Starve a cold or feed a fever? Identifying cellular metabolic changes following infection and exposure to SARS-CoV-2.

Viral infections induce major shifts in cellular metabolism elicited by active viral replication and antiviral responses. For the virus, harnessing cellular metabolism and evading changes that limit replication are essential for productive viral replication. In contrast, the cellular response to infection disrupts metabolic pathways to prevent viral replication and promote an antiviral state in the host cell and neighboring bystander cells. This competition between the virus and cell results in measurable shifts in cellular metabolism that differ depending on the virus, cell type, and extracellular environment. The resulting metabolic shifts can be observed and analyzed using global metabolic profiling techniques to identify pathways that are critical for either viral replication or cellular defense. SARS-CoV-2 is a respiratory virus that can exhibit broad tissue tropism and diverse, yet inconsistent, symptomatology. While the factors that determine the presentation and severity of SARS-CoV-2 infection remain unclear, metabolic syndromes are associated with more severe manifestations of SARS-CoV-2 disease. Despite these observations a critical knowledge gap remains between cellular metabolic responses and SARS-CoV-2 infection. Using a well-established untargeted metabolomics analysis workflow, we compared SARS-CoV-2 infection of human lung carcinoma cells. We identified significant changes in metabolic pathways that correlate with either productive or non-productive viral infection. This information is critical for characterizing the factors that contribute to SARS-CoV-2 replication that could be targeted for therapeutic interventions to limit viral disease.

Long-Term Effects of Lithium Use on Children and Adolescents: A Retrospective Study from Turkey.

Background: The aim of this study was to evaluate the long-term effects of lithium treatment on white blood cell (WBC) count, serum creatinine, and thyroid-stimulating hormone (TSH) levels in children and adolescents with bipolar disorder (BD) and non-BD in a Turkish children and adolescent sample. Methods: The study is based on retrospective chart review. Children and adolescent patients with BD and non-BD prescribed lithium in a mental health and neurological disorders hospital between 2012 and 2017 were included in the study. Data were collected from the electronic medical files. Laboratory values for WBC count, serum creatinine, and TSH levels at baseline within the week before the onset of lithium, and at 1st, 3rd, 6th, and 12th month of treatment were recorded. Results: A total of 143 patients (82 females, 61 males; 100 BD, 43 non-BD) aged 9-18 were included. Non-BD diagnoses were psychotic and schizoaffective disorders, unipolar depression, attention-deficit/hyperactivity disorder, conduct disorder, severe mood dysregulation syndrome, borderline personality disorder, and autism. Mean age of the participants were 15.90 ± 1.16 years for the bipolar group and 14.88 ± 1.79 years for the nonbipolar group. Patients with BD reported more adverse effects. There was a statistically significant increase in WBC counts and TSH levels at any time point. A statistically significant elevation in serum creatinine was found at 3rd and 12th month of treatment. During the course of lithium treatment, WBC counts exceeded 13,000 in 14 (9.8%) patients, and TSH levels exceeded 5.5 mU/L in 41 patients (28.6%). Twenty-one (14.68%) patients were started on thyroxin replacement. Basal TSH levels and duration of the lithium treatment were higher in the participants with TSH levels exceeding 5.5 mU/L. Lithium maximum dose, lithium blood level, basal TSH level, and duration of treatment were higher in the participants receiving thyroxin replacement. No patients had serum creatinine levels exceeding the normal reference values. Conclusion: Our study suggests that lithium is a generally safe and tolerable agent for children and adolescents with BD and non-BD; however, close monitoring of thyroid functions particularly in patients with a higher basal TSH level and longer duration of lithium use is important.

Correlations between metabolites in the synovial fluid and serum: A mouse injury study.

