Schizophrenia
Pharmacoeconomic Effects
Majority of patients are unable to work and require social welfare
High incidence of physical and social disability
Patients require care services
on daily basis - family member, friend or care worker
Cost of €460.6 million in Ireland in 2006
Co-morbidities and hospital admissions
Psychiatric Therapy
Medication
Symptoms
Misconception
Symptoms – does not cause split personality or violence. Violence is usually linked to drug or alcohol misuse.
Infamous serial killers who were diagnosed as having a psychotic illness were also drug and alcohol abusers - Jeffrey Dahmer, Daniel Gonzales (drug fuelled killing spree - 'Freddy Krueger Killer'), Richard Chase ('Vampire of Sacramento')
Negative
Negative symptoms can often appear years before first psychotic episode - known as prodromal period
Loss of motivation
Anhedonia
Deterioration in appearance and hygeine
Social withdrawal
Positive
Disorganised or unpredictable behaviour
Confused thoughts/Difficulty concerntrating
Cognitive
Poor executive function
Decreased episodic memory
Decreased processing speed
Etiology
Immigrants
Immigrants and their second generation offspring showed rates of schizophrenia up to 10 times higher than those of the general population
Risk Factors:
Cannabis Use
Re-hospitilisations, psychosocial functioning, alcohol abuse and relapse more common among cannabis abusers
Ethnicity
Urban Living
Social Deprivation
Prenatal and Perinatal Complications
Transmitter Abnormality
Genetics
Combination of environmental factors and genetics
About 33% chance of both identical
twins developing the disease, compared to 7%
chance in non-identical twins
Not due to a single gene mutation
Neurodevelopmental
Ventricular enlargement
Slight defects of the head, hair, eyes, mouth, feet and hands
Stress-Vulnerability
Pathophysiology
Glutamate Hypothesis
Serotonin Hypothesis
5HT1A receptors have been shown to be increased in the frontal cortex, hippocampus, and thalamus in schizophrenia - causing decreased dopaminergic activity
Dopamine Hypothesis
D1 Receptors
Dihydrexidine is a selective D1 agonist
that has shown positive results in clinical trials where there was significant increase in bilateral prefrontal cortical perfusion after infusion of the drug
D2 Receptors
Treatment
No treatment to alleviate negative and cognitive symptoms
Future Treatment
Natalizumab
Target risk genes - DISC-1, neuregulin and RGS proteins
Novel targets - drugs targeting glutamatergic, cholinegeric and nicotinic receptors and signalling proteins such as PDE and AKT. Theoretically rationale but no proof.
CBT or Family Interventions
Third Generation Antipyschotic?
Aripirazole
Reduced incidence of hyperprolactinemia and EPSE's
Partial 5HT1A agonist
5HT2A antagonist
Partial D2 agonist
Second Generation Antipsychotics
Reduced incidence of EPSE's
Pharmaceutics: Risperdal Consta® Depot IM Injection
First Generation Antipsychotics
Side Effects
Hyperprolactinemia, sedation, weight gain. muscarinic and alpha adrenergic - decreased tuberoinfundibular dopamine activity
Mainly associated with movement disorders - decreased nigrostriatal dopamine activity
Chemistry: Chlorpromazine developed from phenothiazine compounds
Diagnosis
Brain Imaging
PF4015: PET Scans
PET images contain more or less intense colour to provide information about chemical activity within certain organs and tissues.
Prognosis
Natural causes in over 50%
· Non-natural causes:
o Most common in males was suicide
o Most common in females was CVD
o Suicide was particularly high in the first year after diagnosis in young patients
Reduced Life Expectancy
CVD in females
Suicide in males
Earlier Diagnosis Improves Outcome
Diagnosis – earlier you see the GP the better. Bonn scale shows good evidence for prodromal diagnosis.
Prodromal Diagnosis
Bonn Scale (BSABS)
Perplexity and Cenethesias
Cognitive, Personal or Self-Disorder
Disturbed Contact
Diminished Affectivity
Or two of:
Consistent Change in Personal Behaviour
Negative Symptoms
Catatonia
One of:
Thought Disorder
Delusions
Hallucinations
