Aetiology
Schizophrenia is a multi-factorial illness. The most widely accepted model is a stress diathesis model.[21] According to this theory, a person with a biological, psychological, and/or social vulnerability encounters one or more stressful impacts over time, which may lead to symptoms.[22] Studies have consistently shown there is a large genetic component to schizophrenia, with heritability estimated at around 80%.[23][24] Environmental factors, including obstetric complications, early-life adversity, and childhood residence in urban areas, may interact with genetic risks to influence liability to schizophrenia.[25][26]
Pathophysiology
Although pathophysiology of schizophrenia is not fully understood, a host of underlying structural and functional brain abnormalities are known to be associated with the condition.[27] Several neuroanatomical differences have been identified in brain imaging studies carried out during the at-risk mental state period (a period of months to years prior to disease debut) and early stages of schizophrenia.[28] 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; and reversal or loss of asymmetry between cerebral hemispheres.[29]
Synaptic pruning (which occurs during adolescence) may be disrupted in schizophrenia, leading to impaired neural communication, in people who go on to develop schizophrenia.[23] This hypothesis is supported by imaging studies showing increased grey matter loss and alterations in functional brain networks as people become ill.[30][31] These brain changes may be related to neuroinflammation. Neuroinflammatory markers are elevated in postmortem neural tissue from patients with schizophrenia; animal models show these markers to be associated with microglial-mediated synaptic pruning and dendritic retraction.[31]
There is strong evidence that psychotic symptoms are related to an imbalance of neurotransmitters. Many neurotransmitters play a role, including dopamine, serotonin, and glutamate.[32] Though definitive data are lacking, there is support for a hyperdopaminergic theory, which proposes that hyperactivity of dopaminergic neurons in the mesolimbic tract is a key imbalance.[33][34] Medications blocking dopamine decrease psychotic symptoms, whereas those that increase dopamine levels cause symptoms to flare.
Excessive stimulation of glutamate neurons at the hippocampus is another supported theory that could explain the long-term course in chronic schizophrenia.[35][36]
Classification
International classification of diseases (ICD-11)[4]
The World Health Organization ICD-11 criteria for schizophrenia require at least two of the following symptoms (by the individual’s report or through observation by the clinician or other informants) most of the time for a period of 1 month or more. At least one of the qualifying symptoms should be from item (A) through (D) below:
Persistent delusions (e.g., grandiose delusions, delusions of reference, persecutory delusions).
Persistent hallucinations (most commonly auditory, although they may be in any sensory modality).
Disorganised thinking (formal thought disorder) (e.g., tangentiality and loose associations, irrelevant speech, neologisms). When severe, the person’s speech may be so incoherent as to be incomprehensible (‘word salad’).
Experiences of influence, passivity, or control (i.e., the experience that one’s feelings, impulses, actions, or thoughts are not generated by oneself, or are being placed in one’s mind or withdrawn from one’s mind by others, or that one’s thoughts are being broadcast to others).
Negative symptoms such as affective flattening, alogia or paucity of speech, avolition, asociality, and anhedonia.
Grossly disorganised behaviour that impedes goal-directed activity (e.g., behaviour that appears bizarre or purposeless; unpredictable or inappropriate emotional responses that interfere with the ability to organise behaviour).
Psychomotor disturbances such as catatonic restlessness or agitation, posturing, waxy flexibility, negativism, mutism, or stupor. Note: If the full syndrome of catatonia is present in the context of schizophrenia, the diagnosis of 'catatonia associated with another mental disorder' should also be assigned.
Diagnostic and statistical manual of mental disorders, fifth edition, text revision (DSM-5-TR)[3]
Due to a lack of specificity, the DSM classification no longer includes schizophrenia subtypes. However, the latest criteria allow for a catatonia specifier, course specifiers (see below), and a symptom-based severity specifier (see below). As the disease may vary in character, specifiers may be added 1 year after the appearance of active-phase symptoms.
Course specifiers
Multiple episodes (in acute episode).
Multiple episodes (currently in partial remission): when the patient is between acute episodes and there are residual symptoms that do not meet the full diagnostic criteria.
Multiple episodes (currently in full remission): when no clinically significant symptoms exist between episodes.
Continuous: when symptoms exist throughout most of the disease course with subthreshold symptom periods being very brief relative to the overall course.
First episode (in acute episode).
First episode (in partial or full remission): if after the initial episode, minimal or no symptoms exist.
Unspecified: used when an unspecified pattern has been present.
Symptom-based severity specifier
The current severity may be rated using a quantitative assessment of the primary symptoms of psychosis (i.e., abnormal psychomotor behaviour, delusions, disorganised speech, hallucinations, negative symptoms, impaired cognition, depression, and mania). The peak severity of the symptoms over the last week is rated on a 5-point scale ranging from 0 (not present) to 4 (present and severe). The diagnosis of schizophrenia can be made without using this severity specifier.
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