who is affected by schizophrenia
Affects almost 1% of the population worldwide, the ratio of men to women who are diagnosed is 1.4:1 (more men than women).
- More men have it than women, unlike bipolar which is about even
what is schizophrenia
A brain disorder that affects thought and perception, making it difficult for people to determine what is real. Hallucinations and delusions are frequent symptoms, but changes in social interactions, motivation, mood, and impaired cognitive functions are the most disabling and difficult to treat.
- Perception of reality is altered
- Mood is affected
- There are hallucinations
When is Schizophrenia’s onset
Onset in early adulthood, earlier for men than women. There is a “prodomal period” of 2-5 years before diagnosis, with subclinical behavioral changes noted by friends and family
where is schizophrenia found
- Globally one of the top ten causes of disability. Urbanicity is a risk factor.
- Potentially a developmental disorder that manifests in adulthood
why is schizophrenia caused
The precise cause of schizophrenia for each individual is unknown. Both genes and environment play an important role, with genetic risk factors contributing to 80% of the overall risk. Many of the environmental risk factors for schizophrenia are associated with prenatal development and early childhood
what are positive symptoms for schizophrenia
psychosis
- presentation of behaviors that are not normally seen in healthy people
list positive symptoms for schizophrenia
- hallucinations
- delusions
- disturbances of the flow, order, and content of thought
- neologism (creation of new words or expressions)
- nonsensical rhymes
how can positive symptoms for schizophrenia be addressed
with anti-psychotic medication
what are negative symptoms for schizophrenia
lack of behaviors that are normally present in healthy people
list negative symptoms of schizophrenia
- avolition (decreased motivation)
- Anhedonia – decreased ability to experience pleasure or identify activities as being pleasurable.
- Flattened affect – lack of emotion or expression of emotion.
- Poverty of speech – small vocabulary
- Social withdrawal
how can negative symptoms of schizophrenia be addressed
they are harder to address than positive symptoms
features of schizophrenia
- Postadolescent onset with sex differences – males earlier than females and perhaps more severe symptoms
- Subtle neurological changes: enlarged lateral ventricles, reductions in white matter tracts, and reduced cerebral grey matter (reduced synapses, not cell number)
How can we tell whether a disease is genetic or is caused by environmental exposure to causal risk factors
- Twin studies are very informative.
- Monozygotic twins = identical twins – they have the same genetic code * and experience the same prenatal environment.
○ Started off as one person and split in the womb
- Monozygotic twins = identical twins – they have the same genetic code * and experience the same prenatal environment.
- Dizygotic twins – fraternal twins – genetically they have the same similarity as siblings that are born at different times. However – they experience the same prenatal environment.
what is concordance
likelihood that two people will have the same diagnosis
environmental risk factors of schizophrenia
- Maternal infection in 2nd trimester
- Maternal starvation
- Infection with Plasmodium gondii (cat feces)
- Obstetric complications
- Physical or psychological abuse/trauma in childhood
- Low socioeconomic status
- Urbanicity
- Drug exposure (amphetamine, cannabis, phencyclidine)
how was schizophrenia treated before antipsychotics
- Lifetime institutionalization
- Induce fever
- Induce hypoglycemic shock
- Induce seizures with electrical stimulation
- Frontal lobotomy
○ Then substituted to Chloral hydrate and other barbiturates - Freudian psychotherapy
the discovery of chlorpromazine
- French surgeon Henri Laborit used a compound developed by Rhone-Poulenc – he was looking for a new anesthetic drug.
○ His patients became very calm when he gave it to them
○ He mentioned it to a psychiatrist friend, who started giving it to patients instead of lobotomies - Chlorpromazine was developed in 1950 and given to schizophrenia patients in 1952 after it was reported to generate a “chemical lobotomy” in patients.
- Other antipsychotics developed based on the chemical structure of chlorpromazine and screened with behavioral tests in rodents.
- Screens look for drugs that reduce motor activity elicited by amphetamine. Almost 20 antipsychotics were developed without knowing their mechanism of action (what receptors they were binding).
chlorpromazine and other antipsychotics are all
D2 dopamine receptor antagonists
too much dopamine leads to
paranoia, delusions
The first antipsychotics all worked by
blocking dopamine receptors (D2 dopamine receptor antagonists)
what were the first generation antipsychotics
chlorpromazine, haloperidol
how were these first gen APS meds discovered
Identified based on their ability to antagonize dopamine-mediated behaviors in rodents (locomotor activity)
effects of these first generation APS
- Induce serious motor impairments at or near therapeutic dose (due to D2R antagonism) – similar to Parkinson’s disease symptoms (muscle rigidity, slow movement, dystonia).
- Cause anhedonia (due to D2R antagonism) – non-compliance leading to relapse.
- Cause sedation and somnolence (due to antagonism at H1 histamine receptors) especially chlorpromazine.
- Have anti-emetic properties (used to treat vomiting).
- Cause weight gain.
- Do not cause withdrawal symptoms – relapse after discontinuation (hospitalization) 6 months.
___ marked the shift from first gen to second gen APS meds
Cloazapine
