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Objective: Substance Use Disorders (SUD) are common in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Although predictors of SUD in this population are relevant for prevention and treatment, they need further clarification. Affective temperaments potentially associated with SUD in adult ADHD patients were explored. Methods: ADHD patients with and without SUD were compared for sociodemographic, clinical, and psychological characteristics through: Adult ADHD Self-Report Scale; Wender Utah Rating Scale; Temperament Evaluation Memphis for Pisa, Paris, and San Diego-Autoquestionnaire. Logistic regression investigated factors associated with SUD. Results: We included one-hundred and thirty-six ADHD patients with (n = 51, 37.5 %) and without SUD (n = 85, 62.5 %). The presence of SUD was associated with irritable temperament (p = 0.009), as well as more frequent school failure (p = 0.038), legal problems (p = 0.039), and lifetime suicide attempts (p = 0.014). Limitations: The cross-sectional design, the relatively small sample size, and the use of self-administered questionnaires. Conclusions: This study confirms the greater overall severity of adult ADHD-SUD compared with ADHD-only patients and suggests the potential role of irritable temperament as a predictor of substance-related problems.

Background and Objectives: Amelanotic/hypomelanotic melanomas (AHMs) account for 2–8% of all cutaneous melanomas. Due to their clinical appearance and the lack of specific dermoscopic indicators, AHMs are challenging to diagnose, particularly in thinner cutaneous lesions. The aim of our study was to evaluate the clinicopathological and dermoscopic features of thin AHMs. Identifying the baseline clinical–pathological features and dermoscopic aspects of thin AHMs is crucial to better understand this entity. Materials and Methods: We divided the AHM cohort into two groups based on Breslow thickness: thin (≤1.00 mm) and thick (>1.00 mm). This stratification helped identify any significant clinicopathological differences between the groups. For dermoscopic analysis, we employed the “pattern analysis” approach, which involves a simultaneous and subjective assessment of different criteria. Results: Out of the 2.800 melanomas analyzed for Breslow thickness, 153 were identified as AHMs. Among these, 65 patients presented with thin AHMs and 88 with thick AHMs. Red hair color and phototype II were more prevalent in patients with thin AHMs. The trunk was the most common anatomic site for thin AHMs. Patients with thin AHMs showed a higher number of multiple melanomas. Dermoscopic analysis revealed no significant difference between thin AHMs and thick AHMs, except for a more frequent occurrence of residual reticulum in thin AHMs. Conclusions: Thin AHMs typically affect individuals with lower phototypes and red hair color. These aspects can be related to the higher presence of pheomelanin, which provides limited protection against sun damage. This also correlates with the fact that the trunk, a site commonly exposed to intermittent sun exposure, is the primary anatomical location for thin AHMs. Multiple primary melanomas are more common in patients with thin AHMs, likely due to an intrinsic predisposition as well as greater periodic dermatologic follow-ups in this class of pati

In patients with advanced triple-negative breast cancer (TNBC), translational research efforts are needed to improve the clinical efficacy of immunotherapy with checkpoint inhibitors. Here, we report on the immunological characterization of an exceptional, long-lasting, tumor complete response in a patient with metastatic TNBC treated with dual PD-1 and LAG-3 blockade within the phase I/II study CLAG525X2101C (NCT02460224) The pre-treatment tumor biopsy revealed the presence of a CD3+ and CD8+ cell infiltrate, with few PD1+ cells, rare CD4+ cells, and an absence of both NK cells and LAG3 expression. Conversely, tumor cells exhibited positive staining for the three primary LAG-3 ligands (HLA-DR, FGL-1, and galectin-3), while being negative for PD-L1. In peripheral blood, baseline expression of LAG-3 and PD-1 was observed in circulating immune cells. Following treatment initiation, there was a rapid increase in proliferating granzyme-B+ NK and T cells, including CD4+ T cells, alongside a reduction in myeloid-derived suppressor cells. The role of LAG-3 expression on circulating NK cells, as well as the expression of LAG-3 ligands on tumor cells and the early modulation of circulating cytotoxic CD4+ T cells warrant further investigation as exploitable predictive biomarkers for dual PD-1 and LAG-3 blockade. Trial registration: NCT02460224. Registered 02/06/2015.

