SEMINARS IN NEUKOLO(;Y-VOLUME
10, NO. 5 SEPTEMBER 1990
Psychiatric Consequences of Basal Ganglia Disease
T h e first experimental work on the function of the basal ganglia was reported by Magendie in 1839.' He injected chromic acid into the basal ganglia of a rabbit and found that it kept running even if it could get no further because of an obstruction. Schiff in 1845 showed that destruction of the rabbit's basal ganglia produced immobility until a sensory stimulus produced the running movements.' This first experimental work, then, suggested that the basal ganglia have more than a simple role in motor function and make a contribution to complex behavior. This period and the next 80 years saw the first descriptions of basal ganglia lesions in pseudobulbar palsy (Bright, 1831), paralysis agitans or Parkinson's disease (Oppolzer, 1861), chorea (Broadbent, 1865), athetosis (Gowers, 1876), and pseudosclerosis or Wilson's disease (Westphal, 1883)' T h e significance of these lesions, however, remained unclear, since postmortem examination of other patients with these conditions showed no gross disorder of the basal ganglia and gross lesions could be found in the basal ganglia of people who had shown no. evidence of motor disorder. T h e term "basal ganglia" was introduced by Ringer in 1879 to describe the putamen and globus pallidus. It gradually came into general use, but there was no agreement on the exact composition of these ganglia, which for different authors encompassed a number of adjacent structures, including caudate nucleus, thalamus, habenular ganglion and the subthalamic nucleus of Luys. T h e caudate nucleus and putamen together were also known as the striatum and the caudate nucleus, putamen, and globus pallidus as the corpus striatum. L e ~ ywho , ~ gave an account of this early work u p to 1940, declared that 1912, when Wilson first described his disease,%as the time when the "gestalt" of the basal ganglia-that is, their function
and the consequences of their dysfunction-suddenly became apparent. This gestalt, however, was a neurologic gestalt. Psychiatry was completely left out of the picture. For example, in his otherwise detailed historical account, Lewy makes no mention of contemporary pathologic findings in the basal ganglia of patients with catatonic schizophrenia, such as those of Lehmann in 1898."'The proceedings of the 1940 meeting of the Association for Research in Nervous and Mental Diseases (AKNMD) devoted to diseases of the basal ganglia, in which Lewy's historical account appears, makes not a single mention of psychiatry, ignoring completely the work reviewed in the next few paragraphs. This was because by 1912 neurology and psychiatry were parting intellectual company and by 1940 the rupture was complete. Wilson's article in Brain in 1912 on progressive lenticular disease, subsequently called Wilson's disease, certainly broke new ground in many w a y s . H e described what is still one of the few completely treatable neurologic diseases. He introduced a new concept-extrapyramidal motor disorder-and suggested that paralysis agitans, which was only just being accepted as an organic diseasc of the nervous system, was an extrapyramidal disorder. He suggested that gross anatomic lesions were not necessary to produce extrapyramidal disorder, but that dynamic modification of function was enough. This was only 8 years after the first suggestion of neurotransmitters." Significantly, in the present context, 8 ol'the 12 patients he described in his article had prominent psychiatric symptoms, with previous diagnoses such as hysteria and schizophrenia." until the beginning of this century, the cerebral cortex was believed to be "the seat of all psychical operation^,^ but the first half of this century saw a gradual appreciation that subcortical structures and systems could contribute to psychiatric
Consultant Neuropsychiatrist, Burden Neurological Hospital, Stoke Lane, Stapleton, Hristol, United Kingdom Reprint requests: Dr. Rogers, Burden Neurological Hospital, Stoke Lane, Stapleton, Bristol, UK Copyright 1990 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, N Y 10016. Ail rights reserved.
