P-6-4 Compulsivesive buying, depression and antidepressants

369

P-6 Obsessive compulsive disorders

References Golden RN, Hsiao JK, Lane E, Ekstrom D, Rogers S Hicks R, Potter WZ {1990) Abner real neuroendocrine responslVlty to acute i v clomipramme challenge in depressed patients. Psychiatry Res 31:39 47 Golden RN. Ruegg R. Brown TM, HaggerSyJ, Garbutt JC. Pedersen CA, Evans DL, (19901 Abnormal neuroendrocnneresponswlty to clomqpramine m depression Psychophar macol Bull 26 3:317-320 Saiz J, Lopez-lbor JJ, Vinas R, Hernandez M (1992): The clomipramine challenge test in obsessive compulsive disorder Int Chn Psvchopharmacol. 7 Suppl 141~42

Single photon emission computed tomography (HMPAO-SPECT) in obsessive compulsive disorder, after symptom provocation with m-chlorophenylpiperazine K.L. Ho Pian. A.S de Leeuw, W.l, deBruin, J.A. den Boer. H.G.M Westenberg, J Buijs. PAnema, PPvan Riik Departementof

Biological PsychiatO/, Department of Nuc/ear Medicine, Academic Hospita/ Utrecht, RO. Box 85500, 3508 GA Utrecht, The Nether~ands Treatment studies in Obsessive Compulsive Disorder (OCD} have revealed selective serotonin (5HT) reuptake inhibitors to be the most effective drugs ChaLlenge studies with mCPR a nonselective 5HT2C agonlst, may induce OCD symptoms. These data suggest that serotonin neuronal pathways are implicated in QCD. Imaging studies have consistently shown the in volvement of the frontal cortex and basalganglia in OCD Under basehne conditions a higher regional cerebral blood flow (rCBFI was seen m these regions, which decreased after effective treatment We investigated the response of patients with OCD to a challenge test with mCPP under double-blind, placebo-controlled conditions. Each challenge-test a SPECT scan was p e r f o r m e d It was assumed that mCPP would increase obsessive and/or compulsive symptoms and that this would alter the neuronal activity in the regions of interest (ROrs), e g. frontal cortex and basal ganglia, which would be visible as an alteration in cerebral blood flow at the SPECT scan Seven patients with QCD were included in th~s study After oral adminis tration of mCPP 0.5 mg/kg or placebo {t = 0) the physical, biochemical and behavioral effects were m e a s u r e d At t ~ 180 the tracer 99-m-TcHMPAO was injected. SPECT acquisition started a r t = 2 4 0 ROrs were measured as a ratio of the cerebellum Resu/ts: mCPP showed no increase Jr/obsessive and/or compulsive syrup toms b u t a significant increaseiP anxiety was seen rCBF wassignlficantly increased in the ratio right caudate nucleL frontal, panetal and right tempo ral cortex with a trend for the right thalamus and right putamen. A significant decrease in rCBF was found in the cerebellum, which ~mplicates an effect of mCPP on general cerebral blood flow This will need %rther investigation

References Baxter, L R {1992) Neuroimagmg studies of obsessive compulsive disorder Psycbimr Clin NorthAm 15,871 884 Clomipramme Collaboratwe Study Group (1991) Clomipramlne in the treatment ol patients with obsessive-compulsive disorder Arch Gen Psychiat 48 730-738 Kahn, R S , Wetzler, S. (1991) m Chlorophenvlplperazlne as a probe of serotonin function Biol Psychiatry 30, 11391166

Pathological gambling and taurine in the cerebrospinalfluid C, Nordin 1 3, C Bergh 2. T h EkIJndh 1 1 Departrnent of C#mca/ Neurosc/ence and Famdy Med/cme, Divisions of Psychiatry at the Karo/inska /nstitute, Hudd/nge Hospita/, S-141 86 Huddinge, Sweden, 2 Department of Chmca/Neurosc~ence and Famffy Medicine, Applied Neuroendecrinology at the Karohnska Institute, Huddinge Hospital, S 141 86 Huddlnge, Sweden," 3 Department of Psych/art% Umversity Hospital, S-581 85 Linkdping, Sweden Pathological gambling is an impulse control disorder associated with psy chosocial decay, drug and alcohol abuse, depression, anxiety, and an altered state of consciousness. Gamblers have a higher centrally produced fraction of the noradrenaline (NA) metabolite HM PG in the cerebrospinal fluid (CSF). and a greater urinary output of NA than controls (Roy et al., 1988), These results are m keeping with a functional disturbance of the NA system We have now lumbar punctured 10 male pathological gamblers (fulfilling the DSM-III-R criteria} and seven healthy male controls under standardized conditions, i e at t h e L 4 - S l e v e l a t 8 a m. after at least eight hours of fasting and strict bedrest, With the sublect in a sitting position, CSF was drawn m