Background: Genital involvement in atopic dermatitis(AD) can have a significant impact on the patient's quality of life. However, inspection of genital areas is not usually conducted during routine examination and patients may be reluctant to inform the clinician or show this area. Objective: to evaluate the efficacy of tralokinumab in AD patients with genital involvement. Methods: Adult patients with moderate/severe AD and genital involvement receiving tralokinumab have been analyzed. Primary endpoints were EASI, DLQI, PP-NRS, genital-IGA (g-IGA) and genital itching (GI) at week 16. Results: out of 48 patients with moderate/severe AD under treatment with tralokinumab, 12 patients (25%) showed a genital involvement. Seven patients reported itching in the genital area (58%), while none reported a positive history of genital infections. Median scores at T0 were EASI 17.5, PP-NRS 8 and DLQI 14. After 16 weeks of treatment, we observed a median EASI of 3, a median PP-NRS of 1 and a median DLQI of 1. Finally, concerning the genital response, after 16 weeks of treatment, we observed a statistically significant decrease in mean GI and g-IGA scores. Conclusion: despite the small size of our sample, tralokinumab can be considered as a valid treatment option for AD with genital involvement.

Sense of agency (SoA) indicates a person's ability to perceive her/his own motor acts as actually being her/his and, through them, to exert control over the course of external events. Disruptions in SoA may profoundly affect the individual's functioning, as observed in several neuropsychiatric disorders. This is the first article to systematically review studies that investigated intentional binding (IB), a quantitative proxy for SoA measurement, in neurological and psychiatric patients. Eligible were studies of IB involving patients with neurological and/or psychiatric disorders. We included 15 studies involving 692 individuals. Risk of bias was low throughout studies. Abnormally increased action-outcome binding was found in schizophrenia and in patients with Parkinson's disease taking dopaminergic medications or reporting impulsive-compulsive behaviors. A decreased IB effect was observed in Tourette's disorder and functional movement disorders, whereas increased action-outcome binding was found in patients with the cortico-basal syndrome. The extent of IB deviation from healthy control values correlated with the severity of symptoms in several disorders. Inconsistent effects were found for autism spectrum disorders, anorexia nervosa, and borderline personality disorder. Findings pave the way for treatments specifically targeting SoA in neuropsychiatric disorders where IB is altered.

Background: Use of social media (SM) has exponentially grown particularly among youths in the past two years, due to COVID-19-related changing lifestyles. Based on the Italian COvid Mental hEalth Trial (COMET), we investigated the association between SM use and depressive symptoms among Italian young adults (aged 18–24). Methods: The COMET is a nationwide multi-center cross-sectional study that investigated socio-demographic data, social networking addiction (BSNAS), depression, anxiety, and stress (DASS-21), as well as impulsiveness (BIS-15) and aggressiveness (AQ) in a large sample of youngsters, in order to assess the association between BSNAS and DASS-21 indices. Mediation analyses were performed to evaluate the role of impulsiveness and aggressive personality traits in the association between SM use (SMU) and depression. Results: 75.8% of the sample (n = 491) had a problematic SMU. SMU was reduced by high AQ and high DASS-21 scores (F = 42.338, p < 0.001, R2 = 0.207). Mediation analyses showed that SMU negatively predicted depressive symptomatology with the interaction mediated by AQ total (ß = − 0.1075), physical (ß = − 0.207) and anger (ß = − 0.0582), BIS-15 total (ß = − 0.0272) and attentional (ß = − 0.0302). High depressive levels were predicted by high AQ scores, low SMU levels, low verbal and physical AQ, and low attentional BIS-15 (F = 30.322, p < 0.001, R2 = 0.273). Depressive symptomatology negatively predicted SMU with their interaction mediated by AQ total (ß = − 0.1640), verbal (ß = 0.0436) and anger (ß = − 0.0807), BIS-15 total (ß = − 0.0448) and attentional (ß = − 0.0409). Conclusions: SMU during the early phases of the COVID-19 pandemic could have a beneficial role in buffering negative consequences linked to social isolation due to quarantine measures, despite this association being mediated by specific personality traits.

