June 12, 2006

Neurodevelopment and Schizophrenia

There is a book that come out a few years back, published by Cambridge Press in 2004 - that is titled, appropriately "Neurodevelopment and schizophrenia".

As it happens - the famous Dr. Frederick Freese (a board member of NAMI and person who has recovered from schizophrenia to become a noted psychologist and professor) has recently reviewed this book - and while its written for psychologists and advanced students of psychiatry - both the review and the book has valuable information.

Dr. Freese notes, in his review:

"Some of the book's 24 chapters are particularly relevant for consumers and practicing clinicians. In Chapter 9, Sahebarao P. Mahadik covers recent findings concerning schizophrenia and nutrition. He makes very compelling arguments for including omega-3 essential polyunsaturated fatty acids and antioxidants, such as vitamins E and C, in the dietary intake of virtually all persons with schizophrenia.

In Chapter 14, Chih-Ken Chen and Robin Murray reveal new, eye-opening evidence about how serious the consequences can be for people prone to schizophrenia who abuse such drugs as cannabis and amphetamines.

The book's final three chapters focus on the clinical implications of recent research findings.

Some chapters appear to be less immediately relevant for clinicians, and as Michael Rutter suggests in the well-written foreword, there are sections that are "not light bedtime reading."

Read the full book review here: Neurodevelopment and Schizophrenia.

You can purchase the book at amazon.com - here: Neurodevelopment and Schizophrenia

As it happens, we have a copy of the book in our library - and so have included a short excerpt of the Foreward of the book to provide a better overview of what is covered.

Although both Kraepelin and Bleuler noted that premorbid abnormalities in child-hood could be present many years before a schizophrenic psychosis developed (Marenco and Weinberger, 2000), until the late 1980s and 1990s, most people viewed schizophrenia as an adult-onset mental illness. As a result, most biological studies focused on a search for possible neurodegenerative changes that might account for the onset of the condition. During the 1960s and 1970s (see Garmezy, 1974; Offord and Cross, 1969), evidence began to accumulate from developmentally oriented follow-up and follow-back studies that abnormalities in interpersonal relationships, neurodevelopmental immaturities, and attentional deficits in child-hood all predicted the later onset of schizophrenia (see Rutter and Garmezy, 1983). However, it was not until 1987 (Murray and Lewis, 1987; Weinberger, 1987) that psychiatrists concerned with adult patients firmly took on board the notion that schizophrenia might be a neurodevelopmental disorder. Since then, there has been a veritable explosion of research tackling this proposition using a variety of research strategies. In parallel, there has been an upsurge in studies of brain development and function, giving rise to a much evident that there are important neural changes that extend into late adolescence and early adult life.

It remains the case that we have much to learn still about how these changes relate to both normal and abnormal development, but they provide a possible basis for the transition from the premorbid features of childhood to the overt psychosis seen in adult life. This transition is also discussed with respect to the evidence that there may be new abnormal brain changes that occur at this time.

The velo-cardio-facial syndrome is put forward as a possible model for the inter-play between genes, brain, behavior, and cognition, and it is also suggested that structural magnetic resonance imaging could provide a useful endophenotype for genetic studies. This reflects the growing awareness that susceptibility genes probably do not act directly on mental disorders and that, therefore, it may be useful to examine genetic effects on neurobiological abnormalities representing more proximal effects of genes.

The neurodevelopmental hypothesis has been accompanied by indications of the possible contributory causal role of epigenetic factors, malnutrition, pre- and perinatal risk factors (including infection), minor physical anomalies, and adverse rearing environment. The evidence on all of these is succinctly reviewed, with the conclusion that the risk effects are probably real even though their effect size is small.

Initially, with the advent of persuasive findings in genetics and in biological psychiatry more generally, it became unfashionable to consider either social risk factors or the effects of drug abuse: both of which had constituted a major focus of interest in the 1960s and 1970s. However, animal studies and migration studies of humans have shown that there is now reasonable evidence that social factors are influential, even though we do not understand how they operate. What is quite different from the 1960s and 1970s is the appreciation that it is necessary to understand how social factors may impact on brain development and that there may well be a synergistic interplay between environmental risk and genetic vulnerability, with the risks largely dependent on the presence of genetic susceptibility. Much the same message derives from the study of recreational drugs, with the specific suggestion that the drug effects associated with heavy early usage affect neurotransmitters in ways that may precipitate the onset of psychosis when combined with genetic susceptibility.

Further chapters provide a more detailed consideration of the possible role of the dopamine system, of mis-wired limbic lobe or thalamocortical circuitry, of estrogen and X-chromosome effects on brain development, of premorbid structural brain abnormalities, and of neurodegenerative models.

From a clinical perspective, it is crucial to know whether the neurodevelopmental features are specific to schizophrenia or apply to a broader range of psychiatric conditions. In frustrating fashion, the evidence suggests both substantial commonalities and important specificities. A key chapter considers whether the extensive evidence of premorbid abnormalities means that it should now be possible to identify children who are likely to develop schizophrenia. It is concluded that this is not yet possible, yet combining risk factors from different functional domains can usefully enhance the accuracy of predictive models. The final chapter discusses how it may be possible for the pathophysiology to be explained by an integrative neurochemical model and how there is now the beginning of a basis for possible preventive interventions.

