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Biomedical subjects

E Hollander

Publications and source records attributed to E Hollander.

At least 37 records · Page 2Linked to original sources
PubMed2000

Decreased platelet monoamine oxidase activity in female bulimia nervosa.

UNLABELLED: The involvement of brain serotonin systems in the pathophysiology of eating disorders has been repeatedly demonstrated in recent studies. Platelet MAO activity is an index of brain serotonin activity and lowered platelet MAO levels have been found in association with impulsive behaviors. In addition, some preliminary reports indicate that platelet MAO could be lowered in eating disorder patients. METHODS: 47 patients with DSM-IV eating disorders were studied, including 30 with bulimia nervosa and 17 with anorexia nervosa binge eating-purging type. Platelet MAO activity was measured by isotopic methods using C-14 benzylamine and compared with a control group of 30 healthy subjects. Impulsive personality features were studied with specific rating scales. RESULTS: Platelet MAO activity was significantly lower (4.4+/-2.4 nmol/h/10(8) platelets) in the bulimic patients than in the control group (6.9+/-2.5) (p<0.001). No significant differences were found between pure bulimics and binge eating-purging anorectics. Platelet MAO was inversely and significantly correlated with scores on impulsivity scales and with borderline personality disorder characteristics. CONCLUSIONS: Platelet MAO activity is lowered in patients with bulimia, which may reflect dysfunction in impulse control mechanisms. Since platelet MAO has a predominant genetic component, there is need for studies on the association of low platelet MAO and higher risk for developing eating disorders.

Adult↗
PubMed2000

Pharmacotherapy of obsessive-compulsive disorder: experience with the selective serotonin reuptake inhibitors.

Since the introduction of the selective serotonin reuptake inhibitors (SSRIs) a decade ago, they have become first-line agents in the treatment of obsessive-compulsive disorder (OCD). Numerous clinical trials have confirmed their efficacy, and established their superior risk-benefit ratio in comparison with clomipramine, a non-selective serotonin reuptake inhibitor. Relatively higher doses and longer duration of treatment may be necessary to effect a response in OCD, with long-term treatment being required to maintain therapeutic gains. Despite the advances represented by the SSRIs, treatment resistance remains a problem. While no one solution exists, various strategies, including pharmacotherapy augmentation, look promising.

Clinical Trials as Topic↗
PubMed2000

Increased inhibitory activity of protein kinase C on the serotonin transporter in OCD.

Different observations show a reduced functionality of the serotonin (5-HT) transporter in obsessive-compulsive disorder (OCD) that might be due to a disturbance of its regulation at intracellular level. Protein kinase C (PKC) has been reported to provoke a decrease in the number of the 5-HT transporter proteins. Therefore, we investigated whether OCD patients differed from control subjects in the effect of PKC upon the 5-HT transporter, after stimulation of this enzyme with 4beta-12-tetradecanoylphorbol 13-acetate (beta-TPA). Fifteen patients affected by OCD, according to DSM-IV criteria, were compared with a similar group of healthy subjects. The determination of 5-HT uptake was carried out according to the method of Arora and Meltzer with slight modifications. At baseline, OCD patients showed a significant decrease in the maximal velocity (V(max)) of 5-HT uptake, as compared with control subjects, with no change in the Michaelis-Menten constant (K(m)). The activation of PKC with beta-TPA provoked a significant decrease in V(max) values in both groups, but the effect was significantly more robust in OCD patients who, in turn, also showed also an increase in K(m) values. These findings could indicate the presence of hyperactivity of PKC in OCD that could be the result of increased activity of the phosphatidylinositol pathway. In addition, this suggests new potential therapeutic targets in OCD.

Adolescent↗
PubMed2000

Feeling unreal: a PET study of depersonalization disorder.

