Publications by authors named "Doron Gothelf"

145 Publications

Stimulant Treatment Effect on Anxiety Domains in Children with Attention-Deficit/Hyperactivity Disorder With and Without Anxiety Disorders: A 12-Week Open-Label Prospective Study.

J Child Adolesc Psychopharmacol 2021 Jul 30. Epub 2021 Jul 30.

The Child Psychiatry Division, Sheba Medical Center, Edmond and Lily Safra Children's Hospital, Ramat Gan, Israel.

The effect of stimulants on anxiety domains has not been systematically studied. We assessed prospectively the impact of stimulant treatment in children with attention-deficit/hyperactivity disorder (ADHD) on the severity of anxiety domains and on ADHD with comorbid anxiety disorders. Children with ADHD ( = 57, aged 6-15 years) started a stimulant or were switched from one stimulant to another. Assessments were conducted at four time points (baseline and weeks 2, 6, and 12) and consisted of parental questionnaires (ADHD rating scale, screen for child anxiety related disorders [SCARED]), and side effect questionnaire completed by a child psychiatrist. A significant improvement in total SCARED scores was obtained after 12 weeks stimulant treatment in children both with and without anxiety disorders. Significant reductions were detected in generalized anxiety, separation anxiety, and school avoidance SCARED subscales, but not in panic and social anxiety subscales. ADHD symptoms significantly improved both in children with and without anxiety comorbidities. We found specific effects of stimulants on anxiety domains. Stimulant treatment, even for ADHD children diagnosed with comorbid anxiety disorders, is relatively safe regarding the risk of anxiety exacerbation. Moreover, the presence of anxiety symptoms or disorders does not interfere with the beneficial effect of the stimulants on the ADHD core symptoms. Clinical trial regestration number: IRB SMC-6893-20.
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http://dx.doi.org/10.1089/cap.2021.0011DOI Listing
July 2021

Internalizing symptoms impede adolescents' ability to transition from in-person to online mental health services during the 2019 coronavirus disease pandemic.

J Telemed Telecare 2021 Jul 30:1357633X211021293. Epub 2021 Jul 30.

Sackler School of Medicine, 58408Tel Aviv University, Israel.

Introduction: Online mental health services were previously found to be effective in many studies. However, this method was not generally used in Israel. By the end of 2019, the coronavirus disease 2019 pandemic erupted, forcing mental health services to transition to online meetings to maintain the standard of care. In this cross-sectional study, we investigated the attitudes of adolescent patients toward this involuntary new mode of care.

Methods: Forty-four adolescents (mean age 14.62 ± 2.12 years, 54.5% females) and 40 of their primary caregivers completed a battery of questionnaires that included the telemedicine satisfaction questionnaire, session evaluation questionnaire, working alliance inventory, and pediatric symptom checklist.

Results: Both adolescents and their caregivers reported a reasonable experience with the online medium and a feeling that the meetings were overall powerful, helpful, and comfortable as demonstrated by medium to high scores on the telemedicine satisfaction questionnaire and session evaluation questionnaire questionnaires. A therapeutic alliance was generally maintained according to working alliance inventory scores. However, working alliance inventory scores were negatively correlated with higher levels of internalizing symptoms and parental stress.

Discussion: Our findings point to the possibility that anxious/depressed adolescents will have greater difficulties re-establishing therapeutic alliance when transitioned from in-person to online meetings. This may be due to the introduction of an "invisible" third party to the therapeutic setting-the computer. Psychologists and psychiatrists should be aware of these difficulties and respond adequately to maintain the standard of care.
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http://dx.doi.org/10.1177/1357633X211021293DOI Listing
July 2021

Trajectories and risk factors for anxiety and depression in children and adolescents with cancer: A 1-year follow-up.

Cancer Med 2021 Aug 26;10(16):5653-5660. Epub 2021 Jul 26.

The Chaim Sheba Medical Center, Ramat Gan, Israel.

Background: There is limited data on the longitudinal trajectories of psychiatric disorders in children with cancer and risk factors for their persistence. The current study aimed to longitudinally assess the trajectories and risk factors for anxiety and depressive symptoms and disorders in children and adolescents with cancer.

Methods: Children and adolescents with cancer and their parents completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Depression and Anxiety Module and were interviewed by the semi-structured Affective and Anxiety Modules of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), at 4 time points, 1, 4, 7, and 12 months following the diagnosis of cancer.

Results: Of the 99 patients enrolled, 48% met criteria for anxiety and/or depressive disorders at least once during the follow-up period. There was a significant decrease in PROMIS pediatric and parent anxiety and depression scores (all p's < 0.01) and in the rate of depressive disorders over time (p = 0.02), while rates of anxiety disorders remained stable. Anxiety PROMIS pediatric and parent scores at baseline, having brain tumors and being in the acute treatment phase significantly predicted the presences of anxiety disorders at endpoint.

Conclusions: Our results highlight the importance of screening for anxiety and disorders in children with cancer, especially among those with brain tumors and at the acute phase of treatment.
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http://dx.doi.org/10.1002/cam4.4100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366094PMC
August 2021

Clinical Features in a Large Cohort of Patients With 22q11.2 Deletion Syndrome.

J Pediatr 2021 Jul 17. Epub 2021 Jul 17.

Pediatric Department A and Immunology Service, Edmond and Lily Safra Children's Hospital, Jeffrey Modell Foundation Center, Tel Hashomer, Israel; Sheba Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objectives: To evaluate various clinical aspects, specifically regarding immune status, in a large cohort of patients with DiGeorge syndrome.

Study Design: Data were collected for 98 patients with DiGeorge syndrome treated at a tertiary medical center. This included general information, laboratory results, and clinical features.

