VOL. 11, NO. 2,1985 Akinesia, Tardive 255 Dysmentia, and Disorder in Schizophrenia

by Elkhonon Goldberg Abstract with initiating usual activities"

(Rifkin, Quitkin, and Klein 1975, Downloaded from Two iatrogenic effects of antipsy- p. 672). "Less extreme instances may chotic medications other than tardive be seen only as diminished social dyskinesia have been recently activity or interest in work" (Rifkin described in schizophrenic popula- et al. 1978, p. 488). The authors tions: akinesia and tardive indicate that manifestations of dysmentia. These effects involve akinesia are different from those of http://schizophreniabulletin.oxfordjournals.org/ activational, cognitive, and affective . rather than motor changes, and The second report (Wilson et al. closely resemble two most common 1983) introduced the phenomenon of prefrontal syndromes: dorsolateral "tardive dysmentia." The authors and fronto-orbital/mediobasal. It is point out that the phenomenon possible that the widely reported involves "changes in affect, activa- "frontal lobe dysfunction" in some tional level, and interpersonal inter- chronic schizophrenic patients at action" and resembles hypomania. least in part reflects iatrogenic They describe it as follows: changes in the mesolimbic/mesocor- tical dopamine system, which The patients tended to be projects extensively into prefrontal loquacious and to speak in loud voices. They showed thought areas. The degree of iatrogenic versus disconnection and were generally genuine contribution to the frontal circumstantial and aimless in at Pennsylvania State University on April 24, 2014 lobe dysfunction in schizophrenia conversation. Disassociated, needs to be ascertained further, and inappropriate statements were the heterogeneity of known frontal common. The prevailing mood was generally one of euphoria, but lobe syndromes must be taken into unheralded, inexplicable, explosive account in describing schizophrenic changes in affect occurred as good populations. The mechanisms of humor changed rapidly to noniatrogenic contributions to the explosive hostility or sullen petulance. Social withdrawal and frontal lobe dysfunction in schizo- autistic preoccupation were phrenia may reflect a variety of punctuated by episodes of overre- anatomical sources and require active behavior when the subject further examination. talked loudly, often close to the observer's face, and was quite intrusive and invasive of the privacy of others, [p. 188] Tardive dyskinesia has long been recognized as an iatrogenic effect of Although the two described antipsychotic drugs. Recently, two phenomena are quite different, in fact types of iatrogenic neuroleptic- opposite in certain respects (the first induced effects of an activational, characterized by predominant aspon- cognitive, and affective rather than taneity, the second by predominant motor nature have been described in behavioral disinhibition), and their schizophrenic patients. clinical descriptions are scant, they The first set of reports (Rifkin, are conspicuously similar to the two Quitkin, and Klein 1975; Rifkin et al. most commonly specified syndromes 1978) introduced the phenomenon of "akinesia" and described it as "a Reprint requests should be sent to Dr. behavioral state of diminished E. Goldberg, Department of , spontaneity characterized by few Albert Einstein College of and gestures, unspontaneous speech, and, Montefiore Medical Center, 111 E. 210th particularly, apathy and difficulty St., Bronx, NY 10467. 256 SCHIZOPHRENIA BULLETIN

