Bio

Honors & Awards


  • The Gazit Globe Postdoctoral Fellowship Award, Gazit Globe (2012-2013)
  • Child Psychiatry Residency, Magna Cum Laude, Israel Psychiatric Association (2009)
  • B.Med.Sc. Graduate, Magna Cum Laude, Medical School, Goldman Medical School, Ben-Gurion University (2000)

Professional Education


  • Doctor of Medicine, Ben Gurion University Of The Negev (2005)
  • Child and Adolescent Psychiatry, Nes-Ziyyona - Beer Yaakov Mental Health Center, Tel Aviv University, Israel (2010)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


I was trained as a child psychiatrist at the Nes-Ziyyona - Beer Yaakov Mental Health Center, affiliated to Tel Aviv University in Israel. As a clinician I have had extensive opportunities to work with children with a range of mental disorders. In parallel to my clinical work I joined the Behavioral Neurogenetics Clinic at Sheba Medical Center, Israel and began conducting neurogenetics research with specific focus on velocardiofacial syndrome and Williams syndrome. My clinical background has fostered my interest in research questions that have immediate relevance to improving the quality of life of children who suffer from psychiatric and neurodevelopmental disorders. In September 2012, I joined the Center for Interdisciplinary Brain Sciences Research at the Department of Psychiatry and Behavioral Sciences at Stanford University working under the mentorship of Dr. Allan Reiss. In my current research, I am studying the brain structure and function of girls who suffer from Turner syndrome. My main research focuses on attention and executive function (a cognitive domain underlying the ability to plan, organize and maintain attention) deficits in Turner Syndrome and other neurogenetic syndromes.

Publications

Journal Articles


  • Risk Factors and the Evolution of Psychosis in 22q11.2 Deletion Syndrome: A Longitudinal 2-Site Study JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Gothelf, D., Schneider, M., Green, T., Debbane, M., Frisch, A., Glaser, B., Zilkha, H., Schaer, M., Weizman, A., Eliez, S. 2013; 52 (11): 1192-1203

    Abstract

    22q11.2 Deletion syndrome (22q11.2DS) is associated with high rates of schizophrenia, other neuropsychiatric disorders, and cognitive deficits. The objectives of this 2-center study were to longitudinally assess the trajectories of psychiatric disorders in 22q11.2DS from childhood to adulthood, and to identify risk factors for their emergence.A total of 125 children and adults with 22q11.2DS were evaluated at 2 time points, baseline and follow-up (4 years apart), using standardized psychiatric and cognitive measures.The rate of mood disorders tended to decrease during childhood and increase during late adolescence. Statistically significant predictors for the presence of a psychotic disorder as well as the severity of positive symptoms at follow-up were identical, and consisted of an anxiety disorder at baseline, lower baseline Full Scale IQ, and a greater decrease in verbal IQ scores between time points. Nine of 10 individuals with an emerging psychotic disorder had an anxiety disorder at baseline. The age of onset for a psychotic disorder was between 14 and 22 years in 82.6% of cases.It is important to evaluate the presence of anxiety disorders in children and adolescents with 22q11.2DS, as they are major risk factors for the emergence of psychotic disorders, which usually occur during late adolescence in this at-risk population.

    View details for DOI 10.1016/j.jaac.2013.08.008

    View details for Web of Science ID 000326480800010

    View details for PubMedID 24157393

  • Phenotypic psychiatric characterization of children with Williams syndrome and response of those with ADHD to methylphenidate treatment AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS Green, T., Avda, S., Dotan, I., Zarchi, O., Basel-Vanagaite, L., Zalsman, G., Weizman, A., Gothelf, D. 2012; 159B (1): 13-20

