Stereoacuity

Stereoacuity describes the ability to visually perceive depth. It is a product of having two eyes facing in the same direction. Depth perception has an evolutionary advantage and is a feature shared by many successful predators. Stereoacuity allows for better hand-eye coordination and has been attributed with a role in the development of tools by primates and humans1. The ability to see in 3D confers an advantage in modern human life, allowing the performance of complicated manual tasks common to many occupations.

Requirements for stereoacuity are:

* Normal ocular and orbital anatomy

* Overlapping visual fields

* Equal sensory input

* Equal higher central processing

The most common cause of monocular vision in children is lack of overlapping fields caused by a misalignment of the eyes, known as strabismus or squint.

Strabismus

Strabismus (Squint) occurs when there is a failure to align the eyes. It is the most common paediatric ophthalmic condition occurring at a rate of aprox 3% in Caucasian populations.

A constant discrepancy of gaze has the suffix -tropia while an intermittent one is termed -phoria. Either may be convergent or divergent (prefixed by eso- or exo- respectively). Furthermore a squint may be catagorised as a concomitant or incomitant, a description of whether the angel of deviation is constant. These catagorisations lead to a collection of phenotypes and it is currently unclear whether these have disparate aetiologies.

There is a definite heritable element to strabismus and this has been displayed in ALSPAC2 for convergent squint (OR 2.39 for a positive family history of esotropia).

A previous (unpublished) analysis of genome wide associations of Single Nucleotide Polymorphims (SNP) with squint and stereo was conducted within ALSPAC (ref B711) to tease out the heritable element of the condition. The strongest association was with a SNP in a gene on Chromosome 1 - PDE4B.

PDE4B

PDE4B gene is located on chromosome 1p31. Its gene product is one of a family of enzymes that regulate intracellular pathways via cAMP. It has been proven to be expressed in brain tissue3.

Most significantly, in this context, PDE4B is a well characterised susceptibility locus for schizophrenia and bipolar affective disorder3-5.

Squint, Stereo and Schizophrenia

Minor Physical Anomalies scales such as the Waldrop scale have been identified as phenotypic markers to aid in the diagnosis of schizophrenia. Although the original Waldrop scale did not include squint, it has been modified to incorporate squint with more accurate predictive power6.

Squint has also been shown to be an independent risk marker for schizophrenia7,8.

Additionally, binocular depth perception has been shown to be reduced in psychiatric illness9.

PLIKSi

The Psychosis Like Symptoms Interview is an interview assessment of children reporting episodes of hallucinations, feelings of persecution, delusional symptoms and though disorder.

Children who report such symptoms have been shown to be at a higher risk of developing psychiatric illness9.

Questions Raised

Is there any association between squint/stereo and psychiatric illness?

How to Answer this Question

ALSPAC is uniquely placed as it has both phenotypic data on squint, stereo and psychiatric variables as well as genotypic data. As such we propose an investigation into the following

* Assoc squint & stereo phenotypes and schizophrenia phenotypes (PLIKSi)

1 Foundations of Binocular Vision, a clinical perspective, Steinman, 200

2 Williams, C., Northstone, K., Howard, M., Harvey, I., Harrad, R. A., & Sparrow, J. M. (2008). Prevalence and risk factors for common vision problems in children: Data from the ALSPAC study. Br J Ophthalmol, 92(7), 959-64.

3 Fatemi, S. H., King, D. P., Reutiman, T. J., Folsom, T. D., Laurence, J. A., Lee, S., et al. (2008). PDE4B polymorphisms and decreased PDE4B expression are associated with schizophrenia. Schizophr Res, 101(1-3), 36-49.

4 Numata, S., Ueno, S., Iga, J., Song, H., Nakataki, M., Tayoshi, S., et al. (2008). Positive association of the PDE4B (phosphodiesterase 4B) gene with schizophrenia in the japanese population. J Psychiatr Res, 43(1), 7-12.

5 Millar, J. K., Mackie, S., Clapcote, S. J., Murdoch, H., Pickard, B. S., Christie, S., et al. (2007). Disrupted in schizophrenia 1 and phosphodiesterase 4B: Towards an understanding of psychiatric illness. J Physiol, 584(Pt 2), 401-5.

6 Yoshitsugu, K., Yamada, K., Toyota, T., Aoki-Suzuki, M., Minabe, Y., Nakamura, K., et al. (2006). A novel scale including strabismus and 'cuspidal ear' for distinguishing schizophrenia patients from controls using minor physical anomalies. Psychiatry Res, 145(2-3), 249-58.

7 Schiffman, J., Maeda, J. A., Hayashi, K., Michelsen, N., Sorensen, H. J., Ekstrom, M., et al. (2006). Premorbid childhood ocular alignment abnormalities and adult schizophrenia-spectrum disorder. Schizophr Res, 81(2-3), 253-60.

8 Toyota, T., Yoshitsugu, K., Ebihara, M., Yamada, K., Ohba, H., Fukasawa, M., et al. (2004). Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B. Hum Mol Genet, 13(5), 551-61.

9Gunawardana 2010 schizo research - in press.