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Time for a broad phenotype in schizophrenia?

Psychiatric Unit, Faculty of Medicine, Valencia University, Spain. E-mail: julio.sanjuan{at}uv.es

E. J. Aguilar

University Hospital, Hospital, Valencia, Spain

R. de Frutos

Genetics Department, Faculty of Biology,Valencia University, Spain

Weiser et al (2005) suggested that it is now time for a shift from narrow to broad phenotypes in schizophrenia research. They proposed deconstructing the schizophrenia syndrome and focusing on cognitive impairment. Although we agree that there is a need for alternative phenotypes in schizophrenia, we do not believe that cognitive impairment is the best candidate. Weiser et al claim that the lack of specificity is one of the main problems of biological studies. In spite of thousands of studies of the cognitive impairment in schizophrenia, no single cognitive function has shown clinical diagnostic value.

In order to understand the pathophysiology of schizophrenia we need to understand the neurobiology of the most specific symptoms. Although auditory hallucinations may appear in other mental disorders or even in the general population, ‘voices’ remain the hallmark of psychoses, and particularly schizophrenia-spectrum disorders. Therefore auditory hallucinations are, in our opinion, a good alternative phenotype.

Although neuroimaging techniques have allowed a much better understanding of the pathophysiology of auditory hallucinations, there are few studies of genetic vulnerability to such hallucinations. Our research has focused on the molecular genetics of auditory hallucinations and supports the possible role of the CCK-AR gene in their development and persistence (Sanjuan et al, 2004). We also found a relationship between allelic variation of the serotonin transporter gene and emotional response to auditory hallucinations (Sanjuan et al, 2005). These are just some examples of how deconstructing the syndrome could help to identify alternative phenotypes.

Advances in neuroscience have been made by focusing on a small area and trying to understand it using all possible approaches. Applying this principle in psychiatry could constitute the ‘core symptom approach’. We would like to remember Rosenthal & Quinn’s (1977) advice in a beautiful study of a unique case of monozygous quadruplets concordant for schizophrenia and hallucinations: ‘If we listen intently to what these voices are telling us, we may achieve a better understanding of the mechanisms that underlie them’.

REFERENCES

Rosenthal, D. & Quinn, O. W. (1977) Quadruplet hallucinations. Phenotypic variations of a schizophrenic genotype. Archives of General Psychiatry, 34, 817 –827.[CrossRef][Medline]

Sanjuan, J., Toirac, I., Gonzalez, J. C., et al (2004) A possible association between the CCK-AR gene and persistent auditory hallucinations in schizophrenia. European Psychiatry, 19, 349 –353.[Medline]

Sanjuan, J., Rivero, O., Aguilar, E. J., et al (2005) Serotonin transporter gene polymorphism (5-HTTLPR) and emotional response to auditory hallucinations in schizophrenia. International Journal of Neuropsychopharmacology, 26, 1–3. 1–3.

Weiser, M., van Os, J. & Davidson, M. (2005) Time for a shift in focus in schizophrenia: from narrow phenotypes to broad endophenotypes. British Journal of Psychiatry, 187, 203 –205.[Abstract/Free Full Text]

This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sanjuan, J. Articles by de Frutos, R. Search for Related Content PubMed PubMed Citation Articles by Sanjuan, J. Articles by de Frutos, R.