Osteoarthritis occurs frequently after joint injury. Currently, osteoarthritis is diagnosed by radiographic changes that are typically found after the disease has progressed to multiple tissues. The primary objective was to compare potential metabolomic biomarkers of joint injury between synovial fluid and serum in a mouse model of posttraumatic osteoarthritis. The secondary objective was to gain insight into the pathophysiology of osteoarthritis by examining metabolomic profiles after joint injury. Twelve-week-old adult female C57BL/6 mice (n = 12) were randomly assigned to control, Day 1, or Day 8 postinjury groups. Randomly selected stifle joints were subjected to a single rapid compression. At Days 1 and 8 postinjury, serum was extracted before mice were euthanized for synovial fluid collection. Metabolomic profiling detected ~2500 metabolites across serum and synovial fluid. Of these, 179 were positively correlated and 51 were negatively correlated between synovial fluid and serum, indicating the potential for the development of metabolomic biomarkers. Synovial fluid captured injury-induced differences in metabolomic profiles at both Days 1 and 8 after injury whereas serum did not. However, synovial fluid and serum were distinct at both time points after injury. In synovial fluid, pathways of interest mapped to amino acid synthesis and degradation, bupropion degradation, and transfer RNA (tRNA) charging. In serum, pathways were amino acid synthesis and degradation, the phospholipase pathway, and nicotine degradation. These results provide a rich picture of the injury response at early time points after joint injury. Furthermore, the correlations between synovial fluid and serum metabolites suggest the potential to gain insight into intra-articular pathophysiology through analysis of serum metabolites.

Metabolomic Profiling and Mechanotransduction of Single Chondrocytes Encapsulated in Alginate Microgels.

Articular cartilage is comprised of two main components, the extracellular matrix (ECM) and the pericellular matrix (PCM). The PCM helps to protect chondrocytes in the cartilage from mechanical loads, but in patients with osteoarthritis, the PCM is weakened, resulting in increased chondrocyte stress. As chondrocytes are responsible for matrix synthesis and maintenance, it is important to understand how mechanical loads affect the cellular responses of chondrocytes. Many studies have examined chondrocyte responses to in vitro mechanical loading by embedding chondrocytes in 3-D hydrogels. However, these experiments are mostly performed in the absence of PCM, which may obscure important responses to mechanotransduction. Here, drop-based microfluidics is used to culture single chondrocytes in alginate microgels for cell-directed PCM synthesis that closely mimics the in vivo microenvironment. Chondrocytes formed PCM over 10 days in these single-cell 3-D microenvironments. Mechanotransduction studies were performed, in which single-cell microgels mimicking the cartilage PCM were embedded in high-stiffness agarose. After physiological dynamic compression in a custom-built bioreactor, microgels exhibited distinct metabolomic profiles from both uncompressed and monolayer controls. These results demonstrate the potential of single cell encapsulation in alginate microgels to advance cartilage tissue engineering and basic chondrocyte mechanobiology.

Factors affecting disclosure time of sexual abuse in children and adolescents.

BACKGROUND: The aim of this study is to determine the factors affecting early and delayed disclosure time of child sexual abuse (CSA). Early disclosure of CSA is considered to be crucial for child protection. METHODS: A total of 125 sexually abused children and adolescents, who had been evaluated by child adolescent psychiatry and forensic medicine specialists, were enrolled in this study. Files of medical and criminal data were analyzed retrospectively and synchronously by child adolescent psychiatrist and forensic medicine specialist authors who had evaluated victims using the standard procedures of Düzce University Faculty of Medicine Child Abuse Assessment Council. Univariate and multivariate logistic regression analyses were conducted to evaluate predictors. RESULTS: Delayed disclosers were found to be younger than early disclosers. Among the delayed disclosers, there were also more victims of intrafamilial CSA, fewer victims of penetration, and fewer voluntary disclosures. Multivariate logistic regression revealed that "younger age" and "intrafamilial CSA" were independent predictors of delayed disclosure of CSA. CONCLUSIONS: The results of our study contribute to an understanding of the factors related to delayed disclosure and underline the need for age-appropriate education and prevention programs targeted to increase the awareness of sexual abuse, particularly intrafamilial abuse, and to promote voluntary disclosure in children and adolescents, especially for younger age groups. The education of potential recipients of CSA and further education of professionals is extremely important in order to support children and adolescents' voluntary disclosure of CSA.

Psychological well-being and marital satisfaction in response to weight loss after bariatric surgery.

PURPOSE: To compare the marital satisfaction (MS) and psychological well-being (PWB) of men and women before and after bariatric surgery for obesity. METHODS: The subjects of this prospective observational study were obese patients who underwent bariatric surgery. MS and PWB were assessed before, and 6 months after the surgery, using specific scales for MS and PWB. RESULTS: The correlation matrix showed that age was not correlated with any of the scores from the PWB scales, and only with the total MS scores of men (P < 0.05). The pre-surgical BMI-post-surgical BMI (ΔBMI) was correlated negatively and significantly with the post-surgical total MS, especially for women, but it was not correlated with the sexual satisfaction of either gender. The score of positive interpersonal relationships was negatively correlated with the ΔBMI, especially for women (P < 0.05), whereas personal improvement was positively correlated for men (P < 0.05). There was also a significant correlation between ΔBMI and purpose in life for both genders. Post-surgical ΔBMIs were not associated with the other two indicators of PWB, namely, autonomy and environmental mastery for both genders. CONCLUSIONS: For women, weight loss after bariatric surgery seemed to improve PWB and MS when assessed 6 months post-operatively; however, the psychiatric assessment of patients before and after the surgery is crucial.