that follow focal damage to the inappropriate use of pretentious lobe lesions may be described prefrontal areas of the and are language. Erotic behavior, sexual as: (1) toward apathy and indif- Downloaded from exhibitionism, or lewd remarks are ference ("pseudodepressed"), and frequently observed in neurological not rare. Euphoric excitation may (2) toward puerility and euphoria and neurosurgical clinics. take on an atypical hypomanic ("pseudopsychopathic"). . . . The clinical and neuroanatomical aspect, "moria": the patient Patients who suffer the "pseudo- heterogeneity of "frontal" syndromes overexcited, manifesting erotic depressed" type of frontal lobe has been pointed out by numerous behavior, bothers the examiner personality alteration appear to with inappropriate jokes and have lost all initiative. They http://schizophreniabulletin.oxfordjournals.org/ authors (Kleist 1934; Blumer and caustic or facetious remarks respond in an automaton-like Benson 1975; Hecaen and Albert (Witzelsucht). fashion . . . slowness, indifference 1978; Damasio 1979; Luria 1980). The diverse aspects of excitation and apathy . . . characterize the Hecaen and Albert (1978) provide and euphoria are rarely perma- personality alteration produced by nent. In general, they appear prefrontal convexity lesions, the these descriptions of the two main episodically, superimposed on an condition we term "pseudo- ones: underlying background of abulia depressed." and apathy. The euphoric periods . . . The "pseudopsychopathic" Lack of initiative or spontaneity is may alternate with periods of type of frontal lobe personality is a characteristic feature of frontal apparent depression. True best characterized by the lack of lobe . This is linked to a depression, however, is rarely adult tact and restraints. Such general diminution of motor seen; rather, a picture of asthenia patients may be coarse, irritable, activity. The patient no longer and akinesia imitates a true facetious, hyperkinetic or promis- voluntarily carries out the depression. A disorder of activity, cuous; they often lack social graces necessary daily activities of life, rather than of affectivity, is the and may, on impulse, commit anti- such as getting out of bed in the hallmark. social acts. Paranoid or grandiose morning, washing or dressing Loss of impulse control, thinking may be present. While at Pennsylvania State University on April 24, 2014 himself, feeding himself, or even manifested by outbursts of they may flare with anger, they do urinating or defecating in the irritability, is common. These not bear a grudge. Outwardly, at toilet. . . . The actual ability to do outbursts may be the first least, their behavior resembles that the various activities of daily living behavioral change noted; often of the sociopathic personality . . . is not impaired — the patient is not they reach such a degree of the "pseudopsychopathic" paralyzed, apraxic, or confused. violence that they force a family to personality traits apparently When he is vigorously urged to do institutionalize the patient, follow to the orbital something, he can do it. What is [pp. 367-368] frontal lobe or pathways traversing impaired is the ability to initiate this region, [pp. 157-158] spontaneously a desired or an automatic motor task. Various authors (Kleist 1934; Blumer and Benson 1975; Damasio Blumer and Benson (1975) attribute This rupture between the patient the early descriptions of the two and the external world, this 1979; Luria 1980) attempted to diminution of activity in manipu- specify critical lesion loci within the syndromes to Kleist (1934): lating real objects, and this frontal lobes differentially responsible [Kleist] confirmed Welt's thesis reduction of interpersonal for the two aforedescribed of the significance of lesions to the exchange are what appear to be a orbital brain, and related changes loss of interest on the part of the syndromes. According to these authors, the toward immoral, unfaithful, patient. Whether there is a true deceitful, thievish, and defiant loss of interest or an apparent loss first one, consisting of affective behavior to orbital lesions. Kleist of interest due to an impairment of flatness and reduced motor and also noted puerile and facetious spontaneous initiation of activity, behavior in patients with orbital the effect on the examination cognitive activity, follows lesions of the dorsolateral prefrontal convexity; lesions. Euphoria was observed as remains the same. [p. 368] a frequent early mental change in the second one, associated with patients with frontal-orbital Frequently one sees an apparent behavioral disinhibition, loosened ; the euphoria was usually heightening of affective tone, with social controls and judgment, and transient and at times changed to a euphoria and lack of concern for wide oscillations of affect with dysphoric mood. Kleist presumed the present or the future. This predominant euphoria, follows that the unity of personality and man's self-determination were behavioral change does not, lesions of the fronto-orbital/medio- however, necessarily reflect a true related to the orbital brain and its alteration of mood. Such patients, basal surfaces. connections. In contrast, lesions of in the midst of apparent euphoria, Blumer and Benson (1975) suggest: the upper portions of the frontal often state that they are not at all lobes (convexity) were associated happy. A puerile or silly attitude The two types of personality with lack of psychic and motor may be maintained, often with an changes occurring after frontal initiative. Lack of thought VOL. 11, NO. 2,1985 257

