Schizophrenia

Schizophrenia is a multifactorial illness. The most widely accepted model is stress diathesis.[17] According to this theory, a person with genetic vulnerability encounters a series of stressful influences over time, which may lead to symptoms.[18] Studies have consistently shown there to be a significant genetic component to schizophrenia, with heritability estimated at around 80%.[19][20] Environmental factors, including obstetric complications, early-life adversity, and childhood residence in urban areas, may interact with genetic risks to influence liability to schizophrenia.[21][22]

Although the pathophysiology of schizophrenia is not fully understood, a host of underlying structural and functional brain abnormalities are known to be associated with the condition.[23] Several neuroanatomic differences have been identified in brain imaging studies carried out during the at-risk period (months to years prior to disease debut) and early stages of schizophrenia.[24] 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.[25]

Synaptic pruning (which occurs during adolescence) may be disrupted, leading to impaired neural communication, in people who go on to develop schizophrenia.[19][26] This hypothesis is supported by imaging studies that demonstrate increased gray matter loss and alterations in functional brain networks.[27][28] These brain changes may be related to neuroinflammation. Neuroinflammatory markers are elevated in post-mortem neural tissue from patients with schizophrenia; animal models show these markers to be associated with microglial-mediated synaptic pruning and dendritic retraction.[28]

It is believed that the manifestation of schizophrenia symptoms is related to an imbalance of neurotransmitters. Many neurotransmitters play a role, including dopamine, serotonin, and glutamate.[29] Though definitive data are lacking, there is modest support for the hyperdopaminergic theory, which proposes that hyperactivity of dopaminergic neurons in the mesolimbic tract is a key imbalance.[30][31] 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 characterizes the typical disease course. The excessive stimulation of glutamate neurons at the hippocampus leads to their toxicity and eventual degeneration.[32]

Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5-TR)[1]

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 behavior, delusions, disorganized 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.

Pathophysiology

Classification

Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5-TR)[1]