BackgroundBipolar disorder (BD) is a chronic mental illness displaying recurrent episodes of impaired mood, in alternance with euthymic or subsyndromal periods. The comorbidity between BD and post-traumatic stress disorder (PTSD) is attracting attention due to its frequency, diagnostic difficulties, and worsening prognosis. Consequently, identifying molecular substrates of post-traumatic vs. depressive symptoms in BD would provide much benefit for patients’ rescue. This study thus focused on tryptophan (TRP) metabolism, at the crossroad between neurotransmission, immunity and inflammation, under distinct BD mental conditions.MethodsWe compared plasma TRP, serotonin (5-HT), kynurenine (KYN) and quinolinic acid (QUIN) among 20 euthymic-BD patients with PTSD (PTSD group) or 20 with depressive episode (DEP group) and 24 controls (CTL group). Metabolic ratios were calculated to monitor TRP-path fluxes. All participants underwent clinical examinations by psychometric instruments as the: Structured Clinical Interview for DSM-5 disorders (SCID-5), Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale (YMRS), Impact of Event Scale-Revised (IES-R), Mood Spectrum-Self-Report lifetime version (MOODS-SR), Trauma and Loss Spectrum-Self Report lifetime version (TALS-SR), Work and Social Adjustment Scale (WSAS). Blood withdraws were also achieved, followed by plasma measurements through ELISA.ResultsBoth DEP and PTSD-groups revealed markedly lower 5-HT and 5-HT/TRP values than controls, with additionally decreased 5-HT in DEP- vs. PTSD-subjects. DEP-patients also showed reduced TRP and increased QUIN, KYN and QUIN ratios vs controls, while PTSD-subjects displaying only increased QUIN/KYN values. Additionally, several correlations between biochemical and clinical parameters were reported. Noteworthy, 5-HT and 5-HT/TRP were negatively correlated with all psychometric measures, while all biochemical parameters studied, except KYN, were correlated with poor socio-personal functioning; otherwise, KYN-shunt parameters better distinguished the severity of DEP symptoms than the PTSD ones.ConclusionsSubstantially, BD-patients with low 5-HT and severe burden could be distinguished based on KYN profiles/trajectories when affected by depression or PTSD, entailing different neuroinflammatory/neuroendocrine patterns in mood vs. post-traumatic stress dimensions. This will encourage deeper assessment of BD metabolic/inflammatory biomarkers, allowing for refined patients’ stratifications and targeted therapeutic interventions.

IntroductionA growing body of literature is focusing on third-generation antipsychotics and their unique characteristics, but few studies have examined gender as a crucial factor in response profiles. The present study aims to address this gap by analyzing the outcomes of 12-month naturalistic treatment with cariprazine to elucidate changes in specific psychopathological domains between men and women.MethodsThe present 12-month longitudinal naturalistic study involved a sample of individuals diagnosed with schizophrenia according to the DSM-5-TR treated with cariprazine at the outpatients’ psychiatric services of a major university and community hospitals in Italy. The assessments conducted included sociodemographic data, the Structured Clinical Interview for the DSM-5 (SCID-5), and the Positive and Negative Symptom Scale (PANSS) Total and Subscale scores, as well as the PANSS-derived Marder factors. The PANSS was administered at three time points: before starting the treatment with cariprazine (T0), after 6 months (T1), and after 12 months (T2).ResultsFifteen male and 17 female subjects were assessed at the three time points. The mean dose of cariprazine was 4.2 ± 1.3 mg for men and 4.0 ± 1.5 mg for women. Both genders exhibited improvements in all PANSS subscale symptoms after 6 and 12 months of cariprazine treatment compared to the baseline, with the only exception of the Uncontrolled hostility/excitement Marder factor among men. Progressive improvements through time points in symptom subsca\les were found in both sexes, reaching numerical differences in every PANSS subscale in both sexes at T2. Gender specifc response profiles emerged after 6 and 12 months of treatment in the PANSS subscales and items in men and women.DiscussionCariprazine exhibited significant efficacy in both sexes, with no significant differences between men and women despite a gender specific response profile emerged. Additional studies are needed to further investigate the efficacy profile and long-term outcome of cariprazine treatment by gender.

