Biomedical subjects

Eric Hollander

Publications and source records attributed to Eric Hollander.

At least 55 records · Page 3Linked to original sources

PubMed2004

Increased repetitive behaviours and prolactin responsivity to oral m-chlorophenylpiperazine in adults with autism spectrum disorders.

Autism is a neurodevelopmental disorder characterized by dysfunction in three primary behavioural domains: repetitive behaviours, social deficits, and language abnormalities. There is evidence that abnormalities exist in the serotonin (5-HT) system in autism spectrum patients. Furthermore, 5-HT is known to play a role in repetitive and social behaviours. This study examined the effect of m-chlorophenylpiperazine (m-CPP) on repetitive behaviours and prolactin response in 11 adults with autism or Aspergers disorder and 8 age- and gender-matched healthy controls via randomized double-blind, m-CPP and placebo challenges. The primary outcome measure was an instrument rating six repetitive behaviours: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a significant increase in repetitive behaviours at end-point following oral m-CPP in comparison to placebo. Additionally subjects with autism spectrum disorders showed a significantly increased prolactin response to m-CPP compared to normal controls, with neither group responding to placebo. This study provides further evidence for altered 5-HT sensitivity in individuals with autism spectrum disorders, as well as a possible relationship between repetitive behaviours in autism spectrum disorders and abnormalities in the 5-HT system.

Adolescent↗

PubMed2004

Impact of recent findings on study design of future autism clinical trials.

There are specific challenges to studying the design of pharmacologic trials in child/adolescent and adult autism, such as subject stratification and parallel versus crossover designs. This article describes how optimal study design is influenced by subject selection and outcome measures chosen. Lessons learned in study design from the Research Units on Pediatric Psychopharmacology Autism Network trial with risperidone, Seaver Center trials with fluoxetine and valproate, Dartmouth trials with amantadine, and National Institutes of Health secretin trials are highlighted. The Internet System for Assessing Autistic Children system for managing multicenter clinical trials in autism and statistical issues in autism research are also described.

Adolescent↗

PubMed2004

Comorbidity in compulsive hoarding: a case report.

A 56-year-old male presented with compulsive hoarding along with attention-deficit/hyperactivity disorder and schizotypal personality disorder. Hoarding has been described as difficult to treat both pharmacologically and behaviorally, and this patient's comorbid conditions also contributed to his overall impairment. The patient's treatment regimen of fluvoxamine, amphetamine salts, and risperidone, along with behavioral therapy, has helped with hoarding behaviors, motivation, procrastination, and increased socialization. Hoarding may be a unique subtype of obsessive-compulsive disorder with poorer prognosis and distinct neuroanatomic dysfunction. Augmentation with stimulants may provide benefits in aspects of hoarding such as procrastination, especially in patients with comorbid attention-deficit hyperactivity disorder.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

Regional glucose metabolism within cortical Brodmann areas in healthy individuals and autistic patients.

A new Brodmann area (BA) delineation approach was applied to FDG-PET scans of autistic patients and healthy volunteers (n = 17 in each group) to examine relative glucose metabolism (rGMR) during performance of a verbal memory task. In the frontal lobe, patients had lower rGMR in medial/cingulate regions (BA 32, 24, 25) but not in lateral regions (BA 8-10) compared with healthy controls. Patients had higher rGMR in occipital (BA 19) and parietal regions (BA 39) compared with controls, but there were no group differences in temporal lobe regions. Among controls, better recall and use of the semantic-clustering strategy was associated with greater lateral and medial frontal rGMR, while decreased rGMR in medial-frontal regions was associated with greater perseverative/intrusion errors. Patients failed to show these patterns. Autism patients have dysfunction in some but not all of the key brain regions subserving verbal memory performance, and other regions may be recruited for task performance.

Adolescent↗

PubMed2004

Social anxiety in outpatients with schizophrenia: a relevant cause of disability.

