B&B Week 5 Flashcards
where is the hypothalamus located?
inferior to the thalamus and forms the walls and floor of the inferior portion of the third ventricle
how is the hypothalamus divided functionally?
can be divided into functional areas of nuclei along a lateral/medial axis and anterior/posterior axis
what is the function of the hypothalamus?
main regulator of homeostasis in the body
what is the function of the lateral region of the hypothalamus?
carries two way signals between forebrain and brainstem
eating, arousal
what is the function of the medial zone of the hypothalamus?
most functionally important nuclei are here
ADH secretion, satiety, GH secretion
what is the function of the anterior zone of the hypothalamus?
cooling of body temp, sleep, eating
what is the function of the posterior zone of the hypothalamus?
up regulation of body temp
arousal
wakefulness
what are the afferents that feed into the hypothalamus?
general somatic, visceral, gustatory information from SC and brainstem
limbic afferents–> from hippocampus (via fornix to mamillary bodies) and from amygdala
olfactory info
cortical info from forebrain
thalamus
retinal collaterals
what are the efferents that flow from the hypothalamus?
descending fibres to brainstem and spinal cord (visceral motor nuclei)
ascending fibres to forebrain
what is the function of the limbic system?
together with the hypothalamus, the limbic system provides an anatomical substrate for emotional, drive related and motivated aspects of behavior
comprises both cortical and subcortical structures
what are the cortical structures associated with the limbic system?
LIMBIC LOBE–> parahippocampal, cingulated and subcallosal gyri, which are interconnected by the cingulum
what are the subcortical structures associated with the limbic system?
hippocampus, amygdala, septal nuclei
what structure gives rise to the efferents that carry limbic information out into the forebrain, brainstem and spinal cord?
hypothalamus
where is the hippocampus?
cortex, in the medial temporal lobe
forms the floor of the lateral ventricle
what is the hippocampus responsible for?
learning and memory
it is informed of all sensations
regulates behavior, autonomic function, and endocrine function
where is the amygdala found?
deep within the uncus, rostral to the hippocampus
sits above and in front of the temporal horn of the lateral ventricle and is anterior to the tail of the caudate nucleus
what are the following portions of the amygdala responsible for?
- basolateral nuclei
- central nuclei
- corticomedial nuclei
- emotional significance to a stimulus–> integrates sensory information
- regulate visceral responses to emotional stimuli (fight/flight, physiological changes due to emotional state)
- smell of food and emotional response to food (appetite) and also release of cortisol
where are the septal nuclei located?
medial wall of the frontal lobe
what do the septal nuclei connect to?
olfactory bulb, hippocampus, amygdala
cholinergic neurons that have projections to hypothalamus, amygdala, hippocampus and frontal cortex
what does the papez circuit do?
experience of emotion involves reciprocal interactions between cortex and diencephalon
what structures are considered part of the limbic system?
hypothalamus (though it is structurally part of the diencephalon, the hypothalamus is functionally part of the limbic system), hippocampus, amygdala, septal nuclei, (papez circuit), parahippocampal, cingulated and subcallosal gyri
what structures make up the papez circuit?
mammillary bodies–> thalamus anterior nuclei–> cingulate cortex–> hippocampus–> back to mammillary bodies
each of these communicates with other structures
what are the key neurotransmitters of the limbic system and the hypothalamus?
NE, dopamine, serotonin
what physiological systems do the hypothalamus and the limbic system regulate in order to maintain homeostasis?
- endocrine secretion
- autonomic function
- homeostatic functions
- thermoregulation
- food intake
- body water regulation
- fluid balance
- blood pressure
- sleep wake cycles/circadian rhythms - basic drives
- motivation
- goal oriented behaviors
- emotional behaviours - learning and memory (hippocampus only)
what is the role of the hypothalamus in the limbic system?
typically acts as the effector of the limbic system
the fornix columns cut through the hypothalamus on their pathway to the mammillary bodies, dividing it into medial and lateral areas
what are the mammillary bodies?
distinct nuclei located in the posterior part of the hypothalamus
they receive information from the hippocampus and reciprocally relay to the anterior hypothalamic nuclei and the midbrain
what are the three regions of the medial nuclei of the hypothalamus and what nuclei are found in each region?
- anterior/preoptic–> preoptic, suprechiasmatic, supraoptic, paraventricular, anterior nuclei
- middle/tubercle–> dorsomedial, ventromedial, arcuate nuclei
- posterior–> mammillary bodies, posterior nuclei
describe the lateral nuclei of the hypothalamus
diffuse nuclei
long fibre tracts passing through and interconnecting the hypothalamus with rostral areas and brainstem
list the functions of the hypothalamus
- regulation of endocrine function
- regulation of autonomic function
- temperature regulation
- food intake regulation
- regulation of sleep/wake cycle and circadian rhythm
- reproduction and sexual function
how does the hypothalamus perform the following function?
regulation of endocrine functon
supraoptic and paraventricular nuclei produce hormones and they are stored in the posterior pituitary
releasing/inhibiting hormones are released that control anterior pituitary hormone production and release
how does the hypothalamus perform the following function?
regulation of autonomic function
- anterior hypothalamus activates parasympathetic response
2. posterior hypothalamus activates sympathetic response
how does the hypothalamus perform the following function?
temperature regulation
temperature sensitive neurons respond to skin and core body (blood) temp via:
- activating heat loss centre in anterior hypothalamus (resulting in cutaneous vasodilation and sweating) or
- by activating the heat gain center in the posterior hypothalamus (resulting in peripheral vasoconstriction, shivering)
how does the hypothalamus perform the following function?
food intake regulation
the feeding center is located in the lateral hypothalamus
satiety center is in the ventromedial nucleus
both areas integrate signals to affect feeding and drinking
how does the hypothalamus perform the following function?
regulation of sleep/wake and circadian rhythms
suprachiasmatic nucleus regulates the circadian rhythms (i.e with input from retina, +++serotonin innervation)
lesions result in abnormal sleep patterns
i.e anterior hypothalamus lesion leads to insomnia
posterior hypothalamus lesion leads to impaired wakefulness
how does the hypothalamus perform the following function?
reproduction and sexual function
neurons in the preoptic nucleus and the ventromedial nucleus are sensitive to estrogens and androgens–> involved in signalling hormone secretion and activating behavior
structurally, what is the limbic system?
a ring of cortex on the medial surface of the cerebral hemisphere and includes the:
- cingulate gyrus (just above the corpus collosum)
- parahippocampal gyrus (medial gyrus of the temporal lobe)
where is the entorhinal cortex found and what does it do?
the entorhinal cortex is found in the anterior part of the parahippocampal gyrus of the limbic system
it is responsible for receiving cognitive and sensory information from cortical association areas
this cortex transmits information to the hippocampal formation for consolidation and subsequently returns it to the association areas where it is encoded as memory traces
that structures are included in the hippocampal formation?
