Using genomics to predict antidepressant response in suicidal depressed children

2016 ◽  
Vol 33 (S1) ◽  
pp. S53-S53
Author(s):  
Maya Amitai ◽  
Alan Apter
Keyword(s):  
Children And Adolescents ◽  
Clinical Response ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Rating Scale ◽  
Expression Profiles ◽  
Plasma Concentrations ◽  
Depression And Anxiety ◽  
Children’S Depression ◽  
Tnf Α ◽  
Depressed Children

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.

Safety, Tolerability, and Efficacy of Desvenlafaxine in Children and Adolescents with Major Depressive Disorder: Results from Two Open-Label Extension Trials

CNS Spectrums ◽  
2018 ◽  
Vol 24 (5) ◽  
pp. 496-506 ◽  
Author(s):  
Sarah Atkinson ◽  
Louise Thurman ◽  
Sara Ramaker ◽  
Gina Buckley ◽  
Sarah Ruta Jones ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Children And Adolescents ◽  
Rating Scale ◽  
Transition Period ◽  
Extension Study ◽  
Open Label ◽  
Major Depressive ◽  
Children’S Depression ◽  
Flexible Dose

ObjectiveTwo similarly designed extension studies evaluated the long-term safety and tolerability of desvenlafaxine for the treatment of children and adolescents with major depressive disorder (MDD). Efficacy was evaluated as a secondary objective.MethodsBoth 6-month, open-label, flexible-dose extension studies enrolled children and adolescents who had completed one of two double-blind, placebo-controlled, lead-in studies. One lead-in study included a 1-week transition period prior to the extension study. Patients received 26-week treatment with flexible-dose desvenlafaxine (20–50 mg/d). Safety assessments included comprehensive psychiatric evaluations, vital sign assessments, laboratory evaluations, 12-lead electrocardiogram, physical examination with Tanner assessment, and Columbia-Suicide Severity Rating Scale. Adverse events (AEs) were collected throughout the studies. Efficacy was assessed using the Children’s Depression Rating Scale–Revised (CDRS-R).ResultsA total of 552 patients enrolled (completion rates: 66.4 and 69.1%). AEs were reported by 79.4 and 79.1% of patients in the two studies; 8.9 and 5.2% discontinued due to AEs. Treatment-emergent suicidal ideation or behavior was reported for 16.6 and 14.1% of patients in the two studies. Mean (SD) CDRS-R total score decreased from 33.83 (11.93) and 30.92 (10.20) at the extension study baseline to 24.31 (7.48) and 24.92 (8.45), respectively, at week 26.ConclusionDesvenlafaxine 20 to 50 mg/d was generally safe and well tolerated with no new safety signals identified in children and adolescents with MDD who received up to 6 months of treatment in these studies. Patients maintained the reduction in severity of depressive symptoms observed in all treatment groups at the end of the lead-in study.

scholarly journals Activity/rest rhythm of depressed adolescents undergoing therapy: case studies

2016 ◽  
Vol 38 (4) ◽  
pp. 216-220
Author(s):  
Maria Eugênia Mesquita ◽  
◽  
Maria Eliza Finazzi ◽  
Bruno Gonçalves ◽  
Lee Fu-I ◽  
...  
Keyword(s):  
Rating Scale ◽  
Spectral Power ◽  
Activity Monitors ◽  
School Aged Children ◽  
Clinical Evaluations ◽  
Diagnostic And Statistical Manual ◽  
Children’S Depression ◽  
Study Results ◽  
Depressed Children ◽  
Course Of Depression

Abstract Introduction: Disorders of circadian rhythms have been reported in studies of both depressed children and of depressed adolescents. The aim of this study was to evaluate whether there is a relationship between the 24-hour spectral power (24h SP) of the activity/rest rhythm and the clinical course of depression in adolescents. Methods: Six 14 to 17-year-old adolescents were recruited for the study. They were all suffering from major depressive disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria, as identified by the Schedule for Affective Disorders and Schizophrenia for School Aged Children: Present and Lifetime Version (K-SADS-PL). Depressive symptoms were assessed using the Children's Depression Rating Scale - Revised (CDRS-R) and clinical evaluations. Locomotor activity was monitored over a period of 13 consecutive weeks. Activity was measured for 10-minute periods using wrist-worn activity monitors. All patients were prescribed sertraline from after the first week up until the end of the study. Results: We found a relationship between high CDRS values and low 24-hour spectral power. Conclusions: The 24h SP of the activity/rest rhythm correlated significantly (negatively) with the clinical ratings of depression.

