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Pathophys, Exam 3: Schizophrenia & Bipolar Affective Disorder

Terms in this set (111)

What was schizophrenia initially described as?
initially described by Emil Karepelin as "Dementia Praecox" (1896) -- early onset dementia; early descriptions were about cognitive dysfunctions, not the psychosis
Who coined the term "schizophrenia"?
Blueler
What is psychosis?
false sense of reality
What is the problem with DSM and schizophrenia?
lumps everyone into the same category based on what you SEE; we use behaviors on the outside; tells us nothing about the endophenotype -- what's going on at the cellular level (there are multiple endophenotypes of schizophrenia)
When is typical schizophrenia onset?
adolescence or young adulthood
What is the general DSM 5 Dx for schizophrenia?
-positive symptoms (delusions, hallucinations, disorganized speech/behavior)
-negative symptoms (catatonia, affective flattening, withdrawal, avolition)
-social-occupational disturbance
-6+ months
What a delusion?
false belief; disconnect between what you believe and what is real; kernel of truth to every delusion; ex - you believe you have $10 million in the bank and you believe in and act on that
What is specific diagnostic criteria for schizophrenia?
2 or more of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated):
-at least one must be delusions, hallucinations, or disorganized speech (frequent derailment, incoherence)
-gross disorganized or catatonic behavior
-negative symptoms (diminished emotional expression or avolition)
-level of functioning in work, interpersonal areas, or self-care is markedly below the level achieved prior to onset (schizo pts don't have the capacity to have a relationship with you; prefer people not to be near them)

-continuous signs of disturbance for at least 6 months
-schizoaffective disorder and depressive or bipolar disorder with psychotic features ruled out
-disturbance is not attributable to the physiological effects of a substance/med/drug or another medical condition (i.e., not drug induced psychosis or brain tumor)
What is dx for schizophreniform disorder?
meet schizophrenia dx criteria EXCEPT for the 6 months part -- not long enough yet to call it schizophrenia; at least 1 month but less than 6 months
What is the dx for brief psychotic disorder?
presence of 1 or more of the following symptoms:
-at least one of these must be delusions, hallucinations, or disorganized speech
-grossly disorganized or catatonic behavior

-duration at least 1 day but less than 1 month, with eventual full return to premorbid level of functioning
-disturbance is not better explained by another disorder and is not attributable to the physiological effects of a substance or another medical condition
What is the dx for a delusional disorder?
-presence of 1 or more of delusions with duration of 1 month or longer
-criterion A for schizo has never been met (delusions, hallucinations, disorganized speech) - do NOT hallucinate
-functioning is NOT markedly impaired, behavior is not obviously bizarre/odd
-not attributable to the physiological effects of a substance or another medical condition and it not better explained by another mental disorder
-specify subtype: erotomanic, grandiose, jealous, persecutory, somatic, mixed, unspecified type: with bizarre content
What are the associated features of schizophrenia? Which may be most disabling?
cognitive disturbances (most disabling, actually not delusions/hallucinations): memory, sensory filtering, attention, emotion recognition, eye-tracking

interpersonal dysfunction
What type of memory do schizo pts have difficulty with?
working memory -- where you take a bunch of info and try to assimilate and do something with it
Schizo pts have trouble with sensory filtering, what does this mean?
delays in how quickly you process sensory inputs; a lot of schizo patients smoke -- nicotine actually corrects sensory gaiting, making pts feel more normal
In terms of attention, what can we identify in pts as a precursor to schizophrenia?
identify early cognitive deficits (i.e., often do very poorly in school)
What is eye-tracking in schizo pts?
eye-tracking is the ability to follow a moving target; it is impaired in schizo pts -- the eye repeatedly falls back and then catches up with jerky movements
What is the issue with emotion recognition in schizo pts?
difficulty figuring out someone's emotions -- often misread cues = difficult to have a relationship
What is onset and prevalence of schizophrenia worldwide?
