Psychiatry Research EG

The heterogeneity of schizophrenia, together with its different underlying causes and pathophysiologies, has led to the proposal of a number of putative subtypes for this disorder. Hence, the concept of the deficit syndrome was introduced to reflect a distinct subtype within the syndrome of schizophrenia [1,2]. It identifies a relatively homogenous subgroup of patients having three primary (or idiopathic) negative symptoms, with combinations of two or more manifesting in the 12 months preceding the diagnosis and present constantly during periods of clinical stability [3]. The prevalence of deficit schizophrenia (DSZ) has been reported to be about 15% among patients with first-episode schizophrenia and 25–30% among those with chronic schizophrenia [1]. Patients with DSZ show poorer premorbid adjustment and greater genetic load for schizophrenia than those with nondeficit schizophrenia (NDSZ). In addition, they have a more frequently insidious onset, as well as more resistance to antipsychotic treatment, and show a worse long-term outcome [4]. Although schizophrenia is a complex genetic disorder running in families, many questions arise when results show that most of the affected individuals with schizophrenia lack a family history of the disease [5,6]. However, the human genes and their phenotypes remain constant until disequilibrium occurs resulting in disorders, which are then propagated through further changes [6]. Genetic disequilibrium includes mutations, selection, migration, and other consequences of individual mating choices. Schizophrenia is an example of such a disequilibrium affecting multiple loci and has been related to population drift; hence, it can persist in the population as a relatively prevalent disorder [7]. These multiple loci pool in certain individualswho are likely to be more affected by the clinical phenotypes; thus, it becomes common for healthy individuals in the general population to possess one or a few schizophrenia- associated endophenotypes, although actual prevalence rates are poorly documented [8,9]. Although several laboratory tests have been conducted and biological markers related to the central etiopathology of the illness have been identified [10], focusing on the endophenotypes has led to a marked difference in the way the disease is perceived. Endophenotypes are considered as quantifiable biological variations or deficits that are types of stable trait markers or indicators of presumed inherited vulnerability to a disease [11]. They are sometimes called ‘intermediate phenotype’, ‘biological marker’, ‘subclinical trait’, or ‘vulnerability marker’ [12]. They are associated with the illness in a state-independent manner and are stable over time. Characteristically, they are heritable (variance in the endophenotype is associated with genetic variance), cosegregate within families, and are found in some unaffected relatives of individuals with the disorder (because they represent vulnerability for the disorder, not the disorder itself) at a higher prevalence than in the general population [11,12]. While studying schizophrenia, endophenotype strategies are being used increasingly by researchers because, unlike the disorder, endophenotypes are presumed to have more straightforward inheritance patterns. They are not visible to the naked eye and are only assessed by experimental or laboratory-based methods rather than by clinical observation [6]. One of the important endophenotypes of schizophrenia is neurological soft signs (NSS) [12,13], which are nonlocalizing neurological abnormalities that are observed when an individual performs certain simple tasks and areestablished to be an area of abnormality in schizophrenia and related disorders, suggesting evidence of brain dysfunction [14,15]. They are presumed to have genetic origins because they are more frequently present in schizophrenic patients than in other psychiatric patients and nonpsychiatric comparison individuals and, interestingly enough, in relatives of schizophrenic patients who are intermediate between patients and normal comparison individuals [16,17].