bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Factors and Neurocognitive Traits
Authors: Bates John A. , Malhotra Anil K. 
Published: August 2016

ABSTRACTGenetic contributions to phenotypic variation in general intelligence have been studied extensively. Less research has been conducted on genetic contributions to specific cognitive abilities, such as attention, memory, working memory, language, and motor functions. However, the existing data indicate a significant role of genetic factors in these abilities. Stages of information processing, such as sensory gating, early sensory registration, and cognitive analysis, also show evidence of genetic contributions. Recent molecular studies have begun to identify candidate genes for specific cognitive functions. Future research, identifying endophenotypes based on cognitive profiles of neuropsychiatric disorders, may also assist in the detection of genes that increase susceptibility to major psychiatric disorders.
Neuropsychological Testing for Assessment of Treatment Effects: Methodologic Issues
Authors: Barr William B. 
Published: August 2016

ABSTRACTNeuropsychological (NP) testing is now recognized as an important method for evaluating treatment effects. However, there are limitations to how these tests are currently used in most drug treatment protocols. Changes in cognition are typically defined in statistical terms, with little knowledge as to whether the observed differences are meaningful in any other sense. Methods for assessing changes in test scores need to account for test-retest reliability, practice effects, regression to the mean, and the impact of initial performance. All of these factors may vary according to the individual characteristics of the subject. This article reviews two methods from the NP literature that have attempted to account for these sources of test-retest bias. The reliable change index provides a confidence interval for predicted change by taking into account the test-retest reliability of the measure. Standardized regression-based measures use a more sophisticated statistical approach that enables them to better account for other potential sources of confound. Use of this methodology has been limited to studies of epilepsy surgery and sports-related concussion. These methods have the potential for enhancing the interpretation of NP test data in drug treatment protocols by providing an empirically based definition of clinically meaningful change.
Narcolepsy: Differential Diagnosis or Etiology in Some Cases of Bipolar Disorder and Schizophrenia?
Authors: Douglass Alan B. 
Published: August 2016

AbstractDoes narcolepsy, a neurological disease, need to be considered when diagnosing major mental illness? Clinicians have reported cases of narcolepsy with prominent hypnagogic hallucinations that were mistakenly diagnosed as schizophrenia. In some bipolar disorder patients with narcolepsy, the HH resulted in their receiving a more severe diagnosis (ie, bipolar disorder with psychotic features or schizoaffective disorder). The role of narcolepsy in psychiatric patients has remained obscure and problematic, and it may be more prevalent than commonly believed. Classical narcolepsy patients display the clinical “tetrad”—cataplexy, hypnagogic hallucinations, daytime sleep attacks, and sleep paralysis. Over 85% also display the human leukocyte antigen marker DQB10602 (subset of DQ6). Since 1998, discoveries in neuroanatomy and neurophysiology have greatly advanced the understanding of narcolepsy, which involves a nearly total loss of the recently discovered orexin/hypocretin (hypocretin) neurons of the hypothalamus, likely by an autoimmune mechanism. Hypocretin neurons normally supply excitatory signals to brainstem nuclei producing norepinephrine, serotonin, histamine, and dopamine, with resultant suppression of sleep. They also project to basal forebrain areas and cortex. A literature review regarding the differential diagnosis of narcolepsy, affective disorder, and schizophrenia is presented. Furthermore, it is now possible to rule out classical narcolepsy in difficult psychiatric cases. Surprisingly, psychotic patients with narcolepsy will likely require stimulants to fully recover. Many conventional antipsychotic drugs would worsen their symptoms and make them appear to become a “chronic psychotic,” while in fact they can now be properly diagnosed and treated.
Psychopharmacologic Strategies for the Treatment of Aggression in Juveniles
Authors: Steiner Hans , Saxena Kirti , Chang Kiki 
Published: August 2016

ABSTRACTMaladaptive aggression in youth is one of the most common and troublesome reasons for referrals to child psychiatrists. It has a complex relationship with psychopathology. There are several syndromes, which are primary disturbances of clustered maladaptive aggression, most notably oppositional defiant disorder and conduct disorder. However, problems with aggression also appear in a wide range of other disturbances, such as bipolar disorder, posttraumatic stress disorder, and mood disorders. Additionally, aggression is normative, serves an adaptive purpose and can be situationally induced. These complexities need to be carefully addressed before targeting maladaptive aggression psychopharmacologically. We summarize the literature on the psychopharmacology of maladaptive aggression in youth, focusing on disorders without cognitive impairment. We delineate the subtypes of aggression which are most likely to respond to medication (reactive-affective-defensive-impulsive in their acute and chronic form) and conclude with a discussion of specific medication strategies which are supported by controlled clinical trials and clinical experience.
Genetic Approaches to the Study of Synaptic Plasticity and Memory Storage
Authors: Abel Ted , Kaplan Michael P. 
Published: August 2016

