Predictors of clinical severity in subjects attending the Emergency Department for substance use: a ten-year cross-sectional study.

OBJECTIVE: Substance-related referrals to the Emergency Department (ED) are rising. Multiple substance use is frequent, and psychiatric patients represent a high-risk population. Our study aimed at identifying risk factors for increased severity in ED attendances for substance use. METHODS: We retrospectively evaluated consecutive patients attending the ED over ten years for substance-related problems, subdivided according to the triage code as having a life-threatening (LT), potentially life-threatening (P-LT), and non-life-threatening (N-LT) condition. RESULTS: Substance/drug intake for deliberate self-harm was a risk factor for being classified as LT compared to both P-LT (OR = 6.357; p ≤ 0.001) and N-LT (OR = 28.19; p ≤ 0.001). Suicide attempts (OR = 4.435; p = 0.022) and multiple substance use (OR = 1.513; p = 0.009) resulted as risk factors for P-LT, compared to N-LT. Psychiatric diagnosis (OR = 1.942; p = 0.042) and multiple substance use (OR = 1.668; p = 0.047) were risk factors for being classified as LT rather than N-LT. CONCLUSIONS: In our sample, self-harming overdoses were the strongest risk factor for highest overall severity in a real-world setting. Psychiatric disorders and multiple substance use also increased the risk for greater severity at presentation. Substance use worsens patients' clinical picture and management, suggesting the need for consultation-liaison psychiatry services in emergency contexts and highlighting the role of EDs as key sites for identification and early intervention.

Type of cycle, temperament and childhood trauma are associated with lithium response in patients with bipolar disorders.

BACKGROUND: Lithium stands as the gold standard in treating bipolar disorders (BD). Despite numerous clinical factors being associated with a favorable response to lithium, comprehensive studies examining the collective influence of clinical variables alongside psychopathological dimensions are lacking. Our study aims to enhance comprehension of lithium response in individuals with BD by integrating clinical variables with psychopathological traits and early adverse events. METHODS: We assessed 201 patients with BD for clinical characteristics, childhood trauma, temperament traits, impulsivity, and aggression. Lithium response was evaluated using the gold standard Alda scale, and predictors of lithium response were estimated through a multivariate model. RESULTS: On the total sample, 61 (30.3%) patients were lithium responders according to the Alda scale. Comparatively, lithium responders, in contrast to non-responders, demonstrated a higher prevalence of the mania-depression-interval (MDI) cycle, a more frequent diagnosis of BD type I, and reported an earlier age of onset. They also exhibited less lifetime substance abuse, emotional, physical, and sexual abuse, while scoring higher on hyperthymic and irritable temperament scales. In multivariate analyses, only the MDI cycle (OR,3.47; 95%CI,1.61-7.50) hyperthymic (OR,1.20; 95%CI,1.02-1.41) and irritable temperament (OR,1.28; 95%CI,1.08-1.52) persisted as significant predictors of a positive response to lithium treatment, while emotional (OR,0.87; 95%CI,0.76-0.98) and physical abuse (OR,0.83; 95%CI,0.70-0.98) were predictors of non-response. CONCLUSIONS: In evaluating lithium response in BD, our study highlights the importance of considering clinical variables alongside temperament and childhood adversities. The assessment of hyperthymic and irritable temperament, emotional and physical abuse together with the type of cycle is of particular importance. Furthermore, our findings underscore the significance of systematically assessing the type of cycle in patients with BD through the use of life charts.

Childhood sexual abuse and suicide attempts in patients with substance use disorders: The mediating role of emotion dysregulation.

