Table of Contents
1. History of schizophrenia
- one of the most disabling of all brain diseases
- severe and persistent
- in literature from earliest times
- schizophrenia-like symptoms labeled as seers, witches, devils
- 19th century: human brain disease
- then "humane" treatment for "insanity": care and protection
- mid 20th century: antipsychotic drugs
- 21st century: 2-3 generations of antipsychotics, with genetics, risks, evolving anatomy
- dopamine: articulation of a modern biological hypothesis for schizophrenia
- first antipsychotic chlorpromazine was discovered accidentally
- dopamine mechanism well supported, however, support for dopamine hypothesis of pathophysiology has been inconsistent
- more recently focused on "dimensions" of dysfunction in pathophysiology (vs normal neural circuits)
1.1. Dx
- Emil Kraepelin (1856-1926): set the foundation for modern psychiatric diagnostic systems
- separated organic psychoses, then separated two primary: manic depressive psychosis and dementia praecox (paranoia, catatonia, hebephrenia as subtypes)
- Eugen Bleuler (1857-1939): 1911 - "schizophrenia" was introduced by
- "splitting" of psychic functions
- primary and secondary symptoms
- the four As: abnormal associations, autistic behaviour, abnormal affect, ambivalence
- Kurt Schneider (1887-1967): first rank symptoms
- hallucinations (3rd person auditory hallucinations)
- thought withdrawal or insertion or broadcasting
- delusional perceptions
- delusions of control
- Karl Jaspers (1883-1969)
- role in developing existential psychoanalysis
- work on psychological meaning of schizophrenic hallucinations and delusions
- Adolf Meyer (1866-1950)
- founder of psychobiology
- schizophrenia as reaction to stress
- Ernst Kretschmer (1888-1926)
- body types as a predisposing factor to schizophrenia
2. Epidemiology
- 8th ranked disability-adjusted life year
- 2.6% of the total
- 4.9% of YLD (years lost to disability)
- global DALYs stable from 1990 to 2010
- global disease, with evidence from all populations across the world
- 1% lifetime prevalence in US
- 0.05% of total population of US is treated for schizophrenia
- M=F
- male earlier onset
- peak 10-25yo vs female 25-35
- female: bimodal - second peak in middle age (3-10% after 40yo)
- <10 and >60 extremely rare
- female better prognosis
- male more negative symptoms
2.1. Risk factors
- Family history and genetic load
- More likely born in winter and early spring
- Gestational and birth complications, exposure to influenza epidemics, maternal starvation during pregnancy, Rhesus factor incompatibility, and an excess of winter births
- populated urban areas
3. Etiology
- Genetic factors, monozygotic twins: 50% concordance rate
- a-7 nicotinic receptor, DISC 1, GRM 3, COMT, NRG 1, RGS 4, and G 72
- older father's age >60 has been correlated
- Dopamine hypothesis: too much
- ?too much, too sensitive
- ?tracts: likely mesolimbic and mesocortical
- positive Sx
- Serotonin: too much -> both positive and negative symptoms
- evidence: serotonin activity of clozapine and its effectiveness
- Norepinephrine: anhedonia
- likely selective neuronal degeneration within norepi reward path
- GABA
- some patients have loss of GABAergic neurons in the hippocampus
- regulatory effect on dopamine (inhibitory)
- Glutamate
- evidence: phencyclidine (antagonist) produces similar effects as schizophrenia
- hyper/hypoactivity and glutamate-induced neurotoxicity
- acetylcholine and nicotine:
- evidence: postmortem studies
- decreased muscarinic and nicotinic receptorsin the caudate-putamen, hippocampus, and some pre-frontal areas
- Neuropathology
- cerebral cortex, thalamus, brainstem
- lateral and third ventricle enlargement
- reduced symmetry in frontal, temporal, and occipital lobes
- anatomical abnormalities in prefrontal cortex: similar to frontal lobe syndrome
- Neural circuits
- relationship between hippocampal morphological abnormalities and disturbances in prefrontal cortex metabolism or function
- Eye Movement disorders
- Eye movement dysfunction may be a trait marker for schizophrenia; it is independent of drug treatment and clinical state and is also seen in first-degree relatives of pro bands with schizophrenia