Results: The median age at diagnosis was 2.0 years (range, 0.0-36.5 years). The most common symptoms that led to diagnosis were congenital heart defect, speech delay, palate anomalies, and developmental delay. Common clinical features included recurrent infections (76 patients), congenital heart diseases (61 patients), and otorhinolaryngology disorders (61 patients). Twenty patients had anemia; the incidence was relatively high among patients aged 6-59 months. Thrombocytopenia was present in 20 patients. Recurrent chest infections were significantly higher in patients with T cell and T cell subset deficiencies. Decreased T cell receptor excision circles were more common with increasing age (P < .001). Of the 27 patients hospitalized due to infection, pneumonia was a leading cause in 13.

Conclusions: Awareness of DiGeorge syndrome's typical and uncommon characteristics is important to improve diagnosis, treatment, surveillance, and follow-up.
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http://dx.doi.org/10.1016/j.jpeds.2021.07.020DOI Listing
July 2021

Relationship between intelligence quotient measures and computerized neurocognitive performance in 22q11.2 deletion syndrome.

Brain Behav 2021 08 2;11(8):e2221. Epub 2021 Jul 2.

Department of Psychiatry, Brain Behavior Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Intelligence quotient (IQ) testing is standard for evaluating cognitive abilities in genomic studies but requires professional expertise in administration and interpretation, and IQ scores do not translate into insights on implicated brain systems that can link genes to behavior. Individuals with 22q11.2 deletion syndrome (22q11.2DS) often undergo IQ testing to address special needs, but access to testing in resource-limited settings is challenging. The brief Penn Computerized Neurocognitive Battery (CNB) provides measures of cognitive abilities related to brain systems and can screen for cognitive dysfunction. To examine the relation between CNB measures and IQ, we evaluated participants with the 22q11.2DS from Philadelphia and Tel Aviv (N = 117; 52 females; mean age 18.8) who performed both an IQ test and the CNB with a maximum of 5 years between administrations and a subsample (n = 24) who had both IQ and CNB assessments at two time points. We estimated domain-level CNB scores using exploratory factor analysis (including bifactor for overall scores) and related those scores (intraclass correlations (ICCs)) to the IQ scores. We found that the overall CNB accuracy score showed similar correlations between time 1 and time 2 as IQ (0.775 for IQ and 0.721 for CNB accuracy), correlated well with the IQ scores (ICC = 0.565 and 0.593 for time 1 and time 2, respectively), and correlated similarly with adaptive functioning (0.165 and 0.172 for IQ and CNB, respectively). We provide a crosswalk (from linear equating) between standardized CNB and IQ scores. Results suggest that one can substitute the CNB for IQ testing in future genetic studies that aim to probe specific domains of brain-behavior relations beyond IQ.
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http://dx.doi.org/10.1002/brb3.2221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413730PMC
August 2021

Inter-rater reliability of subthreshold psychotic symptoms in individuals with 22q11.2 deletion syndrome.

J Neurodev Disord 2021 06 14;13(1):23. Epub 2021 Jun 14.

The Behavioral Neurogenetics Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel.

Background: Pathways leading to psychosis in 22q11.2 deletion syndrome (22q11.2DS) have been the focus of intensive research during the last two decades. One of the common clinical risk factors for the evolution of psychosis in 22q11.2DS is the presence of positive and negative subthreshold psychotic symptoms. The gold standard for measuring subthreshold symptoms is the Structured Interview for Prodromal Syndromes (SIPS) and its accompanying Scale of Prodromal Symptoms (SOPS) ratings. Although the scale has been used by many centers studying 22q11.2DS, the inter-site reliability of the scale in this population has never been established.

Methods: In the present study, experienced clinical assessors from three large international centers studying 22q11.2DS independently rated video recordings of 18 adolescents and young adults with 22q11.2DS.

Results: The intraclass correlations coefficients (ICCs) among three raters for the SOPS total scores, as well as for the positive, negative, and disorganization subscale scores, were good-to-excellent (ICCs range 0.73-0.93). The raters were also able to reliably determine the subjects' subthreshold syndrome status (ICC = 0.71). The reliability of individual items was good-to-excellent for all items, ranging from 0.61 for motor disturbances [G3] to 0.95 for bizarre thinking.

Conclusions: Our results show that trained clinicians can reliably screen for subthreshold psychotic symptoms in individuals with 22q11.2DS. To increase assessment reliability, we suggest specific clarifications and simplifications to the standard SIPS interview for future studies.
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http://dx.doi.org/10.1186/s11689-021-09372-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204529PMC
June 2021

Association among income loss, financial strain and depressive symptoms during COVID-19: Evidence from two longitudinal studies.

J Affect Disord 2021 08 5;291:1-8. Epub 2021 May 5.

University of Pennsylvania Perelman School of Medicine, Department of Psychiatry, Philadelphia, PA, USA; Lifespan Brain Institute of the Children's Hospital of Philadelphia and Penn Medicine, Philadelphia, PA, USA; Children's Hospital of Philadelphia Department of Child Adolescent Psychiatry and Behavioral Sciences, Philadelphia, PA, USA. Electronic address:

Background: COVID-19 pandemic has major ramifications for global health and economy, with growing concerns about economic recession and implications for mental health. Here we investigated the associations between pandemic-related income loss with financial strain and mental health trajectories over a 1-month course, in two independent cohorts.

Methods: Two independent studies were conducted in the U.S and in Israel at the beginning of the outbreak (March-April 2020, T1; study I: N = 2904, study II: N = 1267) and at a 1-month follow-up (T2; study I: N = 1318, study II: N = 241). Mixed-effects models were applied to assess associations among COVID-19-related income loss, financial strain, and pandemic-related worries about health, with anxiety and depression, controlling for multiple covariates including pre-COVID-19 income.

Results: In both studies, income loss and financial strain were associated with greater depressive symptoms at T1, above and beyond T1 anxiety, worries about health, and pre-COVID-19 income. Worsening of income loss was associated with exacerbation of depression at T2 in both studies. Worsening of subjective financial strain was associated with exacerbation of depression at T2 in one study (US).