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Daniel Rogers, M.R.C.P., M .R . C. Psych
disorder. A few years after Wilson's article, epidemic encephalitis swept across Europe and produced among its sufferers every known psychiatric s y n d r ~ m e The . ~ encephalitis mainly affected subcortical brain structures, including the basal ganglia, and this suggested a link between these structures and psychiatric disorder. This possibility was explored by psychiatrists who had not been completely taken over by the psychodynamic revolution that had swept through psychiatry. In 192 1, Dide and colleagues%uggested that a parkinsonian syndrome formed part of the catatonic form of schizophrenia. Unlike Parkinson's disease, there was no rest tremor and it was reversible. They suggested that it must be due to disorder of the basal ganglia and adjacent subcortical areas. They had found in postmortem study of schizophrenic patients that subcortical lesions, including basal ganglia lesions, were more common and extensive than cortical lesions. G ~ i r a u done ,~ of these authors, believed that catatonia was being explained in psychologic terms, since it was often associated with prominent psychiatric disorder. Viewed neurologically, however, it showed all the classic manifestations of basal ganglia disorder. He suggested that catatonia should be regarded as an extrapyramidal disorder, along with Wilson's disease, chorea, athetosis, and parkinsonism. All these conditions could be associated with psychiatric disorder, although the association was most prominent with catatonia. Other European authors such as Haskovec," who coined the term "akathisia" at the beginning of the century, insisted on a subcortical basis for psychiatric disorder. Reiter," again describing extrapyramidal motoy disturbances in schizophrenia, lamented the development of neurology and psychiatry along separate lines. He supported the view that the extrapyramidal system, and more specifically the basal ganglia, produced both neurologic and psychiatric disorder and suggested that the pathologic basis for such disorder might be more chemical than morphologic. Farran-Ridge12 described various symptoms of schizophrenia, such as strong upward deviation of the eyeballs, fluttering of the eyelids, chewing movements of the mouth, greasiness of the skin, respiratory disorders, and choreiform movements, which he argued pointed directly to lesions or functional disturbance of the basal ganglia. Steckl%uggested that extrapyramidal motor disorder formed part of a large proportion of psychiatric illnesses, such as schizophrenia (forming the catatonic syndrome), affective disorder (contributing to psychomotor retardation), and hysteria. Disturbance of an identical cerebral system involving the brainstem, basal ganglia, and frontal
lobes explained why analogous symptoms appeared in conditions of very different etiology. Other authors supported involvement of the basal ganglia in catatonic schizophrenia.I4 This had to be a functional disorder of the basal ganglia to explain the variability and reversibility of the symptoms and the lack of significant anatomic alterations in the basal ganglia. Even Bleuler, who had coined the term "schizophrenia" to replace dementia praecox and was the champion of Freudian interpretation of its symptomatology, accepted that certain of the motor symptoms of schizophrenia were also found in basal ganglia diseases.15Interest in this area, however, subsequently diminished as the encephalitis epidemic disappeared and the psychologic explanatory paradigm of psychiatric disorder which had hijacked psychiatry remained predominant. Some interest, however, persisted. T h e first attempt to look specifically at the psychiatric disorder accompanying known basal ganglia diseases was by Brenner and colleagues in 1947." They described 17 patients with Wilson's disease, Huntington's chorea, dystonia musculorum deformans, and double athetosis. The patients had a variety of psychiatric disorders, including affective disturbance and psychotic symptoms as well as cognitive disorder, but there was no characteristic psychiatric disorder accompanying these basal ganglia diseases. In fact, the characteristic feature of the psychiatric accompaniments to these diseases was their variability. 'This suggested that psychiatric disorder must be the result of disorder of other brain regions. What was fairly consistent for most of the patients was the effect of their psychic state on their abnormal movements. The movements were typically more prominent with emotional excitement and less prominent with distraction. The authors pointed out that this feature had, until then, been seen as a hallmark of psychiatric conditions, such as hysteria, but that it should be accepted as the hallmark of basal ganglia disorder. A corollary was that psychotherapy could play a palliative role even in progressive disease of the central nervous system. The First International Congress of Neuropathology in Rome in 1952 devoted a whole section to the histopathology of schizophrenia. Hopf" and other European investigators maintained, just as Lehmann and others at the turn of the century had done, that catatonic schizophrenia was associated with pathologic changes in the basal ganglia. Neuropathologists from Great Britain and the United States, however, remained sceptical.I8 Kleist, a European author, who had consistently insisted on a cerebral basis for schizophrenia throughout the heyday of psychodynamic ascend-
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PSYCHIATRIC CONSEQUENCES OF BASAL GANGLIA DISEASE-ROGERS
263