- hippocampus
- dentate gyrus
*these structures are characterized by their S shaped scroll/seahorse shape and are located on the floor of the lateral ventricle deep to the parahippocampal gyrus in the temporal lobe
the hippocampus is composed of several 3 layered areas of cortex that are rolled upon one another
nerve fibres originating from the hippocampus converge to form the FIMBRIA –> the fornix is a continuation of these fimbriae, receiving axons from the hippocampus
describe the course of the fornix
it is a continuation of the fimbriae that originate in the hippocampus
the fornix follows the course of the lateral ventricles with most fibres terminating anteriorly in the mammillary bodies of the hypothalamus
where does the dentate gyrus lie?
between the fibriae of the hippocampus and the parahippocampal gyrus
what shape are the amygdalae?
almond shaped
what does the hippocampus do?
learning and forming new memories
likely to be an initial storage site for memories
believed to be an encoding area that translates short term memories into long term memories
the overlying cortex is also involved in memory function
what happens if both medial parts of the temporal lobes are removed?
one cannot form new memories regarding facts or events and this condition is less severe if the overlying cortex is intact
what is the function of the amygdalae?
emotional learning and modulation of fear, anxiety, rage and aggression
what happens if there is bilateral amygdala damage?
Kluver-Bucy syndrome
characterized by changes in
- aggression (if complete, you get docility and fearlessness. if partial you get bursts of aggression)
- emotional depression
- visual agnosia
- hypersexuality
- inappropriate attention to sensory stimuli
what is the definition of normal personality?
personality refers to the combination of characteristics or qualities that form an individual’s distinct character
it is a complex pattern of deeply embedded psychological characteristics expressed in behaviors
internal characteristic
relatively constant over time
includes both biological (temperament) and learned (character) elements
list the 5 personality dimensions
- openness to experiences
- conscientiousness
- extraversion
- agreeableness
- neuroticism
what are the defining characteristics and antagonistic characteristics associated with the following personality dimension?
openness to experiences
defining: intellectual, creative, insightful
antagonistic: shallow, unimaginative, unreflective
what are the defining characteristics and antagonistic characteristics associated with the following personality dimension?
conscientiousness
defining: organized, efficient, dependable, perfectionist, persistent
antagonistic: careless, erratic, forgetful
what are the defining characteristics and antagonistic characteristics associated with the following personality dimension?
extraversion
defining: sociable, expressive, spontaneous, energetic, verbose
antagonistic: withdrawn, silent, shy, inhibited
what are the defining characteristics and antagonistic characteristics associated with the following personality dimension?
agreeableness
defining: cooperative, amiable, empathetic, respectful
antagonistic: antagonistic, harsh, impolite
what are the defining characteristics and antagonistic characteristics associated with the following personality dimension?
neuroticism
defining: insecure, self-critical, anxious, touchy, excitable, jealous
antagonistic: unemotional, autonomous
define personality disorder
an enduring patterns of inner experience and behaviour that deviates markedly from expectations of individuals culture in at least two areas: cognition, affectivity, interpersonal functioning, impulse control
this enduring pattern is:
- inflexible and pervasive
- causes subjective distress or functional impairment
- is stable and of long duration
- is not due to substance use or a general medical condition (i.e head trauma)
the personality disorders are grouped into three clusters based on descriptive similarities
what are the 3 clusters of personality disorders?
- Cluster A: paranoid, schizoid and schizotypal personality disorders
- Cluster B: antisocial, borderline, histrionic and narcissistic personality disorders
- Cluster C: avoidant, dependent, and obsessive compulsive disorders
how might someone appear that has a Cluster A personality disorder?
Cluster A: paranoid, schizoid and schizotypal personality disorders
individuals with these disorders may appear odd or eccentric
how might someone appear that has a Cluster B personality disorder?
Cluster B: antisocial, borderline, histrionic and narcissistic personality disorders
individuals with these disorders may often appear dramatic, emotional or erratic
how might someone appear that has a Cluster C personality disorder?
Cluster C: avoidant, dependent, and obsessive compulsive disorders
individuals with these disorders may appear anxious or fearful
why is the clustering system for personality disorders not always the best?
because it has not been consistently validated and individuals frequently present with co-occurring disorders from different clusters
what is the key personality pattern of a paranoid personality disorder? what would the medical presentation of the patient be?
cluster A
key personality pattern: distrust, suspicious, guarded, self righteousness such that others’ motives are interpreted as malevolent
presentation: “you have nothing to offer me”
what is the key personality pattern of a schizoid personality disorder? what would the medical presentation of the patient be?
cluster A
key personality pattern: detachment from social relationships and a restricted range of emotional expression
presentation: indifferent, remote, does not connect
what is the key personality pattern of a schizotypal personality disorder? what would the medical presentation of the patient be?
cluster A
key personality pattern: acute discomfort in close relationships, cognitive or perceptual distortions, and eccentricities of behavior
presentation: odd, may blur reality and fantasy, difficult to report symptoms
what is the key personality pattern of a antisocial personality disorder? what would the medical presentation of the patient be?
cluster B
key personality pattern: disregard for, and violation of, the rights of others
presentation: superficially charming, hostile when confronted
what is the key personality pattern of a borderline personality disorder? what would the medical presentation of the patient be?
cluster B
key personality pattern: instability in interpersonal relationships, self-image, and affects; marked impulsivity
presentation: unpredictable, impulsive, suicide risk
what is the key personality pattern of a histrionic personality disorder? what would the medical presentation of the patient be?
cluster B
key personality pattern: excessive emotionality and attention seeking behavior
presentation: “everything hurts all over”
what is the key personality pattern of a narcissistic personality disorder? what would the medical presentation of the patient be?
cluster B
key personality pattern: grandiosity, need for admiration, lack of empathy
presentation: “i am special; my problem is unique”
what is the key personality pattern of a avoidant personality disorder? what would the medical presentation of the patient be?
cluster C
key personality pattern: social inhibition, feelings of inadequacy, hypersensitivity
presentation: hesitant, embarrassed, self conscious
what is the key personality pattern of a dependent personality disorder? what would the medical presentation of the patient be?
cluster C
key personality pattern: submissive and clinging behaviour related to an excessive need to be taken care of
presentation: seeks constant reassurance and feedback
what is the key personality pattern of a obsessive-compulsive personality disorder? what would the medical presentation of the patient be?
cluster C
key personality pattern: preoccupation with orderliness, perfectionism, control
presentation: “i have researched by symptoms extensively”
how are psychiatric disorders diagnosed?
