British Journalof Psychiatry (1989), 155,73—78 Brain White-Matter Lesions and Psychosis BRUCE L. MILLER, IRA M. LESSER,KYLE BOONE, MARK GOLDBERG, ELIZABETH HILL, MILTON H. MILLER, 0. FRANK BENSON and MARK MEHRINGER In a prospectivestudy of late-life onset psychosis,five of the first 27 patients studied had extensive white-matter lesionsdemonstrated by MRI and/or CT. None of 60 age-matched psychiatricallyhealthycontrolsdemonstratedsuchlesions.All five patientshada milddementia and a frontal behaviouralsyndrome. In addition, every patient performed poorly on neuro psychologicaltests of frontalfunction.Dysfunctionof the frontalcortexassociatedwith white matter lesionsappearsto contributeto the clinicalpictureof somecasesof late-lifepsychosis. Late in life, elderly patients can develop a psychiatric picture that resembles schizophrenia. Some accept this as part of the spectrum of schizophrenia (Roth, 1955; Kay & Roth, 1961; Bridge & Wyatt, 1980; Gold, 1984), although others suggest that many patients with late-onset psychosis have organic disease (Leuchter & Spar, 1985). With DSM-III (American Psychiatric Association, 1980), otherwise as having ‘¿ atypical psychosis'. would meet criteria psychosis, a topic which has received little acknowledgement in the literature, is discussed. Method Patients with the first onset of psychosis after the age of 45 wereevaluatedwith the followingprotocol: a psychiatric patient with the onset of psychosis after the age of phrenia of the white-matter lesions in the pathogenesis of the this confusion was partially addressed by classifying any 45 who with MRI and computerised tomography (CT). Five of 27 patients studied had this pathology, which has not previously been reported in LLP. These five patients are described in detail, and the significance for schizo interview (the Structured Clinical Interview forDSM-III-R In recent years there has been increasing evidence that silent vascular disease may be an important factor in the pathogenesis of some late-life psychoses (LLP). Miller et al(1986) described four patients with LLP with no clinical evidence for structural brain disease, who had extensive brain lesions demonstrated by (SCID;Spitzereta!, 1986));a medicalhistory;a neurological examination; an EEG; an MRI scan (1.5 Tesla magnet with T1-and T2-weightedimages); and a CT scan. The Mini Mental StateExamination(MMSE; Foisteinet a!, 1975), Hachinskiischaemiascale(Hachinskieta!, 1974),Hamilton Rating Scale for Depression (Hamilton, 1967) and Brief Psychiatric Rating Scale (Overall & Gorham, 1962)were administered to help evaluate dementia, risks for cerebro tweentheselesions and thepsychosis was notcertain, vascular disease,and psychiatricsymptoms. Patients were and it is possible that they were not causal. For this excludedfrom the study if the MMSE rating was lessthan reason a prospective study comparing patients with 24. A battery of neuropsychologicaltests wasadministered, LLP with normal age-matched controls was started including the Wechsler Adult Intelligence Scale (Satz-Mogel in an attempt to define better the relationship between format) (Wechsler, 1981; Adams et a!, 1984), Wechsler newer neuroimaging techniques. The relationship be structural brain disease and this psychiatric syndrome. Preliminary reported Memory Scale (Wechsler & Stone, 1945), Rey—Osterrieth Complex Figure Test (Osterrieth, 1944),the Wisconsin Card results from this study have been 1988) Sort (Berg, 1948),Stroop Test (Stroop, 1935),Consonant Trigrams (Stuss et a!, 1982), and Verbal Fluency Tests half had serious structural brain abnor and EEG read by experienced neuroradiologists or electroencephalographers,who wereblind to subjectstatus. The patientswerecomparedwith60age-and sex-matched and the authors (Miller & Lesser, described a variety of abnormalities in these patients. Approximately (Benton & Hamsher, 1976). The patients had CT, MRI, malities, including tumour, and vascular and post traumatic lesions involving cortical and/or subcortical structures; the control group of age-matched subjects without a history of major psychiatric problems had no serious abnormalities on magnetic resonance controls, recruited through an advertisement requesting that normal elderly individuals were wanted for a study on normal ageing. All control subjects had an MRI scan. imaging (MRI). Although a varietyof brainareas were damaged in the patient group, in the majority the injury involved frontal or subfrontal structures. The largest subgroup of patients with LLP were Case