Abnormalities of dorsolateral prefrontal function in women with premenstrual dysphoric disorder: a multimodal neuroimaging study.
OBJECTIVE
To 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.


METHODS
PET 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.


RESULTS
In 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.


CONCLUSIONS
Abnormal 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.
Section on Integrative Neuroimaging, Clinical Brain Disorders Branch, Gene, Cognition, NIMH Intramural Research Programs, NIH, Bethesda, MD, USA.
Erica B
EB
Baller
Shau-Ming
SM
Wei
Philip D
PD
Kohn
David R
DR
Rubinow
Gabriela
G
Alarcón
Peter J
PJ
Schmidt
Karen F
KF
Berman
D000328:Adult; D001931:Brain Mapping; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D016729:Leuprolide / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000097:blood*; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D011293:Premenstrual Syndrome / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D011374:Progesterone / Q000627:therapeutic use; D011446:Prospective Studies
D011374:Progesterone; D004958:Estradiol; D016729:Leuprolide; D010100:Oxygen