Parkinson's Disease and Depression

Home , Helmut Beckmann, Peter Riederer

590 Journal of Neurology, Neurosurgery, and Psychiatry 1997;63:590–596 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.63.5.590 on 1 November 1997. Downloaded from Parkinson’s disease and depression: evidence for an alteration of the basal limbic system detected by transcranial sonography

Thomas Becker, Georg Becker, Jochen Seufert, Erich Hofmann, Klaus W Lange, Markus Naumann, Alfred Lindner, Heinz Reichmann, Peter Riederer, Helmut Beckmann, Karlheinz Reiners

Abstract disease.1 The average prevalence of depression Objectives—Depression is a frequent in Parkinson’s disease is around 40% with a symptom in Parkinson’s disease. Compel- range from 4%-70%.2 Although it is evident ling evidence suggests a role of the brain- that the degree of impairment and psychologi- stem in the control of mood and cognition. cal and social factors inﬂuence the mood of In patients with unipolar depression tran- patients with Parkinson’s disease3 there are scranial sonography (TS) studies have several lines of evidence pointing towards shown structural alteration of the mesen- organic factors in the pathogenesis of depres- cephalic brainstem raphe which could sion in the disease.4–16 Transcranial sonography suggest an involvement of the basal limbic (TS) is a valuable tool in visualising both nor- system in the pathogenesis of primary mal and diseased brain parenchyma, and mood disorders. The objective of the brainstem anatomy can be reliably Department of present study was to evaluate whether a depicted.17–23 In a TS study in patients with Psychiatry, University similar alteration could be found in de- Parkinson’s disease the substantia nigra was of Würzburg, pressed patients with Parkinson’s disease found to be hyperechogenic, which is thought Füchsleinstrasse 15, 24 D-97080 Würzburg, using TS. to reﬂect tissue degeneration. Germany Methods—Thirty patients with Parkin- Recent TS studies provide evidence of

T Becker son’s disease and 30 age and sex adjusted structural alteration in the brainstem in pa- copyright. P Riederer controls were examined by TS. Raphe tients with major depression. In two studies of H Beckmann echogenicity was rated semiquantita- a total of 140 psychiatric patients and 60 controls we assessed the echogenicity of the Department of tively. The severity of motor symptoms Neurology, University and depression was rated using standard mesencephalic brainstem raphe and found a of Würzburg, research instruments. significant reduction of raphe echogenicity in Josef-Schneider-Strasse Results—Raphe echogenicity was signifi- unipolar depressed patients (not in bipolar dis- 25 26 11, D-97080 Würzburg, cantly reduced in depressed patients with order or schizophrenia). The raphe echo Germany identified in the midline of the pontine and G Becker Parkinson’s disease compared with non- J Seufert depressed patients with Parkinson’s dis- mesencephalic brainstem corresponds to fibre M Naumann ease and control subjects. Raphe tracts and nuclei associated with the dorsocau- 27 28 A Lindner echogenicity correlated negatively with dal limbic system (basal limbic system ). H Reichmann degree of motor impairment, and diVer- Therefore, findings point towards a morpho- http://jnnp.bmj.com/ K Reiners ences in raphe echo between depressed logical alteration of the basal limbic system as and non-depressed patients with Parkin- one potential pathogenetic factor in depres- Department of sion. Neuroradiology, son’s disease were upheld when motor University of impairment was controlled for. In the present TS study we assessed raphe Würzburg, Conclusion—These preliminary findings echogenicity in patients with Parkinson’s dis- Josef-Schneider-Strasse suggest that, as in unipolar depression, a ease with and without concomitant depressive 11, D-97080 Würzburg, morphological alteration of the brainstem syndromes to examine whether alteration of Germany the raphe system could be a common denomi- on September 30, 2021 by guest. Protected E Hofmann raphe might be involved in the pathogenesis of depression in Parkinson’s disease. nator in the pathogenesis of depressive syn- Section of This raphe alteration may reflect involve- dromes. Neuropsychology, ment in the basal limbic system in the Department of pathogenesis of secondary depression. Psychology, University This concept is in line with current knowl- Patients and methods of Freiburg, Postfach, edge on the pathogenesis of both depres- PATIENTS D-79085 Freiburg, Thirty patients with Parkinson’s disease (mean Germany sion in Parkinson’s disease and primary K W Lange depressive disorders. age 68.3 years; five women, 25 men) were included. They had all been outpatients at the Department of Neurology for more than one Correspondence to: (J Neurol Neurosurg Psychiatry 1997;63:590–596) Dr Thomas Becker, Institute year and fulfilled research criteria for probable of Psychiatry, De Crespigny 29 Park, Denmark Hill, London Keywords: Parkinson’s disease; depression; basal limbic Parkinson’s disease, One neurologist (HR) in SE5 8AF. system; transcranial sonography charge of the department’s specialist Parkin- son’s disease outpatient clinic who was not Received 10 July 1997 and in involved in subsequent clinical or sonographic final revised form 8 May 1997 Depression and anxiety have commonly been examinations selected patients with Parkin- Accepted 15 May 1997 recognised in patients with Parkinson‘s son’s disease both with and without depressive Parkinson’s disease and depression 591 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.63.5.590 on 1 November 1997. Downloaded from