BACKGROUND: Suicide attempts (SA) are a public health concern because of increasing prevalence and clinical implications. Childhood trauma (CT) and emotion dysregulation (ED) have been proposed as predictors of SA, but few data are available in patients with Substance Use Disorder (SUD). OBJECTIVE: Our study aims to investigate the association of sociodemographic/clinical variables, CT typologies, and ED features with SA in SUD patients. PARTICIPANTS AND SETTING: Subjects with SUD were screened in an outpatient setting. The final sample consisted of 226 patients, subdivided according to the presence of lifetime SA (SUD, n = 163 vs. SUD-SA, n = 63). METHODS: Participants were compared for sociodemographic and clinical information. CT and ED were assessed through the Childhood Trauma Questionnaire - Short Form (CTQ-SF) and the Difficulties in Emotion Regulation Scale (DERS), respectively. We performed a mediation analysis to test the effect of CT and ED on SA. RESULTS: Patients with a history of SA (27.9 %) displayed more psychiatric comorbidities (p = 0.002) and hospitalizations (p < 0.001), higher scores at CTQ-SF sexual abuse (p < 0.001) and DERS 'impulse' (p = 0.002), 'goals', 'non-acceptance', 'strategies' (p < 0.001) subscales. The relationship between CTQ-SF sexual abuse and SA was significantly mediated by DERS 'strategies' (p = 0.04; bootstrapped 95 % LLCI-ULCI = 0.004-0.024). CONCLUSIONS: CT and different dimensions of ED were associated with SA in SUD patients. In our sample, the effects of childhood sexual abuse on SA were mediated by limited access to emotion regulation strategies. SUD patients are burdened with higher all-cause mortality, and CT and lifetime SA can worsen clinical outcomes. Clarifying the reciprocal interactions of psychopathological dimensions may help deliver targeted interventions and reduce suicide risk in specific populations.

Childhood Trauma and Self-harm in Youths with Bipolar Disorders.

BACKGROUND: Bipolar disorders (BD) in youth are associated with a high risk of self-harm behaviors. Childhood trauma (CT) is a relevant environmental stressor that is related to both BD diagnosis and self-harm in adulthood. It is not yet established whether CT may impact self-harm risk in youth. Therefore, the aim of this study was to investigate the distribution patterns of CT in youth BD with and without self-harm. METHODS: We assessed 273 participants (aged 13-25 years), 96 youths with BD according to DSM-5 criteria and 177 healthy controls (HC). History of CT was obtained using the Childhood Trauma Questionnaire (CTQ). The association between CT and self-harm was tested using multivariate statistical models. RESULTS: Over 45% of participants with BD reported lifetime self-harm. The BD Self-harm group reported more emotional abuse, emotional neglect, sexual abuse, and physical abuse than HC. The BD No-Self-harm group reported more emotional abuse than HC. The BD Self-harm group reported more emotional abuse and neglect than the BD No-Self-harm group. The BD Self-harm group also reported separated parents, hospitalizations, smoking, use of antiepileptics, antipsychotics and lithium. Emotional abuse was an independent predictor of self-harm in youths with BD. CONCLUSION: Findings support the importance of assessing CT, in particular emotional abuse, in youth with BD at risk for self-harm.

Substance use disorders in adults with attention-deficit/hyperactivity disorder: The role of affective temperament.

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.

Acylcarnitines metabolism in depression: association with diagnostic status, depression severity and symptom profile in the NESDA cohort.

Background: Acylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Studies linking AC levels to depression are few and provide mixed findings. We examined the association of circulating ACs levels with Major Depressive Disorder (MDD) diagnosis, overall depression severity and specific symptom profiles. Methods: The sample from the Netherlands Study of Depression and Anxiety included participants with current (n=1035) or remitted (n=739) MDD and healthy controls (n=800). Plasma levels of four ACs (short-chain: acetylcarnitine C2 and propionylcarnitine C3; medium-chain: octanoylcarnitine C8 and decanoylcarnitine C10) were measured. Overall depression severity as well as atypical/energy-related (AES), anhedonic and melancholic symptom profiles were derived from the Inventory of Depressive Symptomatology. Results: As compared to healthy controls, subjects with current or remitted MDD presented similarly lower mean C2 levels (Cohen's d=0.2, p≤1e-4). Higher overall depression severity was significantly associated with higher C3 levels (ß=0.06, SE=0.02, p=1.21e-3). No associations were found for C8 and C10. Focusing on symptom profiles, only higher AES scores were linked to lower C2 (ß=-0.05, SE=0.02, p=1.85e-2) and higher C3 (ß=0.08, SE=0.02, p=3.41e-5) levels. Results were confirmed in analyses pooling data with an additional internal replication sample from the same subjects measured at 6-year follow-up (totaling 4195 observations). Conclusions: Small alterations in levels of short-chain acylcarnitine levels were related to the presence and severity of depression, especially for symptoms reflecting altered energy homeostasis. Cellular metabolic dysfunctions may represent a key pathway in depression pathophysiology potentially accessible through AC metabolism.

