Theoretical Models of Depression A Biological Model 1 Genetics Heritability estimate 30 40 female 20 30 male Serotonin transporter gene chromosome 17 Long versus short versions long L protective short S risk 4 severe negative events LL 17 depressed SS 43 depressed 2 Neurobiology Multiple neurotransmitter systems involved Serotonin social drive stress response amygdala anterior cingulate Dopamine pleasure reward goal directed activity initiative motivation also Glutamate Norepinephrine Acetylcholine etc CRH master protein regulates neurotransmitter function in brain coordinates stress response 3 Neuroendocrine hormones Cortisol stress hormone Runaway stress response body shutdown Toxic to brain reduced BDNF brain derived neurotophic factor Inflammatory hormones promote brain s stress response shutdown 4 Frontal Cortex reduced left frontal activity 5 Sleep Architecture increased REM decreased slow wave sleep B Environmental Mutation Ilardi Humans lived in hunter gatherer conditions for 99 of existence Modern day aboriginal peoples e g Kaluli of New Guinea rarely get depressed The more modern a society higher rate of depression U S today 23 U S 1940s 2 3 developing nat 2 5 Amish 2 Why Built in antidepressant and protective features of ancient life 1 aerobic exercise increases BDNF serotonin dopamine function 2 omega 3 fatty acids 1000 2000 mg EPA also DHA 3 natural sunlight 10 000 lux reset body clock make Vitamin D especially for seasonal onset depression 4 sleep target 8 hrs 5 social connection community 6 engaging activity vs idle alone time rumination Therapeutic Lifestyle Change TLC www psych ku edu TLC C Psychodynamic Model For Freud depression anger turned inward Personality factors oral or anal fixation dependency perfectionism D Cognitive Model Beck s model depression caused by negatively biased thoughts Automatic thoughts involuntary negative interpretation of events Logical errors give rise to automatic thoughts ex all or nothing thinking Schemas core beliefs taken as a given I m a loser No one will ever love me Treating Depression A Drug Treatments 1 SSRIs Prozac Paxil Zoloft Celexa Lexapro SNRIs Effexor Pristiq Cymbalta Short term Full recovery 20 35 favorable response 40 60 Across 47 studies in FDA database meds beat placebo in fewer than half of studies overall placebo 80 of drug response For depression of mild moderate seveere severity SSRI SNRI roughly equal to placebo sugar pill in response rates Only in very severe depression meds clearly superior to placebo High relapse rates when SSRI SNRI discontinued STAR D Trial 4000 patients start on Celexa keep trying new meds until patient recovers 6 of all patients fully recover for 1 year Standard of care 1 year for 1st depression 2 years for 2nd 5 years for 3rd 2 Tricyclics imipramine Tofranil amitriptyline Elavil Similar response rate as SSRI but lethal overdose potential Until 20 years ago most popular antidepressant now less widely used 3 Atypical antidepressants Wellbutrin Remeron etc Wellbutrin works on dopamine reward circuits spontaneous orgasm Remeron hits dopamine serotonin circuits evidence of highest response rate but major weight gain 4 St John s Wort hypericum Largest U S study St John s placebo but both Zoloft B Electroconvulsive Therapy ECT Electric current passed through cortex convulsive seizures Typical ECT regimen 3 times per week 2 4 weeks 80 response rate but only 50 of med non responders Used lots with elderly Very high relapse rates most relapse in year following treatment Permanent cognitive impairment especially memory C Psychotherapy 1 Cognitive Therapy CT Aaron Beck developed in 1960 s Most widely researched form of psychotherapy dozens of wellconducted research studies 16 20 sessions over 3 4 months 50 60 favorable response rates short term Focus on cognitive modification i e identify and change negative thoughts and behavioral activation 2 Interpersonal Therapy IPT Psychodynamic short term Less well researched but available evidence suggests IPT CBT