OBJECTIVE: The goal of this study was to assess brain glucose metabolism and its relationship to dissociation measures and clinical symptoms in DSM-IV depersonalization disorder. METHOD: Positron emission tomography scans coregistered with magnetic resonance images of eight subjects with depersonalization disorder were compared to those of 24 healthy comparison subjects. The two groups did not differ in age, sex, education, performance on a baseline neuropsychological battery, or performance on a verbal learning task administered during [(18)F]fluorodeoxyglucose uptake. A cortical analysis by individual Brodmann's areas was performed. RESULTS: Compared to the healthy subjects, subjects with depersonalization disorder showed significantly lower metabolic activity in right Brodmann's areas 22 and 21 of the superior and middle temporal gyri and had significantly higher metabolism in parietal Brodmann's areas 7B and 39 and left occipital Brodmann's area 19. Dissociation and depersonalization scores among the subjects with depersonalization disorder were significantly positively correlated with metabolic activity in area 7B. CONCLUSIONS: Depersonalization appears to be associated with functional abnormalities along sequential hierarchical areas, secondary and cross-modal, of the sensory cortex (visual, auditory, and somatosensory), as well as areas responsible for an integrated body schema. These findings are in good agreement with the phenomenological conceptualization of depersonalization as a dissociation of perceptions as well as with the subjective symptoms of depersonalization disorder.

Adult↗
PubMed2000

Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging.

OBJECTIVE: Cytoarchitectonic changes in the anterior cingulate cortex, hippocampus, subiculum, entorhinal cortex, amygdala, mammillary bodies, and septum were reported in a postmortem study of autism. Previously, the authors found smaller cingulate volume and decreased metabolism of the cingulate in seven autistic patients. In this study, they measured the volume and glucose metabolism of the amygdala, hippocampus, and cingulate gyrus in an expanded group of 17 patients with autism spectrum disorders (autism [N=10] or Asperger's disorder [N=7]) and 17 age- and sex-matched healthy volunteers. METHOD: Subjects performed a serial verbal learning test during (18)F-deoxyglucose uptake. The amygdala, hippocampus, and cingulate gyrus were outlined on magnetic resonance imaging scans, volumes of the structures were applied to matching coregistered positron emission tomography scans, and three-dimensional significance probability mapping was performed. RESULTS: Significant metabolic reductions in both the anterior and posterior cingulate gyri were visualized in the patients with autism spectrum disorders. Both Asperger's and autism patients had relative glucose hypometabolism in the anterior and posterior cingulate as confirmed by analysis of variance; regional differences were also found with three-dimensional significance probability mapping. No group differences were found in either the metabolism or the volume of the amygdala or the hippocampus. However, patients with autism spectrum disorders showed reduced volume of the right anterior cingulate gyrus, specifically in Brodmann's area 24'. CONCLUSIONS: Compared with age- and sex-matched healthy volunteers, patients with autism spectrum disorders showed significantly decreased metabolism in both the anterior and posterior cingulate gyri.

Adult↗
PubMed2000

Impulsivity.

Disorders characterized by impulsivity include disorders of impulse control (intermittent explosive disorder, pyromania, kleptomania, pathological gambling and trichotillomania), paraphilias, sexual impulsions and sexual addictions and impulsive aggression personality disorders (borderline, antisocial, histrionic and narcissistic personality disorders). Impulsivity has a substantial impact on both individuals and society. Impulse control disorders may be conceptualized as a subset of the obsessive-compulsive spectrum. In this article, we examine the genetic and neurobiological aetiology of these disorders and possible treatment options. The link between serotonergic dysfunction and the pathophysiology of impulsivity is discussed, and studies that examine the efficacy of various selective serotonin reuptake inhibitors and other alternatives in the treatment of impulsive disorders such as pathological gambling, sexual addictions and borderline personality disorder are presented.

Disruptive, Impulse Control, and Conduct Disorders↗
PubMed2000

Venlafaxine in children, adolescents, and young adults with autism spectrum disorders: an open retrospective clinical report.