ancy, continued to maintain that motor features of schizophrenia were analogous to the motor disorders of basal ganglia diseases.lg Mettler, in the United States, was rather exceptional at this time in suggesting that the schizophrenic syndrome was basically a perceptual disorder caused by dysfunction of the basal ganglia, which produced secondary cortical d y ~ f u n c t i o nHe . ~ ~was ahead of his time in attributing more than a purely motor function to the basal ganglia, but the neurotransmitter revolution was still around the corner and when it came to a possible mechanism to explain the characteristic variability and reversibility of psychiatric symptoms and their relationship with emotional triggers, he could only suggest vasospasm in the basal ganglia. T h e 1960s saw major advances in the understanding of the anatomy and neurochemistry of the basal ganglia. Anatomic studies showed a highly organized neuronal projection to the basal ganglia from all areas of cortex." Projection from neocortex suggested a cognitive input to motor function, and projection from limbic cortex, an affective input. T h e basal ganglia were shown to contain by far the highest concentration of dopamine in the brain. Ascending projection systems from brainstem to basal ganglia were shown to have dopamine as their major neurotransmitter. These projection systems consisted of the nigrostriatal tract and the mesolimbic system. The mesolimbic system projected to the anterior extremity of the basal ganglia or limbic striatum, consisting of nucleus accumbens, olfactory tubercle, and nucleus of the stria terminalis. These were then added to the constituents of the basal ganglia. It was these structures that received inputs from the limbic cortex, amygdala, and hippocampus. These advances in basic neuroscience coincided with renewed interest in the cerebral basis for psychiatric disorder and produced renewed suggestions of a prominent role for basal ganglia dysfunction in psychiatric disorder. In 1972, Klawans and colleagues suggested that the dopaminergic system in the basal ganglia could be a final common pathway for the schizophrenic syndrome and that there should be a relationship between this syndrome and known basal ganglia disorder involving dopaminergic mechanisms." Stevens25n 1973 suggested that schizophrenia could represent dysfunction of the mesolimbic dopamine projection system in a manner similar to dysfunction of the nigrostriatal dopamine system in known basal ganglia disorders such as Parkinson's disease. In 1975, WebsterZ4,at a meeting of the psychiatry section of the Royal Society of Medicine devoted to the basal ganglia, suggested that distinguishing 264
VOLUME 10. NUMBER 3 SEPTEMBER 1990
motor activity and behavior was more a reflection of the particular interests of different investigators than a meaningful separation of categories in cerebral terms. In 1976, the ARNMD held the second meeting that it devoted exclusively to the basal ganglia.25Teuber, in his contribution, suggested that more advances had been made in understanding the function of the basal ganglia since the first ARNMD meeting on the basal ganglia in 1940 than in any other field in neurology. These advances, he said, had encouraged a much broader definition of the term "motor"; he also stated that basal ganglia function included complex perceptual and cognitive aspects of behavior. There was, however, only one contribution, by Bowen, on behavioral alterations in patients with basal ganglia lesions, and that was confined to Parkinson's disease. T h e psychiatric consequences of basal ganglia disease rated only three paragraphs of discussion in the whole proceedings, although this, of course, was more than in the 1940 meeting. Many neurologists who accepted a role for the basal ganglia in complex behavior did not extend this new thinking to psychiatric disorder. The traditional view of the basal ganglia as being concerned with motor function and cerebral cortex with cognitive function continued to be maintained.26 There was, however, renewed interest in the possibility of basal ganglia dysfunction in schizophrenia." T h e concept of Parkinson's disease and schizophrenia as contrasting conditions in terms of their dopamine dysfunction was put f o r ~ a r d , ~ ' along with suggestions that L-dopa-induced psychosis and some forms of idiopathic psychosis could be related to a kindling phen~rnenon.'"~~' Bowman and Lewiss1compared the cerebral areas pathologically affected in 22 neurologic diseases which had at least one symptom in common with schizophrenia with 22 neurologic diseases with no symptoms in common. T h e basal ganglia showed an unusual degree of involvement in those diseases that shared symptoms with schizophrenia: they were affected in 9 of these 22 diseases compared with only 1 of the 22 with no shared symptoms.31 Histologic changes in the basal ganglia of patients with schizophrenia, especially with catatonic features, continued to be reported.'%bnormal movements, one of the hallmarks of basal ganglia disorder, were shown to be a prominent feature of schizophrenia unrelated to medication."' Explanations of psychiatric symptoms in terms of breakdown of basal ganglia function such as gating sensory input to affect motor behavior were sugg e ~ t e d .T" h ~ e previous name for schizophrenia, dementia praecox, was resurrecteds4 and the contri-
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SEMINARS I N NEUROLOGY
PSYCHIATRIC CONSEQUENCES OF BASAL GANGLIA DISEASE-ROGERS
the 1 9 4 0 s . l T ~ m m i n gadds s ~ ~ that a wide range of psychiatric disorders themselves have associated motor disorder, as was appreciated in the 1920s and has been shown in recent clinical and experimental s t ~ d i e s . ~ ~ , ~ ~ The fact that there is no distinct psychiatric disorder accompanying basal ganglia disease, but rather a wide spectrum of different psychiatric disorders, could be taken as evidence that there is no direct link between the basal ganglia and psychiatric disorder, as Brenner et a1 concluded in their initial r e p o r t . l V h e increasingly appreciated contribution of basal ganglia disorder to a wide variety of idiopathic psychiatric disorders, however, suggests a different interpretation. This is that the basal ganglia make a major contribution to different psychiatric disorders but with no one-to-one relationship between individual basal ganglia lesions and distinct psychiatric disorders. This was found to be the case for movement disorders a century ago. Now that we are in the neurotransmitter era with emphasis on neurotransmitter-based neuronal systems rather than topographically discrete anatomic systems, we can appreciate that disruption of discrete neurotransmitter systems in the basal ganglia is crucial for the appearance of different symptoms and syndromes and that pathologic insults to the basal ganglia may affect the various neurotransmitter systems indiscriminately. It is accepted that basal ganglia disorders are typically movement disorders, but disorder of movement is only one aspect of their symptomatology. They typically involve psychiatric and cognitive impairment as well, and one could argue that it is only for historical reasons that the movement disorder is given pride of place in the symptomatology. Cummings" rightly argues that these disorders should be seen as complex disorders of psychomotility in which the underlying neurophysiologic abnormality is manifested in the motor, cognitive, and emotional realms.
