Biological psychiatry in perspective

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Biological psych iatry in perspec tiveMGGelderOxford University Department of Psychiatry, Warneford Hospital, Oxford, UK

Biological psychiatry is a technical term that denotes physiological andbiochemical approaches to psychiatric ae tiology and, despite the usual wide rmeaning of the word biological, excludes psychosocial app roac hes /Biologic al'causes of severe psychiatric disorder have bee n suspected from the earliest times,and in some periods an excessive focus upon them has led to neglect ofpsychological and social approaches to treatm ent, to the detriment of patients. It isimportant that current research into biological psychiatry should be carriedforw ard in conjunction with the imp ortant advances that have been m ade inpsychological and social research.The causes of psychiatric illness are complex a ndit is unlikely that any single app roa ch , biolog ical or psychosocial, will be sufficienton its own.The great potential of b iological psychiatry w ill be realize d on ly if it isview ed w ithin these wide r historical and scientific perspectives.

The term biological psychiatry often puzzles those who are working inother branches of science and medicine. The word biology refers to thestudy of living things and therefore encompasses physiological, biochem-ical and psychological forms of investigation. In psychiatry, however, ithas become conventional to use the term biological to encompassphysiological, biochemical and genetic studies in contrast to social andpsychological investigations. The general reader who is coming for thefirst time to the subject of this volume should understand this conventionand should view the studies described in this volume in the context ofpsychological and social investigations. The general reader should alsokeep in the mind two other perspectives, the historical and the scientific.

The historical perspectiveFrom the earliest times, it has been recognised that mental disorders haveboth physiological and psychological causes. In Hippocratic writings ofPostal addrets: the 4th century BC, serious forms of mental illness were ascribed mainlyProfessor M G GeMer, t o somatic causes, which were expressed in the then current ideas thatn . - ^ T T ? h e a l t h 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 theBritish Medico) BullmHn 1996^2 (No. 3H0 1-4G 7 T t i . British Council 1996


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Biological psychiatry

term melancholia. These ideas were overtaken in the m iddle ages by theview th at mental illness could best be explained inreligious terms of sinand evil but in the 17th and 18th centuries interest in physical causes ofsevere 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 evenwith the use of the new science of neuropathology developed in the 19thcentury. At that time, another aetiological theory came to the fore. Ithas long been recognized that mental illness tends to run in families,but, in 1809, the French psychiatrist Morel suggested that the disorderbecame more severe in successive generations of the same family and hesuggested that inheritance can interact with certain adverse environ-mental factors, such as abuse of alcohol, and that the resulting changescould be transmitted to the next generation. This idea, which seemsimprobable today, was consistent with the then current notions ofinheritance of acquired characteristics. These views had two unfortu-nate effects: they led to therapeutic pessimism and they gave support tothe eugenic movement which held that the mentally ill should beseparated from society and prevented from reproducing. The story ofthis period of research is an important reminder that scientific advancesuncritically accepted can lead to harmful as well as to beneficial changesin policy.Although ideas concerning the aetiology of severe mental illness weredominated by these neuropathological and genetic theories, it is notablethat practising doctors were aware that these ideas could notsatisfactorily explain the illness of their patients. For example, theFrench psychiatrist Esquirol, writing in 184 5, recognized the importanceof heredity but stressed that psychological and social factors couldpredispose to or precipitate illness. Among his examples of adversepsychosocial factors were domestic problems, disappointments in love,and 'reversals of fortune', and he recognised also a wide group ofphysical causes such as the abuse of alcohol, the effects of childbirth andlactation, and epilepsy. The German psychiatrist Wilhelm Griesingerwriting later in the century put forward similar views in his influentialtextbook The P athology and Therapy of Mental D isorders. He w rote1:

A closer examination of the aetiology of insanity soon shows that inthe great majority of cases it was not a single specific cause under theinfluence of which the disease was finally established but acomplication of several, sometimes numerous causes, b oth predispos-ing and exciting. Very often the germs of disease are laid in those earlyperiods of life from which the commencement of the formation ofcharacter dates. It grows by education and external influences.4 0 2 Bntisb Medical Bulletin 1996;52 (No. 3)


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Biological psychiatry in perspective

