Sensitivity to ovarian hormone fluctuations can lead to mental distress during the luteal phase of the menstrual cycle, such as in premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), and also during pregnancy and postpartum, as in perinatal depression (PND).

In two cohorts, we investigated the relationship between history of PMS/PMDD and PND symptoms. We also examined how premenstrual symptoms are associated with perinatal symptom trajectories and dimensional phenotypes of PND symptoms, which remains unidentified.

From early pregnancy until 6 months postpartum, participants of two large longitudinal cohorts were followed using the Edinburgh Postnatal Depression Scale (EPDS). Premenstrual symptoms were self-reported retrospectively.

Both pre-pregnancy PMS and PMDD were associated with higher EPDS scores across pregnancy and postpartum, even after adjustment for confounders. The odds of developing PND were higher among those reporting PMS and PMDD, ranging up to 1.68 (95% CI 1.25–2.29) (6–13 weeks postpartum) and 3.05 (95% CI 2.26–4.10) (late pregnancy) respectively for PMS and PMDD, throughout the perinatal period. Premenstrual symptomatology was associated more with certain PND trajectories based on the time of occurrence and persistence of symptoms. However, PND symptom severity did not differ depending on premenstrual symptomatology in any trajectory. Prior PMS/PMDD was associated with underlying dimensions of symptom constructs of PND, including severe and moderate symptoms of depressed mood, anxiety and anhedonia.

Women with a history of PMS/PMDD require coordinated care by psychiatrists, other mental health clinicians, midwives and gynaecologists during pregnancy as well as postpartum.

A key step toward understanding psychiatric disorders that disproportionately impact female mental health is delineating the emergence of sex-specific patterns of brain organisation at the critical transition from childhood to adolescence. Prior work suggests that individual differences in the spatial organisation of functional brain networks across the cortex are associated with psychopathology and differ systematically by sex.

We aimed to evaluate the impact of sex on the spatial organisation of person-specific functional brain networks.

We leveraged person-specific atlases of functional brain networks, defined using non-negative matrix factorisation, in a sample of n = 6437 youths from the Adolescent Brain Cognitive Development Study. Across independent discovery and replication samples, we used generalised additive models to uncover associations between sex and the spatial layout (topography) of personalised functional networks (PFNs). We also trained support vector machines to classify participants’ sex from multivariate patterns of PFN topography.

Sex differences in PFN topography were greatest in association networks including the frontoparietal, ventral attention and default mode networks. Machine learning models trained on participants’ PFNs were able to classify participant sex with high accuracy.

Sex differences in PFN topography are robust, and replicate across large-scale samples of youth. These results suggest a potential contributor to the female-biased risk in depressive and anxiety disorders that emerge at the transition from childhood to adolescence.

Due to historical under-recognition of attention-deficit hyperactivity disorder (ADHD) among girls and women, little is known about female-specific factors that may affect individuals with ADHD, including those related to changes in ovarian hormones (e.g. across the menstrual cycle).

We investigated whether females with a self-reported clinical diagnosis of ADHD are more likely to experience premenstrual dysphoric disorder (PMDD). We also examined associations between PMDD and ADHD defined by a symptom and impairment threshold.

Participants were aged between 18 and 34 years, were assigned female at birth and were recruited via Prolific.com (n = 715). Participants self-reported clinician diagnosis of ADHD, depression and anxiety. ADHD symptoms were assessed via the Adult ADHD Self-Report Scale (ASRS), to which we applied a DSM-5-based symptom and impairment cut-off (‘ASRS-based ADHD’). PMDD symptoms were assessed via the Premenstrual Symptoms Screening Tool (PSST), which identifies provisional PMDD. Using Poisson regression models, we compared risk for provisional PMDD among females with ADHD (self-reported clinical diagnosis [n = 102] or ASRS-based [n = 229]) with a non-ADHD reference group (n = 305). We additionally compared risk for provisional PMDD among individuals with ADHD and depression/anxiety diagnoses, ADHD only and a non-ADHD reference group.

The prevalence of provisional PMDD was elevated among individuals with a self-reported clinical ADHD diagnosis (31.4%), and among participants with ASRS-based ADHD (41.1%), compared with the non-ADHD reference group (9.8%). Individuals with ASRS-based ADHD and depression and/or anxiety diagnoses were at highest risk for provisional PMDD (relative risk 4.53 [3.10, 6.61]) compared with the non-ADHD reference group.

Clinicians should be aware that individuals with a diagnosis of ADHD, or with high ADHD symptom levels, and who have a menstrual cycle may be more likely to experience PMDD. Future research should investigate the underlying mechanisms that link ADHD and disorders associated with hormonal sensitivity, such as PMDD.

Psychological symptoms in perimenopause and early menopause are common. The impact of menopausal hormone therapy (MHT) on menopausal mood symptoms is unclear.

