Search Results (744)

The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Although the aetiology of IBD remains largely unknown, several studies suggest that an individual’s genetic susceptibility, external environmental factors, intestinal microbial flora, and immune responses are all factors involved in and functionally linked to the pathogenesis of IBD. Beyond the gastrointestinal manifestations, IBD patients frequently suffer from psychiatric comorbidities, particularly depression and anxiety. It remains unclear whether these disorders arise solely from reduced quality of life or whether they share overlapping biological mechanisms with IBD. This review aims to explore the bidirectional relationship between IBD and depressive disorders (DDs), with a focus on four key shared mechanisms: immune dysregulation, genetic susceptibility, alterations in gut microbiota composition, and dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis. By examining recent literature, we highlight how these interconnected systems may contribute to both intestinal inflammation and mood disturbances. Furthermore, we discuss the reciprocal pharmacologic interactions between IBD and DDs: treatments for IBD, such as TNF-alpha and integrin inhibitors, have demonstrated effects on mood and anxiety symptoms, while certain antidepressants appear to exert independent anti-inflammatory properties, potentially reducing the risk or severity of IBD. Overall, this review underscores the need for a multidisciplinary approach to the care of IBD patients, integrating psychological and gastroenterological assessment. A better understanding of the shared pathophysiology may help refine therapeutic strategies and support the development of personalized, gut–brain-targeted interventions. Full article

Background: About half of all Major Depressive Disorder (MDD) patients have anxiety disorder. There is a neurologic basis for the comorbidity of balance (vestibular) disorders and anxiety. To detect comorbid anxiety disorder in MDD patients and, importantly, to investigate its relationship with depressive severity, we use Electrovestibulography (EVestG), which is predominantly a measure of vestibular response. Methods: In a population of 42 (26 with anxiety disorder) MDD patients, EVestG signals were measured. Fourteen (eight with anxiety disorder) were not on any anti-depressants, anti-psychotics or mood stabilizers. Using standard questionnaires, participants were depression-wise labelled as reduced symptomatic (MADRS ≤ 19, R) or symptomatic (MADRS > 19, S) as well as with or without anxiety disorder. Analyses were conducted on the whole data set, matched (age/gender/MADRS) subsets and compared with medication free subsets. Low-frequency EVestG firing pattern modulation was measured. Results: The main differences between MDD populations with and without anxiety disorder populations, regardless of being medicated or not, were (1) the presence of an increased 10.8 Hz component in the dynamic movement phase recordings, (2) the presence of asymmetric right versus left 7.6–8.9 Hz and 12.1–13.8 Hz frequency bands in the no motion (static) phase recordings, and (3) these differences were dependent on depressive severity. Conclusions: The EVestG measures are capable of quantifying anxiety in MDD patients. These measures are functions of depressive severity and are hypothesized to be linked to Hippocampal Theta (~4–12 Hz). Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic immune-mediated neurological disorder that primarily affects young adults and is frequently accompanied by psychiatric comorbidities such as depression and anxiety, both of which significantly diminish patients’ quality of life (QoL). This study investigated the effect of two oral disease-modifying therapies (DMTs), fingolimod and cladribine, on mental health and QoL in patients with relapsing-remitting MS (RRMS). The aim of the study was to compare levels of depression, anxiety, and health-related quality of life (HRQoL) in RRMS patients treated with fingolimod or cladribine, and to evaluate their associations with clinical and radiological parameters. Materials and Methods: Eighty RRMS patients aged 18 to 50 years with Expanded Disability Status Scale (EDSS) scores of 3.0 or less, no recent disease relapse, and no history of antidepressant use were enrolled. Forty patients were treated with fingolimod and forty with cladribine. Depression and anxiety were assessed using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). QoL was evaluated using the Multiple Sclerosis QoL-54 (MSQOL-54) instrument. Additional clinical data, including MRI-based lesion burden, EDSS scores, age, disease duration, and occupational status, were collected. Results: No statistically significant differences were observed between the two groups regarding HDRS and HARS scores (p > 0.05). However, patients treated with fingolimod had significantly higher scores in the Energy/Fatigue subdomain (7.55 ± 2.02 vs. 6.56 ± 2.57, p = 0.046) and Composite Mental Health (CMH) score (64.73 ± 15.01 vs. 56.00 ± 18.93, p = 0.029) compared to those treated with cladribine. No significant differences were found in the independent items of the MSQOL-54. A negative correlation was identified between total lesion load and QoL scores. Conclusions: Although fingolimod and cladribine exert comparable effects on depression and anxiety levels, fingolimod may be associated with better mental health outcomes and reduced fatigue in RRMS patients. Furthermore, lesion burden and clinical parameters such as age and EDSS score may independently influence QoL, regardless of the DMT used. Full article