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bution of subcortical structures, including the basal ganglia, to dementia associated with extrapyramidal disorders became increasingly re~ognized.'~ Basal ganglia dysfunction also became implicated in other psychiatric illnesses, such as obsessive-compulsive disorder. Again, there were suggestions of this in the early literature." Recent studies using quantitative x-ray computed tomography," magnetic resonance imaging," and positron emission t o m ~ g r a ~ hhave ~ ~ shown " . ~ ~involvement of the basal ganglia, especially in their relationship to the frontal lobes, in patients with obsessive-compulsive disorder. Other studies have shown basal ganglia damage related to affective disorder,41as well as personality and behavior disorder.** Laplane and colleague^^^ have suggested, like their predecessors in the 1920s, that basal ganglia lesions can give rise to a clinical picture that is either purely motor, purely behavioral, or both, and that some aspects of severe depression, catatonic schizophrenia, and obsessive-compulsive disorder can be related to structural and physiologic disturbances in the systems linking the frontal associative cortex and the basal gang1ia.l" 'Ihe psychiatric accompaniments of known basal ganglia disorders are well described in Lishman's textbook.Tummings" has recently comprehensively reviewed the associated psychiatric disorder of nine extrapyramidal diseases with proven or presumed basal ganglia involvement-postencephalitic and idiopathic Parkinson's disease, Huntington's disease, Wilson's disease, idiopathic basal ganglia calcification, Tourette's syndrome, spinocerebellar degeneration, progressive supranuclear palsy, and Meige's syndrome. The associated psychiatric disorder .consists of depression, mania, obsessive-compulsive disorder, schizophrenia-like psychosis, and conduct disorder, or combinations of these. These psychiatric syndromes can form a prominent part of the clinical picture along with the neurologic deficits. They can be present in a substantial proportion of those affected by the different movement disorders. Certain psychiatric disorders may be particularly associated with certain diseases, such as depression with Parkinson's disease and obsessive-compulsive disorder with Tourette's syndrome, but there is no overall association of any particular psychiatric disorder with extrapyramidal disorder. Movement disorders are typically associated with a wide variety of different psychiatric disorders. The feature common to all the movement disorders is the interaction with environmental factors, stress typically aggravating the movement disorder and relaxation alleviating it. These findings are in complete agreement with the first study of this question by Brenner et a1 in
CONCLUSIONS Appreciation of the psychiatric implications of basal ganglia disease has been present for nearly a century now. T h e early evidence fbr this is buried in the literature. This is probably due to the separation of neurology and psychiatry at the beginning of the century. Review of the historical evidence leaves no doubt that the psychiatric consequences of basal ganglia disease are highly significant. There is no one characteristic psychiatric disorder associated with basal ganglia diseases. They are associated with a wide variety of psychi265
atric disorders, and basal ganglia disorder contributes to a wide spectrum of psychiatric diseases. The way forward is to consider basal ganglia diseases as psychomotility rather than movement disorders. Doing this effectively requires the rapprochement of neurology and psychiatry.
REFERENCES 1. Webster KE. Structure and function of the basal ganglia. Proc R Soc Med 1975;68:203-10 2. Lewy FH. Historical introduction. In: 'I'he diseases o f t h e basal ganglia. Baltimore: Williams & Wilkins, 1942: 1-20 3. Wilson SAK. Progressive lenticular degeneration. Brain 19 l2;34:295-509 4. Guiraud P. Conception neurologique d u syndrome catatonique. Encephale 1924; 19:57 1-9 5. Elliott TR. O n the action of adrenalin. J Physiol 1904; 3 1:20-2 6. Lishman WA. Organic psychiatry, 2nd ed. Oxfbrd: Blackwell, 1987 7. Charcot JM, Marie P. Hysteria. In: Tuke IIH, e d . Dictionary of psychological medicine, vol I. London: Churchill, 1892:639 8. von Economo C. Encephalitis lethargica (trans. by KO Newman). London,OUP, 193 1 9. Dide, Guiraud, Lafage. Syndrome parkinsonien clans la demence precoce. Rev Neurol 192 1;28:692-4 10. Haskovec L. Le psychisme sous-cortical. Rev Neurol 1925; 1:976-88 11. Reiter PJ. Extrapyramidal motor disturbances in dementia praecox. Acta Psychiatr Neurol 1926; 1 :287-305 12. Farran-Ridge C. Some symptoms reterable to the basal ganglia occurring in dementia praecox and epidemic encephalitis. J Ment Sci 1926;72:513-23 13. Steck f i . Les syndromes extrapyramidaux dans les maladies mentales. Arch Suisses d e Neurol Psychiatr 1926,1927; 19: 195-233;2O:Y2-136 14. Claude H , Baruk H , Thevenard A. Le syndrome rnoteur d e la demence precoce catatonique. Encephale 19'27; 22:74 1-67 15. Rleuler EP. T h e physiogenic and psychogenic in schimphrenia. Am J Psychiatry 1930;110:203-1 1 16. Rrenner C, Friedman APP, Merritt H H . Psychiatric syndromes in patients with organic brain disease 1.Diseases of the basal ganglia. Am J Psychiatry 1947; 103:733-7 17. Hopf A. Uber histopatholgische veranderungen in1 pallidurn und striaturr~bei schizophrenia. In: Proc First International Congress on Ncuropathology, vol 3. Turin: Rosenberg & Sellier, 1952:629-35 18. Stevens JR. T h e rreuropathology of schizophrenia. Psychol Med 1982; l2:695-700 19. Kleist K. Schi~ophreniasymptoms and cerebral pathology. J Ment Sci 1960; 106:246-55 20. Mettler FA. Perceptual capacity, functions of the corpus striatum and schizophrenia. Psychiatr Q 1955;29:89-I 11 21. Iverson S. Behaviour after neostriatal lesions in animals. In: Divac 1, Oberg E, eds. T h e neostriatum. Oxford: Pergamon, 1979: 195-2 10 22. Klawans HL, Goctz C, Westheimer R. Pathophysiology of schizophrenia and the striatum. Dis Nerv Sys 1972; 33:7ll-9