OBJECTIVE:A mutual influence between mood disorders and obesity has been reported. Maladapting eating behaviors associated with mood spectrum swings may play a pivotal role in the development and maintenance of obesity. Considering that, the aim of the present study is to investigate the relationship between problematic eating behaviors, namely emotional eating, grazing and night eating, with impulsivity and lifetime mood spectrum (mood, energy, cognition, rhythmicity and vegetative functions) in severe obese patients seeking bariatric surgery. METHODS:304 obese outpatients were recruited at the Psychiatric Unit of the University Hospital of Pisa. Participants completed psychometric tools including the Emotional Eating Scale (EES), the Italian-Night Eating Questionnaire (I-NEQ), the Grazing Questionnaire (GRAZ), the Barratt Impulsiveness Scale (BIS-11), and the Mood Spectrum Self-Report - lifetime version (MOODS-SR). Descriptive analyses and linear correlation were performed. RESULTS:The sample was predominantly female (71.4%), with a mean age of 47.5 ± 10.9 years and a mean BMI of 43.3 ± 6.3 kg/m2. Impulsivity was positively correlated with depressive and manic mood, energy, and cognitive MOODS-SR domains. Emotional eating, night eating, and grazing were significantly associated with the MOODS-SR total score (r=0.422, p=0.000; r=0.321, p=0.001; r=0.321, p=0.000, respectively) and with specific depressive and manic subdomains of the MOODS-SR. CONCLUSION:Loss-of-control eating behaviors were positively associated with lifetime depressive and manic mood spectrum features in bariatric patients, highlighting the importance of assessing these dimensions to promote a tailored and integrated treatment.

INTRODUCTION:Real-world evidence on desvenlafaxine effectiveness and tolerability in Major Depressive Disorder (MDD) remains limited, particularly in clinically heterogeneous populations. This multicentre observational study evaluated the real-world effectiveness and tolerability of desvenlafaxine, focusing on depressive and anxiety symptoms, response, remission, and side-effects burden. METHODS:This multicentre prospective observational study included 197 outpatients with DSM-5-TR Major Depressive Episode initiating desvenlafaxine. Assessments were conducted at baseline (T0), one month (T1), and three months (T2). Depressive symptoms (MADRS) were the primary outcome; anxiety (HAM-A), manic symptoms (YMRS), and tolerability (ASEC) were secondary outcomes. Response was defined as ≥50% MADRS reduction and remission as MADRS <10. RESULTS:Participants (mean age 46.1 ± 14.6 years; 55.3% female) showed clinically relevant baseline severity (MADRS 30.8 ± 7.3). MADRS scores decreased significantly over time in both unadjusted and adjusted models (both p < 0.005), with greater reductions at T2. A significant time × dose association was observed at T1 (p = 0.013), although no dose-related difference persisted at T2; prior hospitalisation was associated with attenuated improvement (p < 0.005). Anxiety symptoms improved significantly across follow-up (p < 0.005). Response and remission rates increased markedly from T1 to T2 (response: 12.4% to 66.7%; remission: 3.9% to 32.6%; both p < 0.005). Overall side-effect burden decreased significantly (p < 0.005), with reduced prevalence of most adverse events. Mean YMRS scores remained low throughout follow-up, with no clinically meaningful increase from baseline. CONCLUSIONS:In this multicentre real-world cohort, desvenlafaxine was associated with substantial improvements in depressive and anxiety symptoms, increasing response and remission rates, favourable tolerability. These findings support desvenlafaxine as an effective and well-tolerated treatment option in routine clinical practice.

