This short volume, edited by the Editor-in-Chief of the renown American
Journal of Psychiatry, brings together for the first time in book form to my
knowledge current strides in the research towards the Holy Grail of human
genetics; finding the genetic markers of mental illness. A recent article in
Science News highlighted that scientists are making great inroads into finding
such markers (e.g. the International HapMap Project, incidentally referred to
in Research Advances in Genetics and Genomics, while the completed map
is published in the Oct. 27 Nature, and all data from the project are
publicly available online at: http://www.hapmap.org/). The Science News article stated that:

"A new map that delineates small genetic differences among people
may be a powerful tool for figuring out why some individuals get certain
diseases and how to customize their treatments." http://www.sciencenews.org/articles/20051029/fob5.asp

It was lucky for me that this article appeared just as I was finishing
Andreasen’s edited book because the book for the most part is extremely complex
and not for the faint-hearted. I fear that many psychiatrists, psychologists
and clinicians working with patients who have mental illnesses won’t make it
past chapter 2. I persisted because I find the whole subject fascinating. I’m
glad I did because chapter 3 was both well-written and a revelation (in my
opinion it should have been the first chapter after chapter one.)

The Science News article simplified the whole field for me and helped me
understand the overall thrust of this book. There are seven chapters in Research
Advances in Genetics and Genomics, along with a foreword, introduction and
an afterword, written by a number of experts in the field. This isn’t the book
for novices in this field — I recommend you start somewhere else first. There
are valuable insights however. For example, the editor stated in her
introduction that the book has been written to:

"commemorate and honor the "double helix discovery" and
to prepare psychiatrists for the "genomic era" that will unfold
during the 21^st century" (p.xiii)

and goes on to say
(pxiv):

"It will take time and a great deal of work…to
learn…about the movement from molecules to minds– how our genes contribute to
who and what each of us is, and how and why some of us move from the normal
continuum into a state of pathology."

It achieves its first
aim, in that it lauds Watson and Crick to the extent of reprinting their
original paper (an aside — it was
lovely to read this for the first time!), while not convincing me on the second
— preparing psychiatrists for the genomic era. I think that another book might
achieve that, this one for the most part just blinds us with molecular biology
and complex terminology.

Chapter 2 was particularly difficult to follow (convoluted, very dry
writing), while both chapter 3 and chapter 6 I found well-written as well as
fascinating. This book is basically made up of a handful of research papers and
as such there is always going to be overlap and lack of cohesion. The
introduction and afterword also didn’t manage to pull the whole story together
for me.

A few key points came through however:

a.)    The need for replication in a number of
independent research centers before results should be taken for fact.

b.)    The difficulty of using the classification
systems currently available to map on to genotypes or phenotypes — there is no
consensus either in the diagnostic markers for mental illness nor in the
methodology the different laboratories use.

c.)    The importance of taking that old bug-bear
‘environmental factors’ into account when searching for genetic markers. Social
relationships, populations (including cultural differences) and effects of
medication also need to be taken into account.

d.)    The difference between genetics and genomics as
defined by Insel and Collins in chapter 3:

"Genetics is the study of human genes and their
effects. Genomics is the more ambitious study of all the genes in the genome,
including their function, their interaction, and their role in a variety of
disorders that are not due to single genes" (p.28)

e.)    The fact that mental illnesses are on the whole
polygenetic — even relatively straightforward mental illnesses have more than
one gene implicated — autism may have more than 10.

f.)      Even if we do find markers they still don’t
tell us everything because scientists don’t know where in the sequence they are
tapping (they could be further down the chain than they realize). It therefore
remains difficult to find the ‘source’ gene.

g.)    When specific genetic markers are found these
will have undoubtedly wide-spread implications for psychiatric practice.

h.)    Above all, that this is a complex field.

Investigating the
effects of mutations has been a fruitful line of research and animal models can
tell us a great deal about how the human brain might function. As Laurence H.
Tecott stated in the wonderful chapter entitled: The Genes and Brains of Mice and Men:

"genes cannot be systematically manipulated in
humans, so we must therefore turn to other organisms to investigate gene
function" (p.85) and "approximately 99% of mouse genes have human
counterparts." (p.86)

This author also
showed the only sense of humor I could spot in the entire book (genetic
research is clearly a serious
subject) when he stated:

"Mice are notoriously noncompliant with
questionnaires and interviews" (p.98)

This book would have benefited from much more of this human touch. More
emphasis was given to the techniques that are currently being used to unravel the
complexities apparent in this field of research.

As is clear from this review, I am not a geneticist but a
neuropychologist who is fully aware that genes will play a large part in
unraveling the individual differences we clinicians see in presenting patients
on a daily basis. The genome approach puts the emphasis back on the patient to
my view, where it belongs, while at the same time ethical considerations must
be kept at the forefront and sensitivity to damaged individuals and their
carers will only become even more important than it already is. Research
Advances in Genetics and Genomics somehow manages to lose the person in
among the technology and researchers in this field would, in my opinion, do
well to remember that these are human
problems we are ultimately trying to treat. The book didn’t address the
possibility of making designer babies
and the whole ethics question.

Many readers will be put off by the complexity and at times convoluted
writing in Research Advances in Genetics and Genomics and by the fact
that it is essentially a bunch of research papers stuck piecemeal together to
form a book. I fear that it may only
really appeal to students and researchers already working in this field, a pity
because this is the future, whether
we like it or not.

 

© 2005 Ruth Mark

 

Ruth E. Nieuwenhuis-Mark, Ph.D., is lecturer of neuropsychology at the
University of Tilburg in the Netherlands. She specializes in Alzheimer’s
disease, stroke, epilepsy and other neurological disorders. Her personal
website can be viewed at: www.remark.be

Categories: Genetics, MentalHealth, Psychology