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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.

The COVID-19 pandemic poses multiple psychologically stressful challenges and is associated with an increased risk for mental illness. Previous studies have focused on the psychopathological symptoms associated with the outbreak peak. Here, we examined the behavioural and mental-health impact of the pandemic in Israel using an online survey, during the six weeks encompassing the end of the first outbreak and the beginning of the second. We used clinically validated instruments to assess anxiety- and depression-related emotional distress, symptoms, and coping strategies, as well as questions designed to specifically assess COVID-19-related concerns. Higher emotional burden was associated with being female, younger, unemployed, living in high socioeconomic status localities, having prior medical conditions, encountering more people, and experiencing physiological symptoms. Our findings highlight the environmental context and its importance in understanding individual ability to cope with the long-term stressful challenges of the pandemic.

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.

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.

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.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic poses multiple psychologically-stressful challenges and is associated with increased risk for mental illness. Previous studies have mostly focused on the psychopathological symptoms associated with the outbreak peak.MethodsWe examined the behavioural and mental health impact of the pandemic in Israel using an online survey. We collected 12,125 responses from 4,933 adult respondents during six weeks encompassing the end of the first outbreak and the beginning of the second. We used clinically validated instruments (Brief Symptom Inventory 18 (BSI-18), Perceived stress scale (PSS), Brief COPE inventory) to assess anxiety- and depression-related emotional distress, symptoms, and coping strategies, as well as questions designed to specifically assess COVID-19-related concerns.ResultsRespondents indicated worrying more about the situation in their country and their close ones contracting the virus, than about their own health and financial situation. The reported distress correlates with the number of new COVID-19 cases and higher emotional burden was associated with being female, younger, unemployed, living in low socioeconomic status localities, encountering more people, and experiencing physiological symptoms. Unexpectedly, older age and having a prior medical condition were associated with reduced emotional distress.ConclusionsOur findings show that inequalities in mental-health burden associated with the COVID-19 pandemic are relevant also following the initial outbreak, and highlight the environmental context and its importance in understanding individual ability to cope with the long-term stressful challenges of the pandemic.

Objectives: Suicidality during hospitalization is a common phenomenon with potential devastating consequences. We attempted to identify risk factors for in-hospital suicidality in a high risk group of adolescent inpatients hospitalized for suicidal behaviors (SB). Methods: The database of a tertiary adolescent psychiatric ward was screened for patients hospitalized consecutively for SB during 2001-2010. Data on documented demographic, clinical, and behavioral risk factors were collected. Suicidal events during hospitalization were classified according to the Columbia Classification Algorithm of Suicide Assessment. Results: The sample included 122 inpatients (53% female) aged 10-19 (Mean=15.77, Standard Deviation=2.89) years admitted for SB. Thirty-seven youth (30%) exhibited SB during the hospitalization period (the "suicidal group"), ten of which attempted suicide while hospitalized. There were no significant differences in demographic and clinical parameters between the suicidal and the non-suicidal groups. Younger age, history of drug use and a history of non-suicidal self-injury (NSSI) were independent predictors of a SA during hospitalization. A previous SA added significant risk to SA during hospitalization only in the group that had a history of NSSI. Conclusions: A high risk of SB exists among adolescents hospitalized for suicidality. The risk assessment for SA during hospitalization should include age, history of drug use and previous SA combined with a history of NSSI. Future studies should expand the efforts to identify potential risk factors of SB during hospitalization in this unique high-risk group.

