final Flashcards
treatments for emotional disorders, anxiety, and schizophrenia
describe the brain structure abnormalities in those with depression.
-overactive amygdala
-reduction in volume of hippocampus
-underactive and reduced dorsal/prefrontal cortex
-underactive and reduced nucleus accumbens
how were MAOIs discovered?
-iproniazid was used to treat tuberculosis, and it was found that mood elevations occurred in patients
-from this discovery, the monoamine hypothesis was generated, which said that monoamine deficits cause a depressed mood
-there were issues with this theory because antidepressants increase monoamines within minutes, but symptom relief takes 2-4 weeks
-AOIs were then developed which prevent MAO from breaking down monoamine neurotransmitters
what is the mechanism of action of tricyclics?
-block the reuptake of both norepinephrine and serotonin
-antagonist for cholinergic receptors which causes dry mouth, dry eyes, constipation, and urinary retention
-antagonist for norepinephrine causing negative cardiovascular effects
-antagonist for histamines causing sedative effects
what is Ketamine? how did it come to be an antidepressant? how can it help? what are the concerns?
-NMDA antagonist that blocks glutamate receptors
-FDA approved nasal spray to be taken with an antidepressant; for treatment, the patient takes it twice per week then once every other week or two for maintenance
-leads to an immediate reduction in symptoms which lasts for 2 weeks
-drug abuse and acute psychedelic effects because it increases dopamine in the nucleus accumbens
describe the response time length for antidepressants
-at 2 weeks, clinically significant effects occur
-full effects happen at 4 weeks
what is the placebo effect for antidepressants? what does this imply?
-clinically significant improvements occur in the placebo-treated patients
-strong placebo effects and cautious clinical drug testing leads to a failure to find clinically significant effects
what is the effect of chronic antidepressant administration on dopamine?
-increases dopamine in the nucleus accumbens
-increases D2 receptors in the limbic system
-increases neuronal density in limbic system
what is an unidentified bright object?
part of the neurobiology of those with bipolar disorder; excessive activity in cortical white matter areas of the brain
describe the therapeutic index of lithium
-narrow therapeutic index
-the gap between the effective dose and a toxic dose is small
-there is an overlap in the acute therapeutic effects and the adverse effects
what is th mechanism of action of lithium?
-enters neurons through Na+ channels
-protective effects against neurodegeneration
-inhibits glycogen synthase kinase 3 (GSK-3) enzyme which promotes programmed cell death and regulates inflammation
what is the current best treatment for bipolar disorder?
-mood stabilizers
-atypical antipsychotics + antidepressant which has a quicker response time than just antipsychotics and may have a greater reduction in symptoms than lithium
-anticonvulsants which are GABAA positive modulators, inhibit GSK-3 activity, and inhibit Na+ channel functioning which affects high-frequency action potentials
what information does the prefrontal cortex send to the amygdala?
-inhibits reaction to fearful stimuli
-determines how we behave
-approach/avoid behavior
what information does the hippocampus send to the amygdala?
-information about the context surrounding a stimulus
what information does the thalamo-amygdala pathway send to the amygdala?
-crude, unprocessed information
-it is a short route
-does not provide fine information
what information does the thalamo-cortical-amygdala send to the amygdala?
-sensory information processed in the cerebral cortex where it can be properly perceived
-it is a long route and allows for more refined information
describe the metabolism difference between short and long acting benzodiazepines
-short acting benzodiazepines have a half-life of 12-24 hours
-long-acting benzodiazepines have a half-life of 20-40 hours and have active metabolites
what are BZ 1 sites? where are they found? what brain areas are they found in (3) and what do they do in those areas?
-high affinity for GABAA receptor sites
- α1 subunit
-thalamus which causes reduced cortical arousal and reduced seizure activity
-substantia nigra which causes reduced cortical activity and reduced seizure activity
-cerebellum which causes reduced balance and coordination
what are BZ II sites? where are they found? what parts of the brain are they found in (3) and what do they do in those areas?
-weaker affinity GABAA receptor sites
- α2, α3, α5 subunits
-cortex which causes reduced alertness and reduced cognitive function
-hypothalamus which causes reduced anxiety/stress response
-amygdala which causes reduced anxiety
which antidepressants are used to treat anxiety? what is the response time? how well does it work?
