Neuroendocrine mechanisms of mood disorders during menopause transition: A narrative review and future perspectives.

The menopause transition is an important period in a woman's life, during which she is at an increased risk of mood disorders. Estrogen and progesterone fluctuations during the menopausal transition and very low levels of estradiol after menopause have a profound effect on the central nervous system (CNS), causing an imbalance between excitatory and inhibitory inputs. Changes in neurotransmission and neuronal interactions that occur with estradiol withdrawal disrupt the normal neurological balance and may be associated with menopausal symptoms. Hot flushes, depressed mood and anxiety are all symptoms of menopause that are a consequence of the complex changes that occur in the CNS, involving many signaling pathways and neurotransmitters (i.e. γ-aminobutyric acid, serotonin, dopamine), neurosteroids (i.e. allopregnanolone), and neuropeptides (i.e. kisspeptin, neurokinin B). All these pathways are closely linked, and the complex interactions that exist are not yet fully understood. This review summarizes the neuroendocrine changes in the CNS during the menopausal transition, with particular emphasis on those that underlie mood changes.

Complementary and Integrative Medicine in Treating Headaches, Cognitive Dysfunction, Mental Fatigue, Insomnia, and Mood Disorders Following Traumatic Brain Injury: A Comprehensive Review.

Traumatic brain injury (TBI) is a complex condition associated with a range of persistent symptoms including headaches, cognitive dysfunction, mental fatigue, insomnia, and mood disorders. Conventional treatments for TBI-related symptoms can be insufficient, leading to interest in complementary and integrative medicine (CIM) approaches. This comprehensive article examines the existing literature on CIM modalities, including mind-body interventions, acupuncture/acupressure, herbal remedies, nutritional supplements, biofeedback, yoga, and tai chi in the context of managing secondary complications following TBI. The article highlights potential benefits and limitations of CIM modalities, while acknowledging the need for further research to better establish efficacy and safety in this specific population.

Astroglial Dysfunctions in Mood Disorders and Rodent Stress Models: Consequences on Behavior and Potential as Treatment Target.

Astrocyte dysfunctions have been consistently observed in patients affected with depression and other psychiatric illnesses. Although over the years our understanding of these changes, their origin, and their consequences on behavior and neuronal function has deepened, many aspects of the role of astroglial dysfunction in major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) remain unknown. In this review, we summarize the known astroglial dysfunctions associated with MDD and PTSD, highlight the impact of chronic stress on specific astroglial functions, and how astroglial dysfunctions are implicated in the expression of depressive- and anxiety-like behaviors, focusing on behavioral consequences of astroglial manipulation on emotion-related and fear-learning behaviors. We also offer a glance at potential astroglial functions that can be targeted for potential antidepressant treatment.

Minocycline Abrogates Individual Differences in Nerve Injury-Evoked Affective Disturbances in Male Rats and Prevents Associated Supraspinal Neuroinflammation.

Chronic neuropathic pain precipitates a complex range of affective and behavioural disturbances that differ markedly between individuals. While the reasons for differences in pain-related disability are not well understood, supraspinal neuroimmune interactions are implicated. Minocycline has antidepressant effects in humans and attenuates affective disturbances in rodent models of pain, and acts by reducing neuroinflammation in both the spinal cord and brain. Previous studies, however, tend not to investigate how minocycline modulates individual affective responses to nerve injury, or rely on non-naturalistic behavioural paradigms that fail to capture the complexity of rodent behaviour. We investigated the development and resolution of pain-related affective disturbances in nerve-injured male rats by measuring multiple spontaneous ethological endpoints on a longitudinal naturalistic foraging paradigm, and the effect of chronic oral minocycline administration on these changes. Disrupted foraging behaviours appeared in 22% of nerve-injured rats - termed 'affected' rats - and were present at day 14 but partially resolved by day 21 post-injury. Minocycline completely prevented the emergence of an affected subgroup while only partly attenuating mechanical allodynia, dissociating the relationship between pain and affect. This was associated with a lasting downregulation of ΔFosB expression in ventral hippocampal neurons at day 21 post-injury. Markers of microglia-mediated neuroinflammation were not present by day 21, however proinflammatory microglial polarisation was apparent in the medial prefrontal cortex of affected rats and not in CCI minocycline rats. Individual differences in affective disturbances following nerve injury are therefore temporally related to altered microglial morphology and hippocampal neuronal activation, and are abrogated by minocycline.

