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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.

Both attempted and fatal suicides are important public health issues and the relationship between these behaviors has great relevance to clinical practice.To determine how the epidemiology of attempted and fatal suicide relate to each other over time.In an 18-year period consecutive admissions for suicide attempts (The relative rates of attempted and fatal suicide changed over time independent of both age and gender up to age 64. Rates of suicide and attempted suicide did not correlate over time in this age group. This was not true for the over 65 age group where attempted suicide and fatal suicide were significantly correlated over time in both men and women.In subjects over 65 attempted suicide is highly associated with eventual suicide. This relationship is much less clear in younger age groups. Thus age of attempt is of great importance when considering the prognostic import of a suicide attempt.

The rate of youth suicidal behaviors has gradually increased over the last 15 years and continues to grow during the COVID-19 pandemic. This trend burdens mental health services and demands significant developments in risk detection and delivery of interventions to reduce the risk. In this article we outline significant advances and recent findings in youth suicide research that may facilitate strategies for identifying and preventing suicide risk among youth at risk in general and in specific risk groups.The rise in suicide and suicidal behaviors is most likely to affect young people of racial, ethnic, sexual, and gender identity minorities and those living in poverty or experiencing maltreatment. The suicide rate in children is rising and demands special attention. Proximal risk factors for suicidal behavior compared with suicidal ideation have been suggested to identify near-term suicidal risk. Effective and scalable prevention strategies were identified, and the role of new technologies in suicide prevention among youth is to be determined.To reach broader suicide prevention in youth and reduce the pressure on mental healthcare, public health approaches and improved service access for minority youth and those living in underserved areas of the world are needed.

Introduction: Exposure to a range of stressful life events (SLE) is implicated in youth psychopathology. Discrepancy between parents’/children’s’ reports (especially regarding SLE) is a major concern in child psychiatry. This study was designed to assess parent–youth discrepancies regarding SLE and its association with severity of psychopathology at baseline and response to treatment. Additionally, we assessed the association between three plasma pro-inflammatory cytokine levels and SLE. Methods: SLE were assessed in children/adolescents suffering from depressive/anxiety disorders using the life events checklist (LEC), a self-report questionnaire measuring the impact of negative life events (NLE) and positive life events (PLE), as reported by the children and their parents. Severity of depression/anxiety disorders and response to antidepressant treatment were evaluated and correlated with both measures of LEC. We also corelated SLE with levels of three pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). Results: Participants were 96 parent-child dyads (39 boys, 57 girls) aged 6-18 (mean=13.90, SD=2.41y). Parents reported higher severity of NLE than their children. Discrepancy in PLE was associated with more severe psychopathology and reduced response to treatment. No association with cytokine levels was found. Discussion: Discrepancy in informant reports regarding life events in depressed/anxious youth, especially regarding PLE, is associated with more severe psychopathology and reduced response to pharmacotherapy. It is important to increase congruency regarding SLE between parents and children to improve response to treatment.

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.

Tic disorders (TD) are developmental neuropsychiatric conditions often accompanied by comorbid conditions, and psychosocial hardships for child and family. The etiology of tics is unknown, and is complex and multifactorial. Stress is known to aggravate tic expression as well as associated comorbidities. Consequently, this study focused on possible connections between stress, emotion regulation, tic expression, and related psychopathology. Sixty consecutive admissions were assessed for perceived stress, emotional dysregulation, severity of obsessions and compulsions, anxiety, depression, attention deficit disorder, and tic expression at a TD clinic, in a university affiliated pediatric hospital. The results indicated that stress and emotion dysregulation were significantly related to both tic expression and severity of comorbidities. We discuss the role of emotion regulation dimensions regarding TD and related psychopathology as well as the mediating role of emotion regulation, and how they may contribute to the development of improved therapies for children with TD.