three consecutive 6 mi-fractions Amino acids in the third (13-18 ml) CSF fraction were measured by HPLC. We found that the mean CSF level of taurine was significantly lower m gamblers than in controls [7.4 + SD 2.2 vs 10.9 ~ SD 3.4 (#mol/L); t -2.57; p < 0 0 5 ] Furthermore, in both gamblers and controls the taurme level correlated with height, but there was a significant difference between slopes of the regression lines (F 1:13 - 6.27; p < 0.05). There was no difference between gamblers and controls with respect to the level of GABA. Taunne is an inhibitory {Okamoto et al. 1983) and antiepileptic (van Gelder, 1972) amino acid, facts that are of interest for further discussions on the ae :iology of pathological gambling and the associated lack of impulse control. Whether the altered state of consciousness in gamblers has a connection with lowered taurme concentrations in the CSF is an intriguing question. The significant difference between slopes in the regression analysis of taunne and height is notable since height did not differ between gamblers and controls. The importance of height for levels of compounds in the CSF ~s unclear but it might have a connection with CSF circulation. The material is limited and the findings have to be interpreted with caution However, the present results are consistent with the hypothesis that taurine (but not GABA)is involved in the aetiology of pathological gambling. Prospective studies are urgent.

References Okamoto, K. K~mura, H and Sakai, Y (1983} Evidence for taurme as an inhibitory neurotransmltter m cerebellar stellate intemeufons: selective antagonism by TAG (6 ammomethyl-3-methyl-4H,1,2.4-benzothiadiazine-1,1-dioxide) Brain Res. 265, 163 168 Roy, A, Adinoffr B Roerich, L, Lamparski, D, CusteL R, Lorenz, V, Barbaccia, M., Guldotti. A, Costa, E and Linnoila, M. (1988) Pathological gambling A psychobiological study Arch. Gen Psychiatry45, 36~373. van Gelder, N M (1972) Antagonism by taurine of cobalt induced epilepsy m cat and mouse Brain Res 47, 157-165

Compulsivesive buying, depression and antidepressants M. Lejoyeux 1, V. Tassain 2. j. Adds 2. 1 Department ofPsych/atG, Groupe Hospitaher Bichat-Beaujon, 75018 Pans, France," 2 Department of Psychiatry, Hopital Louis Mourier, 92700, Co/ombes France Compulsive buying involves repetitive purchases of expensive and/or unuseful goods. They can lead to debts and familial disturbances. The articles are not bought because they are needed or a bargain, or even out of an ntnnsic desire for the thing itself. Compulsive buyings are often associated with psychiatric morbidity and especially with depression. Patients usually describe compulsive buying in reaction to negative affect states. In order to precise the relation between depression and compulsive buym g we specifically studied buying behaviour in 100 depressed inpatients. We assesed buying behaviour with a 19-item check-list especially designed for the evaluation of compulsive buying among psychiatric patients. We tried to assess the behavior itself and its consequences. Since we focused on buying ~mpulses. we did not study the general spending behavior. We thus selected 19 items (questions with yes or no answers) which represented maior basic dimensions of compulsive buying. These dimensions were: ~mpulsivity of buying, feeling an urge to buy and shop. emotions typically felt before, during and after purchasing, postpurchase guilt and regrets, engagement for short-term gratification, tangible consequences of buying, attempts to control spending by avoiding stores or other methods. Compulsive buyings related to a manic state were excluded from our study. Diagnosis of depression were made, according to DSM III R criteria, with the Schedule for Affective Disorders and Schizophrenia, It appeared that 8% of the depressed inDatients presented compulsive buyings All depressed patients presenting compulsive buyings were women, in all cases, buying corresponded to periods of intense sadness At these moments, the patients could not resist to the desire to go out for shopping and to spend important amount of money. They described their shopping episodes as an intense urge to "go into a store and get something new". Many patients also noted that their buyings had antidepressant and anxiolytic effects. After a very short period of euphoria, patients were invaded by culpability and sense of gudt. They left shops while regretting their behaviour. In all cases of compulsive buyings, the expenses provocated debts difficult to reimburse Two cases o ~ women presenting compulsive buyings were prospectively followed, at the admission and after one month of antidepressant treatment (clom~pramme 150 rag/day). In the two cases, abnormal behaviour disap-