Vortioxetine improves physical and cognitive symptoms in patients with post-COVID-19 major depressive episodes.

Major Depressive Episodes (MDE) following COVID-19 are frequent, can have a characteristic clinical picture, and are associated with immune-inflammatory changes. Vortioxetine is known to improve physical and cognitive performance in patients with depression and shows anti-inflammatory and anti-oxidative activities. This study aimed to retrospectively evaluate the effects of vortioxetine after 1 and 3 months of treatment in 80 patients (44.4% males, 54±17.2 years) with post-COVID-19 MDE. The primary outcome was improvement in physical and cognitive symptoms measured by specific items of Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS), Short Form-36 Health Survey Questionnaire (SF-36), Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire for Depression (PDQ-D5). Changes in mood, anxiety, anhedonia, sleep, and quality of life were also investigated, as well as the underlying inflammatory status. Results show that, alongside reduction of depressive symptoms (HDRS, p<0.001), vortioxetine (mean dose: 10.1±4.1 mg/day) significantly improved physical features (all measurements p<0.001) and cognitive functioning (DDST, p=0.02; PDQ-D5, p<0.001) throughout treatment. We also observed significant reductions in inflammatory indexes. Therefore, vortioxetine might be a favorable therapeutic choice in post-COVID-19 patients with MDE because of its beneficial effects on physical complaints and cognition, features that appear to be specifically affected in relation to SARS-CoV-2 infection, and its good safety/tolerability profile. High prevalence and clinical and socioeconomic implications of COVID-19 consequences are a major public health concern and developing tailored, safe interventions is crucial to promote full functional recovery.

Use of Lithium in Pediatric Bipolar Disorders and Externalizing Childhood- related Disorders: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Lithium is the standard treatment for bipolar disorders (BD) in adults. There is a dearth of data on its use in the pediatric age. This review aimed to investigate the use of lithium in pediatric bipolar disorder (BD) and other externalizing childhood-related disorders. METHODS: We applied the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria (PRISMA) to identify randomized controlled trials evaluating the use of lithium in pediatric (BD), conduct disorder (CD), attention deficit hyperactivity disorder, oppositional defiant disorder, and disruptive mood dysregulation disorder. The primary outcome of our study was to evaluate the efficacy of lithium compared to a placebo or other pharmacological agents. The secondary outcomes were acceptability and tolerability. RESULTS: Twelve studies were eligible, 8 on BD and 4 on CD. Overall, 857 patients were treated with lithium. No studies for externalizing disorder diagnoses were identified. Regarding BD patients (n = 673), efficacy results suggested that lithium was superior to placebo in manic/mixed episodes but inferior to antipsychotics. Lithium efficacy ranged from 32% to 82.4%. Results on maintenance need to be expanded. Comorbidity rates with other externalizing disorders were extremely high, up to 98.6%. Results in CD patients (n= 184) suggested the efficacy of lithium, especially for aggressive behaviors. No severe adverse events directly related to lithium were reported in BD and CD; common side effects were similar to adults. CONCLUSION: This systematic review supports the use of lithium in BD and CD as an efficacious and generally well-tolerated treatment in the pediatric age. However, evidence is limited due to the paucity of available data.

Primary emotional systems, childhood trauma, and suicidal ideation in youths with bipolar disorders.