The Burden of Care and Burnout in Individuals Caring for Patients with Alzheimer's Disease.

Alzheimer's disease imposes a severe burden upon patients and their caregivers. We examined the relationship between the sociodemographic factors, burden of care and burnout level of 120 of 203 professional caregiving staff dealing with Alzheimer's disease patients in eight geriatric care centers in Istanbul/Turkey. The Zarit Caregiver Burden Scale was used to measure the level of burden of care, and the Maslach burnout inventory to measure the level of burnout. High levels of emotional exhaustion were present in 25% of our sample, and depersonalization was found in 30% reduced personal accomplishment was present in 26% of the caregivers.

Correction to: Is emotion recognition the only problem in ADHD? Effects of pharmacotherapy on face and emotion recognition in children with ADHD.

The author would like to correct the error in the publication of the original article. The corrected details are given below for your reading.

Association of Suicide Attempts and Non-Suicidal Self-Injury Behaviors With Substance Use and Family Characteristics Among Children and Adolescents Seeking Treatment for Substance Use Disorder.

BACKGROUND: Numerous studies in youth and adults suggest strong association between substance use disorders and non-suicidal self-injury (NSSI) and suicidal behaviors. There is paucity of studies exploring the association of substance use with history of suicide attempts (HSA) and NSSI in children and adolescents in Turkey. OBJECTIVE: We aimed to examine the prevalence of NSSI and HSA and their relationship with substance use and family characteristics among youth seeking treatment for substance use in Turkey. METHOD: Participants were children and adolescents who were admitted to the Bakirkoy Trainee and Research Hospital for Psychiatric and Neurologic Disorders in Istanbul between January 2011 and December 2013. Two thousand five hundred eighteen participants were included. Questionnaires were applied to all patients. The association of NSSI and HSA with substance use, family characteristics, and subject characteristics were analyzed. RESULTS: The prevalence of NSSI and HSA behaviors among substance using youth in our sample were 52% and 21% respectively. Cannabis and cocaine use was found to be a significant risk factor for HSA, and polysubstance use was associated with both NSSI and HSA. Parental separation/divorce, parental mental disorders, alcohol and drug use, and crime were the risk factors for HSA. A positive history of physical and sexual abuse increased the risk of HAS, and a history of neglect increased the risk of NSSI. Conclusions/importance: We suggest that results showing relationship between substance use and associated social features with NSSI and HSA may contribute to elaborating effective and targeted preventive and intervention programs for these high-risk youth groups in Turkey.

Is emotion recognition the only problem in ADHD? effects of pharmacotherapy on face and emotion recognition in children with ADHD.

The objectives of this study were to evaluate both face and emotion recognition, to detect differences among attention deficit and hyperactivity disorder (ADHD) subgroups, to identify effects of the gender and to assess the effects of methylphenidate and atomoxetine treatment on both face and emotion recognition in patients with ADHD. The study sample consisted of 41 male, 29 female patients, 8-15 years of age, who were diagnosed as having combined type ADHD (N = 26), hyperactive/impulsive type ADHD (N = 21) or inattentive type ADHD (N = 23) but had not previously used any medication for ADHD and 35 male, 25 female healthy individuals. Long-acting methylphenidate (OROS-MPH) was prescribed to 38 patients, whereas atomoxetine was prescribed to 32 patients. The reading the mind in the eyes test (RMET) and Benton face recognition test (BFRT) were applied to all participants before and after treatment. The patients with ADHD had a significantly lower number of correct answers in child and adolescent RMET and in BFRT than the healthy controls. Among the ADHD subtypes, the hyperactive/impulsive subtype had a lower number of correct answers in the RMET than the inattentive subtypes, and the hyperactive/impulsive subtype had a lower number of correct answers in short and long form of BFRT than the combined and inattentive subtypes. Male and female patients with ADHD did not differ significantly with respect to the number of correct answers on the RMET and BFRT. The patients showed significant improvement in RMET and BFRT after treatment with OROS-MPH or atomoxetine. Patients with ADHD have difficulties in face recognition as well as emotion recognition. Both OROS-MPH and atomoxetine affect emotion recognition. However, further studies on the face and emotion recognition are needed in ADHD.