symptoms. The aim was to include about equal CONTROL GROUP numbers of patients with Parkinson’s disease As a comparison group, 30 age and sex with and without depression. Two patients with adjusted control subjects without Parkinson’s Parkinson’s disease (67 and 72 year old disease (mean age 65.2 years, six women, 24 women, Hoehn and Yahr grades 2 and 3), in a men) underwent neurological, psychiatric, and total sample of 32 patients with Parkinson’s TS examinations, and the questionnaires listed disease who underwent TS, were not included above were completed. Neurological diagnoses in this study because they had no suYcient of controls were as follows: seven patients had a acoustic bone window for transcranial sonogra- cerebral ischaemia (time since the first ischae- phy. The echogenicity of the substantia nigra mic event ranged from one to 18 months with and the width of the ventricular system in the a median of six months), seven patients had same group of patients with Parkinson’s disease been referred due to disc herniation (with a history of back pain of up to 11 years), three (n=30) have been reported elsewhere.24 had supratentorial brain tumours, and two had All patients with Parkinson’s disease received myelopathy. Two patients had myasthenia optimised medical treatment, including anti- gravis, two had a diagnosis of peripheral Parkinson’s disease medication (average doses neuropathy, one epilepsy, and one patient had a of medication and numbers of patients using subarachnoid haemorrhage. In addition, five that medication were levodopa 510 mg/day healthy subjects were included. None of the (n=20), carbidopa 481 mg/day (n=9), lisuride control subjects had parkinsonian symptoms or 0.6 mg/day (n=5), bromocriptine 9.8 mg/day symptoms fulfilling DSM-III-R criteria of (n=10), amantadine 283 mg/day (n=3), depression. selegiline-HCL 8.3 mg/day (n=12)). All patients recieved physiotherapy. In addition, six TRANSCRANIAL SONOGRAPHY patients were taking antidepressant medication For TS examination we employed a colour (average amitriptyline dosage 50 mg/day coded, phased array ultrasound system, (n=4), doxepin 20 mg/day (n=4)). Duration of equipped with a 2.25 MHz transducer (Sono- Parkinson’s disease ranged from 1 to 20 years line CF, Siemens, Erlangen, FRG). The axial (mean duration 9.7 (SD 5.8) years). All resolution of the method in the focus zone is patients gave informed consent according to about 1 mm. Results of the TS examination the Declaration of Helsinki. depend on the examiner’s skill, and all TS examinations were carried out by one experi- enced examiner (GB) who was unaware of the copyright. RESEARCH INSTRUMENTS psychiatric status of the patient. Patients were All 30 patients with Parkinson’s disease first asked to lie on the examination table in a underwent TS, and subsequently had supine position while TS was performed neurological and psychiatric examinations per- through a preauricular acoustic bone window. formed by another physician, all on the same The ultrasound system indices chosen were: day. Hoehn and Yahr grades of patients with penetration depth 16 cm, dynamic range 45 Parkinson’s disease ranged from stages 2 to 4.30 dB, high persistence, reject 7; image brightness The severity of Parkinson’s disease was quanti- and time gain compensation were adapted to fied using the Columbia University Rating the requirements of the special examination Scale (CURS).31 At the time of TS examin- situation. Supratentorial and infratentorial ation, mean score (SD) on the CURS rating brain areas were scanned in axial planes by tilt- scale was 27.7 (13.1). The psychiatric evalua- ing the probe at the acoustic window. http://jnnp.bmj.com/ tions were performed using a semistructured The mesencephalic brainstem can be de- psychiatric interview. The psychiatric diagnosis picted as a butterfly shaped structure of low was made according to the diagnostic criteria echogenicity surrounded by the hyperechogenic of DSM-III-R.32 Patients were diagnosed as basal cisterns (figure). The red nuclei, the aqueduct, and the brainstem raphe are hyperecho- depressed only if the descriptive criteria of a 17 25 26 major depressive syndrome (criterion A, diag- genic areas within the mesencephalon. The nostic criteria for major depressive episode32) aim of the TS examination was to identify the on September 30, 2021 by guest. Protected were fulfilled. The severity of depressive symp- pontine and mesencephalic brainstem raphe (ascending and descending pathways and toms was assessed using the 21 item Hamilton brainstem nuclei adjacent to midline). The depression scale (HDS). The mini mental state picture showing the best raphe visualisation examination (MMSE) was administered to 33 was selected for analysis. Echogenicity of the rule out dementia syndromes. The overall brainstem raphe was rated semiquantitatively severity of depression was assessed using the on a three point scale using the hyperechogenic clinical global impression (CGI) score.33 Fol- 34 red nucleus as a reference point: 1=raphe not lowing a suggestion by Starkstein et al HDS visible/ isoechogenic raphe compared with items on early morning awakening, anergia, adjacent brainstem parenchyma, 2=slightly and motor retardation (items 5-8, 13, and 16) echogenic raphe, 3=normal raphe echogenicity were excluded in an additional analysis because (echogenicity of the raphe is identical to that of ratings on these items did not diVer between the red nucleus). For technical reasons further depressed and non-depressed patients with quantification of ultrasound echogenicity is not Parkinson’s disease. This reduced HDS is des- feasible.17 Printouts of TS images were re- ignated HDS*. All patients were asked to com- evaluated by a second, independent ultrasound plete the “Befindlichkeitsskala” by von Zerssen examiner (MN) to assess interrater reliability. (Bf-S).33 Also, the width of the third ventricle was 592 Becker, Becker, Seufert, Hofmann, Lange, Naumann, et al J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.63.5.590 on 1 November 1997. Downloaded from

