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Keywords = social rhythm dysregulation

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21 pages, 337 KiB  
Article
The Inaccuracy of the Mood Disorder Questionnaire for Bipolar Disorder in a Community Sample: From the “DYMERS” Construct Toward a New Instrument for Detecting Vulnerable Conditions
by Elisa Cantone, Antonio Urban, Giulia Cossu, Michela Atzeni, Pedro José Fragoso Castilla, Shellsyn Giraldo Jaramillo, Mauro Giovanni Carta and Massimo Tusconi
J. Clin. Med. 2025, 14(9), 3017; https://doi.org/10.3390/jcm14093017 - 27 Apr 2025
Viewed by 1498
Abstract
Background/Objectives: The Mood Disorder Questionnaire (MDQ) is a widely used tool for the early detection of Bipolar Disorder (BD), yet its diagnostic accuracy remains debated. In particular, the MDQ often yields false positives in individuals with anxiety, stress-related, or personality disorders, raising questions [...] Read more.
Background/Objectives: The Mood Disorder Questionnaire (MDQ) is a widely used tool for the early detection of Bipolar Disorder (BD), yet its diagnostic accuracy remains debated. In particular, the MDQ often yields false positives in individuals with anxiety, stress-related, or personality disorders, raising questions about its clinical utility. This study aimed primarily to evaluate the sensitivity, specificity, and predictive values of the MDQ in identifying BD within a large, community-based sample using structured clinical interviews. Additionally, we explored the construct of DYMERS (Dysregulation of Mood, Energy, and Social Rhythms Syndrome), a proposed condition characterized by mood instability, hyperactivation traits, and rhythm dysregulation among MDQ-positive individuals without a formal psychiatric diagnosis. Methods: A total of 4999 adults were surveyed across six Italian regions using a stratified random sampling method. Psychiatric diagnoses were established using DSM-IV-TR criteria via the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS). The MDQ was administered face to face in its validated Italian version, with a positivity cut-off of ≥7. The MDQ exhibited low sensitivity and high specificity (0.962; 95% CI: 0.961–0.963). Results: Among 2337 analyzable cases, the MDQ showed high specificity (96.2%) but low sensitivity (42.9%) for BD, indicating limited effectiveness as a screening tool. In clinical terms, this implies that while MDQ-positive individuals are unlikely to be false positives, a substantial proportion of true BD cases are not identified. Notably, a significant subgroup of MDQ-positive individuals without psychiatric diagnoses displayed features consistent with DYMERS. Conclusions: Our findings confirm the limited screening value of the MDQ for BD in community samples. However, MDQ positivity may help identify a broader spectrum of mood and rhythm dysregulation not captured by current diagnostic systems. Future research should focus on validating DYMERS as a clinical entity and on developing targeted diagnostic instruments capable of capturing this emerging dimension of psychopathology. Full article
(This article belongs to the Section Mental Health)
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17 pages, 890 KiB  
Communication
Short Communication on Proposed Treatment Directions in Bipolar Disorder: A Psychotherapy Perspective
by Jelena Milic, Iva Zrnic, Milica Vucurovic, Edita Grego, Sanja Djurdjevic and Rosa Sapic
J. Clin. Med. 2025, 14(6), 1857; https://doi.org/10.3390/jcm14061857 - 10 Mar 2025
Viewed by 2383
Abstract
Background/Objectives: Bipolar disorder (BD) is a chronic, severe mental health condition characterized by episodes of mood instability, including manic and depressive episodes. While pharmacological interventions remain foundational in BD treatment, psychotherapy offers significant benefits by addressing the psychological and behavioral components that [...] Read more.
