This case study investigated the psychophysiological stress responses of a diver during and after a 24-h hyperbaric exposure. Comprehensive biomarker analysis revealed relevant changes in oxidative stress parameters and cardiac muscle markers. Notably, a critical time point at 6 h (T2) emerged, characterized by peak oxidative stress and diminished antioxidant capacity, followed by progressive cardiac strain as evidenced by elevated creatine kinase isoenzime (CK-MBm) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels. Despite these physiological challenges, no pathological tissue damage was detected, indicating effective endogenous defense mechanisms. Moreover, no significant psychophysiological symptoms were detected before, during, and after the dive, except for tiredness and insomnia. Cognitive assessments reflected adaptive shifts in response strategies under prolonged stress, emphasizing the importance of monitoring to prevent operational risks. These findings highlight the need to consider dive duration carefully, suggesting that introducing rest intervals or personnel rotation around the critical T2 threshold may mitigate physiological fatigue and optimize performance. This study provides valuable insights into human adaptation to extended hyperbaric conditions and informs safety protocols for commercial and military diving operations.

Major depressive disorder (MDD) continues to pose a major therapeutic challenge due to its clinical heterogeneity. This chapter looks at the development of antidepressant treatments, starting with early interventions such as electroconvulsive therapy (ECT), monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Although these treatments targeted the monoaminergic system, they had significant limitations in terms of safety and efficacy. The introduction of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) improved tolerability but left unmet needs, particularly in terms of treatment resistance and side effects. In response, research has expanded beyond monoamines and focused on new mechanisms. A breakthrough came with N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine and esketamine, which achieved fast-acting effects and shifted the focus to glutamatergic modulation. Other developments in this area include modulators such as partial agonists, positive allosteric modulators (PAMs), and negative allosteric modulators (NAMs). In addition, gamma-aminobutyric acid (GABA) modulation has gained attention, with neurosteroids such as zurolone (approved for postpartum depression [PPD]) representing a new therapeutic approach. Other new strategies target the opioid system, particularly kappa-opioid receptor (KOR) antagonism, whose role in the treatment of anhedonia and depression is being investigated. Psychedelics, including psilocybin, have come back into focus as potential treatments due to their ability to elicit rapid and sustained antidepressant effects via agonism of the serotonin 2A receptor (5-HT2A), although their efficacy and safety require further research. In addition, innovative treatments targeting orexin, trace amine-associated receptor 1 (TAAR1) and members of the Q subfamily of voltage-gated potassium channels (KCNQ) are also in development. Despite these advances, some challenges remain. These include diagnostic heterogeneity, incomplete understanding of neurobiological mechanisms, limitations of preclinical models, lack of reliable biomarkers, and economic obstacles. Future advances could be driven by artificial intelligence (AI), which has the potential to revolutionize drug discovery, optimize clinical trials, and personalize treatments for patients.

IntroductionInsomnia and obstructive sleep apnea (OSA) are each linked to elevated risks of depression. When comorbid (COMISA), these risks increase further, highlighting the need for effective depression screening. This study evaluated the screening accuracy of a novel software, MEB-001, for detecting current major depressive episode (cMDE) in individuals identified as with and without suspected COMISA (sCOMISA).MethodsWe conducted a retrospective sub-analysis from a prospective multicenter study at U.S. sleep clinics, including 296 adults who underwent routine polysomnography (PSG). Electrocardiogram and electroencephalogram signals, along with items 1 and 2 of the self-report depression screener Patient Health Questionnaire, 9 items (PHQ-9), were used to generate MEB-001 screening output. The Mini International Neuropsychiatric Interview (MINI) served as the diagnostic reference for cMDE. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for MEB-001 and PHQ-9 (cut-off ≥10), with subgroup comparisons conducted using Fisher's exact and McNemar's tests (p < 0.05).ResultsMINI identified cMDE in 15.5% of participants (16.9% in sCOMISA; 14.2% in non-COMISA). Against the MINI, MEB-001 achieved 84.8% sensitivity, 72.0% specificity, 35.8% PPV, and 96.3% NPV in the full cohort; PHQ-9 ≥10 showed similar performance (89.1, 68.4, 34.2, and 97.2%, respectively). MEB-01's performance did not differ between sCOMISA and non-sCOMISA (all p ≥ 0.68), and no significant McNemar differences were found in the subgroups (p > 0.19).DiscussionMEB-001 demonstrated consistent cMDE screening performance comparable to the PHQ-9, supporting its potential utility in sleep clinic settings.