- take a full hx of HPI, PMI, meds, social hx, family hx etc…
- general and detailed physical exam with focus on presenting symptoms
- include a neuro exam to get a sense of brain, nerves, muscles
- psychiatric exam–> determine person’s mental condition; MSE is an important part of the clinical assessment process
- diagnosis of psych disorders involves use of the DSM V
* DSM IV and earlier used an axial diagnosis system–> DSM V has no axes
why is the mental status exam (MSE) an important part of the psychiatric clinical assessment process?
because it provides a structured way of observing and describing a patient’s current state of mind, under the domains of appearance, attitude, behaviour, mood and affect, speech, thought process, thought content, perception, cognition, insight and judgement
what is the purpose of performing the MSE as part of the psych assessment?
obtain a comprehensive cross-sectional description of the patient’s mental state which, when combined with the biographical and historical information of the psych hx, allows the clinician to make an accurate diagnosis and formulation, which are required for coherent treatment planning
briefly state what each axis stood for in DSM IV
- axis I–clinical syndromes (i.e depression, schizophrenia)
- axis II–developmental disorders and personality disorders (i.e autism, mental retardation//paranoid, borderline)
- axis III–physical conditions which play a role in the development, continuance or exacerbation of axis I and II disorders (i.e brain injury or HIV/AIDS)
- axis IV–severity of psychosocial stressors
- axis V–global assessment of functioning
what are the fundamental features of an anxiety disorder?
unwanted emotions (panic attacks), thoughts (obsessions) and actions (avoidance)
list the different types of anxiety disorders
- panic/agorophobia
- phobic disorders
- trauma-related disorders
- OCD
- generalized anxiety disorder
what is panic/agorophobia disorder?
recurrent, discrete periods of intense fear or discomfort with 4 or more of the following:
- palpitations
- tachycarida
- sweating
- trembling
- dyspnea
- choking
- chest pain
- nausea
- chills/hot flashes
- dizziness
- derealization
- fear of losing control
- fear of death
- paresthesias
what are the types of panic/agorophobia disorders?
- unexpected
- situationally bound (always occur)
- situationally predisposed (sometimes)
define agorophobia
fear of being in a place that may be difficult to escape from in case of a panic attack
what are the types of phobic disorders?
either specific phobia or social phobia
what are examples of specific phobic disorders?
severe, excessive, persistent fear; typically avoided, recognized as irrational
can be due to animals, nature, situational, blood-injection injury and others
what are social phobia disorders?
severe, persistent fear of social interactions and performance in social situations
can be generalized (most social situations) or specific (i.e only if a meal is served)
name two trauma-related anxiety disorders
PTSD and acute stress disorder
what is PTSD?
anxiety disorder
must have been exposed to trauma, and have been having the following sx for the past year:
re-experiencing
avoidance and numbing
hyperarousal
what is acute stress disorder?
anxiety disorder
must have been exposed to trauma, other PTSD syx but less than one month
emotional numbing, reduced awareness, derealization, depersonalization, dissociative amnesia
what is obsessive compulsive disorder?
anxiety disorder
obsessions–> unwanted, recurrent thoughts, actions or images, “ego-dystonic”
compulsions–> repetitive behaviours intended to reduce stress or prevent harm
what is generalized anxiety disorder?
excessive anxiety lasting more than 6 months, associated with: restlessness tension difficulty concentrating irritability insomnia
what is the etiology of anxiety disorders?
typically chronic and arise in stressful life situations
more common in WOMEN (except for OCD which is equal)
often associated with other anxiety disorders, mood disorders, substance abuse and EDs
genes and environment interact with each other and independently predispose to anxiety disorders
both conditions fear reactions and maladaptive beliefs play a role (i.e some is learned)
what is the pathophysiology of anxiety disorders? i.e what neural structures and neurotransmitters are involved?
limbic system is important, especially the AMYGDALA
neurotransmitters: GABA, serotonin (raphe nucleus) and NE (locus ceruleus)
complex interaction between several brain areas (cortex, amygdala, hippocampus, HPA axis)
OCD–> orbitofrontal cortex has interactions with amygdala and basal ganglia
what are the cognitive pathways associated with anxiety disorders?
anxiety sensitivity–> fear of fear, due to beliefs about consequence of being afraid (i.e ridicule)
stimulus–> perceived threat–> apprehension–> body sensation–> interpretation of sensations
tendency in panic disorder to overanalyze body sensations which creates more panic–> vicious cycle
what is the treatment for anxiety disorders?
take into account patient preference, addiction potential and relapse rates etc…
meds: SSRIs, benzodiazepines
CBT: especially through exposure therapy and cognitive restructuring
combination
what are the risk factors for mood disorders?
- family member with mood disorder
- women more than men
- care taking position
- history of abuse
- stress
what role does genetics play in mood disorder risk?
highly heritable, especially in bipolar disorders
common genes exist for schizophrenia and bipolar
what is the pathophysiology of mood disorders?
most convincing evidence involved 5-HT1A receptors
HPA axis could play a role (as it controls cortisol and circadian rhythms)–> depressed patients are shown to be hypercortisolemic and have bigger pituitary glands, bigger adrenal glands and increased CRH
what are the subtypes of mood disorders?
- depressive disorders (unipolar depression)
- bipolar disorders
- other mood disorders
list the types of depressive disorders
- major depressive disorder
- dysthymic disorder
- minor depression
- DDNOS
what are the characteristics of major depressive disorder?