Background/Objectives: Bipolar disorder (BD) is a chronic, severe mental health condition characterized by episodes of mood instability, including manic and depressive episodes. While pharmacological interventions remain foundational in BD treatment, psychotherapy offers significant benefits by addressing the psychological and behavioral components that contribute to mood episodes and overall functioning. The primary objective of this short communication is to propose new directions in psychotherapy for treating bipolar disorder, focusing on integrative models that combine evidence-based therapies such as Cognitive Behavioral Therapy (CBT), Interpersonal and Social Rhythm Therapy (IPSRT), Family-Focused Therapy (FFT), and mindfulness-based approaches. By integrating these therapies, clinicians can target both cognitive distortions and emotional dysregulation while simultaneously stabilizing sleep–wake cycles and improving interpersonal functioning. The secondary objective emphasizes the importance of better understanding and psychoeducation in family therapy, which can promote a better understanding of BD among family members and ensure more effective management of the disorder in daily life. Methods: We explore the potential of Cognitive Behavioral Therapy (CBT), Interpersonal and Social Rhythm Therapy (IPSRT), Family-Focused Therapy (FFT), and mindfulness-based interventions in enhancing symptom management and preventing relapse. Results: We identified psychoeducation and family therapy as critical components in supporting patients and improving treatment adherence. These therapeutic interventions play a pivotal role in enhancing patient engagement, improving coping strategies, and facilitating better overall treatment outcomes. Conclusions: We propose a multidisciplinary approach, integrating psychotherapy with pharmacotherapy, to optimize long-term outcomes and improve the overall quality of life for individuals with bipolar disorder. Full article
(This article belongs to the Special Issue Patient-Oriented Treatments for Bipolar Disorder)
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14 pages, 729 KiB  
Review
An Initial Scoping Review of Dysregulation of Mood, Energy, and Social Rhythms Syndrome (DYMERS) Regarding Burnout in Healthcare Professionals During COVID-19
by Carol Nash
J. Clin. Med. 2025, 14(3), 1035; https://doi.org/10.3390/jcm14031035 - 6 Feb 2025
Cited by 1 | Viewed by 1340
Abstract
Background/Objectives: Dysregulation of Mood, Energy, and Social Rhythms Syndrome (DYMERS) characterizes the poor regulation of biological (sleep/waking), social, and behavioral rhythms that affected the level of burnout in healthcare professionals during the pandemic in particular. The aim is to provide an initial [...] Read more.
Background/Objectives: Dysregulation of Mood, Energy, and Social Rhythms Syndrome (DYMERS) characterizes the poor regulation of biological (sleep/waking), social, and behavioral rhythms that affected the level of burnout in healthcare professionals during the pandemic in particular. The aim is to provide an initial scoping review of publications on this topic. Methods: The keywords “Stress Rhythms Dysregulation Bipolar Disorder Burnout DYMERS Healthcare professionals COVID-19” were searched on 9 December 2024 following PRISMA 2020 guidelines, using five primary databases (OVID, ProQuest, PubMed, Scopus, Web of Science), one register (Cochrane COVID-19 register), and one supplementary database (Google Scholar). Included were peer-reviewed publications. Excluded were duplicates, reports lacking either a research study or any keywords, or including irrelevant information regarding them. Results: The returns for all the databases were (n = 0) except for ProQuest (n = 4) and Google Scholar (n = 14). Of these, three ProQuest returns were duplicates of the Google Scholar search. The remaining report contained irrelevant information on healthcare professionals. The Google Scholar search results produced two relevant reports—neither duplicated with ProQuest. The excluded contained a duplicate in the search itself, three that did not mention healthcare professionals, two that contained irrelevant information concerning them, four returns that were not a research study, and three that were not peer-reviewed. Conclusions: The two studies published on this topic are by various members of the same investigating institution. DYMERS has provided valuable insights regarding burnout in healthcare professionals. The suggestion is for further DYMERS research by this team and others, anticipating future pandemics. Full article
(This article belongs to the Special Issue Stress, Rhythms Dysregulation and Bipolar Spectrum)
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27 pages, 979 KiB  
Review
The Role of the Chronotype in Developing an Excessive Body Weight and Its Complications—A Narrative Review
by Marta Pelczyńska, Małgorzata Moszak, Julita Wojciechowska, Anita Płócienniczak, Jan Potocki, Joanna Blok, Julia Balcerzak, Mikołaj Zblewski and Paweł Bogdański
Nutrients 2025, 17(1), 80; https://doi.org/10.3390/nu17010080 - 28 Dec 2024
Cited by 3 | Viewed by 4221
Abstract
The chronotype, the personal predisposition towards morning or evening activities, significantly influences health conditions, sleep, and eating regulations. Individuals with evening chronotypes are often at a higher risk for weight gain due to misalignment between their natural tendencies of functioning and social schedules, [...] Read more.