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23. Stevens J . An anatomy of'schizophrenia? Arch Gen I'sychiatry 1973;29: 177-89 24. Webster KE. Structure and function of the basal ganglia. Proc R Soc Med 1975;68:203-10 25. Yahr MD, ed. T h e basal ganglia. New York: Raven Press, 1976 26. Marsden CD. T h e enigma of the basal ganglia and movement. T I N S 1980;3:284-7 27. I d s k y T I , Weinhold PM, Levine FM. Implications of basal ganglionic dysfunction SVI- schizophrenia. Biol Psychiatry 1979;14:3-11 28. lverson SD. Striatal function and stereotyped behaviour. In: Cools et al, eds. Psychobiology of the striatum. North Holland: Elsevier, 1977:W-1 17 29. Moskovitz C, Moses H , Klawans HL. Levotlopa induced psychosis: a kindling phenomenon. Am J Psychiatry 1978; 1353669-75 30. Stevens J R , 1.ivermore A. Kindling of the mesolimbic dopamine system: anirnal model of' psychosis. Neurology (NY) 1978;28:36-46 3 1. Bowman M, Lewis MS. Sites of' subcortical damage in diseases which resemble schizophrenia. Ncuropsychology 1980; 18:597-601 32. Owens DGC, Johnstone EC, Frith CD. Spontaneous involuntary disorders of movement: their prevalence, severity and distribution in chronic schizophrenics with and without treatment with neuroleptits. Arch
10, NO. 5 SEPTEMBER 1990
Psychiatric Consequences of Basal Ganglia Disease
T h e first experimental work on the function of the basal ganglia was reported by Magendie in 1839.' He injected chromic acid into the basal ganglia of a rabbit and found that it kept running even if it could get no further because of an obstruction. Schiff in 1845 showed that destruction of the rabbit's basal ganglia produced immobility until a sensory stimulus produced the running movements.' This first experimental work, then, suggested that the basal ganglia have more than a simple role in motor function and make a contribution to complex behavior. This period and the next 80 years saw the first descriptions of basal ganglia lesions in pseudobulbar palsy (Bright, 1831), paralysis agitans or Parkinson's disease (Oppolzer, 1861), chorea (Broadbent, 1865), athetosis (Gowers, 1876), and pseudosclerosis or Wilson's disease (Westphal, 1883)' T h e significance of these lesions, however, remained unclear, since postmortem examination of other patients with these conditions showed no gross disorder of the basal ganglia and gross lesions could be found in the basal ganglia of people who had shown no. evidence of motor disorder. T h e term "basal ganglia" was introduced by Ringer in 1879 to describe the putamen and globus pallidus. It gradually came into general use, but there was no agreement on the exact composition of these ganglia, which for different authors encompassed a number of adjacent structures, including caudate nucleus, thalamus, habenular ganglion and the subthalamic nucleus of Luys. T h e caudate nucleus and putamen together were also known as the striatum and the caudate nucleus, putamen, and globus pallidus as the corpus striatum. L e ~ ywho , ~ gave an account of this early work u p to 1940, declared that 1912, when Wilson first described his disease,%as the time when the "gestalt" of the basal ganglia-that is, their function
and the consequences of their dysfunction-suddenly became apparent. This gestalt, however, was a neurologic gestalt. Psychiatry was completely left out of the picture. For example, in his otherwise detailed historical account, Lewy makes no mention of contemporary pathologic findings in the basal ganglia of patients with catatonic schizophrenia, such as those of Lehmann in 1898."'The proceedings of the 1940 meeting of the Association for Research in Nervous and Mental Diseases (AKNMD) devoted to diseases of the basal ganglia, in which Lewy's historical account appears, makes not a single mention of psychiatry, ignoring completely the work reviewed in the next few paragraphs. This was because by 1912 neurology and psychiatry were parting intellectual company and by 1940 the rupture was complete. Wilson's article in Brain in 1912 on progressive lenticular disease, subsequently called Wilson's disease, certainly broke new ground in many w a y s . H e described what is still one of the few completely treatable neurologic diseases. He introduced a new concept-extrapyramidal motor disorder-and suggested that paralysis agitans, which was only just being accepted as an organic diseasc of the nervous system, was an extrapyramidal disorder. He suggested that gross anatomic lesions were not necessary to produce extrapyramidal disorder, but that dynamic modification of function was enough. This was only 8 years after the first suggestion of neurotransmitters." Significantly, in the present context, 8 ol'the 12 patients he described in his article had prominent psychiatric symptoms, with previous diagnoses such as hysteria and schizophrenia." until the beginning of this century, the cerebral cortex was believed to be "the seat of all psychical operation^,^ but the first half of this century saw a gradual appreciation that subcortical structures and systems could contribute to psychiatric
Consultant Neuropsychiatrist, Burden Neurological Hospital, Stoke Lane, Stapleton, Hristol, United Kingdom Reprint requests: Dr. Rogers, Burden Neurological Hospital, Stoke Lane, Stapleton, Bristol, UK Copyright 1990 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, N Y 10016. Ail rights reserved.