2 or more weeks of depressed mood plus anhedonia (inability to feel pleasure) plus 4 other depressed symptoms
physical symptoms–> appetite change, sleep disturbance, psychomotor agitation, low energy
psychological symptoms–> guilt, suicidal ideation, poor concentration
what is dysthymic disorder?
2 or more years of depressed mood on most days with other depression symptoms
what is minor depression?
fewer symptoms than major depression and shorter time span; meds are not effective
what is DDNOS?
doesnt meet criteria for major or minor depression or dysthymic
what is the treatment for depressive disorders?
psychotherapy for all types
antidepressants for major depression and dysthymia
list the types of bipolar disorders
- bipolar I disorder
- bipolar II disorder
- cyclothymic disorder
- BDNOS
what is bipolar disorder I?
1 or more manic or mixed episode followed by a major depressive episode
what is bipolar disorder II?
1 or more major depressive episode followed by 1 or more hypomanic episode
what is cyclothymic disorder?
2 or more years of episodes of hypomania and depression (less than major depression)
what is BDNOS?
doesnt meet criteria for bipolar I/II or cyclothymic
what are manic episodes?
last more than 1 week with the following sx:
physical–> irritable, risk taking, pressured speech, decreased sleep, functional impairment
psychological–> grandiosity, flight of ideas or racing thoughts, goal directed actions
what are hypomanic episodes?
same sx as mania but less severe–> last about 4 days
what is the natural history of bipolar disorders?
early onset, lifelong relapse, high rates of depression and suicide
what is the tx for bipolar disorders?
usually need a mood stabilizer before antidepressant to decrease risk of rapid cycling
what are two other types of mood disorder?
mood disorder due to general medical condition
substance induced mood disorder (i.e medication, drug of abuse, toxin etc)
what is normal depression?
normal reaction to a life event, normal functioning should return in less than a year
usually returns within weeks or months
what is the lifetime prevalence of the following anxiety disorders?
- panic disorder
- agorophobia
- specific phobia
- social phobia
- PTSD
- OCD
- BAD
- 1-2%
- 1-2%
- 7-11%
- 3-13%
- 8%
- 2.5%
- 5%
what is the lifetime prevalence of major depression and bipolar disorder?
major depression:
10% men
20% women
bipolar:
1-2%
what is the hypothesized abnormality underlying schizophrenia?
due to functional EXCESS of dopamine
based on the hypothesized abnormality underlying schizophrenia, what is the most appropriate pharmacological intervention?
use a dopamine receptor antagonist to block synaptic transmission of dopamine
what is the hypothesis behind the cause of depression?
due to a functional DEFICIENCY of biogenic amines (i.e NE, serotonin (5-HT) and probably dopamine
list 4 classes of drugs that can be used in the treatment of depression
- tricyclic antidepressants (TCAs)
- serotonin reuptake inhibitors (SRIs)–selective –> SSRI
- monoamine oxidase inhibitor (MAOIs)
- noradrenergic and specific serotonergic antidepressants (NaSSAs)
MOA of tricyclic antidepressants?
inhibit reuptake of noradrenaline (NA) and serotonin (5-HT)
what are the three classes of side effects associated with tricyclic antidepressants? what are specific examples of each?
- anticholinergic (because blocks NE)–> urinary retention, constipation, dry mouth etc…
- Antiadrenergic (because blocks NE)–> block peripheral alpha-1 receptors leading to decrease in venoconstriction (postural hypotension in the elderly)
- antihistaminic–> can be good or bad; i.e useful in helping to fall asleep
- cardiotoxic–> main reason these have fallen out of use
what is the main reason tricyclic antidepressants aren’t used as much anymore?
cardiotoxicity
MOA of serotonin reuptake inhibitors?
used to treat depression
selectively inhibit the reuptake of serotonin (5-HT)
side effects of SSRIs?
agitation, GI (nausea), sleep (increase or decrease) sexual dysfunction (in 20-60% of cases)
name two examples of TCAs
nortriptyline
amitriptyline
name two examples of SSRIs
fluvoxamine
fluoxetine
MOA of MAOIs?
monoamine oxidase breaks down monoamines by oxidizing them
the old MAOIs–> irreversible inhibition of MAO-A and MAO-B
the new MAOIs–> reversible inhibition of MAO-A
side effects of the old MAOIs?
food and drug interactions
DONT MISS WITH SSRIs (or other classes of antidepressant)
side effects of new MAOIs?
drug interactions (demerol and NSAIDs)
DONT MIX WITH SSRIs or other drug classes
name two MAOIs
phenelzine
tranylcypromine
MOA of noradrenergic and specific serotonergic antidepressants (NaSSAs)?
block pre-synaptic adrenergic and serotonergic receptors: alpha-1 adrenergic, alpha-2 adrenergic, 5-HT2a, 5-HT2c and 5-HT3
why is there a lag time in effectiveness seen in noradrenergic and specific serotonergic antidepressants (NaSSAs)?
the 3-4 lag time is thought to be due to the time it takes for down regulation of these receptors
name a noradrenergic and specific serotonergic antidepressants (NaSSAs)
mirtazapine
what is the hypothesis behind the cause of mania (bipolar disorder?
due to a functional EXCESS of biogenic amines, thought to be at the 2nd messenger level (specifically the phosphoinositide system)
name 3 classes of drugs that can be used in the treatment of mania/bipolar disorder
- lithium
- anticonvulsants
- atypical anti-psychotics
MOA of lithium in the treatment of bipolar?
thought to interfere with phosphoinositide second messenger system and thereby dampen down overactive neurotransmission
why must you consider renal function when administering lithium to a patient?
