bluuebunny/crossref_metadata_2025 huggingface dataset:
The Importance of Steady-State Plasma Dopa Levels in Reducing Motor Fluctuations in Parkinson's Disease
Authors: Lees Andrew J.
Published: August 2016

When levodopa (L-dopa) is administered intravenously to patients with severe Parkinson's disease, a therapeutic response may be seen within a 1/2 hour. However, when the drug is administered orally in lower doses to less disabled patients, a delay of 1–2 weeks often occurs before motor deficits start to improve. Recent data from the Early versus Late Levodopa study suggest that maximum improvement at a fixed dosage may take ≤3 months to develop. A nonspecific feeling of well-being and reduced tiredness are often the first benefits to occur, followed by greater alacrity and less stiffness. Rest tremor is slower to improve, but may eventually disappear altogether and remain well controlled throughout the rest of the course of the malady. Gait, balance, and speech may also improve, but the effect is usually more modest and a decline is common after several years of sustained treatment.
Genetic Factors and Neurocognitive Traits
Authors: Bates John A. , Malhotra Anil K.
Published: August 2016

Genetic 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

Neuropsychological (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

Does 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

Maladaptive 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

Long-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

Deep 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

Alzheimer'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

Recognition 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

Secondary 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

Background:

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

Since 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

Social 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

Introduction: 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.
Do Children and Adolescents Have Differential Response Rates in Placebo-Controlled Trials of Fluoxetine?
Authors: Mayes Taryn L. , Tao Rongrong , Rintelmann Jeanne W. , Carmody Thomas , Hughes Carroll W. , Kennard Beth D. , Stewart Sunita M. , Emslie Graham J.
Published: August 2016

Objective:

Recent acute efficacy trials of antidepressants in youth have suggested that high placebo-response rates in children (<12 years of age) indicate that children may be more responsive to non-specific treatment interventions. Yet, these studies generally have not presented age-specific outcome data. The objective of this study was to compare the efficacy outcomes for children (<12 years of age) and adolescents (≥12 years of age) using the combined data from two previously published double-blind, placebo-controlled trials of fluoxetine.

Methods:

Children (<12 years of age) and adolescents (≥12 years of age) with major depressive disorder were randomized to fluoxetine or placebo for 8–9 weeks of treatment. Outcome was assessed using the Children's Depression Rating Scale-Revised (CDRS-R) and Clinical Global Impressions scale.

Results:

Random regression of the CDRS-R showed a treatment group by age group interaction (F1,338=4.10, P=.044), indicating that the treatment effect was significantly more pronounced in children than adolescents. Within children, response at exit to fluoxetine was significantly better than placebo (56.9% vs 33.3%; P=.009). Adolescent response rates at exit were not significantly different between the groups (51.1% vs 38.6%; P=.128). Remission rates were low for both groups.

Conclusion:

In the combined fluoxetine trials, drug-placebo difference was greater in children compared with adolescents. Contrary to expectations, the placebo-response rate was lower in the children than the adolescents.
Delirium Following Ingestion of Marijuana Present in Chocolate Cookies
Authors: André Charles , Jaber-Filho Jorge A. , Bento Rafael M.A. , Damasceno Lúcia M.P. , Aquino-Neto Francisco R.
Published: August 2016

Objective: To describe a case of marijuanainduced delirium and the techniques used to detect psychoactive agents and metabolites in urine.

Methods: A case of delirium following involuntary ingestion of cannabis is described. A urine sample was analyzed applying various chemical procedures, using high-resolution gas chromatography coupled with mass spectrometry technique. 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid was quantified by the methodology for steroids and cannabis.

Results: A 26-year-old man was hospitalized with severe agitation and psychotic behavior 36 hours after suspected involuntary ingestion of cannabis contained in a brigadeiro, a typical Brazilian cookie, consumed during a party. Treatment with neuroleptics resulted in complete regression of the symptoms over 2 weeks. The urine sample revealed marijuana ingestion, demonstrated by the presence of its metabolite, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in

Conclusion: Severe delirium can follow oral ingestion of cannabis integrated into homemade cookies.
Long-Term, Open-Label Venlafaxine Extended-Release Treatment in Children and Adolescents with Major Depressive Disorder
Authors: Emslie Graham J. , Yeung Paul P. , Kunz Nadia R.
Published: August 2016

Introduction: Because major depressive disorder (MDD) is often chronic and recurrent, even pediatric patients who are treated successfully during an acute episode may need longer-term treatment. Yet, data on long-term treatment with antidepressants in pediatric MDD are limited.

