Abnormalities of Dorsolateral Prefrontal Function in Women With Premenstrual Dysphoric Disorder: A Multimodal Neuroimaging Study

• Published in: The American journal of psychiatry 2013-03, Vol.170 (3), p.305-314
• Main Authors: Baller, Erica B., Wei, Shau-Ming, Kohn, Philip D., Rubinow, David R., Alarcón, Gabriela, Schmidt, Peter J., Berman, Karen F.
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Biological and medical sciences; Brain Mapping; Depression; Drug Therapy, Combination; Estradiol - therapeutic use; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Leuprolide - therapeutic use; Magnetic Resonance Imaging; Medical imaging; Medical sciences; Memory, Short-Term - drug effects; Memory, Short-Term - physiology; Miscellaneous; Mood disorders; Neurology; Non tumoral diseases; Oxygen - blood; PMS; Positron-Emission Tomography; Prefrontal Cortex - blood supply; Prefrontal Cortex - drug effects; Prefrontal Cortex - physiopathology; Premenstrual syndrome; Premenstrual Syndrome - drug therapy; Premenstrual Syndrome - physiopathology; Premenstrual Syndrome - psychology; Progesterone - therapeutic use; Prospective Studies; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Women
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.2012.12030385

Under controlled hormonal conditions, women with PMDD displayed abnormal patterns of dorsolateral prefrontal cortex activation during working memory. In addition, the magnitude of abnormal activation was related to the degree of PMDD disability and disease burden, indicating a neural substrate of vulnerability that may confer earlier age at onset or more severe clinical presentation of PMDD. ObjectiveTo investigate the neural substrate of premenstrual dysphoric disorder (PMDD), the authors used [15O]H2O positron emission tomography (PET) regional cerebral blood flow (rCBF) and blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal measurements during working memory in conjunction with a 6-month hormone manipulation protocol.MethodPET and fMRI scans were obtained from women with prospectively confirmed PMDD and asymptomatic comparison subjects while they completed the n-back task during three hormone conditions: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate, leuprolide plus estradiol, and leuprolide plus progesterone. Fifteen patients and 15 matched comparison subjects underwent PET imaging. Fourteen patients and 14 comparison subjects underwent fMRI. For each hormone condition, rCBF was measured with [15O]H2O PET, and BOLD signal was measured with fMRI, both during an n-back working memory paradigm. Global Assessment of Functioning Scale (GAF) scores and clinical characteristics were obtained for each patient before hormone manipulation, and symptoms were measured before and during the protocol.ResultsIn both the PET and fMRI studies, a main effect of diagnosis was observed, with PMDD patients showing greater prefrontal activation than comparison subjects. In the patient group, the degree to which dorsolateral prefrontal cortex activation was abnormally increased correlated with several dimensions of disease: disability as indicated by GAF scores, age at symptom onset, duration of PMDD, and differences in pre- and postmenses PMDD symptoms.ConclusionsAbnormal working memory activation in PMDD, specifically in the dorsolateral prefrontal cortex, is related to PMDD severity, symptoms, age at onset, and disease burden. These results support the clinical relevance of the findings and the proposal that dorsolateral prefrontal cortex dysfunction represents a substrate of risk for PMDD. The concordance of the fMRI and PET data attests to the neurobiological validity of the results.