News Article | November 2, 2016
BOSTON - While schizophrenia is best known for episodes of psychosis - a break with reality during which an individual may experience delusions and hallucinations - it is also marked by chronic neurocognitive deficits, such as problems with memory and attention. A multi-site cognition study led by psychologists at Beth Israel Deaconess Medical Center (BIDMC) found that these neurocognitive symptoms are evident prior to the onset of psychosis in a high-risk stage of the disorder called the prodromal phase. Published today online in advance of print in JAMA Psychiatry, the findings suggest that these impairments may serve as early warning signs of schizophrenia, as well as potential targets for intervention that could mitigate the onset of the psychotic disorder and significantly improve cognitive function. "To our knowledge, this is the largest and most definitive study of cognition in the high-risk period before onset of for psychosis/schizophrenia," said corresponding author Larry J. Seidman, PhD, a psychologist at BIDMC and professor of psychology at Harvard Medical School. "This is part of a paradigm shift in the way we are focusing on the earlier, prodromal phase of the disorder in an effort to identify those most likely to develop psychosis." Seidman and colleagues collected neurocognitive functioning data from participants at eight university-based, outpatient programs in the United States and Canada over the course of four years. The observational study compared 689 males and females deemed at clinical high risk (CHR) of developing psychosis to 264 male and female healthy controls (HC). Using 19 standard tests of executive and visuospatial abilities, attention and working memory, verbal abilities and declarative memory, the researchers found that the high-risk group performed significantly worse than the control group on all 19 measures. Among the high-risk individuals only, those who later progressed to a psychotic disorder performed significantly worse than their high-risk peers who did not develop psychosis during the study. "Currently, when mental health professionals assess people coming in for evaluation, we don't know who will eventually develop schizophrenia," said Seidman. "Our group's focus is on identifying early warning signs and then developing interventions to improve a person's chances for not getting it, making it milder or delaying it." Impaired working memory (the ability to hold information like a phone number in mind for a short time while it's in use) and declarative memory (the ability to recall things learned in the last few minutes) turned out to be the key neurocognitive functions that are impaired in the high-risk, prodromal phase prior to the onset of full-blown psychosis. These findings, said Seidman, are in keeping with the experiences of many people with schizophrenia who report sudden difficulties reading, concentrating or remembering things in the earliest days of the disorder. Schizophrenia "conjures up dread" in our culture, Seidman said, but he notes that it is likely these cognitive deficits - not the delusions and hallucinations people fear so much - that keep roughly 80 percent of people with schizophrenia out of work or school. Recent focus on the prodromal period and the growing promise of early intervention is giving patients and their families more realistic hope that better outcomes are possible, he added. "People can hear voices and still function pretty well, but they basically cannot function at all when their cognition is impaired," he said. "We are also testing a number of cognitive remediation and enhancement treatments to determine their role in the evolution of the illness. There's more evidence suggesting that early intervention reduces the number of people who transition to schizophrenia." This study represented the second phase of the North American Prodrome Longitudinal Study (NAPLS), the multi-site research consortium formed in 2003 to focus on early intervention and prevention of schizophrenia. By pooling their data, NAPLS researchers have been able to identify individuals at high risk for developing a psychotic disorder as well as the biological risk factors associated with converting to psychosis. This summer, the collaborators, led by researchers at Yale, published a risk calculator that can help professionals predict patients' risk of developing psychosis. In addition to BIDMC and Yale, the other NAPLS sites are based at Emory University, the University of Calgary, University of California Los Angeles (UCLA), University of California San Diego (UCSD), University of North Carolina Chapel Hill, University of San Francisco, and Zucker Hillside Hospital. "A significant number of people are able to remain in or go back to work and school," Seidman said. "This early intervention approach is giving people more hope, and that really matters." Study coauthors include Daniel I. Shapiro, PhD; Williams S. Stone, PhD; Kristen A. Woodberry, MSW, PhD; and Ashley Ronzio, BS, all of BIDMC; Barbara A. Cornblatt, PhD, MBA, of Zucker Hillside Hospital, Queens, NY; Jean Addington, PhD, of the University of Calgary, Calgary, Alberta; Carrie E. Bearden, PhD; of UCLA; Kristin S. Cadenhead, MD, and Ming T. Tsuang, MD, PhD, DSc, of UC San Diego; Tyrone D. Cannon, PhD, Thomas H. McGlashan, MD, and Scott W. Woods, MD, of Yale University; Daniel H. Mathalon, PhD, MD, of UC San Francisco; Diana O. Perkins, MD, of UNC, Chapel Hill; and Elaine F. Walker, PhD, of Emory University. This work was supported by grants from the National Institute of Mental Health (U01MH081928, P50 MH080272, R01 MH096027, U01 MH081857, U01 MH081984, P50 MH066286, R01 MH60720, U01 MH082022, K24 MH76191, U01 MH081902, U01 MH082004, U01 MH081988, U01 MH082022); grant SCDMH82101008006 from the Commonwealth of Massachusetts; Clinical Translational Science Award UL1RR025758 and General Clinical Research Center Grant M01RR01032 from the National Center for Research Resources to Harvard University at Beth Israel Deaconess Medical Center; and by grant P41RR14075 from the National Center for Research Resources. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .
Altemus M.,Cornell University |
Sarvaiya N.,Zucker Hillside Hospital |
Neill Epperson C.,University of Pennsylvania
Frontiers in Neuroendocrinology | Year: 2014
sex differences is discussed. Sex differences are prominent in mood and anxiety disorders and may provide a window into mechanisms of onset and maintenance of affective disturbances in both men and women. With the plethora of sex differences in brain structure, function, and stress responsivity, as well as differences in exposure to reproductive hormones, social expectations and experiences, the challenge is to understand which sex differences are relevant to affective illness. This review will focus on clinical aspects of sex differences in affective disorders including the emergence of sex differences across developmental stages and the impact of reproductive events. Biological, cultural, and experiential factors that may underlie sex differences in the phenomenology of mood and anxiety disorders are discussed. © 2014.
News Article | December 28, 2016
With adult use or medical cannabis legal in more than half the country, smoking pot is becoming more normalized. But does that mean kids will be more likely to try it? According to epidemiologist Magdalena Cerda at the University of California, Davis, Violence Prevention Research Program, the answer is, largely,yes, but more so in states with conservative weed laws. In a study published Tuesday in The Journal of the American Medical Association (JAMA) Pediatrics, Cerda and her fellow researchers assessed the effects of marijuana legalization in Colorado and Washington on attitudes about pot and on how minors were using it. The researchers used surveys from Monitoring the Future (a yearly program funded by the National Institute on Drug Abuse) between 2010 and 2015 to look at the perceived risks of occasional pot use and at self-reported pot use within 30 days among eighth, tenth, and twelfth grade students before and after legalization. The changes in Colorado and Washington were then compared to students in other parts of the country where weed had not been legalized. The researchers found that the perceived risks of pot use declined everywhere, but more so and especially among Washington eighth and tenth graders, whose marijuana use also increased by eight percent among eighth graders and by 20 percent among tenth graders within a 30 day span between 2013 and 2015. (Between 2010 and 2012, Washington eighth graders' pot use increased by two percent and for tenth graders, by four percent.) The researchers also noted that the perceived risks of pot use declined everywhere, but more so and especially among Washington eighth and tenth graders, whose marijuana use also increased in within a 30 day span. A little over 60 percent of Washington eighth graders and 47 percent of tenth graders saw marijuana use as a health risk between 2013 and 2015, in contrast to the 75 percent and 63 percent respectively in 2010 through 2012. They didn't find these differences, however, in Colorado, or among twelfth graders in Washington. Why did Washington experience a change that Colorado didn't? "The authors suggest that this may have been because Colorado's medical marijuana laws were much more liberal before legalization than those in Washington," according to JAMA. Since 2009, Colorado has had a medical marijuana program, with not only for-profit dispensaries but also advertising of marijuana products. After 2009, the perceived risk of marijuana use decreased among youth in Colorado. "There was a more robust commercialization effort around medical marijuana prior to recreational marijuana being legalized," said Cerda. "That might have contributed to the fact that even before marijuana was legalized, the use was already quite high and the perceived harm was quite low." Kids' attitudes about weed might also be connected to what their parents think of it. Dr. Scott Krakower, assistant unit chief of psychiatry for Zucker Hillside Hospital in New Hyde Park, New York, said that if parents think there's less harm associated with pot use, children will likely follow. "Combine that with a legalized market where you can readily buy it," he said, "and it will be easier to obtain, and children will be more likely to use it." Get six of our favorite Motherboard stories every day by signing up for our newsletter.