To assess the impact of 17β-oestradiol ± micronised progesterone or the levonorgestrel-releasing intrauterine device, and/or transdermal testosterone, on depressive and anxiety symptoms in peri- and postmenopausal women.

A real-world retrospective cohort study set in the largest specialist menopause clinic in the UK. The Meno-D questionnaire measured mood-related symptoms.

The study included 920 women: 448 (48.7%) perimenopausal, and 435 (47.3%) postmenopausal. Following initiation/optimisation of MHT, mean Meno-D scores decreased by 44.59% (95% CI −46.83% to −42.34%, P < 0.001) after average 107 days follow-up. Mood symptoms significantly improved (P < 0.01 per symptom). Improvement occurred in peri- and postmenopausal women. All MHT regimens improved mental health including both progestogen types (body-identical progesterone and levonorgestrel-releasing intrauterine device), MHT initiation strategy (oestradiol ± a progestogen versus oestradiol ± a progestogen and testosterone, 45.38 v. 48.53%, respectively, P = 0.47) and MHT optimisation strategy (MHT users treated with a higher oestradiol dose versus testosterone added versus both a higher oestradiol dose and testosterone, 34.70, 43.93 and 43.25%, respectively, P = 0.38).

Use of menopausal hormone therapy was associated with significant improvement in mood in peri- and postmenopausal women. Prospective studies and randomised clinical trials are needed to assess the effects of different regimens in different patient populations over longer time periods.

Stress, a major risk factor for mental health problems, is influenced by hormonal fluctuations from the menstrual cycle and hormonal oral contraceptives (OC). Despite widespread use, the impact of hormonal intrauterine devices (IUDs) on stress is limited to one study.

This study examines psychoendocrine stress responses in women using IUDs, OCs and women with a natural, regular menstrual cycle (NC) to better understand how endogenous and exogenous hormones influence stress.

Using a repeated-measures design, we investigated stress responses in IUD and OC users and NC women. The Maastricht Acute Stress Task and its control task were applied twice within 4 months to assess subjective, endocrine and physiological stress correlates. Detailed endogenous and exogenous hormonal profiles were obtained, and women completed a 7-day diary (via ecological momentary assessment) after each appointment.

Based on subjective, physiological and cortisol responses, stress induction was successful in all groups. IUD users reported higher subjective stress, negative affect and anxiety and lower positive affect compared to NC women. OC users exhibited a blunted cortisol response and higher heart rate but reported less acute stress and negative emotions than the other groups in the 7-day diary. Oestradiol and progesterone were suppressed in OC and IUD users compared with NC women. Progesterone, testosterone and oestradiol were differently associated with skin conductance, socio-emotional stress and negative affect.

IUD and OC use distinctly affect stress response, possibly because of their diverging metabolic pathways and hormone levels. IUD users showed higher emotional reactivity to stress in both lab and daily life, while OCs influenced physiological correlates. These findings highlight that exogenous hormone administration, previously thought to have limited systemic effects, affects women’s psychological well-being, underscoring the need for further research into stress-related disorders among women using hormonal contraceptives.

Mood disorders are among the leading causes of disease burden worldwide, with 20–70% of affected individuals experiencing comorbid premenstrual disorders. This systematic review and meta-analysis investigated the comorbidity of premenstrual dysphoric disorder (PMDD) or premenstrual syndrome (PMS) with non-reproductive mood disorders.

We aimed to determine the pooled prevalence of PMDD/PMS with adult mood disorders, assess the impact of comorbidity on clinical course and summarise the associated neurobiological findings.

Eligible studies were identified through Embase, MEDLINE and APA PsycINFO from inception to 22 January 2024 (PROSPERO, no. CRD42021246796). Studies on women (‘females‘) with diagnoses of PMDD/PMS and mood disorders were included. Risk of bias was assessed using National Institutes of Health quality assessment tools. A random-effects, pooled-prevalence meta-analysis was conducted using the Comprehensive Meta-Analysis software, categorising diagnostic sampling strategies as follows: mood disorders diagnosed first, PMDD/PMS diagnosed first or concurrent diagnoses. A narrative synthesis explored secondary outcomes, including illness course and biomarkers.

A total of 39 studies were included, with 36 of these (n = 3646) contributing to the meta-analysis. Seven studies focused on bipolar disorders, 18 on unipolar depressive disorders and 14 on mixed samples of bipolar and unipolar disorders. Random-effects pooled-prevalence meta-analyses showed consistently high comorbidity rates between PMDD/PMS and mood disorders, ranging from 42% (95% CI: 30%, 55%) to 49% (95% CI: 38%, 60%) across sampling strategies. Risk of bias varied, with methodological heterogeneity noted.

