Publications by authors named "Eric Hollander"

220 Publications

Challenges in assessing change in autistic adults: scale limitations and discrepancies in reporting in clinical trials.

Int J Psychiatry Clin Pract 2021 Mar 28:1-5. Epub 2021 Mar 28.

Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.

Autism Spectrum Disorder (ASD) is a developmental disorder marked by deficits in social communication and social interaction, together with restricted and/or repetitive patterns of behaviours, activities or interests. As more adults are being diagnosed with ASD, and more diagnosed children are aging into adulthood, the need for effective treatments and support services for autistic adults is quickly growing. As such, clinical research targeting autistic adults has emerged in recent years. Currently, caregiver ratings are commonly used as outcome measures in child treatment studies, but these scales present challenges when utilised to assess the autistic adult population. In this commentary, we seek to unveil the difficulties and obstacles in assessing change in clinical treatment trials for autistic adults. Specifically, this article uses case examples to explore the limitations of rating scales. Steps for improving the accuracy of ratings, and for developing novel self-rating scales for autistic adults are discussed. It is hoped that in exploring these difficulties in more depth, clinical research with adult ASD populations will continue to improve and that reliable, valid and sensitive outcome measures will be developed to ensure the highest quality treatments emerge.
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http://dx.doi.org/10.1080/13651501.2021.1900871DOI Listing
March 2021

Presentation and management of anxiety in individuals with acute symptomatic or asymptomatic COVID-19 infection, and in the post-COVID-19 recovery phase.

Int J Psychiatry Clin Pract 2021 Jun 26;25(2):115-131. Epub 2021 Feb 26.

Autism and Obsessive Compulsive Spectrum Program, Department of Psychiatry and Behavioral Sciences, Psychiatric Research Institute at Montefiore-Einstein, Albert Einstein College of Medicine, Bronx, NY, USA.

COVID-19 is associated with neuropsychiatric complications, the most frequent one being anxiety. Multiple biological and psychosocial factors contribute to anxiety in COVID-19. Among the biological factors, stress, genetics, gender, immune system, resilience, anosmia, hypogeusia, and central nervous system infection with SARS-CoV-2 are key. Anxiety is a complication of COVID-19 that may exacerbate the infection course, and the infection may exacerbate anxiety. We present the mechanisms of anxiety in symptomatic or asymptomatic COVID-19. We discuss the presentation of anxiety in patients without or with prior psychiatric illness, and with co-morbidities. Timely diagnosis and management of anxiety in COVID-19 patients is important. Given the frequent complication of COVID-19 with Acute Respiratory Distress Syndrome and Intensive Care Unit stay, anxiety may be a long-term complication. We review the diagnostic tools for anxiety in COVID-19, and summarise pharmacologic and non-pharmacologic treatments. We provide recommendations for diagnosis, treatment, prevention and follow up of anxiety in COVID-19.Key pointsPatients with COVID-19 (symptomatic or asymptomatic) exhibit a high frequency of neuropsychiatric complications with highest percentage attributed to anxiety.Multiple biological and psychosocial risk factors for anxiety exist in COVID-19-ill individuals. Biological risk factors include stress, resilience, genetics, gender, age, immune system, direct infection of the central nervous system (CNS) with SARS-CoV-2, comorbid psychiatric and general medical illnesses, ARDS and ICU stay. Anosmia and hypogeusia are COVID-19-specific anxiety risk factors. Knowledge of the anxiety risk factors is essential to focus on timely interventions, because anxiety may be a complication of and exacerbate the COVID-19 course.An inverse correlation exists between resilience and anxiety because of COVID-19, and therefore efforts should be made to increase resilience in COVID-19 patients.In COVID-19, important anxiety mechanism is neuroinflammation resulting from activation of the immune system and an ensuing cytokine storm.The general approach to management of anxiety in COVID-19 should be compassionate, similar to that during trauma or disaster, with efforts focussed on instilling a sense of hope and resilience.In selecting pharmacological treatment of anxiety, the stress response and immune system effects should be key. Medications with cardio-respiratory adverse effects should be avoided in patients with respiratory problems.Anxiety is a disorder that will require for long-term follow up at least one month after COVID-19.
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http://dx.doi.org/10.1080/13651501.2021.1887264DOI Listing
June 2021

Body dysmorphic disorder: a treatment synthesis and consensus on behalf of the International College of Obsessive-Compulsive Spectrum Disorders and the Obsessive Compulsive and Related Disorders Network of the European College of Neuropsychopharmacology.

Int Clin Psychopharmacol 2021 03;36(2):61-75

Department of Clinical and Pharmaceutical Sciences, University of Hertfordshire and Hertfordshire Partnership University NHS Foundation Trust, Hatfield, UK.