Introduction: Longitudinal psychopathological predictors of relapse in alcohol use disorder are unclear. Methods: Relapses, sociodemographic and psychopathological risk factors were assessed in 171 alcohol use disorder outpatients within a 1-year follow up. Impulsivity and alexithymia were evaluated using the Barratt Impulsiveness Scale and the Toronto Alexithymia Scale, respectively. Results: At endpoint, 39% of patients maintained abstinence, 30.9% relapsed at ≤1 month from detoxification (early), 30.1% at >1 month (subsequent). Baseline Barratt Impulsiveness Scale score was predictive of early versus subsequent relapse (odds ratio 1.12, p = 0.005) and versus abstinence (odds ratio 1.17, p < 0.001). Toronto Alexithymia Scale score was a risk factor for subsequent versus early relapse (odds ratio 1.13, p = 0.003) and versus abstinence (odds ratio 1.21, p < 0.001). Discussion and Conclusions: Impulsivity predicted relapse within the first 4-weeks; alexithymia showed delayed effects. Time-varying effects of specific relapse factors emphasise the need for preliminary careful assessment and personalised interventions to promote long-term abstinence.

Background: Affective temperaments represent the stable, biologically determined substrates of mood disorders. The relationship between affective temperaments and bipolar disorder (BD) or major depressive disorder (MDD) has been described. However, the strength of such relationship should be tested while considering other factors influencing the diagnosis of BD/MDD. Literature also lacks a comprehensive description of the interplay between affective temperament and characteristics of mood disorders. The aim of the present study is to address these issues. Methods: This is a multicentric observational study including 7 Italian university sites. Five-hundred-fifty-five euthymic subjects with BD/MDD were enrolled and further divided in those with hyperthymic (Hyper, N = 143), cyclothymic (Cyclo, N = 133), irritable (Irr, N = 49), dysthymic (Dysth, N = 155), and anxious (Anx N = 76) temperaments. Linear, binary, ordinal and logistic regressions were performed to assess the association between affective temperaments and i) diagnosis of BD/MDD; ii) characteristics of illness severity and course. Results: Hyper, Cyclo and Irr were more likely to be associated with BD, together with earlier age of onset and presence of a first-degree relative with BD. Anx and Dysth were more associated with MDD. Differences in association between affective temperaments and characteristics of BD/MDD were observed for hospital admissions, phase-related psychotic symptoms, length and type of depression, comorbidity and pharmacological intake. Limitations: Small sample size, cross-sectional design, recall biases. Conclusion: Specific affective temperaments were associated to certain characteristics of illness severity and course of BD or MDD. Evaluation of affective temperaments might help a deeper understanding of mood disorders.

Background: Different craving typologies (i.e., reward, relief, obsessive) have been identified in alcohol use disorder (AUD) but have been less investigated in specific populations like AUD patients with polysubstance use (PSU). The role of dysfunctional personality traits and reward pathways has been reported in both AUD and PSU. We hypothesized that patients with AUD-PSU might show a prevalent reward craving, alongside specific sociodemographic, clinical, and personality features, and aimed at investigating differences in 423 severe AUD outpatients with and without PSU. Methods: One hundred fifteen patients (27.1% of the sample, 67% males, 42 ± 11.6 years old) displayed PSU. Sociodemographic, clinical features and psychopathological/personality dimensions were assessed through: Craving Typologies Questionnaire (CTQ); Obsessive–Compulsive Drinking Scale (OCDS); UPPS-P Impulsive Behavior Scale (S-UPPS-P); Difficulties in Emotion Regulation Scale (DERS). A binomial logistic regression explored factors associated with PSU. Results: We found higher CTQ ‘reward’ scores (p < 0.001) in AUD-PSU patients, and a significant association between reward craving and PSU through logistic regression (OR:1.13; p = 0.005). Earlier AUD onset (p < 0.001), greater rates of binge drinking (p = 0.029), more legal problems (p = 0.015), but no significantly higher S-UPPS-S and DERS scores, were detected in AUD-PSU patients. Conclusions: Reward craving was associated with increased risk for PSU in severe AUD patients. Given AUD-PSU participants greater severity and detrimental treatment responses imputed to PSU, identifying prevalent craving types among risk factors for PSU in AUD may help to implement therapeutic strategies. Addressing neurobiological and behavioral mechanisms through combined psychotherapies, pharmacological and neuromodulation treatments could support tailored interventions with better long-term outcome.