Adolescent suicidal behavior is the most common reason adolescents present to the emergency department in pediatric hospitals. Recently, suicidal behavior has become more common in preadolescent children. It is important to understand the underlying nature of non-fatal suicidal behavior in children and how they may differ from adolescent to implicate unique prevention and management for this population. The current study aims to investigate the psychosocial characteristics associated with suicidal ideation and behaviors in an emergency department sample of 183 children and adolescents aged 7–18. All participants completed a diagnostic interview, self-report and parent-report questionnaire of psychosocial risk factors. Cross-sectional correlational and regression analyses were used to determine significant correlates of suicidal outcomes within the two age groups. The results indicated that among adolescents, suicidal thoughts and behavior were more common in females compared to males, while among children, the prevalence of males and females was similar. Depression was correlated with suicidal ideation for both adolescents and children. Moreover, anxiety and conduct symptoms correlated with suicidal behavior in children, whereas depression, anxiety, and emotional symptoms correlated with suicidal behavior in adolescents. These results add to the growing knowledge about risk factors associated with suicidality among children compared to adolescents, suggesting the importance of targeting different mechanisms in developing assessment and intervention strategies for the two populations.

This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3–16 years) with CTD (n = 327); first-degree relatives (3–10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27–3.42, p p = 0.01) and was inversely associated with ADHD symptom severity (β = − 2.52, 95% CI − 4.16–0.88, p

Background and Goals: Suicide attempts occur mostly during adolescence and are much more frequent in females than in males, although males tend to commit suicide more often than females. This study aims to examine the association between female gender, gender conflict, depression, stress and suicide attempts in adolescent girls. Methods: Participants included 86 adolescent girls aged 12-21 (μ=15.7, SD=3.07) with depression (n=29), attempted suicide (n=15) or both (n=42), admitted consecutively to a tertiary medical center and 93 healthy controls from the community. Depression, suicidal ideation and behavior, gender identity and conflict, personality factors, and stress were compared between the study group and controls and each of the three study-subgroups and controls. Results: A difference was found in the perception gap of own femininity versus others' expectations of the subject’s femininity, between the suicide attempters both with and without depression and the controls. Personality factors were also found to be related to depression and suicide attempts. Suicide attempters with depression showed more harm avoidance than those without depression. Novelty seeking was significantly higher in non-depressed suicide attempters than in controls but not when compared to suicide attempters with depression. Conclusion: It seems that suicide attempts and depression may not only be related to female gender identity. Conflicting gender expectations may result in increased stress, raising the risk for suicide attempts, particularly in girls with high harm avoidance.

Background There is clear evidence that tic disorders (TDs) are associated with psychosocial stress as well as emotional and behavioral problems. Studies have shown that individuals with TDs have higher acute physiological stress responses to external, single stressors (as reflected by saliva cortisol). The aim of the present study was to examine a physiological marker of longer-term stress (as reflected by hair cortisol concentration) in children and adolescents with TDs and unaffected siblings of individuals with TDs. Methods Two samples of a European cohort were included in this study. In the COURSE sample, 412 children and adolescents aged 3–16 years with a chronic TD including Tourette syndrome according to DSM IV-TR criteria were included. The ONSET sample included 131 3–10 years old siblings of individuals with TDs, who themselves had no tics. Differences in hair cortisol concentration (HCC) between the two samples were examined. Within the COURSE sample, relations of HCC with tic severity and perceived psychosocial stress as well as potential effects and interaction effects of comorbid emotional and behavioral problems and psychotropic medication on HCC were investigated. Results There were no differences in HCC between the two samples. In participants with TDs, there were no associations between HCC and tic severity or perceived psychosocial stress. No main effects of sex, psychotropic medication status and comorbid emotional and behavioral problems on HCC were found in participants with TDs. Conclusion A link between HCC and TDs is not supported by the present results.

The study of survivors of a serious suicide attempt (SSA)––an attempt that would have been fatal had it not been for the provision of rapid and effective emergency treatment––can help researchers understand the suicidal mind. Serious suicide attempters are epidemiologically very similar to those who died by suicide, and thus can serve as valid proxies for studying suicides. In this paper, our objective was to briefly review the main risk factors that may facilitate more dangerous suicide behavior with high levels of intent. Our review highlights several dimensions of risk factors for SSAs, including psychopathology, mental pain, communication difficulties, decision-making impulsivity, and aggression. Several studies have indicated that the interaction between some of these dimensions, especially between mental pain and interpersonal difficulties, may serve as major catalysts for SSAs. Suicidal risk assessment should incorporate a designated evaluation of these risk factors as part of suicide prevention models.

