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