A Retrospective Investigation of Clozapine Treatment in Autistic and Nonautistic Children and Adolescents in an Inpatient Clinic in Turkey.

OBJECTIVE: The aim of this retrospective study is to examine the clinical outcomes and safety of clozapine in children and adolescents with schizophrenia or other psychotic disorders/autism spectrum disorder (ASD) or affective disorders. METHODS: The inpatient and outpatient files of all children and adolescents treated with clozapine over a period of 34 months (from October 2011 to July 2014) were reviewed. Demographic and clinical data were examined to describe clinical and metabolic findings, dosing, and tolerability of clozapine treatment in youth with schizophrenia, other psychotic disorders, ASD, or bipolar disorder. RESULTS: The 37 pediatric patients included 26 patients with schizophrenia or other psychotic disorders, 7 patients with ASD complicated by schizophrenia or other psychotic disorders or affective disorders, and 4 patients with ASD only. In all groups (n = 37) there was a significant reduction (p < 0.001) in Brief Psychiatric Rating Scale (BPRS) points after clozapine treatment during the inpatient period (38.78 ± 27.75 days). In patients with schizophrenia or other psychotic disorders co-occurring with ASD or not (n = 31), there was a significant improvement in psychotic symptoms according to Positive and Negative Syndrome Scale (PANSS) total scores and subscores (p < 0.001). Of the 26 patients with schizophrenia or other psychotic disorders, 8 (30.8%) showed a positive response (>30% symptom reduction on BPRS). In patients with ASD complicated by schizophrenia or other psychotic disorders or bipolar disorders (n = 7), there was a significant reduction (p = 0.017) in BPRS scores after clozapine treatment. The discontinuation rate for clozapine was 10.8%, and the most frequently observed side effect was hypersalivation (54.1%). Neutropenia associated with clozapine was observed in only one patient (2.7%). CONCLUSIONS: Clozapine seems to be effective and safe in children and adolescents with schizophrenia or other psychotic disorders co-occuring with ASD or not. There is a need for further studies for determining the efficacy of clozapine in children and adolescents with bipolar affective disorder or ASD.

The Assessment of Family Functions, Dyadic Adjustment, and Parental Attitude in Adolescents with Substance Use Disorder.

INTRODUCTION: Family structure and family attitudes have been reported to be important factors in the development of substance use disorders. In this study, we aimed to assess the relationship between substance use and family functions, parental attitude, and parental dyadic adjustment of adolescents with substance use disorder. METHODS: The study was conducted on 50 patients, comprising 9 female and 41 male adolescents between the ages of 14 and 18 years, treated at Bakirköy Mental Health Hospital, Substance Abuse Research, Treatment and Education Center for Children Adolescents (ÇEMATEM), Turkey, with the diagnosis of substance use disorder according to DSM-5 and their parents and a control group comprising 50 healthy adolescents without any psychopathology or substance use disorder and their parents. The study was designed as a matched case-control study for age and gender. Sociodemographic Data Form (SDF), Parental Attitude Scale (PAS), Dyadic Adjustment Scale (DAS), and Family Assessment Device (FAD) were applied to both groups. RESULTS: When the study and control groups were compared with regard to the PAS, the study group scores determined for "involvement-acceptance," "psychological autonomy," and "control-supervision" dimensions were significantly lower than the control group scores. Compared with the control group, dyadic adjustment was lower in terms of "dyadic cohesion," "dyadic consensus," and "affectional expression." Living with biological parents and the togetherness of parents were lower in the study group. "Problem solving," "communication," "roles," "affective responsiveness," "affective involvement," "behavior control," and "general functioning" dimension scores according to FAD were also significantly higher in the study group. CONCLUSION: Compared with togetherness of the controls, the dyadic adjustment of their parents was lower and family functions as perceived by the parents and adolescents were unhealthier in the adolescents using substances. These findings indicate that the family functions, dyadic adjustment, and parental attitude styles need to be assessed in the risk groups to determine familial risk factors and to structure protective measures. These assessments may guide clinicians and policy-makers toward good clinical practice and help build protective measures.

