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MDD, Antidep, Anxiet
MDD & antidepressain
| Term | Definition |
|---|---|
| What symptoms of MDD are in the DSM-5? (9) | Depressed mood, Anhedonia, changes in appetite/weight gain or loss, Excessive sleep or insomnia, psychomotor agitation/retardation, anergia, guilt or worthlessness, cognitive difficulty, suicide ideality or suicide |
| Which symptoms must be displayed for MDD? | Depressed mood (dysphoria) or Anhedonia |
| What is the time and minimum criteria for MDD? | 5 + symptoms for same two-week period |
| What are the two etiologic genetic factors of MDD? | Serotonin (5HTTLPR); and Neurotrophic factor (BDNF) |
| What does 5HTTLPR stand for? | Serotonin Transporter-Linked Promotor Region |
| What do Long/ Short alleles mean? | Alleles that produce 5-HTT and SERT (Serotonin Reuptake Transporter) ; Short= fewer reuptake transporter proteins |
| What are the short alleles associated with regarding depression? | More severe depression |
| What does BDNF stand for? | Brain-Derived Neurotrophic Factor |
| What Chromosome codes for BDNF? | Chromosome 11 |
| What is the role of BDNF? | Neuronal survival and growth, synaptogenesis, differentiation in development |
| What allele produces normal efficient BDNF? | Val (Valine) |
| What does having Val/Val allele mean for BDNF? | Higher, efficient production and secretion of BDBF |
| What allele leads to altered BDNF? | Val66Met/ Met (Methionine) |
| Having a Val/Met allele does what to the brain? | Reduced hippocampal volume, impaired memory, increased risk of anxiety, depression, PTSD, neurodegenerative diseases |
| What does having a Long allele do? | Creates higher 5-HTT mRNA transcription; great number of SERTS |
| Why is a higher # of SERTS (Serotonin reuptake transporters) good? | Results in faster 5-HT synaptic clearance |
| What does having a Short allele mean for anxiety? | Slower/less 5-HT removal from synapses |
| What does Long/Long allele mean? | Having normal limbic system structures |
| What does having Long/Short or Short/Short allele mean? | Smaller amygdala and cingulate cortex . and less communication between two |
| What does a smaller amygdala and cingulate cortex do to our threat evaluation? | Skews our perspective of what is a threat and ability to calm amygdala of non threats |
| Environmental factors for MDD and anxiety? | Stress!! -->activation of sympathetic nervous system, HPA axis, glucocorticoids and overproduction of cortisol |
| What brain structures are reduced in MDD? | Hippocampus, prefrontal, Amygdala, cingulate cortex, thalamus, putamen--reduced glial count too!! |
| General findings in MDD patients | Higher cortisol levels, Hypo-hippocampal volume, Hypofrontality (frontal cortex); increased levels of inflammation and bacterial markers |
| What does chronic stress (excess cortisol) do to the body/brain? | Impair cognitive skills, sleep disturbances, altered mood states, prevent growth of new cells, kill brain cells in limbic system areas, prevent reuptake of Glu and glucose |
| Monoamine Theory of Depression | depression=result of low monoamine NT activity (5-HT, NE); 1st biological explanation of psych disorder |
| What are the four classes of antidepressants that elevate synaptic levels of monoamine NTs? | Monoamine Oxidase Inhibitors (MAOI's), Tricyclic AD's, Selective 5-HT reuptake inhibitor (SSRI), Serotonin + NE Reuptake Inhibitor (SNRI's) |
| What antidepressant targes glutamate | Ketamine |
| What receptors does Ketamine target? | Glutamate NMDA receptors (antagonist) |
| What antidepressant was used to cure tuberculosis? | MAOI's/ monoamine oxidase inhibitors |
| What do monoamine oxidase inhibitors (MAOI's) do? | Inhbit mao enzymes for depredating NTs |
| What dietary restriction is associated with taking MAOI's? | foods with Tyramine--> increase release of monoamines |
| What do Tricyclic ADs do? | 1. Blockade NE and 5-HT reuptake transporters 2. Blockade postsynaptic receptors (histamines & ACH -muscarinic) |
| What are symptoms of seretonin syndrome? | Hyperthermia , sweating, dilated pupils, agitation, seizure, sexual dysfunction |
