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Biomedical subjects

Eric Hollander

Publications and source records attributed to Eric Hollander.

At least 19 recordsLinked to original sources
PubMed2006

A preliminary study of cortisol and norepinephrine reactivity to psychosocial stress in borderline personality disorder with high and low dissociation.

The goal of the current study was to investigate subjective and neurohormonal reactivity to acute psychosocial stress in borderline personality disorder (BPD) as a function of dissociative symptoms. Five BPD subjects with high dissociation, 8 BPD subjects with low dissociation, and 11 healthy control subjects were compared in basal urinary cortisol and norepinephrine, as well as in plasma cortisol and norepinephrine reactivity to the Trier Social Stress Test (TSST). Subjective stress rating and emotional response to the TSST were also measured. The three groups differed significantly in cortisol stress reactivity, with the high-dissociation BPD group demonstrating the most robust response. The three groups did not significantly differ in norepinephrine stress reactivity. In the combined BPD sample, dissociation severity tended to be inversely correlated with basal urinary norepinephrine, was positively correlated with norepinephrine stress reactivity. Childhood trauma was inversely correlated with basal urinary cortisol. In conclusion, despite its small sample size this pilot study suggests that dissociative symptomatology may be a marker of heightened biological vulnerability to stress in BPD, and merits further study.

Acute Disease↗
PubMed2006

Family-based association study of TPH1 and TPH2 polymorphisms in autism.

The TPH1 and TPH2 genes encode the rate-limiting enzymes that control serotonin biosynthesis, and serotonin is clearly altered in autism. In the current study, eight SNPs in the TPH1 gene region and eight SNPs within the TPH2 gene were examined by family-based association tests in a large cohort of 352 families with autism and in clinically defined subsets of these families with either severe obsessive-compulsive behaviors (sOCB) or self-stimulatory behaviors (SSB). We found no evidence for association between autism and single SNPs or haplotypes of the TPH1 and TPH2 genes in the cohort of all families or in the sOCB and SSB subsets. In particular, we failed to replicate the association between autism and variants of the TPH2 gene, rs4341581 (TRANSMIT P = 1; PDT P = 0.323; FBAT P = 0.446) and rs11179000 (TRANSMIT P = 0.174; PDT P = 0.293; FBAT P = 0.374). Furthermore, no evidence for linkage was observed between autism and SNPs in the TPH1 and TPH2 genes (although linkage at the TPH2 locus was observed in the SSB subset). Thus, it appears unlikely that the TPH1 and TPH2 genes play a significant role in the susceptibility to autism or to autism endophenotypes including sOCB and SSB.

Autistic Disorder↗
PubMed2006

Epidemiologic and clinical updates on impulse control disorders: a critical review.

The article reviews the current knowledge about the impulse control disorders (ICDs) with specific emphasis on epidemiological and pharmacological advances. In addition to the traditional ICDs present in the DSM-IV-pathological gambling, trichotillomania, kleptomania, pyromania and intermittent explosive disorder-a brief description of the new proposed ICDs-compulsive-impulsive (C-I) Internet usage disorder, C-I sexual behaviors, C-I skin picking and C-I shopping-is provided. Specifically, the article summarizes the phenomenology, epidemiology and comorbidity of the ICDs. Particular attention is paid to the relationship between ICDs and obsessive-compulsive disorder (OCD). Finally, current pharmacological options for treating ICDs are presented and discussed.

Adolescent↗
PubMed2006

Oxytocin increases retention of social cognition in autism.

