Mental health articles

Schizophrenia is a familial disorder and that genetic influences are involved in the clustering of schizophrenia in families. The liability to schizophrenia seems to be manifested in families not only through the occurrence of the classical disorder, but through other related phenotypes as well. That is, the predisposition to schizophrenia may be expressed in a number of different ways, including schizophrenia-like personality traits and cognitive dysfunctions, personality disorders, and possibly some other nonschizophrenic psychoses. Disorders that occur more frequently in the biological relatives of schizophrenic individuals than in the biological relatives of nonschizophrenic individuals are called schizophrenia spectrum disorders. Disagreement exists as to the exact composition of this spectrum, however. An accurate description of its boundaries is necessary so that researchers can determine which phenotypes reflect susceptibility to schizophrenia and thus which phenotypes should be included in genetic research on schizophrenia. Examining how the various spectrum disorders aggregate in families can also provide information about the mode of genetic transmission of the liability.

The notion of a spectrum of schizophrenic disorders first arose nearly a hundred years ago, when psychiatrists and practitioners began to notice an excess of eccentric personality and character traits among the relatives of their patients with schizophrenia. This less severe, nonpsychotic, familial syndrome was characterized by social anxiety, aloofness, limited emotional response, and odd or disordered thinking. Thus, Bleuler reasoned that schizophrenia might manifest itself in alternate forms and coined the term latent schizophrenia, which he applied to individuals who evidenced affective flattening, social withdrawal, and related characteristics, in the absence of psychotic symptoms. He noted that such a dimensional construct might be important for studies of the hereditary basis of schizophrenia. The first systematic family study involving the schizophrenia spectrum was conducted at Kraepelin’s Psychiatric Institute in 1916 (Rudin, 1916). Researchers noticed increased rates of schizophrenia and also of other potentially related psychotic disorders in the siblings of schizophrenic probands. The first behavior genetic study of schizophrenic spectrum disorders was conducted in 1941 inSweden, when Essen-Moller decided to count twins who had mental disorders with schizophrenic features concordant with their schizophrenic co-twins. EssenMoller noted the existence of schizophrenia-like personality traits in the schizophrenics’ co-twins and found concordance rates of 64% for MZ pairs and 15% for DZ pairs. Early twin studies conducted in England and Japan found similar concordance rates.

In addition, both studies found an excess of traits such as aloofness, lack of feeling, and suspiciousness in the unaffected MZ co-twins and first-degree relatives of schizophrenic probands. The study of schizophrenia spectrum disorders gained momentum in 1963 when Kety and his colleagues began the first large-scale adoption study of schizophrenia in Denmark. The Danish Adoption Study was composed of a series of studies designed to gather information about which disorders occurred more frequently among the biological relatives of schizophrenic adoptees than among the biological relatives of control adoptees. In the first, or Copenhagen, sample, Kety looked at hospital records and conducted personal interviews with the biological and adoptive relatives of schizophrenic adoptees. Rates of latent schizophrenia—a DSM-II (American Psychiatric Association, 1968) disorder based on Bleuler’s construct—were significantly elevated in the biological relatives of schizophrenic probands (14.8%) compared to those of control adoptees (0.9%). Rates were low and equal in the adoptive relatives of both the schizophrenic and nonschizophrenic adoptees. These findings provided empirical support for a schizophreniclike, nonpsychotic disorder found in the relatives of individuals with schizophrenia.

Moreover, the use of an adoption design provided support for Bleuler’s idea that latent schizophrenia was related to schizophrenia itself through genetic factors. In 1975, Kety began gathering information for adoptees who lived throughout the rest of Denmark. The findings gathered from this Provincial sample replicated those of the Copenhagen sample. When both samples were combined to form a National sample, the rates of latent schizophrenia in the biological relatives of schizophrenic probands was 10.8%, whereas the corresponding rates in the biological relatives of control probands was 1.7%\. The results of Kety’s studies were used to develop empirically based diagnostic criteria for DSM-III schizophrenia spectrum disorders \. These included the diagnosis of ‘‘schizotypal personality disorder’’ (SPD), an operationalization of the schizophrenic-like, nonpsychotic syndrome of latent schizophrenia. (The term ‘‘schizotypal’’ was chosen because it means ‘‘like schizophrenia.’’) These criteria were later reapplied blindly to the same samples, and Kety’s original results based on global diagnoses were confirmed. For example, DSM-III schizotypal personality disorder was found in 13.6% of the biological relatives of schizophrenic adoptees in the Copenhagen sample, versus 2.0% of the biological relatives of control adoptees. The application of DSM-III criteria to the relatives of probands in the National sample resulted in rates of schizophrenia spectrum disorders (defined as schizophrenia; schizoaffective disorder, mainly schizophrenic subtype; and schizotypal and paranoid personality disorders) of 23.7% in the first-degree biological relatives of adoptees with DSM-III schizophrenia and 4.7% in the first-degree biological relatives of controls. Lowing, Mirsky, and Pereira found that 15.4% of the adopted-away offspring of schizophrenic mothers in the sample had DSM-III SPD, compared with 7.7% of the adopted-away offspring of controls. The Danish Adoption Study was the first to provide empirical evidence for the increased prevalence of a less severe, nonpsychotic, genetically related form of schizophrenia. Subsequent family, twin, and adoption studies have confirmed the presence of SPD in the families of schizophrenic individuals. Kendler & Gardner found that odds ratios (OR) for SPD in the first-degree biological relatives of schizophrenic probands were homogeneous across three independent family studies and computed a common OR estimate of 5.0 for SPD. Higher rates of schizophrenia were also found among the relatives of probands with SPD, compared with the relatives of psychiatric and normal controls. Researchers now seek to further clarify the nature of SPD by determining its heritable components, that is, which of the components of SPD are seen more frequently in the biological relatives of individuals with schizophrenia and which are affected by genetic influences common to schizophrenia. It appears that SPD may be a heterogeneous category, that is, only part of the disorder defined by DSMIV (American Psychiatric Association, 1994) may be heritable. In particular, family, twin, and adoption studies suggest that, among schizotypal criteria, only eccentricity, affective constriction, and excessive social anxiety are genetically related to schizophrenia. Analyses of interviews of the biological relatives of schizophrenic probands from the Danish Adoption Study found that these relatives were more likely to describe themselves as having been withdrawn or antisocial as children.

Tags: definition, disorders, schizophrenia, spectrum