Factors Associated with High Parent- and Youth-Rated Irritability Score in Early-Onset Mood Disorders: A Cross-Sectional Study with the Affective Reactivity Index (ARI).

Correct classification of irritability is extremely important to assess prognosis and treatment indications of juvenile mood disorders. We assessed factors associated with low versus high parent- and self-rated irritability using the affective reactivity index (ARI) in a sample of 289 adolescents diagnosed with a bipolar or a major depressive disorder. Bivariate analyses were followed by multilinear logistic regression model. Factors significantly and independently associated with high versus low parent-rated ARI score were: more severe emotional dysregulation and bipolar disorders diagnosis. Factors significantly and independently associated with high versus low self-rated ARI score were: lower children depression rating scale (CDRS-R) difficulty of having fun item score, greater children depression inventory (CDI-2) self-report score, more severe emotional dysregulation, and greater CDRS-R appetite disturbance item score. High parent-rated irritability was strictly related with a bipolar disorder diagnosis, whereas high youth-rated irritability was related to depressive phenotype characterized by appetite/food-intake dysregulation, mood lability, and less anhedonia and apathy.

Childhood Clinical Features Preceding the Onset of Bipolar Versus Major Depressive Disorders During Adolescence.

OBJECTIVE: To identify childhood psychopathological features that predict the onset of adolescent Bipolar (BD) versus Unipolar Major Depressive Disorder (UD) during adolescence. METHOD: We analyzed clinical data from 495 juveniles diagnosed with DSM-5 UD (n = 359), and BD (n = 136), using bivariate analysis and multivariate logistic regression model. RESULTS: BD subjects exhibited earlier onset of any psychiatric feature compared to UD. Antecedents associated with later BD were: oppositional defiant > specific phobias > ADHD > obsessive compulsive (OCD). Antecedents selectively associated with later UD were: social anxiety and separation anxiety. Factors significantly and independently associated with later BD diagnosis were: [a] emotional dysregulation at onset of the mood disorder; [b] first depressive episode with mixed features; [c] antecedent ADHD; [d] antecedent OCD, and [e] antecedent oppositional-defiance. CONCLUSION: Identifying developmental differences in BD and UD symptoms can aid clinicians in early identification and treatment planning for bipolar disorder in youth.

Urgent Psychiatric Consultations for Suicidal Ideation and Behaviors in Italian Adolescents during Different COVID-19 Pandemic Phases.

Access to the emergency department (ED) for acute psychiatric problems, especially for suicide attempts (SA), has increased in the last decade. This increase has exceptionally accelerated after the COVID-19 pandemic. The aim of this project was to study the increase in acute psychiatric care demand of children and adolescents in the short and medium term after the pandemic, in relation to public health measures and in comparison with a pre pandemic reference period. We retrospectively studied 5445 child psychiatric (CP) consultations requested for any reason and for suicide attempt (SA), suicidal ideation (SI) and non-suicidal self-injury (NSSI) in a pediatric ED during three different pandemic periods in Italy (from March 2020 to May 2022) and compared them to a pre-pandemic reference period (from January 2018 to February 2020). Monthly CP consultations for any reason increased significantly by 2.2 times from 70.9 in 2018 to 157 in 2022 (p < 0.001). During the pandemic, monthly CP consultations for any reason increased significantly from 75/month in the first lockdown to 153/month in the second lockdown, remaining stable in the following year. CP consultations for SA increased significantly from 5/month in the first lockdown to 16/month in the second. Consultations for SI increased gradually but significantly from the pre-pandemic period to the end of the pandemic. Juveniles evaluated for SA during the pandemic vs. pre-pandemic more frequently attempted suicide by self-poisoning and less frequently by precipitation, and they were more likely to be diagnosed with a major depressive disorder. CP consultations for any reason and for suicide attempts significantly increased in the decade before the pandemic and peaked in the second lockdown period in Italy.

Urgent psychiatric consultations for suicide attempt and suicidal ideation before and after the COVID-19 pandemic in an Italian pediatric emergency setting.

