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.

Stress-related emotional and behavioural impact following the first COVID-19 outbreak peak.

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.

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

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-1ß) 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-1ß 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-1ß 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.

An increase in IL-6 levels at 6-month follow-up visit is associated with SSRI-emergent suicidality in high-risk children and adolescents treated with fluoxetine.

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-1ß were measured by enzyme linked immunosorbent assays before and after six months of treatment. IL-6 and IL-1ß 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.

Increased circulatory IL-6 during 8-week fluoxetine treatment is a risk factor for suicidal behaviors in youth.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat anxiety and/or depression in pediatric populations. However, the response rates are low (approximately 50%). Moreover, SSRI use is frequently associated with adverse events (AE). Currently there are no available biomarkers for treatment response/AE. Identification of biomarkers predicting early response and/or AE could help maximize the benefit-risk ratio for the use of SSRIs, and accelerate matching of treatments to patients. Pro-inflammatory cytokines were proposed as potential biomarkers. METHOD: Ninety-two patients (35 boys and 57 girls) with major depressive disorder and/or anxiety disorders, aged 13.90 ±â€¯2.41 years, were treated with fluoxetine (FLX) for 8 weeks. Plasma concentrations of TNFα, IL-6, and IL-1ß were measured by enzyme linked immunosorbent assays before and after FLX treatment. Clinical response and AE were measured using several clinical scales, including the Clinical Global Impression - improvement, Children's Depression Rating Scale-Revised, the Beck Depression Inventory, the Screen for Child Anxiety Related Emotional Disorders, the Columbia suicide severity rating scale, and the Suicide Ideation Questionnaire. RESULTS: IL-6 levels increased after treatment only in the group of children who developed FLX-associated suicidality. CONCLUSION: An increase in IL-6 levels during treatment may be a risk factor for the emergence of FLX-associated suicidality (OR = 1.70). Further studies are necessary to clarify the role and mechanism(s) of this cytokine in the pathogenesis of this life-threatening AE.

Predictors of Suicidal Behaviors during Hospitalization among Adolescents Admitted Due to Suicidal Behaviors: A 10-Year Retrospective Naturalistic Study.

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.

An exploratory study of adolescent response to fluoxetine using psychological and biological predictors.

BACKGROUND: Not 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. METHODS: Forty-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. RESULTS: There 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. CONCLUSIONS: In 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.

Nonfunctional Redundant Acts Characterize OCD, Even in OCD-Unrelated Tasks: A Demonstration in Questionnaire Completion.

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.

Levels of depression and satisfaction with life as indicators of health services consumption.

OBJECTIVE: To evaluate the correlation between depression, satisfaction with life, and primary healthcare services consumption. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Pharmacogenetics of citalopram-related side effects in children with depression and/or anxiety disorders.

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-HTR1Dß, 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-HTR1Dß 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-HTR1Dß 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-HTR1Dß polymorphism may be involved in citalopram-related agitation in children and adolescents treated for depression and/or anxiety.

The Relationship Between Plasma Cytokine Levels and Response to Selective Serotonin Reuptake Inhibitor Treatment in Children and Adolescents with Depression and/or Anxiety Disorders.

OBJECTIVE: 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. METHODS: 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-1ß 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-1ß. All three proinflammatory cytokines were significantly (p < 0.05) higher in SSRI-refractory than in SSRI-responsive patients. CONCLUSIONS: Higher levels of TNF-α, IL-6, and IL-1ß might predict nonresponse to fluoxetine treatment in children.

The Association in Elderly Hospitalized Patients, Between Psychotropic Drugs and Hip Fractures Resulting from Falls.

BACKGROUND/STUDY CONTEXT: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Effects of long-term valproic acid treatment on hematological and biochemical parameters in adolescent psychiatric inpatients: a retrospective naturalistic study.

The objective of this study was to determine the long-term hematological and biochemical side effects of valproic acid (VPA) in psychiatric adolescent inpatients. A retrospective naturalistic study design was used. Participants were psychiatric inpatients treated with VPA, alone or in combination with other medications. Electronic medical files were reviewed for changes in hematological and biochemical parameters following a course of VPA treatment. One hundred and four adolescents aged 12-18 (mean 15.76±1.58) years fulfilled the study criteria. The mean blood level and duration of VPA treatment were 65.81±22.18 mcg/ml and 98.57±135.94 days, respectively. The mean levels of thyroid-stimulating hormones and triglyceride levels increased significantly from the first to the last measurement. Platelet count decreased significantly following VPA treatment. No correlation was observed between these parameters and age, duration of treatment, or VPA levels. No serious adverse events were reported. Long-term VPA treatment in adolescents with psychiatric disorders is associated with significant increases in triglyceride levels. Moreover, VPA-treated adolescent psychiatric inpatients may be at risk of developing pituitary-thyroid axis dysregulation and decreased platelet count. Therefore, baseline measurement of thyroid functions and metabolic and hematological parameters and monitoring throughout the treatment are recommended.

Short-term effects of lithium on white blood cell counts and on levels of serum thyroid-stimulating hormone and creatinine in adolescent inpatients: a retrospective naturalistic study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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, p<0.001); in 25% of patients, TSH levels at the last measurement were above normal (≥4 mU/L). Only one patient developed TSH values >10 mU/L (the threshold considered clinically significant). Positive correlation was found between pre- and posttreatment TSH levels (Pearson's r=0.60; n=51, p<0.05). 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. CONCLUSIONS: 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.

[Pharmacogenetics and anxiety disorders: analysis of recent findings].

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.

Social aspects of suicidal behavior and prevention in early life: a review.

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.

[Autism spectrum disorders: updates and new definitions].

Autism spectrum disorders (ASD) include several clinically different disorders. Despite the impression that in recent years there has been a rise in the incidence of this disorder, it seems that the apparent rise stems from the widening of diagnostic criteria rather than from a true rise in disorder incidence. Notwithstanding the wide range of clinical symptoms, reliabLe information on the etiology of this disorder is lacking. However, new data points to an important genetic component and to structural changes in the brain. There is a wide range of comorbidities with additional neurodevelopmental disorders. The currently offered treatment is multi-disciplinary and includes primarily behavioral therapy and symptomatic treatment with psychotropic drugs.

[Childhood and adolescent-onset schizophrenia: new information and definitions].

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.