descriptions Case1 those with extensive and confluent lesions in the deep An 86-year-old right-handed woman was brought to hospital by her daughter because of increasing paranoia white matter underlying the cortex, demonstrated 73 74 MILLER ET AL associated with belligerence. Four years earlier, she started to complain that visitors were entering her house at night, and were attempting to steal from her. Also, she developed brief episodes during which she believed her daughter was an imposter, when she would throw objects at the daughter, and would hit her. There was no history of serious medical problems, and she was not taking medication. She had a history of pro gressive visual and hearing loss, and was registered as blind. She was alert but irritable, and was co-operative for only 5-15 minutes at a time. Blood pressure was 190/90 mmHg. She described night-time visitors, but denied that her daughter had been replaced by an imposter. She was orientated to time (month and year), and remembered two of three words over five minutes. Speech and language were normal. Her basic neurological examination assassinate him and President significant medical Reagan. In addition, he no longer cleaned his flat properly. There was no history of illness. He was alert and co-operative, with a blood pressure of 155/100 mmHg. He described his delusions in vivid detail, but seemed unconcerned. His affect varied widely from flat to euphoric. He had trouble remembering the exact date, but recalled three of three words after five minutes. Speech, language comprehension, and naming were normal, as was his copying of a three-dimensional drawing. Basic neuro logical examination was normal, except for significant hearing and visual acuity deficits. His MMSE score was 25, and the DSM—III—R diagnosis was of schizophrenic disorder. Neuropsychological tests revealed impaired recall of was normal, new verbal and non-verbal information. Verbal IQ was 95 and performance IQ was 105. Perseveration errors were DSM—III—R diagnosis(AmericanPsychiatricAssociation, set. Laboratory investigations, including EEG, were normal. Both CT and MRI (Fig. 2) showed diffuse confluent white matter lesions, in addition to multiple small lacunae and generalised atrophy. The delusions persisted after treatment with haloperidol. except for absent ankle jerks and severe impairments of vision and hearing. The MMSE score was 26, and the 1987) was delusional disorder. The EEG was normal, but CT showed diffuse cerebral atrophy, with scattered lacunar infarcts, and diffuse diminished attenuation in the deep white matter underlying the frontal and parietal cortex (Fig. 1). She refused MRI and neuropsychological testing, and was unresponsive to neuroleptics. Case 3 Case 2 A 73-year-old man was admitted to hospital after complaining that men who were hired by the CIA wanted to FIG. 1 CT noted on tests requiring categorisation or shifting of mental scan from case I shows parietal lucencies and atrophy. confluent subfrontal and A 72-year-old man was admitted to hospital because he was being increasingly aggressive at his board-and-care home, where he had hit some of his fellow boarders. His personal hygiene had deteriorated, and he had been incontinent FIG. 2 T2-weighted MRI scan from case 2 shows increased in subfrontal, subparietal, and suboccipital white matter. signal 75 WHITE-MATFER LESIONS AND PSYCHOSIS and had stated that he had heard God speaking to on several occasions. He had a long history of hyperten sion, and was taking several medications, including him. Also, he insisted that he was a captain in the prazosin(1mg/t.i.d), temazepam(30mg q.h.s), L-thyroxine merchant marines, although this was not true. There was a complicatedmedicalhistory,with chronicobstruc (0.1 mg q.d.), and carbidopa with L-dopa (25/250 tablets q.i.d.). Four years earlier, he had a coronary artery bypass tive pulmonary disease, diabetes, hypertension, and and had a pacemaker inserted. He was pleasant and co-operative. He repeatedly complained that someone had inserted a doorknob under his skin at the site of the cardiac pacemaker, but seemed unconcerned about this. He knew the month and year but not the day, and could not remember three words for five minutes. He could not name low-frequency heart disease. His medications included ibuprofen (400mg t.i.d.), chlorpropamide (250 mg t.i.d.), clonidine (2mg t.i.d.), aminophylline (200 mg b.i.d.), digoxin (25 mg q.d.), and furosemide (40 mg q.d.). He wasdisinhibited,withpressuredspeechand flightof ideas. He