formation (impoverished and effectively "simulate" a syndrome greater extent than that of nigro- stereotyped modes of thinking) typically associated with a structural striatal A9 DA neurons, and Downloaded from characterized these patients, [p. 153] lesion in prefrontal areas, both in identified a class of "atypical" neuro- animals (Tassin et al. 1978; Simon, leptics that selectively affect the A10 Thus, there is a high degree of Scatten, and LeMoal 1980; Oades dopamine neurons but not A9 consensus in the neurological and 1982) and in humans (Goldberg et al. dopamine neurons. In an extensive neuropsychological literature 1982). Behavioral effects of inter- review, Joyce (1983) also argues that regarding the existence, clinical ference with the mesolimbic/ the atypical antipsychotics have both http://schizophreniabulletin.oxfordjournals.org/ features, and underlying neuro- mesocortical dopamine projections, a greater affinity to and activity in anatomy of two major frontal in other words, closely resemble the the mesolimbic/mesocortical system syndromes. The first (dorsolateral effects of lesions in the target areas than in the nigrostriatal system. convexital) bears a remarkable of these projections. Brozoski et al. Thus, at least theoretically, cases clinical similarity to the iatrogenic (1979) demonstrated that the may exist in which iatrogenic akinesia described by Rifkin and his behavioral effects of dopamine "mesolimbic/mesocortical" effects of associates (Rifkin, Quitkin, and Klein depletion in a circumscribed area of antipsychotic drugs are more 1975; Rifkin et al. 1978), and the dorsolateral prefrontal convexity pronounced than or totally unac- second one (orbitofrontal) is as were quite similar to those of companied by "nigrostriatal" effects. remarkably similar in its clinical surgical ablation of the same area in Indeed, whereas Wilson et al. (1983) features to the tardive dysmentia rhesus monkeys. observed a positive relationship described by Wilson et al. (1983). It would therefore be almost between the severity of tardive This similarity between known predictable on a priori grounds that dyskinesia and the features of tardive at Pennsylvania State University on April 24, 2014 neurological syndromes and the if neuroleptic-induced effects can dysmentia, in some of the patients iatrogenic effects of antipsychotic occur in the mesolimbic/mesocortical described by Rifkin and his associates medications can be approached in system, these effects would have (Rifkin, Quitkin, and Klein 1975; light of the pathway distribution of essential features of a "frontal Rifkin et al. 1978) "akinesia" the mesolimbic/mesocortical syndrome." developed without tardive dopamine system. The possibility that iatrogenic dyskinesia. Whereas the nigrostriatal effects of neuroleptics can develop The observations by Rifkin et al. dopamine system projects predomi- outside of the traditionally (1978) and Wilson et al. (1983) are nantly into the basal ganglia, the considered nigrostriatal system, clearly preliminary and the reported mesolimbic/mesocortical dopamine notably in the mesolimbic/mesocor- phenomena require further study. system projects substantially into the tical system, has been raised by Whereas the existence of akinesia has basal forebrain and the prefrontal several investigators (Wilson et al. been demonstrated in several double- cortex. Both orbitofrontal/mesio- 1983). White and Wang (1983) blind studies, the empirical basis for frontal and dorsolateral cortices demonstrated that prolonged accepting the existence of tardive receive dopamine projections, the treatment with antipsychotic drugs dysmentia is less compelling, since former being more abundant decreases the number of sponta- the original study reporting it was (Bannon and Roth 1983; Brown, neously active neurons both in conducted under open, nonblind Crane, and Goldman 1979). In these substantia nigra and in the ventral conditions. Even if one assumes the prefrontal regions higher concentra- tegmental area. The latter, of course, existence of these syndromes, it is tions of dopamine are found than in is the point of origin of the not clear whether they can be any other cortical area, both in abso- mesolimbic/mesocortical dopamine accounted for solely by exposure to lute terms and relative to other system with abundant projections neuroleptics or, as Mukherjee (1984) transmitter systems (Lindvall et al. into the and the proposed with respect to tardive 1974; MacBrown and Goldman 1977; basal forebrain (Simon et al. 1976; dysmentia, exposure to neuroleptics Brown, Crane, and Goldman 1979). Cooper, Bloom, and Roth 1978; has to be combined with certain Furthermore, it has been demon- Simon et al. 1979). White and Wang preexisting cerebral dysfunctions. strated that destruction of the ventral (1983) further demonstrated that the Furthermore, available clinical tegmental area, which is the point of decline of spontaneous activity of descriptions of akinesia and tardive origin of the mesolimbic/mesocor- mesolimbic/mesocortical A10 DA dysmentia are too scant to enable tical dopamine system, can neurons occurs faster and to a their definitive comparison with 258 SCHIZOPHRENIA BULLETIN

known neurological syndromes. the neuroleptic-induced effects frequently reveal patterns of selective