Body dysmorphic disorder (BDD) is characterized by a preoccupation with a perceived appearance flaw or flaws that are not observable to others. BDD is associated with distress and impairment of functioning. Psychiatric comorbidities, including depression, social anxiety, and obsessive-compulsive disorder are common and impact treatment. Treatment should encompass psychoeducation, particularly addressing the dangers associated with cosmetic procedures, and may require high doses of selective serotonin reuptake inhibitors* (SSRI*) and protracted periods to establish full benefit. If there is an inadequate response to SSRIs, various adjunctive medications can be employed including atypical antipsychotics*, anxiolytics*, and the anticonvulsant levetiracetam*. However, large-scale randomized controlled trials are lacking and BDD is not an approved indication for these medications. Oxytocin* may have a potential role in treating BDD, but this requires further exploration. Cognitive-behavioural therapy has good evidence for efficacy for BDD, and on-line and telephone-assisted forms of therapy are showing promise. CBT for BDD should be customized to address such issues as mirror use, perturbations of gaze, and misinterpretation of others' emotions, as well as overvalued ideas about how others view the individual.
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http://dx.doi.org/10.1097/YIC.0000000000000342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846290PMC
March 2021

Intranasal oxytocin versus placebo for hyperphagia and repetitive behaviors in children with Prader-Willi Syndrome: A randomized controlled pilot trial.

J Psychiatr Res 2021 05 4;137:643-651. Epub 2020 Nov 4.

Autism and Obsessive Compulsive Spectrum Disorders Program, Psychiatric Research Institute of Montefiore Einstein (PRIME), Albert Einstein College of Medicine, New York, USA.

Objective: The effects of intranasal oxytocin and placebo on hyperphagia and repetitive behaviors were compared in children and adolescents with Prader Willi Syndrome (PWS).

Methods: Children and adolescents with PWS were enrolled in an 8-week double-blind placebo-controlled intranasal oxytocin randomized trial. Twenty-three (23) subjects were assigned to oxytocin (N = 11) or placebo (N = 12). Hyperphagia was measured with the Hyperphagia Questionnaire (HQ), and repetitive behavior was measured with Repetitive Behavior Scale- Revised (RBS-R).

Results: There were modest significant treatment by-time interactions indicating reduction in hyperphagia and repetitive behaviors across time for placebo but no reduction for oxytocin. Total HQ score showed a greater average reduction of 1.81 points/week for the placebo group vs. oxytocin, with maximum reduction at week 4. There were also greater reductions on HQ-Drive and HQ-Behavior subscales on placebo vs. oxytocin. RBS-R subscales followed similar patterns to the HQ, with a significantly greater reduction in sameness subscale behaviors (average 0.825 points/week) in the placebo group compared to the oxytocin group. Oxytocin was well tolerated, and the only adverse event that was both more common and possibly related to oxytocin vs. placebo was nocturia (n = 1 vs 0).

Conclusion: Placebo was associated with modest improvement in hyperphagia and repetitive behaviors in childhood PWS whereas intranasal oxytocin was not associated with improvement in these domains. More work is needed to understand the meaning and mechanism of these findings on hyperphagia and repetitive behaviors in PWS.
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http://dx.doi.org/10.1016/j.jpsychires.2020.11.006DOI Listing
May 2021

Predictors of Caregiver Strain for Parents of Children with Autism Spectrum Disorder.

J Autism Dev Disord 2021 Sep;51(9):3039-3049

Department of Pediatrics, Emory University School of Medicine, 2015 Uppergate Dr, Atlanta, GA, 30322, USA.

Parents of children with autism spectrum disorder (ASD) face higher levels of caregiver strain compared to parents of children with other disabilities. This study examined child clinical features that predict high levels of caregiver strain for 374 parents of children with ASD. Caregiver strain was measured using the Caregiver Strain Questionnaire (CGSQ) objective, subjective internalized, and subjective externalized subscales. Confirmatory factor analysis indicated an acceptable fit for the original CGSQ three-factor solution. The strongest child predictors across CGSQ subscales were: disruptive behavior for objective strain, autism severity and disruptive behavior for subjective internalized strain, and oppositional behavior and hyperactivity for subjective externalized strain. Individualized interventions that attend to specific elements of parental strain may reduce strain and improve family wellbeing.
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http://dx.doi.org/10.1007/s10803-020-04625-xDOI Listing
September 2021

Clinical characteristics and comorbidity associated with female gender in obsessive-compulsive disorder.

J Psychiatr Res 2020 12 22;131:209-214. Epub 2020 Sep 22.

Luigi Sacco University Hospital, Psychiatry 2 Unit, University of Milan, Milan, Italy; "Aldo Ravelli" Center for Nanotechnology and Neurostimulation, University of Milan, Milan, Italy; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; "Centro per Lo Studio Dei Meccanismi Molecolari Alla Base Delle Patologie Neuro-psico-geriatriche", University of Milan, Milan, Italy.

Introduction: Obsessive-compulsive disorder (OCD) is a heterogeneous condition characterized by largely variable phenotypic expressions. Previous findings suggested that gender may be a relevant factor in mediating this heterogeneity. The present study aimed at exploring gender differences in a large clinical sample of Italian OCD patients.

Methods: Socio-demographic and clinical variables of a sample of 229 consecutive OCD outpatients were included in a common database. Patients were assessed through structured clinical interviews, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression (CGI) scale.

