- Email: [email protected]
Towards a brave new brain
Towards a brave new brain Brave New Brain: Conquering Mental Illness in the Era of the Genome Nancy C Andreasen. Oxford: Oxford University Press, 2001. Pp 352. $29.95. ISBN 0195145097. sychiatry is changing: “20 years ago people impressed one another at parties by discussing cathexis, counterphobic reactions, or libidinal drives. Today they get together informally and sip Evian laced with a lime slice while discussing the amygdala or the frontal lobes.” Nancy Andreasen may go to some unusual parties, but there’s no doubting the intellectual clout she brings to this book about “broken brains and troubled minds”. As editor-in-chief of the American Journal of Psychiatry, and a world-leading biological psychiatrist in her own right, she knows what she’s talking about—and has ambitious things to say. She fiercely argues against the “false dichotomies” that have bedevilled psychiatry in the past: “diseases of the brain” versus “problems in living”, psychotherapy versus psychopharmacology, genes versus environment, and (the oldest split of them all) mind versus body. Three contemporaries—Sigmund Freud, Emil Kraepelin, and Alois Alzheimer—set the terms of this debate
Art Wolfe
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at the beginning of the 20th century. Freud described and treated what we would now judge as anxiety-related disorders in his Viennese patients, while in Munich, Kraepelin first conceptually separated schizophrenia from manic depressive illness. His colleague, Alzheimer, studied the plaques and tangles of the dementia that came to bear his name. Although these ideas were developed in subsequent years, the basic classification remained the same. Organic mental illnesses such as Alzheimer’s dementia were clearly brain diseases, whereas neurotic conditions like anxiety seemed to stem from adverse life events. Functional illnesses, such as schizophrenia, occupied a contentious middle ground. Kraepelin presciently classified schizophrenia as early dementia (dementia praecox), but others disagreed. A lack of diagnostic or aetiological certainty allowed the illness to be attributed in some psychodynamic formulations to a schizophrenic mother; later biological reductionism led to the dopamine hypothesis of schizophrenia.
This picture of a termite mound in Tarangire Park, Tanzania, is one of the many beautiful pictures in Art Wolfe’s new book of photography Africa (London: The Harvill Press, 2001). His pictures bring the landscape and wildlife of this continent vividly to life.
THE LANCET • Vol 358 • September 29, 2001
The former was damagingly mistaken; the latter merely inadequate. Psychiatry needs to be able to encompass and explain Freudian talking cures and the irreversible accumulation of dead sludge found in patients with Alzheimer’s dementing brains. Yet these two parts of the specialty draw on different intellectual traditions. Psychotherapy shares with the humanities a subjective, historical perspective—one that seeks to understand in empathic retrospect. Neuroscience, by contrast, espouses a prospective, value-free scepticism. Both approaches are valid, and both are a necessary part of psychiatric practice. Yet the specialty has struggled for decades to find a model—a kind of pluralistic psychiatry—that might encompass and integrate them both. Shaping this “brave new brain” is the task that engages Andreasen in her book. A neuroscientist by training, and probably also by disposition, Andreasen describes her great excitement at being able to “get inside the heads” of her patients when computed-tomography scanning was introduced. The complexity of brain science was no deterrent: “Cardiology”, she writes, “was too easy by comparison”. But she is not a scientific reductionist: patients’ stories and personal narratives play an important part in the book. Andreasen’s integrative argument is based on developments in neuroscience research. It has always been clear that any notion of mind must involve the brain: in Eisenberg’s formulation, “for every twisted thought, there is a twisted molecule”. Yet the relation between brain and mind has traditionally been thought to be in one direction only. “The brain secretes thought”, as someone once said, “like the kidney secretes urine”. Recent neuroscience research confirms this relation, but with a twist. We are starting to understand not only “how the molecule makes the mind”, but also that “the mind makes the molecule”. Andreasen’s discussion begins with an outline of the difficulties faced by psychiatric genetics. Mental illnesses are complex: their inheritance is polygenic, and of variable penetrance and expressivity. Worse, although phenotypic diagnosis is now reliable, it is not neces-
1105
For personal use. Only reproduce with permission from The Lancet Publishing Group.