ABSTRACTLong-term memory is believed to depend on long-lasting changes in the strength of synaptic transmission known as synaptic plasticity. Understanding the molecular mechanisms of long-term synaptic plasticity is one of the principle goals of neuroscience. Among the most powerful tools being brought to bear on this question are genetically modified mice with changes in the expression or biological activity of genes thought to contribute to these processes. This article reviews how strains of mice with alterations in the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate-response element-binding protein signaling pathway have advanced our understanding of the biological basis of learning and memory.
Mechanisms and the Current State of Deep Brain Stimulation in Neuropsychiatry
Authors: Greenberg Benjamin D. , Rezai Ali R. 
Published: August 2016

ABSTRACTDeep brain stimulation (DBS) is established as a therapy for movement disorders, and it is an investigational treatment in other neurologic conditions. DBS precisely targets neuroanatomical targets deep within the brain that are proposed to be centrally involved in the pathophysiology of some neuropsychiatric illnesses. DBS is nonablative, offering the advantages of reversibility and adjustability. This might permit therapeutic effectiveness to be enhanced or side effects to be minimized. Preclinical and clinical studies have shown effects of DBS locally, at the stimulation target, and at a distance, via actions on fibers of passage or across synapses. Although its mechanisms of action are not fully elucidated, several effects have been proposed to underlie the therapeutic effects of DBS in movement disorders, and potentially in other conditions as well. The mechanisms of action of DBS are the focus of active investigation in a number of clinical and preclinical laboratories. As in severe movement disorders, DBS may offer a degree of hope for patients with intractable neuropsychiatric illness. It is already clear that research intended to realize this potential will require a very considerable commitment of resources, energy, and time across disciplines including psychiatry, neurosurgery, neurology, neuropsychology, bioengineering, and bioethics. These investigations should proceed cautiously.
Current Concepts in the Prevention of Alzheimer's Disease
Authors: Sano Mary 
Published: August 2016

ABSTRACTAlzheimer's disease represents a significant challenge to the aging population. Since most estimates suggest that AD has a multifactorial etiology, the challenge to find preventative approaches is particularly great. With the aging of the population and the very high incidence from the eighth decade on, the challenge is further enhanced by the need to think of relatively safe interventions given the relative frailty of this elderly population. The need to find safe treatments, or ones with well-understood safety profiles, has led to the examination of known agents for potential dementia-preventing properties. Data supporting these interventions comes from observational studies, laboratory analyses, and clinical trials. Potential mechanisms for prevention of AD include anti-inflammatory and antioxidant approaches. Modulation of risk factors associated with cardiac disease may also reduce the risk of AD. Known agents have been examined for their potential to modify amyloid pathology. Trial designs to address prevention of AD include both primary and secondary prevention studies as well designs to assess slowing disease progression. Information can also be gathered when dementia evaluation is added to ongoing studies. As results from these studies becoming available, we will be able to refine our approach to managing this disease.
Optimizing Treatment of Schizophrenia Enhancing Affective/Cognitive and Depressive Functioning
Authors: Ginsberg David L. , Schooler Nina R. , Buckley Peter F. , Harvey Philip D. , Weiden Peter J. 
Published: August 2016

ABSTRACTRecognition and treatment of schizophrenia has largely focused on positive symptoms of the disorder, such as delusions, hallucinations, and disorganization. However, other important symptoms, such as depression, cognition, and social functioning, have not received comparable attention. Fifty percent of schizophrenic patients suffer from comorbid depression, which is a major risk factor for suicide in this population, while 10% to 25% suffer from comorbid obsessive-compulsive disorder. Cognitive deficits commonly observed in patients with schizophrenia include problems with concentration, attention, and memory, as well as problem-solving and verbal skills. These deficits are observed at early stages of the illness and can predict deficits in functional capabilities, such as occupational and social skills, educational attainment, and the ability to live independently. The severity of such impairments affects all patients in this population, including up to 10% of patients working full time and up to one third of those working part time. In light of the debilitating effects of depression, cognitive impairment, and other aspects of affective functioning on the quality of life of patients with schizophrenia, physicians need to partner with their patients to address these concerns and determine an appropriate treatment regimen. This can be done with simple functional-based cognitive questioning, the use of evidence-based psychosocial practices, and psychoeducation on the many pharmacotherapeutic options. It is recommended that depressive or suicidal symptoms of schizophrenia be treated with an antidepressant or mood stabilizer only if the symptoms have not subsided after treatment of the psychosis with an atypical antipsychotic. Additionally, relative to older medications, atypicals have demonstrated benefit in improving some of the cognitive impairments.
Every Crisis Is an Opportunity
Authors: Friedman Matthew J. 
Published: August 2016