    Abstract

    Williams syndrome (WS) is associated with cognitive deficits, special behavioral phenotype, and high rates of psychiatric disorders. The aims of the present study were: (1) To compare the rates of psychiatric disorders and repetitive behaviors in children with WS to children with idiopathic developmental disability (DDs); (2) To longitudinally assess the change in psychiatric disorders during adolescence in WS; (3) To assess retrospectively the effectiveness and safety of methylphenidate (MPH) treatment in WS children with ADHD. The study consisted of a cohort of 38 children and adolescents (age 13.1?±?5.2 years) with WS and a sample of age-matched DDs (age 15.0?±?3.1 years). A current follow-up evaluation was conducted after 5.6?±?1.6 years for 25 subjects (65.8%) of the WS cohort. The rate of most psychiatric disorders was found similar in children with WS and DD controls. Specific phobia, especially from noises, obsessive-compulsive symptoms (e.g., aggressive obsessions and repetitive questions), and stereotypic behaviors (e.g., glancing), were more common in WS than DDs. In a longitudinal follow-up of the WS children, we found a decrease in the rate of anxiety disorders. In addition, a clinically significant improvement was reported in 72.2% of WS children with ADHD following MPH treatment. Sadness/unhappiness was the most common side effect associated with MPH treatment in WS, occurring in 2/3 of treated individuals. The present study further elucidates the neuropsychiatric phenotype of WS. Our results also suggest that MPH treatment for ADHD in WS warrants future prospective controlled trials.

    View details for DOI 10.1002/ajmg.b.31247

    View details for Web of Science ID 000298536800003

    View details for PubMedID 22052570

  • The Effect of Methylphenidate on Prefrontal Cognitive Functioning, Inattention, and Hyperactivity in Velocardiofacial Syndrome JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Green, T., Weinberger, R., Diamond, A., Berant, M., Hirschfeld, L., Frisch, A., Zarchi, O., Weizman, A., Gothelf, D. 2011; 21 (6): 589-595

    Abstract

    Methylphenidate (MPH) is commonly used to treat attention-deficit/hyperactivity disorder (ADHD) in all children, including those with velocardiofacial syndrome (VCFS). Yet concerns have been raised regarding its safety and efficacy in VCFS. The goal of this study was to examine the safety and efficacy of MPH in children with VCFS.Thirty-four children and adolescents with VCFS and ADHD participated in a randomized, controlled trial with a 2:1 ratio of MPH versus placebo. All subjects underwent a cardiological evaluation before and after MPH administration. The primary outcome measure was prefrontal cognitive performance following a single dose of MPH or placebo. A follow-up assessment was conducted after a 6-month treatment with MPH.Compared with placebo, single MPH administration was associated with a more robust improvement in prefrontal cognitive performance, including achievements in the Hearts and Flowers executive function task and the visual continuous performance task. After 6 months of treatment, a 40% reduction in severity of ADHD symptoms was reported by parents on the Revised Conners Rating Scale. All subjects treated with MPH reported at least one side effect, but it did not necessitate discontinuation of treatment. MPH induced an increase in heart rate and blood pressure that was usually minor, but was clinically significant in two cases. No differences in response to MPH were observed between catechol-O-methyltransferase Met versus Val carriers.The use of MPH in children with VCFS appears to be effective and relatively safe. A comprehensive cardiovascular evaluation for children with VCFS before and during stimulant treatment is recommended.

    View details for DOI 10.1089/cap.2011.0042

    View details for Web of Science ID 000298399800010

    View details for PubMedID 22149470

  • Psychiatric Disorders and Intellectual Functioning Throughout Development in Velocardiofacial (22q11.2 Deletion) Syndrome JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Green, T., Gothelf, D., Glaser, B., Debbane, M., Frisch, A., Kotler, M., Weizman, A., Eliez, S. 2009; 48 (11): 1060-1068

    Abstract

    Velocardiofacial syndrome (VCFS) is associated with cognitive deficits and high rates of schizophrenia and other neuropsychiatric disorders. We report the data from two large cohorts of individuals with VCFS from Israel and Western Europe to characterize the neuropsychiatric phenotype from childhood to adulthood in a large sample.Individuals with VCFS (n = 172) aged 5 to 54 years were evaluated with structured clinical interviews for psychiatric disorders and age-appropriate versions of the Wechsler intelligence tests.The frequency of psychiatric disorders was high and remarkably similar between samples. Psychotic disorders and depression were uncommon during childhood but increased in rates during adulthood (depressive disorders: 40.7% in young adults [aged 18-24 years]; psychotic disorders: 32.1% in adults [age >24 years]). Cognitive scores were inversely associated with age in subjects with VCFS, including patients without psychosis. Specifically, Verbal IQ (VIQ) scores negatively correlated with age, and the subjects with VCFS and psychotic disorders had significantly lower VIQ scores than nonpsychotic VCFS subjects.Neuropsychiatric deficits in individuals with VCFS seem to follow a developmental pattern. The VIQ scores are negatively associated with age and rates of mood, and psychotic disorders increase dramatically during young adulthood. The data presented here support careful monitoring of psychiatric symptoms during adolescence and young adulthood in VCFS. Prospective longitudinal studies are needed to examine the nature of age-related cognitive changes and their association with psychiatric morbidity in VCFS.