BACKGROUND: Bipolar disorders (BD) in youths are strongly associated with suicidal ideation. Childhood trauma is a prominent environmental stressor associated with both BD diagnosis and suicide. Primary emotional systems are altered in adult BD and may contribute to suicide risk in youths. OBJECTIVE: The aim of this study was to investigate primary emotional systems distribution patterns and childhood trauma in youths' BD with and without suicidal ideation (BD-IS, BD-NIS). PARTICIPANTS AND SETTING: We assessed 289 participants, 103 youths with DSM-5 BD and 186 healthy controls (HCs). METHODS: Primary emotional systems were obtained with Panksepp's Affective Neuroscience Personality Scale (ANPS), and history of childhood trauma using the Childhood Trauma Questionnaire (CTQ). Suicidal ideation was assessed through the Columbia Suicide Scale for the Rating of Suicide Severity (C-SSRS). The associations with suicidal ideation were tested using two different multivariate models. RESULTS: Over 48 % of participants reported lifetime suicidal ideation and differed on clinical variables from BD-NIS. According to the first model (Wilk's Lambda = 0.72, p < 0.0001), BD-IS scored higher on Panksepp's ANGER and lower on PLAY and CARE than BD-NIS. Both BD-SI and BD-NSI scored higher on ANGER and SEEK and lower on PLAY and CARE than HCs. BD-IS reported more emotional abuse than BD-NIS. They also reported more emotional, sexual, and physical abuse, and emotional neglect than HCs. Only ANGER (OR = 1.13, 95 % CI = 1.01-1.26, Wald = 5.72) and CTQ-Emotional abuse (OR = 1.26, 95 % C.I. = 1.04-1.52, Wald = 5.72) independently predicted suicidal ideation. CONCLUSIONS: Findings support the importance of assessing primary emotional systems and childhood trauma, in particular emotional abuse, in youths with BD at risk for suicide.

What Came First, Mania or Depression? Polarity at Onset in Bipolar I and II: Temperament and Clinical Course.

(1) Background: Bipolar disorder (BD) is divided into type I (BD-I) and type II (BD-II). Polarity at onset (PO) is a proposal to specify the clinical course of BD, based on the type of the first episode at disorder onset-depressive (D-PO) or manic (M-PO). At the same time, affective temperaments represent preexisting variants of the spectrum of affective disorders. Our objectives were to investigate the hypothesis that temperament may exert an influence on PO, and that this factor can serve as an indicator of the forthcoming course of the disorder, carrying significant therapeutic implications. (2) Methods: We included 191 patients with BD and examined clinical variables and temperament; the latter was assessed using the short version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Auto-questionnaire (TEMPS-A-39-SV). We tested the associations between these variables and PO using standard univariate/bivariate methods followed by multivariate logistic regression models. (3) Results: 52.9% of the sample had D-PO and 47.1% had M-PO. D-PO and M-PO patients scored higher for dysthymic and hyperthymic temperaments, respectively (p < 0.001). Also, they differed in BD subtypes, age at first affective episode, illness duration, number of depressive episodes, seasonality, suicide risk, substance use, lithium, and benzodiazepine use (p < 0.05). Only BD-II and age at first depressive episode were predictors of D-PO, whereas BD-I, age at first manic/hypomanic episode, and hyperthymic temperament were predictors of M-PO (p < 0.01). (4) Conclusions: Our findings point to the importance of carefully assessing temperament and PO in patients with BD, to better predict the clinical course and tailor therapeutic interventions to individual patients' needs.

Predictors of polysubstance use in patients with severe alcohol use disorder: the role of reward craving.

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.

Post-COVID-19 Psychiatric Symptoms in the Elderly: The Role of Gender and Resilience.

COVID-19 represents an overwhelming stressor to mental health. Elderly individuals are particularly at risk, but it is still unclear whether the risk is equally distributed among men and women. The aim of this study was to define gender differences in persistent psychiatric symptoms after COVID-19 illness and to test their association with resilience factors. Methods: We assessed 348 individuals aged >65 years at a multidisciplinary post-COVID-19 service. Mood and anxiety symptoms were investigated, as well as psychological distress and resilience, as assessed with the Kessler-10 (K10) Scale and the Connor-Davidson Resilience Scale (CD-RISC), respectively. Multivariate and linear regression analyses were used to test the distribution patterns of psychiatric symptoms and resilience factors. Results: In the total sample, 214 (61.5%) were men (a mean age of 73.25 years ±6.04) and 134 (38.5%) were women (a mean age of 72.69 years ±6.43; p = 0.407). Men and women significantly differed in marital status (χ2 = 25.17; p < 0.001, more men were married), living alone (χ2 = 11.62; p < 0.01, fewer men were living alone), hospitalization during COVID-19 illness (χ2 = 12.35; p < 0.001, more men were hospitalized during COVID-19), and subjective health status before COVID-19 infection (χ2 = 4.32; p < 0.001, men reporting better subjective health than women). Women reported more psychiatric symptoms and fewer resilience factors than men. Low resilience levels significantly predicted psychological distress in both men and women. Conclusions: The female elderly population affected by COVID-19 showed a greater vulnerability to psychiatric symptoms. Our data point to the need to strengthen resilience resources, especially in women.

