Psychosis Flashcards
Definition of Schizophrenia
- Need 2 or more of for 6 months:
- Delusions, hallucinations, disorganized speech, disorganized/catatonic behaviour, negative symptoms (flat affect, alogia, avolition, anhedonia)
- Also affects attention, conecntration, memory
- Onset in late teens/ 20s, earlier onset in men
Etiology of schizophrenia
- environmental (maternal infection, nutrient deficiency, adversity, immigrant, cannabis, decreased motor/ cognitive/ social function)
- genetics (higher risk in twins/ children/ siblings)
- Over 150 associated SNPs i.e 22q11.2 deletion
Pathophysiology of schizophrenia
- drugs that increase DA
- increases in mesolimbic pathway leads to positive symptoms
- decreases in mesocortical pathway leads to negative symptoms and cognitive impairment
- decreased cortical thickness
What are the 4 dopamine pathways?
- Nigrostriatal
- Mesolimbic
- Mesocortical
- Tuberoinfundibular
What makes up the striatum? What 3 pathways run towards it?
- Caudate nucleus and Putamen
1. Limbic - emotion and motivation
2. Associative (DA release is increased here in schizo) - higher level cognition
3. Sensorimotor - body and eye movements
*info from the cortex flows through these 3 pathways to the striatum, which integrates output to the thalamus for feedback to the cortex
DDx for delusions/ hallucinations
- epilepsy, frontal lobe tumors, SLE, hypoxia, B12/thiamine deficiency, levodopa, prednisone, cannabis, cocaine, benzo withdrawal, bipolar
How to distinguish primary vs secondary psychosis
- Primary (i.e. schizophrenia) has normal consciousness i.e. will be able to tell you the date
- Prominent visual hallucinations are more common in secondary psychosis
Distinguishing schizophrenia vs drug induced vs medically induced
Schizo –> gradual, normal consciousness, multiple auditory hallucinations, remitting and relapsing
Substance –> sub/acute, consciousness and orientation may be altered, SUD, resolves
Medical –> variable onset, acute, Px findings, consciousness may be altered, orientation impaired, resolves
Common symptoms characteristic of schizophrenia?
audible thoughts, arguing voices, voices commenting on actions, somatic passivity (being controlled), thought withdrawal and broadcasting
Psychotic disorders and their criteria
Schizophrenia - over 6 months
Schizophreniform - 1 to 6 months
Brief psychotic disorder - 1 day to 1 month
Schizoaffective - psychosis and a mood disorder (depression or mania)
Delusional disorder - only delusions
Substance/ Medication induced psychosis
Prognosis after first schizophrenic episode
- decline is more pronounced in early stages
- relapse rate is 2 years post 1st episode
- life span is decreased 10 years (not only suicide!)
Worse prognosis if chronically progressive
Better prognosis if remitting/ relapsing
What are risk factors of schizophrenia? What factors lead to a poor prognosis?
- male, decreased cognition, older paternal age, obstetric complications
- low SES, SUD, early onset, longer time untreated, increased lateral ventricle
Describe the mesocortical pathway
- VTA to the PFC
- cognition, emotion, affect
- issues here lead to the (-) sx of schizophrenia
Describe the mesolimbic pathway
- VTA to the nucleus accumbens
- memory, emotional behaviours, reward
- activity here leads to the (+) sx of schizophrenia
Describe the nigrostriatal pathway
- SN to the basal ganglia
- controls motor movement
Describe the tuberoinfundibular pathway
- hypothalamus to the infundibular area
- controls prolactin secretion
1st Generation Antipsychotics
- MOA
- drawbacks
- side effects
- examples, and which ones are high/low potency for D2
- antagonize D2, H1, A1, M1 receptors
- antagonism of mesolimbic D2 treats (+) sx
- BUT antagonism of mesocortical D2 may lead to (-) sx (neuroleptic induced deficit syndrome), as well as extrapyramidal sx in nigrostriatal, and increased prolactin via inhibition of the TI pathway
- anti-H (sedation and weight gain), anti A (dizziness and lower BP), anti M (dry mouth, constipation, blurry vision, and urinary retention)
- Chlorpromazine low potency for D2
- Haloperidol high potency for D2
2nd Generation Antipsychotics
- MOA
- examples
- antagonize D2, H1, A1, M1, 5HT2A and some are partial agonists of 5HT1A
- 5HT2A receptor normally inhibits the release of DA, so antagonizing this receptor increases release of DA which can improve (-) sx as well as extrapyramidal sx and help inhibit prolactin release
- Clozapine, Quetiapine, Risperidone
3rd Generation Antipsychotics
- MOA
- Examples
- antagonize H1, A1, M1, 5HT2A and partial agonists of D2, D3 and 5HT1A
- partial agonism helps with extrapyramidal sx and inhibiting prolactin secretion, also lessens orthostatic hypoTN/ sedation/ dizziness/ dry mouth/ constipation
- Apriprazole (which has the most partial agonist activity)
What are the treatment guidelines for schizophrenia?