BACKGROUND: Oxytocin dysfunction might contribute to the development of social deficits in autism, a core symptom domain and potential target for intervention. This study explored the effect of intravenous oxytocin administration on the retention of social information in autism. METHODS: Oxytocin and placebo challenges were administered to 15 adult subjects diagnosed with autism or Asperger's disorder, and comprehension of affective speech (happy, indifferent, angry, and sad) in neutral content sentences was tested. RESULTS: All subjects showed improvements in affective speech comprehension from pre- to post-infusion; however, whereas those who received placebo first tended to revert to baseline after a delay, those who received oxytocin first retained the ability to accurately assign emotional significance to speech intonation on the speech comprehension task. CONCLUSIONS: These results are consistent with studies linking oxytocin to social recognition in rodents as well as studies linking oxytocin to prosocial behavior in humans and suggest that oxytocin might facilitate social information processing in those with autism. These findings also provide preliminary support for the use of oxytocin in the treatment of autism.

Adult↗
PubMed2006

The neuroscience of affiliation: forging links between basic and clinical research on neuropeptides and social behavior.

Animal studies point to the role of two neuropeptides-oxytocin and vasopressin-in the regulation of affiliative behaviors including mating, pair-bond formation, maternal/parenting behavior, and attachment. These findings may have important implications for understanding and treating clinical disorders marked by social deficits and/or disrupted attachment. This review focuses on advances made to date in the effort to forge links between basic and clinical research in the area of neuropeptides and social behavior. The literature on oxytocin and its involvement in stress response, affiliation, and prosocial behavior is reviewed, and the implications of these findings for such disorders as autism as well as other social and stress-related disorders including social phobia, post-traumatic stress disorder, and some personality disorders are considered. Finally, unresolved issues and directions for future research are discussed.

Animals↗
PubMed2006

Positron emission tomography imaging of risperidone augmentation in serotonin reuptake inhibitor-refractory patients.

We studied 15 nondepressed patients with obsessive-compulsive disorder (OCD) who were nonresponders to serotonin reuptake inhibitors with an additive trial of risperidone. Positron emission tomography with (18)F-deoxyglucose and magnetic resonance imaging was obtained at baseline and following 8 weeks of either risperidone or placebo in a double-blind parallel group design. Risperidone treatment was associated with significant increases in relative metabolic rate in the striatum, cingulate gyrus, the prefrontal cortex, especially in the orbital region, and the thalamus. Four of 9 patients who received risperidone showed clinical improvement (CGI score of 1 or 2 at 8 weeks) while none of the 6 patients who received placebo showed improvement. Patients with low relative metabolic rates in the striatum and high relative metabolic rates in the anterior cingulate gyrus were more likely to show a clinical response. These metabolic predictors of clinical response are consistent with earlier PET studies showing similar prediction when either neuroleptics or serotonin reuptake inhibitor treatments are administered individually. Our results are consistent with a frontostriatal circuit change related to both dopaminergic and serotonergic systems and with the presence of psychopharmacological subtypes within OCD.

Adult↗
PubMed2006

Lack of evidence for association of the serotonin transporter gene SLC6A4 with autism.

BACKGROUND: The serotonin transporter (5-HTT) has long been considered likely to play a role in autism. Hyperserotonemia has been consistently found in a proportion of autistic patients, and the use of selective serotonin reuptake inhibitors (SSRIs) can have a positive effect in treating some symptoms of autism. Specific variants of the 5-HTT gene, SLC6A4, especially the insertion-deletion 5-HTTLPR promoter locus, have been found to modulate its expression and transporter function. METHODS: We examined the transmission of the short or long allele of 5-HTTLPR locus to affected individuals, using a large cohort of 352 families. In addition, we screened five single nucleotide polymorphisms (SNPs) in the 5' region of SLC6A4 previously reported to be positively associated with autism, as well as 4 additional SNPs also in the 5' region. RESULTS: No association of the 5-HTTLPR locus with autism was found. Furthermore, no evidence for association of any of the nine SNPs covering the SLC6A4 gene, or any of their haplotypes, was observed in our study. Using obsessive-compulsive behaviors (OCB), severe OCBs or rigid-compulsive subsets of our cohort gave the same negative results. CONCLUSIONS: SLC6A4 variants do not appear to be significantly involved in the liability to autism.

Autistic Disorder↗
PubMed2006

Is obsessive-compulsive disorder an anxiety disorder?