Citalopram in Children and Adolescents with Depression or Anxiety

2002 ◽  
Vol 36 (11) ◽  
pp. 1692-1697 ◽  
Author(s):  
Jennifer L Baumgartner ◽  
Graham J Emslie ◽  
M Lynn Crismon
Keyword(s):  
Anxiety Disorder ◽  
Adverse Effects ◽  
Children And Adolescents ◽  
Emotional Disorders ◽  
Rating Scale ◽  
Depressive Symptomatology ◽  
Care Center ◽  
Tertiary Care ◽  
Secondary Outcome ◽  
Children’S Depression

OBJECTIVE: To investigate the efficacy and tolerability of citalopram in children and adolescents. METHOD: Retrospective chart review of 17 outpatients treated with citalopram at a tertiary care center. Subjects were diagnosed with a depressive or anxiety disorder with or without comorbidities and may have received concurrent medications. The primary outcome measure was the Clinical Global Impression Improvement Scale (CGI-I). Secondary outcome measures were the Children's Depression Rating Scale—Revised (CDRS-R), Inventory of Depressive Symptomatology, and Screen for Child Anxiety-Related Emotional Disorders (SCARED). Adverse effects were assessed via chart documentation. RESULTS: Patients were treated with a mean citalopram dose of 22.4 ± 7.3 mg for 12 weeks. Thirteen patients (76%) had CGI-I scores ≤2: 8 of 12 patients with depression and 5 of 5 patients with an anxiety disorder. The mean time to response was 7.6 ± 3.6 weeks. Additionally, 6 of 8 patients had ≥50% reduction from baseline CDRS-R score, with 3 patients (38%) meeting criteria for remission. Three of 4 patients had a >50% reduction for baseline SCARED-parent score. Overall, adverse effects appeared minor and transient. One patient discontinued citalopram due to intolerable adverse effects, and 1 patient required dose reduction. CONCLUSIONS: Citalopram appears to be effective and well tolerated in this group of children and adolescents with depressive or anxiety disorders and a high degree of comorbidity. Controlled studies in this patient population are indicated.

scholarly journals Antenatal Depression and Anxiety Affect Postpartum Parenting Stress: A Longitudinal, Prospective Study

2010 ◽  
Vol 55 (4) ◽  
pp. 222-228 ◽  
Author(s):  
Shaila Misri ◽  
Kristin Kendrick ◽  
Tim F Oberlander ◽  
Sandhaya Norris ◽  
Lianne Tomfohr ◽  
...  
Keyword(s):  
Parenting Stress ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Rating Scale ◽  
Early Recognition ◽  
Short Form ◽  
Antenatal Depression ◽  
Stress Index ◽  
Depression And Anxiety ◽  
Third Trimester ◽  
In Pregnancy

Objective: Postpartum depression has been associated with parenting stress, impacting attachment and child development. However, the relation between antenatal depression or anxiety and postpartum parenting stress has not been investigated. We studied the effect of antenatal depression and anxiety and treatment with selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors (antidepressants [ADs]) on postpartum parenting stress. Method: Ninety-four pregnant women (part of a larger study examining prenatal AD exposure on infants) were prospectively monitored for depression and anxiety during the third trimester and 3- and 6-months postpartum using the Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale. Parenting stress was assessed using the Parenting Stress Index—Short Form at 3- and 6-months postpartum. Results: Both antenatal third trimester depression and anxiety were significant predictors of 3- and 6-month postpartum parenting stress, after controlling for maternal age, number of children, and exposure to prenatal ADs (all Ps < 0.001). Third trimester depression accounted for 13% to 22% of the variance in postpartum stress at 3 and 6 months. Prenatal AD use was not a significant predictor in any of the models (all Ps > 0.2). Twenty of 41 mothers on ADs achieved remission (HDRS = 7) in pregnancy and had average parenting stress scores of about 1 standard deviation lower than those who did not at 3- and 6-months postpartum ( t = 3.32, df = 32, P = 0.002 and t = 2.52, df = 32, P = 0.02, respectively). Conclusions: Our findings indicate that antenatal depression and anxiety directly impact postpartum parenting stress, regardless of antenatal AD treatment. Ongoing maternal mental illness in pregnancy is an important predictor of postpartum parenting stress. Early recognition and treatment to remission is key.