| Some SSRIS | Fluoxetine, Citalopram, Escitalopram, Sertraline |
| What do SNRI's do? | Blockade 5-HT and NE reuptake transporters, less severe side effects of SSRIs |
| Monoamine theory issues | Accidental discovery doesn't account for role of stress Increase NT levels in 24-48 hrs, but takes 4-6 weeks for symptom relief doesnt work for TRD only works for 40-60% patients |
| Ketamine with clinical trials | 0.5 mg IV drip (90-120 min) AD effects-8-24 hrs AD effects last: 2 weeks works w/ MDD, TRD, Bipolar depression |
| How does Ketamine work as an antidepressant? | Promotes the production of BDNF (restores neural growth) |
| What is the 3rd nervous system? | Enteric nervous system-->NS of the digestive system |
| What is the "Second Brain"? | The gut/Enteric nervous system |
| How many Glial cells and NTS support the gut? | 500 million neurons; 40 NTs |
| How much Dopamine and Serotonin are in the gut? | 50% of DA, 95% 5-HT |
| How much do Microbes outnumber human cells (ratio) | 10 to 1 |
| Dysbiosis | Any change to the gut population and functioning of microbiome |
| Causes of Dysbiosis (7) | Change in diet, Toxins, Alcohol (2 + drinks daily), Medications & antibiotics, poor hygiene, unprotected sex, stress |
| Results of Dysbiosis | Decreased bacteria function and diversity, impaired epithelial barrier, bacterial translocation--> leads to inflammation |
| What is "Leaky gut Syndrome?" | When the intestinal lining (epithelial barrier) is impaired and leads to "leakage" of bacteria into the blood stream and body |
| Stress on the gut | Glucocorticoids weaken tight epithelial junctions; allow for gram-negative bacteria to enter bloodstream |
| Cytokines | Inflammation response, markers of where damage is Interleukins, Tumor-necrosis factors |
| What cytokines are elevated in MDD? | IL-6 (Interleukins) and TNF-a |
| Relationship of cytokines and monoaminergic ADs | Elevated cytokine levels --> resistance to monoamine ADs |
| Probiotics | Living organisms that alter gut microbiome, Attenuates HPA response to stress |
| Prebiotics | Indigestible food products that stimulate the growth of desirable microorganisms Increase hippocampal BDNF and NMDA & AMPA receptors levels |
| General features of Anxiety | Lifetime prevalence: 28%, 3-% of Gen pop given time, Women > Men |
| Anxiety has a a high comorbidity with- | Depressive disorders and Substance use Disorders |
| Panic disorder symptoms | Acute feelings of terror, shortness of breath, clamminess, sweating, irregular heart beat, dizziness, faintness, feelings of death, anticipatory anxiety |
| Generalized Anxiety Disorder symptoms | Persistent feelings of worry, impairment of daily functioning.expectations |
| Social Anxiety Disorder | Excessive fear of exposure to other people, isolation |
| Biomarkers of Anxiety Disorders | Measure in blood plasma, saliva or CSF Elevated cortisol Reduced BDNF Increases in inflammation Elevation of histamines Dysregulation of: GABA, 5-HT, DA |
| Monk study: Adolescents with GAD | Showed reduced activity in Ventral Lateral PFC--> increased activity in amygdala |
| Fisher and Pfleiderer: Panic Disorder brain | During episode: Decreased activity of orbitofrontral cortex and ACC; increased activity of amygdala |
| Imaging studies of PD patients | Decreased Cerebral Blood LFow (CBF) to limbic system structures, decreased frontal activity |
| Doxapram to PD and non-Panic disorder | PD: displayed greater decrease in PFC--> corelated to larger increase in amygdala |
| Treatment of Anxiety | Amino acids: GABA and Glutamate , SSRI's, Antihistamines, Anti-hypertensives |
| Treatment for Anxiety: Glutamate | (Trials) pre-synaptic mGluRs autoreceptors, reduced glutamate activity |
| Treatment for Anxiety: GABA | Benzodiazepines--> GABA-A agonists (Xanax, valium) |
| SSRI's for Anxiety: | Higher doses--> anxiolytics (Fluvoxamine and paroxetine); more rapid onset, better outcomes than CBT |
| Antihistamine | (Hydroxyzine) Combats excessive histamines (bad in large amounts) short term relief of symptoms (mostly for panic disorder), sedation |
| Anti-Hypertensives | (Clonidine) NE a2 agonist!! Reduces NE release, used off-label for panic disorder |
Created by:
fuehrerek