fluctuated between irritability, anger, and euphoria. The delusions were described with detachment objects (e.g. ‘¿ door hinge'), and followed two-step but and lack of emotion. He had trouble with memory tasks, not three-step commands. Motor tone was increased, but language was fluent and comprehension was good. Basic neurological examination was normal, with the and a coarse rapid tremor was noted. Gait was wide basedand slow,and toesweredowngoing.His MMSEscore exceptionofsevere sensorincuralhearingloss,and moderate was 24, and his psychiatric diagnosis was of delusional visual disturbance secondary to bilateral cataracts. The disorder. Neuropsychologicaltesting revealed impairment in learning and some responses were confabulatory. Mild impairment of constructional and mathematical abilities psychiatric diagnosis was of bipolar disorder, manic phase with psychotic features. The CT scan showedwellcircumscribedlucencies,which seemed to undercut both frontal and parietal lobes. His were present. Verbal and performance IQ were 74. behaviourdid not improvewith neuroleptics,and he was The CT scan showedmultiplesubcorticalwhite-matter discharged to a nursing home. lucencies, and several lacunar infarcts in the basal ganglia. The patient's delusional syndrome did not respond after the L-dopa was decreased, and he was discharged to a nursing home. Case4 A 62-year-old right-handed man was admitted to hospital Discussion The five elderly patients described here were all seen because of a behavioural disorder associated with prominent delusions. Although two of the patients showed minor neurological deficits (cases 3 and 4), only one of these had a history of to assessa memorydisturbanceassociatedwith paranoia and delusions.In the monthsbeforeadmission,he began stroke. Hypertension was present in four of the five to accuse others of trying to steal his money. There was patients, and serious deafness and/or visual deficits a pasthistoryof diabetes, hypertension, hearingloss,and in three. Intellectual impairment was not recognised a vague history of stroke in the year before admission. families or Thepatienthada blood pressureof 160/92 mmHg. He as a major problemby thepatients' primary health care personnel, yet neurobehavioural repeatedly stated that people had stolen from him at work. Although irritable and easily angered, at times he was and neuropsychological batteries did demonstrate evidence for dementia in every patient. However, euphoric. The basic neurological examination was normal, was normal,and thedementia except for mild dysmetria and a wide-based ataxic gait, languagefunction and a moderate sensorineural-typehearing loss was syndrome was not apparentunlessspecial tests demonstrated. His psychiatric diagnosis was of delusional assessing frontal lobe and memory function were disorder. performed. average range. Unshakable delusions were a prominent feature of (paranoid) disorder, Case5 phrenia, and one had a manic syndrome. Although Hisfull-scale IQ was88,witha significant discrepancy The clinical features of these patients differed between verbal (95)and performance IQ (78). Verbal and from those seen in classic schizophrenia: none had non-verbal memory skills, visual perceptual and construc a prior history of psychiatric illness, nor was there tional abilities, frontal systems, and attentional abilities all were impaired. In contrast, language skills, mathematical evidence of a formal thought disorder, yet each had ability,andgeneralinformationwerewithinthelowto high complex delusions with or without hallucinations. TheEEGwasnormal,butthe CF scanshowedmultiple the psychiatric presentation, and although difficult lacunae inthedeepwhite matter andbasal ganglia. He did to quantify, all had relative sparing of personality. not respondto drugtherapy. Three had a DSM-III-.R diagnosis of delusional A 68-year-old right-handed man was referred to hospital after an attempt to have sexual relations with a 13-year one met criteria there was some variability for schizo in the specific psychiatric presentations, all patients had strikingly similar old niece, a behaviourthat seemed ‘¿ of outcharacter'. large subfrontal white-matter lesions on CF and Beforeadmissionhe had becomeincreasinglydisinhibited, MRI. 76 Considering all the clinical and radiographic MILLER ET AL data, been noted that many patients with reduplicative these conditions could be rediagnosed as organic delusional or organic affective disorders, but this diagnostic information was not apparent upon entry to the study, when