However, should their existence be described by Rifkin et al. and Wilson "hypofrontality" in schizophrenic Downloaded from confirmed, and in particular should et al., on the one hand, and the well- patients, assessments of structure, their similarity to the known frontal known frontal syndromes,.on the e.g., pneumoencephalography, syndromes be born out, these other hand, directly raises the computed tomography (CT), by and phenomena will be extremely question as to the origins of such large do not. Although many studies important for two reasons. "frontal features" in schizophrenic revealed diffuse changes (Johnstone et http://schizophreniabulletin.oxfordjournals.org/ The first reason is clinical. To the populations. Although in the study al. 1978; Weinberger et al. 1979a, extent that there are iatrogenic effects by Rifkin, Quitkin, and Klein (1975), 1979b), these changes were not of antipsychotic drugs other than signs of akinesia were shortlived and characterized by frontal prepon- extrapyramidal in nature, they have disappeared rapidly following the derance. Among numerous CT to be recognized and taken into changes of of medicational schedule, studies of schizophrenic patients, account. Because the effects observed this in itself is no guarantee that only one revealed selective prefrontal by Rifkin et al. and Wilson et al. other more subtle iatrogenic effects hypodensity to the best of my involve higher order activational, (other than tardive dyskinesia) are as knowledge (Golden et al. 1981). cognitive, and affective changes easily reversible. In most if not all Several post-mortem studies rather than motor changes, their studies, samples in which frontal revealed microscopic changes in identification may be more difficult pathology was revealed consisted of prefrontal cortex of schizophrenics and more confounded by the features chronic, institutionalized patients (Tatetsu 1964; Miyakawa et al. of the original disease than is the with long histories of treatment with 1972). These changes, however, are

identification of tardive dyskinesia. antipsychotic medications. In these no more extensive than those in at Pennsylvania State University on April 24, 2014 The second reason is more populations it is extremely difficult to various other structures, which theoretical in nature and is related to distinguish between features of the include hippocampi, nucleus our understanding of the schizo- underlying disease and persistent accumbens, vast areas of phrenic disorder. Recently, numerous iatrogenic features, providing that diencephalon and brainstem, attempts have been made to describe such exist; and even taking the cerebellar vermis, and nonspecific schizophrenic populations both in patients off medications for a limited cortical changes (Weinberger, terms of brain region-specific deficits period of time before the study may Wagner, and Wyatt 1983). and the neuroanatomy of involve- not be enough to disentangle the two One has to conclude that existing ment (Seidman 1983). Among factors. Just as a persistent nigro- neuropathological studies do not various formulations that emerged striatal iatrogenic syndrome in the provide sufficient basis for identi- from these attempts, the claims of form of tardive dyskinesia is possible fying prefrontal areas as the the "frontal involvement" in schizo- (Jeste et al. 1979; Smith and Baldes- outstanding locus of deficit in schizo- phrenia are probably most promi- sarini 1980; Jeste and Wyatt 1982; phrenic patients. nent. Findings that led to these claims Kane and Smith 1982), so is a Wilson et al. (1983) discuss the are based on various techniques: persistent mesolimbk/mesocortical issue of the changing phenomenology (1) neuropsychological studies iatrogenic syndrome which will of the schizophrenic disorder over the that reveal pronounced cognitive predictably include frontal signs. past several decades and the possible deficit consistent with frontal damage Among possible manifestations of role of the advent and use of antipsy- (Flor-Henry 1976; Flor-Henry and frontal pathology in schizophrenia, chotic drugs in this change. Unfortu- Yeudall 1979; Kolb and Whishaw those related to function can be nately, most neuropsychological, 1983); (2) metabolic studies using accounted for either by genuine or by cognitive, and regional neuroana- positron emission tomography (PET) iatrogenic mechanisms. On the other tomical studies of schizophrenia are (Farkas et al. 1980; Buchsbaum et al. hand, macroscopic structural changes relatively recent. We therefore cannot 1982); (3) blood flow studies (Ingvar in the frontal lobes could be less reliably judge whether the "frontal" 1976; Mathew et al. 1981); and (4) readily accounted for by iatrogenic signs in schizophrenia of the kind electrophysiological studies (Heath mechanisms. It is of interest in reported in these studies predated the 1977; Stevens 1977; Morihisa, Duffy, this respect that whereas various advent of neuroleptics or whether and Wyatt 1983) which reveal frontal assessments of function (neuro- they emerged together with the latter. Early descriptions of avolition and dysfunction. psychological, cognitive, electro- apathy in schizophrenic patients The remarkable similarity between physiological, PET scan, blood flow) VOL. 11, NO. 2,1985 259