-little to do with socioeconomic class (third world countries and US prevalence about the same)
-about 1% of the population
-often develops in early adulthood
-can emerge at any time
Is schizophrenia generally chronic or acute?
chronic; most suffer with moderate-to-severe lifetime impairment; life expectancy less than average
How does schizophrenia vary in males vs females?
affects males and females about equally; but females tend to have better long-term prognosis; onset differs between genders
True or false: schizophrenia has a strong genetic component
true
What are the 5 core symptom clusters of schizophrenia? What is the middle cluster -- i.e., the other clusters lead to it?
-positive symptoms
-negative symptoms
-cognitive symptoms
-mood symptoms
-social/occupational dysfunction in the center
What are "positive" symptoms of schizo?
delusions/illusions; hallucinations; disorganized speech; catatonia; bizarre behavior; aggression
What are the "negative" symptoms of schizo?
most "a" words -- i.e., lack of something; blunted affect (poor emotional expression); alogia (inability to speak); avolition (poverty of movement); anhedonia (inability to feel pleasure); withdrawal (isolated); amotivation (lacking motivation, NOT energy)
What are the cognitive symptoms of schizo?
attention/concentration; memory; executive functions (decision making); abstraction
What are the mood symptoms of schizo?
dysphoria; suicidality; hopelessness
What are the social/occupational dysfunction symptoms of schizo?
employment; interpersonal relationships; self-care
What is the dopamine hypothesis of schizo?
hypothesizes people with schizo have it because of too much dopamine activity; clinical efficacy of antipsychotics correlates with dopamine D2 blockage; psychotic symptoms can be induced by dopamine agonists
What is Sommi's golden rule of psychiatry?
if it sounds simple it's wrong or not the whole explanation
Why do antipsychotics cause dry mouth?
block muscarinic receptors (not just dopaminergic receptors)
What are the four major dopamine pathways?
-nigrostriatal tract
-mesolimbic tract
-mesocortical tract
-tuberoinfundibular tract
What is the nigrostriatal tract (extrapyramidal pathway)?
begins in the substantia nigra and ends in the caudate nucleus and putamen of the basal ganglia
What is the mesolimbic tract?
originates in the midbrain tegmentum and innervates the nucleus accumbens and adjacent limbic structures
What is the mesocortical tract?
originates in the midbrain tegmentum and innervates anterior cortical areas
What is the tuberoinfundibular tract?
projects from the arcuate and periventricular nuclei of the hypothalamus to the pituitary
What are ascending pathways in the brain?
go from deep structures in the brain; the pathways by which sensory information from the peripheral nerves is transmitted to the cerebral cortex
What does the basal ganglia help with?
memory
What does the limbic area of the brain help with?
deriving emotions
What does the mesocortical area of the prefrontal cortex help with?
utilizing working memory; emotional regulation; mood; attention
Considering the major dopamine pathways in schizophrenia helps us see what?
where some of the symptoms derive from
What is hypofrontality?
lack of activity in the prefrontal cortex; reduced activation of the dorsolateral prefrontal cortex contributes to negative symptoms and cognitive defects; functional imaging studies (PET scans) report reduced activation upon pt exposure to processing task; evidence of executive functioning deficits; lack of dopamine in prefrontal cortex = inattention, inability to concentrate, poor memory
Schizophrenia pts will show hypofrontality in a PET scan, but who else can?
nonschizophrenia psychosis pts
What dopaminergic pathway/alteration results in the negative and cognitive symptoms of schizophrenia?
hypoactivity in the mesocortical pathway
What dopaminergic pathway is part of the extrapyramidal system?
nigrostriatal pathway
What dopaminergic pathway/alteration results in positive symptoms of schizo?
hyperactivity in the mesolimbic pathway
What pathway regulates prolactin release?
tuberoinfundibular pathway
In which dopaminergic pathway do we think there is too much dopamine = positive symptoms of schizo?
mesolimbic pathway
What is serotonin? How does it relate to schizophrenia?
-major monoamine NT
-more ubiquitous than dopamine
-plays a role in concentrations of dopamine varying in different areas
-serotonin is pretty much everywhere in the brain, starts in lower parts (raphe) and goes elsewhere
-too much serotonin in schizo pts
-agonist-challenge studies: administration of mCPP (partial serotonin agonist) exacerbates symptoms in UNMEDICATED schizo pts but has NO effects on healthy volunteers
How do serotonin-dopamine interactions relate to schizophrenia?
