Neutrophil to-lymphocyte and platelet-to-lymphocyte ratios as biomarkers for suicidal behavior in children and adolescents with depression or anxiety treated with selective serotonin reuptake inhibitors.

BACKGROUND: Both the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR) have been proposed as biomarkers of suicidal risk in adults with depression. We examined whether these ratios may be considered biomarkers for suicidal behavior in young patients with major depressive or anxiety disorders before treatment with selective serotonin reuptake inhibitors (SSRIs), or as biomarkers for the adverse event of SSRI-associated suicidality. METHODS: Children and adolescents meeting criteria for major depressive or anxiety disorder were recruited. Serum levels of three pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) were assessed; and NLR and PLR calculated, from blood samples collected at baseline and after 8 weeks treatment with SSRI. A Mann-Whitney test was performed to evaluate differences in NLR and PLR between children with and without a history of a suicide attempt prior to treatment. We compared hematological parameters before and after treatment, and between children who developed SSRI-associated suicidality versus children without treatment emergent suicidality. RESULTS: Among 91 children and adolescents (aged 13.9 ± 2.4 years), baseline NLR and PLR were significantly higher among those with a history of a suicide attempt versus those without such history. Statistically significant correlations were found for the suicide ideation subscale in the Columbia suicide severity rating scale with both baseline NLR and PLR. Baseline NLR and PLR were similar in children who did and did not develop SSRI-associated suicidality after 8 weeks. In the final logistic regression model (χ2 = 18.504, df = 4, p value = 0.001), after controlling for sex, depression severity and IL-6 levels, NLR was significantly associated with a past suicide attempt (ß = 1.247, p = 0.019; OR [95% CI] = 3.478 [1.230-9.841]), with a NLR cut-off value of = 1.76 (area under the curve = 0.75 (95% CI = 0.63-0.88, sensitivity = 73%, and specificity = 71%, p value = 0.003). CONCLUSIONS: High NLR and PLR values may be associated with suicidal behavior in depressed and anxious children and adolescents. NLR appears as a better predictor of suicide attempt than PLR, and thus may be a useful biomarker of suicidality in young patients with depression or anxiety.

Tic disorders in children and adolescents: does the clinical presentation differ in males and females? A report by the EMTICS group.

Tic disorders have a strong male predominance, with a male-to-female ratio of 4:1 in Tourette syndrome (TS) and 2:1 in persistent tic disorders. In other neurodevelopmental conditions, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), the disparity in sex distribution has been partially related to differences in symptom presentation between males and females. In tic disorders, however, little research has been conducted on this topic, probably due to the limited access to large samples with a significant proportion of females. The aim of this study was to describe sex differences in the clinical presentation of tic disorders in children and adolescents in one of the largest pediatric samples with TS/persistent tic disorders (n = 709, 23.3% females) recruited as part of the European Multicenter Tics in Children Study (EMTICS). Validated measures assessed the severity of tics and comorbid psychiatric symptoms. Using mixed-effect models, we found that sex had a significant influence on the severity of tics, ADHD symptoms, ASD symptoms, and emotional problems. Males had more severe symptoms than females, except for emotional problems. We also observed a statistically significant interaction between sex and age on the severity of tics and compulsions, with females showing higher symptom severity with increasing age than males. These findings indicate that the clinical presentation of TS/persistent tic disorders varies with sex. Males seem to exhibit a more noticeable pattern of clinical symptoms at a younger age that may contribute to their earlier detection in comparison to females.

Social isolation in mice: behavior, immunity, and tumor growth.