(Kraepelin 1919; Bleuler 1950), in reticular nuclei, thus serving as a This implies that frontal lobe

fact, resemble certain features of the unique point of convergence of disease can be "simulated" by a Downloaded from dorsolateral frontal syndrome. various influences within the brain broad range of conditions at least in Several colleagues with longer careers (Nauta 1971; Carpenter 1976). some respects. The above concerns than mine in the field pointed out Because of this complexity, Nauta apply to most brain structures, but that, in retrospect, they are quite (1971) suggested that inferring particularly to prefrontal cortex. certain that they had observed function from anatomy is more

According to Nauta (1971), a http://schizophreniabulletin.oxfordjournals.org/ frontal phenomenology in schizo- difficult with respect to the frontal unique feature of the frontal cortex is phrenic patients before the advent of lobe than other systems. It may be in its "reciprocal relationship neuroleptics. It is likely that the equally difficult to infer the anatomy with ... (1) parietal and temporal mechanisms of frontal phenomen- of a deficit from its functional regions of involved in ology in schizophrenic patients are manifestations (metabolic, electro- the processing of visual, auditory complex and may include both physiological, or cognitive) when the and somatic sensory information, genuine and iatrogenic components. frontal lobe is involved. and (2) the telencephalic limbic Two types of possible genuine Frontal lobes are associated with system and its subcortical corre- mechanisms of frontal dysfunction in the highest, phylogenetically and spondents ..." (p. 181). This makes schizophrenia can be hypothe- ontogenetically youngest levels of the frontal cortex a "mediator of sized: those which entail an actual cognitive control (Luria 1980). On information exchange between the lesion in prefrontal areas (macro- the other hand, a diffuse central cerebral cortex and the limbic scopic structural, microscopic, or nervous system (CNS) disease is system" (p. 184) by virtue of its

biochemical), and those, paradox- likely to affect such levels first and being "one and perhaps the only at Pennsylvania State University on April 24, 2014 ically, which do not. foremost. It is possible, therefore, realm of neocortex where neural The extent to which abnormalities that a rather global cognitive pathways representing the internal of the dopamine system may play a dysfunction implicit in schizophrenia milieu converge with conduction significant role in schizophrenia is likely to mimic a frontal lobe systems representing the external (Horn and Snyder 1971; Stevens dysfunction more readily than any environment as reported by all 1973; Snyder 1976) would in itself other area-specific kind of cognitive exteroceptive modalities" (pp. imply an intimate frontal dysfunction. It may not be necessary, 182-183). Prefrontal cortex appears, involvement due to the distribution in other words, to postulate a therefore, to be central to that which of the mesolimbic/mesocortical selective frontal lobe disease to can be termed "coordination between dopamine projections. This is an account for a behavioral pattern sensory/perceptual and homeostatic/ example of the first type of consistent with a frontal lobe motivational domains." The deficit of mechanism, and the search for other dysfunction. Alternatively, given the such interface being the central such mechanisms of direct frontal uniquely rich system of projections feature of schizophrenia is precisely lesions in schizophrenia will connecting the frontal lobes with a what emerges as the common undoubtedly continue. wide range of diverse brain systems, denominator across numerous formu- The second type of mechanisms, the frontal lobes, more than any lations, both early and recent, while genuine in the sense of not other system, are likely to be the attempting to capture the core of being iatrogenic, may act more point of summation of dysfunctions schizophrenic disorder. One would indirectly. This is due to the unique generated by many morphologically therefore expect that manifestations position of prefrontal cortex at the or chemically diverse systems due to of schizophrenia will resemble those top of neurocognitive hierarchy a multifocal or diffuse CNS disease, of frontal lobe damage in certain (Teuber 1964; Nauta 1971; Luria or to reflect anatomically specific but important respects. It may be most 1980). More than any other brain remote CNS events or disturbances. parsimonious to conclude that this is structure, prefrontal cortex serves the • The latter possibility is illustrated by so precisely because frontal damage role of interrelating various morpho- the previously mentioned observ- is present and plays a role in the logically and functionally diverse ations that lesions of the ventral mechanisms of schizophrenic systems which include posterior mesencephalic tegmentum can disorder. Yet a parsimonious expla- cortices, the , striatum, simulate prefrontal damage (Simon, nation is not always the correct one, , hypothalamus, dorso- Scatten, and LeMoal 1980; Goldberg and there may be more than one medial thalamus, and mesencephalic et al. 1982; Oades 1982). cause or chain of events leading to 260 SCHIZOPHRENIA BULLETIN

