PMDD isn’t “just a mood disorder”
Premenstrual Dysphoric Disorder (PMDD) is a cyclical condition characterised by marked depressed mood, anxiety, feelings of hopelessness, self-deprecating thoughts, rage and overwhelm in the luteal phase of the menstrual cycle. These symptoms arise in response to the normal hormonal fluctuations of our cycle, and for some, they can be life threatening. Neurobiological mechanisms have been emerging in recent research, and some also point to a more global inflammatory upregulation in PMDD. What has been missing is a clear map of what else travels with PMDD - specifically, comorbidities, the conditions that occur alongside it more than chance would predict. A new 2026 preprint led by Christina Steyn, a Wellcome Trust-funded researcher at the University of Edinburgh, set out to draw exactly that: the physical and mental health conditions that cluster around PMDD (1). This study included a whopping 750,000+ participants.
The reasons it’s important to study comorbidities in research, are because:
1. If a certain condition occurs at higher rates in PMDD - it can point to shared underlying biology
2. The links can reveal how a condition might be operating across the body in all its complexities
3. It helps shape where future treatments and screening could focus.
And that’s the real takeaway: PMDD is not just PMS, not ‘just part of being a woman’. It isn’t even ‘just a depressive disorder’ as the diagnostic manual suggests. It is a complex condition that affects both brain and body at a systemic level. This is one reason why certain treatments fall short, and managing it usually requires a range of different approaches.
PMDD was associated with 24 hormone-related, neurodevelopmental, nutritional, liver, metabolic, digestive and immune conditions. Find out the specifics below.
The smartest part of this study? Who they compared PMDD to
Steyn's team drew on Our Future Health, the UK's largest population health cohort. From the pool, 4,047 people were identified with a lifetime PMDD diagnosis and analysed.
Rather than only measuring PMDD against a control group with no psychiatric history (a group of 691,000 people), they actually also compared women with PMDD to women with major depressive disorder who did not have PMDD (56,000 people). This was a very clever comparator…
Why set PMDD against depression? It helps isolate what’s specific to PMDD, not just what typically comes along with any mood disorder. It is a much higher bar than comparing against healthy controls, and it is what makes these findings so robust and insightful.
Hormone-related conditions were significantly more common in PMDD than depression
Endometriosis: 2.2x higher odds in PMDD than depression
PMOS (previously PCOS): 1.9x higher odds
Benign breast disease: 2x higher odds
This was the group of conditions that separated PMDD most clearly from depression.
Neurodevelopmental conditions were significantly more common in PMDD than depression
ADHD: 2.2x higher odds in PMDD than depression
Autism: 1.9x higher odds
Developmental learning disorders: 1.5x higher odds
This fits a fast-growing body of research connecting neurodivergence and PMDD, an overlap so pertinent that DITTO is currently undertaking its own systematic review and meta-analysis on the co-occurrence of PMDD and ADHD. The neurobiology of these conditions is complex and heavily shared, which may be part of why they appear side by side so often. Our piece on ADHD and PMDD goes into some shared mechanisms.
Certain mental health conditions were significantly more common in PMDD than depression - body dysmorphia had the strongest link.
Body dysmorphia: 2.3x higher odds in PMDD than depression
OCD: 1.6x higher odds
PTSD: 1.5x higher odds
Eating disorder: 1.2x higher odds
Interestingly, anxiety was not significantly higher in PMDD than in depression.
Something that really stuck out to us, was that body dysmorphia was the highest linked co morbidity in the study compared to depression Though research is still thin, we have a theory about why body dysmorphia is a bigger problem in PMDD. Brain scan studies find a brain region called the ‘fusiform gyrus’ has reduced grey matter volume in those with PMDD, and this is the exact region that’s also flagged in those with body dysmorphia (3). This is the brain’s visual processing hub and is involved in self-perception and seeing the full picture rather than its small parts, which could be working differently in both conditions.