Neuroendocrine and circadian dysfunctions are thought to underlie bipolar disorder (BD) and could be implemented as markers of complex symptom conditions, including the presence of Post-Traumatic Stress Disorder (PTSD) comorbidity. The primary objective of this study was to investigate neuroendocrine profiles in different BD phenotypes through the measure of nocturnal urinary levels of Cortisol (stress-response factor) and 6-sulfatoxymelatonin (aMT6s; light/dark signal) in euthymic BD patients diagnosed with PTSD (PTSD group) or with major depressive episodes without trauma symptoms (DEP group). Both groups were compared against healthy controls (CTL). Nighttime urinary levels of aMT6s and Cortisol were analyzed by competitive ELISA, with ensuing values normalized for specific gravity. The Cortisol-to-aMT6s ratio (Cort/aMT6s) was calculated as an exploratory proxy for the homeostatic balance between HPA-mediated catabolic/coping activities and Melatonin-related reparative functions. Clinical severity and psychosocial activities were assessed by using mood HAM-D, YMRS, trauma IES-R and functioning WSAS scales. Results revealed distinct biological patterns: PTSD subjects showed increased nocturnal Cortisol compared to DEP and CTL groups, whereas DEP patients exhibited lower aMT6s levels and an elevated Cort/aMT6s ratio. Cortisol and aMT6s correlated positively in PTSD, while the ratio correlated positively with Cortisol solely in controls. Clinically, Cortisol correlated positively with IES-R and functional impairment (WSAS), whereas aMT6s correlated negatively with HAM-D and YMRS scores. Present findings suggest a possible neuroendocrine divergence in BD patients with depression versus PTSD: nocturnal Melatonin deficiency may be associated with depression, while HPA-axis hyperactivity and altered crosstalk between the two systems may characterize PTSD comorbidity, with the Cort/aMT6s ratio as a potential index of impaired daily functioning. These results could be promising for the use of biomarkers linked to allostatic and circadian responses within the BD spectrum.

Obesity is a growing health concern in Western countries and the link between obesity and mental disorders has been extensively studied, although less attention has been paid to post-traumatic stress spectrum symptoms (PTSS). This observational study aimed at exploring the correlations between lifetime trauma exposure and its related PTSS and maladaptive eating behaviours in obese patients who are candidates for bariatric surgery. A total of 189 obese candidates for bariatric surgery were recruited at the Azienda Ospedaliero-Universitaria Pisana (AOUP) and assessed by the Trauma and Loss Spectrum-Self-Report (TALS-SR Lifetime Version), Emotional Eating Scale (EES), Night Eating Questionnaire-Italian Version (I-NEQ), Grazing Questionnaire (GQ), and Eating Disorder Examination (EDE-Q), Eating Disorder Inventory (EDI). Based on the TALS-SR (Lifetime Version) scores, patients were dichotomised as either with low PTSS scores or high PTSS scores. Results showed high PTSS scores in more than a third of the sample (36.5%), with these individuals showing statistically significant higher total and EES domain scores, total and controllability GQ domain scores, I-NEQ mood/sleep domain scores, and EDE-Q shape concern domain score. A logistic regression showed an association between higher burden of emotional eating and greater probability of lifetime PTSS. PTSS appear to be frequent among bariatric surgery candidates and are related with maladaptive eating behaviours, suggesting accurate evaluation to optimise surgical outcomes.

Major depressive disorder is a leading cause of disability worldwide, with significant challenges in treatment response, adherence and functional recovery. Despite the availability of numerous antidepressants, a substantial proportion of patients fail to achieve remission with initial therapy, underscoring the need for effective first-line treatment options. Desvenlafaxine, a serotonin-noradrenaline reuptake inhibitor, has demonstrated efficacy and safety in major depressive disorder, while its pharmacokinetic properties result in minimal drug–drug interactions. This narrative review evaluates clinical evidence supporting the use of desvenlafaxine as a first-line treatment and examines patient subgroups that may benefit most from this antidepressant. A comprehensive literature review was conducted to evaluate the evidence on desvenlafaxine in the treatment of major depressive disorder. This was supplemented by clinical insights discussed during a virtual advisory board meeting held on 16 December, 2024, attended by the authors—psychiatrists from Italy, Germany, Spain, Ireland and Portugal—together with representatives from Neuraxpharm, who market desvenlafaxine. The available evidence suggests that desvenlafaxine offers early symptom relief, sustained efficacy across diverse major depressive disorder symptom clusters, and benefits for patients with anhedonia, fatigue, cognitive dysfunction and functional impairment. Its tolerability and safety profile, including a lower risk of weight gain and drug–drug interactions, contributes to its ease of use and improved adherence. Based on the authors’ clinical consensus, desvenlafaxine may be particularly suitable for working-age adults, perimenopausal and menopausal women, those with general medical comorbidities or polypharmacy concerns, and individuals requiring an antidepressant with a broad mechanism of action. In addition, its predictable pharmacokinetics make it a practical choice in primary care settings. While most current guidelines typically recommend selective serotonin reuptake inhibitors as first-line treatment, the favourable tolerability profile and efficacy of desvenlafaxine across diverse symptom clusters may support its consideration as a first-line option in select patient populations. Depression is a common mental health condition that can seriously impact on a person’s daily life, work and relationships. Many people with depression struggle to find an effective treatment, and even when they do, side effects such as weight gain or sexual dysfunction can make it difficult to continue taking medication. Desvenlafaxine is a type of antidepressant known as a serotonin-noradrenaline reuptake inhibitor. It works by targeting two important chemical pathways in the brain—serotonin and noradrenaline—which help improve depressive symptoms. This article reviews the scientific evidence on how well desvenlafaxine works, how safe it is, and which patients may benefit most from it as a first-choice treatment for depression. This article is based on a review of the existing published literature and clinical insights from a meeting of psychiatry experts from different countries. The findings suggest that desvenlafaxine can provide relief from symptoms of depression early in treatment, is effective for patients with low energy, difficulty concentrating or lack of motivation, and is less likely than some other antidepressants to cause weight gain. Based on the available evidence and the experts’ experience, desvenlafaxine may be particularly useful for patients who take multiple medications as it has a lower risk of interactions with other drugs. While not suitable for everyone, desvenlafaxine may be a valuable option for many people with depression, particularly those who need quick symptom relief, actively employed adults, perimenopausal women, individuals with comorbid physical health conditions, and those who struggle with fatigue and cognitive problems.