Autism is characterized by social deficits, communication and language impairments, narrow restricted interests, repetitive behaviors, inattention, and hyperactivity. While selective serotonin reuptake inhibitors have demonstrated efficacy in treating core symptoms of autism, norepinephrine reuptake inhibitors have demonstrated efficacy in symptoms of attention-deficit hyperactivity disorder (ADHD). An open, retrospective clinical study with venlafaxine evaluated its effect on core symptoms of autism as well as associated features of ADHD. Ten consecutive subjects meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for an autism spectrum disorder were treated with venlafaxine, initiated at 12.5 mg per day and adjusted on a flexible basis. Six of 10 completers were judged to be sustained treatment responders, by scoring 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions improvement scale. Venlafaxine was effective in low dosages (mean, 24.37 mg/day; range, 6.25 to 50 mg/day) and was well tolerated. Improvement was noted in repetitive behaviors and restricted interests, social deficits, communication and language function, inattention, and hyperactivity. Controlled treatment trials with venlafaxine are warranted in autism spectrum disorders.

Adult↗
PubMed2000

Decreased platelet monoamine oxidase activity in female anorexia nervosa.

OBJECTIVE: To study if platelet MAO activity, previously described as a serotonergic index, is modified in a sample of pure restrictive anorectic patients. METHOD: Twenty-five female patients with DSM-IV anorexia nervosa restricting type were studied and compared with 30 healthy female controls. Platelet MAO activity was measured by isotopic methods using C-14 benzylamine. Impulsive personality features were measured with specific rating scales and temperament studied with Cloninger's TCI. RESULTS: Platelet MAO activity was significantly lower (4.3+2.7 nmol/h/ 108 platelets) in the anorectic patients than in the control group (6.7+2.8) (P<0.01). Platelet MAO was inversely correlated with scores on impulsivity scales and positively correlated with the dimension 'persistence' of Cloninger's TCI. CONCLUSION: Platelet MAO activity is lowered in a group of patients with anorexia nervosa and might involve some dysfunction in the regulation of impulse control.

Adolescent↗
PubMed1999

Clomipramine vs desipramine crossover trial in body dysmorphic disorder: selective efficacy of a serotonin reuptake inhibitor in imagined ugliness.

BACKGROUND: Body dysmorphic disorder (preoccupation with an imagined or slight defect in appearance) is a common and disabling disorder associated with high rates of delusional symptoms and suicide attempts. Although preliminary studies suggest that serotonin reuptake inhibitors may be effective for body dysmorphic disorder, to date no controlled treatment studies have been published. METHODS: Forty patients were enrolled and 29 were randomized into a 16-week, double-blind, crossover-design study of clomipramine, a potent serotonin reuptake inhibitor, and active control desipramine, a selective norepinephrine reuptake inhibitor. Outcome measures included specific ratings of body dysmorphic disorder severity, delusionality, and functional impairment. RESULTS: Clomipramine was superior to desipramine in the acute treatment of body dysmorphic disorder symptoms as measured by assessment of patients' obsessive preoccupation with perceived body defects, repetitive behaviors in response to this preoccupation, and global ratings of symptom severity. Treatment efficacy was independent of the presence or severity of comorbid diagnoses of obsessive-compulsive disorder, depression, or social phobia. Likewise, clomipramine was equally effective regardless of whether the patients had insight or held their dysmorphic misperception with delusional intensity. Clomipramine was also superior to desipramine in improving functional disability. CONCLUSIONS: Clomipramine is more effective than desipramine in the treatment of body dysmorphic disorder and is effective even among those patients who are delusional.

Adrenergic Uptake Inhibitors↗
PubMed1999

Interactions between the right ventricle and pulmonary vasculature in the fetus.