In adults there is growing evidence that antidepressant (AD) treatment results in a decline in inflammatory cytokines. This is the first report, to our knowledge, of the relationship between response to selective serotonin reuptake inhibitor (SSRI) treatment for anxiety and/or depression and cytokine levels in children and adolescents.Forty-one patients who met Diagnostic and Statistical Manual for Mental Disorders, 4th ed. (DSM-IV) criteria for major depressive disorder (MDD) or anxiety disorders participated in study. Their ages ranged from 9 to 18 (14.12 ± 2.30) years. The patients were treated with fluoxetine for 8 weeks. Plasma concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were measured by enzyme linked immunosorbent assays (ELISA) before and after fluoxetine treatment. Clinical response was measured with several scales, including the Children's Depression Rating Scale-Revised (CDRS-R), the Beck Depression Inventory (BDI), and the Screen for Child Anxiety Related Emotional Disorders (SCARED) Results: The overall response rate was 56%. Antidepressant treatment significantly reduced TNF-α levels (p = 0.037), with no significant changes in the levels of IL-6 and IL-1β. All three proinflammatory cytokines were significantly (p 0.05) higher in SSRI-refractory than in SSRI-responsive patients.Higher levels of TNF-α, IL-6, and IL-1β might predict nonresponse to fluoxetine treatment in children.

Pharmacogenetic approach to antidepressant (AD) response is a promising avenue toward individualizing AD treatment. This is particularly relevant in pediatric populations because of concerns about the suicide risk of serotonin selective reuptake inhibitors (SSRIs), resulting in a black-box warning. However, to date, no specific gene or polymorphism has been consistently implicated as a marker of AD side effect (SE) in the pediatric population. The aim of this study was to examine the association between polymorphisms in genes related to the serotonergic system and citalopram SE's in children and adolescents with major depressive disorder (MDD)/dysthymia and/or anxiety disorders. Outpatients (N = 87, 44 % males), aged 7-18 years with a DSM-IV-TR diagnosis of MDD/dysthymia and/or an anxiety disorder were treated in an 8-week open trial with 20-40 mg/day of citalopram. SE's were rated using a questionnaire devised specifically for this study. Association analysis between known/candidate genetic variants in three genes (5-HTR2A, 5-HTR1Dβ, 5-HTR2C) and SE's was conducted. Agitation was more common in boys than girls (male:female 42.1 vs. 18.7 %, χ 2 = 5.61, df = 1, p = 0.018). Subjects with 5-HTR1Dβ CC genotype showed more agitation vs. both CG and GG genotypes (CC:CG:GG 71.4 vs. 33.3 vs. 18.1 %, χ 2 = 8.99, df = 2, p = 0.011). The 5-HTR1Dβ CC genotype was associated with more reports of agitation. It has been suggested that agitation may be an intermediate phenotype to suicidal behavior. Thus, it seems that 5-HTR1Dβ polymorphism may be involved in citalopram-related agitation in children and adolescents treated for depression and/or anxiety.

Psychotropic drug treatment has been associated with increased risk for falls and hip fractures in elderly patients. The authors examined the association between drug treatment and hip fractures resulting from falls in elderly hospitalized patients, focusing on the medications' anticholinergic properties.This retrospective case-control study was conducted in an acute geriatric ward in a general medical center. Medical records, including demographic, clinical, biochemical, and pharmacological variables, of elderly patients with hip fractures from falls (N = 185), admitted during a 2-year period, were reviewed and compared with a control group (N = 187) of patients matched for age and gender and without hip fractures.The usage rates of antipsychotics, antidepressants, mood stabilizers, and various nonpsychiatric medications were similar in the two groups, except for hypnotics-anxiolytics (higher rates in hip-fracture patients). The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and diastolic blood pressure constituted very modest predictors of falls (R(2) = .038, p = .004). There were no significant differences in the anticholinergic burden values, clinical dementia ratings, and comorbidity burden between the two groups.The rate of psychotropic drug use in general and their anticholinergic burden are similar in acutely admitted elderly patients with or without hip fractures. However, higher usage rate of anxiolytics found in the patients with hip fractures may indicate that this is a risk factor for hip fractures related to falls in elderly patients living in the community.