Obsessive-compulsive disorder (OCD) is classified as an anxiety disorder in the DSM-IV-TR [American Psychiatric Association, 2000. Diagnostic and statistical manual of mental disorders, Fourth ed., rev. Washington, DC: Author]; however, the notion of a spectrum of obsessive-compulsive (OC) related disorders that is comprised of such disparate disorders as OCD, body dysmorphic disorder, certain eating disorders, pathological gambling, and autism, is gaining acceptance. The fact that these disorders share obsessive-compulsive features and evidence similarities in patient characteristics, course, comorbidity, neurobiology, and treatment response raises the question of whether OCD is best conceptualized as an anxiety or an OC spectrum disorder. This article reviews evidence from comorbidity and family studies, as well as biological evidence related to neurocircuitry, neurotransmitter function, and pharmacologic treatment response that bear on this question. The implications of removing OCD from the anxiety disorders category and moving it to an OC spectrum disorders category, as is being proposed for the DSM-V, is discussed.

Anxiety Disorders↗
PubMed2006

Impulsive-compulsive sexual behavior.

Impulsive-compulsive sexual behavior is a little studied clinical phenomenon which affects approximately 5% to 6% of the population. In the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision, it is classified as an impulse control disorder not otherwise specified or a sexual disorder not otherwise specified. It may be placed in a possible new category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition called substance and behavioral addictions. This clinical entity is reviewed and the merit of classifying it as an addiction is assessed. Information is presented regarding its diagnostic criteria, epidemiology, types of behavior it can involve, relationship to hypersexuality, comorbidities, treatment, and etiology. The data regarding this disorder and its overlap with chemical addiction is limited. If the two disorders are to be grouped together, further data are needed.

Adolescent↗
PubMed2006

Serotonin dysfunction in pathological gamblers: increased prolactin response to oral m-CPP versus placebo.

OBJECTIVE: Acute administration of the partial serotonin (5-HT) agonist meta-chlorophenylpiperazine (m-CPP), that is used also as a street drug, has been reported to induce a "high" and craving response in various impulsive and substance addiction disorders. INTRODUCTION: To clarify altered 5-HT metabolism in pathological gamblers and to explore the specific role of serotonergic system in non-substance addictions, we assessed behavioral ("high" and "craving") and neuroendocrine (prolactin and cortisol) responses to an oral single dose of m-CPP and placebo in pathological gamblers and matched controls. Moreover, the relationship between neuroendocrine outcome and clinical severity has been assessed. METHOD: Twenty-six pathological gamblers and 26 healthy control subjects enter a double-blind, placebo-controlled-crossed administration of orally dose m-CPP 0.5 mg/kg. Outcome measures included prolactin and cortisol levels, gambling severity, mood, craving and "high" scales. RESULTS: Pathological gamblers had significantly increased prolactin response compared to controls at 180 minutes and at 210 minutes post-administration. Greater pathological gamblers severity correlated with increased neuroendocrine responsiveness to m-CCP, suggesting greater 5-HT dysregulation. Pathological gambling patients had a significantly increased "high" sensation after m-CPP administration compared with control. CONCLUSION: These results provide additional evidence for 5-HT disturbance in pathological gamblers and they support the hypotheses that the role of the 5-HT dysfunction related to the experience of "high" might represent the pathway that leads to dyscontrolled behavior in pathological gamblers. Furthermore, the "high" feeling induced by m-CPP in pathological subjects may represent a marker of vulnerability to both behavioral and substance addictions.

Adult↗
PubMed2006

A double-blind placebo-controlled pilot study of olanzapine in childhood/adolescent pervasive developmental disorder.