Li+ and Na+ compete at an ionic level
anything that affects electrolytes or kidney function can make Li+ toxic
*hyponatremia promotes reuptake of Li+ and can lead to toxicity–> Na+ losing diuretics (thiazide) can do this (enhances proximal tubule Li+ reabsorption)
what are the symptoms of lithium toxicity?
tremor
edema
hypothyroidism
what test should you run on a patient before administering lithium to treat bipolar?
electrolytes
kidney function
ECG
TSH
betahCG
what is the MAO of anticonvulsants (in this case to treat bipolar)?
enhance GABA, an inhibitory neurotransmitter
what specific anticonvulsants are used to treat bipolar?
valproate
carbamazepine
lamotrigine
how do atypical anti-psychotics treat bipolar?
dampen dopaminergic activity?
what is the hypothesis behind the cause of anxiety/anxiety disorders?
due to CNS excitation of hyperactivity
multifactorial
may involve NA, 5-HT and/or GABA
list 3 types of drugs used in the treatment of anxiety disorders
- benzodiazepines
- antidepressants
- beta blockers
MOA of benzodiazepines in the treatment of anxiety disorders?
enhances the effects of GABA (inhibitory NT)–> open Cl- channels so neurons become hyperpolarized and less excitable
name another substance that potentiates benzodiazepines
EtOH
why can benzodiazepines becomes addicting?
withdrawal sx mimic anxiety
MOA of antidepressants in the treatment of anxiety?
may treat “anxious depression” via 5-HT receptor down regulation effects
for which anxiety disorders are SSRIs indicated?
panic and OCD
MOA of beta blockers in the treatment of anxiety?
inhibit epinephrine mediated sympathetic actions on beta receptors
only effective for physiologic sx of anxiety (tremor, palpitations etc)
PRN
non-selective beta blockers are toxic for asthmatics
what is a big difference in side effects in benzodiazepines and beta blockers in the treatment for anxiety?
benzos are sedating
beta blockers are non sedating
name 4 factors that influences psychotherapy outcomes
- patient characteristics –> i.e motivation, capacity for interpersonal functioning, intelligence
- therapeutic alliance–> i.e positively valued and productively collaborative relationship between patient and therapist
- patient expectations–> i.e patients belief in therapy improves outcomes, if patient sees relevance in therapy, there is an improved outcome and shared rationale on treatment
- modality/brand of therapy–> i.e adherence to the modality of therapy (i.e therapist doing what is required for that therapy)
what do short term psychotherapies target?
acute problems like anxiety, depression, and some longer term problems
name 3 types of short term psychotherapy
- CBT
- interpersonal therapy
- mindfulness based cognitive therapy
what do longer term psychotherapies target?
changes in character
what id dialectical behavioral therapy used for?
long term psychotherapy
for borderline personality disorder
based on mindfulness
list the types of psychodynamic therapies
long term psychotherapy
- classical psychoanalysis
- existential
- humanistic
- focus on the relationship issues as motivation
- accept the significance of present day influence of early life experiences (freud)
- use freud’s topographic theory of the mind
- ego–> skills, knowledge, identity, filters/protects psyche
- superego–> conscience, mortality, judgement
- Id–> unconscious libidinal drives (represses libidinal urges which are basis of motivation)
what are some phenomena that may arise in the interaction between patient and therapist?
- projection/transference
- projective identification (counter-transference)
- splitting
- denial
- suppression
what is projection/transference?
from patient to therapist
i.e you remind me of my mother so i hate you
what is projective identification/counter transference?
from therapist to patient
i.e i remind him of his mother, am i now acting like his mother?
what is splitting?
phenomenon in psychotherapy
patient projects positive attributes to one person/group and negative to another–> or switches between extremes over time with the same person
what is denial (in the context of the psychotherapeutic relationship?
sacrificing reality in exchange for decrease in emotional distress
i.e ignore lump in breast and refuse mammogram
what us suppression (in the context of the psychotherapeutic relationship)?
putting something out of your ming without sacrificing reality in order to function better
i.e dont ignore the lump in breast, book mammogram, but then forget about it and distract self with regular tasks
what is cognitive behavioral therapy?
assumed mutual influence of thought, action and mood–> by challenging automatic thoughts, behavior and mood can change
automatic thoughts are in the periphery of awareness–> pathology is associated with cognitive distortions in different disorders
what are some of the cognitive distortions that CBT aims to address?
- jumping to conclusions
- emotional reasoning
- all or nothing
how do patients address cognitive distortions in CBT?
- links the thoughts, feelings and actions in a way that makes the patient more aware of them
- then they can influence and challenge them
- this implicitly produces mindfulness of thoughts and emotions/reactions
- this skill produces resiliency to relapse
list the major risk factors for mood disorders
- women
- ages 25-30 are at highest risk
- marital status–> married or never married individuals have a lower risk compared to widowed, divorced or separating couples
- income–> people that make less than $20 000 are at higher risk
- risk does NOT vary with race
- may be genetic factors–> specific cause has not been found
- several personality disorders may predispose people to getting a mood disorder
- specific life events–> death of a loved one, assault, serious marital problems
- physical trauma in early life seems to increase risk
what are the major risk factors for bipolar disorder 1 and 2?
- not much of a difference between men and women but may be slightly higher in men
- ages 18-27 seem to have highest risk
- BP seems to be higher risk in people who are part of a higher socioeconomic class
- early age of onset and number of ill relatives seems to increase the family risk of bipolar but other variables such as type of relative does not seem to
- stressful life events and social rhythm disruptions seem to play a role in reoccurrence but not initial incidence
what are the major risk factors for anxiety disorders in general?
- gender–> with exception of OCD, women have twice the risk for most anxiety disorders
- age–> in general, phobias, OCD and separation anxiety show up in early childhood while social phobia and panic disorder are often diagnosed during the teen year
- personality factors–> children’s personalities may indicate higher or lower risk for future anxiety disorders
- family history and dynamics–> anxiety disorders tend to run in families; genetic factors may play a role in some cases but family dynamics and psychological influences are also often at work
- anxiety was associated with a lack of social connections and a sense of a more threatening environment
- traumatic events–> trigger anxiety disorders in individuals who are susceptible to them because of psychological, genetic or biochem factors (i.e PTSD)
- medical conditions–> although there has been no causal relationship found, certain medical conditions have been associated with increased risk of panic disorder (migraines, obstructive sleep apnea, mitral valve prolapse, IBS, chronic fatigue syndrome, premenstrual syndrome
what are specific risk factors for generalized anxiety disorder?
most common anxiety disorder amongst elderly
usually begins in childhood and becomes a chronic ailment (particularly when left untreated)
depression commonly accompanies this anxiety disorder and depression in adolescence may be a strong predictor of GAD in adulthood
what are specific risk factors for panic disorder?
age–> usually first occurs in late teens or in mid-30s
gender–> women have twice the risk; panic attacks are very common after menopause
what are specific risk factors for OCD?
equally in men and women
most cases develop in childhood or adolescence although can occur throughout the life span
what are specific risk factors for social phobias?
age–> usually onset during early teen years
gender–> women are more likely though equal numbers seek treatment
what are specific risk factors for PTSD?