OBJECTIVE:We cross-sectionally compared outpatients with severe asthma (SA), chronic rhinosinusitis with nasal polyps (CRSwNP), or both, grouped by current, past, or absent panic disorder (PD) history, to assess clinical differences. Published data on this topic are limited in SA and absent in CRSwNP. METHODS:Between February and March 2024, outpatients at the Personalized Medicine Asthma and Allergy Clinic, Humanitas Research Hospital, were consecutively recruited during follow-up visits. All were previously enrolled in the SANI (Severe Asthma Network Italy) or RINET (Rhinosinusitis Italian Network) registries. Participants completed a self-report survey assessing sociodemographics, lifestyle, medical history, asthma control, nasal obstruction, physical symptoms, cognitive-emotional factors, and quality of life. Provisional diagnoses of PD (PPD) and, additionally, major depressive episode (PMDE) were based on the Patient Health Questionnaire (PHQ). Analyses included Kruskal-Wallis, Dunn's post-hoc, and Fisher's exact tests with Holm's correction (α = 0.05). RESULTS:Among 79 patients (58.2 % women), 7 (8.9 %) had current PPD and 12 (15.2 %) had past PPD. Four (5.1 %) had a PMDE. PPD significantly correlated with poorer asthma control, more severe nasal obstruction, increased dyspnea and physical symptoms, greater asthma-related catastrophizing, focus on bodily sensations, avoidance of activities, and reduced quality of life. CONCLUSIONS:PPD is more prevalent in SA and/or CRSwNP than in the general population. Panic comorbidity links to greater respiratory severity and symptom burden, supporting screening and integrated care. The study is novel in including CRSwNP, advanced-treatment patients, evaluating current and past PPD, and exploring multiple previously unexamined clinical aspects. Further research is warranted.

Introduction:Depression and sleep disorders are strongly linked, with sleep centers (SCs) reporting depressive symptoms in up to 63% of patients and depression diagnoses in 22%. Despite this, routine depression screening is not standard in SCs. This study aimed to identify patients meeting criteria for a current major depressive episode (cMDE) among those self-reporting clinically significant depressive symptoms (CSDS) in U.S. SCs. Method:This retrospective sub-analysis of an ongoing multicenter trial included 147 adults (22-75 years) referred for sleep disorder evaluation. Participants underwent psychiatric assessments using the Mini-International Neuropsychiatric Interview and Patient Health Questionnaire-9 (PHQ-9), with CSDS defined as PHQ-9 ≥10. Descriptive statistics were compared between patients with/without a confirmed cMDE using non-parametric tests. Additional Mann-Whitney U tests assessed sleep characteristics by cMDE, major depressive disorder (MDD), and bipolar disorder (BD) (statistical significance, p < 0.05). Results:Of 147 patients, 57 (38.8%) had a PHQ-9 score ≥10. Among them, 23 (40.3%) were diagnosed with cMDE: 17 (29.8%) met cMDD criteria, and 6 (10.5%) had BD, type I. A significantly lower cMDE prevalence was observed in patients without CSDS. Sleep characteristics showed no significant differences except for a lower N3 percentage in cMDE. BD, type I was associated with higher obstructive sleep apnea comorbidity compared to cMDD. Discussion:Our findings suggest major depression prevalence in SCs is five times higher than in the general population, highlighting the need for routine depression screening and psychiatric confirmation. This also aids in identifying comorbidities and fostering tailored interventions to improve outcomes.