Results: Female OCD patients were more likely than males to have lifetime psychiatric comorbidities (72.6% vs 56.9%; p < 0.05), poly-comorbidities being twice as high compared to males. The female group also showed a significant later onset of symptoms (63.7% vs 44.8%; p < 0.005) and a higher age at first treatment (30.98 ± 13.1 years vs 27.81 ± 11.3; p < 0.005). Moreover, the female subgroup presented higher rates of cleaning and washing compulsions, compared to the male subgroup (28.7% vs 12.6% in the male group; p < 0.005).

Conclusions: The current study supports the notion that OCD in female gender is frequently a comorbid condition with other specific clinical characteristics compared to male patients. These findings should be considered in epidemiologic and therapeutic perspectives.
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http://dx.doi.org/10.1016/j.jpsychires.2020.09.019DOI Listing
December 2020

Neurocovid-19: A clinical neuroscience-based approach to reduce SARS-CoV-2 related mental health sequelae.

J Psychiatr Res 2020 11 15;130:215-217. Epub 2020 Aug 15.

Autism and OCD Spectrum Program, Psychiatric Research Institute of Montefiore Einstein, Albert Einstein College of Medicine, NY, USA.

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, is a disaster due to not only its psychosocial impact but it also to its direct effects on the brain. The latest evidence suggests it has neuroinvasive mechanisms, in addition to neurological manifestations, and as seen in past pandemics, long-term sequelae are expected. Specific and well-structured interventions are necessary, and that's why it's important to ensure a continuity between primary care, emergency medicine, and psychiatry. Evidence shows that 2003 SARS (Severe Acute Respiratory Syndrome) survivors developed persistent psychiatric comorbidities after the infection, in addition to Chronic Fatigue Syndrome. A proper stratification of patients according not only to psychosocial factors but also an inflammatory panel and SARS-Cov-2's direct effects on the central nervous system (CNS) and the immune system, may improve outcomes. The complexity of COVID-19's pathology and the impact on the brain requires appropriate screening that has to go beyond the psychosocial impact, taking into account how stress and neuroinflammation affects the brain. This is a call for a clinical multidisciplinary approach to treat and prevent Sars-Cov-2 mental health sequelae.
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http://dx.doi.org/10.1016/j.jpsychires.2020.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428715PMC
November 2020

Clinical advances in obsessive-compulsive disorder: a position statement by the International College of Obsessive-Compulsive Spectrum Disorders.

Int Clin Psychopharmacol 2020 07;35(4):173-193

Department of Psychiatry, Bellvitge University Hospital-IDIBELL, University of Barcelona, Cibersam, Barcelona, Spain.

In this position statement, developed by The International College of Obsessive-Compulsive Spectrum Disorders, a group of international experts responds to recent developments in the evidence-based management of obsessive-compulsive disorder (OCD). The article presents those selected therapeutic advances judged to be of utmost relevance to the treatment of OCD, based on new and emerging evidence from clinical and translational science. Areas covered include refinement in the methods of clinical assessment, the importance of early intervention based on new staging models and the need to provide sustained well-being involving effective relapse prevention. The relative benefits of psychological, pharmacological and somatic treatments are reviewed and novel treatment strategies for difficult to treat OCD, including neurostimulation, as well as new areas for research such as problematic internet use, novel digital interventions, immunological therapies, pharmacogenetics and novel forms of psychotherapy are discussed.
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http://dx.doi.org/10.1097/YIC.0000000000000314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255490PMC
July 2020

Correction to: Exploring Social Biomarkers in High‑Functioning Adults with Autism and Asperger's Versus Healthy Controls: A Cross‑Sectional Analysis.

J Autism Dev Disord 2020 Dec;50(12):4431-4432

Roche Innovation Center Basel, Roche Pharmaceutical Research and Early Development, NRD, Basel, Switzerland.

The original version of this article unfortunately contained a mistake in CI values in Table 2.
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http://dx.doi.org/10.1007/s10803-020-04522-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852857PMC
December 2020

Exploring Social Biomarkers in High-Functioning Adults with Autism and Asperger's Versus Healthy Controls: A Cross-Sectional Analysis.

J Autism Dev Disord 2020 Dec;50(12):4412-4430

Roche Innovation Center Basel, Roche Pharmaceutical Research and Early Development, NRD, Basel, Switzerland.

Biomarkers for autism spectrum disorder (ASD) are lacking but would facilitate drug development for the core deficits of the disorder. We evaluated markers proposed for characterization of differences in social communication and interaction in adults with ASD versus healthy controls (HC) for utility as biomarkers. Data pooled from an observational study and baseline data from a placebo-controlled study were analyzed. Between-group differences were observed in eye-tracking tasks for activity monitoring, biomotion, human activity preference, composite score (p = 0.0001-0.037) and pupillometry (various tasks, p = 0.017-0.05). Impaired olfaction was more common in the ASD sample versus HC (p = 0.018). Our preliminary results suggest the potential use for stratification and response sub-analyses outcome-prediction of specific eye-tracking tasks, pupillometry and olfaction tests in ASD trials.
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http://dx.doi.org/10.1007/s10803-020-04493-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677266PMC
December 2020

Compulsivity in Alcohol Use Disorder and Obsessive Compulsive Disorder: Implications for Neuromodulation.

Front Behav Neurosci 2019 11;13:70. Epub 2019 Apr 11.

Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, United States.