-not enough dopamine in prefrontal cortex
-we have serotonin and dopamine input to prefrontal cortex --> serotonin will DECREASE dopamine activity in the prefrontal cortex
-no serotonin influence in limbic system = maintained dopamine activity
What is glutamate? What are its receptors? How does it relate to schizo? (not looking for pathway info here)
-major excitatory NT -- 60% of all neurons; most widely distributed in brain
-plays a role in many brain functions including memory and learning
-two basic kinds of receptors: ionotropic (AMPA, NMDA) and metabotropic (mGlu)
-NMDA receptor hypofunction implicated in schizophrenia = not enough glutamate here (PCP model for schizophrenia = NMDA antag PCP makes people psychotic; NMDA antag ketamine infusion produces exacerbations; drug therapy protects against PCP/ketamine worsening)
-several genes associated with schizo code for glutamate functions/receptors -- M3 metabotropic glutamate receptor gene predicts schizophrenia
How is psychosis from amphetamines different from psychosis from PCP? How does this relate to schizo?
amphetamine psychosis has no cognitive defects because it stimulates dopamine receptors in the prefrontal cortex = people who are more attentive and psychotic, don't look like they have schizo because no cog deficits; PCP does have cog deficits
What are glutamate pathways in terms of schizo?
-descending pathways ---> serotonin and dopamine going up sometimes connect to glutamatergic neuron going back down = affects cell bodies, cell bodies for serotonin and dopamine are deep vs glutamate cell bodies in upper; while axonal ends are the reverse = creates circuit
-if we have NMDA receptors/antagonists that aren't working and we get psychosis = some level of hypofunctioning in glutamatergic system
-major glutamate pathway to consider in schizo is the cortico-brainstem pathway that works to inhibit the ventral tegmental area through interneuronal connections via GABA pathways ---> hypofunctioning in this pathway = hyperactivity in mesolimbic area
What are serotonin-glutamate-dopamine interactions in terms of schizo?
-glutamate blocks dopamine function going to the prefrontal cortex
-GABA here is an interneuron transmitter -- might sit between serotonin and glutamate or b/t dopamine and glutamatergic neuron = GABA changes the signal (i.e., stimulating would become inhibiting)
-current drugs affects all NTs --> come up with a cocktail that works
-a lot of this extends over into bipolar disorder, mood disorders, anxiety disorders
What is the spectrum of excitation by glutamate at NMDA receptors?
as you get increasing amounts of glutamate: normal excitation becomes excessive (psychosis, mania, panic) --> excitotoxicity (neuron damage) --> more excitotoxicity (slow neurodegeneration) --> even more excitotoxicity (catastrophic neurodegen)
In comparing the brain scan of two monozygotic twins - one with and one w/o schizo, what is the difference?
twin with schizo has larger ventricles because the brain is smaller -- clear brain loss in schizo twin
What is brain loss in adolescents with schizo?
up to 5%; part of the reason prognosis for schizo is not good -- destruction of brain cells and loss of overall brain capacity
What are the 5 potential mechanisms underlying gray matter loss in schizo pts?
glutamate excitotoxicity; oxidative stress; mitochondrial dysfunction; reduced neurotrophic support; apoptosis
What is BDNF? How does it relate to schizo?
brain derived neurotropic factor; needed to grow new synapses to remember and learn; provides better brain function; reduced in schizo patients
In terms of age, when is the prodromal stage of schizo? When is the first psychotic break? When is it progressive? When is it chronic and relatively stable?
-prodromal = puberty and adolescence (neurodegen starts here)
-first psychotic break in mid-20s, typically involves a lot of episodes (more episodes = less likely to return to normal); takes 5-10 years to stable out (try to target pts here b/c noncompliance w/med, losing brain, etc.)
