The imprinted brain theory had two distinct origins, both in the late 1990s. First, I developed the idea that Freud’s id and ego might be the psychological agents of paternally- and maternally-active imprinted genes respectively, plus X chromosome genes on the mother’s side. Imprinted genes are those which are expressed from one parent only. The classic example is IGF2: a growth-factor gene expressed from the father’s copy, but silent when inherited from the mother. X chromosome genes resemble maternally-active ones to the extent that all mothers are female, and because female mammals have two Xs to the male’s one, such genes are subject to female-benefiting natural selection twice as often as they are to male-benefiting evolution.

The second origin was in my observation that the symptoms of autism could be seen as diametrically opposite to those of paranoid schizophrenia. For a while, both these ideas floated around in my mind independently, but before long I became disillusioned with Freudian psychology (which resembled paranoia too closely for comfort). Then the two ideas coalesced. It occurred to me that autism might be related to enhanced paternal gene expression and/or reduced maternal and X chromosome gene expression, and that paranoia might be the contrary: caused by enhanced maternal and X chromosome gene and/or reduced paternal gene activity. The imprinted brain theory was born with the new century and was soon taken up by Bernard Crespi, Killam Research Fellow in the Department of Biosciences at Simon Fraser University in Vancouver, with whom I published a number of scientific papers outlining the new theory, notably in Behavioral and Brain Sciences in 2008.

Now Crespi, writing with Philip Stead and Michael Elliot in Proceedings of the National Academy of Sciences, has opened up a novel line of enquiry that gives our distinctive, diametric model of mental illness a remarkable and unexpected confirmation. The subject of his study is copy number variation (CNV): the recently-discovered and very surprising finding that individuals vary in the number of copies of particular genes they carry by up to 12% of the total. CNV can result from duplication or deletion of genes, and to this extent resembles imprinted-gene expression, which can produce double expression of normally singly-expressed genes (for example in Beckwith-Wiedemann syndrome, where both parents’ copies of IGF2 are expressed) or no expression at all (as in Silver-Russell syndrome, where neither copy of IGF2 is active). The result is diametrically different outcomes: overgrowth in the former syndrome and growth-retardation in the latter.

Crespi, Stead, and Elliot used CNV, single-gene associations, growth-signalling pathways, and brain-growth outcomes to evaluate 4 models of mental illness (see diagram): (a) Subsumed; (b) Separate; (c) Diametric, and (d) Overlapping. They found that CNV findings support the diametric model, which holds that autism and schizophrenia stand in opposition to one another: at 4 places in the genome deletions pre-dispose to one, while duplications pre-dispose to the other. They also found that single-gene associations are inconsistent with (b), the separate model, because schizophrenia and autism frequently share associated genes. Where brain-growth was concerned, they found that autism goes with enhanced brain growth, whereas schizophrenia is characterized by reduced brain size-just as the diametric model predicts. Indeed, Shinawi et al. report independently in the Journal of Medical Genetics that autism and macrocephaly observed with deletion and microcephaly seen in duplication of a site on chromosome 16 support the diametric model.

What is truly remarkable about these studies is that CNV was unknown to me when I first conceived the diametric model, and did not figure in my original formulation of the theory, which was confined to imprinted and X chromosome genes. The fact that such bottom-up, genome-based analyses of a previously unknown and very surprising genetic mechanism can be shown to endorse my original top-down, symptom-based approach suggests that the new diametric model of mental illness stands on foundations which reach right down to the roots of the genome. I realized a long time ago that the only real proof of the Freudian model of the mind would lie in DNA, but I never expected that such remarkable confirmation of my alternative, diametric model would emerge so soon and in relation to such an unforeseen finding as this!

DNAWellnessinfo.com Resource:  http://www.psychologytoday.com/blog/the-imprinted-brain/200912/copy-dna-underwrites-the-diametric-model-mental-illness