Objective: To evaluate long-term effectiveness and safety of treatment with venlafaxine extended-release (ER) in children and adolescents with MDD.

Methods: Subjects (n=86) 7–17 years of age with MDD entered a multicenter, open-label study of flexible-dose venlafaxine ER for 6 weeks of acute treatment, followed by continuation treatment for up to 6 months total treatment. The primary efficacy variable was the Children's Depression Rating Scale-Revised (CDRS-R) total score (intent-to-treat population).

Results: Mean CDRS-R total score decreased from 60.1±10.0 at baseline to 36.3±13.1 at week 6, and to 33.8±15.0 at 6 months (last observation carried forward). Among completers (n=36), the mean CDRS-R total score was 24.3±7.6 at the end of 6 months of treatment. The most frequent treatment-emergent adverse events were headache (53%), nausea (26%), infection (24%), abdominal pain (22%), vomiting (21%), and pharyngitis (19%). Fifteen (17%) participants discontinued due to adverse events, 9 of whom did so within the first 6 weeks. Serious adverse events (suicide attempt [two], hostility [two], hallucinations, depression, and pharyngitis) occurred in seven patients. There were no suicides.

Conclusion: Most improvement with venlafaxine ER occurs during the first 6 weeks of treatment. Prescribers should be alert to signs of suicidal ideation and hostility in pediatric patients.
Spatial Neglect, Balint-Homes' and Gerstmann's Syndrome, and Other Spatial Disorders
Authors: Vallar Giuseppe
Published: August 2016

Brain-damaged patients with lesion or dysfunction involving the parietal cortex may show a variety of neuropsychological impairments involving spatial cognition. The more frequent and disabling deficit is the syndrome of unilateral spatial neglect that, in a nutshell, consists in a bias of spatial representation and attention ipsilateral to of extrapersonal, personal (ie, the body) space, or both, toward the side of the hemispheric lesion. The deficit is more frequent and severe after damage to the right hemisphere, involving particularly the posterior-inferior parietal cortex at the temporo-parietal junction. Damage to these posterior parietal regions may also impair visuospatial short-term memory, which may be associated with and worsen spatial neglect. The neural network supporting spatial representation, attention and short-term memory is, however, more extensive, including the right premotor cortex. Also disorders of drawing and building objects (traditionally termed constructional apraxia) are a frequent indicator of posterior parietal damage in the left and in the right hemispheres. Other less frequent deficits, which, however, have a relevant localizing value, include optic ataxia (namely, the defective reaching of visual objects, in the absence of elementary visuo-motor impairments), which is typically brought about by damage to the superior parietal lobule. Optic ataxia, together with deficits of visual attention, of estimating distances and depth, and with apraxia of gaze, constitutes the severely disabling Balint-Holmes' syndrome, which is typically associated with bilateral posterior parietal and occipital damage. Finally, lesions of the posterior parietal lobule (angular gyrus) in the left hemisphere may bring about a tetrad of symptoms (left-right disorientation, acalculia, finger agnosia, and agraphia) termed Gerstmann's syndrome, that also exists in a developmental form.
An Open-Label Trial of Aripiprazole Monotherapy in Children and Adolescents with Bipolar Disorder
Authors: Biederman Joseph , Mick Eric , Spencer Thomas , Doyle Robert , Joshi Gagan , Hammerness Paul , Kotarski Megan , Aleardi Megan , Wozniak Janet
Published: August 2016

Introduction: Aripiprazole is a novel second-generation antipsychotic approved for the treatment of bipolar disorder in adults but there is no systematic data available in pediatric bipolar disorder.

Methods: This was an 8-week, open-label, prospective study of aripiprazole 9.4±4.2 mg/day monotherapy to assess the efficacy and tolerability of this compound in treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale, Clinical Global Impressions-Improvement scale, and Brief Psychiatric Rating Scale. Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis.

Results: Fifteen of the 19 bipolar youth (79%) completed the study. Aripiprazole treatment was associated with clinically and statistically significant improvement in mean Young Mania Rating Scale scores (−18.0±6.9, P<.0001). With the important exception of two cases of extrapyramidal symptoms that precipitated dropout, aripiprazole was well tolerated with no statistically significant increase in body weight (1.8±1.7 kg, P=.2).

