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Biomedical subjects

E Hollander

Publications and source records attributed to E Hollander.

At least 19 recordsLinked to original sources
PubMed2007

Diagnosis and treatment of obsessive-compulsive disorder and related disorders.

Obsessive-compulsive disorder (OCD) is currently recognised as one of the most common psychiatric disorders as well as one of the most disabling of all medical disorders. Obsessive-compulsive related disorders (OCRDs), often comorbid with OCD, include many distinct psychiatric conditions (i.e. some somatoform disorders, eating disorders, impulse control disorders and some neurological conditions) which have overlapping symptoms and compulsive qualities with OCD. Although effective treatments exist, OCD and related disorders are often underdiagnosed and undertreated. Serotonin reuptake inhibitors (SRIs) and cognitive behavioural therapy (CBT) represent the first-line treatment for OCD and related disorders. However, the time and the doses of the medications used in the treatment of OCD and related disorders differ from those recommended in depressive disorders. In addition, remission is not common for patients with OCD and related disorders in clinical practice, and poor responders as well as refractory cases may benefit from different treatment strategies including integrated treatment, pharmacological augmentation and brain stimulation techniques.

Chronic Disease↗
PubMed2006

The Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS): an instrument for assessing obsessive-compulsive symptom dimensions.

Obsessive-compulsive disorder (OCD) encompasses a broad range of symptoms representing multiple domains. This complex phenotype can be summarized using a few consistent and temporally stable symptom dimensions. The objective of this study was to assess the psychometric properties of the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS). This scale measures the presence and severity of obsessive-compulsive (OC) symptoms within six distinct dimensions that combine thematically related obsessions and compulsions. The DY-BOCS includes portions to be used as a self-report instrument and portions to be used by expert raters, including global ratings of OC symptom severity and overall impairment. We assessed 137 patients with a Diagnostic and Statistical Manual-IV diagnosis of OCD, aged 6-69 years, from sites in the USA, Canada and Brazil. Estimates of the reliability and validity of both the expert and self-report versions of the DY-BOCS were calculated and stratified according to age (pediatric vs. adult subjects). The internal consistency of each of the six symptom dimensions and the global severity score were excellent. The inter-rater agreement was also excellent for all component scores. Self-report and expert ratings were highly intercorrelated. The global DY-BOCS score was highly correlated with the total Yale-Brown Obsessive-Compulsive Scale score (Pearson r = 0.82, P<0.0001). Severity scores for individual symptom dimensions were largely independent of one another, only modestly correlated with the global ratings, and were also differentially related to ratings of depression, anxiety and tic severity. No major differences were observed when the results were stratified by age. These results indicate that the DY-BOCS is a reliable and valid instrument for assessing multiple aspects of OCD symptom severity in natural history, neuroimaging, treatment response and genetic studies when administered by expert clinicians or their highly trained staff.

Adolescent↗
PubMed2004

Linkage analysis for autism in a subset families with obsessive-compulsive behaviors: evidence for an autism susceptibility gene on chromosome 1 and further support for susceptibility genes on chromosome 6 and 19.

Although there is considerable evidence for a strong genetic component to idiopathic autism, several genome-wide screens for susceptibility genes have been carried out with limited concordance of linked loci, reflecting numerous genes of weak effect and/or sample heterogeneity. In the current study, linkage analysis was carried out in a sample of 62 autism-affected relative pairs with more severe obsessive-compulsive behaviors, selected from a larger (n=115) set of autism-affected relative pairs as a means of reducing sample heterogeneity. Obsessive-compulsive behaviors were assessed using the Autism Diagnostic Interview-Revised (ADI-R). In the sample with more severe obsessive-compulsive behaviors, multipoint NPL scores above 2 were observed on chromosomes 1, 4, 5, 6, 10, 11 and 19, with the strongest evidence for linkage on chromosome 1 at the marker D1S1656, where the multipoint NPL score was 3.06, and the two-point NPL score was 3.21. In follow-up analyses, analyzing the subset of families (n=35) where the patients had the most severe obsessive-compulsive behaviors generated a multipoint NPL score of 2.76, and a two-point NPL score of 2.79, indicating that the bulk of evidence for linkage was derived from the families most severely affected with obsessive-compulsive behaviors. The data suggest that there is an autism susceptibility gene on chromosome 1 and provide further support for the presence of autism susceptibility genes on chromosomes 6 and 19.

Autistic Disorder↗
PubMed2001

Evidence for a susceptibility gene for autism on chromosome 2 and for genetic heterogeneity.

