Biological psychiatry in perspective

MGGelder
Oxford University Department of Psychiatry, Warneford Hospital, Oxford, UK

Biological psychiatry is a technical term that denotes physiological and

biochemical approaches to psychiatric aetiology and, despite the usual wider
meaning of the word biological, excludes psychosocial approaches/Biological'
causes of severe psychiatric disorder have been suspected from the earliest times,
and in some periods an excessive focus upon them has led to neglect of
psychological and social approaches to treatment, to the detriment of patients. It is
important that current research into biological psychiatry should be carried
forward in conjunction with the important advances that have been made in
psychological and social research.The causes of psychiatric illness are complex and
it is unlikely that any single approach, biological or psychosocial, will be sufficient
on its own.The great potential of biological psychiatry will be realized only if it is
viewed within these wider historical and scientific perspectives.

The term biological psychiatry often puzzles those who are working in
other branches of science and medicine. The word biology refers to the
study of living things and therefore encompasses physiological, biochem-
ical and psychological forms of investigation. In psychiatry, however, it
has become conventional to use the term biological to encompass
physiological, biochemical and genetic studies in contrast to social and
psychological investigations. The general reader who is coming for the
first time to the subject of this volume should understand this convention
and should view the studies described in this volume in the context of
psychological and social investigations. The general reader should also
keep in the mind two other perspectives, the historical and the scientific.

The historical perspective

From the earliest times, it has been recognised that mental disorders have
both physiological and psychological causes. In Hippocratic writings of
Postal addrets: the 4th century BC, serious forms of mental illness were ascribed mainly
Professor M G GeMer, t o somatic causes, which were expressed in the then current ideas that
health
n. - ^ ^ T T ? depended on a correct balance of the four body humours (blood,
Department of Psychiatry, r . ' \ '
v/ameford Hospital, phlegm, yellow bile and black bile) and imbalance led to illness.
Oxford OX3 7JX, UK Depressive disorder was related to an imbalance of black bile, hence the

British Medico) BullmHn 1996^2 (No. 3H01-4G7 ©Tti. British Council 1996
Biological psychiatry

term melancholia. These ideas were overtaken in the middle ages by the
view that mental illness could best be explained in religious terms of sin
and evil but in the 17th and 18th centuries interest in physical causes of
severe illness revived. The causes were now sought in the brain itself,
although the nature of this brain disorder was not understood.
Repeated searches failed to show specific pathological changes even
with the use of the new science of neuropathology developed in the 19th
century. At that time, another aetiological theory came to the fore. It
has long been recognized that mental illness tends to run in families,
but, in 1809, the French psychiatrist Morel suggested that the disorder
became more severe in successive generations of the same family and he
suggested that inheritance can interact with certain adverse environ-
mental factors, such as abuse of alcohol, and that the resulting changes
could be transmitted to the next generation. This idea, which seems
improbable today, was consistent with the then current notions of
inheritance of acquired characteristics. These views had two unfortu-
nate effects: they led to therapeutic pessimism and they gave support to
the eugenic movement which held that the mentally ill should be
separated from society and prevented from reproducing. The story of
this period of research is an important reminder that scientific advances
uncritically accepted can lead to harmful as well as to beneficial changes
in policy.
Although ideas concerning the aetiology of severe mental illness were
dominated by these neuropathological and genetic theories, it is notable
that practising doctors were aware that these ideas could not
satisfactorily explain the illness of their patients. For example, the
French psychiatrist Esquirol, writing in 1845, recognized the importance
of heredity but stressed that psychological and social factors could
predispose to or precipitate illness. Among his examples of adverse
psychosocial factors were domestic problems, disappointments in love,
and 'reversals of fortune', and he recognised also a wide group of
physical causes such as the abuse of alcohol, the effects of childbirth and
lactation, and epilepsy. The German psychiatrist Wilhelm Griesinger
writing later in the century put forward similar views in his influential
textbook The Pathology and Therapy of Mental Disorders. He wrote1:

A closer examination of the aetiology of insanity soon shows that in

the great majority of cases it was not a single specific cause under the
influence of which the disease was finally established but a
complication of several, sometimes numerous causes, both predispos-
ing and exciting. Very often the germs of disease are laid in those early
periods of life from which the commencement of the formation of
character dates. It grows by education and external influences.