This review underscores high comorbidity rates between PMDD/PMS and mood disorders, regardless of sampling strategy, and highlights the need for research into clinical and neurobiological characteristics specific to this comorbidity. Limitations include study heterogeneity, reliance on cross-sectional designs and provisional PMDD/PMS diagnoses. Future research should address these gaps to inform diagnostic and therapeutic advancements tailored to this population.

Peripartum depression (PPD) is a prevalent mental health disorder in the peripartum period. However, a recent systematic review of clinical guidelines relating to PPD has revealed a significant inconsistency in recommendations.

This study aimed to collect up-to-date evidence on the effectiveness of interventions and provide recommendations for prevention, screening and treating PPD.

A series of umbrella reviews on the effectiveness of PPD prevention, screening and treatment interventions was conducted. A search was performed in five databases from 2010 until 2023. The guidelines were developed according to the GRADE framework and AGREE II Checklist recommendations. Public stakeholder review was included.

One hundred and forty-five systematic reviews were included in the final analysis and used to form the guidelines. Forty-four recommendations were developed, including recommendations for prevention, screening and treatment. Psychological and psychosocial interventions are strongly recommended for preventing PPD in women with no symptoms and women at risk. Screening programmes for depression are strongly recommended during pregnancy and postpartum. Cognitive–behavioural therapy is strongly recommended for PPD treatment for mild to severe depression. Antidepressant medication is strongly recommended for treating severe depression in pregnancy. Electroconvulsive therapy is strongly recommended for therapy-resistant and life-threatening severe depression during pregnancy. Other recommendations are offered to healthcare professionals, stakeholders and researchers in managing PPD in different contexts.

Treatment recommendations should be implemented after carefully considering clinical severity, previous history, risk–benefit for mother and foetus/infant and women’s values and preferences. Implementation of evidence-based clinical practice guidelines within country-specific contexts should be facilitated.

While biomarkers are widely used in other medical fields, psychiatry has yet to introduce reliable biological diagnostic tools. Female reproductive transitions provide a unique window of opportunity for investigating psychiatric biomarkers. Hormonal changes across menstruation, pregnancy, parturition and perimenopause can have dramatic effects on mental health in vulnerable individuals, enabling the identification of unique biomarkers associated with these fluctuations.

This review integrates current evidence concerning potential biomarkers, with focus on recent human studies in perinatal depression, anxiety and obsessive–compulsive disorder, postpartum psychosis, premenstrual dysphoric disorder and perimenopausal depression.

We identified potential articles to be included in this narrative review by using PubMed to obtain articles in English since 2010 on the six conditions listed above, with the additional keywords of ‘biomarker’, ‘epigenetics’, ‘neuroactive steroid’, ‘immune’, ‘inflammatory’ and ‘neuroimaging’.

There is substantial published evidence regarding potential biomarkers of reproductive psychiatric disorders in the areas of epigenetics, neuroactive steroids, immune function and neuroimaging. This body of research holds significant potential to advance biomarker development, uncover disease mechanisms and improve diagnostic and therapeutic strategies, but there is as yet no clinically useful biomarker in commercial development for any reproductive psychiatric disorder.

There is an urgent need for longitudinal, large-scale and multi-modal studies to examine potential biomarkers and better understand their functions across various stages of reproduction.

Premenstrual dysphoric disorder (PMDD) is common, with at least 3% of the female population affected by one or more of the typical mood symptoms of depression, irritability, mood swings and anxiety. The cyclicity and close relationship to the luteal phase of the menstrual cycle is characteristic for this syndrome and positive allosteric modulators (PAMs) on the GABAA receptor, especially allopregnanolone, are believed to be involved in the symptomatology.

To summarise the research on the role of PAMs and other neuroactive steroids in the pathophysiology of PMDD.

PubMed was searched for articles including the terms Premenstrual syndrome, AND neurosteroids OR allopregnanolone OR GABA OR oestradiol. Many additional publications were previously known to the authors and basic animal research was covered in a secondary step through reference lists.

There is evidence that allopregnanolone, like other PAMs of the GABAA receptor, is sedative in high concentrations and, in a minor proportion of the population, causes anxiety and irritability at lower levels, pointing to an inter-individual difference in sensitivity. In research comparing women with PMDD and healthy controls, differences in brain function and subcomposition of GABAA receptors related to levels of allopregnanolone have been found. Also, the varying levels of neuroactive steroids in general seem to worsen the symptoms. Supressed ovulation is effective but add-back hormones are necessary to prevent severe side-effects and could cause adverse mood in these individuals.

There is yet no effective treatment for PMDD available. Allopregnanolone seems to be a key provocateur of PMDD symptoms in susceptible individuals. Future research should focus on interventions that interfere with the effects of neurosteroids or the plasticity of the GABAA receptor itself.