Schizophrenia 1 Flashcards
What is Schizophrenia?
- Psychiatric condition
- Chronic or recurrent psychosis
- Impaired social and occupational functioning
- Among WHO top 10 illnesses contributing to the global burden of
disease - Psychiatric condition
- Chronic or recurrent psychosis
- Impaired social and occupational functioning
- Among WHO top 10 illnesses contributing to the global burden of
disease
Health Impact
Psychiatric outcomes:
↑Substance Use Disorders
↑Depressive Disorders
↑Anxiety Disorders
* Social anxiety disorder
* Post-traumatic stress disorder
* Obsessive-compulsive disorder
↑ suicidality
Medical outcomes:
↑ Type 2 diabetes*
↑Lipid abnormalities*
↑Metabolic Disturbance*
↑ Cardiovascular disease*
↑Respiratory conditions
↑ rates of psychiatric and medical comorbidities
↓ life expectancy by ~20 years
*Antipsychotics are associated with ↑ risk of these conditions.
HOWEVER, higher rates of these conditions found in patients
with schizophrenia independent to antipsychotic therapy
Schizophrenia and Substance Use Disorders
- People with schizophrenia have higher rates of
substance use - Lifetime prevalence of substance abuse/substance
dependence (DSM-IV-TR) in patients diagnosed with
schizophrenia: 47 to 59% - General population (US): 16%
- Risk factors: younger age, male sex, homelessness,
incarceration, living in urban centres - Nicotine: 90%
- Cannabis: 37%
- Alcohol: 31%
- Amphetamines: 12%
- Opioids: 12%
- Hallucinogens: 4%
- Sedatives: 3%
having the symptoms alone does not necessarily make the clinical diagnosis, but having that disturbance in your interpersonal relationships, ability to function, et cetera, is what does make it a clinical diagnosis.
Psychosis is a very important characteristic feature of schizophrenia, but it’s not the only feature of the illness. Psychosis is present and other psychiatric conditions
Chronicicty must be present for schiz
Suicide
- Significantly higher rate of suicide in people with schizophrenia
- ~5% of people with schizophrenia commit suicide
- 10% of completed suicides occur in people with schizophrenia
- Risk is higher in younger individuals and declines with age
- Treatment can decrease the risk of suicide
- Clozapine among the few medications that has been shown to reduce
suicidality
Impact on Quality of Life
Factors Impacting QoL
- Schizophrenia Quality of Life Survey
(2009) - Symptoms of the disease
- Unemployment
- Financial insecurity
- Housing insecurity
- Stigma
- Interpersonal relationships
- Family/friends/caregivers
- Healthcare providers
- Medication
- Improving symptoms
- Side effects
Stigma
- Public Stigma: the negative or discriminatory attitudes that others
have about mental illness - Internalized/self-Stigma: refers to the negative attitudes, including
internalized shame, that people with mental illness have about their
own condition - Institutionalized Stigma: systemic, involving policies of government
and private organizations that intentionally or unintentionally limit
opportunities for people with mental illness
People with schizophrenia suffer from external stigma from
many sources making self-stigma becomes almost inevitable.
Genetic Factors
- Strong genetic component
- Concordance in monozygotic twins of ~40-50%
- Concordance in dizygotic twins of ~10-15%
- Compared to worldwide prevalence of ~1%
<100% concordance in identical
twins environmental factors
contribute as well - Specific genes involved in the etiology of schizophrenia have not been
identified - Genome-wide association studies have identified several genes as
“candidates” in the development of schizophrenia - Predict a polygenic model: disorder resulting from the additive effects from
multiple genes
External Factors
- Obstetrical complications
- Inflammation
- Cannabis use
- Risk factor for development of psychosis
- Cigarette smoking
- Associated with schizophrenia
- Risk factor for development of schizophrenia vs. presence of a common underlying risk factor for
both schizophrenia and smoking - First-degree relatives of people with schizophrenia have higher rates of smoking compared with
the relatives of healthy controls - Immigration
- Up to 4-fold higher prevalence of schizophrenia observed in immigrant populations compared to
native-born populations - Risk appears higher in immigrant groups that experience more discrimination – may be a result of the stresses they face
mother is pregnant with the fetus, just things that might happen that increase the risk of schizophrenia might be hemorrhaging, preterm labor. Hypoxic events are related to developing schizophrenia, poor maternal nutrition, infections during pregnancy
Inflammation is also one, so increased immune system activation leads to higher levels of pro-inflammatory cytokines
This inflammation may also be responsible for some of the associated conditions such as heart disease and diabetes.
