Cannabinoids and Sleep: Exploring Biological Mechanisms and Therapeutic Potentials.

The endogenous cannabinoid system (ECS) plays a critical role in the regulation of various physiological functions, including sleep, mood, and neuroinflammation. Phytocannabinoids such as Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinomimimetics, and some N-acylethanolamides, particularly palmitoyethanolamide, have emerged as potential therapeutic agents for the management of sleep disorders. THC, the psychoactive component of cannabis, may initially promote sleep, but, in the long term, alters sleep architecture, while CBD shows promise in improving sleep quality without psychoactive effects. Clinical studies suggest that CBD modulates endocannabinoid signaling through several receptor sites, offering a multifaceted approach to sleep regulation. Similarly, palmitoylethanolamide (PEA), in addition to interacting with the endocannabinoid system, acts as an agonist on peroxisome proliferator-activated receptors (PPARs). The favorable safety profile of CBD and PEA and the potential for long-term use make them an attractive alternative to conventional pharmacotherapy. The integration of the latter two compounds into comprehensive treatment strategies, together with cognitive-behavioral therapy for insomnia (CBT-I), represents a holistic approach to address the multifactorial nature of sleep disorders. Further research is needed to establish the optimal dosage, safety, and efficacy in different patient populations, but the therapeutic potential of CBD and PEA offers hope for improved sleep quality and general well-being.

How effective are mood stabilizers in treating bipolar patients comorbid with cPTSD? Results from an observational study.

BACKGROUND: Multiple traumatic experiences, particularly in childhood, may predict and be a risk factor for the development of complex post-traumatic stress disorder (cPTSD). Unfortunately, individuals with bipolar disorder (BP) are more likely to have suffered traumatic events than the general population. Consequently, cPTSD could be comorbid with BD, and this may negatively affect psychopathological manifestations. To date, no one has explored whether such comorbidity also affects the response to treatment with mood stabilizers in BD patients. RESULTS: Here, a cross-sectional study was carried out by comparing the response to treatment, measured by the Alda scale, in a cohort of 344 patients diagnosed with BD type I and II, screened for the presence (or absence) of cPTSD using the International Trauma Questionnaire. The main result that emerged from the present study is the poorer response to mood stabilizers in BD patients with comorbid cPTSD compared with BD patients without cPTSD. CONCLUSIONS: The results collected suggest the need for an add-on therapy focused on trauma in BD patients. This could represent an area of future interest in clinical research, capable of leading to more precise and quicker diagnoses as well as suggesting better tailored and more effective treatments.

Unraveling the Complexity: Exploring the Intersection of Panic Disorder, Dissociation, and Complex Post-Traumatic Stress Disorder.

BACKGROUND: Patients with panic disorder (PD) may experience increased vulnerability to dissociative and anxious phenomena in the presence of repeated traumatic events, and these may be risk factors for the development of complex post-traumatic stress disorder (cPTSD). The present study aims to find out whether the presence of cPTSD exacerbates anxiety symptoms in patients suffering from panic disorder and whether this is specifically associated with the occurrence of dissociative symptoms. METHODS: One-hundred-and-seventy-three patients diagnosed with PD were recruited and divided into two groups based on the presence (or absence) of cPTSD using the International Trauma Questionnaire (ITQ) scale. Dissociative and anxious symptoms were assessed using the Cambridge Depersonalization Scale (CDS) and Hamilton Anxiety Scale (HAM-A), respectively. RESULTS: Significant differences in re-experienced PTSD (p < 0.001), PTSD avoidance (p < 0.001), PTSD hyperarousal (p < 0.001), and DSO dysregulation (p < 0.001) were found between the cPTSD-positive and cPTSD-negative groups. A statistically significant association between the presence of cPTSD and total scores on the HAM-A (p < 0.001) and CDS (p < 0.001) scales was found using regression analysis. CONCLUSIONS: This study highlights the potential link between dissociative symptoms and a more severe clinical course of anxiety-related conditions in patients with PD. Early intervention programs and prevention strategies are needed.