OBJECTIVE: Social anxiety is a frequent but often unrecognized feature in schizophrenia and is associated with a severe level of disability. To precisely define the assessment, impact, clinical correlates, and consequences of social anxiety in schizophrenia, the authors conducted a survey of schizophrenia patients and a comparison cohort of patients with social anxiety disorder. METHOD: A consecutively enrolled group of 80 outpatients with DSM-IV schizophrenia and a consecutive comparison group of 27 patients with social anxiety disorder were recruited from an institutional psychiatric practice and assessed with the Liebowitz Social Anxiety Scale, Scale for the Assessment of Negative Symptoms, Scale for the Assessment of Positive Symptoms, Social Adjustment Scale, and the Medical Outcomes Study 36-item Short-Form Health Survey. RESULTS: Social anxiety scores of schizophrenia patients with comorbid social anxiety disorder (N=29, 36.3%) did not differ from those of subjects with social anxiety disorder as their primary diagnosis. Schizophrenia patients without social anxiety disorder had significantly lower total scores on the Liebowitz Social Anxiety Scale and lower social and performance anxiety subscale scores than did the other two groups. No differences in negative and positive symptom rates were found between schizophrenia patients with and without social anxiety disorder. Schizophrenia patients with social anxiety disorder had a higher lifetime rate of suicide attempts, greater lethality of suicide attempts, more past substance/alcohol abuse disorder, lower social adjustment, and lower overall quality of life. CONCLUSIONS: Social anxiety is a highly prevalent, disabling condition in outpatients with schizophrenia that is unrelated to clinical psychotic symptoms. The Liebowitz Social Anxiety Scale appeared adequate and reliable in assessing social anxiety disorder in patients with schizophrenia. If these data are confirmed, this study will make a contribution to the search for operational guidelines and adequate next-step treatments for social anxiety disorder in schizophrenia patients.

Adult↗

PubMed2004

Beyond refractory obsessions and anxiety states: toward remission.

At the Sixth International Obsessive-Compulsive Disorder Conference (IOCDC), held November 13-15, 2003, in Lanzarote, Spain, 2 issues were discussed that are of great importance to future research on obsessive-compulsive disorder (OCD). The first of these is the possible inclusion of obsessive-compulsive spectrum disorders (OCSD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. OCSD resemble OCD in their clinical symptoms, associated features, comorbidity, family/genetics, etiology, and neurocircuitry, as well as their selective response to treatment with serotonin reuptake inhibitors. The second issue is considering remission as the ultimate goal of treatment for OCD instead of just symptom reduction, as has been suggested in other disorders. These and other issues should be discussed at future meetings of the IOCDC and influence how we conceptualize the disorder and design future treatment trials.

Anxiety Disorders↗

PubMed2004

A qualitative analysis of nonresponse: management of treatment-refractory obsessive-compulsive disorder.

Serotonin reuptake inhibitors (SRIs), especially potent ones given at high doses over long periods of time, are often effective in the treatment of obsessive-compulsive disorder (OCD). However, a large percentage of patients do not respond to treatment with SRIs, and those who do respond often do not fully remit, which should be the standard goal of treatment in OCD. If a patient has been treated for several months and has not yet responded to treatment with several SRIs, the physician should perform a careful assessment of resistant and/or residual clinical symptoms and any comorbid conditions to determine which next-step treatment would be the most appropriate. One strategy for patients who have not responded to treatment with an SRI is to switch them to a serotonin-norepinephrine reuptake inhibitor, because some patients may respond better to agents that target multiple systems. Another promising approach is the augmentation of SRIs with neuroleptics. In addition, open trials have shown that intravenous (IV) clomipramine and IV citalopram may be effective in the treatment of resistant OCD. Novel pharmacotherapeutic treatments and electroconvulsive therapy have been attempted, with mixed success. Recently, researchers have been studying repetitive transcranial magnetic stimulation, vagal nerve stimulation, and neurosurgical approaches such as gamma knife capsulotomy and deep brain stimulation to learn if these procedures are effective in treating treatment-resistant OCD. Repetitive transcranial magnetic stimulation has possibilities not only as a therapy but also as an instrument that can help researchers describe the neurocircuitries involved in OCD. More results are needed before the effectiveness of the nonpharmacologic treatments for OCD can be determined.