[First Episode Psychosis: Relationship of Symptoms, Initial Treatment and Clinical Response]. / Ilk Psikoz Atagi: Belirtiler, Tedavi Baslangici ve Klinik Yanit Iliskisi.

OBJECTIVE: It was aimed to explore the relationship of clinical psychopathology and treatment response with "duration of untreated psychosis" (DUP) and "duration of untreated illness"(DUI) in 15-20 years old (mean age: 17,34 ± 1.69) inpatients in Turkey. METHOD: Mood disorders with psyhotic features were grouped as affective psychoses (18 patients, mean age: 17,28 ± 1,75); schizophrenia, schiozophreniform disorder and other psychotic disorders were grouped as non-affective psychoses (25 patients, mean age: 17,38 ± 1,68). 43 patiens (11 females, 32 males) were evaluated for acute treatment response with Positive and Negative Scale-PANSS and Clinical Global Impressions Scale-CGI. RESULTS: Mean DUP was determined as 6,5 ± 12,4 weeks, mean DUI was determined as 37,8 ± 49,8 weeks. For the affective psychosis (AP) group; mean DUP was 1,9 ± 1,2 weeks, mean DUI was 24,6 ± 37,1 weeks, for the non-affective psychosis (NAP) group; mean DUP was 9,8 ± 15,5 weeks, mean DUI was 47,3 ± 55,9 weeks. Treatment response was better for the non-affective psychosis group and for the patients who had earlier access to treatment. Shorter DUP and DUI was related with better PANSS negative symptom severity at the time of the discharge. CONCLUSION: Better treatment response related with shorter DUP and DUI reveals the significance of early treatment for the disease prognosis.

Sociodemographic characteristics and drug abuse patterns of adolescents admitted for substance use disorder treatment in Istanbul.

BACKGROUND: Adolescent substance use is an increasing major health problem in developing countries. OBJECTIVES: To evaluate the sociodemographic characteristics and drug abuse patterns of children and youth seeking treatment in Turkey. METHODS: This retrospective study reviewed the demographic and clinical data of substance users who visited the substance addiction treatment clinic for children and youth in Bakirköy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery in Istanbul, between January 2011 and December 2012. RESULTS: The sample comprised of 1969 children and youth aged between 11 and 20 (346 female and 1623 male). Cannabis (60.1%), followed by solvents/inhalants (38.3%) and ecstasy (33.4%), were the most prevalent substances used. The use of solvents/inhalants was more common among males, whereas ecstasy and cocaine use were more common among females. The mean age for the onset of substance use was 13 years. The proportion of polysubstance use was 60.2%. There was a mean duration of 2.28 ± 1.91 years between the first substance use and seeking treatment. The risk factors for most of the drug usage were onset of substance use at a young age, gender, treatment admission at older ages, higher parental criminal history, and having substance using parents or relatives. CONCLUSION: Findings of the very early onset of substance and polysubstance use indicated easy accessibility of legal and illicit substances by children and youth in Istanbul. These findings on Turkish children and youth who seek substance use treatment can be useful in developing preventive early interventions and treatment facilities.

Liver enzyme levels in adolescent patients treated with buprenorphine and additional psychotropic agents.

BACKGROUND: There are limited efficacy and safety data for buprenorphine/naloxone treatment in adolescents, and little is known about the incidence and prevalence of liver function abnormalities in young patients using buprenorphine/naloxone. OBJECTIVES: To assess the changes in liver enzyme levels associated with buprenorphine/naloxone treatment and co-medication with psychotropic agents among opioid dependent subjects aged 15-18 years. METHODS: Liver enzyme levels (ALT and AST) were evaluated among 59 adolescent subjects before and following eight weeks of buprenorphine/naloxone treatment. RESULTS: The frequency of additional psychotropic use was 60%. The patients' mean liver enzyme levels at weeks 2 and 4 were significantly higher than the baseline (ALT: p < 0.0001 and p = 0.003, and AST: p < 0.0001 and p = 0.016, respectively). However, there was no statistically significant difference in AST and ALT levels between the baseline and week 8. The majority of the abnormalities seen were clinically nonsignificant elevations (less than two times the upper limit of normal). It is plausible that the abnormalities in liver enzymes could have been mediated by the use of psychotropic medications. CONCLUSIONS: Buprenorphine/naloxone was well tolerated in most adolescent patients, besides clinically nonsignificant liver enzyme elevations. Psychotropic medications may have been associated with the liver enzyme changes early in the course of treatment. Nevertheless, given the relatively small number of adolescents studied to date with buprenorphine/naloxone, additional studies evaluating liver enzymes in young patients receiving buprenorphine/naloxone (and no other psychotropics) are needed.