Alcohol use Disorder (AUD) is one of the leading causes of morbidity and mortality worldwide. The progression of the disorder is associated with the development of compulsive alcohol use, which in turn contributes to the high relapse rate and poor longer term functioning reported in most patients, even with treatment. While the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines AUD by a cluster of symptoms, parsing its heterogeneous phenotype by domains of behavior such as compulsivity may be a critical step to improve outcomes of this condition. Still, neurobiological underpinnings of compulsivity need to be fully elucidated in AUD in order to better design targeted treatment strategies. In this manuscript, we review and discuss findings supporting common mechanisms between AUD and OCD, dissecting the construct of compulsivity and focusing specifically on characteristic disruptions in habit learning and cognitive control in the two disorders. Finally, neuromodulatory interventions are proposed as a probe to test compulsivity as key pathophysiologic feature of AUD, and as a potential therapy for the subgroup of individuals with compulsive alcohol use, i.e., the more resistant stage of the disorder. This transdiagnostic approach may help to destigmatize the disorder, and suggest potential treatment targets across different conditions.
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http://dx.doi.org/10.3389/fnbeh.2019.00070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470293PMC
April 2019

Lifetime bipolar disorder comorbidity and related clinical characteristics in patients with primary obsessive compulsive disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).

CNS Spectr 2020 06 27;25(3):419-425. Epub 2019 May 27.

Department of Psychiatry, Chaim Sheba Medical Center, Tel Hashomer, Israel.

Introduction: Bipolar disorder (BD) and obsessive compulsive disorder (OCD) are prevalent, comorbid, and disabling conditions, often characterized by early onset and chronic course. When comorbid, OCD and BD can determine a more pernicious course of illness, posing therapeutic challenges for clinicians. Available reports on prevalence and clinical characteristics of comorbidity between BD and OCD showed mixed results, likely depending on the primary diagnosis of analyzed samples.

Methods: We assessed prevalence and clinical characteristics of BD comorbidity in a large international sample of patients with primary OCD (n = 401), through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) snapshot database, by comparing OCD subjects with vs without BD comorbidity.

Results: Among primary OCD patients, 6.2% showed comorbidity with BD. OCD patients with vs without BD comorbidity more frequently had a previous hospitalization (p < 0.001) and current augmentation therapies (p < 0.001). They also showed greater severity of OCD (p < 0.001), as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).

Conclusion: These findings from a large international sample indicate that approximately 1 out of 16 patients with primary OCD may additionally have BD comorbidity along with other specific clinical characteristics, including more frequent previous hospitalizations, more complex therapeutic regimens, and a greater severity of OCD. Prospective international studies are needed to confirm our findings.
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http://dx.doi.org/10.1017/S1092852919001068DOI Listing
June 2020

Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial.

Am J Psychiatry 2019 11 21;176(11):931-938. Epub 2019 May 21.

The School of Psychological Science, Tel Aviv University, Tel Aviv, Israel (Carmi); the Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel (Carmi, Barnea-Ygael, Roth, Zangen); Advanced Mental Health Care, Inc., Palm Beach, Fla. (Tendler); the Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles (Bystritsky); the Spectrum Neuroscience and Treatment Center, New York (Hollander); the Temerty Centre for Therapeutic Brain Intervention and the Campbell Family Research Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Ontario (Blumberger, Daskalakis); the Department of Psychiatry, University of Florida, Gainesville (Ward); the Department of Psychiatry, Northwell Health, New York (Lapidus); the Department of Psychiatry and Behavioral Health System, Icahn School of Medicine at Mount Sinai, New York (Goodman); the Lindner Center of HOPE, Mason, Ohio (Casuto); the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati (Casuto); the Department of Psychiatry, University of California San Diego, La Jolla (Feifel); the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Zohar).

Objective: Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsatisfactorily to pharmacological and psychological treatments. Converging evidence suggests a dysfunction of the cortical-striatal-thalamic-cortical circuit in OCD, and a previous feasibility study indicated beneficial effects of deep transcranial magnetic stimulation (dTMS) targeting the medial prefrontal cortex and the anterior cingulate cortex. The authors examined the therapeutic effect of dTMS in a multicenter double-blind sham-controlled study.

Methods: At 11 centers, 99 OCD patients were randomly allocated to treatment with either high-frequency (20 Hz) or sham dTMS and received daily treatments following individualized symptom provocation, for 6 weeks. Clinical response to treatment was determined using the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the primary efficacy endpoint was the change in score from baseline to posttreatment assessment. Additional measures were response rates (defined as a reduction of ≥30% in YBOCS score) at the posttreatment assessment and after another month of follow-up.

Results: Eighty-nine percent of the active treatment group and 96% of the sham treatment group completed the study. The reduction in YBOCS score among patients who received active dTMS treatment was significantly greater than among patients who received sham treatment (reductions of 6.0 points and 3.3 points, respectively), with response rates of 38.1% and 11.1%, respectively. At the 1-month follow-up, the response rates were 45.2% in the active treatment group and 17.8% in the sham treatment group. Significant differences between the groups were maintained at follow-up.