The chronotype, the personal predisposition towards morning or evening activities, significantly influences health conditions, sleep, and eating regulations. Individuals with evening chronotypes are often at a higher risk for weight gain due to misalignment between their natural tendencies of functioning and social schedules, resulting in insufficient sleep, disruptions in eating habits, and decreased physical activity levels. Often, impaired glucose tolerance and changes in melatonin, adiponectin, and leptin secretion, along with alterations in the clock gene functions in subjects with evening preferences, may be predisposed to obesity. These disturbances contribute to metabolic dysregulation, which may lead to the subsequent onset of obesity complications, such as hypertension, type 2 diabetes, sleep apnea, and liver diseases. Targeting critical components of the circadian system and synchronizing people’s chronotypes with lifestyle conditions could deliver potential strategies for preventing and treating metabolic disorders. Thus, it is recommended to take a personalized chronobiological approach to maintain a normal body weight and metabolic health. Nevertheless, future studies are needed to identify the clear mechanisms between the chronotype and human health. This article provides a narrative review and discussion of recent data to summarize studies on the circadian rhythm in the context of obesity. The manuscript represents a comprehensive overview conducted between August and November 2024 using the National Library of Medicine browser (Medline, Pub-Med, Web of Science). Full article
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14 pages, 291 KiB  
Article
Adaptive Hyperactivity and Biomarker Exploration: Insights from Elders in the Blue Zone of Sardinia
by Alessandra Scano, Germano Orrù, Goce Kalcev, Massimo Tusconi, Maura Spada, Laura Atzori, Caterina Ferreli, Flavio Cabitza, Diego Primavera and Federica Sancassiani
J. Clin. Med. 2024, 13(21), 6451; https://doi.org/10.3390/jcm13216451 - 28 Oct 2024
Cited by 1 | Viewed by 1504
Abstract
Background/Objectives: Adaptive hyperactivity characterized by increased activity levels and novelty-seeking traits without mood disorders is prevalent among older adults in Sardinia’s “blue zone,” an area with high longevity. This study aims to evaluate the adaptive nature of hyperactivity concerning quality of life, social [...] Read more.
Background/Objectives: Adaptive hyperactivity characterized by increased activity levels and novelty-seeking traits without mood disorders is prevalent among older adults in Sardinia’s “blue zone,” an area with high longevity. This study aims to evaluate the adaptive nature of hyperactivity concerning quality of life, social rhythms, and mood symptoms in individuals from this region, particularly among elderly adults over 80. Methods: This observational cross-sectional study included adults and older adults over 80 from Sardinia’s blue zone. This study included a sample of patients followed at the Center for Consultation Psychiatry and Psychosomatics for Bipolar Disorder of the University Hospital of Cagliari and a homogeneous comparison sample of patients without psychiatric pathologies, referred to the Dermatology Clinic of the same hospital, for a period of 6 months, from February to August 2024. The general sample, divided into two parts—cases, represented by patients with psychiatric pathology, and controls, patients without psychiatric pathology—was divided in turn into three sub-groups: “adults” (18–64 years), young elders (65–79), and old elders (over 80 years). The participants underwent psychiatric interviews and completed the Mood Disorder Questionnaire (MDQ), Patient Health Questionnaire (PHQ-9), SF-12, and Brief Social Rhythm Scale (BSRS). Data were compared with national and regional normative data. Results: Older adults in the blue zone demonstrated higher MDQ positivity (22.58%) compared to the national averages (0.87%), without corresponding increases in dysregulated rhythms, depressive symptoms, or reduced quality of life. Younger old persons (65–79 years) showed increased rhythm dysregulation (BSRS score: 20.64 ± 7.02) compared to adults (17.40 ± 6.09, p = 0.040), but this trend was not observed in the oldest group (80+ years). No significant differences were found in the CH3SH and (CH3)2S levels between groups. Conclusions: The hyperactivity observed in older adults from Sardinia’s blue zone appears adaptive and not linked to social rhythm dysregulation, depressive symptoms, or a diminished quality of life, suggesting resilience factors which may contribute to longevity. These findings support the potential classification of such hyperactivity as beneficial rather than pathological, warranting further research into biomarkers and psychoeducational interventions to prevent the onset of bipolar disorders in predisposed individuals. Full article
(This article belongs to the Special Issue Stress, Rhythms Dysregulation and Bipolar Spectrum)
14 pages, 3772 KiB  
Article
Hyperactivity and Risk for Dysregulation of Mood, Energy, and Social Rhythms Syndrome (DYMERS): Standardization of a Simple One-Item Screener versus the Mood Disorder Questionnaire (MDQ)
by Uta Ouali, Amina Aissa, Salsabil Rejaibi, Nada Zoghlami, Amine Larnaout, Yosra Zgueb, Mejdi Zid, Hajer Aounallah Skhiri, Goce Kalcev, Massimo Tusconi, Cesar Ivan Aviles Gonzales, Antonio Preti and Diego Primavera
J. Clin. Med. 2024, 13(15), 4433; https://doi.org/10.3390/jcm13154433 - 29 Jul 2024
Cited by 3 | Viewed by 1917
Abstract
Background: This study aims to verify the accuracy of item 10 on the energy level of the Short-Form Health Survey (SF-12) in an item screening according to Mood Disorder Questionnaire (MDQ) results, providing a measure of hyper-energy. Methods: Regression techniques were employed in [...] Read more.
