In the past, people thought about mental illness in terms of what you might call the injury model: being mentally ill was like being injured by a fall, infected by a disease, or eaten up by a cancer—it was damage that took away normal functions. Indeed, senile dementia seemed to underline the point: Like other bodily functions, mental ones could just deteriorate with age.
The diametric view of mental illness, on the other hand, presents a very different—and much more humane—model. According to this way of looking at things, mental illness is not so much an injury as a disturbance in a delicate equilibrium: a bit like walking a tight-rope—fine if you retain your balance, but disastrous if you fall off.
And another big plus of the diametric model is that it relates to the experience of all of us, and not just the mentally ill. Everyone experiences periods of stress or conflict that can threaten their mental equilibrium quite seriously, and induce temporary, sub-clinical symptoms comparable to those of more severe disturbances: withdrawal, depression, anxiety, ambivalence, confusion, compulsions, obsessive thinking, etc.
But just as you can fall off a tight-rope to one side or the other, so the diametric model proposes that mental imbalances can either be in the direction of psychotic spectrum disorders (PSDs), such as schizophrenia, or autistic ones (ASDs) like Asperger’s syndrome. And quite unlike the injury model of mental illness, the diametric model suggests an astonishing possibility. This is that, just as a tight-rope walker could be saved from falling off one side by a push in the opposite direction, so psychotics might benefit from a dose of autism, and autistics a compensating dose of psychosis.
As I have pointed out in those previous posts, there is now good evidence that this compensating mechanism is a reality. But now striking new confirmation comes from the largest study so far of copy number variation (CNV) in schizophrenia (brought to my attention by my colleague and co-author of the imprinted brain theory, Bernard Crespi). As I pointed out in an earlier post, CNVs resembles genomic imprinting in increasing or decreasing the effect of particular genes by way of duplicating or deleting them. According to our theory, maternal and female genes push neurodevelopment towards PSD, and paternal and male genes push it towards ASD.
Crespi, Summers, and Dorus (2009) noted that Williams syndrome cases (top left) with deletions on chromosome 7 have visuo-spatial deficits but are hyper-social and highly verbal to the point of being described as possessing “cocktail party” skills, and also show heightened levels of anxiety and phobias. By contrast, duplication of the same region is associated with spared visuo-spatial skills but severe language impairment, ASD, and seizures (which are commonly associated with ASD). Similarly, Smith-Magenis syndrome (center left), which features deletions on chromosome 17, shows evidence of good verbal skills, high sociability, and a tendency to PSD; while duplication of the same region in Potocki-Lupski syndrome is associated with high risk of ASD and seizures (bottom left).
The single highest known risk factor for PSD is a variant of Prader-Willi syndrome in which, rather than inheriting a copy of chromosome 15 from each parent as happens normally, a child inherits both copies from the mother. This doubles the expression of maternal genes in a critical imprinted region on that chromosome, and the Cambridge Prader-Willi project—the largest such in the world—reports that every single one of such cases it recorded who reaches adulthood was diagnosed with a PSD, just as our theory predicts (Boer, H., et al. Lancet 359: 135-136).
Crespi, Summers and Dorus also note that Velocardiofacial syndrome with deletions on chromosome 22 carries the second highest known risk of PSD after maternal disomy Prader-Willi syndrome (left). They also note that duplication of the same region has been linked with ASD. The authors of the new study concur with the latter observation and add that the new study “provides a clear, opposite-direction dissociation between schizophrenia risk and both ID [intellectual disability] and autism spectrum disorder.” They note that the fact “that schizophrenia risk can potentially be reduced by a lesion that increases neurodevelopmental adversity (indexed by autism spectrum disorder and ID risk), suggests that the dosage-sensitive gene or genes might not just point the way to treatment, it may also hold clues to enhancing resilience among those who would generally be thought to be of elevated risk of the disorder.”
Mental illness, in other words, does not fit the crude injury stereotype. On the contrary, these remarkable and counter-intuitive findings suggest that both PSD and ASD instead fit the diametric model: with tendencies to one being protective of risk to the other, and vice versa. Furthermore, the fact that such a diametric effect can be demonstrated at the most fundamental genetic level as well as at the highest level of elaborated symptoms is a powerful argument for its truth—not to mention its beauty!
(With thanks and acknowledgment to Bernard Crespi who posts his own comment on this finding here.)