    View details for DOI 10.1097/CHI.0b013e3181b76683

    View details for Web of Science ID 000271068100005

    View details for PubMedID 19797984

  • Relative-assessed psychological factors predict sedation requirement in critically ill patients PSYCHOSOMATIC MEDICINE Green, T., Gidron, Y., Friger, M., Almog, Y. 2005; 67 (2): 295-300

    Abstract

    Sedation is frequently required in critically ill, mechanically ventilated patients. Sedation and analgesia requirements may vary substantially among patients. This study examined whether psychological factors predict amount of sedation requirements beyond the effects of other biomedical parameters.This study used a prospective correlative design in an eight-bed medical intensive care unit at a tertiary university hospital. Fifty-five adult patients requiring mechanical ventilation were included. We evaluated by questionnaires three psychological factors of patients--hostility, anxiety and desire for control (DC)--as completed by patients' relatives at entry to the intensive care unit. Daily doses of sedatives required were monitored. The primary outcome measurement was midazolam dose expressed in mg/kg/h.There was a statistically significant correlation between psychological factors and midazolam dose (mg/kg/h): r values = 0.40 for anxiety, 0.43 for hostility, and 0.46 for DC. Age and pulmonary edema were inversely related to midazolam requirements, whereas smoking, chronic obstructive pulmonary disease, fentanyl dose, and therapeutic intervention scoring system were positively correlated with midazolam doses. In a multiple regression, DC accounted for an additional and significant 5.4% of the variance in midazolam after controlling statistically for the effects of the significant background and biomedical predictors. In the final regression equation, DC and fentanyl were the only significant factors associated with higher sedation requirement.Premorbid psychological profile independently predicts sedation requirement in critically ill, mechanically ventilated patients. Early identification of such a profile may help in sedation management and patient care. The possible mechanisms and clinical implications are discussed.

    View details for DOI 10.1097/01.psy.000156928.12980.99

    View details for Web of Science ID 000227885500020

    View details for PubMedID 15784797

  • Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes. J Psychiatr Res. Zarchi , O., Carmel , ., Avni, C., Attias, J., Frisch, A., Michaelovsky, E., Patya, M., Green, T., Weinberger, R., Weizman, A., Gothelf, D. 2013
  • Genotype-phenotype correlation in 22q11.2 deletion syndrome BMC MEDICAL GENETICS Michaelovsky, E., Frisch, A., Carmel, M., Patya, M., Zarchi, O., Green, T., Basel-Vanagaite, L., Weizman, A., Gothelf, D. 2012; 13

    Abstract

    The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22q11.2 with highly variable physical and neuropsychiatric manifestations. We explored the genotype-phenotype relationship in a relatively large 22q11.2DS cohort treated and monitored in our clinic using comprehensive clinical evaluation and detailed molecular characterization of the deletion.Molecular analyses in 142 subjects with 22q11.2DS features were performed by FISH and MLPA methods. Participants underwent clinical assessment of physical symptoms and structured psychiatric and cognitive evaluation.Deletions were found in 110 individuals including one with an atypical nested distal deletion which was missed by the FISH test. Most subjects (88.2%) carried the 3Mb typically deleted region and 11.8% carried 4 types of deletions differing in size and location. No statistically significant genotype-phenotype correlations were found between deletion type and clinical data although some differences in hypocalcemia and cardiovascular anomalies were noted.Analysis of the patient with the distal nested deletion suggested a redundancy of genes causing the physical and neuropsychiatric phenotype in 22q11.2DS and indicating that the psychiatric and cognitive trajectories may be governed by different genes.MLPA is a useful and affordable molecular method combining accurate diagnosis and detailed deletion characterization. Variations in deletion type and clinical manifestations impede the detection of significant differences in samples of moderate size, but analysis of individuals with unique deletions may provide insight into the underlying biological mechanisms.Future genotype-phenotype studies should involve large multicenter collaborations employing uniform clinical standards and high-resolution molecular methods.

