| What is health? | Is a state of complete physical, mental and social well-being and not merely the absence of disease/infirmity |
| Who are some of the pioneers of psychiatry? | Hippocrates (Pleasures, joys, jests sorrows all in brain - 460BC)
Galen (Psychiatry is etiologies of the brain including genetics and environment) |
| What is percentage of people thinking metal illness is resolved? | 45-51% respondants from developed countries believed mental illness is similar to physical, but only 7% believed it could be overcome. |
| What is stigma? | Shame, stain or mockery, because we are ignorant in mental illnesses it is difficult to accept, when we know it is a brain disease there is no more stigma |
| What is the percentage of people w/mental disordes? | 1/4 of people will have mental disorder in their life, and the most serious obstacle for treatment will be stigma. |
| What are some fallacies and myths regarding mental illness? | Mental illness pt are violent and dangerous, unpredictable, irrational, retarded, lack willpower, incurable, cannot get into a relationship, toxic mediactions and talking therapies are useless.
If we think about it most of diseases are chronic, and their treatments are chronic ones, just like mental illness drugs.
Psychiatry is stigmatized since it is thought that they are unable to treat patients, saves people from dangerous people |
| What are the consequences of stigma? | Delay for diagnosis, poor access to mental and physical healthcare, reduced life expectancy, exclusion from higher education and employment, increased risk of contact with criminal justice systems, victimization, poverty
Worst Outcome in psychiatry is Suicide, criminals are not psych pts, they are held accountable. |
| What is the genetic basis of suicide and mental illness? | We have in our genes the instinct of survival, but w/some diseases we get to suicide
Ernest Hemingway (nobel prize, suicide, 5 suicides in family)
Charolette Salomon (6 suicides in 4 gens)
Van Gogh (was bipolar and shot himself)
Elevated expression of Glutamate receptors in NE neurons from locus coeruleus in MDD is seen (higher NMDA receptor subunits, GRIN2B and GRIN2C and metabotropic receptor genes GRM4 and GRM5 all in locus coeruleus.
Antagonists of Glut receptors reduce depressive symptoms faster than antidepressants, as glut is a prominent excitatory input to the NA LC so LC becomes overactive in MDD. |
| What is mood? What is affect? | Mood (sustained emotional state and how you subjectively feel)
Affect (expression of mood observable)
these two are used interchangbly but shouldn't be confused
Mood episodes include depressive episodes , hypomanic episodes and manic episodes (w/ or w/o mixed features)
Note that manic and hypomanic episodes are only seen in bipolar disorder |
| What are the depressive disorders? | Most important is major depressive disorder.
others are disruptive mood dysregulation disorder, persistent depressive disorder (dysthymia), presmenstrual dysphoric disorder, substance-induced depressive disorder, other specific depressive disorder.
They come in a spectrum, may get many small episodes or one big one |
| What are the MDD diagnostic criteria? | 5+ of the following present most of the day nearly everyday for at least 2 weeks
1-depressed mood
2-Loss of interest or pleasure in all activities
3-Significant weight changes
4-Insomnia/Hypersomnia
5-Psychomotor Agitation/Retardation
6-Fatigue
7-Feeling worthlessness guilt
8-Diminished ability to think/concentrate
9-Recurrent thought of death/suicide
These symptoms will cause a significant impairment of social, occupational or other important areas of functioning. |
| What is the definition of MDD? | Malady of stress adaptation in brain or disorder of stress response and adaptation (neuroplasticity) |
| What is the DD of MDD? | hypothyroidism, hyperthyroid, hyperpara, addison, cushing, toxoplasmosis, mono, AIDS, RA, MS, Parkinsons, Abdominal cancer
Hypothyroidism increased risk of MDD 3.56 pts, and anxiety disorders 2.32 pts
Meds (steroids, reserpine, methyldopa, BB, cimetidine, indomethacin, cycloserine, vincristine, vinblastine). |
| What are diagnostic instruments used in MDD? | Structured interviews to dx MDD (MINI, SCID-5, CIDI, highly specific and sensitive, but used for research not therapy)
Scales (BDI, HAMD, not diagnostic, gives severity) |
| How is epidemiology of depression? | 20% of primary care pt have depressive symptoms, 2 time more in females, 2/3 have multiple episodes, each episode increases the risk of recurrence.
