Schizophrenia Mouse

December 29, 2006

Scientists at John Hopkins have announced the creation of a new researchers admitted that “Rodent models of schizophrenia have significant limitations. The neuronal circuits affected in people are more complex than the analogous circuits in rodents. In particular, the relative size of the prefrontal cortex that is involved in the cognitive deficits is much smaller in rodents than in primates. Some of the cognitive symptoms such as hallucinations or delusions are impossible to address.”

Personally, I can’t get too excited because (as you may already know) I am a big believer in the developmental nature of schizophrenia. But, as always, I wish them luck as I am happy to be proven wrong.



December 22, 2006

The triumph of the reductionism of the Greeks is a pyrrhic victory: We have succeeded in reducing all of ordinary physical behavior to a simple, correct Theory of Everything only to discover that it has revealed exactly nothing about many things of great importance. R.B. Laughlin and D. Pines

As stated earlier, contemporary psychiatry seeks fulfillment of its reductionist and essentialist goals through genetics. However the first era of genetics, the identification of individual (and groups of) genes and their individual roles, is nearly over. Its reign has yielded minimal results for biological psychiatry. On the horizon is Functional Genomics, the study of how genes interact with each other and their environment, over time. Functional genomics not only identifies the biological task of a given gene, but it identifies how and in what conditions it is activated. Furthermore, functional genomics recognizes that genes do different things under different conditions, and consequently understands that genetic destinies are at least co-authored by environment.
Ironically, functional genomics is an intrinsically non-essentialist, non-reductionist science. After decades of reductionism “medical research is entering the era of synthesis” it is time to explore “interactions between subsets of possible genetic and environmental agents as causations in particular contexts indexed by time and space.” Functional genomics is interested in how genes interact over time, in response to cellular conditions. This approach inherently acknowledges exogenous environment and culture, opening the door for acknowledgement of the role of factors such as psychogenic ‘triggers’. Additionally, functional genomics defies the traditional diagnostic framework. Rather than further delineating mental illnesses into distinct diseases with unique molecular mechanisms, functional genomic approaches will blur and even disintegrate distinctions between diseases with related disease processes. Illness will be understood as being on a spectrum of human conditions rather than grouped into distinct categories that must be explained by common origins. Rather than attempting to prioritize contributing factors to make a global model for mental illness, models will necessarily be personalized. Already these shifts in understanding are beginning to permeate our culture: in the last two years, three popular science books have been published highlighting the role of mental illness in creativity, entrepreneurship, and human evolution.
Undermining and eliminating the essentialist and reductionist tendencies of psychiatry will have two effects. First, it will lead to the personalization of medical care. The disintegration of diagnostic classifications will lead to treatment strategies fitted to individual patients rather than to global models of disease. This trend will also allow for reconciliation with anti-psychiatry as the personalization of medical care will grant more user choice: eliminating the urgency of many of anti-psychiatry’s protests against psychopharmaceuticals. The dissolution of broad diagnostic criteria will render obsolete the criticisms about the insolvency of psychiatry’s diagnostic system.
Cardiovascular disease is an example of a somatic illness that has already gone through this transformation. The term cardiovascular disease only has meaning in a personal context. Cardiologist Charles Sing indicates that cardiovascular disease “develops as a consequence of interactions between the ‘initial’ conditions, coded in the genotype, and exposures to environmental agents indexed by time and space.” The causes of cardiovascular disease include diet, exercise levels, daily stress, lipid profiles, high blood pressure, poor heart function and many others. Nobody suggests that any of those is contributing factors are inherently more important than any others; these factors are prioritized only to the degree in which they are present in any given patient. Also, few people would argue that they are free of cardiovascular disease; it is understood as a dynamic health condition that should be managed throughout life. Similarly, I suspect that post-psychiatry will adopt treatments strategies incorporating psychopharmaceutical correction of irregular brain function combined with cognitive therapy aimed at assisting individuals in normal construction of the ‘architecture of their mind.’