Mood disorder with mixed, psychotic features due to vitamin b12 deficiency in an adolescent: case report.

Vitamin B12 is one of the essential vitamins affecting various systems of the body. Reports of psychiatric disorders due to its deficiency mostly focus on middle aged and elderly patients. Here we report a case of vitamin B 12 deficiency in a 16-year old, male adolescent who presented with mixed mood disorder symptoms with psychotic features. Chief complaints were "irritability, regressive behavior, apathy, crying and truancy" which lasted for a year. Premorbid personality was unremarkable with no substance use/exposure or infections. No stressors were present. The patient was not vegetarian. Past medical history and family history was normal. Neurological examination revealed glossitis, ataxia, rigidity in both shoulders, cog-wheel rigidity in the left elbow, bilateral problems of coordination in cerebellar examination, reduced swinging of the arms and masked face. Romberg's sign was present. Laboratory evaluations were normal. Endoscopy and biopsy revealed atrophy of the gastric mucosa with Helicobacter Pylori colonization. Schilling test was suggestive of malabsorbtion. He was diagnosed with Mood disorder with Mixed, Psychotic Features due to Vitamin B12 Deficiency and risperidone 0.5 mg/day and intramuscular vitamin B12 500 mcg/day were started along with referral for treatment of Helicobacter pylori. A visit on the second week revealed no psychotic features. Romberg's sign was negative and cerebellar tests were normal. Extrapyramidal symptoms were reduced while Vitamin B12 levels were elevated. Risperidone was stopped and parenteral Vitamin B12 treatment was continued with monthly injections for 3 months. Follow-up endoscopy and biopsy at the first month demonstrated eradication of H. pylori. He was followed monthly for another 6 months and psychiatric symptoms did not recur at the time of last evaluation. Despite limitations, this case may underline the observation that mood disorders with psychotic features especially with accompanying extrapyramidal symptoms lacking a clear etiology may be rare manifestation of vitamin B12 and/or folate deficiency in children and adolescents and be potentially amenable to treatment.

Liver function tests in children and adolescents receiving risperidone treatment for a year: a longitudinal, observational study from Turkey.

OBJECTIVE: To determine the changes in liver function tests after long-term risperidone treatment in a child and adolescent population. METHODS: Weight, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase and serum bilirubin of the patients were assessed in pre-treatment period, and at the sixth and 12th months of treatment. One hundred children and adolescents (aged between 3 and 18 years) were enrolled to the study. RESULTS: Liver enzyme and bilirubin levels are higher than normal in 21.0% of the patients without clinical symptoms. No cases of hepatic failure or jaundice were seen. Only in an 8-year-old boy were there ALT level increases up to three-fold and AST level increases up to two-fold. After discontinuation of the risperidone treatment, enzyme levels were normalized in this patient. Alkaline phosphatase, alanine and aspartate aminotransferases were the most frequently increased enzymes. CONCLUSION: In this study, after long-term risperidone treatment of children and adolescents there was no evidence of clinically significant increases of liver enzymes and bilirubin levels. These results indicate that risperidone treatment may rarely cause serious liver enzyme increases, and may commonly cause clinically insignificant changes in liver function tests.

Risperidone rechallenge for marked liver function test abnormalities in an autistic child.

Risperidone have been reported to commonly lead to asymptomatic elevation of liver enzymes in adult population, and recently in children and adolescents. Results from controlled clinical trials, reports of spontaneous adverse events, and published studies/ case reports suggest that severe hepatotoxicity may be rare but can occur in the pediatric population. In the following case report, we describe a 5-year-old male patient diagnosed as autism with severe distruptive behavior. Substantial improvement was achieved with risperidone therapy. Increase in liver enzymes at the beginning of the risperidone treatment was successfully managed with multidisciplinary approach as the treatment was initially withdrawn, afterwards restarted and carefully continued. We demonstrated that risperidone may be cautiously rechallenged in selected pediatric patients who showed marked psychiatric improvement with risperidone on the face of liver enzymes elevation. Some important patents on risperidone delivery and their use for the treatment of autism are also outlined.