Amygdala structural and functional reorganization as an indicator of affective dysfunction in patients with tinnitus.

The aim of this study was to systematically investigate structural and functional alterations in amygdala subregions using multimodal magnetic resonance imaging (MRI) in patients with tinnitus with or without affective dysfunction. Sixty patients with persistent tinnitus and 40 healthy controls (HCs) were recruited. Based on a questionnaire assessment, 26 and 34 patients were categorized into the tinnitus patients with affective dysfunction (TPAD) and tinnitus patients without affective dysfunction (TPWAD) groups, respectively. MRI-based measurements of gray matter volume, fractional anisotropy (FA), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC) were conducted within 14 amygdala subregions for intergroup comparisons. Associations between the MRI properties and clinical characteristics were estimated via partial correlation analyses. Compared with that of the HCs, the TPAD and TPWAD groups exhibited significant structural and functional changes, including white matter integrity (WMI), fALFF, ReHo, DC, and FC alterations, with more pronounced WMI changes in the TPAD group, predominantly within the left auxiliary basal or basomedial nucleus (AB/BM), right central nucleus, right lateral nuclei (dorsal portion), and left lateral nuclei (ventral portion containing basolateral portions). Moreover, the TPAD group exhibited decreased FC between the left AB/BM and left middle occipital gyrus and right superior frontal gyrus (SFG), left basal nucleus and right SFG, and right lateral nuclei (intermediate portion) and right SFG. In combination, these amygdalar alterations exhibited a sensitivity of 65.4% and specificity of 96.9% in predicting affective dysfunction in patients with tinnitus. Although similar structural and functional amygdala remodeling were observed in the TPAD and TPWAD groups, the changes were more pronounced in the TPAD group. These changes mainly involved alterations in functionality and white matter microstructure in various amygdala subregions; in combination, these changes could serve as an imaging-based predictor of emotional disorders in patients with tinnitus.

Cognition and gut microbiota in schizophrenia spectrum and mood disorders: A systematic review.

FRILEUX, M., BOLTRI M. and al. Cognition and Gut microbiota in schizophrenia spectrum and mood disorders: a Systematic Review. NEUROSCI BIOBEHAV REV (1) 2024 Schizophrenia spectrum disorders and major mood disorders are associated with cognitive impairments. Recent studies suggest a link between gut microbiota composition and cognitive functioning. Here, we review the relationship between gut microbiota and cognition in these disorders. To do this, we conducted a systematic review, searching Cochrane Central Register of Controlled Trials, EBSCOhost, Embase, Pubmed, Scopus, and Web of Science. Studies were included if they investigated the relationship between gut microbiota composition and cognitive function through neuropsychological assessments in patients with bipolar, depressive, schizophrenia spectrum, and other psychotic disorders. Ten studies were identified. Findings underscore a link between gut dysbiosis and cognitive impairment. This relationship identified specific taxa (Haemophilus, Bacteroides, and Alistipes) as potential contributors to bolstered cognitive performance. Conversely, Candida albicans, Toxoplasma gondii, Streptococcus and Deinococcus were associated with diminished performance on cognitive assessments. Prebiotics and probiotics interventions were associated with cognitive enhancements, particularly executive functions. These results emphasize the role of gut microbiota in cognition, prompting further exploration of the underlying mechanisms paving the way toward precision psychiatry.

Neuropathic pain and mood disorders in earthquake survivors with peripheral nerve injuries.

