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Doron Gothelf

Publications and source records attributed to Doron Gothelf.

At least 19 recordsLinked to original sources
PubMed2006

Association of the low-activity COMT 158Met allele with ADHD and OCD in subjects with velocardiofacial syndrome.

Velocardiofacial syndrome (VCFS) is caused by a microdeletion in chromosome 22 and is a risk factor for the development of schizophrenia and other psychiatric disorders. The catechol-O-methyltransferase (COMT), residing in the 22q11.2 microdeletion region, is a major candidate gene for genetic susceptibility to neuropsychiatric disorders in VCFS. Individuals with VCFS carrying the low-activity allele (COMTL) are expected to have the lowest possible COMT activity since they have only a single copy of the gene. We explored the possibility that COMTL is associated with psychiatric disorders commonly found in VCFS. Fifty-five unrelated individuals with VCFS underwent psychiatric evaluation and were genotyped for the COMT 158Val/Met polymorphism coding for COMT high/low-activity alleles. The COMTL allele was significantly more prevalent in VCFS subjects with attention deficit hyperactivity disorder (ADHD) (73.9% vs. 33.3%, OR 5.67, chi2=7.76, p=0.005) and obsessive-compulsive disorder (OCD) (78.6% vs. 33.3%, OR 7.33, chi2=7.24, p=0.007) than in the control group (VCFS subjects without OCD, ADHD and schizophrenia/schizoaffective (SZ/SZaff) disorder). The results of this study suggest that greatly reduced COMT activity, as expected in VCFS COMTL individuals may be a risk factor for psychiatric sequelae in this population. Future longitudinal studies focusing on additional COMT polymorphic sites and other candidate genes from the deleted region will elucidate the molecular pathways leading to schizophrenia and other psychiatric disorders in VCFS.

Adolescent↗
PubMed2006

Follow-up of preschool children with severe emotional and behavioral symptoms.

BACKGROUND: Biological and environmental factors have been related to the persistence of psychopathology in preschool children. The objective of the study was to identify the factors predicting the clinical outcome in preschool inpatients with emotional and behavioral disorders. METHOD: Twenty-eight children aged 3 to 6.5 years attending a therapeutic nursery were evaluated. Clinical data were collected from the children's charts, including: biological parameters, developmental milestones, intelligence level, socioeconomic status, and stressful life events. Severity of symptoms at follow-up was assessed using the Clinical Global Impression Scale. RESULTS: Low socioeconomic status, excess stressful life events, and female gender were associated with poor clinical outcome. Biological factors such as pregnancy and birth complications and genetic factors were not significant predictors. LIMITATIONS: The study was limited by its retrospective design and small sample size. CONCLUSIONS: More effort in social interventions and supportive family therapy may improve the outcome of young children with emotional and behavioral problems.

Child↗
PubMed2005

COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome.

Although schizophrenia is strongly hereditary, there are limited data regarding biological risk factors and pathophysiological processes. In this longitudinal study of adolescents with 22q11.2 deletion syndrome, we identified the catechol-O-methyltransferase low-activity allele (COMT(L)) as a risk factor for decline in prefrontal cortical volume and cognition, as well as for the consequent development of psychotic symptoms during adolescence. The 22q11.2 deletion syndrome is a promising model for identifying biomarkers related to the development of schizophrenia.

Adolescent↗
PubMed2005

The contribution of novel brain imaging techniques to understanding the neurobiology of mental retardation and developmental disabilities.

Studying the biological mechanisms underlying mental retardation and developmental disabilities (MR/DD) is a very complex task. This is due to the wide heterogeneity of etiologies and pathways that lead to MR/DD. Breakthroughs in genetics and molecular biology and the development of sophisticated brain imaging techniques during the last decades have facilitated the emergence of a field called Behavioral Neurogenetics. Behavioral Neurogenetics focuses on studying genetic diseases with known etiologies that are manifested by unique cognitive and behavioral phenotypes. In this review, we describe the principles of magnetic resonance imaging (MRI) techniques, including structural MRI, functional MRI, and diffusion tensor imaging (DTI), and how they are implemented in the study of Williams (WS), velocardiofacial (VCFS), and fragile X (FXS) syndromes. From WS we learn that dorsal stream abnormalities can be associated with visuospatial deficits; VCFS is a model for exploring the molecular and brain pathways that lead to psychiatric disorders for which subjects with MR/DD are at increased risk; and finally, findings from multimodal imaging techniques show that aberrant frontal-striatal connections are implicated in the executive function and attentional deficits of subjects with FXS. By deciphering the molecular pathways and brain structure and function associated with cognitive deficits, we will gain a better understanding of the pathophysiology of MR/DD, which will eventually make possible more specific treatments for this population.