DISSECTING ROOM
sarily valid. Most psychiatric illnesses lack diagnostic markers. But there is an added level of complexity, because of the way genes interact with their environment. Personality, for example, is heritable—and is likely to influence individuals’ exposure to different environments. Genes will also modify the effect of a pathogenic environment on the phenotype. Andreasen uses a political metaphor: “Genes”, she writes, “are not rigid autocrats that dictate our destiny. They are instead a responsive group of legislators that must listen to biological messages and respond”. Neuroscience is also helping us to understand “how the brain teaches itself to learn”. The process is far more dynamic than had previously been realised. Patterns of neuronal activity induce permanent neuronal change, through long-term potentiation of neuronal firing, selective synaptic pruning, and apoptosis. Brain development is therefore shaped by individual physical and psychological experiences. In short: “neurons that fire together wire together”. The Freudian belief that all mental illnesses are due to early childhood experiences may have been abandoned, but life experiences do affect brain development. Such brain plasticity could also provide a neurophysiological explanation for
the effectiveness of psychotherapy. The experience of therapy will, over time, affect “mind functions”, such as emotion and memory, by affecting “brain functions”, such as the connections and communications between nerve cells. This convergence of synaptic and psychodynamic malleability promises one day to “achieve a synthesis between psychoanalytical theories of the unconscious and the conditioning theories of behaviourism, which are probably not as far apart as people once believed”. Research is also offering insights into the brain dysfunction of mental illness. Our understanding of cerebral function traditionally came from clinical descriptions of single brain lesions. Famous cases include the patient “Tan”, who taught Paul Broca that “we speak with our left hemispheres” in 1864, and Phineas Gage, who demonstrated to Harlow that prefrontal cortex was important for making mature social judgments. Yet a simple phrenological approach to mental illness— that psychiatric disorders are caused by defects in single brain areas—is inadequate. Imaging work reveals the complex interconnectedness of our neural network. The functional neuroanatomy of Huntingdon’s disease, for example, is well characterised. Yet although the caudate nucleus is the only
area directly affected, the illness also has profound cognitive and emotional effects. Studies have also implicated neglected brain areas, such as the cerebellum, in cognition. Holistic psychiatry can only benefit from attempts to humanise the science (which tends to neglect the individual), and analyse the humanities (which neglects testable predictions). Mindless neuroscience is just as useless as brainless psychotherapy. One of psychiatry’s stigmatising ironies has been this odd conceptual split, and a synthesis is long overdue. We need a single model capable of explaining how it is, for example, that both cognitive behavioural therapy and electrconvulsive therapy can be effective in treating depression. The new knowledge that Andreasen outlines here—about the interaction between brain plasticity and gene environment— sheds some light on how such a model might look. Her conceptual framework looks strong enough to support psychiatry as it moves with increasing confidence into the new millennium. We can only hope that cocktail party conversation shows similar progress. Michael Smith Department of Psychological Medicine, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow G12 0XH, UK
The Refractory Descriptions and discourses ensioner hurt in crash: a pensioner was airlifted to hospital after a serious road accident involving three cars.” What do you visualise? A doddery driver in the middle of the country road, head turned, chatting to friend, perhaps? Do we wonder about the other two cars and who might have been to blame? That “pensioner”—a friend, now patient—is a parish councillor, a widow, a mother of five, an active grandmother, a humanist, a social worker, the monthly village lunch organiser, the local paper’s village reporter, a student pianist, and a mature student. There are obvious dangers in the use of such narrow, discriminatory categorisations of people, especially in medical practice. Many current initiatives are attempting to move away from reductive labels for patients and their diseases—“the breast-lump in bed number 24”— towards treating people as individuals with diseases. Patient-centred health care is the jargon of the day— promoted in UK Department of Health policy developments by their Patient Partnership Strategies,
P
“
1106