- pre-existing emotional disorder–> hx of depression (i.e) before a traumatic event
- drug or alcohol abuse
- family history of anxiety
- history of abuse (particularly that which threatens family integrity such as spousal or child abuse–> studies suggest up to one third of people who experience this type of abuse develop PTSD)
- early separation from parents
- lack of social support
- poverty
- sleep disorders–> insomnia and excessive daytime sleepiness even within a month after the traumatic event are important predictors for the development of PTSD
what are demographic risk factors for suicide?
male
not married
low education
poverty
what mental disorders increase risk for suicide?
affective/mood disorders
alcohol and drug use disorders
personality disorders
schizophrenia
why might mood and anxiety disorders commonly co-occur?
comorbidity may be due to several factors including similarities in underlying neurochemistry or anatomy, genetic predisposition and similar risk factors
individuals with greater neuroticism are at greater risk for both anxiety and mood disorders (people with higher neuroticism have the tendency to experience negative emotional states such as anger, anxiety and depression)
describe the characteristics of normal and clinical anxiety
anticipation of a future threat
characterized by:
muscle tension
vigilance in preparation for danger
cautious or avoidant behaviors
describe the characteristics of normal and clinical fear
emotional response to a real or perceived threat
characterized by:
- surges of autonomic arousal
- thoughts of immediate danger
- escape behaviours
how does clinical fear and anxiety differ from normal?
- excessive in relation to the degree of threat
- persistent
- characterized by significant distress and/or impairment in social and occupational functioning
what are 3 fundamental features of anxiety and related disorders?
- unwanted emotions (panic attacks, chronic hyperarousal, excessive fear)
- unwanted thoughts (obsessions, excessive worries, intrusive recollections)
- unwanted actions (avoidance, escape, distraction, compulsions)
what anxiety disorders are characterized by panic attacks?
they can occur in all anxiety disorders
what are panic attacks?
they can occur in all anxiety disorders
discrete period of intense fear and discomfort
abrupt onset
peaks within 10 min
peak intensity averages about 20 min length
can occur during waking hours or during sleep
four or more symptoms are required to define a panic attach
attacks with fewer than 4 symptoms are called “limited symptom” panic attacks
are all phobias learned?
no, some are innate
however there is a role for learning in some phobias (i.e pavlovian conditioning, operant conditioning, and maladaptive beliefs)
what are some protective factors for phobias?
learning to associate a stimulus with LACK of harm–> acquisition of “fearless familiarity”
protects against fear acquisition
example is positive experiences with dogs protects against development of dog phobia
what are some of the neuroanatomical structures that have been implicated in anxiety disorders?
- amygdala–> processing of emotional significance of stimuli
- HPA axis
- prefrontal cortex–> assignment of meaning to stimuli, working memory
- hippocampus–> contextual learning for fear conditioning
- frontal-striatal circuits–> implicated in OCD
name 3 parts of the fronto-striatal complex
putamen
dorsal caudate
nucleus accumbens
how is the striatal complex implicated in OCD?
- anterolateral OFC (motor control, response inhibition)–> putamen–> back and forth from thalamus
- dorsolateral PFC (working memory, executive function)–> dorsal caudate–> back and forth with thamalus
- ACC/ventromedial PFC (error monitoring, doubting)–> nucleus accumbens–> back and forth from thalamus
what are dysfunctional beliefs?
extreme, irrational or rigidly held beliefs
i.e
GAD–> worry helps me prepare for danger
panic disorder–> if my heart races i could be having a heart attack
social anxiety disorder–> people are hypercritical and i can’t meet their expectations
PTSD–> i was raped by my neighbour in my own apartment; that means I am never, ever safe, no matter where I am
*twin studies show that dysfunctional beliefs are shaped by environmental factors interacting with genetic factors
what are first line treatments for anxiety disorders?
CBTs and SSRIs
give examples of SSRIs used to treat anxiety disorder
fluoxetine
sertraline
paroxetine
clomipramine
what does the limbic system do?
learning, memory, executive function
what is the modern definition of the limbic system?
definition I: a collection of cortical and subcortical structures that regulate learning, memory and executive function –> these processes involve but are NOT limited to: hippocampus, entorhinal cortex, frontal lobes
definition II: a collection of structures that regulate emotion–> best understood by its RESULTS
- experiences or feelings of emotional state
- expression of behaviors (anger, joy, fear)
what is executive function?
planning of appropriate actions
define emotional state
best defined as a subjective, internal physiological response
why are emotions important?
emotions are critical for survival–> disorders of emotion kill
play a role in memory–> so closely coupled, can’t understand one without the other
plays a role in decision making–> from how a rat avoids danger to the finest of human achievement
emotion provides context
what structure’s comprised Broca’s “limbic lobe”?
cingulate gyrus, amygdala, hippocampus
the cingulate gyrus, hippocampal formation, mammillary body and anterior thalamic nuclei all communicate with one another as part of the limbic system… through which pathways do they each communicate?