Prevalence is unrelated to race, education , income or civil status, lifetime rates vary across countries (1.5-20%)
Lifetime prevalence (16.2%) and 12 months (6-6%)
Nationally, 1/6 met criteria for at least one year DSM V CIDI disorder, 27% serious and 36% moderate, MDD 5%
11% 1 year disorders got tx, 2/3 of tx are given by GP not psychiatrist
Lifetime prevalence in Lebanon 26% (anxiety 16% mood 13% and substance use 2%)
delay very much between onset and tx (6-28 years), war increased risk of first onset anxiety and mood disorder |
| How is the increasing importance of depression? | 4th rank among major causes of disability worldwide in 2000, and became 2nd in 2020 |
| What are biological etiologies of MDD? | We have molecular susceptibility genes, protective genes and transcription factors (BDNF, CREB,PCK) that predispose cell growth, and environment will affect growth, neurotransmission and neural networks then early life adverse effects will cause behavioral cognitive and sensory motor disruptions.
Study of influence of life stress on depression revieled that genotype alone is not sufficient to predict depression, 5-HT transporter gene needs envirnomental life stress to cause depression, life events alone can cause it and if combined with genetics (5-HT transporter) doubled the risk
short allele (s allele) of 5-HT transporter is strongly associated with stress sensitivity increase (childhood maltreatment and specific medical conditions)
We get glial hypoactivity and death |
| How is the physiology of stress? | Normal physio, stress causes CRF release from PVN of hypothalamus, then ACTH release from ant pituitary then increased cortisol then mobilize energy as response to threat
High cortisol will cause increased cell death in hippocampus (apoptosis), brief exposure will increase hippocampal activity helps remember acute stressor.
Hippocampus - feedback on cortisol after we learn about the stressor.
if more cortisol, less - feedback, keeps cortisol high so chronic stress causing hippocampal cell death, MI, ventricular arrhythmias, increased catecholamines thus atherosclerosis and HTN, cortisol antagonizes insulin and causes dyslipidemia |
| What are serotonin and NE pathways in brain? | raphe nucleus, to sleep centers, frontal cortex, hypothalamus, limbic system and basal ganglia (serotonin) and LC to cerebellum, frontal cortex, limbic system and hypothalamus (NE)
Role of monoamines (serotonin, NE and dopamine balance excitatory mechanisms in brain and prefrontal cortex (logic) and limbic system (emotions), any dysregulation causes depressive symptoms (cortex: depressive mood, hypothalamus weight change and pleasyre loss, limbic guilt and suicidal thoughts... |
| What is role of NE and serotonin in BDNF synthesis? | Serotonin and NE aid in BDNF synthesis, which is important for cell development and if inactivated leads to cell death
So neurogenesis is upregulated by BDNF enriched environment, exercise, learning and antidepressants, and is downregulated by stress, adrenal steroids, age and drugs of abuse.
Antidepressants may normalize BDNF levels promoting serotonin and NE conduction |
| What are stressful triggers for depression? | Stressful events undergo kindling phenomenon, when increased depressive episodes, we get increased risk of depression with decreased association with stressful life events. |
| What are brain areas regulating the mood? | Frontal cortex (cognitive function and attention), hippocampus, nucleus accumbens (reward), amygdala (emotions), hypothalamus (sleep, apetite, sex), ventral tegmental area (dopamine projections), dorsal raphe nuclei (serotonin projections), locus coeruleus (NE projections) |
| How is depression and inflammation? | increased level of proinflammatory cytokines (IL6, IL1 and TNF-a), there is a direct correlation between severity of depression and cytokine elevation, celecoxib (COX-2 inhibitor), TNF-a antagonists showed antidepressant properties.
There is an interplay between depression and inflammation, leading to obesity and diabetes in addition to other depression mediators |
| Who are the psychology talkers in etiology of MDD? | Freud and Beck |
| What is the relation between nurture and MDD? | Both adopted and non-adopted children w/mother w/MDD are likely to get MDD
Childhood adversity increases risk of adulthood disease. effects of childhood trauma (mostly emotional and physical abuse + neglect, sex, separation, divorce and hospitalization. |
| How is course and comorbidities of MDD? | 5 Rs of mental illness: after an episode, the patient gets response (better), then remission (stops episode) then relapse (another episode), then Recovery (complete resolution) then recurrence (after total recovery)
Usually recurrence risk increases with episode numbers (1st episode: 50%, 2nd 70%, 3rd >90%)
Comorbidities (CAD1 18% w/episode, MI 16% 6 months post MI, Cancer during illness 20-25%, HIV 1 year 36%, migraine lifetime 22-32%, alzheimer in episode 17-31%, MS lifetime up to 50%
Depression in patients in 2 times more than normal individuals, up to 30% in acute hospitalized pt. |
| How is depression and CVD? | Depression doubles CV mortality/events, possible causes include sympathetic actiavtion, platelet reactivity and immune system reactions.