BACKGROUND:Mentalising skills may be conceptualised as composed by both personal and interpersonal competencies, in turn shaped by early adverse experiences and coping strategies. Although cross-sectional observations described a role for mentalising skills in burnout development, large-scale longitudinal studies on the topic remain limited, especially in relation to psychiatry training. AIMS:The primary aim was to investigate protective and risk factors for higher burnout scores across time. Secondary aims included testing whether psychiatry exhibited different burnout scores across time in comparison to other medical residents. METHOD:A cohort of 1803 medical residents (1131 psychiatry residents) was assessed for mentalising skills, conceptualised as composed of emotional regulation (Difficulties in Emotion Regulation Scale), interpersonal competencies (Interpersonal Competence Questionnaire), coping strategies (Coping Orientation to Problems Experienced) and burnout dimensions (Maslach Burnout Inventory). One-year follow-up was available for 520 psychiatry residents (73.03% response rate) and 234 other medical residents (35.94% response rate). Longitudinal mixed models and bivariate latent change models were employed. RESULTS:Across all residents, greater levels of burnout were associated with higher scores in insecure attachment, emotional dysregulation and maladaptive coping, as well as lower scores in interpersonal skills. Attending at least one supervision per month was associated with lower burnout scores across time. According to a bivariate latent change model, emotional regulation improvements through years were associated with lower burnout scores across time. In psychiatry residents, lower burnout scores across time were observed as compared to other medical residents. Psychiatry residents benefited from a higher protective effect of interpersonal competencies (group by moderator by time interaction) and coping strategies against burnout. CONCLUSIONS:Mentalising skills may mitigate burnout development. Training in psychiatry emerged as a potential mitigating factor against burnout increases. Structured supervisions may foster professional development and emotional resilience.

Beyond specific training in Digital Mental Health (DMH)/Digital Psychiatry (DP), mental health professionals (MHp) should own basic digital abilities and competences and a general openness to integrating technology into both clinical practice and daily life. These digital drivers have not been adequately investigated among MHp in Italy. As part of the DIGIT-PSY project, a multicenter observational study was conducted using the EUSurvey® platform. From May to September 2023, a cohort of multiprofessional MHp from 27 Italian university centers was surveyed to assess digital literacy (DHL), readiness (TR) and acceptability (ATiPP). The main aim was identifying whether these digitally-derived variables could influence the level of digitalization proneness in MH care. Overall, 60