The aim of this study was to investigate the behavioral, immunological, and neurological effects of long-term isolation in an animal model. Male C3H/eB mice wereraised in either social isolation or standard conditions for 6 weeks. At 10 weeks, each group was further divided into 3 sets. (A) Physical strength and behavior were evaluated with the grip strength, hot plate, staircase, and elevated plus-maze tests. Natural-killer cell activity and lymphocyte proliferation were measured. (B) Half the animals were subjected to electric shock with 3 reminders, and freezing time was evaluated at each reminder. Cortisone levels were evaluated after 16 weeks. (C)Mice were injected with 38 C-13 B lymphoma cells and followed for tumor size and survival. Strength evaluation yielded asignificantly lower body weight and grip strength in the socially isolated mice. Behavioral test results were similar in the two groups. The pattern of reactions to stress conditioning differed significantly, with the socially isolated mice showing an incline in freezing with each successive reminder, and the control mice showing a decline. The socially isolated mice had significantly attenuated tumor growth, with no significant difference in survival from control mice. There were no significant between-group differences in immunological parameters. In conclusion, social isolation serves as a model for chronic stress. It was associated with significant changes in stress conditioning reaction, resembling symptoms of post-traumatic stress disorder, and attenuated tumor development. No differences from controls were found in behavior tests, immune parameters, or survival after tumor cell inoculation.Lay summaryThis article explores biological and behavioral consequences of social isolation in a mice model. Our results show that social isolation leads to changes in the Hypothalamic-hypophyseal-adrenal axis, which in turn alter the response to stress. Additionally, social isolation was shown to impact tumor progression.

[THE PRODROME OF PSYCHOTIC DISORDERS].

INTRODUCTION: Psychotic disorders are associated with a severe functional decline and a significant impact on the quality of life. These disorders usually develop gradually, lasting days to months-years. The early phase of psychotic disorders is termed "pre-psychotic" or "prodromal". It is estimated that 30% of the individuals presenting with prodromal symptoms will develop psychosis in three years. This high-risk state is also known as "clinical high risk" (CHR), "ultra-high risk" (UHR), and "at-risk mental state" (ARMS). The diagnostic criteria of high-risk subjects include 3 groups: 1) genetic risk with a functional decline; 2) brief limited intermittent psychotic symptoms group (BLIPS); 3) subthreshold positive psychotic symptoms. In addition to the psychosis risk, these subjects suffer from distress, functional deterioration and psychiatric comorbidities that influence their quality of life. Therefore, many efforts are invested in early identification of the high-risk for psychosis subjects with the primary aim of using interventions to delay or prevent conversion to psychosis. Studies in the field have highlighted specific factors that predict the risk to develop psychosis and even developed predictive models. Interventions including cognitive-behavioral therapy, integrative psychological therapy and pharmacological therapy were found to be associated with postponing the conversion to psychosis. According to current guidelines, cognitive behavioral therapy is the first-choice intervention, and pharmacological interventions should be reserved for patients with comorbidities in need of stabilization of severe and progressive symptoms. Further prospective studies will allow a better identification of high-risk patients and enable the development of interventions for prevention and treatment of this population.

Aggressive symptoms in children with tic disorders.

Episodes of explosive anger and aggression are reported in patients with tic disorders and probably contribute to psychosocial stress and low quality of life. The source of these symptoms is controversial. The objective of the study was to study the relationship between tic disorders, their associated comorbidities, and aggressive behavior. The cohort included 47 children and adolescents (age 7-17 years) with Tourette syndrome or other chronic tic disorders attending a tertiary pediatric Tourette clinic. Associated psychopathology was assessed with the Yale Global Tic Severity Scale, Yale Brown Obsessive Compulsive Scale, Conners ADHD Rating Scale, Screen for Child Anxiety-Related Emotional Disorders, and Child Depression Inventory. Aggression was assessed with the Overt Aggression Scale and scores were compared with a group of 32 healthy age- and sex-matched children. There were no significant differences in aggression scores between the children with tic disorders and controls. Verbal aggression was the most prevalent type of aggression, found in 70% of the patients with tic disorders. The level of aggression was not correlated to tic severity. Comorbid attention-deficit hyperactivity disorder and obsessive-compulsive disorder increased the probability of aggressive behavior in patients with tic disorders. On regression analysis, the only significant predictor of aggression was the severity of attention-deficit hyperactivity disorder. This study suggests that there is no difference in aggressive behavior between children with tics without comorbidities and healthy children. It is possible that aggressive behavior in children with tic disorders is predominantly associated with comorbid attention-deficit hyperactivity disorder.