Background/Objectives: Cardiovascular diseases (CVDs) are frequently associated with psychiatric and cognitive comorbidities. These conditions have been shown to significantly impact quality of life and clinical outcomes. This study aims to evaluate the prevalence of anxiety, depression, and cognitive deficits in patients with CVD and to compare the results with existing evidence in the literature. Methods: A total of 74 patients were assessed using the following standardized screening tools: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI). A systematic review was then conducted to compare the findings with those reported in the literature. Results: Most previous studies using the MoCA reported an over 70% absence of cognitive impairment, whereas this study shows a balanced distribution between the absence of (32.4%) and mild (35%) or moderate (32%) impairment. Studies with the MMSE indicated high rates of absence of cognitive deficits (74–79%), but here, the rate of absence was lower (58%), with an increase in mild impairment (42%). Regarding depression, compared with studies showing only absence or moderate/severe forms, this study reveals a more balanced profile, with 57% without depression and with varying severity levels (22% mild, 19% moderate, and 3% severe). Finally, for anxiety, unlike previous asymmetric distributions, greater variability was observed, with 58% without anxiety and significant percentages of mild (26%), moderate (12%), and severe (4%) anxiety. Conclusions: The results highlight a significant and varied prevalence of anxiety, depression, and cognitive deficits, emphasizing the importance of a multidimensional assessment to improve clinical management and therapeutic outcomes. Full article

Background: Art therapy is increasingly recognized as a valuable complementary intervention for individuals with eating disorders (EDs), who frequently experience comorbid anxiety and difficulties with emotional regulation. However, few studies have examined its short-term effects on state and trait anxiety within structured clinical settings. Methods: This pilot study involved 19 adolescent females (mean age 17.7 ± 2.1 years) diagnosed with anorexia nervosa (AN) or bulimia nervosa (BN) and admitted to the Mariconda Regional Residence for Eating Disorders (ASL Salerno, Italy) in residential or semi-residential treatment. Participants completed a structured six-week cycle of weekly textile-based art therapy sessions, designed to promote emotional expression and body reconnection. State and trait anxiety levels were assessed pre- and post-session using the State-Trait Anxiety Inventory (STAI). Repeated-measures ANOVA was used to analyze state anxiety changes; a linear mixed-effects model was applied to trait anxiety. Results: State anxiety significantly decreased immediately after sessions (p = 0.002). A significant main effect of session (p = 0.01) and a time × session interaction (p = 0.025) indicated variability across sessions. Trait anxiety showed a non-significant trend toward reduction (p = 0.11); however, reductions were significant at sessions 4 (p = 0.015), 5 (p < 0.001), and 6 (p = 0.005). Conclusions: Art therapy may offer immediate reductions in state anxiety and may contribute to a longer-term reduction in trait anxiety with 4–6 sessions. These findings support integrating creative interventions within multidisciplinary ED treatment programs. Future research with larger samples and control groups is needed to confirm and expand upon these preliminary results. Full article