determined by measuring the maximal trans- Table 2 Raphe echogenicity scores in depressed patients verse diameter in the axial scanning plane. with Parkinson’s disease (PD), non-depressed patients with PD, and controls Frontal horn size was assessed by measuring the maximal distance between the origin of the Raphe echogenity scores septum pellucidum and the tip of the frontal horn. 123 Depressed PD patients (n) 8 4 1 STATISTICAL ANALYSIS Non-depressed PD patients (n) 1 6 10 Interrater reliability of raphe ratings was calcu- Control subjects (n) 1 12 17 lated by rank correlation and weighted variance Score 1=raphe not visible/isoechogenic raphe compared with (kw) (previous work having shown that satis- adjacent brainstem parenchyma; score 2=slightly reduced raphe echogenicity; score 3=normal raphe echogenicity (identical with factory agreement is reached when TS is red nucleus). performed by two diVerent examiners).27 The statistical plan included three sequential two- severe in depressed (CURS: 33.4) than in non- group comparisons of (1) depressed versus depressed (CURS: 23.4) patients with Parkin- non-depressed patients with Parkinson’s dis- son’s disease (this diVerence failed to reach ease, and (2) and (3) of each of the patient signiﬁcance: Mann-Whitney U test, P=0.051; groups versus the control group. Between table 1). group comparisons were performed using the ÷2 test. The correlations of diVerent indices RAPHE ECHOGENICITY (scores on clinical rating scales, raphe echo- The level of agreement on raphe echogenicity genicity) were performed using Spearman’s between the two raters was high (in 15 out of rank correlation. The inﬂuence of clinical 30 cases assessments diVered by one score on ratings which might confound group diVer- the rating scale, there was no instance of a two ences was examined using analysis of covari- point score diVerence; rank correlation:

ance (ANCOVA). Group diVerences for con- rs=0.81, P<0.001, concordance analysis: kw = tinuous variables (for example, ventricular 0.74, variance (kw) = 0.01, P<0.0001). width) were examined using the Mann- In the group of patients with Parkinson’s Whitney U test. disease with depression raphe echogenicity was distinctly reduced compared with non- depressed patients with Parkinson’s disease Results and controls; the distribution of raphe echo- CLINICAL DATA