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Daniel Rogers, M.R.C.P., M .R . C. Psych
disorder. A few years after Wilson's article, epidemic encephalitis swept across Europe and produced among its sufferers every known psychiatric s y n d r ~ m e The . ~ encephalitis mainly affected subcortical brain structures, including the basal ganglia, and this suggested a link between these structures and psychiatric disorder. This possibility was explored by psychiatrists who had not been completely taken over by the psychodynamic revolution that had swept through psychiatry. In 192 1, Dide and colleagues%uggested that a parkinsonian syndrome formed part of the catatonic form of schizophrenia. Unlike Parkinson's disease, there was no rest tremor and it was reversible. They suggested that it must be due to disorder of the basal ganglia and adjacent subcortical areas. They had found in postmortem study of schizophrenic patients that subcortical lesions, including basal ganglia lesions, were more common and extensive than cortical lesions. G ~ i r a u done ,~ of these authors, believed that catatonia was being explained in psychologic terms, since it was often associated with prominent psychiatric disorder. Viewed neurologically, however, it showed all the classic manifestations of basal ganglia disorder. He suggested that catatonia should be regarded as an extrapyramidal disorder, along with Wilson's disease, chorea, athetosis, and parkinsonism. All these conditions could be associated with psychiatric disorder, although the association was most prominent with catatonia. Other European authors such as Haskovec," who coined the term "akathisia" at the beginning of the century, insisted on a subcortical basis for psychiatric disorder. Reiter," again describing extrapyramidal motoy disturbances in schizophrenia, lamented the development of neurology and psychiatry along separate lines. He supported the view that the extrapyramidal system, and more specifically the basal ganglia, produced both neurologic and psychiatric disorder and suggested that the pathologic basis for such disorder might be more chemical than morphologic. Farran-Ridge12 described various symptoms of schizophrenia, such as strong upward deviation of the eyeballs, fluttering of the eyelids, chewing movements of the mouth, greasiness of the skin, respiratory disorders, and choreiform movements, which he argued pointed directly to lesions or functional disturbance of the basal ganglia. Steckl%uggested that extrapyramidal motor disorder formed part of a large proportion of psychiatric illnesses, such as schizophrenia (forming the catatonic syndrome), affective disorder (contributing to psychomotor retardation), and hysteria. Disturbance of an identical cerebral system involving the brainstem, basal ganglia, and frontal
lobes explained why analogous symptoms appeared in conditions of very different etiology. Other authors supported involvement of the basal ganglia in catatonic schizophrenia.I4 This had to be a functional disorder of the basal ganglia to explain the variability and reversibility of the symptoms and the lack of significant anatomic alterations in the basal ganglia. Even Bleuler, who had coined the term "schizophrenia" to replace dementia praecox and was the champion of Freudian interpretation of its symptomatology, accepted that certain of the motor symptoms of schizophrenia were also found in basal ganglia diseases.15Interest in this area, however, subsequently diminished as the encephalitis epidemic disappeared and the psychologic explanatory paradigm of psychiatric disorder which had hijacked psychiatry remained predominant. Some interest, however, persisted. T h e first attempt to look specifically at the psychiatric disorder accompanying known basal ganglia diseases was by Brenner and colleagues in 1947." They described 17 patients with Wilson's disease, Huntington's chorea, dystonia musculorum deformans, and double athetosis. The patients had a variety of psychiatric disorders, including affective disturbance and psychotic symptoms as well as cognitive disorder, but there was no characteristic psychiatric disorder accompanying these basal ganglia diseases. In fact, the characteristic feature of the psychiatric accompaniments to these diseases was their variability. 'This suggested that psychiatric disorder must be the result of disorder of other brain regions. What was fairly consistent for most of the patients was the effect of their psychic state on their abnormal movements. The movements were typically more prominent with emotional excitement and less prominent with distraction. The authors pointed out that this feature had, until then, been seen as a hallmark of psychiatric conditions, such as hysteria, but that it should be accepted as the hallmark of basal ganglia disorder. A corollary was that psychotherapy could play a palliative role even in progressive disease of the central nervous system. The First International Congress of Neuropathology in Rome in 1952 devoted a whole section to the histopathology of schizophrenia. Hopf" and other European investigators maintained, just as Lehmann and others at the turn of the century had done, that catatonic schizophrenia was associated with pathologic changes in the basal ganglia. Neuropathologists from Great Britain and the United States, however, remained sceptical.I8 Kleist, a European author, who had consistently insisted on a cerebral basis for schizophrenia throughout the heyday of psychodynamic ascend-
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PSYCHIATRIC CONSEQUENCES OF BASAL GANGLIA DISEASE-ROGERS
263