Suicide Risk in Post-COVID-19 Syndrome.

Post-acute sequelae of COVID-19 include several neuropsychiatric disorders. Little is known about the relationship between post-COVID-19 syndrome and suicidality. The aim of the study was to investigate the risk of suicide in subjects with persistent post-COVID-19 syndrome. One-thousand five-hundred eighty-eight subjects were assessed in the Post-Acute Care Service at the Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS of Rome. Assessment included: (a) sociodemographic characteristics; (b) symptoms during and after COVID-19; (c) psychopathological evaluation. Participants were divided in those with (SUI) or without (NON SUI) suicide risk according to the Mini International Neuropsychiatric Interview. Additionally, subjects with SUI were split into those with high (HIGH SUI) and low (LOW SUI) suicide risk. Between-group comparisons were made with t-tests for continuous variables and χ2 tests for categorical variables. SUI showed greater percentages of physical complaints during and after COVID-19, greater percentages of psychiatric history and presence of psychiatric history in relatives, greater percentages of subjects previously undergoing psychopharmacotherapy, and greater levels of anxiety, mixed depressive symptoms, general psychopathology than NON SUI. HIGH SUI showed greater number of symptoms during and after COVID-19 and higher levels of mixed depressive symptoms than LOW SUI. Percentages of subjects undergoing psychotherapy was higher in LOW SUI than HIGH SUI. Greater levels of physical complaints and psychopathology during post-COVID-syndrome might enhance the risk of committing suicide. Treatment of physical complaints and psychotherapy might reduce suicide risk.

Psychological Distress After Covid-19 Recovery: Reciprocal Effects With Temperament and Emotional Dysregulation. An Exploratory Study of Patients Over 60 Years of Age Assessed in a Post-acute Care Service.

To study the long-term psychological effects of Covid-19 disease, we recruited 61 patients older than 60 years of age and administered the Kessler questionnaire K10 to assess psychological distress and classify them according to mental health risk groups. Patients' affective temperaments were assessed with the 39-item form of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-A-39) and emotional dysregulation with the Difficulties in Emotion Regulation Scale (DERS). Patients were divided in two samples according to their scores on the K10, i.e., a high likelihood of psychological distress group (N = 18) and a low likelihood of psychological distress group (N = 43). The two groups differed on their gender composition, in that more women (N = 11) were in the former and more men in the latter (N = 29) (χ2 = 4.28; p = 0.039). The high likelihood of psychological distress group scored higher on the Cyclothymic (3.39 ± 3.45 vs. 0.93 ± 1.08, p < 0.001) and the Depressive (2.28 ± 2.82 vs. 0.65 ± 1.09, p = 0.01) affective temperaments of the TEMPS and on the lack of Impulse control (12.67 ± 4.04 vs. 9.63 ± 3.14, p = 0.003) and lack of Clarity (15.00 ± 5.56 vs. 9.85 ± 4.67, p = 0.004) scales of the DERS. Our results show that having had Covid-19 may be related with high likelihood for psychological distress in advanced-age people and this may in turn be associated with impaired emotional regulation and higher scores on depressive and cyclothymic temperaments.

Leuprolide acetate: pharmaceutical use and delivery potentials.

INTRODUCTION: Thanks to recent advances in biotechnology, the use of peptides and proteins as drugs has become a concrete clinical reality, and consequently an interesting challenge has emerged for non-parenteral drug delivery. Leuprolide is a synthetic nonapeptide agonist to the luteinizing hormone-releasing hormone (LH-RH) receptor with principal clinical applications for prostate cancer. Although a large number of formulations available, they mainly consist in depot subcutaneous injections or implantable devices. Both of these routes of administration present multiple limitations considering the large clinical applications of this active substance. AREA COVERED: The objective of this review is to critically discuss the formulations currently available on the market for leuprolide optimization and to consider how drug delivery plays an important role in improving the bioavailability of this compound. EXPERT OPINION: Due to its physicochemical properties and its economical market, leuprolide is an interesting candidate for drug delivery to improve the efficacy of existing treatments, dose adjustments, and patient compliance and safety.