370

P-6 0bsessive compulsive disorders

peared with the treatment of depresslon When ~he patlents were no more depressed, thevstoppedthe~r excessivespendings. Six months a t e r both of the patients relapsed We observed that depressive symptoms fulfllhng DSM III criteria of major depression and compulsive buyings reappeared at the same time in the two patients Compulsive buying were thus directly induced by depression Negative emotions, espec~allysadness, increased compulsive buyers' propensity to buy Loneliness, anger, frustration and prntationalso precipitated compulsive buying One of the main factorshnk~ng compulsive buying with depression could be low self e s t e e m This factor,s unammously identified as being very important ~n the et~ology of addictwe buying and depression It is also significantly improved by antidepressant treatment

References Christenson G A , Faber R ~ de Zwaan M e! al Compulstve buying: Descriptive charac teristics and psychiatric comorbidity Journal of Clinical Psychiatry. 1994 55 1 51 11 Lejoyeux M. Hourtane M Ades J Compulsive buying and depression Journal of Chnlcal Psychiatry, In press

Sequential administration of augmentation strategies in treatment-resistant obsessive compulsive disorder R ~lier, R. Bergeron, C Hebert Neurob/o/ogJca/Psyeh/atry Unit, MEG;~~ Universi84, Montreal, Canada H3A 1A 1 Several augmentation strategies have been used with success in depressecJ patients treated with but not respoqding to antidepressant drugs These pharmacological approaches, such as lithium and buspirone addition, have not been found effective in placebo-controlled studies in OCD patients no: responding t o a s e r o t c n i n ( 5 - H T } r e u p t a k e nhibitor{SRI) More recently, tOe addition of the 5 HT1A antagonist/# adrenoceptor antagonist pindolol has been reported to exert a rapid therapeutic effect in depressed patients resls rant to certain SRI or M A g i This potentiation would result from the capaclb/ of pindolol to selectively block the 5-HT1A autoreceptors on the cell body of 5-HT neurons so as to allow a normahzatpon of tbeirfinng activltyln the pres e n c e o f t h e S R I o r t h e M A O I InOCD, however, only potent SRl are effecbve This therapeutic effect would result from the capacity of these drugs to de sensitize the terminal 5-HTID autoreceptor located in brain regions involved :n the mediation of OCDsymptoms. such as the orbitofrontar cortex [hese observations imply that factors modulating 5-HT transmission at the level of t~e ceIl body of S-HT neurons (i e firing activity) would be morelmportantl~" the antidepressant effect of SRI. whereas, factors at the terminal level (l e modulation of 5-HT release) would be mo~e important in the anti-OCD effect of SRI. In order to test th~s hypothesis, we added oindolol, busp~roqe ard tryptophan to OCD patients res stant to treatment ~en patients (5 on fluoxetine 40 rag/day 4 on parexetlne 40 or 60 rng/dav and 1 on chlorimipramine 250 rag/day) were gwen pindolol 2 5 mg th'ice daily The mean Yale-Brown Obsessive Cor"pu~swe Scale (YBQCS) score d,d not change over the next 4 w e e k s (baseline: 26 ± 2, day 2 8 24 ± 3 1 [he Montgomery-Asberg Depression Rating Scale (MADRS) score, however gradually decreased over this four-week period n t h e 8 p a t i e n t s p r e s e n t ~ n g at least miid depressive symptomatology (MADRS > 12; basei net " 7 :± 31, there was a significant ~mprovement at days 14 (10 : 3). 21 (9 ± 31 and 28 (8 ± 3). In 3 patients, subsequent buspirone adddtlon (30-50 mg/cay) d,:~ not produce any change of OCD s y m o t e m s Six patients were then maintained on their SRI and pmdotol regmlen an~J given L-tryptophan 2 g daily, increasing Jt to 4 to 8 g/day as necessary There was no s@nificant changes of OCD symptoms after 2 weeks of tryptophan additron (YBOCS before: 24 ± 2: after: 23 ± 3). However, :here was a significant improvement after 4 and 6 weeks of tryptophan additlo" (YBOCS: 18 ± 2 and 16 4- 2, respectively) These results indicate that pindolol addition to an SRI ,s not eflectwe on OCD symptoms. However. when depresswe symptomatology is present, pindolol exerts a marked antidepressant effect The limited obse[vabons with buspirone addition are consistent with the lack of anti-OCD effect of this 5 HT1A agonist. Finally, tryptophan addition appears to be effective in decreasing OCD symptomatology n OCD patients treated with out net responding to an SRI and pindoloi

References Artigas, F, Perez, V and Alvarez. E {t994) P~ndslo! nduces a rap~d ~mprovem~qt o ~~e pressed patients treated wilh serotonln reuptaKe mnib,tor Arch Gen Psych at E! 248-51 Bile, P and Bergeron, R (1995}. Effectiveness o| pindolol with selectee antleepres£ar~t drugs in the treatment of major del3ress~on u Clin Psycnopharrnacol 15, in #reds

El Mansarl M , Bouchard, C , and Bher. P (1995) Alteration of serotonin release in the guinea ptg orbitofrontal cortex by selective serotonin reuptake inhibitors: Relevance to treatmer,t of obsessive-compulsive disorder. Neuropsychopharmacology 13, in press.

