Schizophrenia and retinitis pigmentosa: Are there mechanisms which blind insanity?

To the Editor

Schizophrenia is a highly heritable psychiatric condition (Rujescu, 2012). There have been previous reports of links between schizophrenia and retinitis pigmentosa (RP) or its associated syndromes (Jumaian and Fergusson, 2003; McDonald et al., 1998). There is a need to examine the possible cause of this association since there is emerging evidence for vitamin metabolic pathways in the pathogenesis of schizophrenia. We report a case of paranoid schizophrenia with comorbid RP and another case of schizophrenia with a family history of RP in a first-degree relative.

Patient S presented with 6 years of continuous illness characterized by delusions of persecution and infidelity, and continuous second person auditory hallucinations. She was treated with olanzapine in the past with poor response and significant weight gain. Her body mass index was 31.2 at the time of admission. She also reported visual difficulties with onset in early childhood. This included difficulty seeing things in dim light, and especially at night. On examination, she had reduced visual acuity (20/40 in the right and 20/60 in the left eye). Ocular fundus examination revealed classical retinal bone spicule pigment changes and disc pallor. Visual field charting showed peripheral field constriction. Further enquiry revealed that there was also a family history of RP in her mother. Her psychiatric symptoms responded to an antipsychotic trial with ziprasidone and she achieved clinical remission.

Patient G, a 32-year-old engineering graduate presented with 3 years of continuous illness, characterized by irritability, suspiciousness, and abusive and assaultive behaviour, along with poor personal care. Mental status examination revealed delusions of persecution, reference, and misinterpretation. Her father suffered from RP. Premorbidly, she was well adjusted and was documented to be excelling in academic performance. She was treated with risperidone at a dose of 6 mg/day. During 2 years of follow-up, she was found to be asymptomatic.

The first case demonstrates the association and comorbidity of these two disorders, suggesting that there could be shared aetiopathogenic mechanisms for both conditions. In both cases, there is familial sharing of these two disorders among first-degree relatives, raising the possibility of shared genetic causation. RP refers to a group of hereditary retinal disorders where photoreceptor cells degenerate resulting in progressive deterioration in visual function. Although there are no consistently replicated linkage findings in schizophrenia, there is some evidence for genes at certain chromosomal regions, especially at 6p24-p22 and 8p22-2 (Gottesman and Moldin, 1997), to be associated with the condition. It is interesting to note that schizophrenia along with many other metabolic disturbances and RP have been found to have coding regions in chromosome 6 encoding the major histocompatibility complex, which is important for immune regulation (Avis et al., 1997). Moreover, schizophrenia and the retinoid cascade have been linked to similar gene loci (Goodman, 1998). Retinoic acid regulates genes that are involved in the regulation of dopamine and dopamine receptors (Citver et al., 2002). The demonstration of the association of these disorders and their familial aggregation clinically suggests that common pathogenic mechanism could be operating. Unraveling this mechanism could pave way to the development of newer methods for the treatment of schizophrenia.