**14. Genetic risk programs for psychosis**

The development of genetic high-risk (GHR) programs was an important step for early detection and intervention, especially in schizophrenia.

In recent years, genetic research have identified specific genes for schizophrenia, some with early phenotypic expression may be considered important biomarkers, for example, the CHRNA7 gene situated on chromosome 15 with importance in genetic transmission and heredity of schizophrenia [29–32].

The phenotype "schizophrenia" has been characterized by the presence of behavioral abnormalities, the related outcome, and its longitudinal course, but not its fundamental biological substrate. The absence of a neuropathological basis for schizophrenia was one reason that some researchers supported the neurodevelopmental hypothesis of schizophrenia issued by Weinberger [33]. Evidence of obstetrical complications being associated with the risk of schizophrenia supported that developmental abnormalities were involved [34].

The premorbid risk factors associated with schizophrenia as motor and cognitive delay and obstetrical complications are nonspecific; their prevalence in the nonaffected population is important, so their positive predictive value for the development of schizophrenia is limited.

Neuroimaging anomalies found in patients diagnosed with first-episode psychosis have been interpreted as supportive of a static structural abnormality associated with schizophrenia that had originated early in neurodevelopment [35].

Recently, the association of molecular genetics with intermediate phenotypes such as cognitive impairment or abnormal brain functioning, as measured with functional neuroimaging, has generated diverse understanding of major psychosis. The combination of different levels may be of particular importance for longitudinal "at risk" studies. These studies can identify individuals who are at true risk of developing major psychosis prior to its full clinical expression, enabling us to treat "at risk" individuals prior to full manifestation of psychosis and prevent its appearance during critical developmental periods such as late adolescence [1, 36].

The measurement of genetic profiles using groups of candidate genes in combination with psychosocial risk factors such as stress and illicit drug use in samples of patients with clinically significant but subthreshold features of psychosis and mood disorder is a key strategy in enhancing predictive power for transition to more established and severe psychotic disorders, in treatment selection, and in longerterm prognosis [1].

Genetic studies suggest that diagnostic boundaries may be modified based on genetic information and some genes such as NRG1, DTNBP1, DISC1, and BDNF may relate to risk for both schizophrenia and mood disorders [37]. The synergistic use of genotyping with phenotypes characterizing brain functioning will contribute to a better understanding of the mechanisms by which genes interact with other genes and/or environmental risk factors.