Antidepressants are being increasingly prescribed for children and adolescents for the treatment of depression, anxiety, and other mental disorders. The selective serotonin reuptake inhibitors (SSRIs) are the major contributors to this trend. Children are especially prone to psychiatric adverse events of SSRIs relative to adults. Recently, attention has been addressed to a specific constellation of emotional and behavioral symptoms associated with SSRI treatment, termed activation syndrome. However, the prevalence, characteristics, and implications of this syndrome have not been systematically examined in the pediatric population. Furthermore, the relationship between SSRI-induced activation and bipolar disorder or other psychiatric adverse events, particularly suicidality and manic conversion, remains unclear. The aim of this review was to report on the current scientific literature on SSRI-induced activation syndrome in young patients and to suggest future directions for research. This information will help to clarify the underlying mechanism of this phenomenon and its prognostic significance and aid clinicians in identifying patients at risk and developing effective management and preventive measures.

Background: Ethological methods used to analyze human obsessive-compulsive disorder (OCD) rituals demonstrated excess of unnecessary repetitions as well as irrelevant, idiosyncratic acts (additions) compared to normal activity. A question that still remains is whether these well-known repetitions and additions are manifested in behaviors unrelated to the OCD rituals. Our objectives were to: (1) assess whether OCD-related repetitions and additions as found in previous studies also affect the patients' activity of filling out questionnaires and (2) evaluate the specificity of these behaviors to OCD as opposed to other anxiety disorders and healthy controls. Sampling and Methods: Several standardized disorder-specific self-report questionnaires were used in order to assess the patient's psychopathologies. The style of filling-out these questionnaires by OCD and non-OCD anxiety outpatients and normal controls was analyzed. Four categories were used: omissions, repetitions, corrections, and additions. Results: The OCD group scored significantly higher on the number of additions as compared with both the anxiety group and the nonclinical group, and significantly higher on the number of corrections and repetitions as compared with the nonclinical group. Conclusions: The hallmarks of OCD, repetitions and additions, are manifested not only in the patient's rituals and thoughts, but in apparently “neutral” tasks that do not a priori involve the intrusive thoughts, urges, and images typical of obsessive-compulsive behavior. Additions seem to be more specific to OCD than repetitions. These two executive faults impede routine functionality of OCD patients in tasks related and unrelated to their rituals. Our study delineates simple, observable behavioral characteristics that distinguish between OCD and non-OCD anxiety patients as well as healthy individuals. These symptomatic behaviors may offer a clue to personality traits or deficits in executive functions that possibly play a part in the pathophysiology of OCD. Our results are an additional indication that nonfunctionality in obsessive-compulsive behavior deserves full attention for a better understanding of the psychopathological mechanisms of OCD.

The purpose of this study was to determine if the known side effects of lithium in adults may be generalized to younger patients with psychiatric disorders.A retrospective naturalistic study design was used. Data were collected from the database of a tertiary pediatric medical center covering the years 1994-2010. Included were patients hospitalized for bipolar and non-bipolar disorders and treated with lithium, alone or in combination with other medications. The electronic medical files were reviewed for changes in thyroid and kidney function and for hematological parameters during the course of treatment.Sixty-one patients 12.5-20.4 years of age (mean 16.94±1.66) met the study criteria: 33 with bipolar disorder and 28 with a non-bipolar disorder. Mean duration of lithium treatment (mean lithium blood level, 0.73±0.24 mEq/L) was 193.68±254.35 days. Mean levels of thyroid-stimulating hormones (TSH) rose significantly from baseline to last measurement (3.16±2.68 vs. 1.52±0.92 mU/L; paired t=-5.19, df=50, p0.001); in 25% of patients, TSH levels at the last measurement were above normal (≥4 mU/L). Only one patient developed TSH values10 mU/L (the threshold considered clinically significant). Positive correlation was found between pre- and posttreatment TSH levels (Pearson's r=0.60; n=51, p0.05). White blood cell count (WBC) also increased significantly following lithium treatment (7195±2151 vs. 7944±2096 cells/mm(3); t=2.83, df=60, p=0.006). No significant changes were noted in serum creatinine levels. There was no difference in these parameters between patients treated with lithium alone or in combination with other medications.Lithium treatment in adolescents with bipolar or non-bipolar disorders is associated with a significant increase in blood TSH levels and WBC count. Lithium-treated adolescent inpatients with a high basal TSH level may be at risk of developing pituitary-thyroid axis dysregulation. Therefore, baseline measurement of thyroid functions and serial monitoring throughout treatment are recommended.