- Initially start with an SGA or TGA and evaluate over 2 weeks
- If no response, switch to a different drug (Clozapine) or increase the dose, consider a long acting injectable
- If the patient doesn’t show 20% sx decrease in the first 2 weeks it is unlikely it will work, but can wait up to 6-8 weeks to fully evaluate
- Threshold should be low for choosing to switch bc of side effects, but keep in mind that some side effects will decrease with time so consider waiting a bit if there is a therapeutic benefit
Unique side effects of clozapine?
What factors increase or decrease its plasma concentration?
What should you consider if refractory (+)/(-)/ aggression?
- agranulocytosis, myocarditis
- increase –> female, pregnant, old, CYP1A2 inhibitors (valproic acid), infection, asian, obese, rapid titration
- decrease –> smoking, inducers (carbamazepine, valproic acid)
- apiprazole/ ECT for (+) sx
- anti-depressant/ ECT for (-) sx
- mood stabilizer or anti-psychotic for aggression
What are general side effects of anti-psychotics? Treatment options
- pseudo-parkinsonism (anticholinergics)
- akathisia (benzos, propranolol, mirtazapine)
- tardive dyskinesia (TGA, cloz/quet)
- hyperprolactinemia (can lead to ED, gynecomastia, hirsutism, acne, etc.)
- weight gain, HTN, insulin insensitivity
Personality
- internal characteristics, consistent over time, based in patterns of behaviour
- can be affected by situation
5 Factor Model of Personality
Openness to experience (intellect, insight, creativity)
Conscientiousness (organized, dependable)
Extraversion (sociable, expressive, energetic)
Agreeableness (cooperative, empathic, respectful)
Neuroticism (insecure, touchy, excitable, anxious)
Personality Disorder DSM-5
Which personality disorders are most common?
- enduring pattern of behaviour that deviates from expectation of one’s culture, distress and impairment
- must affect at least 2 areas: cognition, affect, impulse, interpersonal
- must be pervasive across time and situation
- late adolescence/ early adulthood onset
- OC, antisocial, schizotypical and paranoid are most common
Cluster A Personality Disorders
- Odd-Eccentric, shared schizophrenia vulnerability
- Paranoid - distrust, self-righteous
- Schizoid - detached, does not connect
- Schizotypical - relationship discomfort, blurring of reality and fantasy, perceptual distortions, eccentric
Cluster B Personality Disorders
- Dramatic-Emotional
- Borderline - impulsive, unstable in relationships and mood, suicidal, self harm
- Histrionic - excessive emotions, attention seeking
- Antisocial - disregard for others, superficially charming
- Narcissistic - need admiration, lack empathy
Cluster C Personality Disorders
- Anxious-Fearful
- Avoidant - sensitive, hesitant, feel inadequate
- Dependent - submissive, clingy, need reassurance
- Obsessive-Compulsive - perfectionist, controlling
Motor Circuit
- regulation of gaze and eye orientation
- putamen receives input from sensory/motor areas, then sends input to the thalamus via VA/VL which sends info back to the motor cortex
Associative Circuit
- planning complex motor activity
- when an action is well-learned, activity in this circuit decreases and will increase in the motor circuit
- input from SN, nucleus accumbens and caudate nucleus project to the thalamus
Limbic Circuit
- postures/ gestures/ expressions related to emotion, anticipatory reward, incentive based learning, rich in DA neurons,
- amygdala and hippocampus –> nucleus accumbens –> thalamus –> frontal association areas, orbitofrontal lobe, and anterior cingulate
How do D1 and D2 differ?
- D1 is excitatory, G-protein mechanism increases CAMP which increases intracellular Ca
- D2 is inhibitory, G-protein mechanism blocks CAMP
What leads to catalepsy symptoms due to anti-DA meds in schizophrenia?