Background: This study aims to verify the accuracy of item 10 on the energy level of the Short-Form Health Survey (SF-12) in an item screening according to Mood Disorder Questionnaire (MDQ) results, providing a measure of hyper-energy. Methods: Regression techniques were employed in a dataset comprising 4093 records of respondents to test both linear and nonlinear relationships between predictor and outcome variables (energy level and symptoms considered in the MDQ). We examined the relationship of energy level with cases identified using MDQ with a cut-off of 7. Results: Levels of energy, as rated on item 10 of the SF-12, were related to the MDQ score with sensitivity = 0.72 and specificity = 0.70. In linear regression, the associations were stronger with MDQ items on excessive energy or activity, showing a medium effect size and an explained variance of 10% or higher. A greater association was observed for items on excessive energy and activity, as expected, as well as for items concerning self-confidence, sociability, and talkativeness. Conclusions: This result may have implications for the research on risk factors and the pathogenesis of the dysregulation of mood, energy, and social rhythms syndrome (DYMERS), a syndrome that is hypothesized to occur in stressful conditions like those shown under the COVID-19 pandemic. Full article
(This article belongs to the Special Issue Stress, Rhythms Dysregulation and Bipolar Spectrum)
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10 pages, 1007 KiB  
Article
Improving Social and Personal Rhythm Dysregulation in Young and Old Adults with Bipolar Disorder: Post-Hoc Analysis of a Feasibility Randomized Controlled Trial Using Virtual Reality-Based Intervention
by Federica Sancassiani, Alessandra Perra, Peter K. Kurotschka, Goce Kalcev, Alessia Galetti, Rosanna Zaccheddu, Aurora Locci, Federica Piludu, Lorenzo Di Natale, Valerio De Lorenzo, Michele Fornaro, Antonio Egidio Nardi and Diego Primavera
J. Clin. Med. 2024, 13(13), 3786; https://doi.org/10.3390/jcm13133786 - 27 Jun 2024
Cited by 3 | Viewed by 2635
Abstract
Introduction: Rehabilitative interventions employing technology play a crucial role in bipolar disorder (BD) treatment. The study aims to appraise the virtual reality (VR)-based cognitive remediation (CR) and the interpersonal rhythm approaches to treatment outcomes of BD across different age groups. Methods: Post-hoc analysis [...] Read more.
Introduction: Rehabilitative interventions employing technology play a crucial role in bipolar disorder (BD) treatment. The study aims to appraise the virtual reality (VR)-based cognitive remediation (CR) and the interpersonal rhythm approaches to treatment outcomes of BD across different age groups. Methods: Post-hoc analysis of a 12-week randomizedcontrolled cross-over feasibility trial involving people with mood disorders (BD, DSM-IV) aged 18–75 years old: thirty-nine exposed to the experimental VR-based CR vs 25 waiting list controls. People with BD relapse, epilepsy or severe eye diseases (due to the potential VR risks exposure) were excluded. Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) was used to measure the outcome. Results: Cases and controls did not statistically significantly differ in age and sex distributions. Personal rhythm scores improved over the study follow-up in the experimental vs the control group (APC = 8.7%; F = 111.9; p < 0.0001), both in young (18–45 years) (APC = 5.5%; F = 70.46; p < 0.0001) and, to a lesser extent, older (>46 years) adults (APC = 10.5%; F = 12.110; p = 0.002). Conclusions: This study observed improved synchronization of personal and social rhythms in individuals with BD after a virtual reality cognitive remediation intervention, particularly in social activity, daily activities, and chronotype, with greater benefits in the younger population. Full article
(This article belongs to the Special Issue Stress, Rhythms Dysregulation and Bipolar Spectrum)
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11 pages, 628 KiB  
Article
An e-Health Psychoeducation Program for Managing the Mental Health of People with Bipolar Disorder during the COVID-19 Pandemic: A Randomized Controlled Study
by Alessandra Perra, Federica Sancassiani, Elisa Cantone, Elisa Pintus, Silvia D’Oca, Alessio Casula, Sara Littarru, Sara Zucca, Davide Tumolillo, Irene Pinna, Diego Primavera, Giulia Cossu, Antonio Egidio Nardi, Goce Kalcev and Mauro Giovanni Carta
J. Clin. Med. 2024, 13(12), 3468; https://doi.org/10.3390/jcm13123468 - 14 Jun 2024
Cited by 3 | Viewed by 1837
Abstract
Background: Social rhythm dysregulation has been identified as a determining factor in bipolar disorder (BD) relapses. It directly impacts individuals’ quality of life (QoL). This study aims to present preliminary data on the efficacy of an e-health psychoeducational intervention for BD for improving [...] Read more.