The Premonitory Urge for Tics Scale in a large sample of children and adolescents: psychometric properties in a developmental context. An EMTICS study.

Premonitory urges are uncomfortable physical sensations preceding tics that occur in most individuals with a chronic tic disorder. The Premonitory Urge for Tics Scale (PUTS) is the most frequently used self-report measure to assess the severity of premonitory urges. We aimed to evaluate the psychometric properties of the PUTS in the largest sample size to date (n = 656), in children aged 3-16 years, from the baseline measurement of the longitudinal European Multicenter Tics in Children Study (EMTICS). Our psychometric evaluation was done in three age-groups: children aged 3-7 years (n = 103), children between 8 and 10 years (n = 253), and children aged 11-16 years (n = 300). The PUTS exhibited good internal reliability in children and adolescents, also under the age of 10, which is younger than previously thought. We observed significant but small correlations between the severity of urges and severity of tics and obsessive-compulsive symptoms, and between severity of urges and ratings of attention-deficit/hyperactivity disorder and internalizing and externalizing behaviors, however, only in children of 8-10 years. Consistent with previous results, the 10th item of the PUTS correlated less with the rest of the scale compared to the other items and, therefore, should not be used as part of the questionnaire. We found a two-factor structure of the PUTS in children of 11 years and older, distinguishing between sensory phenomena related to tics, and mental phenomena as often found in obsessive-compulsive disorder. The age-related differences observed in this study may indicate the need for the development of an age-specific questionnaire to assess premonitory urges.

European Multicentre Tics in Children Studies (EMTICS): protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents.

Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive-compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3-10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3-16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host's immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders.

[EXCORIATION (SKIN-PICKING) DISORDER].

INTRODUCTION: Excoriation (Skin-Picking) disorder is a clinically recognized condition which was recently included in the Diagnostic and Statistical manual of the American Psychiatric Association (DSM) - fifth edition, as OCD (obsessive compulsive disorder) related disorder. The disorder's official status has been achieved due to its high frequency and unique clinical picture involving both mental and physical impairment. In this article, we would like to present a concise review of the literature together with an illustrative case. Epidemiological surveys show a prevalence of 3% to 5% for the general population, with heterogeneous gender and age distribution. In recent years the disorder has been categorized under the family of BFRB's (Body Focused Repetitive Behaviours). However, there are some elements associated with movement suppression and tic disorders, as well as disorders belonging to obsessive-compulsive spectrum. The treatment of this disorder may be pharmacological and/or psychological. There is some evidence for the benefit of some SSRI (Selective Serotonin Reuptake Inhibitors) agents as well as for N-Acetyl-Cysteine. Various psychological treatments have been investigated and some of them have proven to be effective. These include cognitive behavioural protocols, some of which have been developed specifically for this disorder.

A study of sensory dysregulation in children with tic disorders.

Disrupted somatosensory processing characterized by over- or under- responsiveness to environmental stimuli plays an important, yet often overlooked, role in typical development and is aberrant in various neurodevelopmental disorders. These dysfunctional somatosensory processes have been conceptualized as an entity termed somatosensory dysregulation (SMD). Since Tourette syndrome (TS) is a prototypical example of developmental psychopathological disorder, we hypothesised that SMD would be a feature found in children suffering from the disorder. Ninety-two subjects representing consecutive admissions to a tertiary paediatric Tourette syndrome clinic were admitted to the study. Comorbid conditions included ADHD, depression, anxiety disorder, and OCD. For purposes of the study, patients completed a battery of self-, caregiver-, and clinician-rated psychological instruments measuring TS core symptoms and comorbidities and quality of life. Sensory modulation was measured by self-report and by objective measures such as stimulation with Von Frey filaments. Almost 50% of the cohort had no SMD. Of the remainder, 14 (15%) had suspected SMD and 32 (34.8%) had SMD. SMD was significantly more common and severe when there were comorbidities. The presence of SMD was associated with more severe impairments in quality of life and less participation in daily activities. The SMD, as measured by subjective measures but not by objective, is probably more associated with central processing rather than peripheral perception.