destabilization of "sensory and orbital/mediobasal aspects of the by having differential impacts on the perceptual vs. homeostatic and frontal lobes in the overall cerebral dopamine autoreceptors, different Downloaded from motivational" alignment. organization are quite different. In medicational histories may have This implies that schizophrenia is fact, it has been proposed that these different effects on the balance particularly suited to present itself as two areas play reciprocal roles in the between the cognitive controls a frontal lobe disease, regardless of cortico-limbic-reticular mechanisms associated with the two prefrontal of arousal: activating and facili- areas. Careful examination of clinical its actual mechanisms. Frontal lobe http://schizophreniabulletin.oxfordjournals.org/ damage may in fact be central to tatory, mediated by the dorsolateral and medicational histories leading, schizophrenic disorder, but it does frontal/amygdaloid/lateral hypotha- alternatively, to akinesia or tardive not have to be in order for the lamic/reticular system; and dysmentia may, in addition to similarity between the two conditions inhibitory, mediated by the fronto- helping understand the mechanisms to exist. orbital/mediobasal/amygdaloid/medial and typology of frontal manifesta- The interpretation of the findings hypothalamic/reticular system tions in schizophrenic populations, of frontal dysfunction in schizo- (Pribram and McGuinness 1975). shed further light on the biochemical phrenia is complicated by the fact Considerably less is known about basis of difference between main that such findings are usually possible differences in the reliance of frontal syndromes as they are seen reported in global terms, without the two frontal regions on various following focal brain lesions, and on much regard for the heterogeneity of biochemical (neurotransmitter and the biochemical basis of the comple- the frontal syndromes. As was neuropeptide) systems. Two recent mentary roles of the two aspects of pointed out before, the effects of findings may be of particular prefrontal areas in normal organization. dorsolateral and fronto-orbital/ relevance to these issues. The first at Pennsylvania State University on April 24, 2014 mediobasal prefrontal damage are finding is related to the reciprocity The observations by Rifkin et al. quite different and in certain respects between the cortical (mesocortical) and Wilson et al. certainly offer an even opposite, in spite of the and subcortical (mesolimbic and additional challenge to our under- morphological proximity of the two nigrostriatal) dopamine systems, such standing of the widely reported areas. The mechanisms of these that interference with the former frontal deficits in schizophrenia. It is locus-dependent differences are not enhances the latter (Pycock, Kerwin, not the purpose of this comment to well understood at this time. Never- and Carter 1980; Bannon and Roth imply that these deficits are solely theless, the descriptions of frontal 1983). The second finding is that of iatrogenic in nature and have nothing dysfunction in schizophrenia will the absence of terminal autoreceptors to do with the underlying schizo- certainly benefit from being more in mesocortical (but not mesolimbic phrenic disorder itself. There is no specific in view of this heterogeneity. or nigrostriatal) dopamine neurons, basis for such an absolute This may contribute to further which leads to different patterns of conclusion, nor do I believe that this subtyping of schizophrenia, response in the corresponding is the case. There is sufficient basis, providing that the descriptions reflect systems following acute and chronic however, for proposing that genuine rather than iatrogenic treatment with neuroleptics (Bannon iatrogenic effects of neuroleptics may phenomena. et al. 1982; Bannon and Roth 1983). contribute to the frontal symptom That the two frontal-like iatrogenic It is possible that the aforementioned picture in chronic schizophrenic effects of neuroleptics described, dopamine systems (mesocortical, patients and that the extent and respectively, by Rifkin et al. and mesolimbic, and nigrostriatal) have nature of this contribution is not Wilson et al. each resemble one of different degrees of contribution to known at this time. Nor is it implied the two prefrontal syndromes is the functions associated with various that possible genuine frontal deficits intriguing. The differences between prefrontal areas. It is not incon- are necessarily caused by mechanisms the two aspects of the frontal lobes ceivable, for instance, that the in which actual frontal lobe damage have been reasonably well studied in mesocortical dopamine system is plays no part. That would indeed be terms of their cytoarchitectonic relatively more intimately involved a twisted statement to make, and characteristics, afferent and efferent in functions associated with the equally without foundation. There is projections, and behavioral dorsolateral areas whereas the sufficient basis, however, for pathology. These studies clearly mesolimbic dopamine system is more proposing that anatomical inter- indicate that the functional roles of involved in those associated with the pretation of frontal dysfunction the dorsolateral and fronto- orbitofrontal areas. If this is so, then requires particular caution, greater VOL. 11, NO. 2,1985 261