Background: Social rhythm dysregulation has been identified as a determining factor in bipolar disorder (BD) relapses. It directly impacts individuals’ quality of life (QoL). This study aims to present preliminary data on the efficacy of an e-health psychoeducational intervention for BD for improving clinical outcomes. Methods: This study used an open-label, crossover, randomized controlled trial design. The inclusion criteria consisted of a BD diagnosis, affiliation with the Consultation Psychiatry and Psychosomatic Center at the University Hospital in Cagliari, Italy, age over 18, and the obtaining of informed consent. Anxiety and depressive symptoms, QoL, and social and biological rhythms were measured using standardized instruments validated in Italian. Results: A total of 36 individuals were included in the experimental group (EG) and 18 in the control group (CG). The final sample consisted of 25 in the EG and 14 in the CG. A statistically significant improvement in QoL was found in the EG post-treatment (p = 0.011). Significant correlations were found between QoL and the dysregulation of biorhythms in the EG at T0 (p = 0.0048) and T1 (p = 0.0014). Conclusions: This study shows that, during extreme distress, an e-health group psychoeducation intervention for people with BD could significantly improve the perception of QoL. The results must be confirmed by studies conducted with larger-sized samples. Full article
(This article belongs to the Special Issue Patient-Oriented Treatments for Bipolar Disorder)
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9 pages, 242 KiB  
Article
The Stability of Social and Behavioral Rhythms and Unexpected Low Rate of Relevant Depressive Symptoms in Old Adults during the COVID-19 Pandemic
by Federica Sancassiani, Giulia Cossu, Elisa Cantone, Ferdinando Romano, Alessandra Perra, Antonio Urban, Samantha Pinna, Stefano Del Giacco, Roberto Littera, Davide Firinu, Luchino Chessa, Enzo Tramontano, Antonio Egidio Nardi and Mauro Giovanni Carta
J. Clin. Med. 2024, 13(7), 2005; https://doi.org/10.3390/jcm13072005 - 29 Mar 2024
Cited by 2 | Viewed by 1247
Abstract
Background: The disruption of social rhythms was found to be associated with depressive disorders during the COVID-19 pandemic; lower rates of these disorders were surprisingly found in old adults. The present study aims to verify the stability of social rhythms during lockdown [...] Read more.
Background: The disruption of social rhythms was found to be associated with depressive disorders during the COVID-19 pandemic; lower rates of these disorders were surprisingly found in old adults. The present study aims to verify the stability of social rhythms during lockdown in a sample of elderly people. Methods: Controlled cohort study (secondary analyses) of a previous randomized-controlled trial with the first evaluation in April 2019 (T0) and then 48 weeks later (T1) during the lockdown. The regulation of social and behavioral rhythms was measured through the Brief Social Rhythms Scale (BSRS); the Patient Health Questionnaire-9 (PHQ9) was adopted to detect relevant depressive symptoms. Results: 93 elderlies (73.36 ± 4.97 years old, 50.5% females) were evaluated at T0 and T1. Neither the total score of BSRS nor any of the 10 items showed a statistically significant difference comparing the two survey periods. The frequency of relevant depressive symptoms was 5.3% at T0 and 6.4% at T1 (OR = 0.8, CI95% 0.2–24). Conclusions: Among elderlies who did not show an increased risk of depression during the lockdown, social and behavioral rhythms remained exceptionally stable during the same period. Considering previous evidence about rhythms dysregulation preceding depression, their stability may be considered a factor of resilience. Full article
(This article belongs to the Section Mental Health)
10 pages, 245 KiB  
Article
Does the Response to a Stressful Condition in Older Adults with Life Rhythm Dysregulations Provide Evidence of the Existence of the “Dysregulation of Mood, Energy, and Social Rhythms Syndrome”?
by Diego Primavera, Cesar Ivan Aviles Gonzalez, Ferdinando Romano, Goce Kalcev, Samantha Pinna, Luigi Minerba, Alessandra Scano, Germano Orrù and Giulia Cossu
Healthcare 2024, 12(1), 87; https://doi.org/10.3390/healthcare12010087 - 29 Dec 2023
Cited by 22 | Viewed by 1631
Abstract
Objective: The COVID-19 lockdown periods have given rise to the “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS). This syndrome is characterized by a poor regulation of biological, social, and behavioral rhythms, including sleep, nutrition, and social contacts. The purpose of this [...] Read more.