genicity scores in controls was very similar to copyright. Thirteen of the 30 patients with Parkinson’s that found in non-depressed patients with Par- disease fulfilled the diagnostic criteria of a kinson’s disease (table 2). The figure shows two major depressive syndrome according to DSM- examples of TS images. DiVerences in raphe III-R (mean age 67.7 years; two women, 11 echogenicity between depressed and non- men), 17 patients with Parkinson’s disease depressed patients with Parkinson’s disease were not depressed (mean age 68.5 years; three and between depressed patients with Parkin- women, 14 men). Three of the 13 depressed son’s disease and controls were significant (÷2: patients with Parkinson’s disease had mild both P<0.01). There was no significant diVer- depression, four had moderate depression, and ence between echogenicity scores in non- six had severe depression. Psychomotor retar- depressed patients with Parkinson’s disease dation was reported in 12 of the 13 depressed and controls (÷2: P=0.72).

patients with Parkinson’s disease, insomnia, http://jnnp.bmj.com/ and early morning awaking in 10, loss of appe- CLINICAL CORRELATIONS tite in eight, somatisation in seven, past or Correlations of demographic data and severity present suicidal ideation in seven, and delu- of illness with raphe echogenicity were exam- sions in five. The duration of the depressive ined. No correlation was found between raphe symptoms ranged from three to 15 years (mean echogenicity and age (Spearman’s rank corre- duration 7.6 (SD 4.2) years) and in two lation, ñ=−0.101, P=0.597). Mean echogenic- patients depression predated the manifestation ity scores in women and men were similar of motor impairment. The diVerences in (women: 2.6 (SD 0.6), men: 2.8 (SD 0.5), ÷2, on September 30, 2021 by guest. Protected MMSE were only slight and failed to reach sig- P=0.09). By contrast, raphe echogenicity in nificance (Mann-Whitney U test, P=0.49; table patients with Parkinson’s disease was signifi- 1). Motor disability was found to be more cantly correlated with the overall severity of depression as assessed by CGI (ñ=−0.646, Table 1 Clinical ratings, self ratings and TS ventricular measures in depressed and non-depressed patients with Parkinson’s disease (PD) and control subjects P<0.001), with HDS ratings (HDS: ñ=−0.594, P<0.001; HDS*: ñ=−0.57, Depressed PD Non-depressed PD Control subjects P=0.001), with self assessment of depressive patients (n=13) patients (n=17) (n=30) Scale mean (SD) mean (SD) mean (SD) symptoms (Bf-S: ñ=−0.489, P<0.05), and with motor impairment as assessed by CURS CURS 33.4 (11.8) 23.4 (12.7) 1.6 (2.1) CGI 5.3 (1.1) 2.1 (0.3) 2.0 (—) (Spearman’s rank correlation, ñ=−0.38, HDS 24.3 (7.9) 2.5 (3.6) 1.6 (1.9) P=0.03). However, the association between HDS* 14.2 (6.2) 1.1 (2.0) 0 (—) reduced raphe echogenicity and depressive Bf-S 39.5 (12.2) 9.5 (9.9) 5.5 (5.5) MMSE 26.2 (3.2) 27.1 (2.7) 28.6 (1.5) state remained significant when the CURS Width of 3rd ventricle (cm) 0.9 (0.3) 0.8 (0.2) 0.7 (0.2) score was included as covariate in an ANCOVA Width of frontal horn (cm) 2.1 (0.2) 1.8 (0.3) 1.7 (0.3) analysis (F2,26=7.1, P<0.01). HDS*=HDS item counts excluding HDS items 5, 6, 7, 8, 13, 16 which assess early morning When motor disability (CURS) was related awakening, anergia, and motor retardation. to the severity of depressive symptoms as 593 Becker, Becker, Seufert, Hofmann, Lange, Naumann, et al J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.63.5.590 on 1 November 1997. Downloaded from copyright. http://jnnp.bmj.com/ on September 30, 2021 by guest. Protected

TS brainstem images and schematic illustrations in (A,B) non-depressed and (C,D) depressed patients with Parkinson’s disease (axial scanning plane through the mesencephalic brainstem): In both patients the mesencephalic brainstem is illustrated as a butterﬂy shaped area of low echogenicity surrounded by the hyperechogenic basal cisterns. (A) In the non-depressed patient with Parkinson’s disease the brainstem raphe (arrow) is unequivocally visualised as a hyperechogenic midline structure in contact with the aqueduct (arrowhead). (C) It is not identiﬁed in the depressed patient with Parkinson’s disease. In both patients with Parkinson’s disease the substantia nigra exhibits increased echogenicity, probably due to iron inclusion or microgliosis (small arrows).24 1= mesencephalic brainstem; 2 = hyperechogenic basal cisterns; 3 = choroid plexus). 594 Becker, Becker, Seufert, Hofmann, Lange, Naumann, et al J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.63.5.590 on 1 November 1997. Downloaded from