Background: Serotonin (5-HT) is a neurotransmitter and a hormone that regulates various functions. Serotonin receptors have been studied in animal experiments in the vestibular system, beginning from the inner ear and vestibular nuclei. However, the role of serotonin in the vestibular system and disorders remains to be clarified. Methods: A review of the literature was performed on different databases according to the PRISMA guidelines. Only publications published on humans and in English have been included. A total of 41 articles were included in this review. Results: There are many publications regarding the use of SSRI/SNRI in vestibular disorders. Regarding persistent postural perceptual dizziness (PPPD) and chronic subjective dizziness (CSD) the available evidence supports multimodality treatment incorporating vestibular rehabilitation, serotonergic medications, and cognitive behavior therapy, although most studies have not included a placebo control group. As for vestibular migraine (VM), SNRI and SSRIs were proposed as preventive therapy and demonstrated a reduction in vertigo attacks in patients with Menière’s Disease (MD), especially when symptoms of anxiety disorder were present. Conclusions: Although SSRIs/SNRIs are considered an off-label therapy for vertigo, several studies have assessed their efficacy in vestibular disorders, as indicated in the data published on PPPD, MD, and VM above all. As some studies report that serotonin receptors are also present in the inner ear and vestibular nuclei, it can be postulated that in cases where the natural levels of serotonin are altered, such as in depression and anxiety, the change in serotonin levels may affect vestibular function and play a role in vestibular disorders.

This chapter provides a comprehensive examination of a broad range of biomarkers used for the diagnosis and prediction of treatment outcomes in major depressive disorder (MDD). Genetic, epigenetic, serum, cerebrospinal fluid (CSF), and neuroimaging biomarkers are analyzed in depth, as well as the integration of new technologies such as digital phenotyping and machine learning. The intricate interplay between biological and psychological elements is emphasized as essential for tailoring MDD management strategies. In addition, the evolving link between psychotherapy and biomarkers is explored to uncover potential associations that shed light on treatment response. This analysis underscores the importance of individualized approaches in the treatment of MDD that integrate advanced biological insights into clinical practice to improve patient outcomes.

Personalized psycho-oncology represents a major challenge for the holistic care of cancer patients. It focuses on individualized psychotherapeutic and psychiatric interventions to address specific psychological needs. This narrative review summarizes the current literature on personalized psycho-oncology and highlights the prevalence and impact of psychiatric/psychological disorders in cancer patients. Personalized approaches, including tailored interventions and interdisciplinary collaboration, have been shown to be effective in improving mental health and overall quality of life. The integration of inflammatory biomarkers into treatment plans is a promising but challenging way to alleviate mental health problems. In addition, there is a need for specific diagnostic tools and treatment guidelines that take into account the specific psychological impact of different types of cancer. Future research should aim to refine these personalized strategies, improve diagnostic accuracy, and evaluate the cost-effectiveness of these interventions to improve both the psychological well-being and treatment outcomes of cancer patients.

Manual sleep staging (MSS) using polysomnography is a time-consuming task, requires significant training, and can lead to significant variability among scorers. STAGER is a software program based on machine learning algorithms that has been developed by Medibio Limited (Savage, MN, USA) to perform automatic sleep staging using only EEG signals from polysomnography. This study aimed to extensively investigate its agreement with MSS performed during clinical practice and by three additional expert sleep technicians. Forty consecutive polysomnographic recordings of patients referred to three US sleep clinics for sleep evaluation were retrospectively collected and analyzed. Three experienced technicians independently staged the recording using the electroencephalography, electromyography, and electrooculography signals according to the American Academy of Sleep Medicine guidelines. The staging initially performed during clinical practice was also considered. Several agreement statistics between the automatic sleep staging (ASS) and MSS, among the different MSSs, and their differences were calculated. Bootstrap resampling was used to calculate 95% confidence intervals and the statistical significance of the differences. STAGER's ASS was most comparable with, or statistically significantly better than the MSS, except for a partial reduction in the positive percent agreement in the wake stage. These promising results indicate that STAGER software can perform ASS of inpatient polysomnographic recordings accurately in comparison with MSS.