Objective: The COVID-19 lockdown periods have given rise to the “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS). This syndrome is characterized by a poor regulation of biological, social, and behavioral rhythms, including sleep, nutrition, and social contacts. The purpose of this cohort study was to examine whether older adults with pre-existing DYMERS had a more negative perception of their health-related quality of life (H-QoL) during the COVID-19 pandemic lockdown, regardless of the presence of concurrent mood disorders. Method: The entire study population (N = 93; age > 65 year) was categorized based on whether they exhibited dysregulated rhythms at the outset of the study. A comparison was made between DYMERS-positive individuals and DYMERS-negative individuals, and we assessed their H-QoL at the conclusion of the study. We also compared the H-QoL of individuals in the cohort who did not have a positive depression score to understand the impact of the rhythm dysregulation alone. Results: The frequency of individuals with a critical health-related quality of life score (SF12 < 25) was higher in the cohort with pre-existing DYMERS during lockdown (33.33% vs. 6.17%). This difference remained significant even when only individuals without depressive symptomatology were considered (27.27% vs. 2.60%). Conclusion: The results of this study indicate that DYMERS can exert a substantial influence on health-related quality of life (H-QoL), even when mood disturbances are not present. Additional research is required to investigate the relationship between DYMERS and other psychiatric conditions as well as its nature as a standalone disorder. Full article
(This article belongs to the Special Issue Ageing, Chronicity and End of Life Care)
18 pages, 1679 KiB  
Review
The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders
by Emilija Knezevic, Katarina Nenic, Vladislav Milanovic and Nebojsa Nick Knezevic
Cells 2023, 12(23), 2726; https://doi.org/10.3390/cells12232726 - 29 Nov 2023
Cited by 165 | Viewed by 45516
Abstract
Cortisol, a critical glucocorticoid hormone produced by the adrenal glands, plays a pivotal role in various physiological processes. Its release is finely orchestrated by the suprachiasmatic nucleus, governing the circadian rhythm and activating the intricate hypothalamic–pituitary–adrenal (HPA) axis, a vital neuroendocrine system responsible [...] Read more.
Cortisol, a critical glucocorticoid hormone produced by the adrenal glands, plays a pivotal role in various physiological processes. Its release is finely orchestrated by the suprachiasmatic nucleus, governing the circadian rhythm and activating the intricate hypothalamic–pituitary–adrenal (HPA) axis, a vital neuroendocrine system responsible for stress response and maintaining homeostasis. Disruptions in cortisol regulation due to chronic stress, disease, and aging have profound implications for multiple bodily systems. Animal models have been instrumental in elucidating these complex cortisol dynamics during stress, shedding light on the interplay between physiological, neuroendocrine, and immune factors in the stress response. These models have also revealed the impact of various stressors, including social hierarchies, highlighting the role of social factors in cortisol regulation. Moreover, chronic stress is closely linked to the progression of neurodegenerative diseases, like Alzheimer’s and Parkinson’s, driven by excessive cortisol production and HPA axis dysregulation, along with neuroinflammation in the central nervous system. The relationship between cortisol dysregulation and major depressive disorder is complex, characterized by HPA axis hyperactivity and chronic inflammation. Lastly, chronic pain is associated with abnormal cortisol patterns that heighten pain sensitivity and susceptibility. Understanding these multifaceted mechanisms and their effects is essential, as they offer insights into potential interventions to mitigate the detrimental consequences of chronic stress and cortisol dysregulation in these conditions. Full article
(This article belongs to the Section Cells of the Nervous System)
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12 pages, 301 KiB  
Article
Does Screening for Bipolar Disorders Identify a “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS)? A Heuristic Working Hypothesis
by Mauro Giovanni Carta, Goce Kalcev, Michele Fornaro, Samantha Pinna, Cesar Ivan Aviles Gonzalez, Antonio Egidio Nardi and Diego Primavera
J. Clin. Med. 2023, 12(15), 5162; https://doi.org/10.3390/jcm12155162 - 7 Aug 2023
Cited by 28 | Viewed by 2046
Abstract
The aim of this paper is to verify if people with a positive score on the Mood Disorder Questionnaire (MDQ) without comorbidity of mood disorders showed a worse level of Health-related Quality of life (HRQol) compared to a control-matched sample of MDQ negatives, [...] Read more.
