Neuro Exam 2

Describe the clinical presentation of depression

SIGE CAPS (Sleep disorders, interest loss, guilt, energy deficient, concentration, appetite, psycho motor fluctuations, suicidal ideation)

Describe the diagnostic criteria for depression

five or more of the SIGECAPS symptoms have been present during the same two week. Including depressed mood or anhedonia (no pleasure) AND symptoms do not coincide with mania AND These symptoms are clinically distressing and cause impairment in multiple settings AND the symptoms are not directly related to a physiological or drug induced cause

what are some drugs that can induce depression

antihypertensives (beta blockers (esp propranolol) Clonidine, methyldopa, reserpine), CNS depressants (alcohol, barbiturates, antielliptics), hormonal agents (corticosteroids, contraceptives, tamoxifen), isotretinoin, interferon, efavirenz

Describe dysthymic disorder

depressed mood on most days for more than two years, low grade chronicity (more than 2 SIGE CAPS symptoms), never been without symptoms for more than two months for 2 years, Does not meet criteria for major depressive disorder

describe major depression with psychotic features

most severe form of depression, hallucinations are usually auditory hallucinations such as voices, and includes delusions (fixed false beliefs)

describe melancholic depression

lack of pleasure in all or almost all activities OR lack of reactivity to usually pleasurable stimuli. (distinct from depressed mood seen with grief, depression worsened the mornings, increased early morning awakenings, marked psycho motor retardation, significant anorexia, excessive guilt)

describe atypical depression

mood brightens with positive events, significant weight gain, hypersomnia, leaden paralysis, interpersonal rejection sensitivity

What is involved in a mental status exam

General appearance, behavior, and speech. Mood and affect, level of intellectual functioning, thought processes.

What are risk factors for suicide

insomnia, anxiety, life stressor, adjustment disorder

What are some questionnaires to evaluate depression

PHQ 9, Montgomery asberg, Hamilton

What is considered a response to antidepressant therapy

an improvement of symptoms, a 50% or more decrease in HAM-D or MADRS

what is considered remission in antidepressant treatment

returning to Wellness or disappearance of symptoms, most frequently measured as HAM-D greater than or equal to 7 or MADRS greater than or equal to 10

what is considered recovery in antidepressant treatment

remission for two months or more

What is considered relapse in antidepressant treatment

return of symptoms after remission

What is considered recurrence in antidepressant treatment

return of symptoms after recovery

what are the monoamine neurotransmitters

Serotonin, norepinephrine, epinephrine, dopamine, and histamine

what are the catecholamine neurotransmitters

dopamine, norepinephrine, and epinephrine

what are the indoleamine neurotransmitters

serotonin

What is a precursor for dopamine

L tyrosine

what enzyme controls the rate limiting step in dopamine production

tyrosine hydroxylase

What receptor is on the surface of vesicles that hold dopamine

VMAT2

how many families of receptors are there for dopamine

2

what are the families of receptors for dopamine

D1 and D2

What transporters control the reuptake of dopamine

dopamine and norepinephrine transporter

what reuptake transporter is not present in the prefrontal cortex

the dopamine reuptake transporter

where can you not find the dopamine reuptake transporter

in the prefrontal cortex

what enzymes are responsible for the metabolism of dopamine

MAOA and MAOB

Which dopamine receptor family is found on the presynaptic nerve

D1

Which dopamine receptor family is found on the postsynaptic nerve

D2

What is the second messenger system that is associated with the D1 receptor family

increase cAMP via Gs, increase PIP2 hydrolysis, calcium mobilization, PKC activation

What is the second messenger system that is associated with the D2 receptor family

Decrease cAMP, increase potassium currents, decrease voltage gated calcium channels

what receptors are in the D1 receptor family and where can you find them

D1-Stratum, neocortex. D2-hippocampus, hypothalamus

what receptors are in the D2 receptor family and where can you find them

D2-stratum, substantia nigra, pituitary gland. D3-Olfactory tubercle, nucleus, accumbens, hypothalamus. D4-frontal cortex, medulla, midbrain

Where in the body does dopamine exert its effects

heart and vasculature, kidney, CNS

What effect does dopamine have on the heart and vasculature

D1 receptor binding leads to vasodilation and decreased cardiac afterload. At high concentrations, circulating dopamine activates alpha adrenergic receptors leading to vasoconstriction

what effect does dopamine have on the kidneys

maintains renal blood flow and glomerular filtration. Influences renin angiotensin system.

what effect does dopamine have on the CNS

Mesolimbic Tract=Reward, Learned Behavior, Mesocortical Tract=Higher order cognitive processes, Nigrostriatal Tract=Movement and locomotion, Tuberoinfundibular Tract=Prolactin secretion, Area postrema=Contains small set of intrinsic dopamine neurons (emesis)

What is a precursor for norepinephrine

dopamine

Where in the brain are norepinephrine receptors highly concentrated

prefrontal cortex and limbic areas

What roles is norepinephrine involved in

arousal, vigilance, learning, and cognition (survival)

How does a norepinephrine deficiency present itself

reduction in concentration, working memory, may cause psycho motor retardation, resulting in apathy and symptoms of depression

What is a precursor for serotonin

tryptophan

what is serotonin a precursor for

melatonin

Describe serotonin receptors and their mechanism

almost all serotonin receptors are G coupled. 5HT3 (in the gut) is ionic

Which serotonin receptor families are inhibitory

5HT-1 and 5

Which serotonin receptors act through G alpha Q

5HT-2

Which serotonin receptors are ionic

5HT-3

Which serotonin receptors are excitatory

5HT-6 and 7

how many families and subtypes of serotonin receptors are there

seven families and at least 14 subtypes of receptors

How does norepinephrine and dopamine dysfunction present

depressed mood, loss of happiness/joy, loss of interest/pleasure, loss of energy/enthusiasm, decreased alertness, decrease self-confidence

how does norepinephrine and serotonin dysfunction present

depressed mood, guild/disgust, Fear/anxiety, hostility, irritability, loneliness

What is BDNF and what role does it play in the brain

brain derived neurotrophic factor. it is involved in neuroplasticity, neurogenesis, cell survival and synaptogenesis

describe the modern theory on why it takes so long for antidepressant therapies to work

downstream mechanisms influencing treatment response, intracellular actions responsible for effects (decreased BDNF)

Describe the effect of a blockade of monoamine transporters

increased levels of circulating monoamines in the synapse, leans to downstream effects and increase in neurotrophic factors.