Brain↗
PubMed2005

Pilot study: fluvoxamine treatment for depression and anxiety disorders in children and adolescents with cancer.

OBJECTIVE: To evaluate the safety, tolerability, and benefit of fluvoxamine for the treatment of major depressive disorder or anxiety disorders in children and adolescents with cancer. METHOD: The study was conducted from 2001 to 2004 at a pediatric hematology-oncology center. Fifteen children and adolescents with cancer were treated with fluvoxamine 100 mg/day in an open prospective 8-week trial. Safety and tolerability were evaluated at baseline and at weeks 4 and 8 by blood tests and the Side Effects Checklist. Clinical benefit was assessed with the Clinical Global Impressions-Improvement, the Children's Depression Rating Scale-Revised, and the Pediatric Anxiety Rating Scale. RESULTS: Fluvoxamine was well tolerated by all subjects. Psychiatric symptoms improved significantly. CONCLUSIONS: In this open trial, fluvoxamine appeared to be well tolerated and was associated with a promising reduction in the depression and anxiety symptoms of pediatric patients with cancer.

Adolescent↗
PubMed2004

Psychosocial situations, quality of depression and schizophrenia in adolescents.

The relationships between acute life events and type of depression were evaluated among inpatient adolescents with schizophrenia. Forty-two adolescent inpatients were assessed, 25 with schizophrenia and 17 with personality disorder. Acute life events and other psychosocial situations were identified with the ICD-10 Axis V semistructured interviews. The Depression Equivalent Questionnaire for Adolescents (DEQ-A) and the Positive and Negative Symptom Scale (PANSS) were used to measure quality and severity of depression. In the patients with schizophrenia, psychosocial situations were related to the anaclitic type of depression, whereas in the subjects with personality disorder, they were highly correlated with introjective depression. In the schizophrenic group, the psychosocial situations related to depression were of a more intrapersonal nature and, in the personality-disordered group, they were more interpersonal. Environmental factors play an important role in the course of schizophrenia in adolescents and should remain a focus of study. Object relations theory may be of heuristic value in the investigation of these factors.

Adolescent↗
PubMed2004

Obsessive-compulsive disorder in patients with velocardiofacial (22q11 deletion) syndrome.

The study of neurogenetic microdeletion syndromes provides an insight into the developmental psychopathology of psychiatric disorders. The aim of the study was to evaluate the prevalence of psychiatric disorders, especially obsessive-compulsive disorder (OCD), in patients with velocardiofacial syndrome (VCFS), a 22q11 microdeletion syndrome. Forty-three subjects with VCFS of mean age 18.3 +/- 10.6 years were comprehensively assessed using semi-structured psychiatric interview and the Yale-Brown obsessive compulsive scale (Y-BOCS). Best estimate diagnoses were made on the basis of information gathered from subjects, parents, teachers, and social workers. Fourteen VCFS subjects (32.6%) met the DSM-IV criteria for OCD. OCD had an early age of onset and generally responded to fluoxetine treatment. It was not related to mental retardation. The most common obsessive-compulsive symptoms were contamination, aggression, somatic worries, hoarding, repetitive questions, and cleaning. Sixteen of the 43 patients (37.2%) had attention-deficit/hyperactivity disorder (ADHD), and 7 (16.2%) had psychotic disorder. The results of our study suggest that there is a strong association between VCFS and early-onset OCD. This finding may be significant in the understanding of the underlying genetic basis of OCD.

Adolescent↗
PubMed2004

Genetic, developmental, and physical factors associated with attention deficit hyperactivity disorder in patients with velocardiofacial syndrome.