A midsystolic plateau differentiates the pattern of fetal pulmonary trunk blood flow from aortic flow. To determine whether this plateau arises from interactions between the left (LV) and right ventricle (RV) via the ductus arteriosus or from interactions between the RV and the lung vasculature, we measured blood flows and pressures in the pulmonary trunk and aorta of eight anesthetized (ketamine and alpha-chloralose) fetal lambs. Wave-intensity analysis revealed waves of energy traveling forward, away from the LV and the RV early in systole. During midsystole, a wave of energy traveling back toward the RV decreased blood flow velocity from the RV and produced the plateau in blood flow. Calculations revealed that this backward-traveling wave originated as a forward-traveling wave generated by the RV that was reflected from the lung vasculature back toward the heart and not as a forward-traveling wave generated by the LV that crossed the ductus arteriosus. Elimination of this backward-traveling wave and its associated effect on RV flow may be an important component of the increase in RV output that accompanies birth.

Animals↗
PubMed1999

B lymphocyte antigen D8/17 and repetitive behaviors in autism.

OBJECTIVE: Monoclonal antibody D8/17 identifies a B lymphocyte antigen with expanded expression in rheumatic fever, Sydenham's chorea, and subgroups of obsessive-compulsive disorder and Tourette's syndrome with repetitive behaviors. The authors examined the rate of D8/17 expression in children with autism and its correlation with severity of repetitive behaviors. METHOD: Blood samples from 18 patients with autism and 14 comparable medically ill children were evaluated for percentage of D8/17-positive B cells by immunofluorescence and for streptococcal antibodies. Severity of repetitive behaviors was also determined. RESULTS: The frequency of individuals with > or =11% D8/17-positive cells was significantly higher in the autistic patients (78%) than the comparison subjects (21%), severity of repetitive behaviors significantly correlated with D8/17 expression, and D8/17-positive patients had significantly higher compulsion scores than D8/17-negative patients. CONCLUSIONS: D8/17 expression is high in patients with autism and may serve as a marker for compulsion severity within autism.

Adolescent↗
PubMed1999

Comorbid social anxiety and body dysmorphic disorder: managing the complicated patient.

Patients with body dysmorphic disorder (BDD) have an obsessive preoccupation with an imagined defect in appearance or, if a slight physical abnormality exists, a grossly excessive concern with it. This preoccupation causes significant distress or impairment of social, occupational, or other functioning. Social anxiety is a prominent component of BDD, and social avoidance resulting from BDD symptoms may markedly impair social functioning. In severe cases, avoidance of social situations in combination with occupational and academic impairment may result in patients becoming housebound. The prevalence of BDD is 1% to 2% in the U.S. population and 11% to 12% in patients with social anxiety disorder. Behaviors associated with BDD include mirror checking, physician visits, hair grooming, use of cosmetics, and social avoidance. Distress over BDD may lead patients to undergo repeated cosmetic surgeries in futile attempts to conceal or correct perceived defects. Additionally, depression and suicide are frequent complications of BDD. Pharmacologic and nonpharmacologic treatments for the management of BDD with coexisting social anxiety are presented in this article.

Adolescent↗
PubMed1999

Managing aggressive behavior in patients with obsessive-compulsive disorder and borderline personality disorder.

Obsessive-compulsive disorder (OCD) is one of the most common psychiatric disorders, occurring in 2% to 3% of the U.S. population. Borderline personality disorder is found in 2% of the U.S. population. These disorders denote the endpoints on a spectrum of compulsive and impulsive disorders. One endpoint marks compulsive or risk-aversive behaviors characterized by overestimation of the probability of future harm, highlighted by OCD. The other endpoint designates impulsive action characterized by the lack of complete consideration of the negative results of such behavior, such as borderline and antisocial personality disorders. This article examines studies testing the efficacy of different medications in treating compulsive and impulsive disorders. Mood stabilizers such as divalproex, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, and neuroleptics have documented efficacy in treating aggression and affective instability in impulsive patients.

Aggression↗
PubMed1998

Treatment of depersonalization disorder with clomipramine.