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 Biological psychiatry in perspective

This statement still rings true today and could form a useful
background to the studies described in this volume.
Despite these wise and balanced views, many of the doctors who cared
for the mentally ill in the second half of the 19th century took a
simplistic organic view. The problem was recognised by Adolf Meyer, a
Swiss doctor who became the dominant figure in American psychiatry in
the late 19th and early 20th century. In the course of medical training in
Switzerland, Meyer had been taught to think of aetiology in the tradition
of Griesinger. When he began work in American psychiatric hospitals,
he was disturbed by the narrowly organic views about aetiology and the
consequent therapeutic nihilism. Meyer set out to promulgate the idea
that mental illness had multi factorial causes and that, even in cases with
the most obvious organic aetiology, there were additional psychosocial
factors which could often be modified to the benefit of the patient.
Meyer called this balanced approach psychobiology, a name that
resembles the modern term biological psychiatry but had an altogether
wider meaning embracing a detailed knowledge of each patient's
biography and the educational and external influences that Griesinger
had emphasized.
Meyer's psychobiology had a beneficial effect on the practice of
psychiatry by bringing about more active programmes of rehabilitation
and resettlement and a better understanding of the psychological and
social causes of mental illness. Its effects on research were less desirable,
because psychobiology was so general and all-embracing it did not
provide a clear guide to priorities in research. In the 1930s, neuroscience
was in an early stage of development and this approach to psychiatric
research together with Meyer's psychobiology were overtaken by
psychoanalysis, which seemed at the time to provide answers to clinical
problems which more scientific approaches could not rival. The gradual
development of better methods of investigation, coupled with the
discovery of drugs with powerful effects in the psychoses, led to a
growing interest in the biological psychiatry which eventually expanded
rapidly as new techniques of brain investigation became available.
These few landmarks in the history of ideas about the causes of mental
illness point to an important general conclusion. Each generation has
based ideas of aetiology on the scientific approaches that were most
active and seemed most plausible at the time. This sometimes led to a
narrow view of aetiology, in which other factors, less easy to investigate,
were neglected. Although, as the above quotations show, observant
clinicians have always been aware of the complexity of the causes of
psychiatric disorders in their patients, others have neglected the wider
causes to the detriment of their patients. This volume reflects the wider
viewpoint for it contains articles on psychological approaches as well as
genetic, biochemical and physiological methods. Nevertheless, the reader

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Biological psychiatry

should bear in mind the wealth of research into social and psychological
causes of severe mental illness that cannot be reviewed here.

The scientific perspective

Three features of causation in psychiatry create difficulties for biological
research: causes may be remote in time; one cause may have several
effects; and one effect may have many causes. The causes of psychiatric
illness are often remote in time. It has long been recognized that
experiences in childhood can affect personality development and
response to stress and it now seems possible that events before or soon
after birth may be a primary cause of schizophrenia acting perhaps upon
the development and maturation of the brain. The details of the process
cannot be explained at present, but the general model has an obvious
parallel in epilepsy in which trauma to the brain may result in disorder
many years later. Nevertheless, it is very difficult to carry out direct
scientific tests of associations so far apart in time. In the case of
schizophrenia, indirect evidence has been called upon, for example the
absence of gliosis in areas of the brain showing structural changes, a
finding which suggests a pathological change before or around the time
of birth2. A second source of indirect evidence is the study, in the brains
of schizophrenics dying of other causes, of genes known to be involved in
brain development (see for example3).
A second difficulty for biological research is that in psychiatry a single
cause can have multiple effects. This is illustrated by the consequences of
syphilitic infection of the brain. When neurosyphilis was common,
psychiatrists recognized that it could lead to dementia, affective
symptoms, or a features resembling those of schizophrenia. Similarly,
Huntington's chorea, which is due to a disorder involving a single gene
and causing movement disorder and dementia, is associated also with
psychiatric disorder including bipolar disorder4. With this diversity of
manifestations of known single causes, it is difficult to decide what range
of disorders should be included in an aetiological investigation. It has
been suggested, on the one hand, that the whole spectrum of psychoses
may have a common cause (see for example5) and, on the other, that
these aetiological studies should consider specific subgroups within
schizophrenia or manic depressive disorder.
A third difficulty is that one effect may have multiple causes. There are
predisposing, precipitating, and maintaining causes of psychiatric
disorder; and there are usually psychological and social causes interacting
with one or more genetic or biochemical cause of the same disorder. For
example Kendler et al6 calculated that about half the liability to major

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 Biological psychiatry in perspective