Velocardiofacial syndrome (VCFS) is a relatively common developmental neuropsychiatric syndrome caused by a 22q11 microdeletion. There is an extensive variability in the phenotypic expression of this disease. The most common psychiatric disorder in VCFS is attention-deficit/hyperactivity disorder (ADHD), affecting 35-55% of patients. This study investigated the association of familial, developmental, and physical factors with the occurrence of ADHD in 51 patients with nonfamilial VCFS. Twenty-one patients (41.2%) were diagnosed with ADHD. There was a significantly greater prevalence of ADHD in the first-degree relatives of the patients with ADHD than in those without (OR = 5.9, 95% CI = 1.6-22.1, P = 0.006). No differences were noted between the ADHD and non-ADHD groups in mean Obstetric Complication Scale Score, gestational age, birth weight, age at first words, walking, and achieving bowel control. The two groups also had similar IQ scores (total, verbal, and performance) and had a similar average degree of severity of facial dysmorphism and cardiac and cleft anomalies. These findings indicate that ADHD in VCFS has a genetic contribution and the patients' VCFS-related developmental factors and physical illnesses play a lesser role.

Adolescent↗
PubMed2004

Schizophrenia in adolescent twins: a case study.

Studies of schizophrenia in twins have historically influenced the psychiatric world in shifting the focus of the etiology of psychiatric disorders from a psychodynamic to a genetic one. Although twinning is as frequent a phenomenon as schizophrenia, clinical issues relating to the development of twins and treatment of psychiatrically sick twins are relatively infrequent in the literature. This article presents the treatment of adolescent schizophrenic twins, and focuses on specific developmental, educational and therapeutic issues that must be considered when treating twins. The recent treatment of identical schizophrenic twins has allowed us to review the literature and revisit some of these issues.

Adolescent↗
PubMed2003

Depression and suicidal behavior in adolescent inpatients with obsessive compulsive disorder.

BACKGROUND: To investigate the prevalence and correlations of suicidal behavior in obsessive compulsive disorder (OCD) among adolescent psychiatric inpatients. METHODS: A total of 348 adolescents, representing consecutive admissions to an adolescent inpatient unit, were assessed. Of these, 40 patients had OCD, 118 had schizophrenia, 59 had an affective disorder, 81 had a conduct disorder and 50 had an eating disorder. In addition, 87 normal community controls were assessed. All subjects were assessed for suicidal behavior by the Childhood Suicide Potential Scale (CSPS), for depression by the Beck Depression Inventory, for impulsiveness by the Impulse Control Scale, for anxiety by the State-Trait Anxiety Scale and for aggression by the Yudowsky Overt Aggression Scale. RESULTS: All the psychiatrically ill subjects, including those with OCD, had high levels of depression, anxiety and impulsiveness, which were far higher than those of the controls. The rate of attempted suicide was, however, much lower in the OCD subjects. In addition, there was a significant inverse correlation between suicidal behavior levels on the CSPS and depression in the OCD subjects, while all other subjects showed the expected significant positive correlation between level of suicidal behavior and depression. LIMITATIONS: This study looked at a referred population and generalization to outpatient and community samples cannot be made. Distinguishing between the primary and the comorbid diagnosis is difficult and some findings are based on small sample size and therefore may be vulnerable to type I error. CONCLUSIONS: Although suicidal ideation and depressive symptoms are common in OCD adolescent inpatients, they seem to be protected against suicide attempts. The inverse relationship between suicidal behavior and depression may mean that suicidal behavior is, in some ways, qualitatively different from that seen in other psychiatrically ill adolescents.

Adolescent↗
PubMed2003

DRD4 exon III polymorphism and response to risperidone in Israeli adolescents with schizophrenia: a pilot pharmacogenetic study.

This study examined the possible association between the polymorphism in the dopamine receptor DRD4 gene and response to risperidone among 24 Israeli Jewish adolescent inpatients with first-episode schizophrenia. Response was categorically determined by a change of >40% on the Brief Psychiatric Rating Scale (BPRS). No significant association was found between the DRD4 genotype and clinical response, although carriers of <7 repeat alleles demonstrated higher response rate (10/20 vs. 0/4, P=0.11). Studies in larger groups of adolescent schizophrenia patients are warranted to clarify the possible association between DRD4 exon III repeat alleles and the response to risperidone.