Nutritional, metabolic, digestive, liver and gut-related conditions were more common in PMDD than depression
Lactose intolerance: 2.5x higher odds
Vitamin A deficiency: 2.1x higher odds
Vitamin D deficiency: 1.6x higher odds
High cholesterol: 1.2x higher odds
IBS: 1.5x higher odds
While research is lacking in PMDD, vitamin D deficiency has been strongly associated with stronger PMS symptoms, likely due to its roles in neurotransmitter function (2). More research is needed to understand why those with PMDD specifically are more likely to have these deficiencies.
Immune-related conditions were significantly more common in PMDD than depression
Hayfever: 1.3x higher odds in PMDD than depression
Underactive thyroid: 1.3x higher odds
Celiac disease: 2x higher odds
Inflammatory bowel disease: 1.4x higher odds
It’s increasingly discussed that there may be involvement of the immune system and inflammation in PMDD (5). Hayfever is interesting, as those with childhood allergies are found to have increased risk of developing PMDD later in life (6). Not only that, but receptors for histamine (the chemical released in allergic reactions) are found in the mood centres of our brain. Chronic inflammation from ongoing allergies may impact the brain in ways that make it more susceptible to PMDD. Some women are also finding, anecdotally, that antihistamines actually ease their PMDD symptoms, but this has not been researched yet.
The current map, and a new perspective?
Some of these overlaps likely reflect shared hormone sensitivities and responsiveness, certain neurochemistry and brain area overlaps, inflammatory or gut-brain mechanisms, and more. It’s an area we are only beginning to understand and where the evidence is still early. What the data show clearly is the breadth. PMDD could involve biology affecting multiple systems across the whole body.
So, PMDD is not just a mood disorder, it is a complex condition that interacts with many different body systems and carries comorbidities that remain understudied. It’s clear to those living with it that it’s more complex than communicated on the surface, considering how hard it is to manage and treat. With more work into the comorbidities surrounding PMDD, researchers, clinicians and individuals living with this can be better equipped to have more personalised and holistic treatment and mitigation plans, ultimately leading to better care for all with PMDD.
References:
1. Steyn, Christina and Rakshasa-Loots, Arish Mudra and Swiffen, Duncan and PDF, See, Physical and Mental Health Comorbidities of Premenstrual Dysphoric Disorder: Analysis of 4,047 Participants in Our Future Health. Available at SSRN: https://ssrn.com/abstract=5817338 or http://dx.doi.org/10.2139/ssrn.5817338
2. Li W, Arienzo D, Feusner JD. Body Dysmorphic Disorder: Neurobiological Features and an Updated Model. Z Klin Psychol Psychother (Gott). 2013;42(3):184-191. doi: 10.1026/1616-3443/a000213. PMID: 25419211; PMCID: PMC4237698.
3. Abdi F, Ozgoli G, Rahnemaie FS. A systematic review of the role of vitamin D and calcium in premenstrual syndrome. Obstet Gynecol Sci. 2019 Mar;62(2):73-86. doi: 10.5468/ogs.2019.62.2.73. Epub 2019 Feb 25. Erratum in: Obstet Gynecol Sci. 2020 Mar;63(2):213. doi: 10.5468/ogs.2020.63.2.213. PMID: 30918875; PMCID: PMC6422848.
4. Jaferi L, Kızılkan MP, Yıldırım D, Akbulut Ö, Gülşen HH, Ergen YM, Demir H, Akgül S. The Influence of Dietary Compliance on Premenstrual Symptoms in Adolescents with Celiac Disease. J Pediatr Adolesc Gynecol. 2026 Aug 21:S1083-3188(26)00471-7. doi: 10.1016/j.jpag.2026.08.006. Epub ahead of print. PMID: 42628909.
5. Cheng M, Jiang Z, Yang J, Sun X, Song N, Du C, Luo Z, Zhang Z. The role of the neuroinflammation and stressors in premenstrual syndrome/premenstrual dysphoric disorder: a review. Front Endocrinol (Lausanne). 2025 Mar 28;16:1561848. doi: 10.3389/fendo.2025.1561848. PMID: 40225329; PMCID: PMC11985436.
6. Yang, Y., Gong, T., Camargo, C.A. et al. Childhood asthma, allergies and risk of premenstrual disorders in young adulthood. Nat. Mental Health 1, 410–419 (2023). https://doi.org/10.1038/s44220-023-00066-4