The Anti-psychiatry Movement

December 19, 2006

The Contemporary Moment: Psychiatry and its Critics II
Anti-psychiatry is a growing movement, which views modern psychiatry’s commitment to the biomedical model as dogmatic and harmful. The movement has attempted to brand psychiatry as pseudoscience for its perceived unwillingness to objectively consider the evidence against the biomedical model of mental illness. Anti-psychiatry has a bedrock of support in disillusioned psychologists, social workers, and psychiatric survivors who view contemporary psychiatry as “mindless and uncaring,” overly reliant on pharmaceuticals, and hostile to psychotherapy. Critics also claim that contemporary psychiatry is beholden to the pharmaceutical industry. They point to the conflicts of interest that are pervasive in the interactions between psychiatrists, scientific journals, and pharmaceutical industry. In addition to concerns about efficacy, the presence of serious side-effects causes detractors to question the safety and innocuousness of psychopharmaceuticals. Tardive dyskinesia and other extra-pyramidal side effects are significant contributors to the mistrust of psychiatry, and particularly psychopharmaceuticals. Further, the anti-psychiatric movement views psychopharmaceuticals as crude mood suppressors; “chemical lobotomies” that can eliminate outward manifestation of positive symptoms, but do little for negative symptoms or internal disturbances. Anti-psychiatry points to psychiatry’s inability to provide genetic or chemical tests for mental illness as an inability to apply its own paradigm to patients; in short, anti-psychiatry perceives contemporary psychiatry as built upon an unproven biological paradigm.
Dr. Thomas Keen describes the conflict between psychiatry and anti-psychiatry as part of the struggle of Moderninst psychiatry in adapting to an increasingly more post-modern world. He suggests that psychiatry is rooted in “the modernist dark ages of professional authority, clincal certainty” and can not survive in a “post-modern society where central, authoritarian discourses are increasingly collapsing und the challenge of pluralism.” His suggestion is that psychiatry must decentralize; it must acknowledge the criticism of anti-psychiatry and actively include patients or ‘end-users’ in the discursive process of framing pschiatric disorders. This transformation is not unique to pyschiatry, but post-modern assaults on the nature of the mind and consciousness are.
Psychiatrists sense that their discipline is becoming increasingly problematic and unwieldy. That less than 500 new residents join the profession annually demonstrates that the medical profession views the field as stagnant. Yet, for the most part psychiatry clings to essentialism and biological reductionism. It is not uncommon for research papers to end with supplications to future research: “It is hoped that [further] study…will provide new insights into the genetic basis of abnormal behaviour.” Psychiatry remains faithful to the promise that genetics will elucidate the basic molecular and genetic mechanisms behind mental illness disease processes and will provide elegant new targets for pharmacological intervention.

Influenced by

  • Thomas Keen. “Post-psychiatry: paradigm shift or wishful thinking? A speculative review of future possibles for psychiatry,” Journal of Psychiatric and Mental Health Nursing, 2003: 32.
  • Philip Thomas and Patrick Bracken. “Critical psychiatry in Practice,”Advances in PsychiatricTreatment, 2004: 364.

Contemporary Psychiatry

December 17, 2006

The Contemporary Moment: Psychiatry and its Critics Pt 1

Today, psychiatry is once again dominated by the biological perspective. There is full investment in the notion that psychiatric illnesses are biological diseases resulting from irregular brain function with specific genetic etiologies. Psychiatry views itself as a branch of medicine, and consequently ascribes to the modernist impulses of reductionism and essentialism that characterize much of medical science. Psychiatry also aspires to transition from its current symptom-complex based diagnostic system to pathoetiology-driven diagnostic taxonomy. This move would signify a shift from a nominalist understanding of disease towards an essentialist one, which would put it on par with the rest of the medical profession. At the moment it is generally acknowledged that the current classification system is imprecise and has significant overlap between diagnostic categories. A lack of precision in the diagnostic classifications remains problematic, and impedes progress in both psychiatric research and treatment.
The foundation of biological security, however, is far from secure. It is a paradigm that is plagued by vexing discrepancies in its body of evidence. For example, recent studies have called into question the true effectiveness of anti-depressant medication. These studies indicate that most psychopharmacueticals work on less than 50% of the intended patient group. The inconsistent effectiveness of psychopharmacological agents belies a lack of knowledge of the disease process behind most psychiatric illnesses. Further, while it has been rigorously proven that most mental illnesses have important hereditary elements, the search for specific genetic causes has largely proven fruitless. While innumerable genes have been linked to incidence of psychiatric illness, no gene or combination of genes have yet proven to be a controlling factor in any of the major psychiatric illnesses. In fact, only 3 chromosomes do not contain genes that have been linked to schizophrenia. It appears that search for specific genetic causes for mental illnesses are complicated by diagnostic overlap, assortive mating and the polygenic nature of most mental illness. Nevertheless, contemporary psychiatry remains confident in and allegiant to molecular biology.