The aim of this paper is to verify if people with a positive score on the Mood Disorder Questionnaire (MDQ) without comorbidity of mood disorders showed a worse level of Health-related Quality of life (HRQol) compared to a control-matched sample of MDQ negatives, identifying a specific syndrome. This is a case-control study based on a database from a community survey. Cases: MDQ-positive without mood disorders; Controls: MDQ negatives matched by sex, age, and psychiatric diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria. Tools: MDQ, the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS) semi-structured interview for psychiatric diagnosis, and the Health Survey Short Form (SF-12) for measuring HRQol. People scoring positive on the MDQ without a diagnosis of mood disorders showed significantly lower scores on the SF-12 compared to people of the same age and of the same sex with an equal diagnosis of psychiatric disorders not related to mood disorders (35.21 ± 6.30 vs. 41.48 ± 3.39, p < 0.0001). In the debate whether a positive score on the MDQ selects an area of “malaise” due to the presence of disorders differing from Bipolar Disorders, or if a positive score on the MDQ may be considered a “subthreshold” form of bipolar disorder in people who may later develop bipolar disorder, a third hypothesis can be advanced, i.e., that a positive score on the MDQ identifies a specific “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS), characterized by a considerable amount of suffering and not attributable to other disorders, and which might represent a trigger for the previously mentioned disorders with which a positive score on the MDQ is associated, probably including, in severe conditions, bipolar disorder. Full article
(This article belongs to the Section Mental Health)
22 pages, 3584 KiB  
Review
Association between Hpa Axis Functioning and Mental Health in Maltreated Children and Adolescents: A Systematic Literature Review
by Pierre-Antoine Leroux, Nolwenn Dissaux, Jean Yves Le Reste, Guillaume Bronsard and Nathalie Lavenne-Collot
Children 2023, 10(8), 1344; https://doi.org/10.3390/children10081344 - 3 Aug 2023
Cited by 6 | Viewed by 3446
Abstract
Background: Previous studies have demonstrated that children who experience maltreatment show a more elevated risk of psychopathological disorders than children from the general population. The HPA (hypothalamic–pituitary–adrenal) axis is not mature at birth and undergoes strong social regulation during the first years of [...] Read more.
Background: Previous studies have demonstrated that children who experience maltreatment show a more elevated risk of psychopathological disorders than children from the general population. The HPA (hypothalamic–pituitary–adrenal) axis is not mature at birth and undergoes strong social regulation during the first years of life. Consequently, early exposure to stress could modify the usual adaptative response to stress. In stressful situations, perturbations in both cortisol response and cortisol circadian rhythm have been observed. Nevertheless, studies that have evaluated the links between child abuse, dysregulation of the HPA axis, and mental disorders have shown diverse results. Because of the variety of methods employed in the different studies, no formal comparisons have been made. In this systematic review, we have brought together these results. Methods: We conducted a systematic review of studies analyzing the correlation between child abuse, mental disorders, and HPA axis activity in patients aged between 6 and 16 years. PubMed, Scopus, Cochrane, and Google Scholar were searched using relevant keywords and inclusion/exclusion criteria (from 2000 to 2020). Results: Fifteen studies from the 351 identified were included. Most patients were children in the child welfare system. Children who had experienced child abuse presented with more severe mental disorders (particularly in the dimensional measure) than children who had not been abused. HPA axis activity was assessed by measuring basal cortisol for some studies and cortisol reactivity for other studies. For children experiencing child abuse, there was a possible association between abuse and a decrease in the reactivity of the HPA axis. In addition, early life stress could be associated with lower matinal cortisol. However, the association between mental disorders and cortisol secretion in maltreated children did not seem obvious. Conclusions: This systematic review demonstrates that mental disorders are more frequent and severe in cases where child abuse has occurred. Moreover, children who experienced child abuse seem to present changes in the reactivity of the HPA axis. Nevertheless, the potential correlation between these changes in the reactivity of the HPA axis and mental disorders in this population needs to be evaluated in further studies. Full article
(This article belongs to the Special Issue Stress and Stress Resilience in Children and Adolescents)
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13 pages, 789 KiB  
Article
Allopregnanolone Is Associated with a Stress-Induced Reduction of Heart Rate Variability in Premenstrual Dysphoric Disorder
by Ajna Hamidovic, John Davis, Fatimata Soumare, Aamina Naveed, Yaseen Ghani, Selma Semiz, Dina Khalil and Margaret Wardle
J. Clin. Med. 2023, 12(4), 1553; https://doi.org/10.3390/jcm12041553 - 16 Feb 2023
Cited by 9 | Viewed by 3891
Abstract
Human survival and wellbeing require appropriate responses to stress, including a highly coordinated and efficient nervous system control of the heart rhythm. During stress, a greater disinhibition of the vagal nerve is reflective of poor stress adaptability, which may be relevant in premenstrual [...] Read more.