Background and purpose:

        Natural disasters, such as earthquakes, frequently result in mood disorders among affected individuals. It is established that neuropathic pain arising from traumatic neuropathies is also linked to mood disorders. This study investigates the influence of neuropathic pain on the development of mood disorders in earthquake survivors with peripheral nerve injuries, following the earthquake centered in Kahramanmaras on February 6, 2023. Additionally, we aim to assess the electro­physiological aspects of neuropathic injuries in these survivors.

The study comprised 46 earth-quake survivors with electrophysiologically confirmed peripheral nerve injuries, with 39 trauma-free survivors serving as the control group. Neuropathic pain, anxiety and depression were assessed using the Douleur Neuropathique 4 (DN4) questionnaire and the Hospital Anxiety and Depression Scale (HADS).

Our findings revealed that the ulnar and peroneal nerves were the most commonly injured structures. Among the survivors with peripheral nerve injury, 31 out of 46 (67%) were found to experience neuropathic pain. Furthermore, plexopathy and multiple extremity injuries were associated with more severe neuropathic pain. However, there was no significant difference in anxiety and depression scores between the two groups and neuropathic pain was found to have no independent effect.

The study indicates that the intensity of neuropathic pain varies based on the localization and distribution of peripheral nerve injuries. However, the presence of peripheral nerve damage or neuropathic pain was not directly associated with HADS scores, suggesting that mood disorders following disasters may have multifactorial causes beyond physical trauma.

Neuroinflammation in osteoarthritis: From pain to mood disorders.

Osteoarthritis (OA) is the most common form of musculoskeletal disease, and its prevalence is increasing due to the aging of the population. Chronic pain is the most burdensome symptom of OA that significantly lowers patients' quality of life, also due to its frequent association with emotional comorbidities, such as anxiety and depression. In recent years, both chronic pain and mood alterations have been linked to the development of neuroinflammation in the peripheral nervous system, spinal cord and supraspinal brain areas. Thus, mechanisms at the basis of the development of the neuroinflammatory process may indicate promising targets for novel treatment for pain and affective comorbidities that accompany OA. In order to assess the key role of neuroinflammation in the maintenance of chronic pain and its potential involvement in development of psychiatric components, the monoiodoacetate (MIA) model of OA in rodents has been used and validated. In the present commentary article, we aim to summarize up-to-date results achieved in this experimental model of OA, focusing on glia activation and cytokine production in the sciatic nerve, dorsal root ganglia (DRGs), spinal cord and brain areas. The association of a neuroinflammatory state with the development of pain and anxiety- and depression-like behaviors are discussed. Results suggest that cells and molecules involved in neuroinflammation may represent novel targets for innovative pharmacological treatments of OA pain and mood comorbidities.

Mood disturbances in newly diagnosed Parkinson's Disease patients reflect intrathecal inflammation.

In Parkinson's disease (PD), neuroinflammation may be involved in the pathogenesis of mood disorders, contributing to the clinical heterogeneity of the disease. The cerebrospinal fluid (CSF) levels of interleukin (IL)-1ß, IL-2, IL-6, IL-7, IL-8, IL-9, IL-12, IL-17, interferon (IFN)γ, macrophage inflammatory protein 1-alpha (MIP-1a), MIP-1b, granulocyte colony stimulating factor (GCSF), eotaxin, tumor necrosis factor (TNF), and monocyte chemoattractant protein 1 (MCP-1), were assessed in 45 newly diagnosed and untreated PD patients and in 44 control patients. Spearman's correlations were used to explore possible associations between CSF cytokines and clinical variables including mood. Benjamini-Hochberg (B-H) correction for multiple comparisons was applied. Linear regression was used to test significant associations correcting for other clinical variables. In PD patients, higher CSF concentrations of the inflammatory molecules IL-6, IL-9, IFNγ, and GCSF were found (all B-H corrected p < 0.02). Significant associations were found between BDI-II and the levels of IL-6 (Beta = 0.438; 95%CI 1.313-5.889; p = 0.003) and IL-8 (Beta = 0.471; 95%CI 0.185-0.743; p = 0.002). Positive associations were also observed between STAI-Y state and both IL-6 (Beta = 0.452; 95%CI 1.649-7.366; p = 0.003), and IL-12 (Beta = 0.417; 95%CI 2.238-13.379; p = 0.007), and between STAI-Y trait and IL-2 (Beta = 0.354; 95%CI 1.923-14.796; p = 0.012), IL-6 (Beta = 0.362; 95%CI 0.990-6.734; p = 0.01), IL-8 (Beta = 0.341; 95%CI 0.076-0.796; p = 0.019), IL-12 (Beta = 0.328; 95%CI 0.975-12.135; p = 0.023), and IL-17 (Beta = 0.334; 95CI 0.315-4.455; p = 0.025). An inflammatory CSF milieu may be associated with depression and anxiety in the early phases of PD, supporting a role of neuroinflammation in the pathogenesis of mood disturbances.