This statement still rings true today and could form a usefulbackground to the studies described in this volume.Despite these wise and balanced views, many of the doctors w ho caredfor the mentally ill in the second half of the 19th century took asimplistic organic view. The problem was recognised by Adolf Meyer, aSwiss doctor w ho became the do minant figure in American psychiatry inthe late 19th and early 20th century. In the course of medical training inSwitzerland, Meyer had been taught to think of aetiology in the tra ditionof Griesinger. When he began work in American psychiatric hospitals,he was disturbed by the narrowly organic views about aetiology and theconsequent therapeutic nihilism. Meyer set out to promulgate the ideathat mental illness had multi factorial causes and that, even in cases withthe most obvious organic aetiology, there were additional psychosocialfactors which could often be modified to the benefit of the patient.Meyer called this balanced approach psychobiology, a name thatresembles the modern term biological psychiatry but had an altogetherwider meaning embracing a detailed knowledge of each patient'sbiography and the educational and external influences that Griesingerhad emphasized.Meyer's psychobiology had a beneficial effect on the practice ofpsychiatry by bringing about more active programmes of rehabilitationand resettlement and a better understanding of the psychological andsocial causes of mental illness. Its effects on research were less desirable,because psychobiology was so general and all-embracing it did notprovide a clear guide to priorities in research. In the 1930s, neurosciencewas in an early stage of development and this approach to psychiatricresearch together with Meyer's psychobiology were overtaken bypsychoanalysis, which seemed at the time to provide answers to clinicalproblems which more scientific approaches could not rival. The gradualdevelopment of better methods of investigation, coupled with thediscovery of drugs with powerful effects in the psychoses, led to agrowing interest in the biological psychiatry which eventually expandedrapidly as new techniques of brain investigation became available.These few landmarks in the history of ideas about the causes of mentalillness point to an important general conclusion. Each generation hasbased ideas of aetiology on the scientific approaches that were mostactive and seemed most plausible at the time. This sometimes led to anarrow view of aetiology, in which other factors, less easy to investigate,were neglected. Although, as the above quotations show, observantclinicians have always been aware of the complexity of the causes ofpsychiatric disorders in their patients, others have neglected the widercauses to the detriment of their patients. This volume reflects the widerviewpoint for it contains articles on psychological approaches as well asgenetic, biochemical and physiological methods. Nevertheless, the reader

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

The scientific persp ectiveThree features of causat ion in psychiatry create difficulties for biologicalresearch: causes may be remote in time; one cause may have severaleffects; and one effect mayhave many causes. The causes of psychiatricillness are often remote in t ime. It has long been recognized thatexperiences in childhood can affect personality development andresponse to stress and it now seems possible that events before or soonafter birth may be a prima ry cause of schizophrenia acting perhaps uponthe development and maturat ion of the brain. The details of the processcannot be explained at present, but the general model has an obviousparallel in epilepsy in which trauma to the brain may result in disordermany years later. Nevertheless, it is very difficult to carry out directscientific tests of associations so far apar t in t ime. In the case ofschizophrenia, indirect evidence has been called upon, for example theabsence of gliosis in areas of the brain showing structural changes, afinding which suggests a pathological change before or a r ound the timeof birth 2 . A second source of indirect evidence is the study, in the brainsof schizophrenics dying of other causes, of genes known to be involved inbrain development (see for example3).A second difficulty for biological research is tha t in psychiatry a singlecause can have multiple effects. This is illustrated by the consequences ofsyphilitic infection of the brain. When neurosyphilis was c ommon ,psychiatrists recognized that it could lead to dementia, affectivesymptoms, or a features resembling those of schizophrenia. Similarly,Hunt ing ton ' s chorea , which is due to a disorder involving a single geneand causing movement disorder and dementia , is associated also withpsychiatric disorder including bipolar disorder 4. With this diversity ofmanifestations of known single causes, it is difficult to decide what rangeof disorders should be included in an aetiological investigation. It hasbeen suggested, on the one hand, that the whole spectrum of psychosesmay have a common cause (see for example 5) and, on the other, thatthese aetiological studies should consider specific subgroups withinschizophrenia or manic depressive disorder.A third difficulty is that one effect may have multiple causes. There arepredisposing, precipitating, and maintaining causes of psychiatricdisorder; and there are usually psychological and social causes interactingwith one or more genetic or biochemical cause of the same disorder. Forexample 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 lifeevents; genetic factors; previous history of major depression; andneuroticism. The factors appeared to interact with 60% of the effect ofgenetic factors directly related to risk of developing major depression,and 40% expressed through increased liability to experience stressfulevents and to have high neuroticism.Despite these complexities, recent advances in neuroscience have led tomajor advances in the understanding of psychiatric aetiology andpromise to reveal much more. Psychiatric research has benefited bothfrom 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, moleculargenetics, cell biology and metabolic studies. The contributions of thesemethods to the study of psychiatric aetiology is illustrated in several ofthe articles of this volume. (For example those by Craddock and Owenon modern genetic approaches and on clinical imaging techniques, bySmith and Jobst, and by Frangou and Murray.) Findings from thesemethods applied to patients have to be evaluated against a knowledge ofthe range of normal variation and some of the new techniques have notbeen 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 beoverestimated as it has been in the past. For example, when studies of thechromosome 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 inthe general population was greater than had been supposed and theassociation with aggressive behaviour was correspondingly weaker7.Also, some associations between biological abnormalities and psychiatricdisorders turn out to be due to normal psychological reactions to the coreabnorm ality. For example, it seems that in panic disorder the greater p artof the psychological changes are due to a fearful reaction to autonomicsymptoms which may arise from a primary disorder of autonomicregulation8.Advances in neuroscience have not depended solely on new techniques,there have been important theoretical developments as well. Some ofthese new ideas, which are highly relevant to psychiatric aetiology, arediscussed by Friston and Cowen who consider connectionist accounts ofbrain function and the important concepts of neural networks, neuralmodulation and neural plasticity, which provide different ways ofconceptualizing the pathological basis of mental disorder.While reading about these striking advances in biological research, it isimportant to remember that some productive approaches to psychiatricaetiology fall outside the conventional confines of biological psychiatryand, therefore, are not described in this volume. Clinical psychology is