Conclusions: High-frequency dTMS over the medial prefrontal cortex and anterior cingulate cortex significantly improved OCD symptoms and may be considered as a potential intervention for patients who do not respond adequately to pharmacological and psychological interventions.
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http://dx.doi.org/10.1176/appi.ajp.2019.18101180DOI Listing
November 2019

Pharmacotherapy in body dysmorphic disorder: relapse prevention and novel treatments.

Expert Opin Pharmacother 2019 Jul 30;20(10):1211-1219. Epub 2019 Apr 30.

a Department of Psychiatry and Behavioral Sciences, Autism and Obsessive-Compulsive Spectrum Program, Anxiety and Depression Program, Albert Einstein College of Medicine , Montefiore Medical Center , Bronx , NY , USA.

: Body dysmorphic disorder is a debilitating disorder that often presents with significant delusionality, low insight, and both medical and psychiatric comorbidities, presenting a challenge for treatment and long-term management. Its typically chronic course requires that therapy be continued indefinitely, but only a few studies of long-term pharmacotherapeutic management exist. : The authors discuss the current understanding of body dysmorphic disorder, focusing specifically on: epidemiology, clinical presentation, challenges in treatment, treatment options, and the importance of the further study of the long-term management of the disorder. : Serotonin reuptake inhibitors are the established drug of choice in patients with body dysmorphic disorder. Initial studies suggest that other agents such as augmentation antipsychotic medication may also be of use in combination with serotonin reuptake inhibitors, but there is a lack of studies comparing new treatments to serotonin reuptake inhibitors. Due to the chronic nature of body dysmorphic disorder, further research is needed to clarify the role of pharmacotherapy in long-term management and relapse prevention. Future studies should explore the long-term use of therapies and combinations of different therapeutics with the goal of effectively managing this debilitating, chronic condition.
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http://dx.doi.org/10.1080/14656566.2019.1610385DOI Listing
July 2019

Early intervention for obsessive compulsive disorder: An expert consensus statement.

Eur Neuropsychopharmacol 2019 04 14;29(4):549-565. Epub 2019 Feb 14.

Sackler Medical School, Tel Aviv University, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel.

Obsessive-compulsive disorder (OCD) is common, emerges early in life and tends to run a chronic, impairing course. Despite the availability of effective treatments, the duration of untreated illness (DUI) is high (up to around 10 years in adults) and is associated with considerable suffering for the individual and their families. This consensus statement represents the views of an international group of expert clinicians, including child and adult psychiatrists, psychologists and neuroscientists, working both in high and low and middle income countries, as well as those with the experience of living with OCD. The statement draws together evidence from epidemiological, clinical, health economic and brain imaging studies documenting the negative impact associated with treatment delay on clinical outcomes, and supporting the importance of early clinical intervention. It draws parallels between OCD and other disorders for which early intervention is recognized as beneficial, such as psychotic disorders and impulsive-compulsive disorders associated with problematic usage of the Internet, for which early intervention may prevent the development of later addictive disorders. It also generates new heuristics for exploring the brain-based mechanisms moderating the 'toxic' effect of an extended DUI in OCD. The statement concludes that there is a global unmet need for early intervention services for OC related disorders to reduce the unnecessary suffering and costly disability associated with under-treatment. New clinical staging models for OCD that may be used to facilitate primary, secondary and tertiary prevention within this context are proposed.
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http://dx.doi.org/10.1016/j.euroneuro.2019.02.002DOI Listing
April 2019

In Search of Biomarkers for Autism Spectrum Disorder.

Autism Res 2018 11 15;11(11):1567-1579. Epub 2018 Oct 15.

Roche Innovation Center Basel, Roche Pharmaceutical Research and Early Development NORD, Basel, Switzerland.

Autism Spectrum Disorder (ASD) lacks validated measures of core social functions across development stages suitable for clinical trials. We assessed the concurrent validity between ASD clinical measures and putative biomarkers of core deficits, and their feasibility of implementation in human studies. Datasets from two adult ASD studies were combined (observational study [n = 19] and interventional study baseline data [n = 19]). Potential biomarkers included eye-tracking, olfaction, and auditory and visual emotion recognition assessed via the Affective Speech Recognition test (ASR) and Reading-the-Mind-in-the-Eyes Test (RMET). Current functioning was assessed with intelligence quotient (IQ), adaptive skill testing, and behavioral ratings. Autism severity was determined by the Autism Diagnostic Observation Scale-2 and Social Communication Interaction Test (SCIT). Exploratory measures showed varying significant associations across ASD severity, adaptive skills, and behavior. Eye tracking endpoints showed little relationship to adaptive ability but correlated with severity and behavior. ASR scores significantly correlated with most adaptive behavior domains, as well as severity. Olfaction predicted visual and auditory emotion recognition. SCIT scores related moderately to multiple severity domains, and was the only measure not related with IQ. RMET accuracy was less related to ASD features. Eye tracking, SCIT, and ASR showed high test-retest reliability. We documented associations of proximal biomarkers of social functioning with multiple ASD dimensions. With the exception of SCIT, most correlations were modest, limiting utility as proxy measures of social communication. Feasibility and reliability were high for eye-tracking, ASR, and SCIT. Overall, several novel experimental paradigms showed potential as social biomarkers or surrogate markers in ASD. Autism Research 2018, 11: 1567-1579. © 2018 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. LAY SUMMARY: More accurate measurements of treatment effects are needed to help the development of new drug treatments for autism spectrum disorders (ASD). This study evaluates the relationship between assessments designed to measure behaviors associated with social communication and cognition in ASD with clinical and diagnostic assessments of symptom severity as well as their implementation. The assessments including eye-tracking, auditory and visual social stimuli recognition, and olfaction identification showed potential for use in the evaluation of treatments for social difficulties in ASD.
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http://dx.doi.org/10.1002/aur.2026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282609PMC
November 2018

Randomized crossover feasibility trial of helminthic ova versus placebo for repetitive behaviors in adult autism spectrum disorder.