the clinician initially evaluated the patient. In several cases, the additional testing was pursued only because the patient was a study participant. paramnesia have periventricular is the Capgras Lesions In the frontal regions and behavioural abnormalities It is well recognised that frontal-lobe lesions may produce changes in behaviour, but may be otherwise neurologically silent (Stuss & Benson, 1984). Although none of the patients had lesions evident in the frontal lobes, all had extensive subfrontal white-matter infarction. In two patients (cases 1 and 5), the white matter underlying the frontal lobe was the pre dominant site of abnormality, and this region was involved in all five cases. Subcortical white-matter lesions can disconnect the frontal areas from the remaining brain, and white-matter diseases such as metachromatic leucodystrophy often start with behavioural changes that include frontal-lobe symptoms and sometimes mimic schizophrenia (Skomer et a!, 1983). Irritability, apathy, behavioural disinhibition, and poor judgement, symptoms commonly associated with frontal-lobe injury, were present in all the patients, and euphoria was present in four. All were brought to hospital because of behavioural disinhibi tion associated with impairment of judgement. It can be argued that in every patient this aspect of their psychiatric syndrome and not the delusions was the major source of concern to family and friends. Irritability and apathy were also present, and in all but case 1, this was seen to fluctuate with periods of euphoria. The group did poorly on tests of frontal function and on the battery of frontal tests, suggesting that the frontal lobes and/or their connections were injured. These fmdings support a role for the frontal cortex in the pathogenesis of some of the abnormal behaviour seen in LLP. Delusions as part of a frontal syndrome Although delusions and hallucinations are not typically indicators of frontal damage, specific delusions have been reported in association with such lesions. Reduplicative paramnaesia syndrome was first described by Pick (1903) in a patient with Alzheimer's disease “¿ who insisted that the hospital she was in was located in her own community rather than in the city of its actual location―. It has since and right hemi sphere dysfunction (Weinstein & Kahn, 1955), and Benson et a!(l976) described three patients recovering from head traumas with a combination of right hemisphere and bifrontal abnormality who had classic reduplicative paramnesia. Another dramatic delusion which has been described following frontal injury syndrome (Alexander et a!, 1979), which features the belief that a person close to the patient has been replaced by one or more identical appearing imposters (a feature of case 1). A third syndrome which may approach delusional proportions and which may be seen in patients with frontal damage is confabulation, particularly the ‘¿ fantastic' or ‘¿ spontaneous' confabulation syndrome (Stuss et a!, 1978). Even where the degree of confabulation is less pronounced, Mercer eta! (1977) demonstrated that a consistent clinical feature was a lack of self criticism, and they postulated a frontal dysfunction. In each of these three syndromes, the patient presents an incorrect response and maintains the response in the face of contrary evidence. Inability to monitor and self-correct appears to be the primary dysfunction underlying these delusions. In all five of the cases described above, there was a striking inability to monitor and self-correct, and the delusions were part of a more generalised frontal syndrome. Sensory deprivation has been described as a risk factor for LLP, with 38% of subjects suffering from significant hearing loss compared with 18% of patients with late-life affective disease (Cooper & Curry, 1975). Two of our patients had serious visual and hearing loss, a third patient had mild sensori neural deafness, whereas two had no sensory deficits. The role of the sensory deficits in the pathogenesis of the psychosis is uncertain, and it is possible that the sensory disturbance in conjunction with the mental impairment contributed to the hallucinations and delusions which were present in four of the five patients. Sensory deprivation is common in the elderly and can lead to modality-specific hallucina tions, but delusional affirmation of the hallucination is unusual (Cummings & Miller, 1987), and the frontal and subfrontal brain injury appeared to be an important contributor to the psychosis in our cases. Aetlology of the white-matter lesions With third-generation CT and, more recently, MRI, it has become increasingly clear that many elderly people have subtle abnormalities in the white matter underlying cortex. In one study, 88% of demented 77 WHITE-MATI'ER LESIONS AND PSYCHOSIS elderly subjects compared with 61% of non demented patients with ischaemic vascular disease had at least one lesion in the white matter (Hershey et a!, 1987). Bradley et a!