for example. New frameworks that combine qualitative and quantitative research approaches and make use of broad expertises in multidisciplinary teams can encourage both single loop learning (incremental improvements to existing practice) and double loop learning (rethinking basic goals, norms, and paradigms). Such an approach promises to enlarge our understanding of disease and lead to more humane research and clinical practice. The benefits and value of narrativebased medicine are increasingly being explored in new publications; by interdisciplinary conference work aimed at researchers, teachers, and practitioners; and by social scientists and others in research projects. The importance of doctor-patient interactions in clinical encounters is now a subject of analysis. Such knowledge
can only be to the advantage and increased satisfaction of practitioners and patients. It is also likely to benefit the health service through decreased complaints and litigation and less wastage of drugs due to greater adherence to chosen treatments. Moreover, an awareness of language in the consultation reduces the blame culture by virtue of better managed discourses aimed at successful shared decision making. Better understanding of the patient by the physician, combined with understanding of the disease, ensures that interventions are not tailored just to the disease or condition, but to the patient as a whole, according to their specific circumstances. The recent launch of DIPEx, a Database of Individual Patient Experiences, (www.dipex.org) scored 20 000 hits on the first day, proving a demonstrable need. It is described as, at once, a 24 h support group for anyone whose life is touched by illness, and a valuable resource for training doctors, nurses, and other health workers. Refractor e-mail: [email protected]
THE LANCET • Vol 358 • September 29, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Art Wolfe
P
at the beginning of the 20th century. Freud described and treated what we would now judge as anxiety-related disorders in his Viennese patients, while in Munich, Kraepelin first conceptually separated schizophrenia from manic depressive illness. His colleague, Alzheimer, studied the plaques and tangles of the dementia that came to bear his name. Although these ideas were developed in subsequent years, the basic classification remained the same. Organic mental illnesses such as Alzheimer’s dementia were clearly brain diseases, whereas neurotic conditions like anxiety seemed to stem from adverse life events. Functional illnesses, such as schizophrenia, occupied a contentious middle ground. Kraepelin presciently classified schizophrenia as early dementia (dementia praecox), but others disagreed. A lack of diagnostic or aetiological certainty allowed the illness to be attributed in some psychodynamic formulations to a schizophrenic mother; later biological reductionism led to the dopamine hypothesis of schizophrenia.
This picture of a termite mound in Tarangire Park, Tanzania, is one of the many beautiful pictures in Art Wolfe’s new book of photography Africa (London: The Harvill Press, 2001). His pictures bring the landscape and wildlife of this continent vividly to life.
THE LANCET • Vol 358 • September 29, 2001
The former was damagingly mistaken; the latter merely inadequate. Psychiatry needs to be able to encompass and explain Freudian talking cures and the irreversible accumulation of dead sludge found in patients with Alzheimer’s dementing brains. Yet these two parts of the specialty draw on different intellectual traditions. Psychotherapy shares with the humanities a subjective, historical perspective—one that seeks to understand in empathic retrospect. Neuroscience, by contrast, espouses a prospective, value-free scepticism. Both approaches are valid, and both are a necessary part of psychiatric practice. Yet the specialty has struggled for decades to find a model—a kind of pluralistic psychiatry—that might encompass and integrate them both. Shaping this “brave new brain” is the task that engages Andreasen in her book. A neuroscientist by training, and probably also by disposition, Andreasen describes her great excitement at being able to “get inside the heads” of her patients when computed-tomography scanning was introduced. The complexity of brain science was no deterrent: “Cardiology”, she writes, “was too easy by comparison”. But she is not a scientific reductionist: patients’ stories and personal narratives play an important part in the book. Andreasen’s integrative argument is based on developments in neuroscience research. It has always been clear that any notion of mind must involve the brain: in Eisenberg’s formulation, “for every twisted thought, there is a twisted molecule”. Yet the relation between brain and mind has traditionally been thought to be in one direction only. “The brain secretes thought”, as someone once said, “like the kidney secretes urine”. Recent neuroscience research confirms this relation, but with a twist. We are starting to understand not only “how the molecule makes the mind”, but also that “the mind makes the molecule”. Andreasen’s discussion begins with an outline of the difficulties faced by psychiatric genetics. Mental illnesses are complex: their inheritance is polygenic, and of variable penetrance and expressivity. Worse, although phenotypic diagnosis is now reliable, it is not neces-
1105
For personal use. Only reproduce with permission from The Lancet Publishing Group.
