Disclosure br Psychosis genetics has ploughed an unyielding

Disclosure
Psychosis genetics has ploughed an unyielding furrow. The time for predictions that with sufficient markers the three prototypical conditions (schizophrenia, bipolar or manic-depressive disorder and unipolar depression) will each be found associated with specific chromosomal loci is long past. Linkage strategies failed to give simple or even consistent solutions. Genome Wide Association studies (GWAs) have done better but the answer – that many (108 at a recent count) autosomal genes each of very small effect are involved – is puzzling. Some researchers point to the anatomical correlates (deficits in grey matter in the insula, cingulate and para-hippocampal gyri) that follow relatively simple rules, perhaps reflecting rates of full report growth, in probands and their first degree relatives. It is now apparent that anatomical variation in the same brain regions is a characteristic also of anxiety states, obsessive–compulsive disorder, and even substance abuse (). A major source of genetic variation has yet to be uncovered. In the psychosis spectrum we are dealing with variation in form and incidence that crosses populations. Moreover the spectrum is associated with a biological disadvantage – fecundity is decreased – more in males than in females (). What balancing advantage keeps these gene(s) in the population? One answer is that it is the feature that defines the species — the capacity for language (). Much is unknown about speciation but a part of what we do know is incorporated in Haldane\'s rule – when in a hybrid cross one sex is inviable or infertile – it is the hetero-gametic sex – that holds across phyla. The generally accepted explanation is that the homo-gametic chromosome – in mammals the X – is involved. The neural correlate of the capacity for language is cerebral asymmetry — in all populations most individuals are right-handed, but some are left-handed, and the proportions are genetically influenced. Genes with lateralized expression have been sought and not found (). The solution comes from a different direction as have appreciated – individuals with sex chromosome aneuploidies have deviations in verbal and spatial abilities consistent with relative hemispheric dominance – deficits in spatial ability in Turner\'s (XO) syndrome are opposed to difficulties with words and language delays in Klinefelter\'s (XXY) and XXX syndromes. Such deficits point to a gene in the XY homologous class (), and a number of imaging studies document that the sex chromosome aneuploidies are associated with consistent deviations in the cerebral torque, the bias from right frontal to left occipital that is characteristic of the human brain ().
Convergent evidence from longitudinal population and high-risk studies has supported that psychiatric disorders in adults typically onset in childhood and adolescence which not uncommonly debut as non-specific symptoms and syndromes (i.e. heterotypy) (). Studying multiple indicators of illness risk and development longitudinally within high-risk subjects is increasingly recognized as important in order to differentiate vulnerability from burden of illness effects and to identify patterns of abnormalities associated with the clinical trajectory of illness development. Taken in this context, the paper in this issue of by Lee and colleagues reports on findings of a cross-sectional study of neural correlates and clinical outcomes up to 2years later in 44 offspring of bipolar parents (). High-risk offspring were divided into subgroups comprising well (HR) or symptomatic/ultra-high-risk (UHR) compared to healthy controls (C). Structural and functional neuroimaging and neurocognitive performance (i.e. processing speed and visual spatial) and global functioning differences were found between the groups and interpreted as evidence of differential indicators of BD vulnerability and illness progression.