Atypical antipsychotics have been shown to improve disruptive and repetitive behaviors in pervasive developmental disorders (PDDs), but they require assessment of potential side effects. This is the first placebo-controlled trial of olanzapine in the treatment of children and adolescents with PDD. Eleven patients with a diagnosis of either autism, Asperger's syndrome, or PDD not otherwise specified (PDD-NOS) and aged 6-14 years were randomized into an 8-week double-blind, placebo-controlled, parallel treatment study with olanzapine. There was a significant linear trend x group interaction on the Clinical Global Impressions- Improvement (CGI-I) and 50% on olanzapine versus 20% on placebo were responders. Olanzapine was associated with significant weight gain (7.5 +/- 4.8 lbs vs. 1.5 +/- 1.5 lbs on placebo). Olanzapine may be a promising treatment for improving global functioning of PDDs, but the risk of significant weight gain remains a concern. Additional studies are needed to determine the efficacy and safety of olanzapine in the treatment of children with PDD.

Adolescent↗
PubMed2006

Topiramate plus paroxetine in treatment-resistant obsessive-compulsive disorder.

We report a case of treatment-resistant obsessive-compulsive disorder (OCD) that was successfully treated with a pharmacological augmentation of topiramate plus paroxetine. The patient, a 45-year-old woman, was on a stable dose of paroxetine (40 mg/day) when she was started on topiramate (up to 150 mg/day). After 9 weeks of this treatment, her clinical condition remarkably improved, as indicated by a significant decrease of the evaluation scales (Yale-Brown Obsessive-Compulsive Scale and Clinical Global Impression Scale). Our case suggests that topiramate might be beneficial in augmentation with selective serotonin reuptake inhibitors in patients with treatment-resistant OCD, although further investigations are warranted to confirm our findings.

Anticonvulsants↗
PubMed2006

Levetiracetam versus placebo in childhood and adolescent autism: a double-blind placebo-controlled study.

The purpose of this study was to determine the safety and efficacy of the anticonvulsant levetiracetam in the treatment of children with autism. A previous open-label study in autistic children treated with levetiracetam demonstrated effectiveness in hyperactivity, impulsivity/aggression, and mood lability. Twenty patients with autism ranging from 5 to 17 years of age were entered into a 10-week, placebo-controlled, double-blind trial of levetiracetam versus placebo. The mean maximum dosage for levetiracetam was 862.50+/-279.19 mg/day. We evaluated global improvement of autism with the Clinical Global Impression-Improvement (CGI-I) Scale and aggression and affective instability with the Aberrant Behavior Checklist (ABC) parent and teacher ratings. We measured repetitive behaviors using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score and impulsivity and hyperactivity with the Conners' Rating Scale-Revised: Long Version for parent and teacher. No significant difference was found between levetiracetam and placebo groups comparing the change in CGI-I (t=0.350, d.f.=13.621, P=0.765), nor on change in ABC, CY-BOCS or Conners' scales. These findings suggest that levetiracetam does not improve behavioral disturbances of autism, but are limited by the small sample size and lack of stratification of the autistic sample at baseline.

Adolescent↗
PubMed2006

Association analysis of the NrCAM gene in autism and in subsets of families with severe obsessive-compulsive or self-stimulatory behaviors.

OBJECTIVES: An autism susceptibility locus (AUTS1, MIM#608636) has been identified in chromosome 7q31. NrCAM is a candidate gene for AUTS1 because it is expressed in the brain and encodes a receptor involved in nervous system development. Polymorphisms in NrCAM have been reported to be associated with autism susceptibility and with substance abuse, implicating NrCAM in reward circuitry. Self-stimulatory, perseverative behavior in autism might be due to defects in reward circuitry. In addition, models of drug addiction have also borrowed from models of obsessive-compulsive behavior designed to reduce anxiety. Thus, our goals were to replicate previous associations of NrCAM with autism, making use of a large cohort, and to clarify whether NrCAM was associated with a specific endophenotype of autism in the repetitive behaviors and stereotyped interests domains. METHODS: We genotyped six NrCAM single nucleotide polymorphisms in 352 families and we tested for association between these polymorphisms and autism in the entire cohort and in two subsets, one with severe obsessive-compulsive behaviors and one with pronounced self-stimulatory behaviors. RESULTS: We found no association between single nucleotide polymorphisms of NrCAM and autism in our large cohort, or in the severe obsessive-compulsive behavior and self-stimulatory behavior subsets. However, we observed a significant overtransmission (21 transmitted vs 6 nontransmitted, chi2=12.054, P=0.0005) of the haplotype G-G-A-G-C-A of rs722519-rs1269622-rs405945-rs6958498-rs401433-rs439587 in the severe obsessive-compulsive behavior subset, likely driven by the G-C haplotype of rs6958498-rs401433, which itself showed significant overtransmission (31 transmitted vs 13 nontransmitted, chi2=8.844, P=0.003). CONCLUSIONS: Overtransmission of particular haplotypes of NrCAM, that may relate to the expression level of NrCAM in the brain, appeared to be associated with autism in the severe obsessive-compulsive behavior subset.