might be related to the stresses that they face. There also might be behaviors that are demonstrated with these people that are seen as unusual to us. I’m like a Western lens.
Neurodevelopmental Hypothesis
- Schizophrenia is a neurodevelopmental disorder
- “schizophrenic lesion”
- Increased vulnerability to insults
- Pre- or perinatal neurodevelopmental abnormalities ↑ vulnerability to postpubertal insults
- External factors e.g., substance use, stress, maternal infection, may contribute
as well - Brain morphology and neuropathology
- Reductions in gray matter volumes in multiple brain regions
- Schizophrenia is a neurodevelopmental disorder
- “schizophrenic lesion”
- Increased vulnerability to insults
- Pre- or perinatal neurodevelopmental abnormalities ↑ vulnerability to postpubertal insults
- External factors e.g., substance use, stress, maternal infection, may contribute
as well - Brain morphology and neuropathology
- Reductions in gray matter volumes in multiple brain regions
Nature + Nurture
* Interaction between genetic predisposition and psychosocial factors
* Everyone has potential – timing, degree and nature of environmental
factors
environmental factors can influence the gene expression. In somebody with schizophrenia, just as a person’s genetic makeup can influence the response to the environmental stressors. So while everyone has the potential to develop schizophrenia, not everyone will. And it comes down to the combined impact of lifestyle, environment, genetic makeup
Neurotransmitters
Studies have identified various dysfunctional neurotransmitter systems in
people with schizophrenia:
* Dopamine Dopamine hypothesis:
- * Dopamine hyperactivity imbalance
* Hyperactive subcortical mesolimbic projections results in D2 hyperstimulation and contributes to positive symptoms of schizophrenia
* Hypoactive mesocortical dopamine projections to the prefrontal
cortex result in hypo-stimulation of D1 receptors, and contribute to
negative and cognitive symptoms of schizophrenia
- Glutamate Glutamate hypothesis
- Gamma-aminobutyric acid (GABA)
- Acetylcholine
Dopamine Hypothesis
*Four Main Dopamine Pathways:
- Mesolimbic
- ↑dopamine D2 hyperactivity positive symptoms
- Dopamine hypothesis
- Can be effectively treated with antipsychotics
- Mesocortical
- ↓dopamine D1 hypo-activity negative and cognitive symptoms
- Dopamine hypothesis
- Nigrostriatal
- ↓ dopamine Extra-pyramidal symptoms (EPS)
- Side effect of antipsychotics, more common with high potency antipsychotics
- Tuberoinfundibular
- ↓ dopamine ↑ increased prolactin
- Side effect of antipsychotics, more common with high potency antipsychotics
- Forms the basis for current pharmacotherapy:
- All drugs with antipsychotic properties block the dopaminergic D2 receptor
- At least 60% antagonism required for antipsychotic effect
- Dopamine alone is not 100% responsible for positive symptoms of
schizophrenia - Not all patients respond to dopamine antagonists.