Exploring the Interplay between Complex Post-Traumatic Stress Disorder and Obsessive-Compulsive Disorder Severity: Implications for Clinical Practice.

Background and Objectives: Traumatic events adversely affect the clinical course of obsessive-compulsive disorder (OCD). Our study explores the correlation between prolonged interpersonal trauma and the severity of symptoms related to OCD and anxiety disorders. Materials and Methods: The study follows a cross-sectional and observational design, employing the International Trauma Questionnaire (ITQ) to examine areas linked to interpersonal trauma, the Hamilton Anxiety Rating Scale (HAM-A), and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) to assess anxious and obsessive-compulsive symptoms, respectively. Descriptive analysis, analysis of variance (ANOVA), and logistic regression analyses were conducted. Results: We recruited 107 OCD-diagnosed patients, categorizing them into subgroups based on the presence or absence of complex post-traumatic stress disorder (cPTSD). The ANOVA revealed statistically significant differences between the two groups in the onset age of OCD (p = 0.083), psychiatric familial history (p = 0.023), HAM-A, and Y-BOCS (p < 0.0001). Logistic regression indicated a statistically significant association between the presence of cPTSD and Y-BOCS scores (p < 0.0001). Conclusions: The coexistence of cPTSD in OCD exacerbates obsessive-compulsive symptoms and increases the burden of anxiety. Further advancements in this field are crucial for mitigating the impact of early trauma on the trajectory of OCD and associated anxious symptoms.

The Impact of Complex PTSD on Suicide Risk in Patients with Bipolar Disorder: A Cross-Sectional Study.

BACKGROUND: Patients with bipolar disorder (BD) are more likely than the general population to experience traumatic events, particularly during childhood, and these may predict and be a risk factor for the development of complex PTSD (cPTSD). The presence of multiple traumas plays a relevant role from a psychopathological point of view, but little is known about the effect this may have on suicide attempts in patients with BD. METHODS: A cross-sectional study was conducted comparing socio-demographic and clinical characteristics, recruiting 344 patients diagnosed with BD I and II, screened for the presence (or absence) of cPTSD using the International Trauma Questionnaire (ITQ). Suicide attempts were assessed directly during the clinical interview and from the patient's medical record. RESULTS: The results emerging from the study indicate that cPTSD can be considered a risk factor for suicide attempts in patients with BD. Furthermore, evidence is provided to support the idea that cPTSD is highly prevalent in patients with BD and is related to a higher psychopathological burden. CONCLUSIONS: The results recommend an urgent and comprehensive assessment of suicidal risk in patients with comorbidity of both bipolar disorder and cPTSD. There is a crucial demand for early intervention initiatives and proactive prevention strategies to address the intricate intersection of these mental health challenges.

Sleep Disturbances in Panic Disorder with Comorbid Complex PTSD: A Possible Relationship and Different Psychopathology?

BACKGROUND: Several studies have shown the possible link between trauma and sleep disturbances, particularly in anxiety disorders. This issue could be because sympathetic hyperarousal is central to both disorders, probably caused by a dysregulation of the noradrenergic system. This study aimed to establish if the comorbidity with complex post-traumatic stress disorder (cPTSD) is associated with sleep disturbances in panic disorder (PD) and if the presence of poor sleep quality is associated with a higher psychopathological burden. METHODS: Participants (N = 211) with PD completed the International Trauma Questionnaire concerning their most troubling experience, the Hamilton Anxiety Rating Scale (HAM-A), and the Pittsburgh Sleep Quality Index (PSQI) to assess anxiety symptoms and sleep disturbances, respectively. RESULTS: The sample was divided into two subgroups based on the presence of cPTSD. No significant differences emerged in the bivariate analyses for what concerns sociodemographic features. As for the scores of the psychopathological scales, the analysis highlighted statistically significant differences between the subgroups. Subjects with cPTSD reported significantly higher HAM-A total scores. As for the disturbances in self-organization (DSO) and PSQI scores, these were all significantly higher in the cPTSD subsample. At the logistic regression, the presence of cPTSD was inserted as the dependent variable, while the PSQI scores of the subscales evaluating subjective sleep quality, sleep duration, sleep efficacy, and the use of hypnotics were used as independent variables. The presence of cPTSD was significantly associated with the PSQI subscores for subjective sleep quality and use of hypnotics. CONCLUSIONS: Patients with PD exhibit more severe sleep disturbances and a higher anxiety burden when experiencing prolonged trauma. Therapeutic advances are needed in this field to target these symptomatologic domains.

