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Parkinson's Disease and Depression 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 con- trols 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 pathogen- esis 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 aque- duct, 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).
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