Normal brain 5HT2 receptors in obsessive-compulsive disorder demonstrated by positron emiss0on tomography B~ver12rS. G o l d m a n 1 , B Gribomont 2 , M . M o n c l u s l p Danhaut 1, J Mendlewicz 2 F. Lotstra 2 1 PETB/omed/eal Cyc/otfon Unit," 2 Psychiatry

Department, Erasrne Hospita/, Free University of Brusse/s, 808 route de Lenmk, 1070 Brusse/s, Belgium Efficacy o ~ serotonergic reuptake inbibitors in the treatment of obsessivecompulsive disorder (OCDI represents a pharmacological clue in favor of the mqphcatlon of the serotonm (SHT) system in this disorder. The aim of our study was to investigate brain 5HT 2 receptor in OCD using the select,re radiohgand [18F]altanserin and positron emission tomography (PET). Niqety-.m,nute dynamic PET studies were carried out in eight drug-free OCD patients and eight sex- and age-matched healthy subjects after intravenous mlection of 0.1 mCi/kg [18F]altanserin (specific activity: 2 - 3 Ci//zM). [18F]altanserin concentration (count/s/pixel) was calculated in 10 cortical regions of interest (ROI)(9 in the cerebrum and 1 in the cerebellum). To evaluate the quantitative distribution of the tracer in the brain, we used a nonlinear regression method (NLR) providing quantitative evaluation of the rate constants (K t and k 2 through ks}in a four-compartmental model (plasma extracellular, specific and non-specific binding). We also used a s~mpie rat o method (count rate in a ROI/count rate in the cerebellar ROI). Using a two-way repeated measure analyse of variance (ANOVA), we found no difference in brain 5HT 2 receptor distribution, obtained by NLR method, between ©CO patients and control subjects. In count rate ratios, Student's t tests faded to demonstrate any difference between the t w o groups of subjects This PET study on untreated patients does not provide evidence for an mphcationofSHT 2 subtype receptor in t h e p a t h o p h y s i o l o g y o f O C D .

References Bwer, F, Goldman. S , Luxen, A, Monclus, M , Forestini, M., Mendlewicz. J and Lotstra F {1994) Multi-compartmental study of [18Flaltanserin binding to brain 5HT2 receptors pr human using positron emission tomography European Journal of Nuclear Medecine 21. 937 946

i P-6-7 ]

Pathogenetic mechanism of obsessive-compulsive disorder

J Kafka, Eva P~lova Faculty of Medicine Umverslty t?J. ,~afarl/<, t/: SNP ~.

I 040 66 Kog/ce, Slovakla The obsessive phenomena have been known s;nce ancient times and psy:hiatnsts have been interested in studying them since the beginning of psychiatry However, patogenetic mechanism remains not completely explained. Oqe of the reasons is the fact that recently obsesive-compulsive disorder is ~ot being viewed of nosolog~cal point of view which we think is rlotfullyiustlfied Clinical description of intrusive phenomena h a s a l o n g t r a dition Obsessive-compulsive disorders (OCD) were considered as a part of psychot c disorders, later they became a central part of concept of neurosis ann on y recently their specific place has been recognized. Tnere exists a group of disorder, with an intrusivness and a compuJsivity wlttlm sorne psychical contents which are intrusive and they determine oebavour or affected individuum. Such a person must deal with these ,solated phenomena on the cognitive level4hese are obsessive images and thoughts on emotional level-these is anxiety and most importantly phobias and on behavioral leveJ these are compulsions. We suppose, that on a conscious e v e l a n i n d i v i d u u m is not capable of adequate processing these phenomena. This results in vanous disorder, that include the phenomenon of intrus,vness eventually developing in the distinct disorder named OCD. Based on known facts and our experience there are three mechanlsms of development of these disorders Innermechanisms-biologicaland psychical-are based on nonspecific impairment in following systems: bazal ganglia, s~ec#icly nucleus caudatus, limbic system, prefrontal and frontal cortex They might be responsible for insufficient integration of these in:ruswe phenomena in "ego" complex or possibly even in more extensive concept of consciousness The third one ~s an external mechanism-the influence of social environment O n t h s l e v e l t h e c o m m u n i c a t l o n a n d p e r s o n a l i t y p r o b l e m s m a y o c c u r . A~I these mechanisms act together and result in various clinical symptoms or syndromes which can be grouped into: (1) symptomatic or syndrome-