Background: Bariatric surgery is the most effective long-term treatment for severe obesity; however, a subset of patients fails to achieve optimal weight loss. This study investigated the role of psychiatric disorders and transdiagnostic psychopathological traits in predicting weight loss outcomes two years after surgery. Methods: This prospective naturalistic study included 125 consecutive bariatric surgery candidates undergoing routine preoperative psychiatric assessment. Psychiatric comorbidities, emotional dysregulation and ADHD-related dimensions were assessed using structured clinical interviews and self-report questionnaires. Weight outcomes were evaluated at 24 months after bariatric surgery, with post-surgical inadequate weight loss defined as percentage of excess weight loss (%EWL) < 50%. Results: Of the 125 patients initially assessed, 89 underwent bariatric surgery and 48 completed the follow-up. At 24 months, 10 patients (20.8%) showed inadequate weight loss. Poorer weight outcomes were associated with older age, sleeve gastrectomy, and lifetime mood disorders, whereas no significant associations emerged with anxiety disorders or binge eating disorder. Patients with inadequate weight loss showed higher levels of emotional dysregulation, while no differences emerged for other ADHD-related dimensions. Emotional dysregulation remained significantly associated with poorer weight outcomes in multivariate analysis. Conclusions: Emotional dysregulation may represent a transdiagnostic factor influencing bariatric surgery outcomes, supporting the importance of integrating emotional and cognitive dimensions into preoperative assessment and postoperative care.

BACKGROUND:Mental pain represents a significant risk factor for suicidal behavior in severe mental disorders. The present study aims to investigate the interplay between childhood traumatic experiences, hopelessness, depressive symptoms and mental pain, using a network analysis approach in a large transdiagnostic sample of participants living in the community. METHODS:The present investigation was conducted using data gathered in a multicentric observational cross-section study organized as a joint project, including different Italian research and clinical settings. Considering the assessment tools adopted in the study, 12 different variables were included as nodes in the EBICglasso network analysis. Stability of the edges and of centrality indices were assessed using bootstrap procedures, considering case-dropping and node-dropping procedures. RESULTS:A total of 2147 participants were included in the analysis. Mental pain represents a central feature in a complex network of relationships, including traumatic experiences, hopelessness, and depressive symptoms. More in deatail, mental pain and, to a lesser extent, affective and cognitive depressive symptoms emerged as the most central and influential nodes of the network, highlighting the strong link existing between these aspects and their importance in the lives of people with mental disorders. CONCLUSIONS:Results confirm the importance of mental pain as a transdiagnostic feature, requiring careful assessment and consideration in all patients, beyond the diagnostic categories and regardless of suicide risk. Assessing and managing the presence and severity of mental pain should be taken into account in clinical practice, in the perspective of providing significant clinical benefits, as well as relevant research insight.

Background/Objectives: Obesity is a major public health challenge of the 21st century, with prevalence rates steadily rising globally. Disordered eating behaviors, particularly emotional eating (EE), complicate the clinical management of obesity and hinder long-term outcomes, such as maintaining weight loss after bariatric surgery. Studies reveal that EE affects 65-75% of overweight or obese adults, and such behavior may stem from a disrupted brain reward system linked to emotional dysregulation and impulsivity. Impulsivity in obesity involves deficient cognitive inhibitory control, creating an imbalance between impulsive and reflective systems. While problematic eating behaviors and obesity are well studied, the role of affective temperaments-innate traits influencing mood, energy, and responses to stimuli-remains underexplored. This study aims to examine the interplay between emotional eating, impulsivity, and affective temperaments in obese patients preparing for bariatric surgery. Methods: A total sample of 304 obese outpatients was consecutively enrolled at the Psychiatry Clinic of the Department of Clinical and Experimental Medicine of the University of Pisa during the presurgical mental health evaluation routinely performed before the bariatric intervention. Sociodemographic and clinical data were collected by psychiatrists during a single consultation. Assessments also included the following psychometric tests: the Structured Clinical Interview (SCID-5), the Emotional Eating Scale (EES), the Barratt Impulsivity Scale-Version 11 (BIS-11), and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Auto-questionnaire (TEMPS-A). Results: A significant correlation was observed between the EES total score and the BIS total score (p = 0.003), as well as with the sub-dimensions of attentional impulsivity (p < 0.001) and motor impulsivity (p = 0.024). In addition, a significant correlation has been found between the total score of EES and the cyclothymic (p < 0.001), depressive (p < 0.001), irritable (p = 0.013), and anxious (0.020) temperaments. When comparing obese patients with EE and without EE (No-EE), higher rates of both current (p = 0.007) and lifetime (p = 0.024) psychiatric comorbidities were observed in the EE group, namely for anxiety disorders (p = 0.008) and eating disorders (p = 0.014). Conclusions: Our study highlights a significant association between EE in obese patients with the cyclothymic, irritable, anxious, and depressive temperaments, and impulsivity dimension. Thus, problematic eating behaviors and temperamental traits may have a bidirectional psychopathological influence in obese patients and need to be carefully evaluated in subjects seeking bariatric surgery.