DISSECTING ROOM
sarily valid. Most psychiatric illnesses lack diagnostic markers. But there is an added level of complexity, because of the way genes interact with their environment. Personality, for example, is heritable—and is likely to influence individuals’ exposure to different environments. Genes will also modify the effect of a pathogenic environment on the phenotype. Andreasen uses a political metaphor: “Genes”, she writes, “are not rigid autocrats that dictate our destiny. They are instead a responsive group of legislators that must listen to biological messages and respond”. Neuroscience is also helping us to understand “how the brain teaches itself to learn”. The process is far more dynamic than had previously been realised. Patterns of neuronal activity induce permanent neuronal change, through long-term potentiation of neuronal firing, selective synaptic pruning, and apoptosis. Brain development is therefore shaped by individual physical and psychological experiences. In short: “neurons that fire together wire together”. The Freudian belief that all mental illnesses are due to early childhood experiences may have been abandoned, but life experiences do affect brain development. Such brain plasticity could also provide a neurophysiological explanation for
the effectiveness of psychotherapy. The experience of therapy will, over time, affect “mind functions”, such as emotion and memory, by affecting “brain functions”, such as the connections and communications between nerve cells. This convergence of synaptic and psychodynamic malleability promises one day to “achieve a synthesis between psychoanalytical theories of the unconscious and the conditioning theories of behaviourism, which are probably not as far apart as people once believed”. Research is also offering insights into the brain dysfunction of mental illness. Our understanding of cerebral function traditionally came from clinical descriptions of single brain lesions. Famous cases include the patient “Tan”, who taught Paul Broca that “we speak with our left hemispheres” in 1864, and Phineas Gage, who demonstrated to Harlow that prefrontal cortex was important for making mature social judgments. Yet a simple phrenological approach to mental illness— that psychiatric disorders are caused by defects in single brain areas—is inadequate. Imaging work reveals the complex interconnectedness of our neural network. The functional neuroanatomy of Huntingdon’s disease, for example, is well characterised. Yet although the caudate nucleus is the only
area directly affected, the illness also has profound cognitive and emotional effects. Studies have also implicated neglected brain areas, such as the cerebellum, in cognition. Holistic psychiatry can only benefit from attempts to humanise the science (which tends to neglect the individual), and analyse the humanities (which neglects testable predictions). Mindless neuroscience is just as useless as brainless psychotherapy. One of psychiatry’s stigmatising ironies has been this odd conceptual split, and a synthesis is long overdue. We need a single model capable of explaining how it is, for example, that both cognitive behavioural therapy and electrconvulsive therapy can be effective in treating depression. The new knowledge that Andreasen outlines here—about the interaction between brain plasticity and gene environment— sheds some light on how such a model might look. Her conceptual framework looks strong enough to support psychiatry as it moves with increasing confidence into the new millennium. We can only hope that cocktail party conversation shows similar progress. Michael Smith Department of Psychological Medicine, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow G12 0XH, UK
The Refractory Descriptions and discourses ensioner hurt in crash: a pensioner was airlifted to hospital after a serious road accident involving three cars.” What do you visualise? A doddery driver in the middle of the country road, head turned, chatting to friend, perhaps? Do we wonder about the other two cars and who might have been to blame? That “pensioner”—a friend, now patient—is a parish councillor, a widow, a mother of five, an active grandmother, a humanist, a social worker, the monthly village lunch organiser, the local paper’s village reporter, a student pianist, and a mature student. There are obvious dangers in the use of such narrow, discriminatory categorisations of people, especially in medical practice. Many current initiatives are attempting to move away from reductive labels for patients and their diseases—“the breast-lump in bed number 24”— towards treating people as individuals with diseases. Patient-centred health care is the jargon of the day— promoted in UK Department of Health policy developments by their Patient Partnership Strategies,
P
“
1106
for example. New frameworks that combine qualitative and quantitative research approaches and make use of broad expertises in multidisciplinary teams can encourage both single loop learning (incremental improvements to existing practice) and double loop learning (rethinking basic goals, norms, and paradigms). Such an approach promises to enlarge our understanding of disease and lead to more humane research and clinical practice. The benefits and value of narrativebased medicine are increasingly being explored in new publications; by interdisciplinary conference work aimed at researchers, teachers, and practitioners; and by social scientists and others in research projects. The importance of doctor-patient interactions in clinical encounters is now a subject of analysis. Such knowledge
can only be to the advantage and increased satisfaction of practitioners and patients. It is also likely to benefit the health service through decreased complaints and litigation and less wastage of drugs due to greater adherence to chosen treatments. Moreover, an awareness of language in the consultation reduces the blame culture by virtue of better managed discourses aimed at successful shared decision making. Better understanding of the patient by the physician, combined with understanding of the disease, ensures that interventions are not tailored just to the disease or condition, but to the patient as a whole, according to their specific circumstances. The recent launch of DIPEx, a Database of Individual Patient Experiences, (www.dipex.org) scored 20 000 hits on the first day, proving a demonstrable need. It is described as, at once, a 24 h support group for anyone whose life is touched by illness, and a valuable resource for training doctors, nurses, and other health workers. Refractor e-mail: [email protected]
THE LANCET • Vol 358 • September 29, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.