World J Biol Psychiatry 2020 04 16;21(4):291-299. Epub 2018 Nov 16.

Autism and Obsessive-Compulsive Spectrum Program, and Anxiety and Depression Research Program Department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.

Inflammatory mechanisms are implicated in the aetiology of autism spectrum disorder (ASD), and use of the immunomodulator Ova (TSO) is a novel treatment approach. This pilot study determined the effect sizes for TSO versus placebo on repetitive behaviours, irritability and global functioning in adults with ASD. A 28-week double-blind, randomised two-period crossover study of TSO versus placebo in ten ASD adults, aged 17-35, was completed, with a 4-week washout between each 12-week period at Montefiore Medical Center, Albert Einstein College of Medicine. Subjects with ASD, history of seasonal, medication or food allergies, Y-BOCS ≥6 and IQ ≥70 received 2,500 TSO ova or matching placebo every 2 weeks of each 12-week period. Large effect sizes for improvement in repetitive behaviours ( = 1.0), restricted interests ( = 0.82), rigidity ( = 0.79) and irritability ( = 0.78) were observed after 12 weeks of treatment. No changes were observed in the social-communication domain. Differences between treatment groups did not reach statistical significance. TSO had only minimal, non-serious side effects. This proof-of-concept study demonstrates the feasibility of TSO for the treatment of ASD, including a favourable safety profile, and moderate to large effect sizes for reducing repetitive behaviours and irritability. NCT01040221.
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http://dx.doi.org/10.1080/15622975.2018.1523561DOI Listing
April 2020

From Treatment Response to Recovery: A Realistic Goal in OCD.

Int J Neuropsychopharmacol 2018 11;21(11):1007-1013

Department of Psychiatry and Behavioral Sciences, Albert Einstein College of medicine, Bronx, NY.

Despite longitudinal studies reporting symptomatic remission rates ranging from 32% to 70%, Obsessive-Compulsive Disorder is considered a persistent and very disabling disorder. However, these studies suggest that recovery can be a realistic goal for a subgroup of the Obsessive-Compulsive Disorder population and that a clear definition of recovery is timely in Obsessive-Compulsive Disorder. The aim of this paper is to discuss the dimensions of and propose an operational definition of recovery in Obsessive-Compulsive Disorder. Considering the impact generated by the definition of recovery for other mental disorders, this article discusses how this concept may shape the future of research and clinical practice in Obsessive-Compulsive Disorder. Ultimately, the hope is that the management of Obsessive-Compulsive Disorder may parallel, and expand upon, some of the current approaches implemented in the care of schizophrenia, so that early diagnosis, stepped-care techniques, and a personalized approach can be used to create recovery-oriented treatment programs and influence policy making for Obsessive-Compulsive Disorder.
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http://dx.doi.org/10.1093/ijnp/pyy079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209853PMC
November 2018

Pharmacological Treatment of Body Dysmorphic Disorder.

Curr Neuropharmacol 2019 ;17(8):697-702

Department of Psychiatry and Behavioral Sciences, Autism and Obsessive-Compulsive Spectrum Program, Anxiety and Depression Program, Albert Einstein College of Medicine, Montefiore Medical Center, NY, United States.

Body dysmorphic disorder is a challenging disorder that manifests as erroneously perceived flaws in one's physical appearance and repetitive behaviors in response to appearance concerns. This disorder is also frequently comorbid with other psychiatric disorders, including major depressive disorder and autism spectrum disorder. It is currently understood to arise from a combination of biological, psychological, and environmental factors. Treatment of body dysmorphic disorder typically consists of a combination of pharmacotherapy and cognitive behavioral therapy. However, not all patients respond to treatment, and BDD symptoms remain even in those who do respond. This review outlines current pharmacological and neuromodulation treatments for body dysmorphic disorder and suggests directions for future studies of novel treatments such as augmentation with atypical antipsychotics and the use of intranasal oxytocin in cases of body dysmorphic disorder that show residual symptomatology even with tailored monotherapy. There is emerging evidence suggesting that non-invasive neurostimulatory techniques, such as repetitive transcranial magnetic stimulation, may be of value in treatment-resistant cases.
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http://dx.doi.org/10.2174/1570159X16666180426153940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059151PMC
January 2020

New perspectives in the treatment of body dysmorphic disorder.

F1000Res 2018 23;7:361. Epub 2018 Mar 23.