Depression is associated w/2.7 times increased mortality risk of IHD independently of IHD risk factors. |
| How is depression and cancer? | MR >25% in pt w/depression symptoms and >39% in pt dx w/major/minor depression, without effect of diminishing those effects.
Study of lebanon breast cancer w/depression, mixed cancer: psych comorbidity 46%, MDD 16% and minor depression 17.6%.
Psychiatric morbidity increase MR by 4.13 times, and depression in breast cancer is 14%, cancer is diagnosed 70% in late stage due to health definition in middle east
MDD can be influenced by social support of cancer patients, not related to treatment stage and related to stage of disease |
| How is religiousity with MDD? | No correlation between it and depression by study in syria pre and post war, even no difference for gender, demographics. |
| What is the Hamilton depression rating scale? | Treatment effect score,17 items, score from 0-52, MDD if above 15, 7-15 we are getting a response >50% reduction, <7 remission
67% of pt respond to antidepressants, 33% remit w/any type of AD, after 1 year of treatment w/4 ADs 67% will remit, relapse is less for pt who achieve remission |
| What are antidepressants indication? | Mood disorders (MDD, dysthymia, subthreshold depression, bipolar [combine with mood stabilizer], schizoaffective depressed type)
Anxiety disorders (OCD, panic, GAD, PTSD, SAD)
Impulse control disorders (Kleptomania, complusive shopping, trichotilo, binge eating, paraphilias)
Affective-spectrum disorders (IBS, migraines, fibromyalgia, chronic pain, enuresis) |
| What are SSRIs? | fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram.
Mode of action (at begining serotonin increases in somatodendritic area in midbrain raphe causing side effects, over time auto receptors downregulate and become desensitized, serotonin release isn't turned off increasing their release and neural impulse flow so therapy w/tolerance to side effects
Side effects (CNS [nervousness, insomnia, fatigue, headache, tremor], GI [nausea, vomit 14%, diarrhea constipation, increased apetite and weight gain], sex [delayed orgasm, decreased libido], endocrine [DM], pregnancy [Fluoxetine OK others no data]) |
| What are SNRIs? | Serotonin NE reuptake inhibitors, Venlafaxine XR, Desvenlafaxine XR, Duloxetine, Milnacipran
Side effects (Same ass SSRI + alter blood pressure at high doses, alter heart rate, anticholinergic dry mouth, constipation and urinary retention) |
| What are NDRIs? | Bupropion (MDD, nicotine withdrawal, lowers seizure threshold, no sexual side effects and no weight increase) |
| What are SNDIs? | a2 antagonists (miratazapine (serotonin 1a agonist, others antagonist, main side effect weight gain and sedation))
SNDI action (LC [cut in brakes blocks presynaptic neurons NE increase release of NE, block presynaptic serotonin increase its release (by decreasing action)]
Raphe [step on accelerator [increase NE release stimulating a1 Rs in post synaptic dendritic neurons of serotonin provoking serotonin release]) |
| What are classic antidepressants? | Tricyclic AD's (Clomipramine, Imipramine, Amitriptyline, Nortriptyline, Desipramine, Doxepine)
Actions (block reuptake pumps for NE, serotonin, serotonin 2A and 2C receptors and disinhibit DA and NE release.
Overdose lethal, second-line for resistant depression)
Side effects (Blockade of muscarinic cholinergic Rs M1 dry mouth, constipation and blurred vision, and M3 insulin action disruption. Histamine 1 Rs cause sedation and weight gain, a1 Adrenergic Rs cause orthostatic HTA, dizziness, and voltage-sensitive Na channels cause seizure, arrhythmia and arrest)
Efficacy (acc to literature) |
| What are other biological/electrical treatments of MDD? | ECT (electroconvulsive therapy, severe depression w/suicide risk, psychotic features or resistant depression.
Side effects include temporary memory loss, anesthesia effects)
TMS, VNS, DBS
Psychological therapies (psychodynamic, CBT, interpersonal therapy)
Social-skills training
Fitness seems to increase hippocampal volume for any age/sex/education level |