Human survival and wellbeing require appropriate responses to stress, including a highly coordinated and efficient nervous system control of the heart rhythm. During stress, a greater disinhibition of the vagal nerve is reflective of poor stress adaptability, which may be relevant in premenstrual dysphoric disorder (PMDD)—a debilitating affective condition thought to be marked by dysregulated stress processing and sensitivity to allopregnanolone. In the present study, women with PMDD (n = 17) and healthy controls (n = 18), who did not take medication, smoke, or consume illicit drugs, and who were free of other psychiatric conditions, participated in the Trier Social Stress Test, during which we measured the high frequency of the heart rate (HF-HRV) and allopregnanolone using ultra-performance liquid chromatography tandem mass spectrometry. Relative to their baseline, women who have PMDD, but not the healthy controls, experienced a reduction in HF-HRV during stress anticipation (p ≤ 0.05) and stress (p ≤ 0.01). Their recovery from stress was significantly delayed (p ≤ 0.05). Absolute peak HF-HRV change from baseline was significantly predicted by baseline allopregnanolone only in the PMDD group (p ≤ 0.01). The present study shows how an interaction between stress and allopregnanolone—which have both been separately implicated in PMDD—underlies PMDD expression. Full article
(This article belongs to the Section Pharmacology)
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32 pages, 6100 KiB  
Article
Duplicated dnmt3aa and dnmt3ab DNA Methyltransferase Genes Play Essential and Non-Overlapped Functions on Modulating Behavioral Control in Zebrafish
by Yu-Heng Lai, Gilbert Audira, Sung-Tzu Liang, Petrus Siregar, Michael Edbert Suryanto, Huan-Chau Lin, Omar Villalobos, Oliver B. Villaflores, Erwei Hao, Ken-Hong Lim and Chung-Der Hsiao
Genes 2020, 11(11), 1322; https://doi.org/10.3390/genes11111322 - 7 Nov 2020
Cited by 7 | Viewed by 4627
Abstract
DNA methylation plays several roles in regulating neuronal proliferation, differentiation, and physiological functions. The major de novo methyltransferase, DNMT3, controls the DNA methylation pattern in neurons according to environmental stimulations and behavioral regulations. Previous studies demonstrated that knockout of Dnmt3 induced mouse anxiety; [...] Read more.
DNA methylation plays several roles in regulating neuronal proliferation, differentiation, and physiological functions. The major de novo methyltransferase, DNMT3, controls the DNA methylation pattern in neurons according to environmental stimulations and behavioral regulations. Previous studies demonstrated that knockout of Dnmt3 induced mouse anxiety; however, controversial results showed that activation of Dnmt3 causes anxiolytic behavior. Thus, an alternative animal model to clarify Dnmt3 on modulating behavior is crucial. Therefore, we aimed to establish a zebrafish (Danio rerio) model to clarify the function of dnmt3 on fish behavior by behavioral endpoint analyses. We evaluated the behaviors of the wild type, dnmt3aa, and dnmt3ab knockout (KO) fish by the novel tank, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm locomotor activity, color preference, and short-term memory tests. The results indicated that the dnmt3aa KO fish possessed abnormal exploratory behaviors and less fear response to the predator. On the other hand, dnmt3ab KO fish displayed less aggression, fear response to the predator, and interests to interact with their conspecifics, loosen shoaling formation, and dysregulated color preference index ranking. Furthermore, both knockout fishes showed higher locomotion activity during the night cycle, which is a sign of anxiety. However, changes in some neurotransmitter levels were observed in the mutant fishes. Lastly, whole-genome DNA methylation sequencing demonstrates a potential network of Dnmt3a proteins that is responsive to behavioral alterations. To sum up, the results suggested that the dnmt3aa KO or dnmt3ab KO fish display anxiety symptoms, which supported the idea that Dnmt3 modulates the function involved in emotional control, social interaction, and cognition. Full article
(This article belongs to the Special Issue Zebrafish Animal Models)
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