Schizophrenia
Definition
An illness:
characterised by psychosis, disorganised speech, negative symptoms, or stereotypical behaviour
occurring for a period of at least 1 month
associated with at least a 6-month period of functional decline
Characteristic factors are:
positive symptoms
auditory hallucinations
thought disorder
delusions
negative symptoms
demotivation
self-neglect
reduced emotion
Onset is usually in early adulthood and may be preceded by years of ill-differentiated symptoms, from behavioural changes and delusions to frank psychosis
Initially, patients are usually referred by family members
As the illness progresses, patients tend to self-refer or are brought in by a case manager or law enforcement officer
Antipsychotic therapy and psychosocial interventions are effective for most patients, but to varying degrees
Suicidal tendency is one of the most dangerous complications
As many as 15% of patients may kill themselves
The risk is highest at the onset of the illness
Risk Factors
Strong
Family history of schizophrenia
The closer the family relationship to an affected relative, the higher the risk. [23]
Substance use
Weak
Parent age at birth <20 or >35 years
Evidence suggests a higher risk if the parent gives birth at age 20 years or less or 35 years or greater. [24]
This correlation is present only in those without family history of schizophrenia
Psychological stress
Evidence suggests a link between psychological stressors and disease onset. [31]
Childhood abuse
Connected with an increased risk of psychosis in adulthood. [32]
Born in winter season
Data are debatable. [33]
Geographic location (distance from Equator)
Outcome of schizophrenia has been inversely correlated with mean daily temperatures. [34]
There is a correlation between greater distance from the Equator (and the associated lower temperatures) and improved outcomes.
Migrant status
There is a reported higher incidence in migrant populations, but not in offspring born in the new location.[35]
Differential diagnosis
Malingering and factitious disorders
Delusional disorder
Heavy metal poisoning
Medicine-induced psychosis
Epidemiology
The incidence in the US varies from 5 to 10 per 10,000 a year and prevalence is approximately 0.1%. [3]
Worldwide, the prevalence of schizophrenia is approximately 1%
The incidence is much lower than the prevalence as schizophrenia is a lifelong illness in most patients
The male to female risk ratio is 1.4:1. [4] [5]
A connection may exist between later female onset and higher pre-morbid functioning.
The age of onset is usually <25 years for males and <35 years for females
More affected people have been born in the winter versus the spring or summer seasons, but these data are controversial. [6] [7]
Additionally, a higher disease incidence has been reported in urban and low-income populations versus rural and higher-income groups. [4]
No variation in prevalence has been found with certainty between ethnic groups. [8]
The incidence and prevalence appears to increase over time. [9]
Patients have a higher mortality than the general population due to medical illness and accidents. [10]
Aetiology
Schizophrenia is a multi-factorial illness
The most commonly used model is stress diathesis. [11]
A person with specific vulnerability encounters a series of stressful influences over time, which may lead to symptoms. [12]
Specific stressors (diathesis) can be biological, environmental, or both
Environmental factors include loss and trauma
Biological factors may be infections and substance abuse among others
Genes also play an important role. [13]
Current evidence suggests a multifactorial/threshold model of schizophrenia heritability
Different signs and symptoms may be linked to genes and some symptoms are found in asymptomatic relatives of patients with schizophrenia
e.g., poor psychosocial functioning
Clinical features
Key diagnostic
presence of risk factors (common)
auditory hallucinations (common)
delusions (common)
avolition (common)
anhedonia (common)
asocial behaviour (common)
affective blunting (common)
alogia (common)
cognitive deficits (common)
somatisation (common)
Other diagnostic factors
bizarre behaviour (common)
tangentiality and looseness of association (derailment) (common)
circumstantiality (common)
pressured speech (common)
distractible speech (common)
depression (common)
suicidality (common)
anxiety (common)
elation (common)
incongruent affect (common)
verbigeration (common)
word salad (common)
de-realisation (uncommon)
non-auditory hallucinations (uncommon)
déjà-vu (uncommon)
stilted goal-directed behaviours (uncommon)
catatonic symptoms (uncommon)
'soft' neurological deficits (uncommon)
Pathophysiology
A range of underlying structural and functional abnormalities have been identified.
Many neuroanatomical differences have been found in schizophrenics using imaging studies
Carried out on patients during the prodrome (a period of months to years prior to disease debut) and early schizophrenia. [14]
These include:
a global reduction in brain volume by 5% to 10%
enlarged lateral and third ventricular volume
decreased volume of the amygdala and hippocampus
slight decrease in the volume of prefrontal cortex
reduction in volume of subcortical structures such as cerebellum, caudate, and thalamic structures
reversal or loss of asymmetry between cerebral hemispheres. [15]
Functionally, schizophrenia patients have:
reduced activation in the prefrontal cortex when performing executive cognitive functioning
a decreased amount of delta sleep
In the P300 and P50 paradigms, 2 related stimuli are repeated at 300 and 50 milliseconds, respectively
Affected patients have a decreased amplitude of the P300 and decreased habituation of the P50-evoked response related to attention when compared with controls without family history of disease
These deficits may diminish following treatment with antipsychotic medications.
It is believed that the underlying cause of these abnormalities is an imbalance between neurotransmitters
Many neurotransmitters play a role, including dopamine, serotonin, and glutamate. [20]
Though definitive data are lacking, there is modest support for the hyperdopaminergic theory:
Medications blocking dopamine decrease psychotic symptoms, whereas those that increase dopamine levels cause symptoms to flare
Excitotoxicity is another theory that explains the long-term deterioration that characterises the typical disease course
According to this theory, excess stimulation at the glutamate neurons leads to their toxicity and eventual degeneration
Link to COMT?
Investigations
Main for exclusion purposes
CT/MRI head
normal in schizophrenia
serum HIV ELISA
normal in schizophrenia; positive in HIV infection
serum rapid plasma reagin (RPR) test
normal in schizophrenia; positive in syphilis infection
FBC
normal in schizophrenia; decreased Hb in anaemia
urine drug screen
normal in schizophrenia
plasma drug level monitoring
Management
acute psychotic episode
1st
commence or review oral antipsychotic medication
adjunct
intramuscular antipsychotic
adjunct
intramuscular lorazepam
adjunct
electroconvulsive therapy (ECT)
chronic symptoms
1st
oral second-generation antipsychotics
plus
psychosocial interventions
plus
health maintenance
2nd
oral first-generation antipsychotics
plus
psychosocial interventions
plus
health maintenance
3rd
intramuscular second- or first-generation antipsychotics
plus
psychosocial interventions
plus
health maintenance
comorbid bipolar spectrum symptoms
plus
mood stabilisers
comorbid depression
plus
antidepressants
comorbid anxiety
plus
anxiolytics
prominent negative symptoms
plus
selected antidepressants or ginkgo extract or ondansetron
Prognosis
The prognosis of schizophrenia is poor
Even with treatment, patients often remain symptomatic
25% to 33% of patients are treatment resistant
A significant percentage of patients will be on lifelong disability and few patients can function independently between acute episodes
The approach to this illness needs to be very comprehensive, considering compliance to medication, social support, case management, and tertiary prevention methods
Furthermore, social skills training, CBT, cognitive remediation, and social cognition training address several key components of social rehabilitation
In conjunction with psychopharmacology this may contribute to domains of functional recovery
Of factors influencing the disease course, family environment, substance abuse, and duration of untreated psychosis are the most important modifiable predictors of outcome
Proper identification is impeded by many factors including substance abuse
Early detection can reduce the duration of untreated psychosis and can predict more favourable outcomes; although some studies fail to support this observation