Changing Ideas of Normality and Abnormality

Danish Pedagogical University 26th October 2006

Nikolas RoseDepartment of Sociology

BIOS Centre for the Study of Bioscience, Biomedicine, Biotechnology and Society

London School of Economics and Political Sciencen.rose@lse.ac.uk

October 2006

From ‘governing the soul’ to ‘governing the brain’?’

• Emergence of the psy sciences across C20 linked to New ways of understanding human conduct (self and others)

New ways of governing human conduct (from family to prison)

New experts to know and govern human conduct

• Are the new brain sciences - neuroscience and genomics – and neurotechnologies – psychopharmaceuticals … - reshaping the ways we govern ourselves? the kinds of humans we take ourselves to be

the kinds of things that we, and others, can do to our selves

• Blurring normality and abnormality? susceptibility, prevention and precaution

States (disease) and traits (personality) in a single field of explanation

Disorders without borders

Michael Rutter’s ‘third way’• Rutter: Genes and Behavior:

Nature Nurture Interplay Explained, Nov. 05

• Agrees with many criticisms of earlier behavioural genetics Faults in twin and adoptee studies Focus on inappropriate indices (e.g. IQ) claims of enthusiasts overstated

• Believes mental disorders arise from combinations of genes of small effect contingent on environmental circumstances

• Pathways unspecific, probabilistic, indistinct.• BUT believes there ARE genetic influences on

behaviour• Hence need for complexity and pluralistic explanatory

models.• Beyond genetic determinism?

From determinism …

• Genetics in C20: Determinism and fatalism Fixed hierarchies of human quality Exclusion/elimination of the unfit or the less

fit• Genomics from 1970s - Gilbert’s ‘vision of the

grail’ The digital instructions for making a human

being 100,000 – 300,00 ‘genes’ Search for ‘gene for’ each diagnostic

category• Genomics from 2002 - too few genes to be

human 20-25,000 coding sequences End of the century of ‘the gene’ and ‘genes

for’… Biology – not destinies but possibilities

The Kallikak Family:A Study in the Heredity of Feeble-

MindednessHenry Herbert Goddard (1913)

Director of the Research Laboratory of the Training School

at Vineland, New Jersey, for Feeble-minded Girls and Boys

http://psychclassics.yorku.ca/Goddard/

…to susceptibility• Human differences

shift from ‘the gene for’ to Single Nucleotide Polymorphisms

3 billion bases (C’s, A’s, G’s, T’s) in the human genome

Any two randomly chosen individuals differ by 0.1%

0.1% = some 15 million SNP difference

• Search for SNPs For disease susceptibility For variations in capacities and traits within ‘normal’ range For responses to medicine

• Intertwined with search for tests to ‘diagnose’ and drugs to target SNPs

May 2000Modern Drug Discovery, 2000, 3(5) 40–42.© 2000 American Chemical Society.

http://biotech.about.com/gi/dynamic/offsite.htm?site=http%3A%2F%2Fpubs.acs.org%2Fhotartcl%2Fmdd%2F00%2Fmay%2Frazvi.html

Susceptibility as uncertainty

• Finding susceptibilities at the level of SNPs does not generate determinism - alters probabilities

• Indeterminacy between DNA and function, increased by evidence of ‘non-coding RNA genes and the modern RNA world’ (c.f. Eddy) differential effects of early environment on gene expression.

(Caspi) effects of experience and ‘culture’ on neural regeneration and

neural connections- brain plasticity (Turner) ‘epigenetics’: changes in cells during development, especially in

gene regulation, that can be transmitted from one generation (of cells or organisms) to the next while not being encoded in the sequence of DNA bases in the genome.

• Hence post genomics is age of genomic indeterminacy - uncertainty

Trying to think psychiatric genomics beyond genetic determinism (1) Irving Gottesman and Todd Gould, The endophenotype concept in psychiatry, American Journal of Psychiatry, 2003, 160: 636-645

• “models of complex genetic disorders predict a ballet choreographed interactively over time among genotype, environment, and epigenetic factors, which gives rise to a particular phenotype” (636)

• “individual cells in the brain are quite different from each other in their transcriptomes, proteomes, and morphological phenotypes, and also in the thousands of connections with other neurons and glia” (637)