Neuroimmunological function in parents of children suffering from cancer.

The main aim of this study is to evaluate the relationship between depression and immunological function in parents of children with cancer. Thirty-two parents participated in the study. The parents completed the following assessments: a list of major stressful events in a Hemato-Oncology ward, beck depression inventory II (BDI-II), posttraumatic diagnostic scale (PDS) and quality of life (QOL) questionnaire. A single blood sample was drawn from parents for evaluation of cortisol levels and lymphocyte cell subgroups. The parents were divided into two groups: Those who suffered from depression as defined by BDI-II cutoff score of 14 (depressed parents (DP), n = 7), and non-depressed parents (non-DP, n = 25). In parents of children with cancer the DP group had statistically significantly higher stressful event scores, dysfunction scores (from the PDS) and CD8 percentage compared to the non-DP group. QOL, CD4 percentage and CD4/CD8 ratio were significantly lower in the DP group. The BDI scores significantly positively correlated with events and dysfunctional scores, and significantly negatively correlated with QOL scores and CD4/CD8 ratio. High psychiatric morbidity was found in parents of children with cancer. The findings of altered immunity in DP provide further evidence that the physiological response to stress and depression may alter immune functions.

Temporally aligned segmentation and clustering (TASC) framework for behavior time series analysis.

Behavior exhibits a complex spatiotemporal structure consisting of discrete sub-behaviors, or motifs. Continuous behavior data requires segmentation and clustering to reveal these embedded motifs. The popularity of automatic behavior quantification is growing, but existing solutions are often tailored to specific needs and are not designed for the time scale and precision required in many experimental and clinical settings. Here we propose a generalized framework with an iterative approach to refine both segmentation and clustering. Temporally aligned segmentation and clustering (TASC) uses temporal linear alignment to compute distances between and align the recurring behavior motifs in a multidimensional time series, enabling precise segmentation and clustering. We introduce an alternating-step process: evaluation of temporal neighbors against current cluster centroids using linear alignment, alternating with selecting the best non-overlapping segments and their subsequent re-clustering. The framework is evaluated on semi-synthetic and real-world experimental and clinical data, demonstrating enhanced segmentation and clustering, offering a better foundation for consequent research. The framework may be used to extend existing tools in the field of behavior research and may be applied to other domains requiring high precision of time series segmentation.

Psychosocial Correlates of Suicidal Ideation and Behavior in Adolescents and Preadolescent Children Discharged from an Emergency Department in Israel.

OBJECTIVES: Adolescent suicidal behavior is highly prevalent in pediatric psychiatric emergency departments, and there is a growing occurrence of such behavior among preadolescent children. This study aims to examine the psychosocial factors associated with nonfatal suicidal behaviors in children (<12 years old) and adolescents (aged 12-18), to gain insight into unique and shared characteristics of suicidal behavior across these two age groups. METHOD: This study investigates the psychosocial characteristics associated with suicidal ideation and behaviors in an emergency department sample of 183 children and adolescents aged 7-18 years in Israel. Participants completed a diagnostic interview, and self-report and parent-report questionnaires of psychosocial measures. Cross-sectional correlational and regression analyses were used to determine significant correlates of suicidal outcomes within the two age groups. RESULTS: Among adolescents, females exhibited a higher prevalence of suicidal thoughts and behaviors, while in children, both boys and girls showed similar rates. Depression correlated with suicidal ideation for both adolescents and children. In children, anxiety and conduct symptoms were associated with suicidal behavior, whereas in adolescents, suicidal behavior was associated with depression and anxiety. CONCLUSIONS: The present findings contribute to the growing understanding of factors associated with suicidal thoughts and behaviors among children in comparison to adolescents. These findings underscore the importance of targeting specific risk factors when developing assessment and intervention strategies tailored to the two age groups.

Suicidal thoughts and behaviors were more common in female adolescents, but similar for boys and girls in children.Different correlates were found for suicidal behavior in children compared to adolescents.This study emphasizes the need for age-specific tailored assessment and intervention.