Zink M.,University of Heidelberg |
Correll C.U.,Zucker Hillside Hospital
Expert Review of Clinical Pharmacology | Year: 2015
Suboptimal outcomes in schizophrenia are a consequence of lacking insight into the etiology, biomarkers and treatment-relevant subgroups, the therapeutic restriction to dopaminergic-modulating antipsychotics that fail to significantly improve negative and cognitive symptoms, non-adherence, and, in the case of treatment-resistance, the underutilization of clozapine. Evidence suggests additional, extra-dopaminergic abnormalities in amino acid neurotransmission, particularly the glutamatergic system. Antidopaminergic antipsychotics modulate this system on several levels, as do mood stabilizers, including lamotrigine, topiramate and pregabaline. Recently, agonists at metabotropic glutamate receptors and glycine uptake inhibitors failed in large placebo-controlled trials for schizophrenia. Problems to overcome for successfully leveraging glutamatergic agents for schizophrenia are patient selection, focus on positive symptoms and late disease stages, and dose-response relationships. Because glutamate guides processes of brain development and maturation, clinical research should focus on the at-risk mental state or first-episode psychosis, address cognition and negative symptoms and use monotherapy designs in parallel to augmentation strategies. © Informa UK, Ltd..
News Article | October 28, 2016
High blood pressure and high resting heart rate in male teens could increase the risk of psychiatric disorders in their adulthood, reports a recent study. Autonomic nervous system that controls the inner functions of the body regulates the resting heart rate and fluctuations in blood pressure. However, the previous studies that dealt with association between autonomic nervous system and psychiatric disorders in patients did not yield consistent results. Meanwhile, a team of researchers from the University of Helsinki, Finland analyzed data of more than 1 million Swedish men, with a mean age of 18 years, recorded at military conscription between 1969 and 2010. The team led by Antti Latvala examined the link between cardiac autonomic functions in late teens and psychiatric disorders like schizophrenia, obsessive-compulsive disorder (OCD) and anxiety disorders in men. It was observed after analyzing around 45-years of follow-up data that elevated resting heart rate of over 82 beats per minute in late teens was associated with 69 percent higher risk of OCD, 21 percent elevated risk of schizophrenia and 18 percent increased risk of anxiety disorders when compared to individuals that had resting heart rate lesser than 62 beats per minute. As far as blood pressure is concerned, there was a 30 to 40 percent increased risk of OCD in men that had diastolic blood pressure higher than 77 mm Hg than men with diastolic blood pressure lesser than 60 mm Hg. In contrast, men with low resting heart rate and low blood pressure exhibited problems like violent behavior and substance use disorder. Dr. Victor Fornari, director of child and adolescent psychiatry at Zucker Hillside Hospital who was not involved in the study noted that it is sensible to believe that a person's psychiatric illness could be related to irregularity in the functions of autonomic nervous system. Dr. Matthew Lorber, acting director of child and adolescent psychiatry at Lenox Hill Hospital said that the base heart rate and blood pressure in people with psychiatric disorder are generally elevated which in turn could be an indication of impending mental disorders. The researchers also clarified that it is not certain yet whether the increased heart rate and blood pressure result in psychiatric disorders or the heart rate and blood pressure are the early symptoms of existing mental problems. "These associations should be confirmed in other longitudinal studies, and the underlying mechanisms should be studied with more detailed measures of autonomic functioning and designs that can more clearly elucidate causal processes," concluded the study published in JAMA Psychiatry on Oct. 26. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.