Conclusion: Open-label aripiprazole treatment was beneficial in the treatment of mania in youth with bipolar disorder. Future placebo-controlled, double blind studies are warranted.
An Innovative Approach to Clinical Communication in Schizophrenia: The Approaches to Schizophrenia Communication Checklists
Authors: Dott Sharon G. , Weiden Peter , Hopwood Penelope , Awad A. George , Hellewell Jonathan S.E. , Knesevich John , Kopala Lili , Miller Alexander , Salzman Carl
Published: August 2016

Side effects from antipsychotic medications can have a profound effect on patients' lives and may adversely affect their willingness to comply with treatment. Identification of side effects through improved communication between psychiatrists, other members of the healthcare team, and their patients might increase treatment compliance. The Approaches to Schizophrenia Communication (ASC) Steering Group developed two simple, practical checklists for use in the busy clinical setting. The ASC–Self-Report (ASC-SR) checklist is completed by the patient and comprises a list of the more common or clinically important side effects of antipsychotic treatment. The ASC-Clinic (ASC-C) checklist is completed by both clinician and patient together, being used as the basis for a semi-structured interview. In a multicenter pilot study set up to evaluate the utility of checklists, 86% of patients responding considered the ASC-SR to be useful in communicating their problems to psychiatrists and other members of the healthcare team. All healthcare team respondents found both checklists to be helpful when discussing side effect problems with their patients. Moreover, 41% and 47% of healthcare team respondents reported that the ASC-SR and ASC-C, respectively, had assisted them in identifying side-effect problems not previously acknowledged. Preliminary evaluation of the ASC-SR and ASC-C in this multicenter pilot study suggests that both tools were user-friendly, encouraged communication between patients and healthcare professionals about antipsychotic drug side effects, and could readily integrated into everyday clinical practice.
Citalopram for Social Anxiety Disorder: An Open-label Pilot Study in Refractory and Nonrefractory Patients
Authors: Simon Naomi M. , Korbly Nicole B. , Worthington John J. , Kinrys Gustavo , Pollack Mark H.
Published: August 2016

There is limited systematic data assessing alternate pharmacotherapy of social anxiety disorder in patients failing to tolerate or fully respond to initial treatment; no data specifically address the efficacy of citalopram in this scenario. We present a prospective open-label trial of citalopram in 10 patients with generalized social anxiety disorder, 6 of 10 of whom had not responded to or not tolerated a prior treatment intervention for the disorder. Citalopram, at a mean dose of 55 mg (SD+12.7 mg) was well tolerated, and patients improved significantly on all outcome measures. Results of this study suggest that citalopram may be a safe and effective treatment for generalized social anxiety disorder, including patients who have failed to tolerate or respond to a prior treatment trial.
The Pharmacological Treatment of Autistic Spectrum Disorders
Authors: Owley Thomas
Published: August 2016

What role do medications play in the overall treatment of autistic spectrum disorders? In this review, the decision-making process involving identifying symptoms, initiating a pharmacological intervention, and monitoring that process is discussed. A review of the literature with an emphasis on controlled trials in autistic spectrum disorders is also undertaken.
Could Stress Cause Psychosis in Individuals Vulnerable to Schizophrenia?
Authors: Corcoran Cheryl , Mujica-Parodi Lilianne , Yale Scott , Leitman David , Malaspina Dolores
Published: August 2016

It has long been considered that psychosocial stress plays a role in the expression of symptoms in schizophrenia (SZ), as it interacts with latent neural vulnerability that stems from genetic liability and early environmental insult. Advances in the understanding of the neurobiology of the stress cascade in both animal and human studies lead to a plausible model by which this interaction may occur: through neurotoxic effects on the hippocampus that may involve synaptic remodeling. Of late, the neurodevelopmental model of SZ etiology has been favored. But an elaboration of this schema that credits the impact of postnatal events and considers a role for neurodegenerative changes may be more plausible, given the evidence for gene-environment interaction in SZ expression and progressive structural changes observed with magnetic resonance imaging. Furthermore, new insights into nongliotic neurotoxic effects such as apoptosis, failure of neurogenesis, and changes in circuitry lead to an expansion of the time frame in which environmental effects may mediate expression of SZ symptoms.
Are Cognitive Symptoms of Schizophrenia Mediated by Abnormalities in Emotional Arousal?
Authors: Mujica-Parodi Lilianne R. , Corcoran Cheryl , Greenberg Tsafrir , Sackeim Harold A. , Malaspina Dolores
Published: August 2016

