Lifting Lidz

Written by Dr Peter J. Gordon, 25^th February 2011

Response to the Re-appraisal: Neurodevelopmental hypothesis of schizophrenia, British Journal of Psychiatry, March 2011. http://bjp.rcpsych.org/content/198/3/173.full 

In this reappraisal, the authors contend that ‘only now can the Neurodevelopmental hypothesis of schizophrenia, be fully appreciated.’[1] Twenty five years of valued research have indeed passed since Weinberger, Lewis and Murray offered their theory, which in scientific stepping stones, has served primarily to confirm the complexity of aetiological understanding.

I agree that evidence is accumulating, albeit indirectly, for the Neurodevelopmental hypothesis, and I find intuitive the logic of the ‘two hit’ model of Keshavan.[2] In this reappraisal, I agree with the authors on three points: that schizophrenia is not a discrete disorder, that there is likely some overlap with autism[3], and that in the same 25 years there has been a complete dearth of maturational studies.

However, the authors, in their determination to expose that there is spectrum allelic risk across a range of psychiatric syndromes, have not actually presented what I would term reappraisal. In particular, environmental factors, such as season of birth effect[4] and obstetric complications[5] are not mentioned. It is more surprising, even allowing for the restrictions of a short article, that this Reappraisal makes no reference of the potential modifying effects of environmental stresses (or otherwise) upon variable allelic expression. Ironically, Paul Gilbert in his e-interview in this month’s ‘The Psychiatrist’ gave social neuroscience as the most promising field of research.[6] He mentioned what Owen et al should have; that some genes can be turned on and off by the social environment, especially when young.

As I work as an old age psychiatrist, I encounter the horrid and far too common clinical presentation of Alzheimer’s disease and so my determination is to keep abreast of many paths of research in neurodegeneration. This sits as some sort of backdrop to my own re-appraisal of the neurodevelopmental hypothesis of schizophrenia. However, unlike the authors, I am more cautious in suggesting anything like ‘full appreciation.’ Research in the cyto-architecture of Alzheimer’s disease is presently resulting in more questions than answers: for example – does tau or amyloid pathology come first, or does caspase activation come before that?[7] It is now even being questioned whether the plaque ‘pathology’ which has been macroscopically visible since the days of Dr Batty-Tuke[8], might be evidence of the ‘healing’ response. Researchers are also beginning to explore the effect of stress upon neural architecture, but thankfully realise that we cannot conclude pathogenesis with certainty until we understand normal maturation (plasticity, pruning, neurogenesis and neural death.)

In Owen et als Reappraisal, where the word environment was mentioned only three times, I was left musing over the ‘proportionality principle[9].’  Beyond Eugen Bleuler, others have associated autism and schizophrenia, and here I would dare suggest Theodore Lidz. This thoughtful, but outmoded doctor, along with his wife, studied most closely the families of sufferers of schizophrenia, and offered conclusions that are not today considered palatable. Yet, perhaps in today’s neurodevelopmental light, the most ‘distant’ fathers of his ‘marital skew’ might be classified autistic? Theodore Lidz, as he revealed approaching death, felt diminished by his lack of courageous opposition to ‘biologism.’ I am brought back here to the proportionality principle: Lidz was as mistaken in his dismissal of biology as the authors of this re-appraisal seem to me of environment. I am reluctant to take any single approach too far, and prefer to weave our biological brain into the narrative of life, and so it is that I conclude contemplating whether perhaps we should keep lifting Lidz rather than closing them?

The older I get, combined with tireless graft, reading and thought, I offer one certainty: psychiatry remains culturally-bound.

As a scientist first I follow the wisdom (as best we have today) of Ray Tallis. In his latest book ‘Aping Mankind’, Tallis reveals the predominant scientific approach: what he refers to as ‘biologism’.