Adolescent↗
PubMed2003

Hyperglycemia from olanzapine treatment in adolescents.

The increasing use of olanzapine for treating adolescent patients has brought with it greater awareness of the recognized side effects of this medication, especially weight gain. Of the reports of glucose dysregulation related to olanzapine therapy, only a few pertain to adolescents. We present five cases: two youths who consequently suffered from overt diabetes and three who responded with glucose dysregulation. According to the Naranjo probability scale, the relation of this phenomenon to olanzapine therapy is "probable." We consider the findings of the presented case series as justification for regular metabolic follow-up for apparently healthy adolescents receiving olanzapine therapy.

Adolescent↗
PubMed2003

Comparison of the suicidal behavior of adolescent inpatients with borderline personality disorder and major depression.

The objective of the study was to examine the hypothesis that some forms of suicidal behavior among adolescents are related to helplessness and depression, whereas others are related to anger and impulsivity. Sixty-five adolescents were studied. Thirty-three had borderline personality disorder (BPD), of whom 17 had made a recent suicide attempt. Thirty-two had major depressive disorder (MDD), of whom 16 had made a recent suicide attempt. Assessments were made with the Child Suicide Potential Scale, the Beck Depression Inventory, the Beck Hopelessness Scale, the Multidimensional Anger Inventory, the Overt Aggression Scale, the Impulsiveness-Control Scale, and the Suicide Intent Scale. Adolescents with BPD had more anger, aggression, and impulsiveness than those with MDD, but similar levels of depression and hopelessness. Suicidal versus nonsuicidal adolescents were more depressed, hopeless, and aggressive, but not more angry or impulsive. There were no significant differences in impulsiveness for the MDD suicidal group versus the MDD nonsuicidal group, but the suicidal BPD adolescents were significantly more impulsive than the nonsuicidal BPD adolescents. In the subjects with BPD, impulsiveness and aggression correlated significantly and positively with suicidal behavior. In the subjects with MDD, no such correlations were seen. In both diagnostic groups, depression and hopelessness correlated positively and significantly with suicidal behavior. Anger did not correlate with suicidal behavior in either of the groups. The suicidal subjects with MDD had significantly higher suicidal intent scores than the suicidal adolescents with BPD. We conclude that the nature of suicidal behavior in adolescents with BPD differs from that seen in MDD with respect to the role of anger and aggression.

Adolescent↗
PubMed2003

Methylphenidate treatment for attention-deficit/hyperactivity disorder in children and adolescents with velocardiofacial syndrome: an open-label study.

BACKGROUND: Velocardiofacial syndrome (VCFS) is a common microdeletion syndrome associated with psychiatric morbidity and developmental disabilities. Although attention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric problem associated with VCFS, there are no reports on methylphenidate treatment in this patient population. Indeed, clinicians have commonly avoided the use of methylphenidate in children with VCFS because of concerns about ineffectiveness or psychotic exacerbation. METHOD: Forty subjects of mean +/- SD age 11.0 +/- 5.0 years with VCFS were assessed for DSM-IV diagnoses using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children, Present and Lifetime Version, and its extended ADHD module (K-SADS-P-ADHD). Those found to have comorbid ADHD were treated with methylphenidate, 0.3 mg/kg once daily. Treatment efficacy was evaluated after 4 weeks with the K-SADS-P-ADHD, the Conners' Abbreviated Teacher Questionnaire, and the Conners' Continuous Performance Test. Side effects were evaluated with a modified version of the Barkley Side Effects Rating Scale. RESULTS: Of the 18 subjects (45%) diagnosed with ADHD, 12 agreed to participate in the study. Their ADHD symptoms, both behavioral and cognitive, improved significantly with treatment. None of the patients showed clinical worsening or psychotic symptoms. Side effects were usually mild and did not warrant discontinuation of methylphenidate. The most common side effects were anorexia and depressive-like symptoms. CONCLUSION: This open-label study indicates that methylphenidate is effective and safe in patients with VCFS. Therefore, its current limited use in this population seems to be unjustified. Larger, controlled clinical and pharmacogenetic studies are needed to confirm these findings.