- D2 receptor blockade on cholinergic neurons present in the indirect pathway
How is reward wired? How does schizophrenia affect this?
- VTA (midbrain), nucleus accumbens, SN
- motivation and reward are combined to create goal oriented behaviour
- VTA –> motivation, executive functioning, drug seeking, emotion, reward
- in schizophrenia, get altered reward (DA) signalling in the mesolimbic pathway leading to distorted salience of stimuli
- in a non-addicted person, the PFC can inhibit drive while conditioned clues and saliency can stimulate it
- in an addicted person, saliency can override the PFC and will no longer be inhibited by it
Gambling disorder DSM-5
Tx?
- 12 months
- at least 4 of:
- increased amounts, restless, cant quit, preoccupied, distressed, lying about extent, affects life, rely on other for $
- CBT, motivational interviewing, no meds approved
- Screen with South Oaks Gambling Screen/ LIE/ BET
How does gambling disorder affect other things? Possible etiology?
- affects SUD tx (often coincide), increases intimate partner violence
- though to have DA basis –> increased bottom-up ventral striatal DA release to cues/gambling tasks/reward prediction, decrease of top down orbitofrontal influence
- increased compulsivity with DA agonists
What is the pathophysiology behind addiction?
- dopamine!
- mesolimbic system involved in behavioural reinforcement/ drive
- reward pathway: VTA –> NA –> PFC
- amygdala activates when seeing craved substance
- D2 receptors are LOWER in addiction, more likely to find methylphenidate pleasant
- more stress = better response to drugs
- new environments can lead to overdose
Role of serotonin
Role of glutamate
Serotonin - mood, sleep, memory, cognition
- raphe nucleus/NA/HC/PFC
- seen to decrease in the cerebral cortex after ecstasy
Glutamate - craving, learning, memory
Effect of:
Nicotine
Opioids
Alcohol
Cocaine
Methamphetamine
Cannabis
Nicotine –> increases DA and NE
Opioids –> increase DA and decrease NE
Alcohol –> increases GABA (inhibitory) and decreases glutamate (excitatory), also increases DA and 5HT
Cocaine –> reuptake inhibitor of NE, DA, 5HT
Methamphetamine –> dumps NE, DA, 5HT into the cleft by reversing transport
Cannabis –> increase DA and 5HT
*withdrawal is the opposite
Impulsivity vs compulsivity?
Impulsivity –> effort to obtain arousal/ gratification (NE and DA)
Compulsivity –> effort to reduce anxiety (5HT)
SUD DSM-5
What is considered remission?
Which substance is most addictive?
- 12 months, 2 of the typical criteria
- 3-12 months is early remission, 12+ months is sustained remission (can still have cravings)
- tobacco is most addictive (nicotine is a gateway drug)
- earlier age = higher risk of addiction
*this exact criteria is same for Cannabis use disorder and OUD
Treatments for SUD?
- Agonists –> methadone for OUD, nicotine patch for smoking
- Partial agonists –> buprenorphine for OUD, varenciline for smoking
- Antagonists –> naltrexone for OUD
- Aversion –> disulfiram for AUD
- Sx Mitigators –> benzos for alcohol withdrawal
- Behavioural –> CBT, MI, SMART, mindfulness
What is considered high risk for drinking? What causes flushing/tachycardia/HTN/nausea? Chronic consequences?
- 7+ drinks a week
- acetaldehyde
- hepatosplenomegaly, caput medusa, macro anemia, hepatitis
What does alcohol withdrawal look like?
What is delirium tremens?
What is Wernicke Korsacoff?
- insomnia, irritability, anxiety
- high BP and HR, tremor, hyperreflexia
Delirium tremens –> hallucinations, tremor, seizures, disorientation, anxiety 3-4 days after, EMERGENCY
Wernicke Korsacoff –> encephalopathy, ataxia, hallucinations, psychosis, memory impairment, low vitamin B, EMERGENCY
THC vs CBD
THC –> psychoactive, lipophilic, partial agonist of CB1
- euphoria, relaxation, psychomotor and memory deficits, increased appetite, tachycardia, analgesia
- slower onset and longer lasting if ingested
CBD –> non-intoxicating, low affinity for CB1/2
- somnolence, lethargy, insomnia, suicidal thoughts, GI
- approved for epilepsy
Where are CB1 and CB2 expressed?