(1984) noted small lesions in 30°lo of all patientsoverthe ageof 65; theselesions were not common in younger patients. Some have suggested that these lesions are small white-matter infarctions (Brant-Zawadzki et a!, 1985). It has been demonstrated that hypertension is present in a higher proportion of patients with these defects than in age matched controls, suggesting a possible vascular aetiology (Brant-Zawadzki et a!, 1985). Their clinical significance isdebated(Hackinski eta!,1987), with suggestions that they correlate with dementia (Brant Zawadzki et a!, 1985) or even are asymptomatic (Hershey et a!, 1987). Although small lesions may be asymptomatic, larger ones often are associated with dementia (Goto et a!, 1981; Steingart et a!, 1987). Some of the original papers on this topic noted that delusions were present in some of the patients (Goto eta!, 1981; Tomonaga et a!, 1982), although the psychiatric features of white-matter lesions have not been extensively characterised, and in most cases have been ignored. We have not seen large subfrontal lesions in the 60 control patients that we have so far studied, and doubt that lesions as extensive as those seen in our five patients are asymptomatic or unrelated to their neuropsychiatric presentation. These five cases demonstrate that the first and primary clinical manifestations of white-matter lesions may be psychiatric. The relationship of these lesions in the subfrontal area to frontal dysfunction needs further study, but in these five cases frontal dysfunction was profound. Neurophysiological studies such as computerised EEG and single-photon emission computerised clarify the relationship tomography (SPECT) may between white-matter lesions and frontal function. Because these lesions are common in the elderly, further study of their clinical significance will be important. When psychosis appears for the first time in late life, a careful search for organic illness, incorporating CT or MRI, should be undertaken. In particular, a subset of patients with white-matter lesions may present with both delusions and a frontal syndrome. Acknowledgements This work was supportedin part by a grantfrom the State of California,Departmentof Mental Health (85-76263)and a PhysicianScientistAward (K 11AG 00284-02)to Dr Miller. We would like to acknowledge Drs Jeffrey Cummings and Lee Chiu for helpwiththe preparationof this paper. A versionof this paper waspresentedat the Annual Meetingof the AmericanPsychiatric Association,Chicago, 11—15 May 1987. References ADAMS, R. L., &aoimsici, J. & J@xi@, ALEXANDER, D. R. L. (1984) Development of a Satz-Mogel short form of the WAIS-R. Journal of Consulting and Clinical Psychology, 52, 908. M. P., Swss, T. & Bn@soi@t, D. F. (1979) Capgras syndrome: a reduplicative phenomenon. Neurology, 29, 334—339. AMERICAN PSYCHIATRIC ASSOCIATION Statistical Manual ofMental (1980) Diagnostic and Disorders (3rd edn) (DSM—III). Washington, DC: APA. —¿ (1987) Diagnostic and Statistical Manual of Mental Disorde,@ (3rd edn, revised)(DSM-III-R). Washington, DC: APA. BENSON, D. F., GARDNER, H. & MEADOWS, J. Reduplicative paramnesia. Neurology, 26, 147-151. C. (1976) BENTON,A. L. & HAMSHER,K. deS (1976) Multilingual Aphasia Examination. Iowa City: University of Iowa. BERG, E. A. (1948) A simple objective test for measuring flexibility in thinking. Journal of General Psychology, 39, 15—22. Bai@uu@y, W. 0., W@ujcu, V., Bwrr-Z,@w@Dzxi, M., et al (1984) Patchy, periventricular white matterlesionsin the elderly:a commonobservationduringNMRimaging.NonlnwzciveMedlcoi Imaging, 1, 35—41. Ba-Z,@w@zxi, M., FaIN, 0., V@ Dyics, C., et al (1985) MR imaging of the aging brain: patchy white-matter lesions and dementia. American Journal ofNeuroradiology, 6, 675-682. Bamos, P. T. & WYAVr,R. J. (1980)Paraphrenia: paranoid states of late life. I. European research. Journal of the American Geriatric Society, 28, 193-200. Cuy@osmios, J. L. & Miuiut, B. L. (1987)Visualhallucinations:an overview. Western Journal of Medicine, 146, 46-51. Coopsjt, A. F. & Cuany, A. R. (1975) The pathology of deafness in