depression could be accounted for by four factors: recent stressful life

events; genetic factors; previous history of major depression; and
neuroticism. The factors appeared to interact with 60% of the effect of
genetic factors directly related to risk of developing major depression,
and 40% expressed through increased liability to experience stressful
events and to have high neuroticism.
Despite these complexities, recent advances in neuroscience have led to
major advances in the understanding of psychiatric aetiology and
promise to reveal much more. Psychiatric research has benefited both
from advances in basic science and from technological developments.
There is now a wide span of scientific approaches to mental illness,
including structural and functional imaging of the brain, molecular
genetics, cell biology and metabolic studies. The contributions of these
methods to the study of psychiatric aetiology is illustrated in several of
the articles of this volume. (For example those by Craddock and Owen
on modern genetic approaches and on clinical imaging techniques, by
Smith and Jobst, and by Frangou and Murray.) Findings from these
methods applied to patients have to be evaluated against a knowledge of
the range of normal variation and some of the new techniques have not
been in use for long enough for it to be certain how great is this variation,
so that the extent and specificity of abnormality may sometimes be
overestimated as it has been in the past. For example, when studies of the
chromosome abnormalities began, the frequency of the XYY abnorm-
ality appeared to be particularly great among highly aggressive patients,
but subsequent studies showed that the frequency of the abnormality in
the general population was greater than had been supposed and the
association with aggressive behaviour was correspondingly weaker7.
Also, some associations between biological abnormalities and psychiatric
disorders turn out to be due to normal psychological reactions to the core
abnormality. For example, it seems that in panic disorder the greater part
of the psychological changes are due to a fearful reaction to autonomic
symptoms which may arise from a primary disorder of autonomic
regulation8.
Advances in neuroscience have not depended solely on new techniques,
there have been important theoretical developments as well. Some of
these new ideas, which are highly relevant to psychiatric aetiology, are
discussed by Friston and Cowen who consider connectionist accounts of
brain function and the important concepts of neural networks, neural
modulation and neural plasticity, which provide different ways of
conceptualizing the pathological basis of mental disorder.
While reading about these striking advances in biological research, it is
important to remember that some productive approaches to psychiatric
aetiology fall outside the conventional confines of biological psychiatry
and, therefore, are not described in this volume. Clinical psychology is

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Biological psychiatry

one of these approaches (though one aspect of the discipline - cognitive

neuropsychology-is represented in this volume by the article by Frith).
Sociological studies have been important in showing how the core
features of functional psychosis can be added to by those of
institutionalism, a key finding for those who are searching for the link
between brain and behaviour. Such studies have also demonstrated the
role of social stressors ('life events') in provoking and maintaining
schizophrenia and affective disorders (see9). Psychiatric epidemiology has
been highly important in showing that the major mental disorders occur
in a wide variety of different societies (arguing strongly against the view
that schizophrenia is a product of social conditions) and epidemiological
methods have been used effectively in the studies of population genetics
which have laid the framework for molecular genetic investigations.

Conclusions
The scientific perspective reminds us that the findings described in this
volume must be considered in the context of equally important
discoveries from social and psychological research into psychiatric
disorder. Psychosocial factors interact with biochemical and physiologi-
cal factors in the aetiology of these conditions, and some of the findings
of 'biological' studies may even be secondary to psychological
disturbances.
The historical perspective reminds us of the danger of focussing clinical
practice too closely on current scientific advances because many aspects
of the care of patients cannot be measured or investigated scientifically.
Many of the important advances in knowledge described in this volume
will doubtless lead to improvements in treatment, but it is important in
the meantime that they do not result in neglect of other, less scientific,
aspects of care. With this caution in mind, there is much in this volume
that gives hope for the future understanding and treatment of psychiatric
disorder.

References

Griesinger W. Mental Pathology and Therapeutics (2nd edn 1867, translated from the German
by C. Lockhart Robertson and J. Rutherford). London: New Sydenham Society, 130
Bruton CJ, Crow TJ, Frith CD et al. Schizophrenia and the brain: a prospective clinico
neuropathological study. Psychol Med 1990; 20: 285-304
Bloom FE. Advancing a neurodevelopmental origin for schizophrenia. Arch Gen Psychiatry
1993; 50 224-7
Peyser CE, Folstein SE. Depression in Huntingdon disease. In: Sarkstein SE, Robinson RG. (Eds)
Depression in Neurological Disease. 1993; 117-38

406 Britith Mtdical Bulletin 1996;52 (No. 3)

 Biological psychiatry in perspective

Crow TJ. The demise of the Kraepehn binary system as a prelude to genetic advance. In: Gershon
ES, Cloninger R. (Eds) Genetic Approaches to Mental Disorders. Washington: American
Psychiatric Press, 1994
Kendler KS, McGuire M, Gruenberg AM et al. The Roscommon family study. (1) Methods,
diagnosis of probands and risk of schizophrenia in relatives. Arch Gen Psychiatry 1993; 50: 527-40
Witkin HA, Mednick SA, Schulsinger F. CnminaUty and XYY and XXY man. Science 1976; 193:
547-8
Clark DM, Salkovskis PM, Hackmann A, Middleton H, Anastasiades P, Gelder MG. A
comparison of cognitive therapy, applied relaxation and imipramine in the treatment of panic
disorder. Br J Psychiatry 1994; 164: 759-69
Brown GW, Harris TO. Social Origins of Depression. London: Tavistock, 1978

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