Department of Psychiatry and Behavioral Sciences, Autism and Obsessive-Compulsive Spectrum Program, Anxiety and Depression Program, Albert Einstein College of Medicine, Montiefiore Medical Center, The Bronx, New York, USA.

Body dysmorphic disorder (BDD) is a disabling illness with a high worldwide prevalence. Patients demonstrate a debilitating preoccupation with one or more perceived defects, often marked by poor insight or delusional convictions. Multiple studies have suggested that selective serotonin reuptake inhibitors and various cognitive behavioral therapy modalities are effective first-line treatments in decreasing BDD severity, relieving depressive symptoms, restoring insight, and increasing quality of life. Selective serotonin reuptake inhibitors have also recently been shown to be effective for relapse prevention. This review provides a comprehensive summary of the current understanding of BDD, including its clinical features, epidemiology, genetics, and current treatment modalities. Additional research is needed to fully elucidate the relationship between BDD and comorbid illnesses such as obsessive-compulsive-related disorders and depression and to develop therapies for refractory patients and those who have contraindications for pharmacological intervention.
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http://dx.doi.org/10.12688/f1000research.13700.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871801PMC
March 2018

Increased white matter metabolic rates in autism spectrum disorder and schizophrenia.

Brain Imaging Behav 2018 Oct;12(5):1290-1305

Crisalid Unit (FJ5), CHI Clermont de l'Oise, 2 rue des Finets, 60607, Clermont, France.

Both autism spectrum disorder (ASD) and schizophrenia are often characterized as disorders of white matter integrity. Multimodal investigations have reported elevated metabolic rates, cerebral perfusion and basal activity in various white matter regions in schizophrenia, but none of these functions has previously been studied in ASD. We used fluorodeoxyglucose positron emission tomography to compare white matter metabolic rates in subjects with ASD (n = 25) to those with schizophrenia (n = 41) and healthy controls (n = 55) across a wide range of stereotaxically placed regions-of-interest. Both subjects with ASD and schizophrenia showed increased metabolic rates across the white matter regions assessed, including internal capsule, corpus callosum, and white matter in the frontal and temporal lobes. These increases were more pronounced, more widespread and more asymmetrical in subjects with ASD than in those with schizophrenia. The highest metabolic increases in both disorders were seen in the prefrontal white matter and anterior limb of the internal capsule. Compared to normal controls, differences in gray matter metabolism were less prominent and differences in adjacent white matter metabolism were more prominent in subjects with ASD than in those with schizophrenia. Autism spectrum disorder and schizophrenia are associated with heightened metabolic activity throughout the white matter. Unlike in the gray matter, the vector of white matter metabolic abnormalities appears to be similar in ASD and schizophrenia, may reflect inefficient functional connectivity with compensatory hypermetabolism, and may be a common feature of neurodevelopmental disorders.
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http://dx.doi.org/10.1007/s11682-017-9785-9DOI Listing
October 2018

Oxytocin and Prader-Willi Syndrome.

Curr Top Behav Neurosci 2018;35:529-557

Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.

In the chapter, we explore the relationship between the peptide hormone, oxytocin (OT), and behavioral and metabolic disturbances observed in the genetic disorder Prader-Willi Syndrome (PWS). Phenotypic and genotypic characteristics of PWS are described, as are the potential implications of an abnormal OT system with respect to neural development including the possible effects of OT dysfunction on interactions with other regulatory mediators, including neurotransmitters, neuromodulators, and hormones. The major behavioral characteristics are explored in the context of OT dysfunction, including hyperphagia, impulsivity, anxiety and emotion dysregulation, sensory processing and interoception, repetitive and restrictive behaviors, and dysfunctional social cognition. Behavioral overlaps with autistic spectrum disorders are discussed. The implications of OT dysfunction on the mechanisms of reward and satiety and their possible role in informing behavioral characteristics are also discussed. Treatment implications and future directions for investigation are considered.
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http://dx.doi.org/10.1007/7854_2017_28DOI Listing
October 2018

An expert opinion on PANDAS/PANS: highlights and controversies.

Int J Psychiatry Clin Pract 2017 Jun 13;21(2):91-98. Epub 2017 Feb 13.

a Department of Neurofarba , University of Florence , Florence , Italy.

Objectives: 'Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections' (PANDAS) identified a unique subgroup of patients with abrupt onset of obsessive compulsive disorder (OCD) symptoms clinically related to Streptococcus infection and accompanied by neuropsychological and motor symptoms. After almost 20 years, PANDAS has not been accepted as distinct disorder and new criteria for paediatric acute-onset neuropsychiatric syndrome (PANS) have been replaced it, highlighting the fact that several agents rather than only Streptococcus might be involved.

Methods: Extensive review of the PANDAS/PANS literature was performed on PubMed.

Results: Although antibiotics have been reported to be effective for acute and prophylactic phases in several uncontrolled studies and non-steroidal anti-inflammatory drugs (NSAID) are used during exacerbations, clinical multicenter trials are still missing. Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT) are still the first line of recommendation for acute onset OCD spectrum. Immunological therapies should be restricted to a few cases.