A psoriasis vulgaris flare is characterized by a rapid intensification of symptoms, which is often triggered by various factors that can worsen the condition. The risk factors for these exacerbations are numerous and include obesity, antihypertensive drugs, and psychological stress. Moreover, links have been documented between type II diabetes, hypertension, and psoriasis vulgaris. The present case report describes a 52-year-old female patient who presented at the clinic with disseminated erythematous-squamous plaques and patches covered by thick, white-pearly, easily detachable scales, along with stress, fatigue, anxiety, severe pruritus, irritability, insomnia, and decreased self-esteem. Her past medical regimen included various conventional topical options, including calcipotriol combined with betamethasone, clobetasol, betamethasone combined with salicylic acid, and betamethasone combined with gentamicin, yet the condition remained refractory, with periodic flare-ups. The integrated and personalized therapeutic approach aimed to target both the dermatological issues and the associated systemic and psychological factors contributing to the condition. The therapeutic strategy implemented in this case combined psychological counseling sessions, a very low-calorie ketogenic diet, oral supplementation with anti-inflammatory and antioxidant vitamins and minerals, topical treatments utilizing urea and Dead Sea-mineral-based formulations, and rosemary extract-based scalp care, without requiring additional conventional treatment. This comprehensive approach led to significant improvement, ultimately achieving complete remission of the patient’s psoriasis. The associated comorbidities were well controlled with the specified medication, without any further complications. Thus, the importance of alternative options was emphasized, particularly in the context of an incurable disease, along with the need for continued research to improve the ongoing therapeutic management of psoriasis vulgaris. Such approaches are essential to reducing the risk of flare-ups and to achieving better management of associated risk factors. Full article

Tobacco use disorder remains a leading cause of preventable mortality, with nicotine playing a central role in the development and maintenance of dependence, mainly through its action on α4β2 nicotinic acetylcholine receptors (nAChRs). Smoking cessation treatments must address both physiological withdrawal and the affective disturbances (such as anxiety, irritability, and mood lability) which often facilitate relapses. This review compares two pharmacotherapies used in smoking cessation, varenicline and cytisinicline (cytisine), with particular focus on their impact on emotional regulation, psychological symptoms, and neuropsychiatric safety. Varenicline, a high-affinity partial agonist at α4β2 nAChRs, has demonstrated superior efficacy in maintaining abstinence and is well-supported by robust clinical data, including in psychiatric populations. However, its use may be limited by adverse effects such as nausea and sleep disorders. Cytisinicline, a structurally similar but less potent partial agonist, has recently gained renewed interest due to its lower cost, favorable tolerability profile, and comparable effectiveness in the general population. Although less extensively studied in patients with serious mental illness, preliminary data suggest cytisinicline may offer a better side effect profile, particularly regarding sleep disturbances and emotional reactivity. Both agents appear to ameliorate withdrawal-related affective symptoms without significantly increasing psychiatric risk. Ultimately, pharmacotherapy choice should be guided by individual clinical features, mental health status, treatment tolerability, and resource availability. Further research is needed to establish cytisinicline’s efficacy and safety across diverse clinical contexts, particularly among individuals with severe psychiatric comorbidities. Full article

Background: Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder characterized by recurrent episodes of intense nausea and vomiting. Despite increasing awareness, a standardized treatment approach remains lacking in pediatric populations. Lifestyle factors and anxiety are common triggers, yet their systematic management has not been fully incorporated into therapeutic strategies. Objective: To evaluate the effectiveness of lifestyle modifications and selective serotonin reuptake inhibitors (SSRIs) in the management of pediatric CVS and to compare their outcomes with standard cyproheptadine prophylaxis. Methods: This retrospective study included 119 patients aged 1.2–17.5 years who were diagnosed with CVS according to Rome IV criteria between September 2021 and January 2025. Clinical, psychiatric, and lifestyle data were retrieved from the university’s digital medical records. Patients were grouped according to treatment modality: cyproheptadine, SSRI, or acute attack management alone. Treatment success at 12 weeks was defined as complete cessation of vomiting episodes or absence of hospitalization, prolonged attacks, and school/work absenteeism. Results: Anxiety symptoms were present in 78.2% of patients. SSRIs were prescribed to 34 patients with moderate to severe anxiety, all of whom achieved treatment success. Lifestyle adherence was observed in 73.9% and was found to be a predictor of treatment success. Cyproheptadine was administered to 66 patients but did not provide additional benefit over effective lifestyle modification. Six patients discontinued cyproheptadine due to drowsiness or weight gain. Conclusions: Lifestyle interventions significantly improve outcomes in pediatric CVS. SSRIs represent a safe and effective prophylactic option for patients with comorbid anxiety or poor adherence to behavioral recommendations. These findings support the integration of psychosocial and lifestyle-based strategies into standard CVS treatment protocols. Full article