In the same way that a war mobilizes the creative energies of a nation and often leads to major advances in science, technology, and medicine, the terrorist attacks on the World Trade Center and the Pentagon provided a powerful impetus to advance the traumatic stress field. Stung by our inability to provide policymakers with recommendations on evidence-based, early interventions for survivors of the September 11, 2001, attacks, we have been forced to confront the major gaps in our current knowledge.These gaps are myriad and include our limited understanding of the natural longitudinal course of psychological consequences from the immediate post-impact phase to months and years later. They also include our inadequate scientific understanding of the psychological and psychobiological mechanisms underlying acute and long-term reactions to traumatic events and sparse empirical literature on which to base decisions concerning best practices for interventions. Questions of vulnerability and resilience have taken on a new urgency as we struggle to determine when to respect natural recovery processes and when to provide a formal intervention. With the recognition that there is little empirical justification for psychological debriefing as a one-stop early intervention panacea for the population-at-large has come intensification of efforts to develop and test a variety of novel early interventions that may be suitable for adults and children during the acute aftermath of catastrophic events.
Conceptually Driven Pharmacologic Approaches to Acute Trauma
Authors: Pitman Roger K. , Delahanty Douglas L. 
Published: August 2016

ABSTRACTSecondary prevention of posttraumatic stress disorder (PTSD) entails intervening in the aftermath of a traumatic event to forestall the development of PTSD. There has been little psychopharmacologic research in this area. This is surprising, given that PTSD is the mental disorder with the most clearly identified cause and onset. In a translational model of PTSD's pathogenesis presented herein: A traumatic event (unconditioned stimulus) overstimulates endogenous stress hormones (unconditioned response); these mediate an overconsolidation of the event's memory trace; recall of the event in response to reminders (conditioned stimulus); releases further stress hormones (conditioned response); these cause further overconsolidation; and the overconsolidated memory generates PTSD symptoms. Noradrenergic hyperactivity in the basolateral amygdala is hypothesized to mediate this cycle. Preventing pre-synaptic norepinephrine release with α2-adrenergic agonists or opioids, or blocking post-synaptic norepinephrine sreceptors with β-adrenergic antagonists such as propranolol, reduces hormonally enhanced memories and fear conditioning. Two controlled studies of trauma victims presenting to emergency rooms suggest that posttrauma propranolol reduces subsequent PTSD, as does one naturalistic clinical study of morphine treatment of burned children. Cortisol both enhances memory consolidation and reduces memory retrieval, leading to mixed predictions. Two controlled studies of intensive care unit patients found that cortisol reduced PTSD. One study did not find benzodiazepines effective in preventing PTSD. Selective serotonin reuptake inhibitors, antiepileptics, and α2-adrenergic agonists have yet to be tried.
Statins and Cognition: What Can We Learn from Existing Randomized Trials?
Authors: Xiong Glen L. , Benson Aaron , Doraiswamy P. Murali 
Published: August 2016

ABSTRACTBackground:Statins are being developed as treatments for Alzheimer's dementia based on evidence from preclinical and observational studies. However, cholesterol plays an integral role in cell membrane signal transduction and suboptimal cholesterol level could potentially impair neuronal function. Additionally, results of observational nonrandomized studies may have been affected by treatment bias.Methods:We performed a systematic literature review in MEDLINE from January 1966 to July 2004 and included published prospective, randomized, and placebo-controlled human studies that examined the cognitive effects of statins.Results:Nine studies with sample sizes ranging from 22 to 20,000 and duration of 3 weeks to 5 years, met criteria for review. Study populations and cognitive outcomes varied. Four studies were ≥6 months or longer. Overall, none of these studies reported finding a positive benefit for any statin on cognition in non-demented subjects although there was inconsistent evidence for acute cognitive worsening in some studies.Conclusion:While statins intuitively have appeal for the prevention or treatment of dementia, any conclusions about their efficacy should await more definitive evidence from on-going prospective clinical trials
The Use of Antidepressants in Functional Gastrointestinal Disorders: New Uses for Old Drugs
Authors: Olden Kevin W. 
Published: August 2016

ABSTRACTSince their introduction 50 years ago, antidepressants have been used in a wide variety of settings involving gastrointestinal (GI) disease. In the 1950s, antidepressants were shown to have some efficacy for the treatment of peptic ulcer disease. This is most likely due to their antihistaminic and anticholinergic effects. Since then, more efficacious and more disease-specific treatments have become available. In the last 20 years, antidepressants have been increasingly used for the treatment of functional gastrointestinal disorders such as irritable bowel syndrome, noncardiac chest pain, and other functional GI disorders. This article will review the rationale for the use of antidepressant drugs for the treatment of functional GI disorders. The role of psychiatric comorbidity in functional GI disorders, the impact of antidepressants on GI motility and visceral sensation, and the ability of these agents to produce improvements in the global well-being and overall quality of life will be reviewed. Finally, guidelines for prescribing and barriers to a patient's acceptance of these agents will be discussed.
How We See Others:The Psychobiology of Schemas and Transference
Authors: Stein Dan J. 
Published: August 2016