To evaluate the correlation between depression, satisfaction with life, and primary healthcare services consumption.A random sample of primary healthcare clinic patients agreed to complete self-report questionnaires on demographics and physical activity, the Geriatric Depression Scale (GDS), Satisfaction with Life Scale and the Visual Analog Scale for Happiness. Treating physicians completed the Cumulative Illness Rating Scale (CIRS) for each patient. The relationships among psychometric, medical, the number of visits to health maintenance organization (HMO)-physicians during the previous year was assessed.Positive correlation was found between visits to HMO-physicians and depression severity, as assessed by GDS (p = .049), and between visits/year and illness severity, as measured by CIRS (p .001). Correlation was also found between depression and number of chronic medications used (p = .005). Physical activity correlated inversely with depression severity (p = .014). Gender and income had no impact on frequency of visits to HMO-physicians, depression, or satisfaction with life.The results indicate that there is a correlation between depression and healthcare service consumption, as represented by number of HMO-physician visits and medication use. Thus, early detection of depression, using tools such as GDS, and early initiation of antidepressive treatment may help to lower the burden on the health system.

BackgroundNot enough is known about predicting therapeutic response to serotonin-specific reuptake inhibitors, and specifically to fluoxetine. This exploratory study used psychological and biological markers for (retrospective) prediction of treatment-response to fluoxetine in depressed and/or anxious adolescents.MethodsForty-one consecutive adolescent outpatients with a primary diagnosis of severe affective and/or anxiety disorders were assessed and treated with an open-label 8-week trial of fluoxetine. Type D personality was assessed with the 14-item questionnaire, the DS14. In addition, TNFα, IL-6, and IL-1b were measured pre- and post-treatment.ResultsThere was an elevation of Type D personality in patients, compared to the adolescent population rate. Post-treatment, 44% of patients were classified as non-responders; the relative risk of non-response for Type D personality patients was 2.8. Binary logistic regression predicting response vs. non-response showed a contribution of initial TNFα levels as well as Type D personality to non-response.ConclusionsIn this exploratory study, the most significant contributor to non-response was Type D personality. However, the measurement of Type D was not prospective, and thus may be confounded with psychiatric morbidity. The measurement of personality in psychiatric settings may contribute to the understanding of treatment response and have clinical utility.

Background Depression and anxiety disorders are among the most common childhood psychiatric disorders. Selective serotonin reuptake inhibitors (SSRIs) are generally considered first-line treatment for both depression and anxiety in this age group. However, it has been reported that 30%–40% of all patients who receive a sufficient dose and duration of treatment fail to respond. Moreover, SSRI use is frequently associated with serious adverse events (AE), including activation symptoms, manic switch and increased suicidal behavior. These are particularly relevant in pediatric populations because of concerns about the suicide threat of SSRIs, resulting in a black-box warning. Currently there is no way of knowing in advance who of the patients will respond or develop AE. The purpose of the current study is to examine the role of circulating small non-coding RNA's (ncRNA's) as a promising candidate biomarker for SSRI treatment response and AE in children and adolescents treated for depression and anxiety disorders. Methods Eighty patients who met DSM-IV criteria for major depressive disorder (MDD) or anxiety disorders participated in the study. Their age ranged from 6 to 18 (14.12 ± 2.30) years. The patients were treated with fluoxetine 20-40 mg/day for 8 weeks. Psychiatric evaluation was conducted using several standardized diagnostic instruments. The changes in depressive and anxiety symptoms from baseline to 8 weeks were assessed, and remitters and non-responders were compared. Suicidal events, as per convention in pharmacological trials, were defined as either a suicide attempt or an onset or worsening in suicidal ideation. Activation was assessed using a new scale devised by our group for the project and mania by the Young Mania Rating Scale. Blood samples from all the participants were collected before treatment initiation and after eight weeks. RNA was purified using QIAGEN kit and libraries were prepared for sequencing using the Illumina TruSeq Small RNA Library Preparation Kit. miRBase based quantification of miRNAs was carried out on each sample. Samples with less than 1,000,000 miRNA reads were excluded. DeSeq2 was performed for statistical analysis. Results The overall response rate was 67%. Seventeen children and adolescents (21%) responded with moderate or severe AE. In total 86 samples were analyzed. Ten differentially expressed miRNA’s were found between the responders with no AE vs. non-responders/responders + moderate or severe AE. Discussion Ongoing studies: A recruitment of a new cohort of children for validation of the finding in the first cohort will follow. The differentially regulated small ncRNA's will form the basis of a study in an animal model of juvenile depression which will hopefully enable us to gain insights into the mechanism of how these models are involved in the biology of response to treatment and perhaps even of juvenile depression.