Introduction: Recommendations for treating panic disorder (PD) in older patients are scarce. The authors have systematically reviewed whether several recommended medications are superior to others and their optimal doses in this age group. Methods: A database search of studies involving patients with PD with/without agoraphobia aged >= 60 years was carried out using PubMed, PsycINFO, Embase, and Clinical Trials.gov, from their inception dates to 1 March 2023. Only four (published from 2002 to 2010) of the 1292 records screened were included. A risk of bias assessment was provided. This systematic review was performed using The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Results: Two studies were randomized clinical trials, whereas two were open-label, including paroxetine, citalopram, escitalopram, and sertraline; three studies reported short-term evaluations, whereas one study included a 26-week follow-up. Medications provided benefits, with good tolerability. Preliminary results suggested greater benefits of paroxetine in reducing panic attacks vs. cognitive - behavioral therapy, and an earlier decrease in PAs with escitalopram vs. citalopram. Risk of bias was considerable. Conclusions: The pharmacological management of PD in older patients has received no attention. Findings are scant, dated, and affected by methodological flaws; thus, they do not provide significant advances.

Depression screening is not part of routine clinical practice in US sleep clinics. Our study aimed to report the prevalence of depression among individuals referred to US sleep clinics. According to our findings, approximately 21

Given the involvement of balance system abnormalities in the pathophysiology of panic disorder and agoraphobia (PD-AG), we evaluated initial evidence for feasibility, acceptability, and potential clinical usefulness of 10 sessions of balance rehabilitation with peripheral visual stimulation (BR-PVS) in an open-pilot 5-week intervention study including six outpatients with PD-AG who presented residual agoraphobia after selective serotonin reuptake inhibitor (SSRI) treatment and cognitive–behavioral therapy, dizziness in daily life, and peripheral visual hypersensitivity measured by posturography. Before and after BR-PVS, patients underwent posturography, otovestibular examination (no patients presented peripheral vestibular abnormalities), and panic-agoraphobic symptom and dizziness evaluation with psychometric tools. After BR-PVS, four patients achieved postural control normalization measured by posturography, and one patient exhibited a favorable trend of improvement. Overall, panic-agoraphobic symptoms and dizziness decreased, even though to a lesser extent in one patient who had not completed the rehabilitation sessions. The study presented reasonable levels of feasibility and acceptability. These findings suggest that balance evaluation should be considered in patients with PD-AGO presenting residual agoraphobia and that BR-PVS might be an adjunctive therapeutic option worth being tested in larger randomized controlled studies.

Abnormalities in cardiorespiratory measurements have repeatedly been found in patients with panic disorder (PD) during laboratory-based assessments. However, recordings performed outside laboratory settings are required to test the ecological validity of these findings. Wearable devices, such as sensor-imbedded garments, biopatches, and smartwatches, are promising tools for this purpose. We systematically reviewed the evidence for wearables-based cardiorespiratory assessments in PD by searching for publications on the PubMed, PsycINFO, and Embase databases, from inception to 30 July 2022. After the screening of two-hundred and twenty records, eight studies were included. The limited number of available studies and critical aspects related to the uncertain reliability of wearables-based assessments, especially concerning respiration, prevented us from drawing conclusions about the cardiorespiratory function of patients with PD in daily life. We also present preliminary data on a pilot study conducted on volunteers at the Villa San Benedetto Menni Hospital for evaluating the accuracy of heart rate (HR) and breathing rate (BR) measurements by the wearable Zephyr BioPatch compared with the Quark-b2 stationary testing system. Our exploratory results suggested possible BR and HR misestimation by the wearable Zephyr BioPatch compared with the Quark-b2 system. Challenges of wearables-based cardiorespiratory assessment and possible solutions to improve their reliability and optimize their significant potential for the study of PD pathophysiology are presented.