Open access funding provided by University of Bern. The SEYLE project is supported by the European Union through the Seventh Framework Program (FP7), Grant agreement number HEALTH-F2-2009-223091. At the time of submission, N. S. was funded by the Swiss National Science Foundation (SNSF) Early Postdoc Mobility fellowship (Grant number: P2BEP3_181901)., Kaess, M., Schnyder, N., Michel, C., Brunner, R., Carli, V., Sarchiapone, M., Hoven, C.W., Wasserman, C., Apter, A., Balazs, J., Bobes, J., Cosman, D., Haring, C., Kahn, J.-P., Keeley, H., Kereszteny, A., Podlogar, T., Postuvan, V., Varnik, A., Resch, F., Wasserman, D.

Following mild traumatic brain injury (mTBI) children usually experience one or more somatic, cognitive, and/or emotional-behavioral post-concussion symptoms (PCS). PCS may be transient, however for some children, persistent post-concussion symptoms (PPCS) might linger for months or years. Identifying risk factors for PPCS may allow earlier interventions for patients at greater risk. We examined pre-injury social difficulties and acute stress reaction as risk factors to PPCS in children. Participants were 83 children (aged 8-16) with mTBI. In a prospective follow-up, pre-injury social difficulties, 24-hours post-concussion symptoms, and acute stress reactions were tested as predictors of one-week and four-months PCS reports. Parents' reports, self-reports, and neurocognitive tests were employed. One-week PCS level was associated with acute stress, and not with 24-hours post-concussion symptoms or pre-injury social difficulties. Four-months PCS level was predicted by pre-injury social difficulties and 24-hours post-concussion symptoms, with no contribution of acute stress. Interestingly, less symptoms at 24-hour from injury were associated with a higher level of PCS at four months. Cognitive functioning at four months was predicted by acute stress, with no contribution of 24-hours post-concussion symptoms or pre-injury social difficulties. Cognitive functioning did not differ between children with and without PPCS. In conclusion, non-injury, socio-emotional factors (pre-injury social difficulties, acute stress) should be considered, alongside injury-related factors, in predicting recovery from mTBI. Pre-injury social difficulties and stress reaction to the traumatic event might pose an emotional burden and limit one's social support during recovery, thus require clinical attention in children following mTBI.

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.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-1β) 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.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 (χHigh 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.

Major depressive disorder (MDD) is associated with alterations in circulatory cytokines, in adults as well as in children and adolescents. Administration of selective serotonin reuptake inhibitors (SSRIs) to MDD pediatric patients modifies cytokine levels. However, most studies only assessed changes over a short time period. In this study, we evaluated long-term effects of the SSRI fluoxetine (FLX) in children and adolescents treated for anxiety and/or MDD, including a high-risk group with pre-treatment suicidality. The study group included ninety-two patients (35 boys and 57 girls) with MDD and/or anxiety disorders, aged 13.90 ± 2.41 years. All patients were treated with FLX and followed for 6 months. The study group included children with pretreatment suicidality (high-risk group;N = 62) and without pretreatment suicidality (N = 30) according to the Columbia Suicide Severity Rating Scale. Plasma concentrations of TNFα, IL-6, and IL-1β were measured by enzyme linked immunosorbent assays before and after six months of treatment. IL-6 and IL-1β significantly increased as a factor of time after 6 months of treatment. The elevation was statistically significant confined to children with pretreatment suicidality. Within the children with pretreatment suicidality, IL-6 levels increased significantly after 6 months only in the children who developed SSRI-associated suicidality. To summarize, an increase in IL-6 levels after 6 months of treatment may be associated with SSRI-emergent suicidality in children with pretreatment suicidality. Further studies are needed to clarify the role and mechanism(s) of IL-6 in the pathogenesis of this life-threatening adverse event.

Objectives: The present study characterized the psychiatric diagnoses and symptoms that led to the administration of antipsychotic medications in children and adolescents with cancer, and to evalua...

