Download Changing Ideas of Normality and Abnormality Danish

Changing Ideas of Normality and
Abnormality
Danish Pedagogical University
26th October 2006
Nikolas Rose
Department of Sociology
BIOS Centre for the Study of Bioscience, Biomedicine,
Biotechnology and Society
London School of Economics and Political Science
[email protected]
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 FeebleMindedness
Henry Herbert Goddard (1913)
Director of the Research Laboratory of
the Training School
at Vineland, New Jersey, for Feebleminded 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 2000
Modern 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.ht
ml
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.
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
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.
NIH joined by advocacy groups to fund research on autism
susceptibility genes
Five 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-2005
http://www.eurekalert.org/pub_releases/2005-10/niom-njb101905.php
http://psychiatry.uchicago.edu/grounds/010910/slides/
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)
Protein Interaction Network
in HD
Genome
Transcriptome
Proteome
Metabolism
Organ’ome’ (the Brain)
Thought Landscape
It is estimated that the human brain contains 100 billion
(1011) neurons averaging 10,000 synapses on each;
that is, some 1015 connections.
Neuronal Network
•
Organism’ome’
Environment’ome’
Experience’ome’
Meaning’ome’
Culture’ome’
Emergent on-line
community
Each has its own regularities, temporalities, emergent properties
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)
Anxiety Disorders
2.7
0.8
8.7
6.8
3.1
3.5
1.0
0.9
18.1
Mood disorders
Major depressive disorder
6.7
Dysthymia
1.5
Bipolar I and II disorders
2.5
Any mood disorder
9.5
Impulse control disorders
Oppositional defiant disorder
1.0
Conduct disorder
1.0
Attention deficit/hyperactivity disorder
4.1
Intermittent explosive disorder
2.5
Any impulse control disorder
8.9
Substance Disorders
Substance Disorder (Any)
3.8
Any Disorder
Any
26.2
1 Disorder
14.4
2 disorders
5.8
3 or more disorders
6.0
Panic Disorder
Agoraphobia without panic
Specific phobia
Social phobia
Generalized anxiety disorder
Posttraumatic stress disorder
Obsessive compulsive disorder
Separation anxiety disorder
Any anxiety disorder
Lifetime Prevalence
(percent)
4.7
1.4
12.5
12.1
5.7
6.8
1.6
5.2
28.8
16.6
2.5
3.9
20.8
8.5
9.5
8.1
5.2
24.8
14.6
46.4
27.7
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 2
Estimated 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
27.4
82.7
Any mental disorder
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. 357376. 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 !