CB1 –> widely expressed in CNS/PNS, psychotropic effects (THC)
CB2 –> expressed in immune tissues (macrophages, B and T cells, GI), cytokine release
Side effects of weed
- acute –> nausea, vomitting, transient psychosis, anxiety, paranoia
- higher risk with polysubstance use and ingestion, young males
- chronic –> increased risk of developing schizophrenia, impaired learning/ attention/ working memory/ coordination, poor social functioning, potentially IQ decline but could be due to SES
Evidence of benefit for weed?
Substantial - chronic pain, antiemetic in chemo, MS spasticity, decreasing opioid use (enhances the analgesic effects of opioids)
Moderate - sleep
Meh - tourette’s, anxiety, PTSD, increase appetite in HIV
What causes tolerance and withdrawal?
- over time receptors become less sensitive
- body can no longer produce enough endogenous opioids
How does pupil size vary in relation to drugs?
- Dilated if withdrawal
- Constricted if opioid overdose
Risk factors for OUD
- 40+, male, current or past Hx of SUD, family hx, depression/ anxiety/ PTSD/ ADD, chronic pain and being prescribed an opioid for it, trauma, ACEs (alter the HPA axis)
- 5-15% of chronic pain patients on opioids have OUD
Social vs structural vs self stigma
Social –> negative labels/images, ignoring
Structural –> barriers to care (witholding until better managed)
Self –> u hate urself
Ways to avoid OUD
- don’t dispense more than 30 days at a time
- do not co-Rx with benzodiazepines
- assess for other SUD
- supervised injection sites, OAT, support programs
- don’t use alone, don’t mix, don’t inject
*if overdose –> ventilation BEFORE chest compressions (respiratory issue)
Demographics of suicide
- starts at 10, increases until 24 and remains high, peaks at 50 and then decreases until 70
- continued decline in women, severe rebound in men
- overrepresented in indigenous (but NOT a risk factor)
- immigrants commit less suicide
Unintentional Self-Injury
Self-Injurious Behaviour
Non-Suicidal Self-Injury
Suicide Gesture
Suicide Attempt
Suicide
USI –> risky behaviour (alcohol overdose, firearms)
SIB –> hair pulling, skin picking, intellectual disabilities
NSSI –> intentional but not wanting to die, cutting/burning/purging
Gesture –> suicidal behaviour/ communication, doesn’t need intent
Attempt –> intent of death w action
Suicide –> resulting in death
Etiology behind NSSI
- genetic susceptibility –> TRAUMA –> increased opioid release and decreased sensitivity –> NSSI to release opioids
- those with a history of suicidality and NSSI have less endorphins in spinal fluid
- those who self-injure report greater euphoria when given opioids
- those who self-injure have lower stress/ cortisol levels
4 Cs of Suicide
Collateral –> ask other people about history, perception of reality, distortion of time, reactionary nature
Confidence –> how well do you know the patient, patient is confident in themself, poor enagement
Common Sense –> careful history taking, active vs passive ideation
Changeability –> NOT: age, sex, fam hx, prior attempts
YES: access, mental health, support, meds
Risks of Suicide (SAD PERSONS)
- sex: male
- age under 19 or over 45
- depression
- previous attempts/ psychiatric care
- excessive alcohol/ drugs
- single/ widowed/ divorced
- no support
- organized/ serious attempt (2)
- stated future intent (2)
- rational thinking loss (2)
8+ –> hospital admission
0-5 –> maybe discharge
+ASARI - assessment of suicide and risk inventory
Motivations for Suicide
- Isolated (egoistic) –> LGBT, trauma, divorced
- Hopeless (fatalistic) –> chronic illness, hardship
- For others (socioistic) –> remorse, shame, revenge, protecting others
- Pressure (anomic) –> school/social pressure, family loss/change
*most suicide interventions address anomic ideation
What should you also test for to rule out secondary causes of psychosis?
- syphilis - neurosyphilis can cause psychotic-like symptoms
- urinalysis for drugs that could be induced psychosis
BC Mental Health Act
- allows patients to be admitted involuntarily
1. Have a mental disorder
2. Require tx in a facility to prevent deterioration/ protect themselves and others
3. Cannot suitably be admitted voluntarily
Substance Induced Psychotic Disorder
- delusions and/ or hallucinations
- evidence of onset after use/ withdrawal
- not better explained by another illness
Stimulant Withdrawal
- dysphoria and 2 of:
- fatigue, unpleasant dreams, insom/hypersomnia, increased appetite, pyschomotor agitation and retardation