Background The DSM-5 recognized that the separation anxiety disorder (SEPAD) may span the entire life course or have an adult-onset. Epidemiological data indicated a 23%-69% prevalence of SEPAD in clinical settings and a high comorbidity with both prolonged grief disorder (PGD) and post-traumatic stress disorder (PTSD). Some authors hypothesize that while life threat represents the key trigger of PTSD, disruptions or threats to interpersonal bonds lead to PGD and SEPAD. This study aims to test the hypothesis that adult-onset SEPAD might be a trauma-related disorder, triggered by events threatening to interpersonal bonds.Methods The sample included 106 consecutive adult outpatients with anxiety and/or mood disorders. SEPAD was diagnosed according to DSM-5 criteria by means of the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS). The Adult Separation Anxiety Checklist (ASA-27) was used to assess symptoms severity. To assess exposure to trauma, the SCID-5 criterion A form for PTSD was administered. Traumatic events were coded as directly experienced (self) or involving close ones (others). Lifetime exposure to separation events was also assessed.Results 60.4% of participants were categorized as not having SEPAD in adulthood or in childhood (NO-SEPAD), 18.9% as childhood-onset SEPAD, and 20.8% as adult-onset SEPAD. Controlling for comorbid disorders, lifetime traumatic events involving self and separation events, traumatic events involving others significantly predicted adult-onset SEPAD. A significant correlation between the age at trauma exposure and the age of SEPAD onset was found.Conclusions Our results are consistent with the hypothesis that adult-onset SEPAD may represent an event-related disorder.

IntroductionDespite an increasing interest in upscaling the digitalization process in mental health care services, there is still a gap in a deeper knowledge of the main barriers and facilitators allowing a capillary and consolidated implementation of digital mental health (DMH) and digital psychiatry (DP), particularly in the Italian context. A multicentric nationwide study (DIGIT-PSY) was designed with the aim to overview the current digitalization level of Italian mental health systems and professionals, by investigating needs/gaps to be addressed to accelerate the availability/access to DMH/DP interventions in Italy, as well as specific internal/external determinants of the process. The final goal of the DIGIT-PSY was to provide a roadmap for implementation strategies to reach a satisfactory level of digitalization of mental health care settings in Italy.MethodsA survey was distributed to a multiprofessional cohort of mental health professionals (psychiatrists, psychiatry trainees, psychologists, technicians in psychiatric rehabilitation and professional mental health educators), from public and private Italian settings, from May 1st, 2023 to September 30th, 2023. Internal/external determinants influencing the level of digitalization, as assessed by using the Digitalization index (DIGi score) were explored, by also comparing mental health (MH) professionals in three groups: a) low (DIGi ranged 4-9); b) moderate (DIGi ranged 10-15); and, c) high level of digitalization (DIGi ranged 16-20).ResultsOnly 16.4% of the sample declared an optimal/good clinical practice experience in the field of DP/DMH interventions, being mostly among psychiatrists and psychologists and those who currently practice psychotherapy (all, p < 0.001). Only 6.5% (N = 90) of mental health professionals received a formal DMH/DP training. The mean DIGi index was 9.9 ± 3.5. MH professionals owning a pre-COVID-19 and/or post-COVID-19 clinical experience in DMH/DP showed the highest DIGI scores (both p<0.001), suggesting a COVID-19 effect in boosting the digitalization of MH services. Working with DMH/DP knowledgeable colleagues and with colleagues who routinely deliver DMH/DP in their clinical practice increased the digitalization level of MH professionals and services (both p<0.001). Both education/training in DMH/DP (p=0.002) and regular clinical practice in DMH/DP (p<0.001) improved the chance to reach a high DIGi score. While working in a public job setting negatively predicted the DIGi index (p=0.007).DiscussionNational initiatives should firstly address education and training needs of the youngest mental health professionals, particularly those without a mentor/supervisor experienced in providing DMH/DP and in educating younger professionals in the digital clinical practice. Sex-sensitive consolidating strategies should be implemented in those mental health services already digitalized. Longitudinal studies should evaluate the efficacy in the long-term of country-based digitalization strategies.