A Following Wave Pattern of Suicide-Related Pediatric Emergency Room Admissions during the COVID-19 Pandemic.

The COVID-19 pandemic and response, which included physical distancing and stay-at-home orders, disrupted the daily lives of children and adolescents, isolating them from their peers, school, and other meaningful contacts. The present study aims to add to the accumulating evidence on the pandemic's impact on child and adolescent suicidal behavior. Data were extracted from Schneider Children's Medical Center of Israel's pediatric emergency room (ER) admissions for psychiatric consultation for suicidal-risk assessment between 1 January 2020, and 16 April 2022. We applied time-lagged cross-correlation analysis and a Granger causality test to assess the temporal relationships between COVID-19 infection waves and patterns of suicide-related ER admissions. The results revealed a significant lagged correlation between national COVID-19 infection rates and ER admission rates. The highest correlation was above 0.4 and was found with a lag of 80 to 100 days from infection rate to ER admission rate. The findings show that the effects of public crises change over time and may be lagged. This may have important implications for mental health services' readiness to serve growing numbers of children and adolescents at risk for suicide.

Moderating Role of Depression on the Association of Tic Severity With Functional Impairment in Children.

BACKGROUND: Chronic tic disorders (CTDs) commonly co-occur with other psychiatric disorders. CTDs have been linked to functional impairment and reduction in quality of life. Insufficient research is available on depressive symptoms in patients with CTD, especially children and adolescents, yielding conflicting findings. To investigate the presence of depressive symptoms in a cohort of children and young adolescents with CTD and to test whether they moderate the link between tic severity and functional impairment. METHODS: The sample consisted of 85 children and adolescents (six to 18 years) with a CTD who were treated in a large referral center. Participants were evaluated using gold-standard self- and clinician-reporting instruments to measure tic symptom severity and tic-related functional impairment (Yale Global Tic Severity Scale), depression (Child Depression Inventory), and obsessive-compulsive symptoms (Children Yale Brown Obsessive Compulsive Scale). RESULTS: Depressive symptoms (mild to severe) were exhibited by 21% of our sample. Study participants with CTD and comorbid obsessive-compulsive disorder (OCD) and/or attention-deficit/hyperactivity disorder had higher rates of depressive symptoms compared with those without comorbidities. Significant correlations were found within and among all tic-related and OCD-related measures, yet depressive symptoms only correlated to tic-related functional impairment. Depression significantly and positively moderated the correlation between tic severity and tic-related functional impairment. CONCLUSIONS: Findings suggest that depression plays an important part as a moderator in the link between tic severity and functional impairment in children and adolescents. Our study highlights the importance of screening for and treating depression in patients with CTD.

Implicit Identification with Death, Clinician Evaluation and Suicide Ideation among Adolescent Psychiatric Outpatients-The Mediating Role of Depression.

Implicit identification with death (i.e., subconsciously self-associating oneself with death), measured by the Death-Suicide Implicit Association Test (D/S-IAT), is associated with Suicide Ideation (SI). Our understanding of the mechanisms underlying this association is limited. The current study examined (1) the mediating role of depression between D/S-IAT and recent SI and (2) the association between SI, D/S-IAT, and clinician evaluation of SI among a clinical sample of adolescents. 148 adolescents aged 10-18 years (69.4% female) from two outpatient clinics were assessed at intake. Participants completed D/S-IAT and self-report measures for recent SI and depression during intake. Findings indicate that depression is a mediator between D/S-IAT and recent SI, controlling for gender, site differences, and past suicidal thoughts and behaviors. D/S-IAT and clinician evaluation were correlated with recent SI but not beyond depression. Our findings highlight the importance of examining the underlying psychological mechanisms regarding the association between D/S-IAT and suicide.

Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome.

BACKGROUND: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year. METHODS: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants. RESULTS: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume. CONCLUSIONS: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.

Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome.

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.

Atypical anorexia nervosa: Rethinking the association between target weight and rehospitalization.