Although there is considerable evidence for a strong genetic component to idiopathic autism, several genomewide screens for susceptibility genes have been performed with limited concordance of linked loci, reflecting either numerous genes of weak effect and/or sample heterogeneity. Because decreasing sample heterogeneity would increase the power to identify genes, the effect on evidence for linkage of restricting a sample of autism-affected relative pairs to those with delayed onset (at age >36 mo) of phrase speech (PSD, for phrase speech delay) was studied. In the second stage of a two-stage genome screen for susceptibility loci involving 95 families with two or more individuals with autism or related disorders, a maximal multipoint heterogeneity LOD score (HLOD) of 1.96 and a maximal multipoint nonparametric linkage (NPL) score of 2.39 was seen on chromosome 2q. Restricting the analysis to the subset of families (n=49) with two or more individuals having a narrow diagnosis of autism and PSD generated a maximal multipoint HLOD score of 2.99 and an NPL score of 3.32. The increased scores in the restricted sample, together with evidence for heterogeneity in the entire sample, indicate that the restricted sample comprises a population that is more genetically homogeneous, which could therefore increase the likelihood of positional cloning of susceptibility loci.

Autistic Disorder↗
PubMed2001

Neuroendocrine predictors of response to intravenous clomipramine therapy for refractory obsessive-compulsive disorder.

The current study examines the neuroendocrine response to intravenous clomipramine (IV CMI) in oral CMI-resistant obsessive-compulsive disorder (OCD) patients on day 1 and day 14 of treatment to identify predictors of response. Forty-four OCD patients with an inadequate response or poorly tolerant to oral CMI were begun at 25 mg IV CMI, increasing to 250 mg by day 10, and continuing on that dose to day 14. On day 1, plasma levels of prolactin (PRL), growth hormone (GH), and cortisol were obtained immediately before the 25 mg IV infusion, and at five 30-minute time points after the infusion. On day 14, hormonal samples were obtained in a similar fashion. Response was assessed by the Clinical Global Impressions (CGI). Low PRL(MAX) to IV CMI and low cortisol levels overall on day 1 were both significantly associated with clinical response at day 14. An overall increase in growth hormone (GH) secretion during the day 14 testing was associated with positive response. A pronounced PRL response to IV CMI on day 14 was exhibited by the nonresponders, whereas a smaller and later but significant increase in PRL was noted in the responders. The findings suggest that in this sample of oral CMI-resistant patients with OCD, neuroendocrine measures derived from pharmacological challenge with IV CMI are capable of distinguishing IV CMI treatment responders from nonresponders. The limitations of IV CMI as a specific probe of serotonin function are discussed.

Administration, Oral↗
PubMed2001

Hypothalamic-pituitary-adrenal axis dysregulation in depersonalization disorder.

BACKGROUND: The purpose of this preliminary study was to investigate HPA axis function in dissociation. METHODS: Nine subjects with DSM-IV depersonalization disorder (DPD), without lifetime Posttraumatic Stress Disorder (PTSD) or current major depression, were compared to nine healthy comparison (HC) subjects of comparable age and gender. RESULTS: DPD subjects demonstrated significant hyposuppression to low-dose dexamethasone administration and significantly elevated morning plasma cortisol levels when covaried for depression scores, but no difference in 24-hour urinary cortisol excretion. Dissociation scores powerfully predicted suppression whereas depression scores did not contribute to the prediction. CONCLUSIONS: Primary dissociative conditions, such as depersonalization disorder, may be associated with a pattern of HPA axis dysregulation that differs from PTSD and merits further study.

Adult↗
PubMed2001

Effect of fluoxetine on regional cerebral metabolism in autistic spectrum disorders: a pilot study.

The regional metabolic effects of fluoxetine were examined in patients with autism spectrum disorders. Six adult patients with DSM-IV and Autism Diagnostic Interview (ADI) diagnoses of autism (n = 5) and Asperger's syndrome (n = 1), entered a 16-wk placebo-controlled cross-over trial of fluoxetine. The patients received (18)F-deoxyglucose positron emission tomography with co-registered magnetic resonance imaging at baseline and at the end of the period of fluoxetine administration. After treatment, the patients showed significant improvement on the scores of the Yale--Brown Obsessive--Compulsive Scale -- Obsessions subscale and the Hamilton Anxiety Scale; Clinical Global Impressions -- Autism scores showed 3 of the patients much improved and 3 unchanged. Relative metabolic rates were significantly higher in the right frontal lobe following fluoxetine, especially in the anterior cingulate gyrus and the orbitofrontal cortex. Patients with higher metabolic rates in the medial frontal region and anterior cingulate when unmedicated were more likely to respond favourably to fluoxetine. These results are consistent with those in depression indicating that higher cingulate gyrus metabolic rates at baseline predict SRI response.

Adult↗
PubMed2001

A preliminary double-blind, placebo-controlled trial of divalproex sodium in borderline personality disorder.