Conclusions: Income loss and financial strain were uniquely associated with depressive symptoms and their exacerbation over time, above and beyond pandemic-related anxiety. In times when a myriad of stressors are affecting mental health worldwide, our findings reveal specific links between the economic impact of COVID-19 and psychiatric outcomes.
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http://dx.doi.org/10.1016/j.jad.2021.04.054DOI Listing
August 2021

Is there a correlation between skull base flexure and palatal anomalies in patients with 22q11 deletion syndrome and velopharyngeal dysfunction?

J Craniomaxillofac Surg 2021 Apr 24. Epub 2021 Apr 24.

Sackler School of Medicine,Tel Aviv University, Tel Aviv, Israel; Communication Disorders Faculty, Hadassah Academic College, Jerusalem, Israel.

The study aimed at assessing the relationship between skull base morphology, represented by skull base and nasopharyngeal angles, and palatal anatomy among patients with 22q11DS and velopharyngeal dysfunction. Retrospective analysis of patients with 22q11DS and velopharyngeal dysfunction. Age, sex, severity of velopharyngeal dysfunction, type of cleft (overt cleft palate, submucous cleft palate, occult submucous cleft palate, or no-CP, and cephalometric skull base angles were reviewed. Correlations between type of palatal anomaly and the angles were assessed. Among 132 patients, 71 were male (53.8%) and 61 were female (46.2%), ages 3.3-40.0 years (mean 8.3 ± 6.10). No difference in the mean cranial-base angle (P = 0.353) or in the distribution of the three types of cranial base angle sizes was found among the palatal anomaly groups (P = 0.137). More men had normal cranial base angles and more women had acute angulation (P = 0.008). A positive correlation was found between the skull base and nasopharyngeal angles (P = 0.001, r = -0.590). No direct correlation was found between cranial base morphology and palatal anomalies in patients with 22q11DS, and velopharyngeal dysfunction. This is probably because skull base and palate morphology contribute independently to velopharyngeal dysfunction.
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http://dx.doi.org/10.1016/j.jcms.2021.04.013DOI Listing
April 2021

A binational study assessing risk and resilience factors in 22q11.2 deletion syndrome.

J Psychiatr Res 2021 06 13;138:319-325. Epub 2021 Apr 13.

The Behavioral Neurogenetics Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel; Sagol School of Neuroscience and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: The presentation of neurogenetic disorders such as 22q11.2 Deletion Syndrome (22q11.2DS) includes broad neuropsychiatric phenotypes that impact functioning and require assessment and treatment. Like in non-syndromal neuropsychiatric disorders, there is heterogeneity in symptom severity and illness course. The study of risk and resilience in the general population has benefited from measurement tools that parse heterogeneity and guide treatment. Suitability of such tools in neurogenetic disorders has not been examined and is essential to establish as prerequisite for examining whether similar processes modulate psychopathology in these populations.

Method: We applied the Risk & Resilience Battery assessing intrapersonal, interpersonal, and environmental domains, to 80 patients with 22q11.2DS, 30 from Philadelphia, USA and 50 from Tel-Aviv, Israel. We also evaluated global functioning and obtained self-reports of anxiety and depression. We examined the Risk & Resilience Battery reliability for each factor and used partial correlations to examine relations between the Risk & Resilience Battery factors and clinical measures.

Results: Across samples, items within each risk and resilience factor showed good to excellent internal consistency. Higher scores on peer victimization, emotion dysregulation, and hostile close relationships were related to reports of anxiety and depression. Higher levels of self-reliance related to lower anxiety while greater security in close relationships related to lower depression.

Conclusion: The Risk & Resilience Battery can be applied to 22q11.2DS samples and advance Gene X Environment research and interventions.
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http://dx.doi.org/10.1016/j.jpsychires.2021.03.058DOI Listing
June 2021

Effectiveness of Metformin for Weight Reduction in Children and Adolescents Treated with Mixed Dopamine and Serotonin Receptor Antagonists: A Naturalistic Cohort Study.

J Child Adolesc Psychopharmacol 2021 Jun 21;31(5):376-380. Epub 2021 Apr 21.

The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Mixed dopamine and serotonin receptor antagonists (DSRAs) are associated with significant weight gain and its complications. Our aim was to evaluate the effectiveness of metformin in reducing body mass index (BMI) and metabolic parameters in children treated with DSRAs. We report a naturalistic study of 49 children and adolescents (mean age 14.9 ± 3.7 years), with BMI >85 percentile for age, treated with DSRAs during 2018-2020 in a child psychiatry clinic. Clinical data, anthropometric measurements, and laboratory tests were compared between those who were (study group,  = 31) and were not (control group,  = 18) treated with metformin. The mean study duration was 9.7 ± 5.9 months. The BMI standard deviation scores (BMI-SDS) of the study group declined significantly (from 2.08 ± 0.40 to 1.81 ± 0.54,  < 0.001), while the BMI-SDS of the control group did not change (from 2.03 ± 0.45 to 2.04 ± 0.47,  = 0.838). In the study group, the decline in the delta BMI-SDS/month was more robust among those with good than poor adherence to metformin (-0.047 ± 0.039 vs. -0.004 ± 0.017,  = 0.003). The decrease in BMI-SDS was greater for patients treated with risperidone and clothiapine than with other DSRAs. Fasting insulin and insulin resistance index (homeostasis model assessment of insulin resistance [HOMA-IR]) declined in the study group (from 25.4 ± 13.8 to 19.9 ± 10.7,  = 0.033 and from 5.4 ± 2.7 to 4.2 ± 2.1,  = 0.028, respectively). Metformin treatment was associated with significant decreases in BMI, fasting insulin, and HOMA-IR. The effect of metformin seems to be dependent on adherence and type of DSRAs.
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http://dx.doi.org/10.1089/cap.2021.0006DOI Listing
June 2021

Stimulant treatment effectiveness, safety and risk for psychosis in individuals with 22q11.2 deletion syndrome.

Eur Child Adolesc Psychiatry 2021 Apr 19. Epub 2021 Apr 19.