scholarly journals A CROSS SECTIONAL DESCRIPTIVE STUDY OF OCD IN CHILDREN AND ADOLESCENTS

2020 ◽  
pp. 1-4
Author(s):  
Chhitij Srivastava ◽  
Abhishek Pratap Singh ◽  
Zeeshan Anwar ◽  
Santosh Kumar Kesharwani
Keyword(s):  
Children And Adolescents ◽  
Rating Scale ◽  
Demographic Data ◽  
Positive Family History ◽  
Clinical Information ◽  
Obsessive Compulsive ◽  
Degree Relative ◽  
Cross Sectional ◽  
Multicentric Study ◽  
Children’S Depression

This study was a part of a bigger multicentric study to examine the socio-demographic and clinical characteristics of children and adolescents (age ≤18 years) with OCD. Our sample comprised 30 subjects with OCD. Socio-demographic data was collected on a proforma specifically designed for this study. Clinical information was obtained on Structured clinical interview for Diagnostic and Statistical Manual, 5th edition Research Version (SCID), Children’s Yale Brown Obsessive Compulsive Scale (CYBOCS), the Children’s Depression Rating Scale–Revised (CDRS) and the Family Interview for Genetic Studies (FIGS). In our sample 70% of participants were male and 67.7% had onset of symptoms before 14 years of age. Most common obsessions in our participants were of doubts about contamination and magical thinking/superstitious while the most common compulsions were those involving checking, washing and rituals involving other persons. Comorbid psychiatric disorders were seen in 63.3% patients with most common being depression, Obsessive Compulsive Related Disorders (OCRDs), intermittent explosive disorder and anxiety disorder. The associated OCD symptoms on CYBOCS including lack of insight, avoidance and indecisiveness were on a spectrum. 46.6% had positive family history of OCD in first degree relative.

scholarly journals The relationship between the plasma proinflammatory cytokine levels of depressed/anxious children and their parents

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomer Mevorach ◽  
Michal Taler ◽  
Shira Dar ◽  
Maya Lebow ◽  
Irit Schorr Sapir ◽  
...  
Keyword(s):  
Immune System ◽  
Anxiety Disorders ◽  
Children And Adolescents ◽  
Healthy Children ◽  
Depression And Anxiety ◽  
Blood Samples ◽  
Immune System Activation ◽  
Tnf Α ◽  
Significant Difference ◽  
Cytokine Levels

AbstractRecent 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.

scholarly journals Should we prescribe antidepressants to children?

2005 ◽  
Vol 29 (5) ◽  
pp. 164-167 ◽  
Author(s):  
Bernadka Dubicka ◽  
Ian Goodyer
Keyword(s):  
Children And Adolescents ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Meta Analysis ◽  
Medical Community ◽  
Pharmaceutical Companies ◽  
Industry Data ◽  
Quality Of Reporting ◽  
Negative Results ◽  
Depressed Children

In June last year, the committee on safety of medicines (CSM) advised against the use of paroxetine in depressed children and adolescents. This was subsequently followed by a similar warning regarding the use of other selective serotonin reuptake inhibitors (SSRIs), with the exception of fluoxetine (http://www.mhra.gov.uk/). The basis of this decision was a detailed review of both the published and the unpublished data. The latter were obtained from pharmaceutical companies who had not reported negative results from clinical trials to the medical community. The addition of the pharmaceutical industry data to published results exerted dramatic effects on the efficacy of available compounds. Thus with the exception of fluoxetine, the risks outweigh the benefits of the SSRIs in the treatment of childhood depression. In particular, there is evidence of a non-significant trend towards increased suicidality with most SSRIs compared with placebo. These findings have been supported by a further recent meta-analysis of the available published and unpublished data (Whittington et al, 2004). A review of the safety and efficacy of antidepressants in children and adolescents by Jureidini et al (2004) has also criticised the quality of reporting of the published trials. The review concluded that the benefits of SSRIs have been exaggerated, including those of fluoxetine, and the adverse effects have been downplayed. The authors suggest that psychological treatments are probably safer and more effective.