-progressive during early adulthood
-chronic during mid-adulthood to senescence
Is comorbidity w/other illnesses or disorders low or high in bipolar disorder?
high (anxiety, alcohol abuse)
How many episodes of mania or depression do most bipolar pts experience?
multiple episodes
What percent of bipolar pts attempt suicide?
25%
What is lifetime prevalence rate of bipolar disorder?
9.8%
True or false: over half of bipolar pts are not recognized as having the disorder
true
True or false: bipolar II is usually limited to a single episode
false
True or false: bipolar pts only attempt suicide when manic
false
Bipolar pts spend most of their time in what state -- depressed, manic/hypomanic, mixed, psychotic?
depressed
What does the number of bipolar episodes correlate with?
number of episodes correlates with residual symptoms between episodes and response to tx
What kind of episodes can occur in bipolar disorder?
manic; mixed; hypomanic; depressed (depressive most common)
In general, what do bipolar symptoms encompass?
encompass exaggerations of normal mood
True or false: a low proportion of bipolar pts get tx despite efficacy of available txs
true
What is euthymia in bipolar disorder?
flatline; doesn't mean they aren't experiencing emotion -- pts experience NORMAL range of emotion
What is subsyndromal depression in bipolar disorder?
low depression
What is hypomania in bipolar disorder?
mania to lesser extent
About how much of their life do bipolar pts spend being sick? How much of that time are they depressed?
spend about half of life sick; of time sick, about 2/3 of it they are depressed
True or false: a depressed person who is bipolar is diff from a depressed person with major depressive illness
true (VERY important)
Classify Bipolar I, Bipolar II and cyclothymia in terms of manic and mixed episodes, hypomanic episodes, and major depressive episodes?
-Bipolar 1: manic and mixed episodes, hypomanic episodes, major depressive episodes
-Bipolar 2: hypomanic episodes, major depressive episodes (NO manic and mixed)
-Cyclothymia: frequent subsyndromal symptoms of hypomania, frequent subsyndromal symptoms of major depressive episodes (NO manic and mixed)
What is the main difference between Bipolar I and Bipolar II?
whether or not they have manic and mixed episodes -- full blown mania differentiates; Bipolar II does NOT have manic and mixed episodes (no full blown mania)
What is cyclothymia in bipolar disorder?
go up and down; weave along the line; subsyndromal symptoms
What is a manic episode of bipolar disorder?
-distinct period of elevated, expansive, or irritable mood and persistently increased goal-directed activity or energy lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalized)
-three or more of the following symptoms present (4 if mood only irritable): inflated self-esteem/grandiosity, insomnia, more talkative, racing thoughts, distractibility, increase in goal-directed activity or psychomotor agitation (purposeless non-goal directed activity), excessive involvement in high-risk activities
-causes marked impairment in social/occupational functioning
-not attributable to physiological effects of a substance or another med condition
What is a hypomanic episode in bipolar disorder?
more subdued than full blown manic episode; does not last as long (at least 4 consecutive days, present most of day, nearly every day); not as intense (not severe enough to cause marked impairment in social/occupational function or hospitalization; if psychotic features the episode IS BY DEFINITION manic)
What is a mixed state in bipolar disorder?
-irritability, angryness often tips this off
-manic or hypomanic episode with mixed features, at least 3 of the following: dysphoria/depression; diminished interest or pleasure in almost all activities; psychomotor retardation; fatigue; feelings of worthlessness or inappropriate guilt; recurrent thoughts of death/suicidal ideation/suicide attempt or plan
If a pt shows mania first, are they Bipolar I or II?
Bipolar I even though they have never been depressed
If a pt has NEVER had a manic episode, are they Bipolar I or II?
Bipolar II
What is cyclothymia in terms of bipolar disorder?