Testing psychometric properties of Shared Decision Making Questionnaire - Physician Version (SDM-Q-Doc) in an Italian real-world psychiatric clinical sample.

OBJECTIVES: The Shared Decision Making Questionnaire-Physician Version (SDM-Q-Doc) is the main tool assessing SDM relationship between patient and physician using the clinician viewpoint. It is reliable in all medical fields, and the validation of its Italian version was still missing. Our aim was to validate the Italian version of the SDM-Q-Doc in a clinical sample of patients suffering from severe mental illness. METHODS: We approached 369 patients affected by major psychiatric disorders (including schizophrenia spectrum disorders, affective disorders and eating disorders) in a real-world outpatient clinical setting. We run the Confirmatory Factor Analysis (CFA) to test the SDM-Q-Doc structure. We calculated the correlations between the SDM-Q-Doc and the Observing Patient Involvement (OPTION) scale, used as comparing test, and McDonald ω coefficient to measure convergent validity and internal consistency respectively. RESULTS: We reached a response rate of 93.2% (344 final participants). The CFA showed a very good fit compared of the Italian version of SDM-Q-Doc (χ2/df=3.2, CFI=.99, TLI=.99, RMSEA=.08, SRMR=.04). We found several correlations between the SDM-Q-Doc and OPTION scale supporting a robust SDM-Q-Doc construct validity, while internal consistency of the scale was McDonald ω coefficient .92. Further, inter-item correlations ranged from .390 to .703, with a mean of .556. CONCLUSIONS: This study confirms the suitability of the Italian version of SDM-Q-Doc, with good reliability and soundness even when compared to other languages validated versions and to OPTION scale. SDM-Q-Doc represents an easy-to-use physician-centered measure to assess patients' involvement in medical decision-making, well performing in the Italian-speaking population.

Effectiveness of SGA-LAIs on Clinical, Cognitive, and Social Domains in Schizophrenia: Results from a Prospective Naturalistic Study.

We hypothesized that shifting from oral second-generation antipsychotics (SGA) to their long-acting injectable (LAI) counterpart would be beneficial for the psychopathological, cognitive, social, and general health domains in outpatients suffering from schizophrenia. We aimed to evaluate the prospective usefulness of SGA-LAI treatment by carrying out a head-to-head comparison of two different medications (i.e., aripiprazole monohydrate (Ari-LAI) and paliperidone palmitate 1 and 3 month (PP1M, PP3M)) in a real-world setting, assessing the effectiveness and tolerability of Ari-LAI and PP1M/PP3M over a 15 month follow-up. A total of 69 consecutive individuals affected by schizophrenia were screened for eligibility. Finally, 46 outpatients (29 treated with Ari-LAI, 13 with PP1M, and four with PP3M) were evaluated through clinical, functional, and neuropsychological assessment administrated at baseline and after 3-, 12-, and 15-month follow-up periods. Moreover, periodic general medical evaluations were carried out. We estimated an overall improvement over time on the explored outcomes, without differences with respect to the type of LAI investigated, and with a global 16.4% dropout rate. Our findings suggest that switching from oral SGA to SGA-LAIs represents a valid and effective treatment strategy, with significant improvements on psychopathological, cognitive, social, and clinical variables for patients suffering from schizophrenia, regardless of the type of molecule chosen.

The mediation role of impulsivity between childhood trauma and dissociative symptomatology in bipolar disorder.