Introduction: Suicidal attempts (SAs) in youth have been increasing during the last decades. Methods: We studied consultations, SA, and suicidal ideation (SI) in a pediatric emergency department (ED). Results: From 1 January 2011 to 31 May 2022, 606,159 patients accessed the ED, 8,397 of who had a child psychiatry consultation (CPC). CPCs increased significantly by 11 times in the last decade (155 in 2011 vs. 1,824 in 2021, p < 0.001); CPCs for SA increased significantly by 33 times, from 6 in 2011 to 200 in 2021 (3.9% of total CPC vs. 11%, p < 0.001). While total CPCs increased constantly during the entire period (annual percent change (APC) of 21.7 from 2011 to 2021 in a 0 joinpoint model), CPCs for SA increased significantly from 2011 to 2016, were approximately stable from 2016 to 2020, and then had a peak in 2021 after the COVID-19 pandemic (APC from 2011 to 2016 of 64.1, APC of 1.2 from 2016 to 2020, and APC of 230 after 2020 in a 2-joinpoint model). Discussion: Total CPCs in ED as well as evaluation for SA and SI increased significantly during the last decade. CPCs for SA had an additional increase after the COVID-19 pandemic. This picture warrants timely and efficient improvements in emergency settings and mental health resources.

Subanalysis of Subjective Cognitive Measures From a Phase 2, Double-Blind, Randomized Trial of REL-1017 in Patients With Major Depressive Disorder.

Objective: Improvement of cognitive function in patients with major depressive disorder (MDD) is an important treatment outcome. REL-1017 (esmethadone HCl) is a novel N-methyl-d-aspartate receptor (NMDAR) channel blocker and a potentially rapidly acting antidepressant. The objective of this study was to define the effects of REL-1017 on subjective cognitive measures in patients with MDD.Methods: Post hoc analysis was conducted of subjective cognitive measures from the Montgomery-Asberg Depression Rating Scale (MADRS) and the Symptoms of Depression Questionnaire (SDQ) from a randomized, double-blind, placebo-controlled, Phase 2a study. The study, designed to assess the safety, tolerability, and efficacy of 2 dosages (25 mg and 50 mg) of REL-1017 as an adjunctive treatment in patients with MDD unresponsive to standard antidepressants, included 62 patients. We analyzed subjective cognitive measures derived from the MADRS and SDQ scales at baseline and up to day 14, 7 days after the last dose of study drug. We developed 2 composite indexes that included subjective cognitive measures selected from the MADRS and SDQ.Results: The subanalysis of single measures and the 2 composite indexes derived from the MADRS and SDQ measures showed clinically meaningful and statistically significant improvements in cognitive function (P < .05).Conclusions: In a Phase 2a clinical trial, REL-1017 improved subjective measures of cognitive impairment, in addition to improving total MADRS and SDQ scores. These results need to be confirmed in larger and longer studies in MDD that include objective measures of cognitive function. Phase 3 studies of REL-1017 for MDD are currently underway.Clinical Trials Registration: ClinicalTrials.gov identifier: NCT03051256.

Gender Differences in the Psychopathology of Mixed Depression in Adolescents with a Major Depressive Episode.

BACKGROUND: Gender differences have been reported in the severity and psychopathological features of major depressive disorders among adults but are poorly reported in adolescent samples. OBJECTIVE: This study aimed to examine gender differences in the psychopathology of mixed depression among adolescents. METHODS: We analyzed 341 outpatients with the current major depressive episode (MDE) retrospectively to identify patients with DSM-5 MDE with mixed features. We compared examiner-rated depressive and (hypo)manic symptoms and self- and parent-reported symptoms between sexes. RESULTS: We identified 76 patients with an MDE with mixed features (67.1% females, 32.9% with bipolar disorder). Depression severity was significantly greater in females versus males (CDRS-R total score 56.2 vs. 48.2, p = 0.014). Depressive symptoms were significantly and independently found to be more severe among females in a logistic regression model, including excessive fatigue (OR 1.68; p = 0.025), low self-esteem (OR 1.67; p = 0.04), excessive weeping (OR 1.62; p = 0.021), and CBCL AAA index (OR 1.04; p = 0.015). None of the depressive symptoms scored greater in males. Males had higher levels of motor activity (2.12 vs. 1.69; p = 0.048) and pressured speech (1.80 vs. 1.24; p = 0.004). Self-rated anxiety (69.3 vs. 56.8, p = 0.047) and CBCL AAA index (207 vs. 189; p = 0.007) were higher in females. CONCLUSION: Adolescent depression with mixed features is more severe in women, with a higher expression of core affective symptoms and excessive fatigue. While in males, slightly higher levels of psychomotor activation are reported, in females, emotional dysregulation and excessive weeping may subtend a difference in a broader spectrum of mixed features.