We tested 28 individuals with schizophrenia (SZ) and 16 healthy individuals on a test of logical reasoning and “cognitive gating,” defined as the ability to discriminate between relevant and irrelevant information in confirming or disconfirming a given belief. The Logical Reasoning and Cognitive Gating Task tests both processes under neutral and affect-laden conditions. This is done by presenting formally identical constructs using benign and emotionally arousing language. When separated by symptom profiles, we found statistically significant differences for performance and arousal response between patients with delusions, patients with formal thought disorder, and patients with neither delusions nor formal thought disorder, as well as between patients and healthy controls. When analyzed by error type, we found that nearly all errors by delusional patients were caused by overly restrictive information choice, a pattern that may be related to a delusional patient's tendency to “jump to conclusions” on Bayesian probabilistic tasks. This is in contrast to patients with formal thought disorder, whose low performance resulted also from overly extensive information choice. The tendencies towards restriction were exacerbated by arousal, which is consistent with studies on cognition and arousal in healthy individuals. After briefly examining research on emotional arousal and SZ, and the interaction between emotional arousal and restriction of perceptual cues in healthy individuals, we conclude by suggesting a model which accounts for the distinctive cognitive characteristics of delusional patients by their possessing distinct vulnerabilities to emotional arousal. Specifically, these results suggest the possibility that delusional patients process information in a manner that is essentially intact. However, delusional patients may possess an acute vulnerability to emotional arousal that might cause delusional individuals to behave cognitively as if they were healthy individuals under significantly more severe forms of stress.
Generalized Anxiety Disorder: Acute and Chronic Treatment
Authors: Rynn Moira A. , Brawman-Mintzer Olga
Published: August 2016

Clinical and epidemiological data suggest that generalized anxiety disorder (GAD) is a chronic illness causing patients to suffer for many years leading to significant distress in daily life functioning. The literature suggests the several conclusions. GAD is a disorder in need of appropriate treatment and often has a chronic course with comorbid conditions, such as major depression and other anxiety disorders. Benzodiazepines, while effective anxiolytic agents acutely, when prescribed for >4 weeks cause rebound anxiety and following prolonged therapy may lead to withdrawal symptoms. Antidepressants cause significant anxiety relief compared with placebo and for psychosocial treatment cognitive-behavioral therapy is an efficacious psychosocial treatment. Many GAD patients are in need of long-term medication management. Furthermore, there is limited data for patients diagnosed with GAD the treatment outcome with the combination of medication and psychotherapy both acutely and long-term; how to best sequence these treatments; for those patients who do not meet remission criteria what is the ideal approach for augmentation; and for patients with treatment-refractory GAD the empirical evidence is lacking on medication switching and augmentation strategies. Research is needed in the area of developing treatment strategies for patients suffering from treatment-refractory GAD. There is still an urgent need to explore treatment combinations and duration strategies in the management of patients suffering with GAD.
Treatment-Resistant Panic Disorder
Authors: Bandelow Borwin , Rüther Eckart
Published: August 2016

A substantial number of patients with panic disorder and agoraphobia may remain symptomatic after standard treatment (including selective serotonin reuptake inhibitors, tricyclic antidepressants, benzodiazepines, or irreversible monamine oxidase inhibitors). In this review, recommendations for the treatment of patients with panic disorder and agoraphobia who do not respond to these drugs are provided. Nonresponse to drug treatment could be defined as a failure to achieve a 50% reduction on a standard rating scale after a minimum of 6 weeks of treatment in adequate dose. When initial treatments have failed, the medication should be changed to other standard treatments. In further attempts at treatment, drugs should be used that have shown promising results in preliminary studies, such as venlafaxine. Combination treatments may be used, such as the combination of an selective serotonin reuptake inhibitor and a benzodiazepine. Psychological treatments such as cognitive-behavioral therapy have to be considered in all patients, regardless whether they are nonresponders or not. According to existing studies, a combination of pharmacologic treatment with cognitive-behavioral therapy can be recommended.
The Clinical Neuropsychiatry of Multiple Sclerosis
Authors: Feinstein Anthony
Published: August 2016

Multiple sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. Although Charcot noted behavioral changes associated with MS, nearly a century would elapse before researchers began defining their full extent and severity. Broadly speaking, abnormalities may be divided into those of mood and cognition. Many patients are afflicted with both and it is essential that clinicians are not only aware of this but understand how to detect problems and provide treatment.

