Schizophrenia: a clinical overview

PET scans of a healthy patient (<i>left</i>) and a patient with schizophrenia (<i>right</i>).
PET scans of a healthy patient (left) and a patient with schizophrenia (right).

Schizophrenia is recognized as a chronic and disabling mental illness that has affected and continues to affect the lives of millions of people all over the world.1 Nonetheless, significant strides have been made to date in understanding and treating patients with this chronic disease.

Pathophysiology

A proposed explanation for the development of schizophrenia is that it is a neurochemical disorder in which low dopamine levels (hypodopaminergic activity) in the mesocortical pathway, particularly the frontal lobes, cause the negative symptoms. High dopamine levels (hyperdopaminergic activity) in the mesolimbic pathway are thought to be responsible for the positive symptoms.1

In addition, serotonergic, nicotinic, and N-methyl-D-aspartate (NMDA) receptors are involved and are the focus of the mechanism of action of newer antipsychotic medications. NMDA receptor dysfunction is thought to contribute to the condition, with NMDA receptor antagonists causing positive symptoms by increasing dopamine release in the limbic area and reducing dopamine release from the ventral tegmental area. 

Genetic and environmental components are also involved in schizophrenia. The risk for schizophrenia is increased among the biological relatives of affected persons—10 times in first-degree relatives; the risk among children who have two parents with schizophrenia is 35%, and concordance rates of 23% to 78% and 8% to 28% have been observed in monozygotic and dizygotic twins, respectively.1,2 

Symptoms

Schizophrenia is defined as a psychotic thought disorder characterized by a mixture of symptoms. These may involve alterations in perception, cognition, emotions, behavior, attention, concentration, motivation, and judgment (Table 1).1,2

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Affected persons may experience difficulty relating to people in their environment as a result of a breakdown in thought processes and a deficit in the ability to display normal emotional responses to others.3 The clinical features that many patients with schizophrenia may exhibit include hallucinations, delusions, loosening of associations, misinterpretations of reality, “negative” symptoms, mannerisms, and catatonia.2

The most commonly identified positive symptoms of schizophrenia are hallucinations and delusions, with auditory hallucinations being the most commonly identified (in 74% of patients with schizophrenia).3 Negative symptoms can be associated with the absence of normal capabilities and may include emotional withdrawal, blunted affect, avolition, anhedonia, and alogia; these are fundamental to understanding the functional limitations caused by the disorder.4-6 

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