- Positive symptoms persist despite adequate antipsychotic treatment in many
people with schizophrenia - Treatment-Resistant Schizophrenia
- Clozapine is extremely effective despite lower D2-occupation
Glutamate Hypothesis
- N-methyl-D-aspartate (NMDA) antagonists (PCP, ketamine) are known to
induce psychotic symptoms (+ve and –ve) - Formed initial basis for glutamate hypothesis
- NMDA antagonists ↑ dopamine in limbic regions (+ve Sx) but ↓ dopamine in
cortical regions (-ve and cognitive Sx) - ↓function of the NMDA glutamate receptor is hypothesized to
contribute to the pathology of schizophrenia - Clinical trials with glycine, D-serine, and D-cycloserine – act on the
glycine modulatory site on NMDA receptor (enhance NMDA-receptor
function) - Improvement in negative symptoms, variable effects on other symptom domains
Neurotransmitters Continued…
Gamma-aminobutyric acid (GABA)
Acetylcholine
Gamma-aminobutyric acid (GABA)
* GABAergic interneurons are
important for regulation of
prefrontal cortical function
* People with schizophrenia have
been found to have
dysfunctional GABAergic
interneurons
Acetylcholine
* Hypothesis that people with
schizophrenia have disruptions
in cholinergic system (e.g.,
acetylcholine deficiency)
* Rationale is based on the higher
prevalence of smoking behaviors
in this patient population
What is Psychosis?
- Loss of touch with reality
- Brain creates false reality to make sense of it
- Many causes:
- Primary psychotic disorder (schizophrenia, schizoaffective disorder)
- Bipolar disorder
- Depression
- Substance use disorder
Clinical Features of Schizophrenia
Impairments in social
interactions, work, self-care
Positive Symptoms
Delusions
Hallucinations
Disorganized
Thinking/Speech
Negative symptoms
Social withdrawal
Blunted/flat affect
Poverty of speech
Psychomotor retardation
Avolition (↓motivation)
Anhedonia (↓pleasure)
Alogia (↓communication)
Cognitive symptoms
Attention deficits
Memory impairment
Reduction of executive functioning
Mood symptoms
Depression
Anxiety
Aggression/hostility
Suicidality
Positive Symptoms
- Hallucinations
- Distortion of perceptions that occur in the absence of an external stimulus
- Delusions
- “Fixed beliefs that are not amenable to change in light of conflicting
evidence” - Distorted thinking/beliefs that are not rooted in reality
- Disorganized speech/illogical thoughts
- Disorganized or catatonic behaviour
Hallucinations
- Auditory
- Most common hallucination (40-80% prevalence)
- Frequently voices
- Visual
- Often unformed – glowing orbs, flashes of colour
- Less commonly fully formed human figures, faces, etc.
- Somatic
- Feelings of being touched, sexual intercourse, pain
- Olfactory and gustatory
- Less common, have not been studied systematically
- Some patients may report a strange taste or smell
. Auditory hallucinations are often the manifestation of the illness that is most responsive to anti-psychotic medication
anti-psychotics turn down the volume of these hallucinations so that they’re able to cope with them better. So again, they might not completely got rid of the hallucinations, but there’ll be less prominent
Visual more common in somebody who has a substance, substance induced presentatio
Hallucinations
- Auditory
- Most common hallucination (40-80% prevalence)
- Frequently voices
- Visual
- Often unformed – glowing orbs, flashes of colour
- Less commonly fully formed human figures, faces, etc.
- Somatic
- Feelings of being touched, sexual intercourse, pain
- Olfactory and gustatory
- Less common, have not been studied systematically
- Some patients may report a strange taste or smell
Delusions
- Experienced by ~80% of patients with
schizophrenia - Fixed, false beliefs
- May have delusional explanations for their
hallucinations - Can be bizarre or non-bizarre:
- Bizarre: clearly implausible
- Non-bizarre: not true, but technically possible
- Must consider any cultural/religious context
when determining if a belief is delusional
Types of delusions:
* Persecutory (Most common)
* Belief that one is going to be harmed, harassed, etc. by
another party
* Referential
* Belief that certain gestures, comments, environmental
cues, and so forth are directed at oneself
* Grandiose
* Person believes that he or she has exceptional abilities,
wealth, or fame
* Erotomanic
* False belief that another person is in love with him/her
* Nihilistic
* Conviction that a major catastrophe will occur
* Somatic
* Preoccupations regarding health and organ function
Speech and Behavior Changes
Disorganized Thinking (Speech)
* Tangential speech
* Circumstantial speech
* Derailment/loose associations
* Neologisms
* Word salad
Changes in Behaviour
* Can be directly observed
* “Grossly disorganized or catatonic
behaviours” (DSM-5-TR)
* Catatonic behaviors
* Stupor
* Purposeless motor activity
* Waxy flexibility
* Echolalia
* Echopraxia
DSM-5-TR. 2022.