Adrenergic Uptake Inhibitors↗

PubMed2004

Serotonin-1D hypothesis of obsessive-compulsive disorder: an update.

Support for the serotonin-1D (5-HT(1D)) hypothesis of obsessive-compulsive disorder (OCD) and related conditions comes from a variety of sources. Some pharmacologic challenges with the 5-HT(1D) agonist sumatriptan, and case reports in which prolonged administration of 5-HT(1D) agonists was associated with a therapeutic effect, suggest that 5-HT(1D) may play a role in obsessive-compulsive symptoms. Genetic studies have also found that polymorphism of the 5-HT(1D) gene may be preferentially transmitted to those patients with OCD. However, taking into account that OCD is a heterogeneous syndrome, the 5-HT(1D) hypothesis requires further investigation in order to disentangle the role of the 5-HT(1D) receptor in this common and often severe disorder.

Humans↗

PubMed2003

Targeted treatments for symptom domains in child and adolescent autism.

CONTEXT: The number of people with autism spectrum disorders has dramatically increased over the past decade, and problem behaviours in autism are an increasing challenge to families, schools, physicians, and other health-care professionals. Pharmacological treatments can effectively target problem behaviours associated with autism. STARTING POINT: Recently, L Namerow and colleagues (J Dev Behav Pediatr 2003; 24: 104-08) presented preliminary data in children and adolescents with autism treated with citalopram, which suggested that selective serotonin-reuptake inhibitors are useful in the reduction of symptom domains such as repetitive behaviours and mood disorders. J McCracken and colleagues (N Engl J Med 2000; 347: 314-21) showed that the atypical antipsychotic risperidone reduced serious behavioural problems, such as tantrums, aggression, or self-injury in children with autism and in children with below-average intelligence quotients. These and other studies show how developments in study design, selection of patients, and outcome measures have allowed treatment trials in autism to progress beyond anecdotal reports and case observations, and show reduction in the severity of specific symptom domains within these disorders. WHERE NEXT? In therapeutic intervention the risk of treatment toxicity must be balanced against the benefits of improved symptom severity. The newer methods enable informed decisions about which patients will benefit from which treatments. Other symptom domains within autism and effects on development need to be evaluated in adequately designed clinical trials. Future strategies include extending treatment to children as young as the preschool years.

Adolescent↗

PubMed2003

Divalproex in the treatment of impulsive aggression: efficacy in cluster B personality disorders.

Impulsive aggressive behavior is common in psychiatric disorders and accounts for significant morbidity and mortality. However, little systematic treatment data exist from placebo-controlled trials for this symptom domain. This was a multicenter, randomized, double-blind, placebo-controlled study in which outpatients with a score of > or =15 on the Aggression scale of the Overt Aggression Scale-Modified (OAS-M) and who fulfilled DSM-IV criteria for Cluster B personality disorder (n=96), intermittent explosive disorder (n=116), or post-traumatic stress disorder (n=34) were randomized to divalproex sodium or placebo for 12 weeks duration. Based on average OAS-M Aggression scores over the last 4 weeks of treatment, a treatment effect was not observed in the intent-to-treat data set (combined across the three psychiatric disorders), but was observed in both intent-to-treat and evaluable data sets for patients with Cluster B personality disorders. In the Cluster B evaluable data set, statistically significant treatment differences favoring divalproex were also observed for component items of the OAS-M Aggression score, including verbal assault and assault against objects, as well as OAS-M Irritability score, and Clinical Global Impression (CGI)-Severity at multiple time points throughout the study. No treatment group difference was noted for overall premature discontinuation rate; however, across psychiatric diagnoses, 21 (17%) patients in the divalproex group prematurely discontinued because of an adverse event, as compared to 4 (3%) patients in the placebo group (p <0.001). While a treatment effect was not observed when all diagnostic groups were combined, in a large subgroup of patients with Cluster B disorders, divalproex was superior to placebo in the treatment of impulsive aggression, irritability, and global severity.