Background/Objectives: Neurofibromatosis type 1 (NF1) and Noonan syndrome spectrum disorders (NSSD) are the most common RASopathies, resulting from germline mutations that affect the RAS-MAPK signaling pathway. Both are associated with increased risk for neurodevelopmental and psychiatric conditions, yet few studies have used structured diagnostic interviews to compare their psychiatric comorbidities. Methods: We conducted clinician-administered DSM-5 diagnostic assessments (KSADS) in 123 children with RASopathies (NF1 = 29, NSSD = 94; ages 5–15). Diagnosis prevalence was compared within each group and to population-based estimates. Results: Psychiatric diagnoses were highly prevalent, at 79.3% in NF1 and 76.6% in NSSD, with ADHD (NF1 = 72.4%, NSSD = 51.1%) and anxiety disorders (NF1 = 37.9% and NSSD = 43.6%) being the most common, rates substantially higher than those reported in general population estimates. Behavioral and sleep disorders were identified in approximately 25% of both groups. Notably, social anxiety disorder was identified in 14.9% of NSSD but not in NF1. Full-scale IQ did not significantly differ by diagnosis status. Specific anxiety disorders, elimination disorders, obsessive–compulsive disorder, and post-traumatic stress disorder were characterized, expanding the known psychiatric phenotype of RASopathies. Conclusions: Children with NF1 and NSSD demonstrate similarly high rates of ADHD, anxiety, and behavioral disorders compared to the general population; in addition, we report sleep disorders in NSSD and characterize psychiatric disorders not previously described in RASopathies. The shared psychiatric profiles may reflect the common effect of RAS-MAPK pathway dysregulation on psychiatric outcomes. These findings highlight the need for early, syndrome-informed mental health screening and intervention in the clinical care of individuals with RASopathies. Full article

Background and objectives: Duloxetine is widely used for the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), and various types of neuropathic pain. While its efficacy is well documented in clinical trials, less is known about how it is perceived and utilized in routine psychiatric practice. To address this knowledge gap, we conducted a cross-sectional observational study involving 80 psychiatrists from Spain to assess real-world clinical attitudes toward duloxetine. Methods: Participants completed a 20-item multiple-choice questionnaire that examined familiarity, perceived efficacy in multiple conditions (MDD, GAD, neuropathic pain, somatization, and quality of life), and perspectives on tolerability, safety, adherence, and overall satisfaction. Results: Survey results indicated that a large majority of psychiatrists frequently prescribe duloxetine, particularly for patients with MDD and comorbid chronic pain. Notably, 94% rated it as either “more effective” or “much more effective” for diabetic peripheral neuropathic pain. Psychiatrists reported a high perceived efficacy of duloxetine: 94% rated it as “more effective” or “much more effective” for diabetic peripheral neuropathy, and 93% gave similarly positive ratings for general neuropathic pain. For somatization, 70% found it “effective” or “very effective”, and 83% observed improvements in quality of life for many of their patients. Psychiatrists generally reported favorable perceptions of duloxetine’s tolerability profile: 97.5% rated it as the antidepressant associated with the least weight gain, and 82.5% perceived fewer sexual side effects compared to other options. Sedation and gastrointestinal side effects were generally considered mild or less severe. In terms of treatment adherence, 69% rated it as “better” or “much better” than other antidepressants, and 80% found its combination with other antidepressants to be “favorable” or “very favorable”. Overall satisfaction was high, with 99% of psychiatrists reporting being either “satisfied” or “very satisfied” with its use. The side effect profile was generally viewed as manageable, with low perceived rates of weight gain, sedation, and sexual dysfunction. Furthermore, 96% of respondents expressed a willingness to recommend duloxetine to their colleagues. Conclusions: Psychiatrists reported highly favorable attitudes toward duloxetine, viewing it as a flexible treatment option in routine care. However, these findings reflect clinicians’ subjective perceptions rather than objective clinical outcomes and should be interpreted accordingly. Full article