In bipolar disorder (BD) patients, trauma has been associated with emotional dysregulation, potentially leading to an increase in impulsivity and dissociative symptomatology. We aimed to investigate the relationship between childhood trauma, impulsivity, and dissociative symptomatology in BD with a special focus on the role of impulsivity as a mediator between childhood trauma and dissociative symptomatology. METHODS: We administered the Childhood Trauma Questionnaire (CTQ), Barratt Impulsivity Scale (BIS-11), Dissociative Experience Scale (DES-II), and Alda scale. Spearman correlation analysis assessed the independent variables associated with CTQ and DES-II. We performed a mediation analysis using the bootstrapping technique to verify the hypothesis that impulsivity represented an intervening variable between childhood trauma and dissociation. RESULTS: CTQ and DES-II scores in 100 BD patients were both significantly associated with the number of lifetime affective episodes, a clinical course of mania-depression-euthymia, suicidal ideation, a history of antidepressant-induced manic switch, poor response to mood stabilizers, mixed features, psychotic symptoms, aggressive behavior, and BIS-11 (p<0.01). At the regression analysis, CTQ was associated with DES-II (p<0.001), while DES-II was associated with the CTQ (p<0.001) and BIS-11 (p< 0.001), as well as with aggression (p=0.002). The mediation analysis showed that impulsivity significantly mediated the effect of childhood trauma on dissociative symptomatology (z=25.71; 0.930-1.084). CONCLUSIONS: Impulsivity might play a key role in onset and prognosis of BD patients. Our findings may help in increasing the knowledge about the possible association between impulsivity, childhood traumatic experiences and dissociative symptomatology. BD patients with dissociative symptoms might benefit from a tailored treatment which could include a training based on emotional and behavioral regulation.

Sleep Disturbances in Generalized Anxiety Disorder: The Role of Calcium Homeostasis Imbalance.

Patients with a generalized anxiety disorder (GAD) often report preeminent sleep disturbances. Recently, calcium homeostasis gained interest because of its role in the regulation of sleep-wake rhythms and anxiety symptoms. This cross-sectional study aimed at investigating the association between calcium homeostasis imbalance, anxiety, and quality of sleep in patients with GAD. A total of 211 patients were assessed using the Hamilton Rating Scale for Anxiety (HAM-A), Pittsburgh Sleep Quality Index questionnaire (PSQI) and Insomnia Severity Index (ISI) scales. Calcium, vitamin D, and parathyroid hormone (PTH) levels were evaluated in blood samples. A correlation and linear regression analysis were run to evaluate the association of HAM-A, PSQI, and ISI scores with peripheral markers of calcium homeostasis imbalance. Significant correlations emerged between HAM-A, PSQI, ISI, PTH, and vitamin D. The regression models showed that patients with GAD displaying low levels of vitamin D and higher levels of PTH exhibit a poor subjective quality of sleep and higher levels of anxiety, underpinning higher psychopathological burden. A strong relationship between peripheral biomarkers of calcium homeostasis imbalance, insomnia, poor sleep quality, and anxiety symptomatology was underlined. Future studies could shed light on the causal and temporal relationship between calcium metabolism imbalance, anxiety, and sleep.

Changes at glutamate tripartite synapses in the prefrontal cortex of a new animal model of resilience/vulnerability to acute stress.

Stress represents a main risk factor for psychiatric disorders. Whereas it is known that even a single trauma may induce psychiatric disorders in humans, the mechanisms of vulnerability to acute stressors have been little investigated. In this study, we generated a new animal model of resilience/vulnerability to acute footshock (FS) stress in rats and analyzed early functional, molecular, and morphological determinants of stress vulnerability at tripartite glutamate synapses in the prefrontal cortex (PFC). We found that adult male rats subjected to FS can be deemed resilient (FS-R) or vulnerable (FS-V), based on their anhedonic phenotype 24 h after stress exposure, and that these two populations are phenotypically distinguishable up to two weeks afterwards. Basal presynaptic glutamate release was increased in the PFC of FS-V rats, while depolarization-evoked glutamate release and synapsin I phosphorylation at Ser9 were increased in both FS-R and FS-V. In FS-R and FS-V rats the synaptic expression of GluN2A and apical dendritic length of prelimbic PFC layers II-III pyramidal neurons were decreased, while BDNF expression was selectively reduced in FS-V. Depolarization-evoked (carrier-mediated) glutamate release from astroglia perisynaptic processes (gliosomes) was selectively increased in the PFC of FS-V rats, while GLT1 and xCt levels were higher and GS expression reduced in purified PFC gliosomes from FS-R. Overall, we show for the first time that the application of the sucrose intake test to rats exposed to acute FS led to the generation of a novel animal model of resilience/vulnerability to acute stress, which we used to identify early determinants of maladaptive response related to behavioral vulnerability to stress.