assessed by HDS and HDS* significant with Parkinson’s disease examined in this study relations were disclosed (HDS: ñ=0.5, P<0.05; (of whom only 43% were depressed). Thus gait HDS*: ñ=0.5; P<0.05). However, no correla- and facial expression could not be considered tion was found between raphe echogenicity and suYcient clues to the mood status of patients, substantia nigra echogenicity (ñ=−0.17, and the examiner did not enter into conversa- P=0.35). Comparing measures of ventricular tion before the end of TS examination and width in subgroups of patients with Parkinson’s echogenicity rating. Blindness to the psychiat- disease, a significant enlargement of the lateral ric status was, therefore, achieved to the best of ventricles was found in depressed patients with our means. However, replication of the present Parkinson’s disease compared with non- findings is mandatory, and further confirma- depressed patients (Mann-Whitney U test, tion through MRI or pathological studies is P<0.05), whereas diVerences in width of the required. third ventricle failed to reach significance (Mann-Whitney U test, P=0.5). BASAL LIMBIC SYSTEM INVOLVEMENT Discussion The present results in patients with a second- In the present study we found a significant ary form of depression corroborate the hypoth- reduction of mesencephalic brainstem raphe esis that morphological alteration of the echogenicity in patients with Parkinson’s dis- mesencephalic raphe is involved in the patho- ease with depression compared with non- genesis of depressive disorders in general. depressed patients with Parkinson’s disease Changes in raphe echogenicity reflect changes and non-depressed, non-parkinsonian con- in tissue impedance and point towards an trols. These findings resemble the decrease in alteration of the brainstem microarchitecture raphe echogenicity previously reported in which could be due to a shift in tissue cell den- primary unipolar depression.25 26 Lateral ven- sity, a change in interstitial matrix composition, tricular enlargement was also found, and this is or an alteration of fibre tract integrity. Sono- in line with previous CT and MRI studies in graphically, the brainstem raphe presents as a old age depression and in depressed patients homogeneous area. However, anatomically, it 35 36 with Parkinson’s disease. corresponds to a network of mesencephalic nuclei and fibre tracts that are part of the basal LIMITATIONS OF THE STUDY limbic system.27 28 37 38 These fibre tracts bidi- Patients with Parkinson’s disease were rectionally link nuclei of the pontine and mes- not recruited from an epidemiologically encephalic midline region with diencephalic copyright. representative sample but from the selected and telencephalic brain areas. They unite patient group of a tertiary referral centre. In the dopaminergic fibre tracts originating mainly control group (of 30), 18 subjects were either from the ventral tegmental area, serotonergic healthy probands or patients with non-cerebral projections from the superior central nucleus neurological disorders, whereas cerebral and the dorsal raphe nucleus, and noradrener- ischemia was the largest diagnostic group gic fibres from the locus coeruleus within the (n=7) among the remaining 12. In this group territory of the mesencephalic raphe.38–40 an impact of the CNS disorder on raphe echo- Various anatomical, physiological, and bio- genicity could not be ruled out. However, the chemical findings underline the importance of distribution of raphe echogenicity scores in the the basal limbic system for aVective equilib- control group was closely similar to findings in

