Toward a functional neuroanatomy of premenstrual dysphoric disorder.
BACKGROUND
Premenstrual dysphoric disorder (PMDD) is a prevalent disorder in the spectrum of affective illness, and is associated with significant morbidity. The neurobiology of this underdiagnosed and undertreated illness is poorly understood. A functional magnetic resonance imaging (fMRI) probe of fronto-limbic function was used to advance understanding of PMDD pathophysiology.


METHODS
We applied BOLD fMRI and Statistical Parametric Mapping to study neural response to emotional words in the context of an emotional Go/NoGo inhibitory control task. We examined alterations in this response across the menstrual cycle, in the premenstrual (late luteal) phase and the postmenstrual (late follicular) phase.


RESULTS
In the premenstrual (vs. postmenstrual) phase, PMDD subjects, compared with asymptomatic subjects, showed an increased amygdala response to negative vs. neutral stimuli, and a decreased ventral striatum response to positive vs. neutral stimuli. PMDD subjects failed to show the asymptomatic subjects' patterns of increased medial and decreased lateral orbitofrontal cortex (OFC) response to negative vs. neutral stimuli in the premenstrual vs. postmenstrual phase. This decreased premenstrual medial OFC response to negative stimuli in PMDD subjects was further enhanced in the context of behavioral inhibition.


CONCLUSIONS
Further studies with larger numbers of subjects are needed.


CONCLUSIONS
The results support a neurobiological model of enhanced negative emotional processing, diminished positive emotional processing, and diminished top-down control of limbic activity in PMDD during the premenstrual phase. These findings provide a basis for a neurocircuitry model of PMDD, and have implications for studies of mood/emotional regulation across the human menstrual cycle in health and disease.
Protopopescu
Xenia
X
Functional Neuroimaging Laboratory, Department of Psychiatry, Weill Medical College of Cornell University, New York, NY 10021, United States. xoprotop@med.cornell.edu
Tuescher
Oliver
O
Pan
Hong
H
Epstein
Jane
J
Root
James
J
Chang
Luke
L
Altemus
Margaret
M
Polanecsky
Margaret
M
McEwen
Bruce
B
Stern
Emily
E
Silbersweig
David
D
D000328:Adult; D000679:Amygdala / Q000503:physiopathology; D001143:Arousal / Q000502:physiology; D001931:Brain Mapping; D003342:Corpus Striatum / Q000503:physiopathology; D004292:Dominance, Cerebral / Q000502:physiology; D004644:Emotions / Q000502:physiology; D005260:Female; D005498:Follicular Phase / Q000502:physiology; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007266:Inhibition, Psychological; D008032:Limbic System / Q000503:physiopathology*; D008183:Luteal Phase / Q000502:physiology; D008279:Magnetic Resonance Imaging; D011939:Mental Recall / Q000502:physiology; D009415:Nerve Net / Q000503:physiopathology; D010100:Oxygen / Q000097:blood*; D011293:Premenstrual Syndrome / Q000503:physiopathology*; D012660:Semantics; D014706:Verbal Learning / Q000502:physiology
D010100:Oxygen