- cingulate gyrus –> cingulum–> hippocampal formation
- hippocampal formation–> fornix–> mammillary body
- mammillary body–> mammilo-thalamic fasciculus–> anterior thalamic nuclei
- anterior thalamic nuclei–> internal capsule–> cingulate gyrus
how are the amygdala and frontal cortex related?
amygdala can affect the frontal cortex and the frontal cortex should normally inhibit the amygdala–> hypothesized that this inhibition is dysfunctional in some anxiety disorders
how does the amygdala communicate with the papez circuit?
via the hippocampal formation
also communicates with the frontal cortex and the hypothalamus
how does the hippocampus manage to be informed of all sensations?
because of all the brain regions it communicates with
what types of functions can the hippocampus access and regulate?
behavior, autonomic function and endocrine function
in addition to learning and memory
describe the connections to the amygdala
- ACTUAL stimulus input from the THALAMUS
- PERCEIVED stimulus from the CORTEX
- RECALLED stimulus from the hippocampus
what part of the amygdala (a nucleus) is the most sexually dimorphic and why? why part of the brain does this nucleus communicate with?
medial nucleus of the amygdala
regulates social behavior
lots of receptors for androgens etc… (amygdala knows the gender of the person, how old they are, and so knows how this info may act in the limbic system)
communicates with the thalamus
what nucleus of the amygdala performs the diagnosis of real or perceived or recall stimuli? what other part of the brain does this nucleus communicate with?
basolateral nucleus
integrates sensory info
“always asking pesky questions”
communicates with cortex, hippocampus and hypothalamus
what nucleus in the amygdala mediates fight or flight? what regions does this nucleus communicate with?
central nucleus
mediates fight or flight
well conserved across all mammals–> only two synapses removed from affecting paraventricular nucleus of the hypothalamus and thus release of cortisol from adrenal gland
communicates with hypothalamus (PVN), frontal cortex and brainstem
list the nuclei of the hypothalamus
- medial preoptic (MPN)
- suprachiasmatic (SCN)
- supraoptic (SON)
- dorsomedial (DMN)
- ventromedial (VMN)
- arcuate nucleus (AN)
- mammillary bodies (MB)
- paraventricular nucleus (PVN)
what does the paraventricular nucleus of the hypothalamus do?
regulates release of cortisol from adrenal gland
regulation by the hypothalamus is mediated by a chain of sequentially released hormones–> HPA axis
what are the consequences of acute elevations in cortisol? what happens if these become chronic and maladaptive?
under acute conditions, are adaptive
- mobilize energy //myopathy, diabetes
- increased vascular tone //hypertension
- suppress digestion //ulceration
- suppress reproduction //amenorrhea, impotence
- immune suppression //increased disease risk
- sharpen cognition //neuron death
how is memory and cortisol related?
“events that are emotionally arousing [or produce an increase in cortisol] may be worth remembering”
therefore, successful behavioral and emotional responses require proper integration across memory, motor and hormone response system
what is the pathway of first, activation, and second, dampening or arousal, in the threat response pathway?
what happens if this second part of the pathway is disfunctional (ie in a misguided fear situation)
first response–> path of panic
stimulus–> thalamus–> amygdala… reticular and autonomic relays cause panic (adrenaline, HR up, BP up); communication with PVN in hypothalamus causes release of cortisol
mediating response–> path of reason
thalamus also communicates with sensory cortex–> frontal cortex–> inhibits amygdala
careful appraisal by sensory and frontal cortexes dampen the amygdala’s reaction and logic prevails… panic is removed and cortisol levels return to normal
**if logic fails, the amygdala will continue to arouse and cause fear and panic–> left unchecked, chronic elevations in cortisol result in a myriad of disorders
the extent to which a stimulus produces a threatening or panic feeling depends on what?
depends on to the extent to which the amygdala is engaged
panic may be overcome by the frontal cortex (higher order reasoning) as well as several other limbic structures
what is the difference between temperament and character?
temperament–> basic biological disposition toward certain behaviors; genetically coded influences of nature
character–> crystallized influence of environment/nurture; characteristics acquired during upbringing
what is a pneumonic to describe the 5 personality dimensions?
OCEAN
Openness to experience Conscientiousness Extraversion Agreeableness Neuroticism (emotional stability)
what is the prevalence of personality disorders in the US population?
about 10%
what % of those with BPD have a hx of self-injurious acts?
70-75%
what is a mnemonic for remembering the major depressive disorder criteria?
SAD SAP ECG
Suicidal thinking/behavious
Anhedonia (losing pleasure in stuff)
Depressed mood
Sleep changes
Appetite changes
Psychomotor changes
Energy loss
Concentration loss or indecision
Guilt
list the component of the mental status examination (MSE)
- appearance and demeanor
- behaviour and movements
- speech (how they sound)
- mood (subjective) and affect (objective)
- thought process (flow of thinking)
- though content including violent ideation
- perception (5 senses)
- cognition (with folstein/MoCA if appropriate)
- insight and judgement
how are fear and anxiety different?
fear is an emotional response to a SPECIFIC EXTERNAL threat (i.e seeing a snake)
anxiety is an emotional response to a NON SPECIFIC INTERNAL threat that may not actually even occur (i.e what if i go walking in the forest and come across a snake?)
threat processing is central to fear/anxiety disorders
what is the Bed nucleus of the stria terminalis (BNST)?
extension of the amygdala
while the amygdala is involved with the response to an immediate, known threat, the BNST likely fulfills a similar role when responding to a non-specific, internal threat
can also mediate freezing, activation of the autonomic nervous system, endocrine output and brain arousal systems, although main inputs are from higher cortical and hippocampal regions rather than sensory cortex or thalamus (like amygdala would be)
what neural structures mediate avoidance behaviors?
connections between the amygdala and the ventral striatum (nucleus accumbens)
avoidance causes negative reinforcement of anxiety–> if you avoid the threat, you will learn the avoidance as a good way of being safe
what is the centre of the stress response circuit?
amygdala (“fear centre”)
what are the major monoamine neurotransmitters? what disease is associated with low monoamine levels?
- catecholamines (dopamine, NE, epinephrine)
- indoleamines (serotonin, melatonin)
according to the monoamine theory of depression (1950s), believe that depression is caused by decreased levels of monoamines (esp. NE, serotonin–> wasnnot clear which was primarily affected)
what amino acid is serotonin formed from?
tryptophan (in the raphe nucleus)
what amino acid is NE formed from?
tyrosine (in the locus ceruleus)
what is the “catecholamine theory of depression”?