The lifetime prevalence of major depression in MS patients approaches 50%. As Scott B. Patten, MD, and colleagues note, these data came from specialist clinics with the potential for ascertainment bias. Shifting their inquiry into a large community-based sample, they report that the rates of mood disorder remain elevated largely in younger MS patients. While it is partly reassuring to find that aging comes with at least one benefit, the gist of this study is to reinforce the message that clinically significant depression is a problem for MS patients. Not only does it adversely affect quality of life and lead to increased suicidal thinking, it exerts more subtle deleterious effects as Peter A. Arnett, PhD, reveals. In a longitudinal study exploring the relationship between depression and cognition, Arnett reports that MS patients with prominent evaluative symptoms of depression (ie, feelings of inferiority, failure) have greater difficulty with cognitive tasks that encompass information processing speed and executive function linked to working memory. A preoccupation with negative thoughts may reduce the cognitive capacity necessary for aspects of attention and working memory.

These data complement the review article of Ralph H.B. Benedict, PhD, ABPP-CN, that focuses on methods of detecting cognitive dysfunction in MS. As with mood disorders, impaired cognition has been linked to difficulties with work, relationships, and, in more extreme cases, basic activities of daily living. Usually, the more subtle pattern of deficits associated with demyelination differ from those seen in cortical-type dementias and will be missed should clinicians rely on screening instruments like the Mini-Mental State Examination. At the same time, the method of choice for eliciting deficits, namely neuropsychological testing is expensive and frequently not readily available. This has meant that alternative instruments, like the Multiple Sclerosis Neuropsychological Screening Questionnaire, assume an added prominence. With good sensitivity, specificity, and ease of administration this informant based scale makes a useful addendum to the neurological examination. It is in the same light that the magnetic resonance imaging (MRI) rating scale by Laury Chamelian, MD, FRCPC, and colleagues should be viewed.
Longitudinal Consistency of the Relationship Between Depression Symptoms and Cognitive Functioning in Multiple Sclerosis
Authors: Arnett Peter A.
Published: August 2016

Background: Lifetime prevalence rates of cognitive dysfunction and depression in multiple sclerosis (MS) have typically been reported to be ∼50%. However, an inconsistent relationship between these two common features of MS has been reported in the literature. Because neurovegetative depression symptoms overlap with MS symptoms, it may be that literature inconsistencies can partly be explained by the fact that only those depression symptom clusters unambiguously reflective of depression are associated with cognitive dysfunction.

Objective: To explore the relationship between different depression symptom clusters and a battery of tests measuring cognitive domains commonly impaired in MS and was examined at two time points 3 years apart.

Methods: The Chicago Multiscale Depression Inventory was employed to measure mood, negative evaluative, and neurovegetative symptom clusters in 53 MS patients who were also administered a battery of neuropsychological tests.

Results: At time point 1, Mood and Evaluative Chicago Multiscale Depression Inventory scales were significantly associated with tasks of complex speeded attention, planning, and working memory. At time point 2, the Evaluative scale was still significantly associated with these domains, in addition to spatial memory; however, all of the significant correlations with the Mood scale dropped out.

Conclusion: These results show that negative evaluative depression symptoms are most consistently predictive of cognitive dysfunction in MS. It may be that negative evaluative depression symptoms use up available cognitive capacity, thus compromising performance on cognitive capacity demanding tasks in MS patients.
Neural Bases and Development of Face Recognition in Autism
Authors: Marcus David J. , Nelson Charles A.
Published: August 2016

This paper critically examines the literature on face recognition in autism, including a discussion of the neural correlates of this ability. The authors begin by selectively reviewing the behavioral and cognitive neuroscience research on whether faces are represented by a “special” behavioral and neural system—one distinct from object processing. The authors then offer a neuroconstructivist model that attempts to account for the robust finding that certain regions in the inferior temporal cortex are recruited in the service of face recognition. This is followed by a review of the evidence supporting the view that face recognition is atypical in individuals with autism. This face-recognition deficit may indicate a continued risk for the further development of social impairments. The authors conclude by speculating on the role of experience in contributing to this atypical developmental pattern and its implications for normal development of face processing.