Peters B.D.,Zucker Hillside Hospital |
Karlsgodt K.H.,Zucker Hillside Hospital |
Karlsgodt K.H.,Feinstein Institute for Medical Research
Schizophrenia Research | Year: 2015
Schizophrenia has been conceptualized as a disorder of both neurodevelopment and a disorder of connectivity. One important aspect of the neurodevelopmental hypothesis is that schizophrenia is no longer thought to have discrete illness time points, but rather a long trajectory of brain changes, spanning many years, across a series of stages of the disease including the prodrome, first episode, and chronic period. As the disease progresses, there is a complex relationship between age related changes and disease related changes. Therefore, neural changes, and specifically white matter based connectivity changes, in schizophrenia may be best conceptualized based on a lifespan trajectory. In this selective review, we discuss healthy changes in white matter integrity that occur with age, as well as changes that occur across illness stages. We further propose a set of models that might explain lifespan changes in white matter integrity in schizophrenia, with the conclusion that the evidence most strongly supports a pattern of disrupted maturation during adolescence, with the potential for later changes that may be a result of disease neurotoxicity, abnormal or excessive aging effects, as well as medication, cohort or other effects. Thus, when considering white matter integrity in psychosis, it is critical to consider age in addition to other contributing factors including disease specific effects. Discovery of the factors driving healthy white matter development across the lifespan and deviations from the normal developmental trajectory may provide insights relevant to the discovery of early treatment interventions. © 2014 Elsevier B.V.
Kane J.M.,Zucker Hillside Hospital |
Correll C.U.,Yeshiva University
Journal of Clinical Psychiatry | Year: 2010
Despite treatment advances over the past decades, schizophrenia remains one of the most severe psychiatric disorders that is associated with a chronic relapsing course and marked functional impairment in a substantial proportion of patients. In this article, a historical overview of the pharmacologic advances in the treatment of schizophrenia over the past 50 years is presented. This is followed by a review of the current developments in optimizing the treatment and outcomes in patients with schizophrenia. Methodological challenges, potential solutions, and areas of particular need for further research are highlighted. Although treatment goals of response, remission, and recovery have been defined more uniformly, a good "effectiveness" measure mapping onto functional outcomes is still lacking. Moreover, the field must advance in transferring measurement-based approaches from research to clinical practice. There is an ongoing debate regarding whether and which first- or second-generation antipsychotics should be used. However, especially when considering individual adverse effect profiles, the differentiation into first- and second-generation antipsychotics as unified classes cannot be upheld, and a more differentiated view and treatment selection are required. The desired, individualized treatment approach needs to consider current symptoms, comorbid conditions, past therapeutic response, and adverse effects, as well as patient choice and expectations. Acute and long-term goals and effects of medication treatment should be balanced. To date, clozapine is the only evidence-based treatment for refractory patients, and the role of antipsychotic polypharmacy and other augmentation strategies remains unclear, at best. To discover novel treatments with enhanced/broader efficacy and improved tolerability, and to enable personalized treatment, the mechanisms underlying illness development and progression, symptomatic improvement, and side effect development need to be elucidated. © Copyright 2010 Physicians Postgraduate Press, Inc.
Kane J.M.,Zucker Hillside Hospital
Journal of Clinical Psychiatry | Year: 2011
Lurasidone is a new second-generation (atypical) antipsychotic approved for the treatment of schizophrenia in adults. The recommended dose is 40-80 mg given once daily, with no titration needed. Lurasidone should be taken with food. The tolerability profile of lurasidone is noteworthy in terms of a good weight and metabolic profile and no cardiovascular adverse effects such as orthostatic hypotension or prolongation of the QTc interval. Lurasidone is associated with some somnolence, akathisia, nausea, and parkinsonism, especially early in treatment. Its preclinical profile suggested it might be helpful for cognitive or depressive symptoms; early findings have shown some benefit in these areas, but additional studies are needed. Lurasidone may be particularly helpful for patients with schizophrenia who are overweight or have endocrine problems (diabetes, dyslipidemia) or comorbid cardiovascular conditions. © Copyright 2011 Physicians Postgraduate Press, Inc.