Quality of life, mood disorders, and cognitive impairment in adults with ß-thalassemia.

Advances in understanding the disease process in ß-thalassemia supported development of various treatment strategies that resulted in improved survival. Improved survival, however, allowed multiple morbidities to manifest and cemented the need for frequent, lifelong treatment. This has directly impacted patients' health-related quality of life and opened the door for various psychiatric and cognitive disorders to potentially develop. In this review, we summarize available evidence on quality of life, depression and anxiety, suicidality, and cognitive impairment in adult patients with ß-thalassemia while sharing our personal insights from experience in treating patients with both transfusion-dependent and non-transfusion-dependent forms.

Effects of cannabidiol in post-stroke mood disorders in neonatal rats.

BACKGROUND: Neonatal rats can manifest post-stroke mood disorders (PSMD) following middle cerebral artery occlusion (MCAO). We investigated whether cannabidiol (CBD) neuroprotection, previously demonstrated in neonatal rats after MCAO, includes prevention of PSMD development. METHODS: Seven-day-old Wistar rats (P7) underwent MCAO and received either vehicle or 5 mg/kg CBD treatment. Brain damage was quantified by MRI, and neurobehavioral and histological (TUNEL) studies were performed at P14 and P37. PSMD were assessed using the tail suspension test, forced swimming test, and open field tests. The dopaminergic system was evaluated by quantifying dopaminergic neurons (TH+) in the Ventral Tegmental Area (VTA), measuring brain dopamine (DA) concentration and DA transporter expression, and assessing the expression and function D2 receptors (D2R) through [35S]GTPγS binding. Animals without MCAO served as controls. RESULTS: CBD reduced MCAO-induced brain damage and improved motor performance. At P14, MCAO induced depressive-like behavior, characterized by reduced TH+ cell population and DA levels, which CBD did not prevent. However, CBD ameliorated hyperactivity observed at P37, preventing increased DA concentration by restoring D2R function. CONCLUSIONS: These findings confirm the development of PSMD following MCAO in neonatal rats and highlight CBD as a neuroprotective agent capable of long-term functional normalization of the dopaminergic system post-MCAO. IMPACT: MCAO in neonatal rats led to post-stroke mood disorders consisting in a depression-like picture in the medium term evolving towards long-term hyperactivity, associated with an alteration of the dopaminergic system. The administration of CBD after MCAO did not prevent the development of depressive-like behavior, but reduced long-term hyperactivity, normalizing dopamine receptor function. These data point to the importance of considering the development of depression-like symptoms after neonatal stroke, a well-known complication after stroke in adults. Our work confirms the interest of CBD as a possible treatment for neonatal stroke.

Access to inpatient mood management services after stroke in Australian acute and rehabilitation hospitals.