the paranoid and affective psychoses of later life. Journal of Psychosomatic Research, 20, 97-105. FOLSTEIN, M. F., Foisrsmi, S. B. & MCHUGH, P. R. (1975) “¿ Mini MentalState―: a practicalmethodfor gradingthe cognitivestate of patients for the clinician. Journal of Psychiatric Research, 12, 185—198. Gow, D. (1984) Late age of onset schizophrenia: present but unaccounted for. Comprehensive Psychiatry, 25, 225-237. Gcro, K., IsHlI, N., & Fu@sAwA, H. (1981) Diffuse white matter disease in the geriatric population. Radiology, 141, 687—695. HACHINSKI,V. C., LAssasi, N. A. & M@asmiu@,J. (1974) Multi infarct dementia. A cause of mental deterioration in the elderly. Lancet, ii, 207—210. HAcmI@4sIcI, V. C., Porrut, P. & MERSKEY, H. (1987) Leuko araiosis. Archives of Neurology, 44, 21—23. HAMILTON, M. (1967) Development of a rating scale for primary depressive illness. British Journal of Social and Cilnical Psychology, 6, 270—296. Hsxsuay, L. A., MODIC,M. T., GaEaNouoH, P. 0., et a! (1987) Magnetic resonance imaging in vascular dementia. Neurology, 37, 29—36. KAY, D. W. K. & Rom, M. (1961) Environmental and hereditary factors in the schizophrenia of old age (“late paraphrenia―) and their bearing on the general problem of causation in schizophrenia. Journalof MentalScience,17, 649-686. LEUCHTER, A. F., & Sp@ut,J. E. (1985) The late-onset psychoses. Clinical and diagnostic features. Journal of Nervous and Mental Disease, 173, 488—493. Mencsa, B., WAPNKE,W., G@an@1Eit H., eta! (1977) A study of confabulation. Archives of Neurology, 34, 429—433. Mzuiit, B. L., Bs@isoN,D. F., Cuw.enos, J. L., et a! (1986) Late onset paraphrenia: an organic delusional system. Journal of ClinicalPsychiatry,47, 204-207. —¿ & Lmma, I. M. (1988) Late-life psychosis and modern neuro imaging. In Psychiatric Clinics of North America (ed. D. Jeste). Philadelphia: W. B. Saunders. 78 MILLERET AL OsrERluEm, P. A. (1944) Le test de copie d'une figure complexe. Archives de Psychologie, 30,206—356. OVERALL, J. W. & Goiuw@i, D. R. (1962) The Brief Sruss, D. T., ALEXANDER, M. P., Lmmajvi@, A., eta! (1978) An extraordinary Rating Scale. Psychological Research, 10, 795-812. Pici@,A. (1903) Clinical studies: III. On reduplicative paramnesia. —¿ , Brain, 26, 260-267. Journalof MentalScience,129, 281-301. Sra@as, J. & AUSTIN, J. (1983) E. F., BENsoN, D. confabulation. F., eta! Neurology, (1982) Evidence for 28, the cortex in memory functions: an interference effect. Journal of Comparative Physiological Psychology,96, 913—925. —¿ & BENSON, D. F. (1984) Neuropsychological studies of the frontal lobes. Psychological Bulletin, 95, 3-28. Metachromatic leukodystrophy (MLD) adult MLD with focal lesions by computerized tomography. Archives of Neurology, 40, 354-355. Spirzpjt, R. L., Wuu4@is, J. B. & GIBBON,M. (1986) Structured Clinical Interview for DSM-III-R Patient Version (SCI1) 8/1/86). New York: New York State Psychiatric Institute. STEINGART, A., HACInNsia,V., Lw, C., et al(1987) Cognitive and neurologic findings in subjects with diffuse white matter lucencies on computed tomographic scan (leuko-araiosis). Archives of Neurology, 44, 32-35. Smoop, J. (1935) Studies of interference in serial verbal reactions. Journal of Esperimental Psychology, 18, 643-661. KAPLAN, involvement of orbitofrontal Rom, M. (1955) The natural history of mental disorder in old age. SKOMER, C., form of fantastic 1166—1172. Psychiatric TOMONA0A, M., YAMAN0uCm, H., Toom, H., et a! (1982) Clinicopathologic study of progressive subcortical vascular encephalopathy (Binswanger type)in the elderly. Journal of the AmericanGeriatricSociety, 30, 524-529. WECHSLER, D. (1981) Wechsler Adult Intelligence Scale-Revised. New York: Psychological Corporation. —¿ & SToles, C. (1945) Wechsler Memory Scale. New York: Psychological Corporation. WEINSTEIN, E. A. & KAHN, R. L. (1955) DenIal of Illness: Symbolic and PhysiologicalAspects. Springfield:CharlesC. Thomas. 5B. L. Miller, MD,Assistant Professor, Department of Neurology; I. M. Lesser, MD,Adjunct Associate Professor, Department of Psychiatry; K. Boone, PhD, Research Neuropsychologist, Department of Psychiatry; M. Goldberg, PhD, MD, Professor and Chair, Department of Neurology; E. Hill, RN, MN, Research Nurse, Department of Psychiatry; M. H. Miller, MD, Professor and Chair, Department of Psychiatry; D. F. Benson, MD, Professor of Neurology; M. Mehringer, MD, Associate Professor, Department of Radiology at Harbor-UCLA Medical Center 5Correspondence: Harbor-UCLA Medical Center, 1000 W. Carson, Torrance, CA 90509, USA.