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Introduction Premenstrual dysphoric disorder PMDD is characterized by the cyclical occurrence of negative mood symptoms in the late luteal phase of the menstrual cycle [ 1 ]. Methods Participants Twenty women were recruited for the study; twelve fulfilled the criteria for PMD and eight had no premenstrual mood symptoms. Subjects with PMD Of the twelve women fulfilling the PMD criteria, five were recruited through our gynaecological clinic and seven had participated in an earlier treatment trial [ 27 ].

Imaging The study was carried out in a stepwise fashion and the subjects were therefore subdived into three cohorts for PET registration. PET scanning protocol PET data were collected using identical acquisition protocols: 15 O-H 2 O scans were recorded in 15 frames of 10 s and [ 11 C]5-HTP scans were recorded in five frames of 60 s, five frames of s, five frames of s and six frames of s. Post-imaging processing All the images for each subject were lined up, as described by Andersson [ 42 ].

Open in a separate window. Fig 1. Fig 2. Statistical analysis The data consisted of brain activity measurements in the left and right sides of four brain regions during two phases, for patients and controls. Results Subject characteristics PMD and control subjects did not differ significantly in age, height, number of pregnancies, number of children born, menstrual cycle length, duration of menstrual bleeding or MADRS score at study entry Table 1.

Table 1 Subject characteristics. Table 2 Group characteristics at PET registration. Table 3 Outcome of linear mixed-model analysis. Fig 3. Fig 4. Fig 5. Fig 6.

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Discussion The main finding of this study was the clear and obvious difference in premenstrual right-to-left-sided asymmetry in dorsolateral prefrontal cortex [ 11 C]5-HTP-derived brain activity between asymptomatic control women and women with PMD. Conclusion It is well known that the dorsolateral prefrontal cortex is crucial for impulse control and for inhibition of affect and aggression [ 23 , 74 ].

Supporting Information S1 File Subject characteristics. PDF Click here for additional data file. S2 File Hormone data. S4 File VAS ratings for 14 variables. S5 File Metadata file. Data Availability All relevant data are available in the paper and its Supporting Information files.

References 1. American Psychiatric Assoc.

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Premenstrual syndrome. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. N Engl J Med. Eriksson E. Serotonin reuptake inhibitors for the treatment of premenstrual dysphoria.

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Int Clin Psychopharmacol. Effect of clomipramine on premenstrual syndrome. Acta Psychiatr Scand. Efficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: a systematic review. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database Syst Rev. Acute tryptophan depletion aggravates premenstrual syndrome. J Affect Disord. Genetic approaches for understanding the role of serotonin receptors in mood and behavior. Curr Opin Neurobiol. Olivier B. Serotonin: a never-ending story. Eur J Pharmacol. Lucki I. The spectrum of behaviors influenced by serotonin.

Biol Psychiatry. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology Berl. Andrade R. Serotonergic regulation of neuronal excitability in the prefrontal cortex. Increase in prefrontal cortex serotonin 2A receptors following estrogen treatment in postmenopausal women.

Am J Psychiatry. Effects of hormone replacement therapy on cerebral serotonin-1A receptor binding in postmenopausal women examined with [carbonyl- 1 1 C]WAY Orbitofrontal cortex activity related to emotional processing changes across the menstrual cycle. Abnormalities of dorsolateral prefrontal function in women with premenstrual dysphoric disorder: a multimodal neuroimaging study.

Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women. Menstrual cycle phase modulates reward-related neural function in women. Hormonal cycle modulates arousal circuitry in women using functional magnetic resonance imaging. J Neurosci.

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Impulsivity, time perception, emotion and reinforcement sensitivity in patients with orbitofrontal cortex lesions. Laboratory induced aggression: a positron emission tomography study of aggressive individuals with borderline personality disorder. Asymmetry in the dorsolateral prefrontal cortex and aggressive behavior: a continuous theta-burst magnetic stimulation study. Soc Neurosci. Volume reduction in prefrontal gray matter in unsuccessful criminal psychopaths. Neuropsychiatry of frontal lobe dysfunction in violent and criminal behaviour: a critical review.

J Neurol Neurosurg Psychiatry. Neural mechanisms of aggression. Nat Rev Neurosci. Compounds with affinity for serotonergic receptors in the treatment of premenstrual dysphoria: a comparison of buspirone, nefazodone and placebo. The neurobiology of impulsive aggression. Psychiatr Clin North Am. Aromatic L-amino acid decarboxylase: a neglected and misunderstood enzyme. Neurochem Res. Measuring serotonin synthesis: from conventional methods to PET tracers and their pre clinical implications.

Kinetic compartment modeling of [11C]hydroxy-L-tryptophan for positron emission tomography assessment of serotonin synthesis in human brain. J Cereb Blood Flow Metab. Brain kinetics of 11 C-labelled L-tryptophan and 5-hydroxy-L-tryptophan in the rhesus monkey. A study using positron emission tomography. J Neural Transm Gen Sect. Determination of 5-hydroxy-L-[betaC]tryptophan and its in vivo-formed radiolabeled metabolites in brain tissue using high performance liquid chromatography: a study supporting radiotracer kinetics obtained with positron emission tomography.

Nucl Med Biol. Lloyd KG, Hornykiewicz O. J Neurochem. Monoamine concentrations in the human brain. A comparison between two methods of tissue handling. J Neural Transm. Regional and laminar distribution of the dopamine and serotonin innervation in the macaque cerebral cortex: a radioautographic study. J Comp Neurol. Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria. Psychiatry Res. First MB. Washington, D. Diagnosis of premenstrual tension syndrome: description and evaluation of a procedure for diagnosis and differential diagnosis.

J Psychosom Obstet Gynecol. Accurate attenuation correction despite movement during PET imaging. J Nucl Med. Agren H, Reibring L. PET studies of presynaptic monoamine metabolism in depressed patients and healthy volunteers. Prefrontal-subcortical and limbic circuit mediation of major depressive disorder.

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Semin Clin Neuropsychiatry. Davidson RJ. Anxiety and affective style: role of prefrontal cortex and amygdala. SAS for mixed models 2 ed. Olsson U. Statistics for life science 2 Lund: Studentlitteratur; Applied multivariate statistical analysis Upper Saddle River, N. Statistics for life science 1 Lund: Studentlitteratur; SAS Insitute Inc.

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It includes information that centres need to administer coursework and must be read in conjunction with the course specification. Please note: Understanding Standards materials are regularly reviewed to ensure they remain up to date. Where any particular areas of concern are identified, which are not addressed by our Understanding Standards events or support materials, we will offer free continuing professional development CPD training, subject to request.

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