affective Disorder (SAD)

1. Disruption in the biological clock b/c changes in avail sunlight

2. Decreased levels of serotonin (may be induced by less sunlight)

3. Melatonin levels may be disrupted & increase in melatonin (feelings of sleepiness)

Light Therapy (Phototherapy)

sits near the light for 45-60 minutes usually each morning or each afternoon

dawn stimulation

uses a light which turns on and gradually brightens in the early morning hours