-patients waves up and down line with mood swings
-for at least 2 yrs (1 yr in children/adolescents) there have been numerous periods of hypomania that do not meet criteria for hypomanic episode and numerous periods with depression that do not meet criteria for major depressive episode
-during this period, hypomanic and depressive periods present for at least half the time and individual has not been without symptoms for more than two months at a time
-criteria for major depressive, manic, or hypomanic EPISODE have never been met
What is mixed states in bipolar disorder?
depressive episode with mixed features: full criteria met for major depressive episode and at least three of the following manic/hypomanic symptoms present for majority of days or most recent depressive episode:
-elevated, expansive mood
-inflated self-esteem/grandiosity
-racing thoughts
-increase in energy or goal-directed activity
-increased/excessive involvement in high-risk activities
-insomnia
What is rapid cycling in bipolar disorder?
-four or more distinct mood episodes within a 12 month period
-can occur in any order
-up to 20% of all bipolar pts
-risk factors: longer length of illness, female, ANTIDEPRESSANT USE, thyroid disease, older age
Why is antidepressant use a big risk factor for rapid cycling in bipolar disorder?
most pts get antidepressants for tx but this actually makes pts worse -- important to get right dx first
What is involved in the integrative model of mood disorders? (i.e., what can lead to development/what is involved)
-genetics and epigenetics (what environment does to genes)(ex: risk factor for schizo is an older father because as you age you expose your body to more = changed genes passed on)
-immune dysregulation (more prominent in bipolar and mood disorders)
-poor neurotrophic support (ability for cells to prune themselves and make new connections to learn more)
What neuroimaging finding is correlated with the number of manic episodes in a bipolar pt?
increased ventricular size
What prefrontal circuitry dysregulation could relate to bipolar pathology?
hypothalamus (important in determining what needs to fire when), amygdala, hippocampus, and basal ganglia dysregulation
What brain effect correlates highly to the number of episodes -- meaning a rapid cycler has worse prognosis in bipolar disorder?
decrements in brain loss/functioning correlate highly to number of episodes
What neuroendocrine/autonomic dysfunction relates to bipolar pathology?
excessive CRF = increased glucocorticoids (stress hormone) = destroys brain over long periods of time; increased sympathetic outflow
What inflammatory markers relate to bipolar pathology?
higher levels of TNF-alpha and IL-4
What does reduced BDNF mean for a bipolar pt?
reduced neuroprotection; increased apoptosis risk; reduced neuroplasticity
What are pathologic findings in terms of NTs in bipolar pts?
reduced GABA; increased glutamate
Unipolar vs bipolar depression in terms of substance abuse?
moderate; very high
Unipolar vs bipolar depression in terms of family history loaded for mood disorders?
sometimes; common
Unipolar vs bipolar depression in terms of first episode before 25?
sometimes; very common
Unipolar vs bipolar depression in terms of seasonality?
occasional; common
Unipolar vs bipolar depression in terms of highly recurrent depression?
less common; more common
Unipolar vs bipolar depression in terms of antidepressant misadventures (get well quickly, get sick quickly, abrupt on/off)?
absent; common
Unipolar vs bipolar depression in terms of rapid on/off pattern?
unusual; common
Unipolar vs bipolar depression in terms of postpartum depression?
sometimes; common
Unipolar vs bipolar depression in terms of mixed depression/hypomania/mania?
absent; common
What 5 general categories should we think about when dx unipolar vs bipolar?
mania symptoms; course of illness; tx response; family history; associated features
Unipolar vs bipolar, how is distractibility/motivation different?
unipolar is less motivated; bipolar is more distractible
What is DIGFAST?
symptoms of hypomania and mania in bipolar disorder; distractibility; insomnia; grandiosity; flight of ideas (racing thoughts); activities (more goal-directed); speech (more talkative); thoughtlessness (risk-taking behaviors)
When deciding if someone is unipolar or bipolar, what should we look backwards for if presenting with depression?
look backwards for symptoms of mania/hypomania/mixed episode; the 5 S's -- sleep, sex/socializing, spending, speeding, special projects; also use collateral sources of history (i.e., family members); mood disorder questionnaire can be helpful in starting the conversation -- if we hit on sex, energy, or lack of sleep the pt is probably bipolar
What substance abuse comorbidity is most common in bipolar disorder? In men or women?
alcohol abuse; women
Why do schizophrenic and bipolar patients die earlier and more often?
because of other medical issues -- especially CV related -- goes back to inflammation
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