Adult↗

PubMed2003

Obsessive-compulsive behaviors in parents of multiplex autism families.

Parents of autistic probands with high and low rates of repetitive behaviors were compared for rates of obsessive-compulsive traits and disorder. The rate of repetitive behaviors was assessed using the Autism Diagnostic Interview-Revised (ADI-R) in 176 autistic probands from 57 multiplex families. Obsessive-compulsive disorder (OCD) in parents was determined by direct interview using a parental history questionnaire, with screening for obsessive-compulsive traits using the Yale-Brown Obsessive-Compulsive Scale checklist. Children who had high total scores on the repetitive behavior domain of the ADI-R were significantly more likely to have one or both parents with obsessive-compulsive traits or disorder compared with children who had low total scores on this domain. Children with high scores on D1/D2 of the ADI-R (narrow restricted interests and rituals) were significantly more likely to have one or both parents with OCD, especially fathers, than those with low D1/D2. The occurrence of obsessive-compulsive traits or disorder in parents of autistic children in multiplex families is significantly more likely if autistic children have a high occurrence of repetitive behaviors. Dichotomizing autistic probands by severity and type of repetitive behaviors (circumscribed interests and compulsive rituals) may yield more homogenous groups, which could be helpful in genetic linkage studies.

Adult↗

PubMed2003

Diagnosis and treatment of pathologic gambling.

Pathologic gambling (PG) is an impulse control disorder characterized by recurrent and maladaptive gambling behaviors that significantly disrupt the patient's functioning in the personal, familial, or vocational spheres. Pathologic gambling is estimated to currently affect 1% to 3.4% of the adult US population and is frequently comorbid with substance abuse or dependence, attention-deficit/hyperactivity disorder (ADHD), and affective disorders. Studies show evidence for the involvement of the serotonergic, noradrenergic, and dopaminergic systems in the etiology of PG. Medication treatment studies performed in PG patients demonstrated the short-term efficacy of various serotonin reuptake inhibitors, opioid antagonists, and mood stabilizers in a subsample of adult pathologic gamblers who seek treatment. This review focuses on recent research examining the neurobiology and treatment of PG.

Adult↗

PubMed2003

WCA recommendations for the long-term treatment of obsessive-compulsive disorder in adults.

What are the latest psychotherapeutic and pharmacotherapeutic treatment recommendations for obsessive-compulsive disorder (OCD)? OCD is a relatively common disorder with a lifetime prevalence of approximately 2% in the general population. It often has an early onset, usually in childhood or adolescence, and frequently becomes chronic and disabling if left untreated. High associated healthcare utilization and costs, and reduced productivity resulting in loss of earning, pose a huge economic burden to OCD patients and their families, employers, and society. OCD is characterized by the presence of obsessions and compulsions that are time-consuming, cause marked distress, or significantly interfere with a person's functioning. Most patients with OCD experience symptoms throughout their lives and benefit from long-term treatment. Both psychotherapy and pharmacotherapy are recommended, either alone or in combination, for the treatment of OCD. Cognitive-behavioral therapy is the psychotherapy of choice. Pharmacologic treatment options include the tricyclic antidepressant clomipramine and the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. These have all shown benefit in acute treatment trials; clomipramine, fluvoxamine, fluoxetine, and sertraline have also demonstrated benefit in long-term treatment trials (at least 24 weeks), and clomipramine, sertraline, and fluvoxamine have United States Food and Drug Administration approvals for use in children and adolescents. Available treatment guidelines recommend first-line use of an SSRI (ie, fluoxetine, fluvoxamine, paroxetine, sertraline, or citalopram) in preference to clomipramine, due to the latter's less favorable adverse-event profile. Further, pharmacotherapy for a minimum of 1-2 years is recommended before very gradual withdrawal may be considered.