Background: Major depressive disorders represent a significant burden to society, and it is recommended that antidepressant therapy should last at least 6 months. In Italy, antidepressant use in clinical practice was reported to increase by 1.7% in 2020 compared to 2019, but only 40% of new prescriptions are characterized by a treatment duration longer than 3 months. Objective: The study aims to describe adherence and persistence to therapy in a subset of antidepressants (citalopram, duloxetine, escitalopram, paroxetine, sertraline, venlafaxine) vs. vortioxetine in Italy during a 2-year period from 2017 to 2019. Methods: A retrospective analysis of the longitudinal patient database reporting data from general practitioners on drug prescriptions in Italy was carried out in a cohort of 8,235 adult patients who were prescribed antidepressants. Results: Overall, 32.4% of the patients adhered to treatment for ≥6 months over a 1-year period. Vortioxetine had a lower risk of low adherence compared to duloxetine, paroxetine, and venlafaxine and a higher risk compared to citalopram, escitalopram, and sertraline. 68.7% of patients discontinued treatment during follow-up. The greatest percentage of patients continuing therapy was seen with duloxetine, while citalopram was associated with the highest proportion of patients discontinuing therapy. No significant differences in discontinuation were observed when comparing vortioxetine to the other antidepressants. Conclusion: Adherence results were considerably less than the 6-month recommendation in this real- world analysis of antidepressant therapies. Also, persistence to therapy was low, with most patients discontinuing treatment. Thus, there is a need for interventions to help patients adhere to their planned therapy.

Psychiatric symptoms have been frequently reported in patients affected by COVID-19, both as new occurring and recurrences of pre-existing diseases. Depressive symptoms are estimated to affect at least 30% of patients following infection, with specific physical and cognitive features and relevant immune-inflammatory alterations. This study aimed to retrospectively characterize post-COVID-19 first-onset and recurrent major depressive episodes (MDE) and to evaluate the effects of antidepressants on physical and cognitive correlates of depression, in addition to mood, anxiety, and underlying inflammatory status. We evaluated 116 patients (44.8% males, 51.1 ± 17 years) with post-COVID-19 first-onset (38.8%) and recurrent (61.2%) MDE at baseline and after one- and three-month treatment with antidepressants (31% SSRIs, 25.9% SNRIs, 43.1% others). We assessed sociodemographic and clinical features and psychopathological dimensions through: Hamilton Depression and Anxiety Rating Scales; Short Form-36 Health Survey Questionnaire; Perceived Deficits Questionnaire-Depression 5-items. The systemic immune-inflammatory index was calculated to measure inflammation levels. Alongside the reduction of depression and anxiety (p < 0.001), physical and cognitive symptoms improved (p < 0.001) and inflammatory levels decreased (p < 0.001) throughout treatment in both groups. Post-COVID-19 recurrent MDE showed a significantly more severe course of physical and cognitive symptoms and persistently higher levels of inflammation than first-onset episodes. Antidepressants proved to be effective in both post-COVID-19 first-onset and recurrent MDE. However, a sustained inflammatory status might blunt treatment response in patients with recurrent depression in terms of physical correlates and cognition. Therefore, personalized approaches, possibly involving combinations with anti-inflammatory compounds, could promote better outcomes in this clinical population.

