Background: Dysphoric milk ejection reflex (D-MER) is a phenomenon that occurs before milk letdown and is described as a wave of negative or devastating emotions, ranging from mild to severe and lasting for seconds to minutes. To date, there has been little research regarding this phenomenon. This study aims to determine the prevalence of D-MER in our population as well as its association with postnatal depression scores and breastfeeding self-efficacy. Methods: Lactating persons between 4 and 12 weeks postpartum at our institution were invited to complete an anonymous 59-question survey via an online platform. Questions asked included patient demographics, presence of symptoms of dysphoria (including timing, duration, and frequency), the Edinburgh Postnatal Depression Scale (EPDS), and the Breastfeeding Self-Efficacy Scale Short Form (BSES-sf). Results: In total, 201 women completed the survey. Twelve women were classified as likely having D-MER (6%). Symptom resolution primarily occurred within a minute to 5 minutes (58%). Mean EPDS scores differed significantly between those with likely D-MER and those without (12.2 vs. 5.4, p = 0.002). BSES-sf scores differed significantly between the two groups (43.1 vs. 52.5, p = 0.009). Preexisting depression or anxiety was not associated with D-MER (p = 0.133), other reported mood disorders differed significantly between those with D-MER and those without (p = 0.004). Demographic characteristics of women with and without D-MER were similar. Conclusion: D-MER prevalence may be lower than previously reported. Patients with likely D-MER appear to have lower breastfeeding self-efficacy and higher depression scores. Those with preexisting mood disorders may be at higher risk of experiencing D-MER.

Posttraumatic stress disorder (PTSD) is a heterogeneous condition that can be characterized by unique typologies of symptoms. To date, no study has examined predominant PTSD typologies using DSM-5 criteria. We used latent class analysis (LCA) to identify typologies of DSM-5 PTSD symptoms in 158 U.S. veterans who screened positive for this condition. A three-class solution provided the best fit to the data, described as Dysphoric (36.2%), High Symptom (34.0%) and Threat (29.8%). The Threat class had higher probabilities of intrusions and avoidance compared to the Dysphoric class; the Dysphoric class had higher probabilities of negative affect, anhedonia and externalizing behavior relative to Threat; the High Symptom class had high probabilities of all symptoms. Compared to the Threat class, the Dysphoric class was more likely to have a lifetime history of major depressive, alcohol and drug use disorders; the High Symptom class was more likely to have a lifetime history of alcohol, drug, and nicotine use disorder, current generalized anxiety, or to have attempted or currently contemplated suicide. The High Symptom class reported greater mental, physical and cognitive impairment and lower quality of life. These findings underscore the importance of a personalized approach to the assessment and treatment of DSM-5 PTSD.

Difficulties in updating working memory (WM) may underlie problems with regulating emotions that contribute to depression. To examine the ability of updating affective materials in WM, 33 dysphoric and 34 non-dysphoric participants were asked to evaluate the self-descriptiveness of emotional adjectives and provide answers to self-relevant questions. Within 3-7 days, they completed a two-back task with a series of self-irrelevant or self-relevant emotional words (they had generated previously) and four conditions (match-set, break-set, perseveration-set, and no-set). After the WM task, an unexpected recall task was administered; controls recalled more positive self-relevant words and intrusions while dysphoric participants recalled more negative self-relevant words and intrusions. In break-set trials of the two-back task, dysphoric individuals showed slower response to self-relevant words regardless of valence. In the match-set and perseveration-set trials, dysphoric participants showed delayed response to self-related negative words. Moreover, longer reaction times for self-relevant negative words were correlated with higher rumination and worse depression. The results suggest that dysphoric undergraduates are interfered more by and have a better memory of self-relevant negative stimuli in WM, which is closely correlated with rumination. This study is among the first to confirm the potential mechanism that could underwrite the involvement of self-schema in effectively regulating negative affect.

Salvinorin A (SalA), a selective κ-opioid receptor (KOR) agonist, produces dysphoria and pro-depressant like effects. These actions have been attributed to inhibition of striatal dopamine release. The dopamine transporter (DAT) regulates dopamine transmission via uptake of released neurotransmitter. KORs are apposed to DAT in dopamine nerve terminals suggesting an additional target by which SalA modulates dopamine transmission. SalA produced a concentration-dependent, nor-binaltorphimine (BNI)- and pertussis toxin-sensitive increase of ASP(+) accumulation in EM4 cells coexpressing myc-KOR and YFP-DAT, using live cell imaging and the fluorescent monoamine transporter substrate, trans 4-(4-(dimethylamino)-styryl)-N-methylpyridinium) (ASP(+)). Other KOR agonists also increased DAT activity that was abolished by BNI pretreatment. While SalA increased DAT activity, SalA treatment decreased serotonin transporter (SERT) activity and had no effect on norepinephrine transporter (NET) activity. In striatum, SalA increased the Vmax for DAT mediated DA transport and DAT surface expression. SalA up-regulation of DAT function is mediated by KOR activation and the KOR-linked extracellular signal regulated kinase-½ (ERK1/2) pathway. Co-immunoprecipitation and BRET studies revealed that DAT and KOR exist in a complex. In live cells, DAT and KOR exhibited robust FRET signals under basal conditions. SalA exposure caused a rapid and significant increase of the FRET signal. This suggests that the formation of KOR and DAT complexes is promoted in response to KOR activation. Together, these data suggest that enhanced DA transport and decreased DA release resulting in decreased dopamine signalling may contribute to the dysphoric and pro-depressant like effects of SalA and other KOR agonists.