Adult↗

PubMed2003

WCA recommendations for the long-term treatment of panic disorder.

What are the symptoms of panic disorder and how is the disorder most effectively treated? One of the most commonly encountered anxiety disorders in the primary care setting, panic disorder is a chronic and debilitating illness. The core symptoms are recurrent panic attacks coupled with anticipatory anxiety and phobic avoidance, which together impair the patient's professional, social, and familial functioning. Patients with panic disorder have medically unexplained symptoms that lead to overutilization of healthcare services. Panic disorder is often comorbid with agoraphobia and major depression, and patients may be at increased risk of cardiovascular disease and, possibly, suicide. Research into the optimal treatment of this disorder has been undertaken in the past 2 decades, and numerous randomized, controlled trials have been published. Selective serotonin reuptake inhibitors have emerged as the most favorable treatment, as they have a beneficial side-effect profile, are relatively safe (even if taken in overdose), and do not produce physical dependency. High-potency benzodiazepines, reversible monoamine oxidase inhibitors, and tricyclic antidepressants have also shown antipanic efficacy. In addition, cognitive-behavioral therapy has demonstrated efficacy in the acute and long-term treatment of panic disorder. An integrated treatment approach that combines pharmacotherapy with cognitive-behavioral therapy may provide the best treatment. Long-term efficacy and ease of use are important considerations in treatment selection, as maintenance treatment is recommended for at least 12-24 months, and in some cases, indefinitely.

Adult↗

PubMed2003

WCA Recommendations for the long-term treatment of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a common and disabling condition. In addition to combat-related PTSD, the disorder occurs in civilians exposed to severe traumatic events, with the community prevalence rate for the combined populations reaching as high as 12%. If left untreated, PTSD may continue for years after the stressor event, resulting in severe functional and emotional impairment and a dramatic reduction in quality of life, with negative economic consequences for both the sufferer and society as a whole. Although PTSD is often overlooked, diagnosis is relatively straightforward once a triggering stressor event and the triad of persistent symptoms-reexperiencing the traumatic event, avoiding stimuli associated with the trauma, and hyperarousal have been identified. However, comorbid conditions of anxiety and depression frequently hamper accurate diagnosis. Treatment for PTSD includes psychotherapy and pharmacotherapy. The latter includes selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and monoamine oxidase inhibitors. Only SSRIs have been proven effective and safe in long-term randomized controlled trials. Current guidelines from the Expert Consensus Panel for PTSD recommend treatment of chronic PTSD for a minimum of 12-24 months.

Antidepressive Agents, Tricyclic↗

PubMed2003

WCA recommendations for the long-term treatment of social phobia.

What is the best approach for treating patients with social phobia (social anxiety disorder) over the long term? Social phobia is the most common anxiety disorder, with reported prevalence rates of up to 18.7%. Social phobia is characterized by a marked and persistent fear of being observed or evaluated by others in social performance or interaction situations and is associated with physical, cognitive, and behavioral (ie, avoidance) symptoms. The onset of social phobia typically occurs in childhood or adolescence and the clinical course, if left untreated, is usually chronic, unremitting, and associated with significant functional impairment. Social phobia exhibits a high degree of comorbidity with other psychiatric disorders, including mood disorders, anxiety disorders, and substance abuse/dependence. Few people with social phobia seek professional help despite the existence of beneficial treatment approaches. The efficacy, tolerability, and safety of the selective serotonin reuptake inhibitors (SSRIs), evidenced in randomized clinical trials, support these agents as first-line treatment. The benzodiazepine clonazepam and certain monoamine oxidase inhibitors (representing both reversible and nonreversible inhibitors) may also be of benefit. Treatment of social phobia may need to be continued for several months to consolidate response and achieve full remission. The SSRIs have shown benefit in long-term treatment trials, while long-term treatment data from clinical studies of clonazepam are limited but support the drug's efficacy. There is also evidence for the effectiveness of exposure-based strategies of cognitive-behavioral therapy, and controlled studies suggest that the effects of treatment are generally maintained at long-term follow-up. In light of the chronicity and disability associated with social phobia, as well as the high relapse rate after short-term therapy, it is recommended that effective treatment be continued for at least 12 months.

