Effect of Time From Onset of Major Depressive Disorder on the Therapeutic Response to Esmethadone (REL-1017).

Objective: The relationship between the duration of major depressive disorder (MDD) and therapeutic response to standard antidepressant treatment (SAT) is unknown. N-methyl-D-aspartate receptor uncompetitive antagonists are emerging drugs for MDD. We investigated whether the antidepressant effect of esmethadone (REL-1017) could be related to the duration of depression.Methods: We analyzed data from a Phase 2a study of adjunctive treatment with esmethadone in MDD patients (DSM-5) with inadequate response to ongoing SAT (May 2018-August 2019). Patients were randomized to treatment with esmethadone 25 mg, esmethadone 50 mg, or placebo for 7 days, followed by an observation period (Days 7-14). Duration of depression was derived from 2 measures: (1) time from onset (TFO), calculated as the difference in years between age at trial enrollment and age at the onset of the first major depressive episode (MDE), and (2) TFO index, calculated by computing the years of illness duration (number of years from the beginning of MDD), divided by age and multiplied by 100. First, bivariate correlations between TFO and change from baseline (CFB) were calculated by Spearman ρ. Linear mixed-model analyses were also conducted.Results: A total of 62 patients participated in the trial. The median values of time from MDD onset for the 62 patients were 11 years (absolute value) and 22% (percentage of life-years). Duration of depression was significantly correlated with Montgomery-Asberg Depression Rating Scale (MADRS) CFB on Day 14, even when controlling for the effect of current depression severity (MADRS baseline). In the linear mixed-model analyses, we found a significant effect of duration on reduction in MADRS score from T0 to subsequent assessments (P < .05). Number of previous MDEs and effect of esmethadone 50 mg when compared to 25 mg were not significant.Conclusion: Esmethadone 25 and 50 mg were more effective in reducing MADRS scores in patients with shorter time from first MDE onset.Trial Registration: ClinicalTrials.gov identifier: NCT03051256.

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.

Neurocognitive and adaptive phenotypes in adolescent inpatients with mood disorders: an exploratory study on disruptive mood dysregulation disorder in the framework of depressive disorders.

Introduction: Few studies on adolescents have investigated intelligence quotient (IQ) in mood disorders. Evidence on Disruptive Mood Dysregulation Disorder (DMDD), a controversial entity among depressive disorders, is more limited. Materials and methods: We performed an exploratory study on adolescent inpatients with unipolar mood disorders to test specific impairment in cognitive and adaptive profile. We also considered common psychopathological comorbidities. We retrospectively collected data on inpatients with a diagnosis of major depressive disorder (MDD), DMDD or Depressive Disorder - Not Otherwise Specified (DD-NOS) evaluated with Wechsler Scales of Intelligence, Adaptive Behavior Assessment System (ABAS-II), and Children's Global Assessment Scale (C-GAS). Results: Out of 198 inpatients (85.9% females), 33.3% had MDD, 60.1% DD-NOS and 6.6% DMDD. DMDD patients had higher rates of ADHD (15.4%) and learning disorders (LD, 23.1%), a lower mean IQ (87.8 ± 10.7; p = 0.001) and ABAS-II scores (general composite 68.8 ± 16.8; p = 0.002) than other groups. In linear regression analysis, DMDD retained a significant correlation with lower IQ and adaptive abilities when controlling for sex, and comorbidities. Among comorbidities, LD correlated with lower perceptual reasoning and IQ, and ADHD with lower conceptual adaptive abilities. In all diagnosis groups, working memory and processing speed were lower than verbal comprehension and perceptual reasoning. Discussion: While impairment in working memory and processing speed is a non-specific correlate of active mood disorder, DMDD is burdened by lower general intelligence and adaptive abilities and higher rate of neurodevelopmental comorbidities. Lower IQ in the normal range is a correlate of DMDD among variables examined, not explained by the effect of neurodevelopmental comorbidities. These findings are discussed with regards to possible implications for the consideration of DMDD as a bridge condition between neurodevelopmental disorders and mood disorders.

