Genetic studies
It has been recognized for many decades that schizophrenia aggregates among relatives of schizophrenic patients to a greater degree than in the general population. However, very little information exists on the correlation of genetics and the symptoms of schizophrenia. It has been proposed that the negative dimension of schizophrenia may represent a genetic subtype of the illness.
In support of this hypothesis, some studies (Kay et al. 1986; McGuffin & Owen 1991), but not all (Pearlson et al. 1985; Alda et al. 1991), showed that first-degree relatives of patients with schizophrenia and high levels of negative symptoms have a higher morbid risk than the relatives of patients with schizophrenia and predominantly positive symptoms. Patients with a family history of schizophrenia are reported to have more treatment-resistant negative symptoms, which are related to poor psychosocial functioning, than those patients with no family history (Malaspina et al. 2000). Moreover, a reanalysis of previously published twin studies showed that negative symptoms in one twin predicts a higher concordance rate (Dworkin et al. 1988).
Kendler et al. (2000) attempted to provide evidence for linkage between families with schizophrenia-related disorders and chromosomal regions based on major symptoms of the illness.
They found that families with positive evidence for linkage on the genomic region 8p (D8S283 - D8S552) were likely to include probands with symptom profiles of thought disorder, affective deterioration, chronic course, poor outcome and minimal depressive symptoms.
Population-based association studies typically use the psychiatric diagnosis, i.e. the symptoms, as the phenotypic expression of illness. However, it is possible to use biological traits correlated with the illness as other indicators of phenotypic expression. For example, a specific pathological indicator such as the p50 auditory sensory gating deficit in schizophrenia may be used to identify susceptibility loci (Freedman 1998). Other examples include impaired prepulse inhibition, impaired habituation to the startle reflex, as well as eye-tracking and eye-blinking abnormalities. Such approaches may identify useful phenotypes for schizophrenia that are not based solely on diagnostic categories.
Strategies like these are continuing to evolve at a rapid pace, each offering the potential for new insights into the genetic factors involved in the expression of schizophrenia.
Response to treatment
Medication is effective in reducing both positive and, to some extent, negative symptoms, but this is covered in detail in other chapters.
Conclusions
The last two or three decades have been a rich era for the conceptualization and study of the role of symptoms in schizophrenia. The concepts of symptom dimensions have been carefully investigated, providing knowledge of cognitive impairment, structural and functional neuroanatomy and genetic bases for schizophrenia. The new horizon involves investigating the construct of an underlying cognitive dysfunction (e.g. cognitive dysmetria, working memory, a disturbance in consciousness, impaired information processing) that contributes to all the symptoms, both positive and negative.
R.L.M. Fuller, S.K. Schultz and N.C. Andreasen
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