Changes in Serum Tumor Necrosis Factor (TNF-α) with Kami-Shoyo-San Administration in Depressed Climacteric Patients

2004 ◽  
Vol 32 (04) ◽  
pp. 621-629 ◽  
Author(s):  
Takahisa Ushiroyama ◽  
Atsushi Ikeda ◽  
Kou Sakuma ◽  
Minoru Ueki
Keyword(s):  
Tumor Necrosis Factor ◽  
Herbal Medicine ◽  
Tumor Necrosis ◽  
Rating Scale ◽  
Therapy Group ◽  
Plasma Concentrations ◽  
Herbal Medicines ◽  
College Hospital ◽  
Tnf Α ◽  
Necrosis Factor

An herbal medicine (Kampo) is widely used to prevent or treat climacteric symptoms. In order to investigate the potential involvement of tumor necrosis factor (TNF)-α in susceptibility to mood disorder in climacteric women and to clarify the relationship between immune function and the efficacy of herbal medicine, we compared serum TNF-α levels in two treated groups, with and without concurrent use of herbal medicine. This study included 113 consecutive depressed menopausal patients who visited the gynecological and psychosomatic medicine outpatient clinic of the Osaka Medical College Hospital in Japan. Fifty-eight patients were administered Kami-shoyo-san according to the definition of above Sho. In contrast, 55 patients who were different in Sho of Kami-shoyo-san were administered antidepressants. Hamilton Rating Scale for depression (HAM-D) scores were determined at baseline and 12 weeks after starting treatment (endpoint). TNF-α concentrations were analyzed before and after 12 weeks of treatment. Kami-shoyo-san significantly increased plasma concentrations of TNF-α after 12 weeks of treatment, to 17.22 ± 6.13 pg/ml from a baseline level of 14.16 ± 6.27 pg/ml (p = 0.048). The percent change in plasma concentration of TNF-α differed significantly between the Kami-shoyo-san therapy group and the antidepressant therapy group at 4 weeks (12.0 ± 7.8% and -1.22 ± 0.25%, respectively, p <0.01), 8 weeks (19.7 ± 3.4% and -2.45 ± 0.86%, respectively, p <0.01), and 12 weeks (21.3 ± 5.4% and -6.81 ± 2.2%, respectively, p <0.001). We found in this study that Kami-shoyo-san, an herbal medicine, increased plasma TNF-α levels in depressed menopausal patients. Cytokines may play various roles in mood and emotional status via the central nervous system and may be regulated by herbal medicines, although the interactions are very complex.

Depression in the Young, Parental Depression and Parenting Stress

2005 ◽  
Vol 13 (1) ◽  
pp. 76-79 ◽  
Author(s):  
Susan Tan ◽  
Joseph Rey
Keyword(s):  
Parenting Stress ◽  
Children And Adolescents ◽  
Univariate Analysis ◽  
Parental Depression ◽  
Diagnostic Interview ◽  
Maternal Depressive Symptoms ◽  
Children’S Depression ◽  
And Gender ◽  
The Relationship ◽  
Depressed Children

Objective: To examine the relationship between depression in children and adolescents, parental depression and parenting stress. Methods: Fifty-three depressed youths, 9-16 years, were matched for age and gender and compared with S3 non-depressed controls. Depression was diagnosed using the Diagnostic Interview for Children and Adolescents-Revised (DICA-R). Parents completed questionnaires on depression and parenting stress. Results: Parents of depressed children reported higher parenting stress and were more likely to perceive their children as ‘difficult’. Univariate analysis demonstrated a relationship between children's depression and maternal depression but not with paternal depression. This became non-significant with multivariate analysis, implying that maternal depressive symptoms may have been due to caring for a depressed, thus ‘difficult’ child. Conclusions: Depressed youth were more likely to be perceived by mothers as ‘difficult’ and caused them significant parenting stress. The same phenomenon did not occur among the fathers. Clinicians need to consider the presence of depression among ‘difficult’ children and look for early depression in mothers of depressed youth.

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