Schizophrenia
Schizophrenia is the prototype of a psychotic disorder, with the core symptoms of delusions and hallucinations as well as disorganized speech. Some patients also display prominent psychomotor disturbances, including catatonia. Together, these florid and often dramatic symptoms are referred to as positive symptoms and contrasted with negative and cognitive symptoms, the latter being responsible for much of the disability that characterizes schizophrenia. Negative symptoms are categorized into a reduced emotional expressivity cluster (restricted or flat affect) and an avolition/apathy/ anhedonia cluster. Many schizophrenia patients struggle with cognitive impairment in the realms of working memory, attention/vigilance, verbal learning and memory, visual learning and memory, reasoning and problem solving, speed of processing, and social cognition. Schizophrenic patients can often have prominent mood symptoms; these are not inconsistent with a diagnosis of schizophrenia. However, if mood symptoms dominate the overall course of a psychotic illness, a diagnosis of schizoaffective disorder can be given. Schizophrenia is a diagnosis of exclusion; various street drug usage, medications, and medical causes of psychosis must initially be excluded before diagnosis because these can mimic the core symptoms of schizophrenia.
Many patients with schizophrenia
experience symptoms that in hindsight are recognized as a prodrome before the
onset of their florid psychosis. Unspecific prodromal symptoms (anxiety,
depression, social withdrawal) eventually give rise to attenuated psychotic
symptoms before schizophrenia declares itself by the onset of psychosis.
Because schizophrenia is a syndrome, not all patients experience symptoms from
all domains. Schizophrenia is also characterized by a fluctuating illness course,
where periods of exacerbation with prominent psychosis alternate with periods
of remission.
Schizophrenia has a prevalence of ≈1.5%, with large public health implications due
to its onset during young adulthood and persistence
throughout life. The typical age at onset is between 15 and 30 years, with
onset after age 45 years being rare. Males are 40% more likely to develop
schizophrenia than females (ratio of 1.4 : 1) and have an earlier onset. Only
about 20% of patients have a good overall prognosis. Patients with
schizophrenia often die decades earlier than people in the general population.
Its excess medical mortality is partly preventable because modifiable risk
factors (i.e., nicotine dependence and the metabolic syndrome) contribute to
deaths from cardiovascular disease. Suicide is responsible for 12% of deaths.
Schizophrenia is highly heritable.
Other important risk factors for schizophrenia include in utero insults during
brain development, such as exposure to infections; obstetric complications; advanced
paternal age; social factors, such as urbanicity or immigration status; and
early heavy cannabis use.
The neuropathology and
pathophysiology of the network dysfunction in schizophrenia remain to be
resolved. Critical brain regions involved include frontal cortical areas,
particularly dorsolateral pre- frontal cortex, the thalamus, and various limbic
and dopaminergic midbrain areas. Although varied developmental pathways can
eventually lead to schizophrenia, psychosis emerges as the result of dopamine
(DA) dysregulation as a final common pathway.
Schizophrenia can be viewed as a
neurodevelopmental disorder that affects brain circuits and develops in stages.
A prodromal stage is characterized by beginning, subtle
symptoms and role failure; eventually, this results in an active psychosis
stage and subsequently gives rise to a stage of chronic disability. According
to this model, psychosis is a late symptom. Therefore prevention of this severe
outcome requires treatment of target patients at earlier stages.
Antipsychotic medications are the
treatment of choice for acute psychosis. After resolution of the initial
psychosis, most patients require maintenance treatment with an antipsychotic
medication to reduce the likelihood of a psychotic relapse. All antipsychotics
are antagonists of dopamine 2 (D2) receptors, and many antipsychotics combine
D2 with 5-hydroxytryptamine 2a (5-HT2a) receptor blockade as their basic
receptor profile. Despite great differences in individual receptor
pharmacologic sites of activity, currently available antipsychotics are equally effective and differ
mostly in their propensity toward side effects. Only clozapine is shown to be
more effective in treatment-refractory patients with schizophrenia. Problematic
long-term side effects of all antipsychotics include tardive dyskinesia and the
metabolic syndrome.
Antipsychotics are not effective against all aspects of schizophrenia. Negative and cognitive symptoms, in particular, show little improvement with antipsychotics alone. Instead, the comprehensive treatment of schizophrenia requires integration of pharmacologic treatment with psychologic therapies and concomitant psychosocial rehabilitation. The availability of cognitive-behavioral therapy and cognitive remediation with rehabilitation holds promise for treating persistent symptoms and cognitive deficits.