3 Chromosomes Mapped Epigenetically

August 15, 2006

The Human Epigenome Project Consortium, a public/private collaboration led by Epigenomics AG and the Wellcome Trust Sanger Institute have published comprehensive epigenetic data for chromosomes 6, 20, and 22. The group, founded in 2003, hopes to identify and catalog all Methylation Variable Positions (MVPs) in the human genome.

The group is excited about their progress with the Human Epigenome Project:

“This is the first study report ever establishing the DNA methylation blueprint for whole chromosomes,” said Alexander Olek, CEO of Epigenomics AG, “and we believe the results justify the effort. As an example, we found that between the specimens examined, a surprisingly high proportion of the genomic sites are differentially methylated. So science may have underestimated the role of DNA methylation in gene regulation and tissue differentiation. The data constitute an important reference tool for further epigenetic studies and will help us to identify new marker candidates for a variety of medical conditions.”

The results were patented, and Epigenomics intends to use the data for for development of diagnostic products. The data is expected to be particularly useful for research into cancer, mental health and aging. The next step is to use the MVPs as a reference for epidimilogical studies to find out how they correlate to health and disease states.

This is genuinely good news, but its not going to stop me from grumbling about the patents.


Nucleosome Code

August 5, 2006

Scientists claim to have discovered an epigenetic code. This could be a fundamental discovery in the field. This weeks New York Times Science Section has a very accessible explanation.

Researchers believe they have found a second code in DNA in addition to the genetic code.

The genetic code specifies all the proteins that a cell makes. The second code, superimposed on the first, sets the placement of the nucleosomes, miniature protein spools around which the DNA is looped. The spools both protect and control access to the DNA itself.Jerry Workman of the Stowers Institute in Kansas City said the detection of the nucleosome code was “a profound insight if true,” because it would explain many aspects of how the DNA is controlled.

In the genetic code, sets of three DNA units specify various kinds of amino acid, the units of proteins. A curious feature of the code is that it is redundant, meaning that a given amino acid can be defined by any of several different triplets. Biologists have long speculated that the redundancy may have been designed so as to coexist with some other kind of code, and this, Dr. Segal said, could be the nucleosome code.

This discovery is very early in the scientific process and needs to be verified. If it pans out, it could provide the basis for more powerful epigenetic epidimiology. I’ll keep tabs on this story as the implications become more clear.


False Starts in Psychiatric Genetics

August 2, 2006

You’ve probably seen the headline a dozen times “Researchers at State College University Discover the Gene for Depression”. And yet it seems like no progress has been made towards understanding the genetic basis for psychiatric diseases. How can this be?

Well the fundamental reason for the lack of progress is that psychiatric diseases, like most interesting genetic traits, are the result of complex interactions between a number of genes. Every study that gets talked about in the media is only a small part of a very complex puzzle. It will take many years of broader more detailed studies to start to uncover the patterns in which these genes interact to cause psychiatric disorders.

However the problem goes deeper than that. The entire search for genetic causes of psychiatric diseases is undermined by the vague and arbitrary nature of psychiatric diagnosis. Many people are shocked to find out that there is no ‘test’ for depression, schizophrenia or any other psychiatric disease. There are only generally accepted guidelines (found in DSM-IV – the current edition of the diagnostic and statistical manual). Human inconsistencies in assigning diagnoses make it extremely difficult to do statistical analysis across studies.

Even more problematic than inconsistency in assigning psychiatric diagnoses, is inconsistency in the diagnoses themselves. Psychiatric diseases are a poorly designed, fuzzy set. That means that patients often fit into the definitions of mulitiple diseases. This ambiguity is a consequence of diagnosis using external symptoms. Because every person is different, their disease manifests in different ways, making it very difficult to identify exactly what their pathology is. Ths suggests that the search for genetic causes to psychiatric diseases may never bear fruit.