ancy, continued to maintain that motor features of schizophrenia were analogous to the motor disorders of basal ganglia diseases.lg Mettler, in the United States, was rather exceptional at this time in suggesting that the schizophrenic syndrome was basically a perceptual disorder caused by dysfunction of the basal ganglia, which produced secondary cortical d y ~ f u n c t i o nHe . ~ ~was ahead of his time in attributing more than a purely motor function to the basal ganglia, but the neurotransmitter revolution was still around the corner and when it came to a possible mechanism to explain the characteristic variability and reversibility of psychiatric symptoms and their relationship with emotional triggers, he could only suggest vasospasm in the basal ganglia. T h e 1960s saw major advances in the understanding of the anatomy and neurochemistry of the basal ganglia. Anatomic studies showed a highly organized neuronal projection to the basal ganglia from all areas of cortex." Projection from neocortex suggested a cognitive input to motor function, and projection from limbic cortex, an affective input. T h e basal ganglia were shown to contain by far the highest concentration of dopamine in the brain. Ascending projection systems from brainstem to basal ganglia were shown to have dopamine as their major neurotransmitter. These projection systems consisted of the nigrostriatal tract and the mesolimbic system. The mesolimbic system projected to the anterior extremity of the basal ganglia or limbic striatum, consisting of nucleus accumbens, olfactory tubercle, and nucleus of the stria terminalis. These were then added to the constituents of the basal ganglia. It was these structures that received inputs from the limbic cortex, amygdala, and hippocampus. These advances in basic neuroscience coincided with renewed interest in the cerebral basis for psychiatric disorder and produced renewed suggestions of a prominent role for basal ganglia dysfunction in psychiatric disorder. In 1972, Klawans and colleagues suggested that the dopaminergic system in the basal ganglia could be a final common pathway for the schizophrenic syndrome and that there should be a relationship between this syndrome and known basal ganglia disorder involving dopaminergic mechanisms." Stevens25n 1973 suggested that schizophrenia could represent dysfunction of the mesolimbic dopamine projection system in a manner similar to dysfunction of the nigrostriatal dopamine system in known basal ganglia disorders such as Parkinson's disease. In 1975, WebsterZ4,at a meeting of the psychiatry section of the Royal Society of Medicine devoted to the basal ganglia, suggested that distinguishing 264
VOLUME 10. NUMBER 3 SEPTEMBER 1990
motor activity and behavior was more a reflection of the particular interests of different investigators than a meaningful separation of categories in cerebral terms. In 1976, the ARNMD held the second meeting that it devoted exclusively to the basal ganglia.25Teuber, in his contribution, suggested that more advances had been made in understanding the function of the basal ganglia since the first ARNMD meeting on the basal ganglia in 1940 than in any other field in neurology. These advances, he said, had encouraged a much broader definition of the term "motor"; he also stated that basal ganglia function included complex perceptual and cognitive aspects of behavior. There was, however, only one contribution, by Bowen, on behavioral alterations in patients with basal ganglia lesions, and that was confined to Parkinson's disease. T h e psychiatric consequences of basal ganglia disease rated only three paragraphs of discussion in the whole proceedings, although this, of course, was more than in the 1940 meeting. Many neurologists who accepted a role for the basal ganglia in complex behavior did not extend this new thinking to psychiatric disorder. The traditional view of the basal ganglia as being concerned with motor function and cerebral cortex with cognitive function continued to be maintained.26 There was, however, renewed interest in the possibility of basal ganglia dysfunction in schizophrenia." T h e concept of Parkinson's disease and schizophrenia as contrasting conditions in terms of their dopamine dysfunction was put f o r ~ a r d , ~ ' along with suggestions that L-dopa-induced psychosis and some forms of idiopathic psychosis could be related to a kindling phen~rnenon.'"~~' Bowman and Lewiss1compared the cerebral areas pathologically affected in 22 neurologic diseases which had at least one symptom in common with schizophrenia with 22 neurologic diseases with no symptoms in common. T h e basal ganglia showed an unusual degree of involvement in those diseases that shared symptoms with schizophrenia: they were affected in 9 of these 22 diseases compared with only 1 of the 22 with no shared symptoms.31 Histologic changes in the basal ganglia of patients with schizophrenia, especially with catatonic features, continued to be reported.'%bnormal movements, one of the hallmarks of basal ganglia disorder, were shown to be a prominent feature of schizophrenia unrelated to medication."' Explanations of psychiatric symptoms in terms of breakdown of basal ganglia function such as gating sensory input to affect motor behavior were sugg e ~ t e d .T" h ~ e previous name for schizophrenia, dementia praecox, was resurrecteds4 and the contri-
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SEMINARS I N NEUROLOGY
PSYCHIATRIC CONSEQUENCES OF BASAL GANGLIA DISEASE-ROGERS
the 1 9 4 0 s . l T ~ m m i n gadds s ~ ~ that a wide range of psychiatric disorders themselves have associated motor disorder, as was appreciated in the 1920s and has been shown in recent clinical and experimental s t ~ d i e s . ~ ~ , ~ ~ The fact that there is no distinct psychiatric disorder accompanying basal ganglia disease, but rather a wide spectrum of different psychiatric disorders, could be taken as evidence that there is no direct link between the basal ganglia and psychiatric disorder, as Brenner et a1 concluded in their initial r e p o r t . l V h e increasingly appreciated contribution of basal ganglia disorder to a wide variety of idiopathic psychiatric disorders, however, suggests a different interpretation. This is that the basal ganglia make a major contribution to different psychiatric disorders but with no one-to-one relationship between individual basal ganglia lesions and distinct psychiatric disorders. This was found to be the case for movement disorders a century ago. Now that we are in the neurotransmitter era with emphasis on neurotransmitter-based neuronal systems rather than topographically discrete anatomic systems, we can appreciate that disruption of discrete neurotransmitter systems in the basal ganglia is crucial for the appearance of different symptoms and syndromes and that pathologic insults to the basal ganglia may affect the various neurotransmitter systems indiscriminately. It is accepted that basal ganglia disorders are typically movement disorders, but disorder of movement is only one aspect of their symptomatology. They typically involve psychiatric and cognitive impairment as well, and one could argue that it is only for historical reasons that the movement disorder is given pride of place in the symptomatology. Cummings" rightly argues that these disorders should be seen as complex disorders of psychomotility in which the underlying neurophysiologic abnormality is manifested in the motor, cognitive, and emotional realms.