OBJECTIVE: Bodyweight restoration is one of the most important targets in adolescent inpatient treatment of anorexia nervosa (AN). This study examined the association between achieving target weight and rehospitalization in two groups of adolescents with AN and atypical anorexia nervosa (AAN) admitted to a specialized inpatient unit. METHOD: Included were 202 adolescent patients hospitalized in a specialized eating disorder unit, 10-18 years old. One hundred fifty-four adolescents were diagnosed with AN, and 48 with AAN. We examined the patients' demographic and clinical characteristics, the achievement of treatment goals, and their rehospitalization history within a year of discharge from the unit. RESULTS: Log-linear regression indicated a significant association between achieving target weight during the inpatient program and rehospitalization at one-year follow-up in the AN group; this association was not significant in the AAN group. DISCUSSION: This study emphasizes the importance of differentiating patients with AAN from those with classical AN. Specifically, it raises questions about the predictive power of target weight at discharge in preventing relapse and its centrality in determining AAN patients' treatment plans.

Psychopharmacology in the Pediatric Oncology and Bone Marrow Transplant Units: Antidepressant Treatment.

Objectives: The aim of this study was to characterize the clinical profiles, tolerability, and efficacy of two groups of antidepressants, selective serotonin reuptake inhibitors (SSRIs), and the atypical antidepressant, mirtazapine, in children and adolescents treated in a large pediatric Hematology-Oncology center. Methods: A review of computerized medical charts of 32 pediatric patients with cancer, from December 2011 to April 2020, was conducted. Efficacy and tolerability of antidepressant medications were retrospectively analyzed. The Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) Scales were used to evaluate psychiatric symptoms severity before and following treatment, while the data on adverse events and drug-drug interactions were retrieved from the computerized medical records. Results: Thirty-two children and adolescents with cancer, 2-21 years of age (mean 14.1 ± 4.6 years), were treated with antidepressants. Fourteen patients (44%) received mirtazapine, whereas 18 patients (56%) received SSRIs: sertraline (25%), escitalopram (25%), or fluoxetine (6%). Treatment choice was dictated either by physician preference or informed by potential drug-drug interactions. The most common psychiatric diagnoses were major depressive disorders (47%), anxiety disorders (19%), and medication-induced psychiatric disorders (19%). The most common psychiatric-medical symptoms were depressed mood (94%) and anxiety (62%). CGI-S improved significantly (p < 0.05) between pretreatment and on-treatment assessments, with no statistically significant difference between SSRI and mirtazapine-treated patients. CGI-I scores at reassessment indicated improvement in most patients (84%). Adverse events of treatment were mild in all patients. Conclusions: The antidepressants used in this study, SSRIs and mirtazapine, were effective and well tolerated in children and adolescents with cancer and psychiatric comorbidities. Given the high rates of depression and anxiety in children with cancer, large-scale, multisite, prospective clinical trials of antidepressants are warranted.

Stress conditioning in mice: alterations in immunity and tumor growth.

The neuroendocrine and autonomic nervous systems are known regulators of brain-immune interaction. However, the functional significance of this interaction under stress is not fully understood. We investigated the effect of a stress paradigm by applying electric foot shock followed by three reminders, on behavior, immune parameters, and lymphoma tumor growth. Male C3H mice were divided into two groups: Group 1-exposed to electric foot shock followed by three reminders, and Group 2-untreated (controls). Sets of mice underwent the elevated plus maze, staircase, and hot plate tests. After foot shock, natural killer (NK) cell activity, and lymphocyte proliferation were measured. In addition, sets of mice were either vaccinated twice with B-cell lymphoma 38C-13 immunoglobulin for determination of anti-idiotype (Id) antibodies in sera, or inoculated with tumor cells and monitored for tumor development and survival time. Mice exposed to electric foot shock followed by the three reminders had higher NK cell activity, levels of anti-Id antibodies, and a higher proliferation rate of splenocytes in response to mitogens, than the control mice. The exposed mice also showed attenuated tumor growth. Thus, the stress paradigm inhibited tumor development and lead to some immune changes that were not accompanied by behavioral changes.