than that of most other dysfunctions Brown, R.M.; Crane, A.M.; and & Wilkins Company, 1980. pp. which are presumed to have focal Goldman, P.S. Regional distribution 403-408. Downloaded from significance. of monoamines in the cerebral cortex Flor-Henry, P. Lateral temporal- Intriguing as the claims of frontal and subcortical structures of the limbic dysfunction and psycho- lobe dysfunction being a major rhesus monkey: Concentrations and pathology. Annals of the New York component of the schizophrenic in vivo synthesis rates. Brain Academy of Sciences, 280:777-795, disorder are, the evaluation of their Research, 168:133-150, 1979.

1976. http://schizophreniabulletin.oxfordjournals.org/ validity and meaning will have to be critically dependent on further Brozoski, T.J.; Brown, R.M.; Flor-Henry, P., and Yeudall, L.T. studies of frontal iatrogenic effects of Rosvold, H.E.; Waters, R.N.; Neuropsychological investigation of neuroleptics. When this is done and Cappelletti, }.; and Goldman, P.S. schizophrenic and manic-depressive genuine, noniatrogenic manifestations Cognitive deficit caused by regional psychosis. In: Gruzelier, ]., and Flor- are identified beyond reasonable depletion of dopamine in prefrontal Henry, P., eds. Hemisphere doubt, we will still be left perplexed, cortex of rhesus monkey. Science, Asymmetries of Function in Psycho- since not every frontal dysfunction is 205:929-932, 1979. pathology. New York: Elsvier North- Holland, 1979. pp. 341-362. necessarily caused by a frontal Buchsbaum, M.S.; Ingvar, D.S.; lesion, structural or chemical; but Kessler, R.; Waters, R.N.; Goldberg, E.; Mattis, S.; Hughes, then again, it may be. It is hoped Cappelletti, ].; van Kamron, D.P.; J.E.O.; and Antin, P. "Frontal that in the process we will find King, A.C.; Johnson, J.L.; Manning, Syndrome Without a Frontal ourselves a step closer both to the R.G.; Flynn, R.W.; Mann, L.S.; Lesion: A Case Study." Presented at understanding of schizophrenic the Fifth European Meeting of the

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Expressed Emotion in Families: Its and overinvolvement—has stimulated at Pennsylvania State University on April 24, 2014 Expressed Significance for Mental Illness, important insights as well as consid- Emotion in authored by Julian Leff and Christine erable controversy. In this volume, Vaughn, has been recently published Leff and Vaughn, together with two Families by The Guilford Press (200 Park other prominent investigators, Avenue South, New York, NY address some of the confusions and 10003). The discovery that misconceptions that have arisen discharged schizophrenic patients regarding the measures of expressed who returned home to parents or emotion and the techniques for spouses often fared worse than those obtaining data, and present impor- living alone led researchers to look tant new findings which significantly for conditions within the family that expand Brown's original insights. The might influence the schizophrenic book will be of great interest to patient's condition. At the vanguard psychiatric researchers as well as to of this endeavor was George Brown, all mental health professionals who whose recognition of the debilitating work with schizophrenic patients and effect of high levels of expressed their families. emotion—such as hostility, criticism,