BACKGROUND:Increasing attention has been recently devoted to treatment-resistant depression (TRD); however, its clinical characteristics, potential risk factors, and course are still debated. Most recently, childhood trauma exposure has been correlated to TRD, but systematic investigation on the role of lifetime trauma is still lacking. The aim of this paper was to revise current evidence on early and recent trauma exposure in TRD. METHODS:A systematic search was conducted from the 1st of June to the 20th of February 2024 in accordance with the PRISMA 2020 guidelines and using the electronic databases PubMed, Web of Science, and Embase. RESULTS:The primary database search produced a total of 1998 record, and finally, the search yielded a total of 22 publications, including 18 clinical studies, 3 case reports, and 1 case series, all from the period 2014 to 2024. LIMITATIONS:Limitations include a small sample size of some studies and the lack of homogeneity in the definition of TRD. Furthermore, we only considered articles in English, we excluded preprints or abstracts, and we included case reports. CONCLUSIONS:This review highlights the role of early and recent trauma in TRD, even in the absence of a full-blown post-traumatic stress disorder (PTSD), highlighting the need for a thorough assessment of trauma in patients with TRD and of its role as a therapeutic target.

In western countries, the COVID-19 pandemic represented a unique scenario of a global threat of contagion of a life-threatening illness, as confirmed by the need for exceptional and never adopted measures represented by national lockdowns. This study aimed to investigate peritraumatic distress in the framework of the lockdown and to measure the impact on the course of depressive symptoms during the “first wave” of the COVID-19 pandemic in Italy. A sample of 131 subjects (52.7% females; mean age 47.0 ± 15.9 years), looking for a first or follow-up psychiatric visit at the outpatient psychiatric services of two Italian university hospitals, was recruited between 1 June 2020 and 30 July 2020 and assessed by the Hamilton Rating Scale for Depression (HAM-D) and the Peritraumatic Distress Inventory (PDI) at the time of enrolment in the study (T0). The HAM-D was administered again after 3 months (T1). Higher PDI scores significantly predicted the persistence or worsening of depressive symptoms. These results give further evidence of the possible interplay between peritraumatic distress and depressive symptoms in the framework of a global health threat such as the COVID-19 pandemic.

Prolonged Grief Disorder (PGD) is marked by enduring and disruptive grief symptoms following the death of a significant other. Although PGD has been recognized as a distinct psychopathological entity within the trauma dimension in the DSM-5-TR, its neurobiological underpinnings remain not fully defined. A systematic literature review was conducted up to September 2025 following PRISMA 2020 guidelines. PubMed, Scopus, Embase and Web of Science were searched using a comprehensive strategy combining MeSH terms and free-text keywords. Eligible studies included human participants, validated grief assessment tools and biomarker assessments. Out of 2140 initial records, 12 studies published between 1989 and 2022 met inclusion criteria. Investigated neuro–psycho–endocrine systems included the hypothalamic–pituitary–adrenal (HPA) axis, catecholamines, oxytocin, endocannabinoids and immune/inflammatory markers. Key findings in pathological grief reactions included altered cortisol rhythms, elevated oxytocin levels, increased pro-inflammatory cytokines and immune system dysregulation. Results are limited by heterogeneity in study designs, small sample sizes, inconsistent use of diagnostic criteria prior to DSM-5-TR and lack of control for psychiatric comorbidities. This review highlights emerging biological correlates of PGD, particularly those involving the stress response, reward-attachment networks and immune/inflammatory pathways. Further standardized, longitudinal research is essential to gain a more defined picture of PGD, to clarify causal mechanisms and to guide targeted therapeutic interventions.