BACKGROUND: Although there is a dire paucity of data on the pharmacologic treatment of depersonalization disorder, there have been a few reports in the literature suggesting that selective serotonin reuptake inhibitors may be of therapeutic benefit. In this study, we undertook to evaluate the efficacy of the potent serotonin reuptake inhibitor clomipramine in treating depersonalization. METHODS: Eight subjects with DSM-III-R depersonalization disorder were entered into a double-blind crossover trial consisting of 8 weeks desipramine and 8 weeks clomipramine. Due to the very small size of the trial findings are presented descriptively. RESULTS: Of 7 subjects who entered the clomipramine trial, two showed significant improvement in depersonalization. Three subjects dropped out early, unable to tolerate adverse effects. Of 6 subjects who entered the desipramine trial, I showed significant improvement in depersonalization. One clomipramine responder was subsequently followed in open maintenance treatment with clomipramine for 4 years, and her depersonalization symptoms remained in almost complete remission, with relapses upon each attempt to taper off or switch medication. CONCLUSIONS: Clomipramine may be a promising pharmacologic treatment for primary depersonalization disorder and warrants further investigation.

Adult↗
PubMed1998

Serotonergic function in social phobia: comparison to normal control and obsessive-compulsive disorder subjects.

Eighteen patients with social phobia, 21 normal control subjects, and 42 obsessive-compulsive disorder (OCD) control subjects were challenged with single doses of the partial serotonin agonist oral m-chlorophenylpiperazine (m-CPP) and placebo. Social phobics did not significantly differ from normal or OCD control subjects in prolactin response to m-CPP. There was a significant difference across groups in cortisol response to m-CPP, such that female social phobics had more robust cortisol responses to the m-CPP challenge. Pairwise comparisons only reached trend significance, perhaps due to the relatively small sample sizes. This study offers preliminary evidence for serotonin dysfunction in social phobia, particularly in female social phobics, but needs to be replicated in a larger sample size.

Adult↗
PubMed1998

SSRIs in the treatment of obsessive-compulsive disorder.

The introduction of the SSRIs (selective serotonin reuptake inhibitors) over the past decade has provided exciting new opportunities for the treatment of obsessive-compulsive disorder (OCD). The serotonin hypothesis, based on the preferential response of OCD to the serotonin reuptake inhibitor, clomipramine, paved the way for research into the efficacy of the SSRIs in the treatment of this disorder. Large, controlled, multicenter studies have found clomipramine and the SSRIs, fluoxetine, fluvoxamine, sertraline, and paroxetine, to be effective and safe in the treatment of OCD. Meta-analytic studies have reported that clomipramine is superior to the SSRIs; however, direct head-to-head comparisons suggest equal efficacy. As SSRIs have a more favorable side-effect profile they may be preferable as first-line treatment of OCD. Improvement following adequate OCD drug treatment is frequently partial whereupon augmentation strategies may become necessary. High rates of relapse have been reported on discontinuation of SRI treatment. Long-term maintenance treatment has been found to be effective in sustaining initial therapeutic gains and bringing about further improvement.

Adolescent↗
PubMed1998

The detection and measurement of depersonalization disorder.

Depersonalization disorder comprises one of the four major dissociative disorders and yet remains poorly studied. There are no reports describing the application of dissociation scales to this population. Our goal was to investigate the applicability of four such scales to depersonalization disorder and to establish screening criteria for the disorder. Two general dissociation scales and two depersonalization scales were administered to 50 subjects with DSM-III-R depersonalization disorder and 20 healthy control subjects. The depersonalization disorder group scored significantly higher than the normal control group in all scales and subscales. Factor analysis of the Dissociative Experiences Scale (DES) yielded three factors as proposed previously, absorption, amnesia, and depersonalization/derealization. A DES cutoff score of 12, markedly lower than those previously proposed for the screening of other dissociative disorders, is required for the sensitive detection of depersonalization disorder. Alternatively, the DES pathological dissociation taxon (DES-taxon) score recently generated in the literature appears more sensitive to the detection of depersonalization disorder and is better recommended for screening purposes. The other three scales were fairly strongly correlated to the DES, suggesting that they may measure similar but not identical concepts, and cutoff scores are proposed for these scales also. General implications for the screening and quantification of depersonalization pathology are discussed.

Adult↗