-SSRIs and SNRIs which increase serotonin/norepinephrine
-2 weeks
-1/3 of patients are treatment resistant
what psychological changes occur due to MDMAs empathogenic effects?
-may reduce resistance to thinking about an event or facilitate emotions surrounding the event
-increases the release of oxytocin
-reduces activity in the amygdala
what is the prodromal phase?
-early subtle signs of schizophrenia
signs include social withdrawal, unusual thoughts or paranoia, decreased motivation, trouble concentrating, and mild depression or anxiety
what is a sensory gating deficit?
diminished capacity to filter out unimportant stimuli in one’s environment
what are the characteristics of typical antipsychotics?
-D2 receptor antagonist
-reduces positive symptoms
-weak efficacy for negative symptoms and cognitive impairment
what are the adverse effects of typical antipsychotics?
-extrapyramidal side effects (EPS) which include tremor, muscle rigidity, and involuntary movements due to D2 receptors antagonism in the basal ganglia
-tardive dyskinesia which is a motor disorder affecting muscles in the face and causing involuntary movements
-neuroleptic malignant syndrome (NMS) which consists of flulike symptoms, blood pressure changes, and autonomic nervous system irregularities
-hyperprolactinemia which is abnormally high blood levels of prolactin and reduced lactation, sexual dysfunction, and disruption in menstrual cycles
what are the characteristics of atypical antipsychotics?
-reduce positive and negative symptoms
-modest gains in cognitive functioning
-reduction in depression and suicide risk
-improvement in 70% of treatment resistant patients
describe the adverse effects of atypical antipsychotics
-lower risk of EPS, NMS, and hyperprolactinemia
-significant weight gain which can increase the risk for type II diabetes
-QT interval prolongation causing prolonged heartbeat which can lead to cardiac arrest
-agranulocytosis which is reduced white blood cell count in the immune system
how do atypical antipsychotic drugs produce an effect?
-serotonin dopamine hypothesis states that states atypical antipsychotics are preferential antagonists of 5-HT2A compared to D2 receptors
-fast D2-off hypothesis which states that antipsychotics cause rapid dissociation of drug from D2 receptors
describe the difference between typical antipsychotics and atypical antipsychotics
-atypical psychotics relieve both positive and negative symptoms while typical antipsychotics help only positive symptoms
-atypical antipsychotics decrease the risk of EPS, NMS, and hyperprolactinemia while these are adverse effects of typical antipsychotics
what are the mechanism of action for atypical antipsychotics?
-5-HT2A receptor antagonist
-weak D2 receptor antagonist
-targets the α2 adrenoceptors causing improved cognitive functioning
-targets the muscarinic receptors causing dry eyes and dry mouth
-targets the histamine receptors which causes sedation
-targets the 5-HT2A receptors causing weight gain
what is the DISC1 gene?
-a gene that is disrupted in those with schizophrenia
-the gene is important in signaling events in neurons, development of neurons, and cell migration which can cause abnormalities in cellular networks
what is the dopamine hypothesis of schizophrenia? what is the evidence for the hypothesis?
-positive symptoms arise from excessive dopamine release in the limbic system causing excess in places like the nucleus accumbens
-antipsychotics act as antagonists for D2 receptors and there is a correlation between D2 binding affinity and effectiveness
-amphetamine and cocaine cause psychotic symptoms via increase in dopamine release
what is the glutamate hypothesis? what is the evidence for the hypothesis?
-diminished levels of glutamate release throughout the cerebral cortex and limbic system
-ketamine and PCP cause users to exhibit behaviors consistent with positive and negative symptoms as well as cognitive impairment
-diminished glutamate may account for reduced dopamine in the prefrontal cortex and excessive dopamine in the limbic system
which is better, the glutamate hypothesis of schizophrenia or the dopamine hypothesis?
-the glutamate hypothesis of schizophrenia because it accounts for both insufficient glutamate and excessive dopamine and explains all of the symptoms, not just the positive ones
-low levels of glutamate in the prefrontal cortex leads to too much dopamine in the nucleus accumbens
what are the stages of the hpa axis
- alarm- increase physiological arousal in preparation for an emergency situation; hypothalamus activates sympathetic nervous system
- resistance- sustained level of physiological arousal; hypothalamus elicits the release of ACTH from the pituitary gland; adrenal gland increases cortisol
- exhaustion- fatigue, susceptibility to disease; immune system and metabolic activity of organs throughout the body are underactive
what is the hpa axis?