Background: Food addiction (FA) is an emerging construct that mirrors the behavioral and neurobiological characteristics of substance use disorders. Despite growing interest, its association with specific psychiatric disorders among bariatric patients remains understudied. Objective: Our aim was to examine the prevalence and strength of associations between FA and seven major psychiatric disorders in individuals who underwent bariatric surgery. Methods: In a sample of 100 post-bariatric patients referred for psychiatric evaluation, FA was assessed using the modified Yale Food Addiction Scale 2.0 (mYFAS 2.0), and psychiatric disorders were diagnosed using the Mini International Neuropsychiatric Interview (MINI). Logistic regression models were used to estimate adjusted odds ratios (aORs) for the association between FA and each psychiatric disorder, controlling for sex, age, body mass index (BMI), employment status, the number of children, clinical comorbidities, physical activity, family psychiatric history, and region of residence. Results: FA was present in 51% of the sample. Descriptive analyses revealed a significantly higher prevalence of major depressive disorder, panic disorder, generalized anxiety disorder, social anxiety disorder, agoraphobia, obsessive–compulsive disorder, and bulimia nervosa among individuals with FA. Multivariate models showed robust associations between FA and bulimia nervosa (aOR = 19.42, p < 0.05), generalized anxiety disorder (aOR = 2.88, p < 0.05), obsessive–compulsive disorder (aOR = 6.64, p < 0.05), agoraphobia (aOR = 3.14, p < 0.05), social anxiety disorder (aOR = 4.28, p < 0.05) and major depressive disorder (aOR = 2.79, p < 0.05). Conclusions: FA is strongly associated with a range of psychiatric comorbidities in post-bariatric patients, reinforcing the need for comprehensive mental health screening in this population. These findings underscore the potential role of FA as a clinical marker for stratified risk assessment, supporting more personalized approaches to mental health monitoring and intervention following bariatric surgery. Full article

Background: There is a certain degree of overlap between persistent postural-perceptual dizziness (PPPD) (ICD-11) and anxiety disorders (ANX) with regard to the phenomenological, pathological and neurobiological characteristics of both conditions. The implementation of an integrative psychotherapy programme may potentially result in the generation of synergistic effects across both patient groups. Objectives: This study assessed (1) whether psychological mechanisms similarly influence symptom severity in PPPD and ANX group, (2) the effectiveness of psychotherapy, and (3) potential neurofunctional biomarkers. Methods: Patients with PPPD (n = 14) and ANX (n = 20) underwent an integrative psychotherapy programme with balance training and mindfulness-based interventions. Emotional and neutral pictures were presented during MRI scans before and after therapy, with healthy controls (HC = 29) for comparison. Clinical and psychological questionnaires were administered, and brain activity was analysed in key regions. Results: The only diagnostic difference in the direct comparison between patients with PPPD and with ANX were the vertigo intensity values before and after therapy. PPPD with comorbid anxiety disorder had significantly more fear of physical symptoms than patients without comorbid anxiety disorder. PPPD showed no change regarding vertigo intensity (VSS), anxiety, or depression scores, but reported decreased impact of vertigo on social functioning (VHQ), and improved personal control after therapy (IPQ). By contrast, anxiety, dizziness, depression, alexithymia, and IPQ scores were significantly reduced after therapy in the ANX group. Neuroimaging revealed decreased activity in the hippocampus and superior temporal gyri (STG) in the PPPD group post-therapy as compared to the pre-therapy measurement, while the ANX group showed reduced activity in the insula, thalamus, hippocampus, and inferior frontal gyrus. Compared to the ANX and HC groups, patients with PPPD showed increased activity in the supramarginal gyrus and STG, both of which could serve as biomarkers for PPPD patients but need to be further validated. Conclusions: Anxiety and vertigo may reinforce each other in PPPD, as symptoms persisted post-therapy, whereas ANX patients improved significantly. Nevertheless, there is some evidence for a successful management of symptoms in the PPPD group. Findings are limited by small sample size and require further research. Full article