Autistic Disorder↗
PubMed2006

Volumetric analysis and three-dimensional glucose metabolic mapping of the striatum and thalamus in patients with autism spectrum disorders.

OBJECTIVE: In patients with autism, behavioral deficits as well as neuroimaging studies of the anterior cingulate cortex suggest ventral rather than dorsal striatal and thalamic abnormalities in structure and function. The authors used imaging studies to map volumetric and metabolic differences within the entire dorsoventral extent of the striatum and thalamus. METHOD: Magnetic resonance imaging (MRI) and positron emission tomography (PET) were used to measure volumes and metabolic activity in the thalamus, caudate, and putamen in 17 patients with autism or Asperger's disorder and 17 age- and sex-matched comparison subjects. Subjects performed a serial verbal learning test during the [(18)F]-fluorodeoxyglucose uptake period. The regions of interest were outlined on contiguous axial MRI slices. After PET/MRI coregistration, region-of-interest coordinates were applied to the PET scan for each individual. Between-group differences in metabolism were assessed by three-dimensional statistical probability mapping. RESULTS: The patients with autism spectrum disorders had greater volumes of the right caudate nucleus than comparison subjects as well as a reversal of the expected left-greater-than-right hemispheric asymmetry. Patients also had lower relative glucose metabolic rates bilaterally in the ventral caudate, putamen, and thalamus. Patients with autism had lower metabolic activity in the ventral thalamus than those with Asperger's disorder, but they did not differ from comparison subjects in metabolic activity in the caudate nucleus. CONCLUSIONS: These results are consistent with a deficit in the anterior cingulate-ventral striatum-anterior thalamic pathway in patients with autism spectrum disorders. The results also suggest an important role for the caudate in helping support working-memory demands.

Adolescent↗
PubMed2006

Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling.

OBJECTIVE: Pathological gambling is a disabling disorder experienced by approximately 1%-2% of adults and for which there are few empirically validated treatments. The authors examined the efficacy and tolerability of the opioid antagonist nalmefene in the treatment of adults with pathological gambling. METHOD: A 16-week, randomized, dose-ranging, double-blind, placebo-controlled trial was conducted at 15 outpatient treatment centers across the United States between March 2002 and April 2003. Two hundred seven persons with DSM-IV pathological gambling were randomly assigned to receive nalmefene (25 mg/day, 50 mg/day, or 100 mg/day) or placebo. Scores on the primary outcome measure (Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling) were analyzed by using a linear mixed-effects model. RESULTS: Estimated regression coefficients showed that the 25 mg/day and 50 mg/day nalmefene groups had significantly different scores on the Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling, compared to the placebo group. A total of 59.2% of the subjects who received 25 mg/day of nalmefene were rated as "much improved" or "very much improved" at the last evaluation, compared to 34.0% of those who received placebo. Adverse experiences included nausea, dizziness, and insomnia. CONCLUSIONS: Subjects who received nalmefene had a statistically significant reduction in severity of pathological gambling. Low-dose nalmefene (25 mg/day) appeared efficacious and was associated with few adverse events. Higher doses (50 mg/day and 100 mg/day) resulted in intolerable side effects.

Adult↗