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.

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.

Long term follow-up of scoliosis progression in type II SMA patients.

The aim of this study is to retrospectively assess onset and progression of scoliosis in type II SMA patients not treated with the approved disease modifying treatments. Scoliosis was evaluated by measuring the scoliosis angle on X-ray obtained in the anteroposterior view in sitting position (Cobb's angle method). Eighty-four patients had at least one assessment of scoliosis angle (287 assessments). There was a positive correlation between age and scoliosis angles (p<0.001) with a progressive increase of scoliosis with age. When subdividing the population by HFMSE score (<10; 11-22;> 22), there was a progressive increase in scoliosis angles with decreasing HFMSE scores. The difference between HFMSE categories was significant (p<0.001). Fifty-four patients had at least two assessments at 6-month distance and were retained for the longitudinal analysis. Using a mixed model, age, functional status and scoliosis angle at baseline were predictive on scoliosis progression. The mean annual rate of increase of scoliosis angle was 5.63 (95%CI: 4.74-6.52). Our results confirm the progression of scoliosis in untreated type II SMA providing details of the progression in relation to different variables. With different therapeutical options being available in many countries, our findings will provide reference data for establishing possible differences in the trajectories of progression with treated type II individuals.

Hammersmith Infant Neurological Examination in low-risk infants born very preterm: a longitudinal prospective study.

AIM: To describe the profile of global and single items of the Hammersmith Infant Neurological Examination (HINE) in a population of low-risk infants born very preterm during the first year of life. METHOD: The HINE was performed at 3, 6, 9, and 12 months' corrected age in a population of low-risk infants born preterm with a gestational age of fewer than 32 weeks and with normal or minimal changes on neuroimaging. RESULTS: A total of 174 infants born preterm (96 males, 78 females; mean gestational age = 27 weeks [SD = 1.8], range 23-31 weeks) fulfilled the inclusion criteria. The 10th centile cut-off score with median and range was reported for the HINE global and subsection scores. A progressive increase in global HINE scores was observed. Most of the single items, especially those related to tone, posture, and reflexes, showed progressive maturation. INTERPRETATION: Our results, which provide longitudinal data for single-item and global scores in a population of low-risk infants born very preterm, can be used as a reference in both clinical and research settings to monitor early neurological signs in these infants. These data could be used as normative data when examining low-risk infants born preterm.

The social smile in infants during the COVID-19 pandemia.

The emergency created by Coronavirus disease 2019 (COVID-19) has inevitably changed human normal social and relational habits. The use of personal protective equipment, like surgical masks, by healthcare workers has been recommended to prevent human-to-human transmission of the novel coronavirus infection. However, the use of these masks could cause slight to considerable and reproducible changes in the infant's attitude towards the operator and health taker during routine clinical assessments. We reported a brief report on the impact of to the use of the surgical masks on the affective behaviour in 40 infants of age 2-9 months (study group) by using a scale to assess pain and distress among pediatric patients, the Face, Legs, Activity Cry and Consolability Scale (FLACC), and in 40 infants with the same ages and characteristics assessed before the COVID-19 pandemia onset (control group). Thirty-seven of the 40 infants in the study group had some signs of discomfort and appeared irritable and less prone to be engaged by the examiner with a different pattern of responses related to age with better responses for younger infants. These infants reported higher significant scores (p < 0.001) in the FLACC scale than those assessed before the COVID-19 onset. Infants appear to react negatively to the use of the surgical mask by the health operator. A different way to assess paediatric patients in early infancy with longitudinal studies should be proposed.

Sleep Disorders in Autism Spectrum Disorder Pre-School Children: An Evaluation Using the Sleep Disturbance Scale for Children.