• “cellular memories regulated by protein modification, morphometric changes, and epigenetic influences make the brain unique among organs. Furthermore, the brain is subject to complex interactions, not just among genes, proteins, cells and circuits of cells, but also between individuals and their changing experiences” (637)

• BUT still search for certainty in the form of endophenotypes And to preserve previous explanatory structure of psychiatric genetics

Trying to think psychiatric genomics beyond genetic determinism (2) Susceptibility as a ‘style of thought’Prathikanti S, Weinberger DR, Psychiatric genetics - the new era: genetic research and some clinical implications , British Medical Bulletin (2005) 73-74: 107-122

“Impressive advances in the last decade have been made in the genetics and neuroscience of neuropsychiatric illness. Synergies between complex genetics, elaboration of intermediate phenotypes … are revealing the effects of positively associated disease alleles on aspects of neurological function. Genes such as NRG-1, DISC1, RGS4, COMT, PRODH, DTNBP1, G72, DAAO, GRM3 … and others have been implicated in schizophrenia .... As the genetics and complex neurocircuits of these disorders are being untangled, parallel applications in pharmacogenomics and gene-based drug metabolism are shaping a drive for personalized medicine. Genetic research and pharmacogenomics suggest that the subcategorization of individuals based on various sets of susceptibility alleles will make the treatment of neuropsychiatric and other illnesses more predictable and effective.”

Operation of the Schizophrenia Susceptibility Gene, Neuregulin 1, Across Traditional Diagnostic Boundaries to Increase Risk for Bipolar Disorder Elaine K. Green et al, Arch Gen Psychiatry. 2005;62:642-648.

A Susceptibility Gene for Affective Disorders and the Response of the Human Amygdala Ahmad R. Hariri, et al., Arch Gen Psychiatry. 2005;62:146-152.

Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3

A McQuillin et al.,

Molecular Psychiatry (2006) 11, 134–142

http://psychiatry.uchicago.edu/grounds/010910/slides/

NIH joined by advocacy groups to fund research on autism susceptibility genesFive institutes at the National Institutes of Health (NIH) and three private autism organizations have formed a consortium to pursue their common goal of understanding a devastating disorder. This public-private partnership has funded five grants representing three projects to identify genes that may contribute to the development of autism and Autism Spectrum Disorders. The National Institute of Mental Health will administer the $10.8 million awards over the next five years. NIH Press Release:19-Oct-2005http://www.eurekalert.org/pub_releases/2005-10/niom-njb101905.php

BUT (1): Probability ….

• Few genomic susceptibilities have been identified in ways that are currently clinically useful

• Even if they were, predictive power of SNP level susceptibility diagnoses is low:

• Genetic scans allocate individuals to subgroups with higher or lower probabilities of developing disorder or responding to drug

• Consequence is only to raise or lower probability, often only slightly, and even in most ‘powerful’ cases not deterministically e.g. APOE 4 occurs in only ~ 40% of cases of Alzheimer’s,

also in ~15% of controls: neither necessary not sufficient for disorder.

…and complexity(Images from http://www.visualcomplexity.com)

GenomeTranscriptome

ProteomeMetabolism

Organ’ome’ (the Brain)It is estimated that the human brain contains 100 billion

(1011) neurons averaging 10,000 synapses on each; that is, some 1015 connections.

Organism’ome’Environment’ome’Experience’ome’Meaning’ome’ Culture’ome’

• Each has its own regularities, temporalities, emergent properties

Protein Interaction Network in HD

Neuronal NetworkEmergent on-line

community

Thought Landscape

Susceptibility as a form of life

• Testing ‘positive’ for susceptibility → not certainly but uncertainty

• But seems to bring future into present → obligation to calculate about it

• An ethic of precaution and prudence• Not calculating future and acting in the present carries moral load• But genomic information does not tell subjects how to live - how soon,

how severe, how rapid …• This true even in most ‘deterministic’ of conditions (e.g. HD)• A new genetic ethics for managing uncertainty• And individuals do not grasp such data in same way as ‘experts’• Does not limit the role for doctors and counsellors - it expands it• ‘Premonitory’ knowledge produces new ‘pastoral’ relations between

doctors, counsellors, patients and relatives

Consequences of looking for susceptibilities for mental disorders?