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bution of subcortical structures, including the basal ganglia, to dementia associated with extrapyramidal disorders became increasingly re~ognized.'~ Basal ganglia dysfunction also became implicated in other psychiatric illnesses, such as obsessive-compulsive disorder. Again, there were suggestions of this in the early literature." Recent studies using quantitative x-ray computed tomography," magnetic resonance imaging," and positron emission t o m ~ g r a ~ hhave ~ ~ shown " . ~ ~involvement of the basal ganglia, especially in their relationship to the frontal lobes, in patients with obsessive-compulsive disorder. Other studies have shown basal ganglia damage related to affective disorder,41as well as personality and behavior disorder.** Laplane and colleague^^^ have suggested, like their predecessors in the 1920s, that basal ganglia lesions can give rise to a clinical picture that is either purely motor, purely behavioral, or both, and that some aspects of severe depression, catatonic schizophrenia, and obsessive-compulsive disorder can be related to structural and physiologic disturbances in the systems linking the frontal associative cortex and the basal gang1ia.l" 'Ihe psychiatric accompaniments of known basal ganglia disorders are well described in Lishman's textbook.Tummings" has recently comprehensively reviewed the associated psychiatric disorder of nine extrapyramidal diseases with proven or presumed basal ganglia involvement-postencephalitic and idiopathic Parkinson's disease, Huntington's disease, Wilson's disease, idiopathic basal ganglia calcification, Tourette's syndrome, spinocerebellar degeneration, progressive supranuclear palsy, and Meige's syndrome. The associated psychiatric disorder .consists of depression, mania, obsessive-compulsive disorder, schizophrenia-like psychosis, and conduct disorder, or combinations of these. These psychiatric syndromes can form a prominent part of the clinical picture along with the neurologic deficits. They can be present in a substantial proportion of those affected by the different movement disorders. Certain psychiatric disorders may be particularly associated with certain diseases, such as depression with Parkinson's disease and obsessive-compulsive disorder with Tourette's syndrome, but there is no overall association of any particular psychiatric disorder with extrapyramidal disorder. Movement disorders are typically associated with a wide variety of different psychiatric disorders. The feature common to all the movement disorders is the interaction with environmental factors, stress typically aggravating the movement disorder and relaxation alleviating it. These findings are in complete agreement with the first study of this question by Brenner et a1 in
CONCLUSIONS Appreciation of the psychiatric implications of basal ganglia disease has been present for nearly a century now. T h e early evidence fbr this is buried in the literature. This is probably due to the separation of neurology and psychiatry at the beginning of the century. Review of the historical evidence leaves no doubt that the psychiatric consequences of basal ganglia disease are highly significant. There is no one characteristic psychiatric disorder associated with basal ganglia diseases. They are associated with a wide variety of psychi265
atric disorders, and basal ganglia disorder contributes to a wide spectrum of psychiatric diseases. The way forward is to consider basal ganglia diseases as psychomotility rather than movement disorders. Doing this effectively requires the rapprochement of neurology and psychiatry.
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23. Stevens J . An anatomy of'schizophrenia? Arch Gen I'sychiatry 1973;29: 177-89 24. Webster KE. Structure and function of the basal ganglia. Proc R Soc Med 1975;68:203-10 25. Yahr MD, ed. T h e basal ganglia. New York: Raven Press, 1976 26. Marsden CD. T h e enigma of the basal ganglia and movement. T I N S 1980;3:284-7 27. I d s k y T I , Weinhold PM, Levine FM. Implications of basal ganglionic dysfunction SVI- schizophrenia. Biol Psychiatry 1979;14:3-11 28. lverson SD. Striatal function and stereotyped behaviour. In: Cools et al, eds. Psychobiology of the striatum. North Holland: Elsevier, 1977:W-1 17 29. Moskovitz C, Moses H , Klawans HL. Levotlopa induced psychosis: a kindling phenomenon. Am J Psychiatry 1978; 1353669-75 30. Stevens J R , 1.ivermore A. Kindling of the mesolimbic dopamine system: anirnal model of' psychosis. Neurology (NY) 1978;28:36-46 3 1. Bowman M, Lewis MS. Sites of' subcortical damage in diseases which resemble schizophrenia. Ncuropsychology 1980; 18:597-601 32. Owens DGC, Johnstone EC, Frith CD. Spontaneous involuntary disorders of movement: their prevalence, severity and distribution in chronic schizophrenics with and without treatment with neuroleptits. Arch
