Women with PMDD significantly differed from control women in displaying a luteal phase-related increase in negative judgments of mood in the facial expression of the photos, both N → S false positives and negative bias. The FDT task was untimed and was based on subjective judgments that do not require any concerted effort of concentration, so results are unlikely to have been influenced by impairments in attention or lack of motivation potentially consequent to the symptoms experienced by women with PMDD during the luteal phase. This inference is supported by the lack of any significant differences between patients and controls on the age discrimination task.
The potential import of these findings is as follows: first, the negative bias on the FDT represents one of several measures that show menstrual cycle-related variation in patients with PMDD but not controls. Other examples include luteal phase-related increases in measures of personality dysfunction (Berlin et al., 2001
) and the reporting of negative life events (Schmidt et al., 1990
). Further, unlike some cognitive measures that have shown abnormalities in patients with PMDD independent of menstrual cycle phase (Keenan et al., 1995
), the bias in affective assessment in PMDD appears to be a state-linked rather than a trait-linked characteristic. Consequently, we can postulate that in women with PMDD, events related to the luteal phase trigger a functional dysregulation in specific brain regions known to play a role in the recognition of emotional facial expression (e.g., amygdala, fusiform gyrus, orbital frontal cortex (OFC), superior temporal sulcus) (Izquierdo et al., 2004
; Killgore et al., 2004
; LaBar et al., 2003
). Disturbances in these same brain regions have been implicated in depression (Elliott et al., 2002
; Lawrence et al., 2004
; Phillips et al., 2003
), and the FDT abnormalities in PMDD during the luteal phase are similar to those in major depression (i.e., decreased specificity and increased negative bias) (Surguladze et al., 2004
). The relevance of luteal phase endocrine changes for the modulation of affective processing is supported by recent fMRI findings that anterior-medial OFC activity for negative vs. neutral stimuli increased premenstrually and decreased postmenstrually (Protopopescu et al., 2005
). Interestingly, performance in our study was not related to severity of mood measures in either patients or controls. While correlations between performance on the FDT and measures of either depression (Gur et al., 1992
) or anxiety (Bouhuys et al., 1997
) have been reported previously, so has the absence of relationship to either mood measure (Elliott et al., 2002
; Lawrence et al., 2004
Second, the bias in affect assessment that we observed may reflect a critical element of the phenomenology of these patients, who report that their perceptions and elicited behaviors differ as a function of menstrual cycle phase. This tendency for women with PMDD to view emotions expressed in faces more negatively during the luteal phase has three possible attendant implications. First, it may significantly contribute to both the generation and perpetuation of the negative affective state during the luteal phase. As has been postulated in MDD, a negative bias in the processing of emotion in facial expression reflects the experience of stimuli as both more emotional and more negative, with consequent elicited behaviors more likely to reinforce rather than reverse the negative affective state (Fu et al., 2004
; Phillips et al., 2003
). Second, it suggests additional avenues of investigation that may more precisely define both the nature of the affective disturbance in PMDD as well as its underlying neurophysiologic basis. For example, Hooker et al. (Hooker et al., 2004
) show that an inability to perform reversal learning with emotionally charged faces is associated with an oversensitivity to negative social cues, cognitive inflexibility, and a differential pattern of brain regional activation on fMRI (Hooker et al., 2004
). Studies by Schultz and colleagues (Schultz 2004
) demonstrate that a reward that is smaller than that expected will actually inhibit the firing of dopamine neurons associated with the expectation of reward. Hence, an affective misperception may contribute to as well as reflect the experience of anhedonia or dysphoria. Third, the state-dependent nature of the negative bias should, in a disorder with rapid (monthly), predictable state changes, permit a more precise delineation of the underlying neurocircuitry than a disorder with much less frequent or predictable state changes.
While the major outcome measures showed diagnostic by phase effects, two secondary measures revealed diagnostic effects independent of menstrual cycle phase. Comparison women showed better performance identifying true positive happy items and in avoiding false negative happy judgments. These findings are consistent with the demonstration that just as depressed patients are biased towards sad information, controls may be biased toward happy information (Elliott et al., 2002
) (although differences specifically in positive bias did not reach significance in our study). Indeed it has been suggested that the medial frontal region may respond differentially to sad targets in depressed patients and to happy targets in controls (Elliott et al., 2002
). It is possible that the recurrence of negative affective states in women with PMDD may be accompanied by perceptual residua that eliminate the normal tendency to “over-identify” happy items even during the asymptomatic phase of the menstrual cycle. The differences in true positive happy and false negative happy items observed between women with PMDD and comparison women did not appear confounded by a past history of depression, as the diagnostic effects remained significant when the analyses were repeated without the six subjects with a past history of depression.
This study has several limitations First, the levels of significance obtained were modest and, while consistent, would not have withstood the most conservative correction for multiple comparisons. Second, we did not have adequate numbers of PMDD women with a past history of MDD to determine whether such a history would predict a different pattern of results. Third, despite reasonable sample sizes, our findings must be viewed as preliminary until replicated in an independent sample. If replicated, the observation of menstrual cycle phase-related, mood-congruent, negative processing biases in women with PMDD would suggest that (luteal phase-specific) affective symptoms in PMDD potentially share a neurobiological commonality with depression. As such, future studies of disturbed perception of emotion in facial expressions in women with PMDD may not only help define the neurocircuitry (with functional imaging) of PMDD but may as well exploit the presence of a specific physiologic variable - the change in reproductive steroids - that is directly relevant to changes in affective state and hence may promote a more detailed general understanding of the physiological disturbances and substrates of affective dysregulation.