Child Psychiatry Division, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, 5262000, Tel Hashmoer, Israel.

This study aimed to retrospectively evaluate an association between stimulant treatment for attention-deficit/hyperactivity disorder (ADHD) in individuals with 22q11.2DS and the development of psychotic disorders, to evaluate long-term effectiveness and safety of stimulant treatment in individuals with 22q11.2DS compared to individuals with idiopathic ADHD, and to explore effects of catechol-O-methyltransferase (COMT) genotype on 22q11.2DS response to stimulants and risk of side effects. Rates of stimulant use and methylphenidate equivalent exposure were compared among individuals with 22q11.2DS, between 51 with psychotic disorders and a control group of 57 22q11.2DS without psychotic disorders, from Tel Aviv and Geneva. In addition, 44 individuals with 22q11.2DS and ADHD from Tel Aviv who initiated stimulants before age 18 years were compared to a control group of 35 age- and sex-matched controls with idiopathic ADHD, for treatment effectiveness (Clinical Global Impression Scale-Improvement), and rates of side effects. Stimulant use history and methylphenidate equivalent exposure did not differ among individuals with 22q11.2DS, between those with and without psychotic disorders. The long-term retrospective follow-up (5.3 ± 4.1 years) of stimulant-treated individuals with 22q11.2DS showed a higher rate of significant clinical improvement of ADHD symptoms, compared to idiopathic ADHD individuals (p = 0.013), and similar side effect rates. There was no effect of the COMT genotype on response to stimulants or on any side effects. This preliminary long-term retrospective analysis suggests that stimulant treatment in 22q11.2DS is apparently safe in terms of psychosis conversion and rates of side effects, and that it is effective in alleviating ADHD symptoms.
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http://dx.doi.org/10.1007/s00787-021-01780-zDOI Listing
April 2021

Neutrophils to lymphocytes ratio and psychosis in 22q11.2 deletion syndrome - Clinical and scientific implications.

Schizophr Res 2021 05 16;231:164-169. Epub 2021 Apr 16.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Child and Adolescent Psychiatry Division, Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.

Background: Individuals with 22q11.2 deletion syndrome (22q11.2DS) are at risk for having both psychotic and immune disorders, thus, implying a possible link between the two. The aim of the current study was to evaluate the usefulness of the neutrophiles to leukocytes ratio (NLR), an inflammatory marker, as a bio-marker for overt and prodromal psychotic symptoms in 22q11.2DS.

Methods: Forty-nine individuals with 22q11.2DS (13 with psychotic disorders and 36 without psychotic disorders) and 30 age- and sex-matched healthy controls underwent psychiatric evaluation using a structured psychiatric interview, the Scale of Prodromal Symptoms (SOPS) and the Global Assessment of Functioning (GAF) scale. Blood samples were collected from all participants on the day of assessment. NLR was calculated, compared among the study groups and correlated with SOPS and GAF scores. The non-psychotic 22q11.2DS group was further divided into high- and low-inflammation groups by NLR values and the analyses were done again.

Results: NLR was higher in the psychotic- and the high-inflammation non-psychotic 22q11.2DS groups compared to the low-inflammation non-psychotic 22q11.2DS group and controls. In the high-inflammation non-psychotic 22q11.2DS group NLR increase was associated with an increase of total negative symptoms scores on SOPS and a decrease in GAF scores.

Conclusion: Our results suggest the potential utility of NLR as a bio-marker for psychotic disorders and subthreshold prodromal symptoms in 22q11.2DS. Furthermore, they imply that a disequilibrium between the innate and adaptive arms of the immune system facilitates the progression of psychosis in at risk populations. Further longitudinal studies are warranted to validate our findings, as this was a cross sectional observation.
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http://dx.doi.org/10.1016/j.schres.2021.03.023DOI Listing
May 2021

The Delivery of Diagnosis by Child Psychiatrists: Process Characteristics and Correlates of Distress.

Front Psychiatry 2021 22;12:632207. Epub 2021 Mar 22.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

We describe the attitudes of child psychiatrists toward diagnosis delivery (DD) and explore potential stressful factors associated with the process. Eighty Israeli child psychiatrists completed a questionnaire on their perceptions of DD of schizophrenia, autism spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). We also conducted semi-structured in-depth interviews with 12 child psychiatrists who were asked to share their personal experience with DD. The questionnaire responses revealed that child psychiatrists perceived schizophrenia and ADHD as the most and least severe disorders, respectively, and its treatment as being ineffective and effective, respectively. They expressed negative perceptions toward DD of schizophrenia and positive perceptions toward DD of ADHD. The results of linear regressions revealed that some factors predicted distress accompanying DD in all three diagnoses, such as lack of professional experience, negative perceptions of DD, and the effect of parents' attitudes of opposition to the diagnosis. The interviews revealed that DD was often described by psychiatrists as an emotional experience and that the psychiatrists' age, and whether the psychiatrists identified more with the child or the parent, affected their attitude toward DD. Lastly, the psychiatrists expressed feelings of loneliness in the procedure of DD and their wish to share and reflect on their experiences with others. These findings may contribute to a better understanding of the clinically important topic of DD in child psychiatry that has not been adequately addressed and help deal with psychiatrists' challenges in this task.
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http://dx.doi.org/10.3389/fpsyt.2021.632207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019702PMC
March 2021

Minding the gap between clinical guidelines and real-life clinical work.

Eur Child Adolesc Psychiatry 2021 May;30(5):681-683

The Child & Adolescent Psychiatry Division, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, 5262000, Tel Hashmoer, Israel.

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http://dx.doi.org/10.1007/s00787-021-01765-yDOI Listing
May 2021

Delivering Difficult News: Simulation-Enhanced Training Improves Psychiatry Residents' Clinical Communication Skills.

Front Psychiatry 2021 5;12:649090. Epub 2021 Mar 5.

MSR-Israel Center for Medical Simulation, Sheba Medical Center, Ramat Gan, Israel.