BACKGROUND: Borderline personality disorder is characterized by affective instability, impulsivity, and aggression and is associated with considerable morbidity and mortality. Since anticonvulsant agents may be helpful in such symptomatology, we compared divalproex sodium with placebo in patients with borderline personality disorder. METHOD: A 10-week, parallel, double-blind design was conducted. Sixteen outpatients meeting Structured Clinical Interview for DSM-IV Axis II Personality Disorders criteria for borderline personality disorder were randomly assigned to receive placebo (N = 4) or divalproex sodium (N = 12). Change was assessed in global symptom severity (Clinical Global Impressions-Improvement Scale [CGI-I]) and functioning (Global Assessment Scale [GAS]) as well as in specific core symptoms (depression, aggression, irritability, and suicidality). RESULTS: There was significant improvement from baseline in both global measures (CGI-I and GAS) following divalproex sodium treatment. A high dropout rate precluded finding significant differences between the treatment groups in the intent-to-treat analyses, although all results were in the predicted direction. CONCLUSION: Treatment with divalproex sodium may be more effective than placebo for global symptomatology, level of functioning, aggression, and depression. Controlled trials with larger sample sizes are warranted to confirm these preliminary results.

Adolescent↗
PubMed2001

An open trial of divalproex sodium in autism spectrum disorders.

BACKGROUND: Autism spectrum disorders are characterized by core deficits in social interaction and speech/communication skills, repetitive behaviors, and restricted interests. Other abnormalities include seizures, electroencephalographic (EEG) abnormalities, affective instability, impulsivity, and aggression. Divalproex sodium is indicated as both an anticonvulsant in epilepsy and a mood stabilizer in bipolar illness and thus might be useful for these complicating symptoms in autism. METHOD: A retrospective pilot study was conducted to determine whether divalproex sodium was effective in treating core dimensions and associated features of autism. Fourteen patients who met DSM-IV criteria for autism, Asperger's disorder, or pervasive developmental disorder not otherwise specified, both with and without a history of seizure disorders or EEG abnormalities, were openly treated with divalproex sodium. Improvement was assessed via the Clinical Global Impressions-Improvement scale. RESULTS: Of 14 patients who completed a trial of divalproex sodium, 10 (71%) were rated as having sustained response to treatment. The mean dose of divalproex sodium was 768 mg/day (range, 125-2500 mg/day), and it was generally well tolerated. Improvement was noted in core symptoms of autism and associated features of affective instability, impulsivity, and aggression. CONCLUSION: Divalproex sodium may be beneficial to patients with autism spectrum disorders, particularly those with associated features of affective instability, impulsivity, and aggression as well as those with a history of EEG abnormalities or seizures. Of note, all patients with an abnormal EEG and/or seizure history were rated as responders. However, these findings must be interpreted with caution, given the open retrospective nature of the study. Controlled trials are needed to replicate these preliminary findings.

Adolescent↗
PubMed2000

Increased growth hormone response to sumatriptan challenge in adult autistic disorders.

Serotonergic (5-HT) abnormalities have been documented in autism. To assess sensitivity of the 5-HT1d receptor, growth hormone response to the 5-HT1d receptor agonist sumatriptan was studied in adult autistic patients and matched normal controls. In this study, 11 adult patients with autism or Asperger's disorder were compared with nine matched controls. All subjects were randomized to single dose sumatriptan (6 mg SQ) and placebo challenges, separated by a 1-week interval, and growth hormone was measured before and during the challenges. The results showed a highly significant diagnosisxdrugxtime interaction on repeated measure analysis covaried for baseline. This suggests that autistic patients had significantly greater growth hormone response to sumatriptan than normal controls, independent of placebo effects. Therefore, abnormalities in 5-HT regulation in autism may be related to increased sensitivity of the 5-HT1d inhibitory receptor in autism.

Adolescent↗
PubMed2000

A randomized double-blind fluvoxamine/placebo crossover trial in pathologic gambling.

BACKGROUND: The study assessed the efficacy and tolerability of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine in the treatment of pathologic gambling (PG). METHODS: A 16-week randomized double-blind crossover design insured that each subject received 8 weeks of fluvoxamine and 8 weeks of a placebo. Fifteen patients entered and 10 subjects, all male, completed the study. RESULTS: Fluvoxamine resulted in a significantly greater percent improvement in overall gambling severity on the PG Clinical Global Impression (PG-CGI) scale. There was a significant drug effect on gambling urge and behavior as measured by the PG modification of the Yale-Brown Obsessive Compulsive Scale and PG-CGI scale improvement scores; however, there was a significant interaction of drug effect with the order of administration of drug and placebo. Post hoc analysis, treating each phase as a separate trial, demonstrated a significant difference between fluvoxamine and the placebo in the second phase of the trial but not in the first. Fluvoxamine side effects were of only mild intensity and consistent with SSRI treatment and were not associated with early withdrawal from the study. CONCLUSIONS: These findings suggest that fluvoxamine is well tolerated and may be effective in the treatment of PG in an acute trial, and that an early placebo effect in PG treatment appears to diminish over time. To confirm this finding and to determine whether improvement persists over an extended period of time, a longer duration parallel-design trial with long-term maintenance follow-up should be conducted in a larger and more diverse PG population.