Adult↗

PubMed2003

WCA recommendations for the long-term treatment of generalized anxiety disorder.

What are the current recommendations for the long-term treatment of generalized anxiety disorder (GAD)? GAD is a common disorder with a lifetime prevalence of 4% to 7% in the general population. GAD is characterized by excessive, uncontrollable worry or anxiety about a number of events or activities that the individual experiences on more days than not over a 6-month period. Onset of GAD symptoms usually occurs during an individual's early twenties; however, high rates of GAD have also been seen in children and adolescents. The clinical course of GAD is often chronic, with 40% of patients reporting illness lasting >5 years. GAD is associated with pronounced functional impairment, resulting in decreased vocational function and reduced quality of life. Patients with GAD tend to be high users of outpatient medical care, which contributes significantly to healthcare costs. Currently, benzodiazepines and buspirone are prescribed frequently to treat GAD. Although both show efficacy in acute treatment trials, few long-term studies have been performed. Benzodiazepines are not recommended for long-term treatment of GAD, due to associated development of tolerance, psychomotor impairment, cognitive and memory changes, physical dependence, and a withdrawal reaction on discontinuation. The antidepressant venlafaxine extended-release (XR) has received approval for the treatment of GAD in the United States and many other countries. Venlafaxine XR has demonstrated efficacy over placebo in two randomized treatment trials of 6 months' duration as well as in other acute trials. Paroxetine is the first of the selective serotonin reuptake inhibitors (SSRIs) to receive US approval for the treatment of GAD. Paroxetine demonstrated superiority to placebo in short-term trials, and investigations into the use of other SSRIs are ongoing. This suggests that other SSRIs, and serotonin and noradrenaline reuptake inhibitors, are likely to be effective in the treatment of GAD. Of the psychological therapies, cognitive-behavioral therapy (CBT) shows the greatest benefit in treating GAD patients. Treatment gains after a 12-week course of CBT may be maintained for up to 1 year. Currently, no guidelines exist for the long-term treatment of GAD.

Antidepressive Agents, Tricyclic↗

PubMed2003

Relationship of personality to dissociation and childhood trauma in borderline personality disorder.

BACKGROUND: Dissociation is a prominent feature in some individuals with borderline personality disorder (BPD), yet our understanding of the meanings and implications of prominent dissociation in BPD remains limited. The purpose of this study was to investigate the relationship between dissociation and childhood trauma in BPD and to explore the relationships of dissociation and trauma to various personality features of BPD. METHODS: Twenty BPD subjects and 24 healthy comparison subjects of similar age and gender were administered the Dissociative Experiences Scale, the Childhood Trauma Questionnaire-short form, the Tridimensional Personality Questionnaire, the Defense Style Questionnaire, the Relationship Style Questionnaire, and the Schema Questionnaire. RESULTS: The BPD group exhibited greater dissociation and childhood trauma, as well as greater pathology in most personality variables, compared with the healthy group. Dissociation in BPD was not significantly related to total childhood trauma, but only to emotional neglect, which accounted for 23% of the variance in dissociation scores. CONCLUSION: Within the BPD group, dissociation was associated with fearful attachment and immature defenses, while total childhood trauma and emotional neglect were associated with overconnection and disconnection schemata. This is a preliminary study with a small sample size, yet the correlates of dissociation in BPD merit further investigation.

Adult↗