Delivering difficult news to individuals diagnosed with mental health disorders and their family members can be challenging. The use of simulated patients (SP) is an effective teaching method to enhance clinical skills, particularly those around communication. We developed, implemented, and evaluated the effectiveness of an SP-based training module to improve psychiatric residents' clinical communication skills in delivering difficult news. We conducted 5-h workshops consisting of 3 components: (1) a high-fidelity simulation session with a professional actor; (2) a 30-min lecture; and (3) role-playing of 3 short scenarios, during which residents rotated taking on different roles (as psychiatrist, patient, or family member). We observed through a 1-way mirror and videotaped each resident's simulation session and followed it with personalized debriefing. Following the workshop, each resident received the full-length video of their simulated interview, together with a list of questions as a take-home assignment. Two months after the workshop, the residents were invited to a second SP-based session, during which 2 independent evaluators, each a board-certified psychiatrist with expertise in medical simulation, evaluated the participants' communication skills using a previously validated instrument. To avoid observation bias, the 2 evaluators rated the videotapes blind to the timing of the simulation (pre- vs. post-training). Participants completed self-report questionnaires on satisfaction and self-confidence, before, after, and 2 months following the workshop. Of the 28 psychiatric residents who participated in the training day, 24 (86%) completed the post-workshop evaluation. Mean communication score increased from 24.9 to 27.8 (paired -test: 5.6, < 0.001). The mean score for the self-confidence questionnaire, calculated on a 1 to 5 Likert scale, increased from 3.4 to 4.0 after the training day, and remained unchanged (4.2) 2 months later ( < 0.001). An SP-based training module proved useful in improving the objectively measured communication skills of psychiatric residents delivering difficult news. The training further enhanced participants' subjective sense of confidence in those clinical skills.
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http://dx.doi.org/10.3389/fpsyt.2021.649090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973022PMC
March 2021

Trajectories of post-traumatic stress symptoms, anxiety, and depression in hospitalized COVID-19 patients: A one-month follow-up.

J Psychosom Res 2021 04 16;143:110399. Epub 2021 Feb 16.

Division of Child and Adolescent Psychiatry, Sheba Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Objectives: Little is known about the mental health outcomes of hospitalized COVID-19 patients. The aims of the study were: (1) to examine the trajectories of anxiety, depression, and pandemic-related stress factors (PRSF) of COVID-19 hospitalized patients one-month following hospitalization; (2) to assess the presence of post-traumatic stress symptoms (PTSS) a month after hospitalization; (3) to identify baseline risk and protective factors that would predict PTSS one month after hospitalization.

Methods: We contacted hospitalized COVID-19 patients (n = 64) by phone, at three time-points: during the first days after admission to the hospital (T1); after ~two weeks from the beginning of hospitalization (T2), and one month after hospitalization (T3). At all time-points we assessed the levels of anxiety and depression symptoms, as well as PRSF. At T3, PTSS were assessed.

Results: The levels of depressive and anxiety symptoms decreased one-month following hospitalization. Moreover, higher levels of anxiety (standardized β = 1.15, 95% CI = 0.81-1.49, p < 0.001) and depression (β = 0.97, 95% CI = 0.63-1.31 p < 0.001) symptoms during the first week of hospitalization, feeling socially disconnected (β = 0.59, 95% CI = 0.37-0.81 p < 0.001) and experiencing a longer hospitalization period (β = 0.25, 95% CI = 0.03-0.47 p = 0.026) predicted higher PTSS scores a month post-hospitalization.

Conclusions: We identified early hospitalization risk factors for the development of PTSS one month after hospitalization that should be targeted to reduce the risk for PTSS.
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http://dx.doi.org/10.1016/j.jpsychores.2021.110399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885629PMC
April 2021

Treatment of eating disorders in adolescents during the COVID-19 pandemic: a case series.

J Eat Disord 2021 Feb 10;9(1):17. Epub 2021 Feb 10.

Pediatric Psychosomatic Department, Sheba Medical Center, 5265601, Tel Hashomer, Israel.

Background: Eating disorders (EDs) are among the most difficult psychiatric disorders to treat in normal conditions. They are likely even more difficult to manage in at-risk conditions such as the COVID-19 pandemic. Currently there is limited evidence about the particular needs and recommended treatment of adolescents with EDs during the COVID-19 outbreak, in particular regarding the use of telemedicine and the involvement of the family in long distance-treatment.

Aims: We sought to discuss the advantages and problems associated with the use of multi-professional long-distance telemedicine treatment in the management of adolescents with EDs and their families during the COVID-19 outbreak.

Methods: We gathered data about the treatment of adolescents with EDs in our pediatric ED-treatment center in Israel during the COVID-19 outbreak in the first 10 months of 2020, and compared it to the respective period in the past five years (2015-2019). Second, we described the management of four young females with anorexia nervosa (AN), treated in the ambulatory, daycare and inpatient facilities of our center during the COVID-19 pandemic.

Findings: Slightly less patients were treated in our center during the COVID-19 pandemic than in the respective period in the past five years. These patients received at that time considerably more treatment sessions from all treatment providers (psychiatrists, clinical nutritionists and psychotherapists). This was related, in part, to the extensive use of telemedicine during that period (more than as third of all sessions were carried out with telemedicine in comparison to no use of long-distance treatment in the previous years). The condition of the four adolescents with AN was compromised at the start of the COVID-19 quarantine. The use of multi-disciplinary long-distance telemedicine treatment resulted in an improvement in the condition in three of the four adolescents, living in well-organized families, with the motivation and ability to adjust to the new conditions, but not in one adolescent whose family experienced more problems. These families might require the use of face-to-face interventions even during pandemic conditions.

Conclusion: The choice of the mode of treatment for adolescents with EDs during pandemic times (telemedicine vs. face-to-face) should consider the functioning of the family.
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http://dx.doi.org/10.1186/s40337-021-00374-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874990PMC
February 2021

The association between witnessing patient death and mental health outcomes in frontline COVID-19 healthcare workers.