Adult↗
PubMed2000

Body dysmorphic disorder.

The understanding of BDD and its treatment has expanded significantly in the past decade as controlled research has followed the leads from case reports and clinical experience. BDD is recognized as a severe, disabling disorder that is more common that had been assumed. Although BDD is still difficult to treat, success has been demonstrated for SRIs and CBT. Much remains to be discovered. To date, little is known about the causes and pathophysiology of BDD. Research that would illuminate these also would increase understanding of its relationship to other disorders, such as OCD, depression, and social phobia, and open up possibilities for prevention and new approaches to treatment. Investigations in brain imaging and genetics are underway. Research in pharmacotherapy and CBT, individually and combined, is needed to refine, extend, and optimize treatment.

Cognitive Behavioral Therapy↗
PubMed2000

Pathological gambling.

With increasing access to gambling facilities through casinos, the Internet, and other venues, PG is a rapidly emerging mental health concern. This impulse-control disorder tends to be comorbid with a wide range of other disorders and is reportedly associated with a high rate of suicide. For most gamblers, gambling is a form of entertainment, but for many individuals, the activity leads to far-reaching disruption of family and work. The personal and societal financial ramifications are severe, and many individuals with PG end up in the criminal justice system. An understanding of the neurobiology of PG is beginning to surface. 5-HT is linked to behavioral initiation and disinhibition, which are important in the onset of the gambling cycle and the difficulty in ceasing the behavior. Norepinephrine is associated with the arousal and risk taking in patients with PG. Dopamine is linked to positive and negative reward, the addictive component of this disorder. Effective treatment strategies for pathological gamblers are emerging. Potentially useful pharmacologic agents include SRIs (clomipramine and fluvoxamine), mood stabilizers for pathological gamblers with comorbid bipolar disorders (lithium), and naltrexone. Cognitive-behavioral psychotherapies offer promising results in the treatment of patients with this disorder. To devise prevention and early-intervention programs, research is needed to identify specific features of the individuals at risk for gambling problems. Education targeting vulnerable youth that show early signs of gambling behavior may be worthwhile and should be investigated further. Funding is necessary to support these endeavors, so perhaps a portion of tax revenues generated from the gambling industry should go toward specialized treatment facilities, educational efforts, and research into the neurobiology and treatment of PG.

Cognitive Behavioral Therapy↗
PubMed2000

Pharmacotherapy for obsessive-compulsive disorder.

SSRIs and the tricyclic antidepressant clomipramine are the first-line therapies for patients with OCD, with the side-effect profile of SSRIs being more favorable than that of clomipramine. As many as 40% to 60% of patients with OCD may not respond to adequate trials of SRIs. Not all patients tolerate SSRIs, and delays in full therapeutic responses often occur. Thus, other pharmacologic approaches to treating patients with OCD have been investigated. Augmentation and monotherapy have been explored with serotonergic enhancers, dopamine and 5-HT antagonists, enhancers of second-messenger systems, and GABAergic agents with varying efficacy.

Antidepressive Agents, Tricyclic↗
PubMed2000

The relationship between repetitive behaviors and growth hormone response to sumatriptan challenge in adult autistic disorder.

Autism is heterogeneous with respect to clinical symptoms and etiology. To sort out this heterogeneity in autism, we investigated whether specific neurobiological markers vary in parallel to core symptomatology. Specifically, we assessed growth hormone response to the 5-HT 1d agonist, sumatriptan, and linked this measure of serotonergic function to the severity of repetitive behaviors in adult autistic patients. Eleven adult patients with autism or Asperger's disorder were randomized to single dose sumatriptan (6 mg SQ) and placebo challenges, separated by a one-week interval. In adult autistic disorders, severity of repetitive behaviors at baseline, as measured by YBOCS-compulsion score, significantly positively correlated with both peak delta growth hormone response and area under the curve growth hormone response to sumatriptan. Thus, the severity of a specific behavioral dimension in autism (repetitive behaviors) parallels the sensitivity of the 5-HT 1d receptor, as manifest by sumatriptan elicited GH response.

Adolescent↗