Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria Olle Eriksson a, * , Anders Wall b , Ina Marteinsdottir c , Hans A ˚ gren d , Per Hartvig e , Gunnar Blomqvist b , Bengt La ˚ngstro ¨m b , Tord Naesse ´n a a Department of Women’s and Children’s Health/Obstetrics and Gynecology, University Hospital, SE-751 85 Uppsala, Sweden b Uppsala Imanet AB, University Hospital, SE-751 85 Uppsala, Sweden c Department of Neuroscience, Section of Psychiatry, University Hospital, SE-751 85 Uppsala, Sweden d Neurotec Department, Division of Psychiatry, Karolinska Institute, SE-171 76 Stockholm, Sweden e Hospital Pharmacy, University Hospital, SE-751 85 Uppsala, Sweden Received 27 July 2004; received in revised form 20 December 2004; accepted 14 February 2005 Abstract The cardinal mood symptoms of premenstrual dysphoria can be effectively treated by serotonin-augmenting drugs. The aim of the study was to test the serotonin hypothesis of this disorder, i.e. of an association between premenstrual decline in brain serotonin function and concomitant worsening of self-rated cardinal mood symptoms. Positron emission tomography was used to assess changes in brain trapping of 11 C-labeled 5-hydroxytryptophan, the immediate precursor of serotonin, in the follicular and premenstrual phases of the menstrual cycle in eight women with premenstrual dysphoria. Changes in mood and physical symptoms were assessed from daily visual analog scale ratings. Worsening of cardinal mood symptoms showed significant inverse associations with changes in brain serotonin precursor trapping; for the symptom birritableQ, r s = À 0.83, and for bdepressed moodQ r s = À 0.81. Positive mood variables showed positive associations, whereas physical symptoms generally displayed weak or no associations. The data indicate strong inverse associations between worsening of cardinal symptoms of premenstrual dysphoria and brain serotonin precursor ( 11 C-labeled 5-hydroxytryptophan) trapping. The results may in part support a role for serotonin in premenstrual dysphoria and may provide a clue to the effectiveness of serotonin-augmenting drugs in this disorder but should, due to small sample size and methodological shortcomings, be considered preliminary. D 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Affective symptoms; 5-Hydroxytryptophan; Positron emission tomography; Premenstrual dysphoric disorder; Premenstrual syndrome; Right caudate nucleus 1. Introduction Premenstrual dysphoric disorder (PMDD) is charac- terized by the cyclical occurrence of disabling mood symptoms in the luteal (premenstrual) phase of the men- strual cycle, with a profound impact on the afflicted woman and her near environment ( American Psychiatric Association, 1994). The cardinal symptoms are irritabil- ity, depressed mood, affective lability and impaired im- pulse control, all of which are effectively alleviated by drugs increasing brain serotonin activity ( Eriksson, 1999). Randomised trials have shown selective serotonin reuptake inhibitors (SSRIs) to be effective pharmacolog- ical treatments in about 60% of women with PMDD ( Rapkin, 2003), and these drugs are considered the 0925-4927/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pscychresns.2005.02.012 * Corresponding author. Tel.: +46 18 6115777; fax: +46 18 559775. E-mail address: olle.eriksson@kbh.uu.se (O. Eriksson). Psychiatry Research: Neuroimaging 146 (2006) 107 – 116 www.elsevier.com/locate/psychresns