    View details for DOI 10.1186/1471-2350-13-122

    View details for Web of Science ID 000314113600001

    View details for PubMedID 23245648

  • The feasibility and safety of S-adenosyl-l-methionine (SAMe) for the treatment of neuropsychiatric symptoms in 22q11.2 deletion syndrome: a double-blind placebo-controlled trial JOURNAL OF NEURAL TRANSMISSION Green, T., Steingart, L., Frisch, A., Zarchi, O., Weizman, A., Gothelf, D. 2012; 119 (11): 1417-1423

    Abstract

    The goal of this trial was to assess the feasibility and safety of using S-adenosyl-L-methionine (SAMe) to treat depressive disorder, attention deficit/hyperactivity disorder (ADHD) and cognitive deficits in individuals with the 22q11.2 deletion syndrome (22q11.2DS). SAMe supposedly enhances the activity of the COMT enzyme. Because individuals with 22q11.2DS have only one copy of the gene responsible for the enzyme, COMT haploinsufficiency may be associated with their psychiatric morbidity and cognitive deficits. We assessed twelve 22q11.2DS individuals with depressive disorder or ADHD in a randomized double-blind cross-over placebo-controlled trial, using SAMe 800 mg bid. Individuals were evaluated for treatment safety and effectiveness during the trial and upon completion at sixth week. Compared to placebo, there were no significant differences in the rate of reported side effects between SAMe and placebo. Despite a general concern that SAMe might induce mania in vulnerable individuals, no manic or psychotic symptoms were exhibited during the SAMe treatment. Individuals with 22q11.2DS with comorbid depressive disorder with or without psychotic symptoms (n = 5) had a larger numerical improvement on relevant clinical scales compared to placebo. No treatment effect was found on ADHD symptoms in subjects who suffered from 22q11.2DS with comorbid ADHD (n = 7). Cognitive performance did not improve or deteriorate following treatment with SAMe compared to placebo. In conclusion SAMe treatment up to 1,600 mg/day for 6 weeks in 22q11.2DS individuals appears to be safe, well tolerated and with no serious side effects. No significant benefit in depressive or ADHD symptoms was detected.

    View details for DOI 10.1007/s00702-012-0831-x

    View details for Web of Science ID 000310086500019

    View details for PubMedID 22678699

  • [The metabolic syndrome and antipsychotics in children and adolescents]. Harefuah Dori, N., Green, T. 2011; 150 (10): 791-?

    Abstract

    Significant weight gain is a well known side-effect of atypical (second generation) antipsychotics. In recent years there is a growing body of evidence that atypical antipsychotics may cause metabolic syndrome which includes: increased waist circumference, lipid and glucose metabolism changes, and in some cases - elevation of blood pressure. During the last decade there has been a substantial increase in the use of atypical antipsychotics among children and adolescents, mainly due to lower rates of extrapyramidal side-effects, but also due to increased diagnosis of schizophrenia and bipolar disorder in youth, and the widespread use of atypical antipsychotics in disruptive behavior disorders. The definition of the metabolic syndrome in youth derives from the adult definition, but it is not universally accepted in pediatrics. The main difficulty lies in establishing the normal values of height and weight during the different stages of growth in childhood and adolescence. The long term implications of the metabolic syndrome diagnosed in young ages are yet to be studied, as are treatment and preventive options. A literature review of recent studies indicates that youth are more susceptible to adverse metabolic side-effects of atypical antipsychotics compared to adults. These side-effects also occur during treatment with lower doses as in disruptive behavioral disorders. Monitoring these metabolic parameters among adults treated with antipsychotics is lacking, and even more so in children and adolescents. Since youth treated with atypical antipsychotics are likely to be treated for long periods of time, it is crucial to diagnose, treat, and prevent those side-effects.