The book provides a rich intellectual meal of great interest and importance. Nevertheless, we have to ask where all these creative ideas and empirical findings get us. The book has two main achievements. First, it provides an excellent compilation of what is known about the neurodevelopmental origins of schizophrenia, what the findings explain, and what research challenges remain (together with invaluable suggestions on how these challenges might be met). The evidence is compelling that, in crucial ways, schizophrenia is a neurodevelopmental disorder and that research using this concept has been immensely productive.

There is the promise of a better understanding of how neurodevelopmental features relate to genetic risk, but that understanding has not yet been achieved. Similarly, although the onset in late adolescence/adult life, long after premorbid manifestations have been evident in childhood, is no longer quite the mystery that it was, the causal pathways have still to be delineated. Nevertheless, the book clearly documents that neurodevelopmental approaches are now mainstream in the study of schizophrenia and that much has been learned in the last decade or so.

The second achievement is that the consideration of neurodevelopmental origins of schizophrenia has thrown invaluable light on the broader issues involved in normal and abnormal brain development. This gives the book an interest that extends well beyond the world of schizophrenia clinicians and researchers. It is not light bedtime reading, but the book does provide an engrossing read that is richly rewarding.

Michael Rutter

The table of contents of the book is as follows:

Each chapter is essentially a short review article that covers the results of a number of studies in a given area. Its excellent information - but enrollment in a medical school is probably a prerequisite for successful understanding of the entire book.

1. Genes and brain development - Timothy A. Klempan, Pierandrea Muglia and James L. Kennedy;

2. Brain development in healthy children and adolescents: magnetic resonance imaging studies - Jay N. Giedd, Michael A. Rosenthal, A. Blythe Rose, Jonathan D. Blumenthal, Elizabeth Molloy, Richard R. Dopp, Liv S. Clasen, Daniel J. Fridberg and Nitin Gogtay;

3. Cognitive development: fMRI studies - Beatriz Luna and John Sweeney;

4. Cognitive development in adolescence: cerebral underpinnings, neural trajectories and the impact of aberrations - Stephen J. Wood, Cinzia R. DeLuca, Vicki Anderson and Christos Pantelis;

5. Brain plasticity and long-term function after early cerebral insult: the example of very preterm birth - Matthew Allin, Chiara Nosarti, Larry Rifkin and Robin M. Murray;

6. Do degenerative changes operate across diagnostic boundaries? The case for glucocorticoids involvement in major psychiatric disorders - Carmine M. Pariante and David Cotter;

7. Velo-cardio-facial syndrome (deletion 22q11.2): a homogeneous neurodevelopmental model for schizophrenia - Stephan Eliez and Carl Feinstein;

8. Can structural MRI provide an alternative phenotype for genetic studies of schizophrenia? - Colm McDonald and Robin M. Murray;

9. Nutritional factors and schizophrenia - Sahebarao P. Mahadik;

10. Schizophrenia, neurodevelopment, and epigenetics - Arturas Petronis;

11. Early environmental risk factors for schizophrenia - Mary Cannon, Kimberlie Dean and Peter B. Jones;

12. Transcriptomes in schizophrenia: assessing altered gene expression with microarrays - David A. Lewis, Karoly Mirnics and Pat Levitt;

13. Is there a role for social factors in a comprehensive development model for schizophrenia? - Jane Boydell, Jim Van Os and Robin M. Murray;

14. How does drug abuse interact with familial and developmental factors in the aetiology of schizophrenia? - Chih-Ken Chen and Robin M. Murray;

15. Developmental dysregulation of the dopamine system and the pathophysiology of schizophrenia - Anthony A. Grace;

16. The development of ‘mis-wired’ limbic lobe circuitry in schizophrenia and bipolar disorder - Francine M. Benes;

17. Development of thalamocortical circuitry and the pathophysiology of schizophrenia - Darlene S. Melchitzky and David A. Lewis;

18. X chromosome, estrogen, and brain development, implications for schizophrenia - Michael Craig, William Cutter, Ray Norbury and Declan Murphy;

19. Premorbid structural abnormalities in schizophrenia - Stephen M. Lawrie;

20. Neurodegenerative models of schizophrenia - L. Fredrik Jarskog, John H. Gilmore and Jeffrey A. Lieberman;

21. Does disordered brain development cut across diagnostic boundaries? - Christian W. Kreipke, David R. Rosenberg and Matcheri S. Keshavan;

22. Can one identify preschizophrenic children? - Eugenia Kravariti, Paola Dazzan, Paul Fearon and Robin M. Murray;

23. High risk studies, brain development and schizophrenia - Matcheri S. Keshavan;

24. Developmental models and hypotheses-driven early interventions in schizophrenia - Matcheri S. Keshavan and Barbara A. Cornblatt.


it's also relatively easy to suggest that immigration effect is due to people from moving from a country with less access for them to health care, to a country with more health care access, where people are diagnosed more often. studies of diagnosis patterns that infer causality or 'social influences' always need to take into consideration how different health care delivery systems might affect their numbers.

Posted by: slc2 at June 13, 2006 10:08 AM

Seems like a great book.

Posted by: CopperKettle at June 16, 2006 06:15 AM

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