(1) Background: A child’s new diagnosis of autism can represent a highly stressful event for parents. Subthreshold autistic traits (ATs) have been linked to higher vulnerability to psychopathology when exposed to stressful situations, and high rates of ATs have been reported among parents of autistic children. This study aimed to evaluate post-traumatic stress spectrum symptoms (PTSS) in parents of preschool children newly diagnosed with autism and to explore differences between mothers and fathers, besides the correlations with ATs. (2) Methods: A total of 134 parents of children newly diagnosed with autism were assessed by trained psychiatrists from the University of Pisa using the Autism Spectrum Quotient (AQ), the Adult Autism Subthreshold Spectrum-Self Report (AdAS-SR), the Trauma and Loss Spectrum-Self Report (TALS-SR), and the Social and Occupational Functioning Assessment Scale (SOFAS). (3) Results: Approximately 10% of parents met DSM-5-TR criteria for symptomatologic PTSD, with nearly 40% experiencing partial PTSD symptoms related to their child’s diagnosis. Mothers showed higher PTSD rates than fathers. The ATs significantly correlated with elevated TALS-SR scores, and logistic regression revealed a positive association between ATs and PTSD (p < 0.001). Linear regression analysis indicated that higher TALS-SR scores predicted lower SOFAS scores (p = 0.004). (4) Conclusions: These findings highlight the potential traumatic impact of a child’s new autism diagnosis on parents, particularly mothers and individuals with ATs. The results underscore the importance of targeted support strategies for parents, considering their key role in early interventions. Further research is needed to better understand parental psychological responses and to enhance support systems, ultimately improving family wellbeing and child outcomes.

Background: Obesity is a major concern in patients with bipolar disorder (BD) and problematic eating behaviors have been suggested to mediate their relationship. The association between problematic eating behaviors and obesity has been studied but limited data have explored the role of BD. We investigated problematic eating behaviors among patients with BD compared with candidates for bariatric surgery (BS), with or without BD, and explored the possible correlations between mood spectrum, impulsivity, body mass index (BMI). Methods: 50 euthymic patients with BD and 200 subjects eligible for BS, 48 with BD (BS + BD) and 152 without BD (BS-BD), were recruited at the Psychiatric Clinic of University of Pisa. Assessments included: Structured Clinical Interview (SCID-5), Emotional Eating Scale (EES), Yale Food Addiction Scale (YFAS), Eating Disorder Inventory (EDI-2), Eating Disorder Questionnaire (EDE-Q), Night Eating Scale (NES), Grazing Questionnaire (GQ), Mood Spectrum Self-Report (MOOD-SR), Barratt Impulsivity Scale (BIS). Results: BS + BD reported significantly higher EDI-2 and EDE-Q scores than the other groups. BD and BS + BD showed significantly higher BIS-11 scores than BS-BD. Among BS, EES and YFAS were associated with mood spectrum symptoms. Limitations: Small BD sample size, BS may have underreported psychiatric symptoms to get approved for surgery, the interview didn't inquire about BS receiving GLP-1 agonists therapy. Conclusions: Results showed a high prevalence of problematic eating behaviors among patients with BD and severely obese. Problematic eating behaviors may aggravate BD symptoms. Mood spectrum symptoms in obese subjects need to be carefully researched in as relate to severity and post-surgical course of BS.

Intensive care unit (ICU) admission can represent a relevant physical and psychological burden in patients, leading to long-term mental health problems such as anxiety, depression, and post-traumatic stress disorder (PTSD). The present study aimed to systematically assess the physical and psychiatric (particularly depressive, anxiety, and post-traumatic stress) symptoms in patients discharged from the ICU of a major University Hospital in Italy (Pisa) 6 months earlier, with particular, attention to differences between patients who developed PTSD and those who did not. The strength of this study is to increase the understanding of PTSD, depressive and anxiety symptoms; in particular, their correlations with the physical sequalae. Subjects were assessed six months after ICU discharge by means of the Glasgow Outcome Scale-Extended (GOS-E), Quality of Life after Brain Injury (QOLIBRI), the 3-level version of the EQ-5D (EQ-5D-3L) questionnaire, Impact of Event Scale-Revised 22-item (IES-R), Patient Health Questionnaire, 9-Item Version (PHQ-9), and Generalized Anxiety Disorder Assessment, 7-item version (GAD-7). The results of this study showed, in accordance with the IES-R, a moderate prevalence of PTSD (25.3%) six month after ICU discharge and a statistically significant higher prevalence (63.6%, p = 0.039) of moderate and severe disabilities in the PTSD group compared to the no-PTSD group, as well as higher depressive and anxiety symptoms and other psychiatric sequelae, suggesting the need for accurate long-term psychiatric assessment in ICU survivors.