Depression, anxiety, and perceived stress are common comorbidities in patients with inflammatory bowel disease (IBD) and may negatively influence the disease course. Likewise, severe IBD may contribute to the development or worsening of psychiatric symptoms. Despite the established relevance of the gut–brain axis and frequent use of psychotropic medications in IBD patients, limited evidence exists regarding the effects of psychiatric treatments on gastrointestinal disease activity. Therefore, the aim of this systematic review is to evaluate the effectiveness of psychiatric therapies on gastrointestinal symptoms and disease activity in patients with IBD. The work was conducted in accordance with PRISMA guidelines. Searches were performed across PubMed, Web of Science, and Scopus up to July 2024. Eligible studies evaluated the effectiveness of psychiatric medications—including antidepressants, antipsychotics, anxiolytics, sedative-hypnotics, mood stabilizers, anticonvulsants, and others—on at least one gastrointestinal outcome in patients with IBD. Outcomes included changes in commonly used clinical and endoscopic scores for Crohn’s disease (CD) and ulcerative colitis (UC), number of bowel movements, stool consistency, presence of blood in stool, severity of abdominal pain, as well as in surrogate markers of disease activity following treatment. Out of 8513 initially identified articles, 22 studies involving 45,572 IBD patients met the inclusion criteria. Antidepressants, particularly bupropion, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and duloxetine, were associated with improvements in IBD activity scores, including Crohn’s Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD, Mayo score and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) for UC. Case reports highlighted potential benefits of pregabalin and lithium carbonate, respectively, showed by the reduction in clinical and endoscopic score of disease activity for pregabalin and improvement of UC symptoms for lithium carbonate, while topiramate showed limited efficacy. Clonidine and naltrexone determined the reductions in clinical and endoscopic score of disease activity, including CDAI and Crohn’s disease endoscopy index severity score (CDEIS) for CD and Disease Activity Index (DAI) for UC. Despite the limited data and study heterogeneity, antidepressants, naltrexone, and clonidine were associated with improvements in IBD activity. Larger, prospective studies are needed to confirm the therapeutic potential of psychiatric medications in modulating IBD activity and to guide integrated clinical management. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) and Parkinson’s disease (PD) are two highly prevalent chronic conditions that often coexist in older adults. Their interaction may influence clinical outcomes, particularly during external stressors such as the COVID-19 pandemic. This study aimed to assess the prevalence and temporal trends of PD among hospitalized patients with T2DM in Spain (2017–2023), evaluate sex-based differences in clinical characteristics and outcomes, examine the impact of the COVID-19 pandemic, and identify predictors of PD diagnosis and in-hospital mortality (IHM). Methods: We conducted a retrospective, nationwide study using the Spanish National Hospital Discharge Database (RAE-CMBD). Adults aged ≥40 years hospitalized with T2DM were included. PD cases were identified using ICD-10 codes. Joinpoint regression assessed temporal trends, and multivariable logistic regression identified factors associated with PD and IHM. Results: Among 5.1 million T2DM-related hospitalizations, 107,931 (2.41%) involved PD. PD prevalence increased over time, particularly among women. Men accounted for most PD cases and were younger than their female counterparts. Depression and anxiety were more frequent in women and associated with PD in both sexes. IHM peaked at 14.6% in 2020, coinciding with the COVID-19 outbreak. Predictors of IHM included older age, higher comorbidity burden, dementia, and COVID-19 diagnosis. Conclusions: The coexistence of PD and T2DM in hospitalized patients is associated with clinical complexity and increased mortality. Personalized, multidisciplinary care is essential to address sex-specific patterns, psychiatric comorbidities, and vulnerability to systemic stressors. Full article