Chronotype is associated with affective temperaments, clinical severity and worse treatment outcomes in bipolar disorders: results from a two-center, cross-sectional study.

OBJECTIVE: The present study was aimed at investigating the clinical correlates of evening chronotype in a population of subjects suffering from bipolar disorders (BD). METHODS: We assessed chronotype using the Morningness-Eveningness Questionnaire. We administered the brief Temperament Evaluation of Memphis, Pisa, and San Diego, the Barratt Impulsiveness Scale, and the Alda Scale to evaluate affective temperaments, impulsiveness, and response to mood stabilisers. We performed bivariate analyses and ran a logistic regression model to analyse clinical variables associated with evening chronotype. RESULTS: In our sample (n = 178), subjects with an evening chronotype (n = 56, 31.5%) more often suffered from BD type I and reported higher prevalence of seasonality, antidepressant-induced mood switches, psychotic, aggressive, mixed, and anxiety features, and substance use disorders. The number of lifetime suicide attempts and mood episodes was higher in this subgroup. Depressive, cyclothymic, irritable, and anxious temperament scores were higher among evening-chronotype subjects, who also displayed greater levels of impulsiveness and worse treatment response. At the logistic regression, evening chronotype was associated with depressive and irritable temperaments. CONCLUSIONS: Subjects with evening chronotype display higher clinical severity and worse BD course. Clinicians should evaluate the presence of evening chronotype in BD subjects, especially in those with irritable or depressive temperament.Key pointsEvening chronotype is a frequent clinical feature in subjects suffering from bipolar disorders (BD);Affective temperaments, particularly depressive and irritable, are associated with evening chronotype in BD;Evening chronotype underpins higher severity of the clinical picture in BD, as well as a worse response to mood stabiliser treatment;Circadian preferences should be systematically assessed in subjects suffering from BD, with particular attention to evening preference.

Astrocytes and the Psychiatric Sequelae of COVID-19: What We Learned from the Pandemic.

COVID-19, initially regarded as specific lung disease, exhibits an extremely broad spectrum of symptoms. Extrapulmonary manifestations of the disease also include important neuropsychiatric symptoms with atypical characteristics. Are these disturbances linked to stress accompanying every systemic infection, or are due to specific neurobiological changes associated with COVID-19? Evidence accumulated so far indicates that the pathophysiology of COVID-19 is characterized by systemic inflammation, hypoxia resulting from respiratory failure, and neuroinflammation (either due to viral neurotropism or in response to cytokine storm), all affecting the brain. It is reasonable to hypothesize that all these events may initiate or worsen psychiatric and cognitive disorders. Damage to the brain triggers a specific type of reactive response mounted by neuroglia cells, in particular by astrocytes which are the homeostatic cell par excellence. Astrocytes undergo complex morphological, biochemical, and functional remodeling aimed at mobilizing the regenerative potential of the central nervous system. If the brain is not directly damaged, resolution of systemic pathology usually results in restoration of the physiological homeostatic status of neuroglial cells. The completeness and dynamics of this process in pathological conditions remain largely unknown. In a subset of patients, glial cells could fail to recover after infection thus promoting the onset and progression of COVID-19-related neuropsychiatric diseases. There is evidence from post-mortem examinations of the brains of COVID-19 patients of alterations in both astrocytes and microglia. In conclusion, COVID-19 activates a huge reactive response of glial cells, that physiologically act as the main controller of the inflammatory, protective and regenerative events. However, in some patients the restoration of glial physiological state does not occur, thus compromising glial function and ultimately resulting in homeostatic failure underlying a set of specific neuropsychiatric symptoms related to COVID-19.