Describe the effects of inhibition of monoamine oxidase

leads to similar cascade as blockade of monoamine transporters (increased levels of circulating monoamines in the synapse, leans to downstream effects and increase in neurotrophic factors)

What are the five mechanisms that are used to treat depression

blockade of monoamine transporters, inhibition of monoamine oxidase, agonistic activity at 5-HT-1 receptors, blockade of 5-HT-2A receptors, antagonism of A2 autoreceptors

What is the effect of antagonism of A2 autoreceptors

increases neurotransmission of monoamines

what are some non-pharm approaches to treating depression

psychotherapeutic interventions (CBT, interpersonal therapy, marital therapy, family therapy), vagus nerve stimulation (specialty), transcranial magnetic stimulation (rare, five days per week), electroconvulsive therapy for refractory depression

What is the black box warning for antidepressive drug therapies

increased risk of suicidality in people younger than 25

what drug class is amitriptyline (Elavil®)

tricyclic antidepressant

what drug class is Imipramine (Tofranil®)

tricyclic antidepressant

what drug class is Trimipramine (Surmontil®)

tricyclic antidepressant

what drug class is Desipramine (Norpramin®)

tricyclic antidepressant

what drug class is Doxepin (Sinequan®)

tricyclic antidepressant

what drug class is Nortriptyline (Pamelor®)

tricyclic antidepressant

what drug class is Protriptyline (Vivactil®)

tricyclic antidepressant

what drug class is Maprotiline (Ludiomil®)

tricyclic antidepressant

what drug class is Amoxapine (Ascendin®)

tricyclic antidepressant

what drug class is Esketamine (Spravato®)

NMDA Antagonists

what drug class is Isocarboxazid (Marplan®)

Monoamine Oxidase Inhibitors (MAOIs)

what drug class is Phenelzine (Nardil®)

Monoamine Oxidase Inhibitors (MAOIs)

what drug class is Tranlycypromine (Parnate®)

Monoamine Oxidase Inhibitors (MAOIs)

what drug class is Selegiline (EMSAM®)

Monoamine Oxidase Inhibitors (MAOIs)

what drug class is Duloxetine (Cymbalta )

Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)

what drug class is Venlafaxine (Effexor)

Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)

what drug class is Desvenlafaxine (Pristiq®)

Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)

what drug class is Levomilnacipran (Fetzima®)

Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)

what drug class is Brexanolone (Zurlesso®), and what is it used for?

GABA Allosteric Modulation, post-partum depression

what drug is used for postpartum depression

GABA Allosteric Modulation

what drug class is Trazodone (Desyrel®)

5-HT2 Antagonists

what drug class is Nefazodone (Serzone®)

5-HT2 Antagonists

what drug class is Quetiapine (Seroquel®)

2nd Generation Antipsychotics

what drug class is Brexpiprazole (Rexulti®)

2nd Generation Antipsychotics

what drug class is Olanzapine/Fluoxetine (Symbyax®)

2nd Generation Antipsychotics

what drug class is Aripiprazole (Abilify®)

2nd Generation Antipsychotics

what drug class is Citalopram (Celexa®)

Selective Serotonin Reuptake Inhibitors (SSRIs)

what drug class is Escitalopram (Lexapro®)

Selective Serotonin Reuptake Inhibitors (SSRIs)

what drug class is Fluoxetine (Prozac®)

Selective Serotonin Reuptake Inhibitors (SSRIs)

what drug class is Paroxetine (Paxil®)

Selective Serotonin Reuptake Inhibitors (SSRIs)

what drug class is Sertraline (Zoloft®)

Selective Serotonin Reuptake Inhibitors (SSRIs)

what drug class is Fluvoxamine (Luvox®)

Selective Serotonin Reuptake Inhibitors (SSRIs)

what drug class is Vilazodone (Viibryd®)

SSRI/5-HT1A partial agonist

what drug class is Vortioxetine (Trintellix®)

SSRI/5-HT1A partial agonist

what drug class is bupropion (Wellbutrin®)

Aminoketone

Describe the mechanism of action of SSRI's

1.) Block the reuptake pump,
2.)Increase somatodendritic serotonin,
3.) Desensitized autoreceptors,
4.) Neuronal impulse turned on,
5.) Increased release of serotonin from axon terminals,
6.) Desensitization of postsynaptic neurons,
7.) Downstream increases in neurotropic factors,
8.) Neurogenesis

What are the most common adverse drug effects with SSRIs

nausea and vomiting, sexual dysfunction, insomnia, headache, activation/anxiety, weight gain (less than TCA's), Potential to lower the seizure threshold

Why can SSRI's cause nausea and vomiting

effects on serotonergic receptors in the gut

How do you decrease nausea and vomiting with SSRIs

take with food

Which of the SSRI's is the most activating and therefore can cause the most insomnia

fluoxetine

Which antidepressant is the most known for lowering the seizure threshold

bupropion