OBJECTIVE: Post-stroke mental health impairments are common, but under-assessed and under-treated. We aim to describe trends in the provision of mood management to patients with stroke, and describe factors associated with adoption of national mood management recommendations for stroke within Australian hospitals. DESIGN: Secondary analysis of cross-sectional data from the biennial Stroke Foundation Audit Program. SETTING: Participating acute (2011-2021) and rehabilitation hospitals (2012-2020) in Australia. PARTICIPANTS: In the acute audit, 22,937 stroke cases were included from 133 hospitals. In the rehabilitation audit, 15,891 stroke cases were included from 127 hospitals. MAIN MEASURES: Hospital- and patient-level mood management processes. RESULTS: Among 133 acute hospitals (22,937 stroke episodes), improvements were made between 2011 and 2021 in utilization of mood screening (17% [2011], 33% [2021]; p < 0.001) and access to psychologists during hospital stay (18% [2011], 45% [2021]; p < 0.001). There was no change in access to a psychologist among those with a mood impairment (p = 0.34). Among 127 rehabilitation hospitals (15,891 stroke episodes) improvements were observed for mood screening (35% [2012], 61% [2020]; p < 0.001), and access to a psychologist during hospital stay (38% [2012], 68% [2020]; p < 0.001) and among those with a mood-impairment (30% [2012], 50% [2020]; p < 0.001). Factors associated with receiving mood management processes included: younger age, not requiring an interpreter and longer length of stay. CONCLUSIONS: Adherence to mood management recommendations has improved over 10 years within Australian hospitals. Those aged over 65, requiring an interpreter, or with shorter hospital stays are at risk of missing out on appropriate mood management.

Electroencephalography findings in menstrually-related mood disorders: A critical review.

The female reproductive years are characterized by fluctuations in ovarian hormones across the menstrual cycle, which have the potential to modulate neurophysiological and behavioral dynamics. Menstrually-related mood disorders (MRMDs) comprise cognitive-affective or somatic symptoms that are thought to be triggered by the rapid fluctuations in ovarian hormones in the luteal phase of the menstrual cycle. MRMDs include premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and premenstrual exacerbation (PME) of other psychiatric disorders. Electroencephalography (EEG) non-invasively records in vivo synchronous activity from populations of neurons with high temporal resolution. The present overview sought to systematically review the current state of task-related and resting-state EEG investigations on MRMDs. Preliminary evidence indicates lower alpha asymmetry at rest being associated with MRMDs, while one study points to the effect being luteal-phase specific. Moreover, higher luteal spontaneous frontal brain activity (slow/fast wave ratio as measured by the delta/beta power ratio) has been observed in persons with MRMDs, while sleep architecture results point to potential circadian rhythm disturbances. In this review, we discuss the quality of study designs as well as future perspectives and challenges of supplementing the diagnostic and scientific toolbox for MRMDs with EEG.

Affective and Cognitive Impairments in Rodent Models of Diabetes.

Diabetes and related acute and long-term complications have a profound impact on cognitive, emotional, and social behavior, suggesting that the central nervous system (CNS) is a crucial substrate for diabetic complications. When anxiety, depression, and cognitive deficits occur in diabetic patients, the symptoms and complications related to the disease worsen, contributing to lower quality of life while increasing health care costs and mortality. Experimental models of diabetes in rodents are a fundamental and valuable tool for improving our understanding of the mechanisms underlying the close and reciprocal link between diabetes and CNS alterations, including the development of affective and cognitive disorders. Such models must reproduce the different components of this pathological condition in humans and, therefore, must be associated with affective and cognitive behavioral alterations. Beyond tight glycemic control, there are currently no specific therapies for neuropsychiatric comorbidities associated with diabetes; animal models are, therefore, essential for the development of adequate therapies. To our knowledge, there is currently no review article that summarizes changes in affective and cognitive behavior in the most common models of diabetes in rodents. Therefore, in this review, we have reported the main evidence on the alterations of affective and cognitive behavior in the different models of diabetes in rodents, the main mechanisms underlying these comorbidities, and the applicable therapeutic strategy.

Efficacy and safety of agomelatine in epilepsy patients with sleep and mood disorders: An observational, retrospective cohort study.