The Mediation Effect of Peripheral Biomarkers of Calcium Metabolism and Chronotypes in Bipolar Disorder Psychopathology.

Calcium (Ca++) metabolism may be impaired in several psychiatric diseases. We hypothesize that calcium imbalance might also correlate with a specific chronotype and could be recognized as a marker of illness severity in bipolar disorder (BD). We aimed to (1) identify the association between calcium imbalance and a specific chronotype in a cohort of BD patients, and (2) test the mediation role of high parathyroid hormone (PTH) levels towards a specific chronotype and illness severity in BD patients. Patients' socio-demographic and clinical characteristics were collected with an ad-hoc schedule. We administered the Hamilton Depression Rating Scale (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Young Mania Rating Scale (YMRS), and the Morningness Eveningness Questionnaire (MEQ). 100 patients affected by BD were recruited. The Kruskal-Wallis test showed a significant difference between the three MEQ groups in PTH levels (p < 0.001) and vitamin D levels (p = 0.048) but not in Ca++ levels (p = 0.426). Dwass-Steel-Critchlow-Fligner Pairwise analyses performed concerning three MEQ groups revealed significantly higher scores on PTH levels in MEQ-E subjects compared to MEQ-M and MEQ-I (in both cases, p < 0.001). No differences emerged between calcium levels among the three chronotypes. The mediation analysis has shown that elevated PTH levels are directly influenced by more severe HAM-A, HAM-D, and YMRS scores. MEQ-E could be a marker related to BD and predispose to various factors influencing mood symptoms. The combination of vitamin D therapy in MEQ-E may help to improve prognosis in this subtype of patients affected by BD.

Psychometric Properties of the 9-Item Shared Decision-Making Questionnaire (SDM-Q-9): Validation of the Italian Version in a Large Psychiatric Clinical Sample.

Objective: The nine-item Shared Decision-Making Questionnaire (SDM-Q-9) is one of the most frequently used tools for assessing patients' involvement in medical decision-making, but so far, it not been validated in Italian. We aimed to validate the Italian version of the SDM-Q-9 in a clinical sample of patients suffering from major psychiatric disorders. Method: We involved 307 consecutive patients affected by major psychiatric disorders (including schizophrenia spectrum disorders, affective disorders and eating disorders) in a real-world outpatient clinical setting. Confirmatory Factor Analysis (CFA) was conducted to examine the latent structure of the SDM-Q-9. Cronbach's alpha and correlations between the SDM-Q-9 and the Observing Patient Involvement (OPTION) scale were calculated to measure internal consistency and convergent validity respectively. Results: The final sample was made up of 289 participants (response rate 94.1%) who completed the assessment. CFA confirmed the unidimensional structure as in the original version (χ2/df= 1.69; CFI= 0.98; TLI= 0.97; RMSEA= 0.05; SRMR= 0.08). Internal consistency of the total scale was Cronbach's α = .86. Regarding construct validity, we found several correlations between the SDM-Q-9 and OPTION scale. Conclusions: Our findings suggest that the Italian version of SDM-Q-9 performs well if compared to other languages validated versions, so it is a useful patient-centred measure to assess the involvement in medical decision-making (SDM) of patients from clinical samples from the Italian-speaking population.

Palmitoylethanolamide and White Matter Lesions: Evidence for Therapeutic Implications.

