Endophenotypes and Biological Markers of Schizophrenia: From Biological Signs of Illness to Novel Treatment Targets
Affiliation: 6001 Research Park Blvd., Madison, WI 53719.
Keywords: Schizophrenia, endophenotypes, biomarkers, treatment targets.
Schizophrenia is a chronic, often disabling mental illness with a lifetime prevalence of ~1% worldwide, and 2-to-3 times
higher mortality rates are reported in schizophrenia patients compared to the general population. Although research has been increasingly
focusing on identifying novel diagnostic and treatment resources for this illness, the diagnosis of schizophrenia is still based on clinical
criteria, which are subjectively assessed and tend to vary across the course of the illness. Endophenotypes are commonly described as
molecular, neuropsychological, neuro-imaging, and electrophysiological parameters that are closely associated to the genetic underpinnings
of a specific disorder. Putative endophenotypes for psychiatric disorders should: 1) be associated with a specific illness in the population,
2) be heritable, 3) be present regardless of the patients clinical status, 4) co-segregate with the illness within families, and 5) be detected
in non-affected family members of psychiatric patients at higher rates than in the general population. Whenever a genetic association
is not present, or has not been investigated, the term biomarker is usually preferred. Endophenotypes and biomarkers are stable over
time and are largely symptom independent, thus enabling an objective diagnosis of schizophrenia. Furthermore, these measures could be
utilized to assess the risk of developing this disorder, and to identify novel pharmacological targets for its treatment. In this article I will
present some of the most promising endophenotypes and biological markers of schizophrenia. For each of them, I will briefly describe
abnormal findings in schizophrenia patients and, whenever available, in their first-degree relatives. I will then review the ability of each
of these measures to identify individuals with schizophrenia (diagnostic value) and to assess the risk for schizophrenia (predictive value).
Finally, I will discuss how some of these endophenotypes and biological markers could be utilized to develop novel treatment targets for
schizophrenia, as well as to further the current understanding of the neurobiology of this disorder.
Rights & PermissionsPrintExport