Background and Objectives: Sleep disorders are common in children with Autism Spectrum Disorder (ASD). The aims of this study were to describe the incidence and characteristics of sleep disorders using a questionnaire completed by the caregiver in a sample of preschool-aged children with ASD and to identify possible differences in a control group of peers. Materials and Methods: Sleep disorders were investigated with the Sleep Disturbance Scale for Children (SDSC) in a population of pre-school-aged (3-5 years) ASD children and in a control group. The Autism Diagnostic Observation Schedule-second ed. (ADOS-2) was further used to assess autism symptom severity. A total of 84 children (69 males; mean age 3.9 ± 0.8 years) with a diagnosis of ASD and 84 healthy controls (65 males; mean age of 3.7 ± 0.8 years) that were matched for age and sex were enrolled. Results: ASD children reported significantly higher (pathological) scores than the control group on the SDSC total scores and in some of the factor scores, such as Difficulty in Initiating and Maintaining Sleep (DIMS), disorders of excessive somnolence (DOES), and sleep hyperhidrosis. A total of 18% of ASD children had a pathological SDSC total T-score, and 46% had an abnormal score on at least one sleep factor; DIMS, parasomnias, and DOES showed the highest rates among the sleep factors. Younger children (3 years) reported higher scores in DIMS and sleep hyperhidrosis than older ones (4 and 5 years). No specific correlation was found between ADOS-2 and SDSC scores. Conclusions: Pre-school children with ASD showed a high incidence of sleep disorders with different distributions of specific sleep factors according to their age. We suggest a screening assessment of sleep disorders using the SDSC in these children with a more in-depth evaluation for those reporting pathological scores on the questionnaire.

Valacyclovir in primary maternal CMV infection for prevention of vertical transmission: A case-series.

BACKGROUND: No treatment is currently approved for cytomegalovirus infection in pregnancy. Valacyclovir has been studied in symptomatic cytomegalovirus infected fetuses and seems to reduce the risk of serious sequelae. OBJECTIVES: We used off-label valacyclovir on pregnant women with primary cytomegalovirus infection to reduce the risk of fetal infection. STUDY DESIGN: We treated 12 pregnant women with 8 g/day valacyclovir after diagnosis of cytomegalovirus infection until amniocentesis. We continued treatment until delivery in case of fetal infection. We periodically performed serology and virology tests on the women from referral until delivery and monitored them for adverse effects while on treatment. All women underwent late amniocentesis. We followed up infants for 5-28 months. RESULTS: At the time of amniocentesis, we observed a transmission rate of 17 %, and at birth we observed a transmission rate of 42 %. Two women with negative amniocentesis and infected newborns had viremia reactivation after valacyclovir discontinuation. We observed no symptomatic infections at birth and one isolated sensory-neural hearing loss at follow-up. CONCLUSIONS: This is the first series of antiviral treatment in women with a diagnosis of cytomegalovirus infection before amniocentesis. Valacyclovir may control cytomegalovirus infection while it is administered and reduce transmission at amniocentesis. Late transmission after treatment discontinuation is a risk. We advocate the need for a controlled trial of valacyclovir therapy starting from diagnosis of maternal infection until delivery, regardless of prenatal diagnosis of infection.

Chronic exposure to high doses of selenium in the first trimester of pregnancy: Case report and brief literature review.

BACKGROUND: Obstetricians usually prescribe supplements during pregnancy without actual indication. The use of selenium during pregnancy has increased, due to its function in several antioxidant mechanisms. CASE: A pregnant woman received 200,000 micrograms (µg) per day of a selenium galenic formulation, since gestational week (g.w.) 7 to 12, due to a prescription error. The patient experienced nausea, vomiting, hand and foot paresthesia, followed by fatigue, loss of fingernails and hair. The woman was referred to our Fetal and Maternal Medicine Unit for surveillance. The mother's blood selenium levels went back to normal 13 weeks after arrest and the baby was born at term, without complications. Clinical evaluation and imaging studies were normal at one month of age. CONCLUSION: This is the first case of severe chronic selenium intoxication during the first trimester of pregnancy. In the present case, no consequences of congenital defects or pregnancy complications occurred. However, since vitamins, minerals, and food supplements may be harmful and prescription errors occur, obstetricians should avoid prescribing supplements in the absence of maternal deficiency.