Hirota T.,Vanderbilt University |
Schwartz S.,Zucker Hillside Hospital |
Correll C.U.,Yeshiva University |
Correll C.U.,Feinstein Institute for Medical Research
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2014
Objective To meta-analyze the efficacy and safety of α-2 agonists in pediatric attention-deficit/hyperactivity disorder (ADHD). Method We searched MEDLINE, EMBASE, Cochrane Library, CINAHL, and PsycINFO until May 2013 for randomized trials comparing α-2 agonists with placebo in ADHD youth. Primary outcome was reduction in overall ADHD symptoms. Secondary outcomes included hyperactivity/impulsivity, inattentiveness, oppositional defiant disorder symptoms (ODD symptoms), all-cause discontinuation, specific-cause discontinuation, and adverse effects. Standardized mean differences (SMD), relative risk (RR), and number-needed-to-treat/number-needed-to-harm (NNT/NNH) were calculated. Data were analyzed separately in monotherapy and as add-on to psychostimulants. Results Altogether, 12 studies (N = 2,276) were included. Across 9 studies (n = 1,550), α-2 agonist monotherapy significantly reduced overall ADHD symptoms (SMD = -0.59, p <.00001), hyperactivity/ impulsivity (SMD = -0.56, p <.00001), inattention (SMD = -0.57, p <.00001), and ODD symptoms (SMD = -0.44, p =.0004). Similarly, α-2 agonist add-on treatment (3 studies, n = 726) significantly reduced overall ADHD symptoms (SMD = -0.36, p <.0001), hyperactivity/impulsivity (SMD = -0.33, p <.0001), and inattention (SMD = -0.34, p <.0001), but effect sizes were lower than in monotherapy trials (p =.03-0.04). As monotherapy, α-2 agonists had lower all-cause (RR = 0.70, p =.01, NNT = 10) and inefficacy-related (RR = 0.39, p <.0001) discontinuations than did placebo; however, intolerability-related discontinuation was similar, despite significantly more common fatigue (NNH = 10), sedation (NNH = 17), and somnolence (NNH = 4) and significantly greater hypotensive (clonidine-IR), bradycardic (clonidine-IR), and QTc prolonging (guanfacine-XR) effects. Added to stimulants, α-2 agonists had all-cause and specific-cause discontinuations that were comparable to those of placebo, but somnolence (NNH = 10) was more common, and hypotensive and bradycardic effects (clonidine-XR and guanfacine-XR) were greater than with placebo. Conclusions α-2 Agonist monotherapy and, possibly to a lesser extent, co-treatment, are significantly superior to placebo for overall, hyperactivity, and inattentive ADHD symptoms. Efficacy advantages need to be balanced against fatigue, somnolence/sedation, hypotension, bradycardia, and possibly QTc prolongation. © 2014 American Academy of Child and Adolescent Psychiatry.
Correll C.U.,Zucker Hillside Hospital
Journal of Clinical Psychiatry | Year: 2011
Antipsychotics are the cornerstone of treatment for psychotic and some nonpsychotic disorders. However, despite pharmacologic advances, considerable areas of need remain. This article reviews desirable properties for future antipsychotics and considers how far current agents have come in achieving those objectives. Preferably, new antipsychotics should have a "balanced" pharmacodynamic profile that addresses the need for efficacy without compromising psychiatric or physical well-being; a safe, fast, and convenient pharmacokinetic profile; a definable therapeutic window, and availability in multiple formulations. Compared with available agents, new antipsychotics should ideally have at least similar efficacy for positive symptoms, agitation, and aggression and better efficacy for negative or cognitive symptoms, relapse prevention, treatment-resistant illness, and associated problems such as depression, anxiety, and substance abuse. Improved tolerability and subjective acceptability to patients are also important in promoting adherence and continued treatment. Finally, they should have improved effectiveness in facilitating functioning, subjective well-being, quality of life, and, ultimately, recovery. Given the complexity of schizophrenia, its unknown etiology and pathophysiology, and challenges in clinical trial design and conduct, it is not surprising that it has remained difficult to develop antipsychotics with novel mechanisms. To achieve true breakthroughs, we need greater insight into the pathophysiology underlying specific disease processes and therapeutic and adverse responses. It is hoped that research on drug-specific biomarkers that can predict response in specific patient groups will advance personalized psychiatric care and improve patient outcomes. © Copyright 2011 Physicians Postgraduate Press, Inc.