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one of these approaches (though one aspect of the discipline - cognitiveneuropsychology-is represented in this volume by the article by Frith).Sociological studies have been important in showing how the corefeatures of functional psychosis can be added to by those ofinstitutionalism, a key finding for those who are searching for the linkbetween brain and behaviour. Such studies have also demonstrated therole of social stressors ('life events') in provoking and maintainingschizophrenia and affective disorders (see9). Psychiatric epidemiology hasbeen highly important in showing that the major mental disorders occurin a wide variety of different societies (arguing strongly against the viewthat schizophrenia is a product of social conditions) and epidemiologicalmethods have been used effectively in the studies of population geneticswhich have laid the framework for molecular genetic investigations.

Conclusions

References

The scientific perspective reminds us that the findings described in thisvolume must be considered in the context of equally importantdiscoveries from social and psychological research into psychiatricdisorder. Psychosocial factors interact with biochemical and physiologi-cal factors in the aetiology of these conditions, and some of the findingsof 'biological' studies may even be secondary to psychologicaldisturbances.The historical perspective reminds us of the danger of focussing clinicalpractice too closely on current scientific advances because many aspectsof the care of patients cannot be measured or investigated scientifically.Many of the important advances in knowledge described in this volumewill doubtless lead to improvements in treatment, but it is important inthe 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 volumethat gives hope for the future understanding and treatment of psychiatricdisorder.

Griesinger W. Mental P athology and Therapeutics (2nd edn 1867, translated from the Germanby C. Lockhart Robertson and J. Rutherford). London: New Sydenham Society, 130Bruton CJ, Crow TJ, Frith CD et al. Schizophrenia and the brain: a prospective cliniconeuropathological s tudy. Psychol Med 1990 ; 20 : 285-304Bloom FE. Advancing a neurodevelopmental origin for schizophrenia. Arch Gen Psychiatry1993; 5 0 2 2 4 - 7Peyser C E, Folstein SE. Depression in Huntin gdo n disease. In: Sarkstein SE, Robinson RG . (Eds)Depression in Neurological Disease. 1993 ; 117-38

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Cro w TJ. The dem ise of the Kraepehn binary system as a prelude to genetic advance. In: GershonES , Cloninger R. (Eds) Genetic Approaches to Mental Disorders. Washington: AmericanPsychiatric Press, 1994Kendler 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: 527-4 0Witkin HA, Mednick SA, Schulsinger F. CnminaUty and XYY and XXY man. Science 1976; 193:5 4 7 - 8Clark DM, Salkovskis PM, Hackmann A, Middleton H, Anastas iades P, Gelder MG. Acomparison of cognitive therapy, applied relaxation and imipramine in the treatment of panicdisorder. Br J Psychiatry 1994; 164: 759-69Brown GW, Harr is TO. Social Origins of Depression. London: Tavistock, 1978

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Biological psychiatry in perspective