AIM To investigate the association between circulating anti-dopamine D2 receptor (D2R) autoantibodies and the exacerbation of tics in children with chronic tic disorders (CTDs). METHOD One hundred and thirty-seven children with CTDs (108 males, 29 females; mean age [SD] 10y 0mo [2y 7mo], range 4-16y) were recruited over 18 months. Patients were assessed at baseline, at tic exacerbation, and at 2 months after exacerbation. Serum anti-D2R antibodies were evaluated using a cell-based assay and blinded immunofluorescence microscopy scoring was performed by two raters. The association between visit type and presence of anti-D2R antibodies was measured with McNemar's test and repeated-measure logistic regression models, adjusting for potential demographic and clinical confounders. RESULTS At exacerbation, 11 (8%) participants became anti-D2R-positive ('early peri-exacerbation seroconverters'), and nine (6.6%) became anti-D2R-positive at post-exacerbation ('late peri-exacerbation seroconverters'). The anti-D2R antibodies were significantly associated with exacerbations when compared to baseline (McNemar's odds ratio=11, p=0.003) and conditional logistic regression confirmed this association (Z=3.49, p

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...

Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are common conditions following motor vehicle accidents (MVAs). Mild TBI and PTSD not only share similar features but may also coexist and interact. Nonetheless, research on psychotherapeutic interventions for PTSD in patients with a history of mTBI, particularly regarding pediatric populations, is limited. The present study compared the efficacy of the prolonged exposure treatment protocol for children and adolescents (PE-A) with PTSD and mTBI (n = 16) versus PTSD alone (n = 21); treatment commenced at least 3 months following an MVA. Emotional status and cognitive functioning were assessed pre- and postintervention using questionnaires and standardized neuropsychological tests. Participants from both groups benefitted from the intervention, as reflected in their emotional status via increased ratings of well-being and decreased ratings of PTSD, anxiety, depression, and postconcussive symptoms, η2 = .21-.50. Ratings of cognitive function also improved for cognitive flexibility, η2 = .30; executive function in everyday life, η2 = .27; and attention and inhibition, η2 = .16. Parental PTSD was the strongest predictor of improvement after intervention, sr2 = .35. Thus, it appears that PE-A is an effective intervention for children with MVA-related PTSD regardless of its comorbidity with mTBI.

Peer victimization is a major stressor adolescents often face in the school environment, and has been linked to depression and suicidal risk. This study analyzed the associations between three beha...

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.

European Union, FP7 [HEALTH-F2-2009-223091]; Projekt DEAL, Lustig S, Kaess M, Schnyder N, Michel C, Brunner R, Tubiana A, Kahn JP, Sarchiapone M, Hoven CW, Barzilay S, Apter A, Balazs J, Bobes J, Saiz PA, Cozman D, Cotter P, Kereszteny A, Podlogar T, Postuvan V, Värnik A, Resch F, Carli V, Wasserman D

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.

Recent studies suggest immune function dysregulation in depression and anxiety disorders. Elevated pro-inflammatory cytokines may be a marker for immune system dysregulation. No study assessed the correlation between the levels of cytokines in children and adolescents with depression/anxiety disorders and their parents. In this study, 92 children and adolescents (mean age 13.90 ± 2.41 years) with depression and/or anxiety disorders were treated with fluoxetine. Blood samples were collected before initiation of treatment. One hundred and sixty-four of their parents (mean age 50.6 ± 6.2 years) and 25 parents of healthy children (mean age 38.5 ± 6.2 years) also gave blood samples. Plasma levels of three pro-inflammatory cytokine (TNF-α, IL-6, IL-1β) were measured by enzyme linked immunosorbent assays (ELISA) and compared between depressed/anxious children and their parents. We also compared cytokine levels between parents of children with depression/anxiety and control parents. Mothers of depressed children had higher TNF-α levels than mothers of controls. No significant difference was detected in the fathers. A positive correlation was found between the IL-1β levels of the depressed/anxious boys and their mothers. No such correlation was observed in the fathers. Our conclusions are that higher levels of proinflammatory cytokines may indicate immune system activation in mothers in response to the distress associated with having depressed/anxious offspring. The correlation between IL-1β levels in the mothers and their depressed/anxious children may indicate familial vulnerability to depression and anxiety. Our observation highlights the need for a better understanding of sexual dimorphism in inflammatory responses to stress.

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.