Binge drinking (BD) represents a public health concern because of increasing prevalence, clinical implications, and social consequences. Determinants of BD have been mainly studied in non-clinical samples, but few data in patients with alcohol use disorder (AUD) are available. Our study aimed at identifying risk factors for BD in AUD patients. We evaluated 373 severe AUD outpatients, subdivided according to the presence of a sustained BD pattern in: non-binge drinkers (n = 256, M = 63.3%, 48.8 ± 10.7 years) and sustained binge drinkers (n = 117, M = 65%, 39.7 ± 9.6 years). We collected sociodemographic and clinical information and assessed impulsivity and emotion dysregulation using the short version of the UPPS-P Impulsive Behavior Scale (S-UPPS-P) and the Difficulties in Emotion Regulation Scale (DERS). We conducted a binomial logistic regression to investigate predictors for BD and a mediation analysis to test the effect of impulsivity and emotion dysregulation on BD. One hundred seventeen patients (31.4%) presented a sustained BD pattern. Positive urgency (OR: 2.235; p = 0.018) and limited access to emotion regulation strategies [DERS strategies (OR: 1.553; p = 0.004)] were risk factors for BD. The relationship between positive urgency and BD was significantly mediated by DERS strategies (p = 0.015; bootstrapped LLCI = 0.008, ULCI = 0.044). In our sample, positive urgency and limited access to emotion regulation strategies were risk factors for sustained BD in AUD patients. The effects of impulsivity on BD were mediated by difficulties in emotion regulation. BD patterns have been associated with poor response to treatment and worse outcome in AUD patients; however, the full impact of this problematic drinking pattern is still underinvestigated. Clarifying the underlying psychopathological dimensions is crucial to deliver targeted interventions.

Functional movement disorders (FMD) involve a broad range of abnormal involuntary movements not consistent with neurological diseases. These conditions often occur in combination with mood and anxiety disorders and are associated with poor clinical outcomes. We report the case of a 57-year-old woman diagnosed with treatmentresistant depression (TRD) and comorbid FMD treated with weekly intranasal administrations of esketamine over a six-month follow-up period. A comprehensive clinical and psychometric assessment was carried out at different time points. After 2 months of treatment, a complete remission of motor and axial functional disturbances (athetosis, trunk torsion and genuflections) was detectable, along with a progressive improvement in depressive symptoms during follow-up until full remission. According to novel lines of evidence, glutamatergic transmission might play a role in the pathophysiology of FMD through aberrant limbic-motor interactions. We report that treatment with esketamine, a noncompetitive N-methyl-d-aspartate glutamatergic receptor antagonist, was associated with remission of FMD symptoms in a patient with TRD. Pharmacological compounds modulating brain glutamatergic activity may be of potential benefit in the clinical management of FMD.

Purpose: Anorexia nervosa-restrictive subtype (AN-R) is a life-threatening disorder relying on behavioural abnormalities, such as excessive food restriction or exercise. Such abnormalities may be secondary to an “objectified” attitude toward body image and self. This is the first study exploring the impact of anomalous self-experience (ASEs) on abnormal body image attitude and eating disorder (ED) symptomatology in individuals with AN-R at onset. Methods: We recruited Italian female participants, 40 with AN-R (mean age 18.3 ± 2.3) and 45 age and educational level-matched healthy controls (HCs) (mean age 18.2 ± 2.6). ASEs, body image attitude, and ED symptom severity were assessed through the examination of anomalous self-experience (EASE), the body uneasiness test (BUT), and the eating disorder examination questionnaire (EDE-Q), respectively. We conducted multivariate analysis of variance to investigate distribution patterns of variables of interest, and mediation analysis to test the effect of ASEs and body image on ED symptomatology. Results: Individuals with AN-R scored higher than HCs on the EASE (p <.0001). A direct effect of ASEs on ED severity (p = 0.009; bootstrapped LLCI = 0.067, ULCI = 0.240) was found in AN-R. After modelling the effect of abnormal body image attitude, the relationship between EASE total score and ED symptomatology was significantly mediated by BUT (p = 0.002; bootstrapped LLCI = 0.001, ULCI = 0.172). Conclusion: Although the exact pathways linking AN-R to self-disorder remain to be identified, a broader exploration of transdiagnostic features in AN, including explorations of different dimensions of self-experience and intersubjectivity, may shed further light on the clinical phenomenology of the disorder. Level of evidence: Level III, case–control analytic study.