BACKGROUND:This study longitudinally evaluated first-onset major depression rates during the pandemic in Italian adults without any current clinician-diagnosed psychiatric disorder and created a predictive machine learning model (MLM) to evaluate subsequent independent samples.METHODS:An online, self-reported survey was released during two pandemic periods (May to June and September to October 2020). Provisional diagnoses of major depressive disorder (PMDD) were determined using a diagnostic algorithm based on the DSM criteria of the Patient Health Questionnaire-9 to maximize specificity. Gradient-boosted decision trees and the SHapley Additive exPlanations technique created the MLM and estimated each variable's predictive contribution.RESULTS:There were 3532 participants in the study. The final sample included 633 participants in the first wave (FW) survey and 290 in the second (SW). First-onset PMDD was found in 7.4% of FW participants and 7.2% of the SW. The final MLM, trained on the FW, displayed a sensitivity of 76.5% and a specificity of 77.8% when tested on the SW. The main factors identified in the MLM were low resilience, being an undergraduate student, being stressed by pandemic-related conditions, and low satisfaction with usual sleep before the pandemic and support from relatives. Current smoking and taking medication for medical conditions also contributed, albeit to a lesser extent.LIMITATIONS:Small sample size; self-report assessment; data covering 2020 only.CONCLUSIONS:Rates of first-onset PMDD among Italians during the first phases of the pandemic were considerable. Our MLM displayed a good predictive performance, suggesting potential goals for depression-preventive interventions during public health crises.

BACKGROUND:We investigated, for the first time, whether there are any sex differences in retrospective self-reported childhood maltreatment (CM) in Italian adult patients with major depressive disorder (MDD) or bipolar disorder (BD). Furthermore, the potential impacts of patients' age on the CM self-report were investigated.METHODS:This retrospective study used the data documented in the electronic medical records of patients who were hospitalized for a 4-week psychiatric rehabilitation program. CM was assessed using the 28-item Childhood Trauma Questionnaire (CTQ), which evaluates emotional, physical, and sexual abuse, as well as emotional and physical neglect. The linear and logistic regression models were used (α = 0.01).RESULTS:Three hundred thirty-five patients with MDD (255 women and 80 men) and 168 with BD (97 women and 71 men) were included. In both samples, considerable CM rates were identified, but no statistically significant sex differences were detected in the variety of CTQ-based CM aspects. There was a significant association, with no sex differences, between increasing patients' age and a decreasing burden of CM.CONCLUSION:Both women and men with MDD or BD experienced a similar and considerable CM burden. Our findings support routine CM assessment in psychiatric clinical practice.

The polygenic and multifactorial nature of many psychiatric disorders has hampered implementation of the personalized medicine approach in clinical practice. However, induced pluripotent stem cell (iPSC) technology has emerged as an innovative tool for patient-specific disease modeling to expand the pathophysiology knowledge and treatment perspectives in the last decade. Current technologies enable adult human somatic cell reprogramming into iPSCs to generate neural cells and direct neural cell conversion to model organisms that exhibit phenotypes close to human diseases, thereby effectively representing relevant aspects of neuropsychiatric disorders. In this regard, iPSCs reflect patient pathophysiology and pharmacological responsiveness, particularly when cultured under conditions that emulate spatial tissue organization in brain organoids. Recently, the application of iPSCs has been frequently associated with gene editing that targets the disease-causing gene to deepen the illness pathophysiology and to conduct drug screening. Moreover, gene editing has provided a unique opportunity to repair the putative causative genetic lesions in patient-derived cells. Here, we review the use of iPSC technology to model and potentially treat neuropsychiatric disorders by illustrating the key studies on a series of mental disorders, including schizophrenia, major depressive disorder, bipolar disorder, and autism spectrum disorder. Future perspectives will involve the development of organ-on-a-chip platforms that control the microenvironmental conditions so as to reflect individual pathophysiological by adjusting physiochemical parameters according to personal health data. This strategy could open new ways by which to build a disease model that considers individual variability and tailors personalized treatments.