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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
      • Relates to an increased incidence of psychosis and psychotic decompensation. [25] [26] 
      • Drug use is very common in affected patients. [27] 
      • Although drugs such as methamphetamines and other stimulants are more likely to exacerbate psychosis, all substances pose a risk. 
        • For example, heavy marijuana use may increase both the vulnerability to schizophrenia and the likelihood of developing the disorder. [28] [29] [30]
  • 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
    • 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
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:
      • Proposes that hyperactivity of dopaminergic neurones is the key imbalance. [21] [22]
    • 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
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