Depress Anxiety 2021 04 5;38(4):468-479. Epub 2021 Feb 5.

The Chaim Sheba Medical Center, Ramat Gan, Israel.

Background: Healthcare workers (HCW) treating coronavirus disease 2019 (COVID-19) patients face high levels of psychological stress. We aimed to compare mental health outcomes, risk and protective factors for posttraumatic stress symptoms (PTSS), probable depression, and anxiety between HCW working in COVID-19 and non-COVID-19 wards.

Methods: A self-report survey, administered in a large tertiary hospital in Israel during the peak of the COVID-19 outbreak was completed by 828 HCW (42.2% physicians, 57.8% nurses. Patient-Reported Outcomes Measurement Information System; the Patient Health Questionnaire-9; the Primary Care-Post Traumatic Stress Disorder Screen for DSM-5 (PC-PTSD-5) were used for assessing anxiety, depression, and PTSS, respectively. Pandemic-related stress factors, negative experiences, and potential protective factors were also assessed.

Results: Median PC-PTSD scores differed significantly between study teams (χ [5] = 17.24; p = .004). Prevalence of probable depression and anxiety were similar in both groups. Risk factors for mental health outcomes included mental exhaustion, anxiety about being infected and infecting family. Overall, higher proportion of the COVID-19 team witnessed patient deaths as compared to the non-COVID-19 team (50.2% vs. 24.7%). Witnessing patient death at the COVID-19 wards was associated with a four-fold increased likelihood of PTSS (odds ratio [OR] = 3.97; 95% confidence interval [CI], 1.58-9.99; p = .0007), compared with the non-COVID-19 wards (OR 0.91; 95% CI, 0.51-1.61; p = .43).

Conclusions: Witnessing patient death appears to be a risk factor for PTSS unique to HCW directly engaged in treating patients with COVID-19. Our findings suggest that helping HCW cope with COVID-19 related deaths might reduce their risk of posttraumatic stress.
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http://dx.doi.org/10.1002/da.23140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014064PMC
April 2021

Phenotypic Characterization of Youth Admitted To Acute Psychiatric Inpatient Unit Following Self-Harm Behavior.

Arch Suicide Res 2021 Jan 6:1-12. Epub 2021 Jan 6.

Objective: Deliberate self-harm (DSH) is a major health concern among adolescents, and is often associated with the need for inpatient psychiatric hospitalization. The aim of this study was to identify clinical and demographic characteristics associated with DSH behavior among adolescents admitted to an acute psychiatric inpatient unit.

Method: We retrospectively analyzed data from the electronic medical records of consecutive admittances to a single acute adolescent inpatient unit ( = 703, mean age 15.2). We compared inpatients with DSH to inpatients without DSH and further compared within the DSH group based on the presence of suicidal intent.

Results: Compared to Non-DSH inpatients ( = 497), youths admitted following DSH ( = 206) were more likely to be female (OR = 2.6, 95%CI 1.7-4), currently in depressive exacerbation (OR = 2.4, 95%CI 1.6-3.6), with concurrent suicidal ideation (OR = 3.9, 95%CI 2.5-5.9), and history of alcohol use (OR = 5.6, 95%CI 3.2-9.5). Within DSH youths, no significant clinical differences were identified between those admitted following a suicide attempt ( = 102) compared to non-suicidal-self-injury ( = 104), who were generally younger.

Conclusions: Findings suggest that early detection and intervention of DSH and depressive crisis is warranted, regardless of the self-harm subtype.HIGHLIGHTSDeliberate self-harm is common among adolescent psychiatric inpatients.Adolescent inpatients with deliberate self-harm are predominantly females with concurrent depression and suicidal ideation.We did not detect significant clinical and demographic differences between self-harmers with or without suicidal intent.
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http://dx.doi.org/10.1080/13811118.2020.1865223DOI Listing
January 2021

Obsessive compulsive symptoms severity among children and adolescents during COVID-19 first wave in Israel‏.

J Obsessive Compuls Relat Disord 2021 Jan 2;28:100610. Epub 2020 Dec 2.

Child and Adolescent Psychiatry Division, Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.

Several current publications have considered persons with obsessive compulsive disorder (OCD) as particularly vulnerable during the COVID-19 period, and to require more frequent symptom monitoring. The purpose of this study was to evaluate whether OCD exacerbated during the first wave of COVID-19 in children and adolescents. Twenty-nine children and adolescents with OCD were evaluated in the midst of the first outbreak of the COVID-19 pandemic in Israel (April-May 2020). Obsessive-compulsive symptoms (OCS) were assessed using the Clinical Global Impression Scale (CGI), by means of a functional questionnaire and by the Obsessive-Compulsive Inventory-child version (OCI-CV) questionnaires. Obsessive-compulsive symptoms were not found to have exacerbated during the period investigated, as evident by a lack of change in CGI severity scores and by improvement rather than deterioration among more participants, based on the CGI improvement scores. Additionally, the children and adolescents reported better general functioning during the COVID-19 period and had relatively low scores on the OCI-CV scale. Our findings indicate that Israeli children and adolescents with OCD coped well with COVID-19 during the first two months of the pandemic and mostly did not experience exacerbation of OCS. However, due to the short duration of exposure to the pandemic at the time of the study, social isolation and lockdown might have masked OCS; thus, further longitudinal studies are needed.
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http://dx.doi.org/10.1016/j.jocrd.2020.100610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709811PMC
January 2021

Anxiety and Depression Symptoms in COVID-19 Isolated Patients and in Their Relatives.

Front Psychiatry 2020 14;11:581598. Epub 2020 Oct 14.

Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

While focusing on the management and care of COVID-19 patients, the mental health of these patients and their relatives is being overlooked. The aim of the current study was to measure anxiety and depression, and to assess their association with socio-demographic and pandemic-related stress factors in COVID-19 patients and their relatives during the initial stage of hospitalization. We assessed isolated hospitalized patients ( = 90) and their relatives (adults and children, = 125) by phone, 25-72 h following patients' admission. The quantitative measures included the Anxiety and Depression modules of the Patient-Reported Outcomes Measurement Information System (PROMIS) and pandemic-related stress factors. Qualitative measures included questions exploring worries, sadness, and coping modes. Both patients and relatives suffer from high levels of anxiety and related pandemic worries, with lower levels of depressive symptoms. Compared to adult relatives, child relatives reported significantly lower anxiety. The multivariable logistic regression analysis revealed an increased risk for anxiety among females and a decreased risk among ultra-orthodox participants. While increased anxiety among patients was associated with feelings of isolation, increased anxiety among relatives was associated with a feeling of not being protected by the hospital. Patients and relatives experience similar high anxiety levels which are more robust in women and lower in ultra-orthodox participants. Our findings indicate that anxiety symptoms of both patients and adult relatives should be addressed.
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http://dx.doi.org/10.3389/fpsyt.2020.581598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591814PMC
October 2020

Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome.

Nat Med 2020 12 9;26(12):1912-1918. Epub 2020 Nov 9.

Centro de Genética y Genómica, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile.

The 22q11.2 deletion syndrome (22q11DS) is associated with a 20-25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline. We studied the association of these phenotypes with two polygenic scores, derived for schizophrenia and intelligence, and evaluated their use for individual risk prediction in 22q11DS. Polygenic scores were not only associated with schizophrenia and baseline intelligence quotient (IQ), respectively, but schizophrenia polygenic score was also significantly associated with cognitive (verbal IQ) decline and nominally associated with sub-threshold psychosis. Furthermore, in comparing the tail-end deciles of the schizophrenia and IQ polygenic score distributions, 33% versus 9% of individuals with 22q11DS had schizophrenia, and 63% versus 24% of individuals had intellectual disability. Collectively, these data show a shared genetic basis for schizophrenia and schizophrenia-related phenotypes and also highlight the future potential of polygenic scores for risk stratification among individuals with highly, but incompletely, penetrant genetic variants.
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http://dx.doi.org/10.1038/s41591-020-1103-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975627PMC
December 2020

The Feasibility of a Parent Group Treatment for Youth with Anxiety Disorders and Obsessive Compulsive Disorder.

Child Psychiatry Hum Dev 2020 Oct 17. Epub 2020 Oct 17.

The Child Psychiatry Division, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

Cognitive behavioral therapy (CBT) is an effective treatment for children and adolescents with anxiety disorders and obsessive-compulsive disorder (OCD). Yet CBT is insufficiently effective in approximately half of cases in clinical trials and in a substantial number of cases children refuse to participate in CBT sessions altogether. Parent training offers a promising alternative to direct child therapy. The present study examined the feasibility of a group implementation of SPACE (Supportive Parenting for Anxious Childhood Emotions), a novel parent training approach aimed at reducing parent's accommodation of children's anxiety symptoms. Based on parent reports (N = 25), following treatment there was a significant decrease in parental accommodation, in family power struggles and in parental sense of helplessness, as well as a significant reduction in anxiety and OCD symptom severity. Results support the promise of group SPACE treatment and underscore the need for additional clinical trial research.
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http://dx.doi.org/10.1007/s10578-020-01082-6DOI Listing
October 2020

Anxiety, pandemic-related stress and resilience among physicians during the COVID-19 pandemic.

Depress Anxiety 2020 10 12;37(10):965-971. Epub 2020 Aug 12.

Sheba Medical Center, Tel Hashomer, Israel.

Background: Physicians play a crucial frontline role in the COVID-19 pandemic, which may involve high levels of anxiety. We aimed to investigate the association between pandemic-related stress factors (PRSF) and anxiety and to evaluate the potential effect of resilience on anxiety among physicians.

Methods: A self-report digital survey was completed by 1106 Israeli physicians (564 males and 542 females) during the COVID-19 outbreak. Anxiety was measured by the 8-item version of the Patient-Reported Outcomes Measurement Information System. Resilience was evaluated by the 10-item Connor-Davidson Resilience Scale. Stress was assessed using a PRSF inventory.

Results: Physicians reported high levels of anxiety with a mean score of 59.20 ± 7.95. We found an inverse association between resilience and anxiety. Four salient PRSF (mental exhaustion, anxiety about being infected, anxiety infecting family members, and sleep difficulties) positively associated with anxiety scores.

Conclusions: Our study identified specific PRSF including workload burden and fear of infection that are associated with increased anxiety and resilience that is associated with reduced anxiety among physicians.
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http://dx.doi.org/10.1002/da.23085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436709PMC
October 2020

Pharmacotherapy of attention-deficit hyperactivity disorder: common quandaries, dilemmas and challenges.

Int Clin Psychopharmacol 2020 11;35(6):300-304

The Child Psychiatry Division, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer.

Multiple studies have shown that pharmacologic treatments for attention-deficit hyperactivity disorder (ADHD), especially stimulants, are generally effective. There is yet a paucity of empirical data, however, for some common clinical conditions overlooked in the ADHD treatment guidelines. Some examples include: in cases of first line treatment failure, it is unclear whether switching from one type of stimulant to another is beneficial. In cases of comorbid ADHD and severe aggressive/disruptive behavior in children, it is unclear whether the best first-line treatment is stimulants or atypical antipsychotics like risperidone. In cases of ADHD with comorbid anxiety disorders, there is no clear evidence regarding optimal treatment. The objectives of this article are to review these issues and propose possible answers for such clinical dilemmas.
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http://dx.doi.org/10.1097/YIC.0000000000000323DOI Listing
November 2020

A three-tier process for screening depression and anxiety among children and adolescents with cancer.

Psychooncology 2020 12 13;29(12):2019-2027. Epub 2020 Aug 13.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objective: To establish and to evaluate the effectiveness of a three-tier screening process of depressive and anxiety disorders among children and adolescents with cancer based on questionnaires (first tier), semistructured psychiatric interviews (second tier), and referral for psychiatric assessment and recommendations for treatment (third tier). We also aimed to determine the rates of depressive and anxiety disorders among participants.