OBJECTIVE: To evaluate the therapeutic efficacy and safety of agomelatine for treating the sleep and mood disorders in epilepsy patients. METHODS: Retrospective data were derived from 113 epilepsy patients for at least 8 weeks. All the subjects were divided into two groups, one was treated with agomelatine, the other was treated with escitalopram. Their depression and anxiety states were assessed by Hamilton Depression (HAMD) and Hamilton Anxiety (HAMA) Scales. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The HAMA, HAMD and PSQI scores in both groups significantly declined after the treatments with agomelatine and escitalopram. However, the agomelatine group exhibited greater improvement in terms of HAMA and PSQI scores compared to the escitalopram group. No severe adverse events were observed in agomelatine group. SIGNIFICANCE: Agomelatine performed better in HAMA and PSQI scores compared to escitalopram, where no significant increase in seizure frequency or side effects were observed. Possibly, agomelatine presents a promising therapeutic option for treating the sleep or mood disorders in epilepsy patients.

Relationship between subjective and objective fatigue and sleep characteristics in individuals with anxiety and mood disorders: An exploratory study.

OBJECTIVE: Fatigue and sleep disturbances are important symptoms of anxiety and mood disorders (AMD). Studies about the relationship between these variables usually rely on self-report assessments. Therefore, the aim of our exploratory study was to investigate the independent correlations between subjective and objective fatigue and sleep characteristics in individuals with AMD. METHODS: In sum, 233 individuals with AMD attending a stress-related disorders day care unit (78.5 % females, mean age 39.0 years old) participated in a cross-sectional study. Participants completed the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Multidimensional Fatigue Inventory-20, and Pittsburgh Sleep Quality Index self-report questionnaires, as well as an exercise capacity workload test for assessing objective fatigue and polysomnography monitoring for evaluation of sleep structure. RESULTS: In individuals with AMD, exercise capacity workload was associated with lower percent of stage 1 sleep (ß = - 0.17, p = 0.006), REM latency (ß = -0.13, p = 0.042), and wake after sleep onset (ß = -0.12, p = 0.039). General fatigue was associated with a higher percent of body movements (ß = 0.12, p = 0.047), as well as mental fatigue was associated with a higher percent of body movements (ß = 0.13, p = 0.029), and a higher score on the PSQI (ß = 0.21, p = 0.002). CONCLUSIONS: Objective sleep characteristics were associated with objective assessment of fatigue, while subjective sleep quality was associated with subjectively assessed mental fatigue.

Anxiety and mood disorders in forcibly displaced people across the world.

PURPOSE OF REVIEW: Displaced persons around the world have intensified in the previous decade and are predicted to rise further with greater global instability. The mental health issues involved with fleeing one's home, and attempting to make a new life in a host country need to be understood and addressed. RECENT FINDINGS: Prevalence of anxiety and mood disorders, including posttraumatic stress disorder appear to be higher for displaced peoples than for the population in the host country. This is consistent across different methods. Traumatic life events in the country of origin as well as during flight contribute to symptom severity. Factors in the host country increasing severity including isolation, discrimination, low social support. There are successfully implemented intercultural interventions at the individual level of the practitioner, as well as at the institutional level. SUMMARY: There are many possibilities for successful interventions in displaced people, realizing this at a scale appropriate to the size of the problem remains a challenge.

Risk factors for mood disorders among offspring of parents with bipolar disorder: Findings from a discordant-sibling study.

The purpose of this naturalistic, prospective study was to identify risk factors for mood disorders in offspring of parents with bipolar disorder (BPD) using the discordant-sibling design by comparing premorbid psychopathology or symptoms, temperament, personality traits and coping style as well as the perception of family-related characteristics among affected and unaffected siblings within the same family. This approach controls for confounding by unmeasured genetic and environmental factors shared within families. Our sample comprised 24 families of a parent with BPD with at least one child that developed BPD or major depressive disorder (n = 31), and at least one child who did not. Offspring were followed for a mean duration of 16.2 (s.d: 4.6) years. Information was collected from the offspring themselves. Generalized linear mixed models only revealed differences in three dimensions of the Dimension of Temperament Survey-Revised (DOTS-R) version: Offspring with mood disorders scored higher on "Approach-withdrawal", "Rhythmicity for daily habits", and "Task orientation" than their unaffected siblings. The higher scores, and not lower scores as expected, on these temperament dimensions observed in offspring that subsequently developed mood disorders may reflect increased vulnerability, but they could also mirror premorbid mood swings or strategies to cope with them.