• Genomic screening tests for susceptibilities• Early intervention, prevention:

Precautionary principle reigns supreme Probably via use of psycho-pharmaceuticals

• Implications depend on practices within which individuals would ‘chose’, feel obliged to, or be required to take test: Huntington’s: fateful knowledge? Schoolchildren: ADHD, Autism Spectrum Disorder, dyslexia…. Mild cognitive impairment: diagnostic creep Offenders: risk assessments prior to sentence or release

• Disorders without borders? Epidemiology and screening expands potential populations for

psychiatry

12-Month and Lifetime Prevalence of Disorders in 9282 Respondents (US)Source: Kessler, R. C. et al. Arch Gen Psychiatry 2005;62:617-627; Kessler, R. C. et al. Arch Gen Psychiatry 2005;62:593-602.

Disorder 12 Month Prevalence (percent)

Lifetime Prevalence (percent)

Anxiety Disorders Panic Disorder 2.7 4.7 Agoraphobia without panic 0.8 1.4 Specific phobia 8.7 12.5 Social phobia 6.8 12.1 Generalized anxiety disorder 3.1 5.7 Posttraumatic stress disorder 3.5 6.8 Obsessive compulsive disorder 1.0 1.6 Separation anxiety disorder 0.9 5.2 Any anxiety disorder 18.1 28.8

Mood disorders Major depressive disorder 6.7 16.6 Dysthymia 1.5 2.5 Bipolar I and II disorders 2.5 3.9 Any mood disorder 9.5 20.8

Impulse control disorders Oppositional defiant disorder 1.0 8.5 Conduct disorder 1.0 9.5 Attention deficit/ hyperactivity disorder 4.1 8.1 Intermittent explosive disorder 2.5 5.2 Any impulse control disorder 8.9 24.8

Substance Disorders Substance Disorder (Any) 3.8 14.6

Any Disorder Any 26.2 46.4 1 Disorder 14.4 2 disorders 5.8 27.7 3 or more disorders 6.0 17.3

Improving the Mental Health of the Population: Towards a strategy on mental health for the European Union:

EC Health and Consumer Directorate General, Green Paper, 2005

ANNEX 2Estimated number of subjects in the general EU population (age 18-65) affected by mental

disorders with past 12 months 46

Diagnosis (DSM –IV) 12-month estimate (%) 12-month estimate (million)

Alcohol dependence 2.4 7.2

Illicit substance dependence 0.7 2.0

Psychotic disorders 1.2 3.7

Major depression 6.1 18.4

Bipolar disorder 0.8 2.4

Panic disorder 1.8 5.3

Agoraphobia 1.3 4.0

Social phobia 2.2 6.7

Generalized Anxiety Disorder(GAD)

2.0 5.9

Specific phobia 6.1 18.5

Obsessive-compulsive Disorder(OCD)

0.9 2.7

Somatoform disorders 6.3 18.9

Eating disorders 0.4 1.2

Any mental disorder 27.4 82.7

Source:Hans-Ulrich Wittchen, Frank Jacobi (2005). Size and burden of mental disorders in Europe: a critical review and appraisal of 27 studies. European Neuropsychopharmacology, Volume 14, Number 4, pp. 357-376. 12—month values rounded by Commission. Percentage values based on Commission’s own calculations.

Psychiatry beyond treatment and cure

• Re-drawing the boundaries of treatable conditions Depression (and SSRI) Anxiety (GAD, SAD, Panic Disorder) ADHD (and Ritalin and Adderal) Mild Cognitive Impairment Cognitive enhancement (Cephalon’s Provigil)

• Extension of remit of psychiatry beyond disease to everyday troubles (as with psychotherapy in C20)

• Blurs boundaries of treatment, cure, prevention and enhancement.

• What is normal, what is abnormal, who is a candidate for psychiatry….

Biological Citizenship in Psychiatry

• Some suggest recognition of disease status, genetic basis, neurochemical pathways, pharmaceutical treatment will REDUCE stigma (e.g. McGuffin et al, 2001)

• Some ‘neurogenetic citizens’ campaigning around ADHD (CHADD), autism spectrum disorder (CAN) etc., esp. families in US.’

• Others resist very idea, arguing it will increase stigma - implying implacable defect arises from the aggressive marketing campaigns

of drug companies, and their allies in psychiatry (who are hand in glove with them)

• i.e. neuro-citizenship is different from other forms of biological citizenship – realities have yet to be charted

Thank you for your attention !