Adolescent↗
PubMed2002

Weight gain associated with olanzapine and risperidone in adolescent patients: a comparative prospective study.

OBJECTIVE: To evaluate weight gain associated with olanzapine, risperidone, and haloperidol treatment and its clinical risk factors in adolescent patients. METHOD: The study was conducted at three adolescent psychiatric departments in two mental health centers in the Tel Aviv area. All patients were Jewish Israelis. Weight and body mass index (BMI) of hospitalized adolescents treated with olanzapine (n = 21), risperidone (n = 21), or haloperidol (n = 8) were prospectively monitored on a weekly basis for the first 12 weeks of treatment. Various clinical risk factors were tested for association with weight gain. RESULTS: The olanzapine and risperidone groups experienced significant weight gain between baseline and endpoint (p < .01), whereas the average weight of the haloperidol group did not change. Average weight gain was significantly higher for the olanzapine group (7.2 +/- 6.3 kg, 11.1% +/- 7.8%) than for the risperidone (3.9 +/- 4.8 kg, 6.6% +/- 8.6%) and haloperidol (1.1 +/- 3.3 kg, 1.5% +/- 6.0%) groups. Extreme weight gain (>7%) was recorded in 19 patients (90.5%), 9 patients (42.9%), and 1 (12.5%) patient, respectively Gender (males), low concern about gaining weight (females), low baseline BMI, and paternal BMI were positively correlated with weight gain, whereas previous neuroleptic history, neuroleptic dosage, response to treatment, and illness duration were not. CONCLUSIONS: Olanzapine and risperidone are associated with extreme weight gain in adolescents, much higher than that reported in adults. This side effect should be taken into consideration before prescribing these medications, especially in patients at high risk.

Adolescent↗
PubMed2002

A follow-up study of adolescent attempted suicide in Israel.

OBJECTIVES: (1) To compare the outcome of adolescent subjects who have made a suicide attempt with the outcome of matched controls, using their psychological and psychometric screening tests for military service at age 16.5 years. Their subsequent performance during military service between ages 18 and 21 was also evaluated. (2) To compare the prognosis of those attempters who received intensive psychiatric inpatient evaluation in a general hospital with the prognosis of those who received emergency room treatment only. METHOD: The computerized military records of 216 adolescents, who had been treated between 1987 and 1988 for attempted suicide in a general hospital emergency room, prior to their induction into the army, were evaluated. They were rated on the following tests: cognitive/educational performance and psychosocial adaptation, psychiatric and psychological health diagnoses, and performance during their military service between 1989 and 1992. RESULTS: Although the female attempters had slightly more problems in the military than the controls, their overall prognosis was surprisingly good. The male suicide attempters did very poorly in their subsequent military service. There was no long-term advantage in having had a psychiatric evaluation performed in a hospital over a brief emergency room evaluation. Most differences between attempters and controls were in service performance, rather than in cognitive and psychometric tests. CONCLUSIONS: There may be marked differences between the sexes in the significance of attempted suicide and in the indications for intervention. The policy of mandatory general hospitalization for suicide attempters may need reevaluation.

Adolescent↗
PubMed2002

Weight gain associated with increased food intake and low habitual activity levels in male adolescent schizophrenic inpatients treated with olanzapine.

OBJECTIVE: The authors studied weight gain mechanisms and energy balance in patients treated with olanzapine. METHOD: The body mass index of male schizophrenic adolescent inpatients treated with olanzapine (N=10) and of 10 matched patients treated with haloperidol (N=10) were measured at baseline and after 4 weeks of treatment. For the patients treated with olanzapine, caloric intake, resting energy expenditure, and physical activity (determined through accelerometry and heart rate monitoring) were assessed at baseline and after 4 weeks of treatment. RESULTS: Body mass index significantly increased in those treated with olanzapine but not in those given haloperidol. The increase in body mass index was due to an increase in caloric intake without change in diet composition. Olanzapine had no significant effect on resting energy expenditure. Daily energy expenditure was very low before and after treatment. CONCLUSIONS: Olanzapine-induced weight gain is associated with a general increase in caloric intake.

Adolescent↗