rium, and compelling evidence suggests that http://jnnp.bmj.com/ healthy adults reported previously.25 26 Also, the the nuclei, fibre tracts, and neurotransmitter design of the study included three way group comparisons (depressed Parkinson’s disease, systems associated with the basal limbic system non-depressed Parkinson’s disease, controls) in are involved in the pathogenesis of primary depression and depression in Parkinson’s which the above reservation did not apply to 41–43 the comparison between the first two groups. disease : (1) histopathological studies have Methodological restraints of TS may raise documented a pronounced reduction of cell further concerns. Whether a structure is density in the brainstem nuclei of the basal depictable or not depends, in part, on the limbic system such as the ventral tegmental on September 30, 2021 by guest. Protected insonation angle. Therefore, TS is dependent area, locus coeruleus, and dorsal raphe nucleus on the examiner’s skill, and standardisation of in patients with Parkinson’s disease (and TS examination is limited by variables such as patients with Alzheimer’s disease) with 44–46 the acoustic bone window and angulation of depression. (2) PET studies suggest hy- the scanning plane. Echogenicity assessment pometabolism in the medial frontal cortex, a requires a semiquantitative assessment (a rater major projection area of the basal limbic judgement), and the TS examiner in the system, in patients with Parkinson’s disease present study (who was also one of the two and concomitant depression resembling find- raters) met patients when he performed TS. ings in primary depression.47–49 (3) Several Thus blindness to diagnosis might be ques- studies have shown low concentrations of tioned. This does not primarily refer to the rat- dopamine, serotonin, and noradrenalin or their ing process (good reliability being achieved metabolites in the CSF of depressed patients with another rater not present at the time of TS with Parkinson’s disease.50–58 (4) In animal examination). The problem lies in a potential studies, lesions of the raphe nuclei, periaque- impact of clinical bias on the TS examination ductal grey, or locus coeruleus and their itself. On the other hand, hypokinesia and projections elicit some of the symptoms found amimia were features in virtually all patients in depressive illness.59–64 Parkinson’s disease and depression 595 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.63.5.590 on 1 November 1997. Downloaded from

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NEUROLOGICAL STAMP

Paul Ferdinand Gachet (1828-1909)

Paul Ferdinand Gachet was a general practitioner with a training in mental ailments. His thesis (1858) entitled Étude sur la Mélancholia contained principles for the moral treatment of the insane. Gachet’s system of therapy for melancholies was based on three principles, admission to hospital, therapeutic activities, and psychological support. For physical therapy Gachet allowed the use of warm baths to calm anxious patients. He strongly condemned the prevalent use of phlebotomy and purgation. Gachet looked after Van Gogh during the painter’s last two months of life in Auvers-sur-Oise in 1880.1 He was an early supporter of the impressionists and a painter and copyright. engraver of considerable talents himself. He was intrigued by the creative mind. His campaign for the establishment of a Society for Mutual Autopsy in which artists would leave their brains for postmortem study to evaluate artistic abil- ity and elucidate the process for creativity met with little enthusiasm. Renoir was one who resisted that invitation. Paul Gachet’s medical records pertaining to Van Gogh have not been found. Gachet had spoken with Theo Van Gogh before seeing Vincent. Theo, in a letter to Vincent, relayed the news that “When I told him how your crisis came about he said to me that he didn’t believe it had any- http://jnnp.bmj.com/ thing to do with madness and that if it was what he thought he could guarantee your recovery, but that it was necessary obvious that if this was true, an epidemic of insanity should to see you and to speak with you in order to make a more have occurred years earlier among the employees of the definitive statement”. Salpetiere. In 1875 through the pages of a popular health There is anecdotal evidence that Gachet considered that annual read by a large audience, Dr Gachet proclaimed, Van Gogh had been overexposed to turpentine vapour, and contrary to widely held opinion, that insanity was curable. that painting for long hours in the sun contributed to his He attacked the law of 1838 which allowed almost unregu- illness. There are many views on the nature of Van Gogh’s lated confinement of the mentally ill and concluded by on September 30, 2021 by guest. Protected illness. Gachet seems to have considered it as more akin to suggesting that the public should divest themselves of the epilepsy without convulsions complicated by periods of idea that mental illness “is an exaggeration or a deviation of depression. He was not convinced that Vincent had pure intelligence and that people who are taxed with originality insanity. Two months after becoming a patient of Dr are monomaniacs and are insane”. Gachet, in the late Sunday afternoon of 27 July 1890, Van In 1990 Antigua published a set of stamps to commemo- Gogh shot himself in the chest with a revolver. Dr Gachet rate the centenary of the death of Vincent van Gogh. found that the bullet had been deflected by the fifth rib. He Among these is Van Gogh’s portrait of Dr Gachet (Stanley died on 28 July about 1 30 am. Gachet persuaded the Gibbons 1517, Scott 1426) painted in two days in June village priest to make an exception and allow this victim of 1880. The painting hangs in the Musee D’Orsay in Paris. suicide to be buried in the cemetery, not far from the art- ist’s “vast fields of wheat”. Dr Gachet had firm views about L F HAAS psychiatric illness. In a letter to the editor of Le Figaro (18 August 1859) Gachet condemned a previous article 1 Fabri R. Dr Paul Ferdinand Gachet: Vincent Van Gogh’s last physician. Transactions and studies of the College of Physicians of Philadelphia claiming mental illness to be contagious pointing out the 1966;33:202-8.