Palmitoylethanolamide (PEA), the naturally occurring amide of ethanolamine and palmitic acid, is an endogenous lipid compound endowed with a plethora of pharmacological functions, including analgesic, neuroprotective, immune-modulating, and anti-inflammatory effects. Although the properties of PEA were first characterized nearly 65 years ago, the identity of the receptor mediating these actions has long remained elusive, causing a period of research stasis. In the last two decades, a renewal of interest in PEA occurred, and a series of interesting studies have demonstrated the pharmacological properties of PEA and clarified its mechanisms of action. Recent findings showed the ability of formulations containing PEA in promoting oligodendrocyte differentiation, which represents the first step for the proper formation of myelin. This evidence opens new and promising research opportunities. White matter defects have been detected in a vast and heterogeneous group of diseases, including age-related neurodegenerative disorders. Here, we summarize the history and pharmacology of PEA and discuss its therapeutic potential in restoring white matter defects.

Internalized-stigma and dissociative experiences in bipolar disorder.

Introduction: Dissociative symptoms have been recently related to bipolar disorder (BD) symptomatology. Moreover, the disease burden carries on a share of perceived self-stigma that amplifies the BD impairment. Internalized stigma and dissociative symptoms often seem overlapping, leading toward common outcomes, with reduced treatment seeking and poor adherence. We hypothesize a potential relationship between dissociation and self-stigma in patients suffering from BD. Materials and methods: In this cross-sectional study we enrolled a total of 120 adult clinically stable BD outpatients. All participants completed the Internalized Stigma of Mental Illness (ISMI), Dissociative Experiences Scale-II (DES-II), and Manchester Short Assessment of Quality of Life (MANSA). Results: Average age and age at BD (BD-I n = 66, 55%; BD-II n = 54, 45%) onset were 46.14 (±4.23), and 27.45 (±10.35) years, with mean disease duration of 18.56 (±13.08) years. Most participants were female (n = 71; 59.2%) and 40 (33%) of them experienced lifetime abuse, with an average of 1.05 (±0.78) suicide attempts. DES scores (mean 31.8, ±21.6) correlated with ISMI total-score, with significant association with spikes in Alienation (13.1, SD±3.1) (p < 0.001) and Stereotype (13.8, SD±3.9) (p < 0.001). Linear regression analysis has shown a significant association between DES total score and alienation (p < 0.001), stereotype (p < 0.001) and MANSA total-score (p < 0.001). Discussion: For the first time, our data suggests that self-stigma is associated to dissociative symptoms, reducing overall quality of life in BD. The early identification of at-risk patients with previous lifetime abuse and high perceived stigma could lead the way for an ever more precise tailoring of treatment management.

N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism.

Similar to canine inflammatory enteropathy, inflammatory bowel disease (IBD) is a chronic idiopathic condition characterized by remission periods and recurrent flares in which diarrhea, visceral pain, rectal bleeding/bloody stools, and weight loss are the main clinical symptoms. Intestinal barrier function alterations often persist in the remission phase of the disease without ongoing inflammatory processes. However, current therapies include mainly anti-inflammatory compounds that fail to promote functional symptoms-free disease remission, urging new drug discoveries to handle patients during this step of the disease. ALIAmides (ALIA, autacoid local injury antagonism) are bioactive fatty acid amides that recently gained attention because of their involvement in the control of inflammatory response, prompting the use of these molecules as plausible therapeutic strategies in the treatment of several chronic inflammatory conditions. N-palmitoyl-D-glucosamine (PGA), an under-researched ALIAmide, resulted in being safe and effective in preclinical models of inflammation and pain, suggesting its potential engagement in the treatment of IBD. In our study, we demonstrated that micronized PGA significantly and dose-dependently reduces colitis severity, improves intestinal mucosa integrity by increasing the tight junction proteins expression, and downregulates the TLR-4/NLRP3/iNOS pathway via PPAR-α receptors signaling in DNBS-treated mice. The possibility of clinically exploiting micronized PGA as support for the treatment and prevention of inflammation-related changes in IBD patients would represent an innovative, effective, and safe strategy.

Sex Differences in Bipolar Disorders: Impact on Psychopathological Features and Treatment Response.