    View details for PubMedID 22111125

  • Creatine monohydrate in resistant depression: a preliminary study BIPOLAR DISORDERS Roitman, S., Green, T., Osher, Y., Karni, N., Levine, J. 2007; 9 (7): 754-758

    Abstract

    Creatine plays a pivotal role in brain energy homeostasis, and altered cerebral energy metabolism may be involved in the pathophysiology of depression. Oral creatine supplementation may modify brain high-energy phosphate metabolism in depressed subjects.Eight unipolar and two bipolar patients with treatment-resistant depression were treated for four weeks with 3-5 g/day of creatine monohydrate in an open add-on design. Outcome measures were the Hamilton Depression Rating Scale, Hamilton Anxiety Scale, and Clinical Global Impression scores, recorded at baseline and at weeks 1, 2, 3 and 4.One patient improved considerably after one week and withdrew. Both bipolar patients developed hypomania/mania. For the remaining seven patients, all scale scores significantly improved. Adverse reactions were mild and transitory.This small, preliminary, open study of creatine monohydrate suggests a beneficial effect of creatine augmentation in unipolar depression, but possible precipitation of a manic switch in bipolar depression.

    View details for Web of Science ID 000250644300011

    View details for PubMedID 17988366

  • [Complex posttraumatic stress disorder]. Harefuah Green, T., Kotler, M. 2007; 146 (11): 883-?

    Abstract

    The characteristic symptoms resulting from exposure to an extreme trauma include three clusters of symptoms: persistent experience of the traumatic event, persistent avoidance of stimuli associated with the trauma and persistent symptoms of increased arousal. Beyond the accepted clusters of symptoms for posttraumatic stress disorder exists a formation of symptoms related to exposure to extreme or prolonged stress e.g. childhood abuse, physical violence, rape, and confinement within a concentration camp. With accumulated evidence of the existence of these symptoms began a trail to classify a more complex syndrome, which included, but was not confined to the symptoms of posttraumatic stress disorder. This review addresses several subjects for study in complex posttraumatic stress disorder, which is a complicated and controversial topic. Firstly, the concept of complex posttraumatic stress disorder is presented. Secondly, the professional literature relevant to this disturbance is reviewed and finally, the authors present the polemic being conducted between the researchers of posttraumatic disturbances regarding validity, reliability and the need for separate diagnosis for these symptoms.

    View details for PubMedID 18087837

  • [The treatment of mood stabilizers in children and adolescents suffering from bipolar affective disorder]. Harefuah Green, T., Shoval, G., Weizman, A. 2005; 144 (11): 810-?

    Abstract

    Bipolar disorder is defined as a mood disorder. It is characterized by alteration in mood, from elation and/or irritability to depression. The prevalence of this disorder in children and adolescents is 1%, and it disrupts the lives of children and adolescents. The treatment of bipolar disorder includes mood stabilizers. In contrast to the extensive literature in adult bipolar disorder, controlled studies of lithium and anticonvulsants in the management of mood disorders in childhood are scarce. This review summarizes recent clinical pharmacologic studies of mood stabilizers, including lithium and anticonvulsants in the management of bipolar disorder in children and adolescents who suffer from this syndrome. In addition, the authors review new anticonvulsants such as lamotrigine, gabapentin and topiramate as mood stabilizers.

    View details for PubMedID 16358659

  • Acute myelogenous leukemia with splenic infarcts presenting as fulminant multi-organ failure LEUKEMIA & LYMPHOMA Green, T., Rabinovitz, A., Sinelnikov, I., Yermiahu, T., Almog, Y. 2003; 44 (12): 2143-2145

    Abstract

    A 60-year-old male was admitted with leukopenia, thrombocytopenia, splenic infarcts and a normal peripheral smear. Within few hours he rapidly deteriorated with fatal multi-organ failure. Autopsy revealed massive infiltration of leukemic cells in several organs. Acute myelogenous leukemia should be considered in a patient presenting with unexplained multiorgan failure.

    View details for DOI 10.1080/1042819031000119244

    View details for Web of Science ID 000186108900018

    View details for PubMedID 14959861

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