A scoping review of hormonal clinical trials in menstrual cycle-related brain disorders: Studies in premenstrual mood disorder, menstrual migraine, and catamenial epilepsy.

Cyclic variations in hormones during the normal menstrual cycle underlie multiple central nervous system (CNS)-linked disorders, including premenstrual mood disorder (PMD), menstrual migraine (MM), and catamenial epilepsy (CE). Despite this foundational mechanistic link, these three fields operate independently of each other. In this scoping review (N = 85 studies), we survey existing human research studies in PMD, MM, and CE to outline the exogenous experimental hormone manipulation trials conducted in these fields. We examine a broad range of literature across these disorders in order to summarize existing diagnostic practices and research methods, highlight gaps in the experimental human literature, and elucidate future research opportunities within each field. While no individual treatment or study design can fit every disease, there is immense overlap in study design and established neuroendocrine-based hormone sensitivity among the menstrual cycle-related disorders PMD, MM, and CE. SCOPING REVIEW STRUCTURED SUMMARY: Background. The menstrual cycle can be a biological trigger of symptoms in certain brain disorders, leading to specific, menstrual cycle-linked phenomena such as premenstrual mood disorders (PMD), menstrual migraine (MM), and catamenial epilepsy (CE). Despite the overlap in chronicity and hormonal provocation, these fields have historically operated independently, without any systematic communication about methods or mechanisms. OBJECTIVE: Online databases were used to identify articles published between 1950 and 2021 that studied hormonal manipulations in reproductive-aged females with either PMD, MM, or CE. We selected N = 85 studies that met the following criteria: 1) included a study population of females with natural menstrual cycles (e.g., not perimenopausal, pregnant, or using hormonal medications that were not the primary study variable); 2) involved an exogenous hormone manipulation; 3) involved a repeated measurement across at least two cycle phases as the primary outcome variable. CHARTING METHODS: After exporting online database query results, authors extracted sample size, clinical diagnosis of sample population, study design, experimental hormone manipulation, cyclical outcome measure, and results from each trial. Charting was completed manually, with two authors reviewing each trial. RESULTS: Exogenous hormone manipulations have been tested as treatment options for PMD (N = 56 trials) more frequently than MM (N = 21) or CE (N = 8). Combined oral contraceptive (COC) trials, specifically those containing drospirenone as the progestin, are a well-studied area with promising results for treating both PMDD and MM. We found no trials of COCs in CE. Many trials test ovulation suppression using gonadotropin-releasing hormone agonists (GnRHa), and a meta-analysis supports their efficacy in PMD; GnRHa have been tested in two MM-related trials, and one CE open-label case series. Finally, we found that non-contraceptive hormone manipulations, including but not limited to short-term transdermal estradiol, progesterone supplementation, and progesterone antagonism, have been used across all three disorders. CONCLUSIONS: Research in PMD, MM, and CE commonly have overlapping study design and research methods, and similar effects of some interventions suggest the possibility of overlapping mechanisms contributing to their cyclical symptom presentation. Our scoping review is the first to summarize existing clinical trials in these three brain disorders, specifically focusing on hormonal treatment trials. We find that PMD has a stronger body of literature for ovulation-suppressing COC and GnRHa trials; the field of MM consists of extensive estrogen-based studies; and current consensus in CE focuses on progesterone supplementation during the luteal phase, with limited estrogen manipulations due to concerns about seizure provocation. We argue that researchers in any of these respective disciplines would benefit from greater communication regarding methods for assessment, diagnosis, subtyping, and experimental manipulation. With this scoping review, we hope to increase collaboration and communication among researchers to ultimately improve diagnosis and treatment for menstrual-cycle-linked brain disorders.