Conclusions: While PANDAS has found no confirmation as a distinct syndrome, and it is not presented in DSM-5, patients with acute onset OCD spectrum, neurocognitive and motor symptoms should be evaluated for inflammatory, infective, immunological and metabolic abnormalities with a comprehensive diagnostic algorithm.
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http://dx.doi.org/10.1080/13651501.2017.1285941DOI Listing
June 2017

Positron emission tomography assessment of cerebral glucose metabolic rates in autism spectrum disorder and schizophrenia.

Brain Imaging Behav 2018 Apr;12(2):532-546

Departments of Psychiatry and Radiology, University of California, San Diego School of Medicine, NeuroPET Center, 11388 Sorrento Valley Road, Suite #100, San Diego, CA, 92121, USA.

Several models have been proposed to account for observed overlaps in clinical features and genetic predisposition between schizophrenia and autism spectrum disorder. This study assessed similarities and differences in topological patterns and vectors of glucose metabolism in both disorders in reference to these models. Co-registered fluorodeoxyglucose PET and MRI scans were obtained in 41 schizophrenia, 25 ASD, and 55 healthy control subjects. AFNI was used to map cortical and subcortical regions of interest. Metabolic rates were compared between three diagnostic groups using univariate and multivariate repeated-measures ANOVA. Compared to controls, metabolic rates in schizophrenia subjects were decreased in the frontal lobe, anterior cingulate, superior temporal gyrus, amygdala and medial thalamic nuclei; rates were increased in the occipital cortex, hippocampus, basal ganglia and lateral thalamic nuclei. In ASD subjects metabolic rates were decreased in the parietal lobe, frontal premotor and eye-fields areas, and amygdala; rates were increased in the posterior cingulate, occipital cortex, hippocampus and basal ganglia. In relation to controls, subjects with ASD and schizophrenia showed opposite changes in metabolic rates in the primary motor and somatosensory cortex, anterior cingulate and hypothalamus; similar changes were found in prefrontal and occipital cortices, inferior parietal lobule, amygdala, hippocampus, and basal ganglia. Schizophrenia and ASD appear to be associated with a similar pattern of metabolic abnormalities in the social brain. Divergent maladaptive trade-offs, as postulated by the diametrical hypothesis of their evolutionary relationship, may involve a more circumscribed set of anterior cingulate, motor and somatosensory regions and the specific cognitive functions they subserve.
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http://dx.doi.org/10.1007/s11682-017-9721-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648637PMC
April 2018

Body Dysmorphic Disorder in Patients With Autism Spectrum Disorder: A Reflection of Increased Local Processing and Self-Focus.

Am J Psychiatry 2017 Apr;174(4):313-316

From the Department of Psychiatry, Albert Einstein College of Medicine, and Montefiore Medical Center, Bronx, N.Y.

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http://dx.doi.org/10.1176/appi.ajp.2016.16050559DOI Listing
April 2017

Body Dysmorphic Disorder in Patients With Autism Spectrum Disorder: A Reflection of Increased Local Processing and Self-Focus.

Am J Psychiatry 2017 Apr;174(4):313-316

From the Department of Psychiatry, Albert Einstein College of Medicine, and Montefiore Medical Center, Bronx, N.Y.

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http://dx.doi.org/10.1176/appi.ajp.2016.16050559DOI Listing
April 2017

Are there new advances in the pharmacotherapy of autism spectrum disorders?

World Psychiatry 2017 Feb;16(1):101-102

Department of Psychiatry, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.

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http://dx.doi.org/10.1002/wps.20398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269487PMC
February 2017

Diametrical relationship between gray and white matter volumes in autism spectrum disorder and schizophrenia.

Brain Imaging Behav 2017 Dec;11(6):1823-1835

Departments of Psychiatry and Radiology, San Diego School of Medicine, NeuroPET Center, University of California, 11388 Sorrento Valley Road, Suite #100, San Diego, CA, 92121, USA.

Autism spectrum disorders and schizophrenia have been variously characterized as separate nosological entities with overlapping deficits in social cognition or diametrical extremes of a phenotypic continuum. This study aimed to determine how these models apply to comparative morphometric data. MRI scans of the brain were obtained in 49 subjects with schizophrenia, 20 subjects with autism and 39 healthy controls. Images were parcellated into 40 Brodmann areas and entered into repeated-measures ANOVA for between-group comparison of global and localized gray and white matter volumes. A pattern of lower gray mater volumes and greater white matter volumes was found in subjects with schizophrenia in comparison to subjects with autism. For both gray and white matter, this pattern was most pronounced in regions associated with motor-premotor and anterior frontal cortex, anterior cingulate, fusiform, superior and middle temporal gyri. Patient groups tended to diverge from healthy controls in opposite directions, with greater-than-normal gray matter volumes and lower-than-normal white matter volumes in subjects with autism and reversed patterns in subjects with schizophrenia. White matter reductions in subjects with autism were seen in posterior frontal lobe and along the cingulate arch. Normal hemispheric asymmetry in the temporal lobe was effaced in subjects with autism and schizophrenia, especially in the latter. Nearly identical distribution of changes and diametrically divergent volumetry suggest that autism and schizophrenia may occupy opposite extremes of the same cognitive continuum.
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http://dx.doi.org/10.1007/s11682-016-9648-9DOI Listing
December 2017
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