Introduction: Sex differences were demonstrated in bipolar disorders (BD) concerning epidemiological, clinical, and psychopathological characteristics, but consensus is lacking. Moreover, data concerning the influence of sex on treatment response in BD is contrasting. The present cross-sectional study aimed to analyze sex differences in a population of BD subjects, with specific focus on psychopathological features and treatment response. Materials and Methods: Subjects diagnosed with BD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th version (DSM-5) were recruited. Socio-demographic and clinical characteristics were collected. The Hamilton Rating Scale for Depression, the Mania Rating Scale (MRS), the brief version of the Temperament Evaluation of Memphis, Pisa and San Diego-Münster version (briefTEMPS-M), and the Barratt Impulsiveness Scale-11 items (BIS-11) were used for psychopathological assessment. Treatment response was appraised with the Alda Scale. We performed bivariate analyses to compare socio-demographic, clinical, and psychopathological characteristics between men and women (p < 0.05). A logistic regression was run to analyze features that were significantly associated with female sex. Results: Among the recruited 219 BD subjects, 119 (54.3%) were females. Women had a lower scholarity (p = 0.015) and were less frequently employed (p = 0.001). As for psychopathological features, a higher MRS total score (p < 0.001) was detected among women, as well as higher BIS-11 total score (p = 0.040), and briefTEMPS-M score for anxious temperament (p = 0.006). Men showed higher prevalence of DSM-5 mixed features (p = 0.025), particularly during a depressive episode (p = 0.014). Women reported longer duration of untreated illness (DUI) (p < 0.001). There were no sex differences in the Alda Scale total score when considering the whole sample, but this was significantly higher among men (p = 0.030) when evaluating subjects treated with anticonvulsants. At the logistic regression, female sex was positively associated with longer DUI (p < 0.001; OR 1.106, 95% CI 1.050-1.165) and higher MRS total score (p < 0.001; OR 1.085, 95% CI 1.044-1.128) and negatively associated with employment (p = 0.003; OR 0.359, 95% CI 0.185-0.698) and DSM-5 mixed features (p = 0.006; OR 0.391, 95% CI 0.200-0.762). Conclusions: The clinical presentation of BD may differ depending on sex. The severity of BD should not be neglected among women, who may also display worse treatment response to anticonvulsants.

COVID-19 and Youth Psychopathological Distress in Umbria, Central Italy: A 2-Year Observational Study in a Real-World Setting.

Introduction: Adolescents and young adults represent a vulnerable population in the context of the Coronavirus disease 2019 (COVID-19) pandemic. The present retrospective study aims to investigate the pandemic's psychological impact on adolescents and young adults by analyzing data from an outpatient mental health service dedicated to youths in Umbria, central Italy. Materials and Methods: The clinical charts of subjects aged 14-24 who first accessed the service in the timeframe between March 1st, 2019, and February 28th, 2021, were reviewed. Subjects were divided into two subgroups according to the period of time when they accessed the service (pre-COVID-19 vs. during- COVID-19 outbreak). Bivariate analyses were performed using the Chi-square test and the Welch's t-test. A secondary analysis was performed considering only subjects suffering from psychiatric disorders. Furthermore, data concerning individuals who were already followed by the service before the pandemic were analyzed by the McNemar's test and the t-paired test to assess changes in treatment features. Results: The number of new accesses during the pandemic period remained stable. After the emergency onset, youths accessing the service showed a higher prevalence of anxiety disorders (p = 0.022). During the COVID-19 period, services were more frequently delivered by using a digital mental health approach (p = 0.001). Psychopharmacological treatment was more frequently prescribed among subjects that were referred to the service after the pandemic onset (p = 0.033). As for substance use, a highly significant reduction in opioid use was observed (p = 0.003). Family therapy was delivered less frequently in the during-COVID-19 subgroup, especially in the subpopulation of subjects suffering from psychiatric disorders (p = 0.013). When considering subjects referred to the service in the pre-COVID-19 period, the number of interventions provided to this population increased after the pandemic outbreak (p = 0.038). Conclusion: In the context of the COVID-19-related public health crisis, youths represent an at-risk population for which pathways to care should be reinforced, and targeted interventions, including psychosocial treatments, should be implemented.