Methods: Participants and their parents completed the Patient Reported Outcomes Measurement Information System (PROMIS) Depression and Anxiety modules. Then, they were interviewed separately using the semistructured Affective and Anxiety Modules of the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). PROMIS cutoff values for diagnosing depressive and anxiety disorders, based on the K-SADS, were calculated by receiver-operating characteristics (ROCs).

Results: Of 91 participants 34 (37.4%) aged 7 to 21 years with cancer met the K-SADS criteria for depressive and/or anxiety disorders. The results of the ROC analyses were stronger for depressive disorders than for anxiety disorders and for more severe cases. The cutoff of 13 on the child-reported PROMIS for a major depressive episode had a sensitivity of 0.80 and a specificity of 0.82, and a cutoff of 14 on the parent-reported PROMIS for generalized anxiety disorder had a sensitivity of 0.78 and a specificity of 0.79.

Conclusions: Using the K-SADS, we found that anxiety and depressive disorders are very common in youngsters with cancer. The three-tier screening process we developed for depression and anxiety in this population provides practical cutoff values for identifying depressive and anxiety disorders in children with cancer.
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http://dx.doi.org/10.1002/pon.5494DOI Listing
December 2020

The interactive effects of test-retest and methylphenidate administration on cognitive performance in youth with ADHD: A double-blind placebo-controlled crossover study.

Psychiatry Res 2020 09 15;291:113056. Epub 2020 May 15.

Sagol Center for Brain and Mind, Baruch Ivcher School of Psychology, Interdisciplinary Center (IDC), Herzliya, Israel.

Studies have shown that Methylphenidate (MPH) affects cognitive performance on the neuropsychological tests and clinical symptoms of individuals diagnosed with attention deficit/hyperactivity disorder (ADHD). This study investigated the acute effects of MPH on neuropsychological tests to explore the interaction between MPH and test-retest effects. Twenty youths with ADHD were tested before and after MPH intake in a double-blind placebo-controlled crossover design and compared to twenty matched controls. Participants were tested on a range of standardized tasks including sustained attention to response, N-Back, and Word/Color Stroop. Identical tasks were administered twice each testing day, before and 1 hour after MPH/Placebo administration. Healthy controls were tested similarly with no intervention. Decreases in response time (RT) variability across tasks and in commission errors were found in ADHD after MPH. Conversely, a significant increase in RT variability and increase in omission errors were observed after the placebo. In the control group, RT variability and omission errors increased whereas commission errors decreased, suggesting fatigue and practice effects, respectively. Test-retest reliability was higher in controls than ADHD. It is suggested that cognitive tests are sensitive objective measures for the assessment of responses to MPH in ADHD but are also affected by repetition and fatigue.
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http://dx.doi.org/10.1016/j.psychres.2020.113056DOI Listing
September 2020

The interactive effects of test-retest and methylphenidate administration on cognitive performance in youth with ADHD: A double-blind placebo-controlled crossover study.

Psychiatry Res 2020 09 15;291:113056. Epub 2020 May 15.

Sagol Center for Brain and Mind, Baruch Ivcher School of Psychology, Interdisciplinary Center (IDC), Herzliya, Israel.

Studies have shown that Methylphenidate (MPH) affects cognitive performance on the neuropsychological tests and clinical symptoms of individuals diagnosed with attention deficit/hyperactivity disorder (ADHD). This study investigated the acute effects of MPH on neuropsychological tests to explore the interaction between MPH and test-retest effects. Twenty youths with ADHD were tested before and after MPH intake in a double-blind placebo-controlled crossover design and compared to twenty matched controls. Participants were tested on a range of standardized tasks including sustained attention to response, N-Back, and Word/Color Stroop. Identical tasks were administered twice each testing day, before and 1 hour after MPH/Placebo administration. Healthy controls were tested similarly with no intervention. Decreases in response time (RT) variability across tasks and in commission errors were found in ADHD after MPH. Conversely, a significant increase in RT variability and increase in omission errors were observed after the placebo. In the control group, RT variability and omission errors increased whereas commission errors decreased, suggesting fatigue and practice effects, respectively. Test-retest reliability was higher in controls than ADHD. It is suggested that cognitive tests are sensitive objective measures for the assessment of responses to MPH in ADHD but are also affected by repetition and fatigue.
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http://dx.doi.org/10.1016/j.psychres.2020.113056DOI Listing
September 2020

Single-Day Simulation-Based Training Improves Communication and Psychiatric Skills of Medical Students.

Front Psychiatry 2020 20;11:221. Epub 2020 Mar 20.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Use of standardized (or simulated) patients (SP) is considered an effective teaching method for improving clinical and communication skills. This study assesses the effect of a single-day simulated patients (SP)-based training course on medical students' communication and basic skills in clinical psychiatry during their psychiatry rotation in a university-affiliated tertiary medical center.

Methods: Forty-two third-year medical students participated. Communication and basic skills in clinical psychiatry were evaluated by a modified Four Habits Coding Scale (4HCS) and the psychiatric interview coding scale before and after SP training. An actual patient interview by the students 1 week after the training was evaluated by an attending psychiatrist blinded to the student's score during the SP-based training. Self-report questionnaires on satisfaction from the training and its impact on their self-confidence were administered at the end of training.

Findings: The mean pre-training 4HCS score of 33.9 increased to 52.3 post-training ( < 0.001). The mean psychiatric interview coding scale score increased from 4.33 to 5.36 ( = 0.002). The self-report questionnaire yielded a mean score of 4.21 on a 1-5 Likert scale, implying high levels of satisfaction and self-confidence.

Conclusions: A single SP-based training course of medical students sufficed to improve clinical and communication skills in psychiatric settings and enhance their subjective perception of those skills.
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http://dx.doi.org/10.3389/fpsyt.2020.00221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099001PMC
March 2020
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