Suicidal behavior in juvenile bipolar disorder and major depressive disorder patients: Systematic review and meta-analysis.

OBJECTIVE: To assess rates and lethality of suicidal behavior in studies of children and adolescents diagnosed with major depressive disorder (MDD) or bipolar disorder (BD). METHODS: This PROSPERO-registered protocol (CRD-42019159676) systematically reviewed reports on suicidal behavior among juveniles (age ≤ 18 years), and pooled data on risk (% of subjects) and rates (%/year), followed by random-effects meta-analysis and multivariable linear regression modeling. RESULTS: Included were 41 reports (1995-2020) from 15 countries involving 104,801 juveniles (102,519 diagnosed with MDD, 2282 with BD), at risk for 0.80-12.5 years. Meta-analytically pooled suicide attempter-rates averaged 7.44%/year [95%CI: 5.63-9.25] with BD and 6.27%/year [5.13-7.41] with MDD. Meta-analysis of 5 studies with both diagnostic groups found significantly greater attempt risk with BD vs. MDD (OR = 1.59 [1.24-2.05], p < 0.0001). In 6 studies, suicide rate with juvenile mood disorders averaged 125 [56.9-236]/100,000/year, similar to adult rates, >30-times greater than in the general juvenile population, and higher among older adolescents. The ratio of attempts/suicides (A/S) was 52.6 among mood-disordered juveniles, indicating greater lethality than among juveniles in the general population (A/S ≥ 250), but somewhat less than in the estimated adult general population (A/S ca. 30). CONCLUSIONS: Rates of suicide attempts in juveniles with a major mood disorder averaged 6580/100,000/year, were greater in BD versus MDD observed under the same conditions, and greater with shorter periods of observation. Lethality (fatalities per suicide attempt) was greater in juveniles diagnosed with major affective disorders than in the juvenile general population, but less than in adults.

Characteristics Associated with Depression Severity in 270 Juveniles in a Major Depressive Episode.

Introduction: Severe depression is prevalent in young persons and can lead to disability and elevated suicidal risk. Objectives: To identify clinical and demographic factors associated with the severity of depression in juveniles diagnosed with a major mood disorder, as a contribution to improving clinical treatment and reducing risk of suicide. Methods: We analyzed factors associated with depression severity in 270 juveniles (aged 6-18 years) in a major depressive episode, evaluated and treated at the Bambino Gesù Children's Hospital of Rome. Depressive symptoms were rated with the revised Children's Depression Rating Scale (CDRS-R) and manic symptoms with the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) Mania Rating Scale (K-SADS-MRS). Bivariate comparisons were followed by multivariable linear regression modeling. Results: Depression severity was greater among females than males (55.0 vs. 47.2), with the diagnosis of a major depressive disorder (MDD) vs. bipolar disorder (BD; 53.8 vs. 49.3), and tended to increase with age (slope = 1.14). Some symptoms typical of mania were associated with greater depression severity, including mood lability, hallucinations, delusions, and irritability, whereas less likely symptoms were hyperactivity, pressured speech, grandiosity, high energy, and distractibility. Factors independently and significantly associated with greater depression severity in multivariable linear regression modeling were: MDD vs. BD diagnosis, female sex, higher anxiety ratings, mood lability, and irritability. Conclusions: Severe depression was significantly associated with female sex, the presence of some manic or psychotic symptoms, and with apparent unipolar MDD. Manic/psychotic symptoms should be assessed carefully when evaluating a juvenile depressive episode and considered in treatment planning in an effort to balance risks of antidepressants and the potential value of mood-stabilizing and antimanic agents to decrease the severity of acute episodes and reduce suicidal risk.