Anxiety disorders are chronic disorders appearing with a high frequency in the general population and causing much distress to those suffering from them. The current common treatment consists of antidepressants, primarily from the serotonin-selective-reuptake-inhibitor (SSRI) class. However, despite the relative effectiveness of these medications the patients' responses vary widely with one third not responding at all. While we do not currently have the ability to predict who will respond positively to the medication, it is hoped that genetic research will make it possible to prospectively identify responders and thus help avoid failed treatment attempts and side-effects. The field of pharmacogenetics is divided into pharmaco-kinetics (genetic factors that influence the drug metabolism in the body) and pharmco-dynamics (genetic factors that affect the response to the drug at the level of the receptors/transporters/enzymes in the target organs). Contrary to the treatment of depression, there is little research available on the pharmacogenetics of anxiety disorders and the existing research coincides with the studies on depression. The primary pharmacogenetic-dynamic findings are related to serotonergic genes of which those with the long allele of the serotonin transporter gene (5-HTTLPR) are expected to respond positively to treatment, and the same is true regarding genetic variants of several serotonin receptors. The pharmacogenetic-kinetic findings focus on the CYP450 enzyme system. The hope is that with the progression of the pharmacogenetic research new genetic variants will be discovered which, when combined with the clinical characteristics of those suffering from anxiety disorders, will enable the development of novel treatment algorithms to be customized for each patient.

Schizophrenia in children and adolescents is a rare and serious representation of adult schizophrenia that indicates phenotypic and neurobiological continuity with the adult version of the illness. Epidemiological, genetic, cognitive and imaging findings support the centrality of the neuro-developmental model in the etiology of the disease. The diagnostic criteria for schizophrenia in children and adolescents, and in adults are identical. However, many of the children suffering from schizophrenia display higher levels of impaired pre-morbid functionality than adults with schizophrenia, and have a worse prognosis. Similar to adult-schizophrenia, prognosis is further worsened by frequent co-morbidities. Currently, treatment mainly consists of anti-psychotic medications, including clozapine. However, there is little evidence as to its effectiveness and side-effects are common in younger age.