-hypothalamic-pituitay-adrenal axis
-hypothalamus releases corticotrophin releasing factor
-release of adrenocorticotropin hormone (ACTH) from pituitary gland
-adrenal gland releases cortisol increases metabolism and immune system
-cortisol increases during traumatic events and recall of event
-prolonged increases in cortisol levels are associated with damage to the hippocampus which can cause damage to neurons, decreased volume, and memory impairment
describe differential reinforcement of low rates test for depression. What is the effect of antidepressants?
-type of schedule of reinforcement where there is a period of time and if the rat presses the lever during the interval, reinforcement is pushed back and the rat has to wait another time period
-antidepressants lead to more efficient responding on the task; they have a decreased response rate and an increased reinforcement rate
describe the elevated plus maze test for anxiety. What do anxiolytics do?
-maze in the shape of a + elevated off the floor; two of the arms are enclosed and the other two are open; generally, rats only like to travel in enclosed spaces
-anxiolytics increase time spent in open arms
what is the diagnosis criteria for depression?
-must have either: depressed mood most of the day or markedly diminished interest or pleasure in activities
-must have at least three of the following symptoms:
-significant increase or decrease in appetite or weight
-insomnia, disrupted sleep, or sleeping too much
-lethargy or physical agitation
-fatigue or loss of energy nearly everyday
-worthlessness or excessive inappropriate guilt
-daily problems in thinking, concentrating, making decisions
-recurring thoughts of death and suicide
what treatment would you give to someone with depression? what is the mechanism of action of the treatment?
-SSRIs which block the reuptake of serotonin
what is the diagnostic criteria for bipolar disorder?
-abnormally and persistent elevated, expansive or irritable mood
-at least three of the following:
-exaggerated optimism
-hyper sociality or sexuality
-delight in everything
-impulsivity and overactivity
-racing thoughts; the mind won’t settle down
-little desire for sleep
what treatment would you give to someone with bipolar disorder? what is the mechanism of action for the treatment?
-antipsychotics which are D2 antagonists
-anticonvulsants which are GABAA positive modulators
-mood stabilizers which enter neurons through Na+ channels and inhibit GSK-3 enzyme that aids in programmed cell death and regulates inflammation
what is the diagnostic criteria for generalized anxiety disorder?
a person is continually tense, apprehensive, and in a state o autonomic nervous system arousal
what is the diagnostic criteria for panic disorder?
-repeated and unexpected panic attacks
-fear of the next attack
-a change in behavior to avoid panic attacks
what is the diagnostic criteria for a specific phobia?
persistent, irrational fear and avoidance of a specific subject, activity, or situation
what is the diagnostic criteria for PTSD?
exposure to actual or threatened death, serious injury, or sexual violence who experience the following for at least 1 month:
-re-experiencing traumatic event
-avoidance of stimuli associated with the event
-negative cognitions and mood including a sense of blame, detachment, anhedonia
-heightened arousal including aggression, sleep disturbances, hypervigilance
what treatment would you describe to someone with GAD? what is the mechanism of action of the treatment?
-buspar
-5-HT1A partial agonist
what treatment would you prescribe to someone with panic disorder? what is the mechanism of action of this treatment?
- a short-acting benzodiazepine
-GABAA positive modulators meaning they increase the ability of natural GABA to bind
what treatment would you prescribe for someone with PTSD?
-MDMA assisted psychotherapy
-the empathogenic effects of MDMA allow for a reduction in resistance to thinking about the event or facilitate emotions surrounding the event by increasing the release of oxytocin and reducing activity in the amygdala
what is the diagnostic criteria for schizophrenia?
-disorganized and delusional thinking, disturbed perceptions and inappropriate emotions and behaviors
-symptoms include:
-positive symptoms: hallucinations, delusions, disorganized thoughts and speech
-negative symptoms: flat effect, social withdrawal, catatonia
what treatment would you prescribe for someone with schizophrenia? What is the mechanism of action of this treatment?
-atypical antipsychotics
-5-HT2A receptor antagonist
-weak D2 receptor antagonist targets
-α2 adrenoceptors targets
-muscarinic receptors targets
-histamine receptor targets