The symptoms of disorganization are independent of the
severity of hallucinations or delusions
tangential speech is when the person gets increasingly further and further off topic. So you ask them a question, you might say, well, how did you feel when you are on All or something like that? And they might start off by acting like they’re going to answer your question, but eventually they get further and further and further off topic, and they never answered your question.
Circumstantial speech is when the person has a really round about way of answering your questions. So they might go on a tangent, but they eventually will answer your question.
derailment is when the person suddenly switches topics. Neologisms is when they just create new words that they don’t exist.
Word salad: throw together different words that make no sense together.
catatonia is a marked decrease in reactivity to the environment essentially. So this can range pretty, pretty broadly from resistance to instructions to full-on maintaining a rigid, inappropriate, or bizarre postures
They might have a complete lack of verbal and motor responses. Other features are repeated movements, staring, grimacing
Negative Symptoms
- Diminished emotional expression
- Apathy
- Flat affect
- Anergia – lack of energy
- Avolition – loss of motivation
- Alorgia – poverty of speech
- Social withdrawal
Notoriously
difficult to treat
Cognitive Symptoms
Impairments in …
* Processing speed
* Attention
* Working memory
* Verbal learning and memory
* Visual learning and memory
* Reasoning/executive functioning
* Verbal comprehension
* Social cognition
Medication side effects:
* Antipsychotic and anticholinergic
medications can impair
cognition
* Is it a symptom of the illness or
adverse effect of the
medication?
* Temporality
Clinical Course
- Heterogeneity:
- Onset: Abrupt vs
insidious - Symptom presentation:
Continuous vs
intermittent - Outcome: Poor vs
nonpoor
prodromal when they start to notice like a little bit of a worsening or change in behavior. And then the onset slash deterioration. So that’s when they become actively psychotic. That’s the active illness where it will become obvious that there’s something off,
Prodrome
- Period of time before the psychotic disorder presents
- Deterioration in personal functioning
- Memory and attention
- Social withdrawal
- Unusual behaviour
- Disrupted communication
- Disrupted affect
- Unusual perceptual experience
- Bizarre ideas
- Poor hygiene
- Reduced interest in daily activity
First Episode Psychosis
- Usually late teens, early 20s
- Only 14-20% recover fully from first episode
- Long term – Over half have episodic problematic symptoms while
other have continuous
Residual Symptoms
- Most patients will continue to experience some degree of symptoms
for the duration of their life, despite adequate treatment - Anxiety
- Suspiciousness
- Socially withdrawn
- Difficulty maintaining close relationships
- Avolition, reduced motivation
- Difficulty with employment
DSM-5-TR
A. Two or more of the characteristic symptoms below are present for a significant portion of time
during a one-month period (or less if successfully treated):
1. Delusions
2. Hallucinations
3. Disorganized speech (eg, frequent derailment or incoherence)
4. Grossly disorganized or catatonic behavior
5. Negative symptoms (ie, affective flattening, alogia, or avolition)
B. For a significant portion of the time since the onset of the disturbance, one or more major areas
of functioning such as work, interpersonal relations, or self-care are markedly below the level
achieved prior to the onset.
C. Continuous signs of the disturbance persist for at least six months. The six-month period must
include at least one month of symptoms (or less if successfully treated) that meet Criterion A
(ie, active-phase symptoms) and may include periods of prodromal or residual symptoms.
D: rule out differential diagnoses
rule out substance/medication induced psychosis