ABSTRACTSocial cognition involves automatic and stimulus-driven processes; these may be important in mediating stereotypes in the community and schemas and transference in the clinic setting. Significant differences in self-related processing and other-related processing may also lead to important biases in our view of the other. The psychobiology of social cognition is gradually being delineated, and may be useful in understanding these phenomena, and in responding appropriately. In the clinic, schemas can be rigorously assessed, and schema-focused psychotherapy may be useful in a number of indications.
Aripiprazole Augmentation in Major Depressive Disorder: A Double-Blind, Placebo-Controlled Study in Patients with Inadequate Response to Antidepressants
Authors: Berman Robert M. , Fava Maurizio , Thase Michael E. , Trivedi Madhukar H. , Swanink René , McQuade Robert D. , Carson William H. , Adson David , Taylor Leslie , Hazel James , Marcus Ronald N. 
Published: August 2016

ABSTRACTIntroduction: Effective management of major depressive disorder (MDD) continues to be a challenging task for psychiatrists and primary care physicians. This trial evaluated the efficacy and safety of adjunctive aripiprazole versus antidepressant monotherapy in patients with MDD and independently replicated the positive findings of two similar trials.Methods: Patients (N=1, 147) with MDD experiencing a major depressive episode and a history of inadequate response to antidepressant monotherapy were enrolled (week 0); 827 received single-blind adjunctive placebo plus open-label antidepressant (escitalopram, fluoxetine, paroxetine controlled release, sertraline, or venlafaxine extended release) for 8 weeks to confirm inadequate response to antidepressants; 349 patients with inadequate response were randomized (1:1) to double-blind, adjunctive placebo (n=172) or adjunctive aripiprazole (n=177; 2–20 mg/day). Primary outcome was the mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total score from baseline (week 8) to endpoint (week 14).Results: Clinically significant improvements in depressive symptoms as assessed by decreases in the MADRS Total score were greater with adjunctive aripiprazole (−10.1) than placebo (−6.4; P<.001). Remission rates were greater for adjunctive aripiprazole than for adjunctive placebo (week 14, 36.8% vs 18.9%; P<.001). Completion rates with adjunctive aripiprazole and placebo were high (83% vs. 87%) and discontinuations due to adverse events were low (6.2% vs 1.7%).Conclusion: For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and previous studies, have shown that discontinuations due to adverse events were low and completion rates were high, and has indicated that both antidepressant and aripiprazole in combination were relatively well-tolerated and safe. This is the third consecutive clinical trial, in the absence of a failed trial, to demonstrate that aripiprazole augmentation to antidepressants is an efficacious and well-tolerated treatment for patients with MDD who do not respond adequately to standard antidepressant monotherapy (ClinicalTrials.gov study NCT00105196).
Applying the Principles of Adult Learning to the Teaching of Psychopharmacology: Storyboarding a Presentation and the Rule of Small Multiples
Authors: Stahl Stephen M. , Davis Richard L. 
Published: August 2016

Medical presentations can be designed as a data dump or as a story. One effective communication strategy is to organize a lecture as a three act play, starting with previews as the first act and ending with reviews as the third act. Previews facilitate learner achievement and may help learners view a medical instructor more positively. Reviews also help consolidate audience learning and ensure that messages have been clearly delivered and received. The main act is in the middle and is the content itself. Delivering this content in small multiples gives learners manageable packets of information and can help them to see the differences and similarities between conditions, deepening their understanding of what was presented.Applying principles of adult learning can enhance the effectiveness of a medical presentation. A previous “Trends in Psychopharmacology” presented an overview of these principles and discussed targeting the learner rather than the content or the lecturer as the focus for a medical presentation. Here we cover the concept of presenting content to a learner as a story and show how to organize or “storyboard” it as a three act play.Lectures can be arranged as a dull recitation of facts or as a story that makes the facts come alive. Generally speaking, a participant is less interested in hearing the facts that a lecturer has to present than in listening to a story the lecturer has to tell. Organizing content into a “three act play” can make a lecture memorable and its lessons practical. Classically, teachers have explained the three parts as: “Say what you are gonna say; say it; then say what you said.” More specifically, the previews are the first part, the presentation itself is the second part, and the reviews are the third part of this structure.