1965
believes depression is related to decreased catecholaminergic (ME) transmission
animal models of altered catecholamine metabolism show abnormal exploratory behavior, conditioned avoidance and reward seeking behavior (animal version of depression?)
interference with serotonin metabolism caused irritability, insomnia, hyperactivity and hypersexual behaviours (animal version of mania?)
what is the serotonin theory of depression?
low levels of 5HT metabolite 5HIAA reported in the CSF of depressed patients
tryptophan depletion studies caused relapse of depression in patients who had previously responded to SSRIs
what are the problems with the monoamine theory of depression?
biochemical effects of antidepressants are almost instantaneous, but clinical effects take several weeks
5-HT or NE/DA depletion do not induce depression in healthy subjects
antidepressants are not effective in all patients
newer theories suggest depression may be related to dysfunction in specific neural circuits–> while function of these circuits involves monoamines, a deficit in neurotransmitters is not the primary pathology
what neural circuits may be dysfunctional in depression?
may result from dysfunctional connectivity including the frontal cortex, hippocampus and amygdala
structural imaging studies have reported decreased size of frontal and cingulate cortices
amygdala volume reduced although amygdala activity is increased (at baseline)
hippocampal volume reduced in depressed patients with smaller volume associated with greater lifetime depressive episodes
in what ways do anxiety and depression symptoms overlap?
sleep disturbance
fatigue
concentration
in what % of patients with depression would you expect to see dysfunction in the HPA axis?
50%
excess secretion of cortisol and failure to suppress cortisol release on dexemethasone test suggests impaired feedback regulation of HPA axis
in endocrine disorders you get increased depression risk (i.e cushings)
what is the heritability of depression, based on twin studies?
35-50%
what receptor do SSRIs block?
SERT transport pump
interferes with recycling of serotonin back to the presynaptic neurons thereby increasing 5HT availability in the synapse
what specific side effect is associated with the SSRI sertraline?
diarrhea
what specific side effect is associated with the SSRI paroxetine?
constipation
what are some CNS side effects associated with SSRI use (increased serotonin side effects)?
initial agitation
initial worsening of anxiety
tremors
insomnia
headache
suicidal ideation
serotonin syndrome
what are some reproductive side effects associated with SSRI use (increased serotonin side effects)?
sexual dysfunction
what are some endocrine side effects associated with SSRI use (increased serotonin side effects)?
hyponatremia
what are some hematologic side effects associated with SSRI use (increased serotonin side effects)?
bleeding (platelets need serotonin to function properly)
what is serotonin syndrome?
triad of clinical changes
- autonomic–> fever, shivering, mydriasis
- cognitive–> agitation, hypervigilance
- neuromuscular–> hyperreflexia, rigidity, myoclonus
**CLONUS (spontaneous, induced, ocular) is the most important finding in establishing the diagnosis of serotonin syndrome
- may be confused with neuroleptic malignant syndrome or anticholinergic toxicity but there are important differences
- increased serotonin results in decreased dopamine
what are SNRIs?
serotonin and norepinephrine reuptake inhibitors
name 4 SNRIs
venlafaxine
duloxetine
desvenlafaxine
levomilnacipran
how do SNRIs work?
blocks SERT and NET (transporter pumps)–> interferes with recycling of NTs back to their respective presynaptic neurons
autoreceptors are stimulated until they downregulate (same as in SSRIs)
what are SEs of SNRIs?
overlap with SSRIs but can also get possible noradrenergic effects:
sweating
increased BP or HR
urinary retention
what is an NDRI?
norepinephrine dopamine reuptake inhibitor
name an NDRI
bupropion (only one available at this time)
how do NDRIs work?
block NET and DAT transporter pumps–> effect is the same as with SNRIs but there is more available neurotransmitter in the synaptic space
**because dopamine modulates the reward center, this med plays a useful role in smoking cessation
in what other way (other than depression) can NDRIs be used?
bupropion–> smoking cessation
what is a mnemonic to remember NDRI side effects?
SHARES
Seizure Headache Agitation Rash Emesis Sleep disturbance
when are NDRIs a particularly good option?
if there have been issues with sexual dysfunction in antidepressant treatment for that patient
what type of drug is vortioxetine? how does it work?
multimodal–> serotonin stimulator/modulator
blocks reuptake of serotonin (SSRI function)
is a 5HT3 antagonist (which can influence the release of 5HT, NE, DA, histamine and ACh)
5HT1a agonist
5HT1b partial agonist
other 5HT receptor subtype effects are either much weaker, receptor density in critical areas is minimal or roles are unclear
**5HT neurons interact with GABA and glutamate receptors but because of the different effects on the different receptors (vs SSRIs) it may be better to fine tune the glutamate system in the hippocampus and PFC
what are NaSSAs?
noradrenergic serotonin specific antidepressants
name a NaSSA
mirtazapine
how does mirtazapine work?
is a NaSSA
primary mechanism is alpha-2 antagonism–> 5HT/NE disinhibition means increased release of both
blocks 5HT3–> antiemetic effect
blocks 5HT 2a/2c–> sleep restoring, antiolytic, antidepressant effects (via increasing NE/DA release in PFC)
blocks histamine–> hypnotic and antiolytic effect, particularly at low doses (but responsible for weight gain)
what are SARIs?
serotonin agonist and reuptake inhibitor
name a SARI
trazodone
how is trazodone primarily used? what is its MOA?
a SARI
primarily used as a sedative versus an antidepressant
at lower doses, it blocks histamine (at 5HT2a)
higher doses are required for the antidepressant effect when the SSRI function begins to kick in
what type of drug is amitriptyline?
TCA and SNRI–> most studied in pain
what type of drug is desipramine?
TCA and NRI
what type of drug is clomipramine?
TCA and SRI –> most studied in OCD
how do the MOAs of MAO-A versus MAO-B drugs differ (both are MAOIs)?
MAO-A metabolizes NE, 5HT, tyramine
MAO-B metabolizes dopamine preferentially
how do MAOIs work?
enhance monoamine function by interfering with the metabolism of these NTs
what other function do mood stabilizing drugs perform?
(except lithium)
are also antiepileptic drugs
are benzos recommended for long term use?
generally recommended for SHORT term use
which benzo is the safest in liver dysfunction?
still metabolized by the liver but LORAZEPAM is the safest in the case of liver dysfunction
for which disorders does the evidence support CBT effectiveness?
most unipolar depression disorders
most anxiety disorders
psychotic illness with a focus on medication compliance
in what disorders is CBT less useful?
chronic disorders such as eating disorders, personality disorders, chronic depression
what is interpersonal therapy?
equally as effective as CBT
focuses more on relationships than self talk–> maybe less helpful with socially avoidant depression patients
in what patients does dialectic behavior therapy tend to be effective?
chronically parasuicidal patients with borderline personality disorder