BackgroundDepression and anxiety disorders are among the most common childhood psychiatric disorders. Selective serotonin reuptake inhibitors (SSRIs) are generally considered first-line treatment for both depression and anxiety in this age group. However, it has been reported that 30%–40% of all patients who receive a sufficient dose and duration of treatment fail to respond. Moreover, SSRI use is frequently associated with serious adverse events (SAE), including activation symptoms, manic switch and increased suicidal behavior. These are particularly relevant in pediatric populations because of concerns about the suicide threat of SSRIs, resulting in a black-box warning. Currently there is no way of knowing in advance who of the patients will respond. Identification of biomarkers that would be early predictors of response and of the occurrence of SAE could help to maximize the benefit–risk ratio for the use of SSRIs, and speed up the matching of treatment to patient. The main objective of this project is therefore to identify and validate biomarkers predicting response and SAE in depressed children and adolescents, thus improving treatment, enabling the development of novel diagnostic tests and suggest novel therapeutic targets for future related drug development.MethodsAs a preliminary pilot, we already obtained blood samples from 80 depressed and anxious children and adolescents over the last year before, during and after eight weeks of fluoxetine (FLU) therapy. Genetic and epigenetic samples were collected from all participants. The patients were treated with FLU 20–40 mg/day for 8 weeks. Clinical response was measured with several scales including the Children's Depression Rating Scale–Revised (CDRS-R), the Beck Depression Inventory (BDI) and the Screen for Child Anxiety Related Emotional Disorders (SCARED).ResultsThe participant's age ranged from 6 to 18 (14.12 ± 2.30) years. The overall response rate was 56%. Ten percent responded with SAE. Regarding Pharmacogenetics, The 5-HTTLPR ss genotype was associated with a poorer clinical response with regard to depressive symptoms as well with fewer reports of agitation compared to the ll genotype. Regarding immune measures, we analyzed cytokine levels from 41 children. Plasma concentrations of TNF-α, IL-6 and IL-1β were measured by enzyme linked immunosorbent assays (ELISA) before and after FLU treatment. Antidepressant treatment significantly reduced TNF-α levels (P = 0.037), with no significant changes in the levels of IL-6 and IL-1β. All three pro-inflammatory cytokines were significantly (P < 0.05) higher in SSRI-refractory than SSRI-responsive patients, i.e.: higher levels of TNF-α, IL-6 and IL-1β might predict non-response to fluoxetine treatment in children.Future plansOut of the study sample we selected 13 remitters and 13 non-responders and 10 children with SAE (activation symptoms, manic/hypomanic switch, increased suicidality), and analyzed expression profiles in peripheral blood at admission and after 8 weeks of treatment using illumine Truseq technique. Hopefully, we shall find significant differences in miRNA profiles between the different groups which may serve as biomarkers indicating AD treatment response and SAE. The differentially regulated miRNA's can be studied in depth in the future in animal models in order to support the hypothesis that they may be involved in the AD mechanism.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Purpose: The present review summarizes the updated literature on the social aspects of suicidal behavior and prevention in adolescents. Recent findings: The predictive role of psychiatric disorders and past history are well recognized in adolescent suicide, but the role of social and cultural factors is less clear. Studies have focused on the importance of ethnicity, gender, family characteristics, and socioeconomic status. More recently, attention has been addressed to broader social risk factors, such as bullying in adolescents, suicide contagion, sexual orientation, and the popular media. Further empirical evidence is needed to advance our understanding of suicidal youth, develop better assessment tools, and formulate effective prevention and treatment programs. Summary: Suicidal behavior remains an important clinical problem and major cause of death in youth. Social factors may be at least as important as genetics. Advancing our understanding of underlying cultural and sociological issues in youth suicide will help clinicians achieve more efficient prediction, prevention and treatment.

Objective To assess the impact of lithium treatment alone or combined with other medications on TSH levels and WBC count in hospitalized bipolar and non-bipolar children, adolescents and young adults using data extracted from electronic medical records. Method The study investigated serum TSH and WBC count in lithium treated hospitalized youth, aged 12–24 years. The study included 122 BP (N = 67) or non-BP (N = 55) disorder inpatients treated with lithium for mean duration of 173 days. TSH and WBC values were examined at baseline and at the end of the hospitalization. Subjects were divided into two groups for analysis: group 1 was treated with lithium as monotherapy and group 2 was treated with lithium combined with other psychotropic agents (polypharmacy). Results The mean end-point TSH levels were significantly higher (3.16 ± 2.68 vs 1.52 ± 0.92 mU/L, P 3 cells, P Conclusions Lithium treatment is associated with significant increase in thyrotropin levels and WBC counts in youth. Higher-baseline TSH level is associated with higher TSH levels in lithium-treated subjects. Close monitoring of thyroid functions in lithium treated children and adolescents is recommended.