bluuebunny/crossref_metadata_2025 huggingface dataset:
What Has Clinical Research in Suicide Prevention Done for You Lately?
Authors: Fawcett Jan
Published: August 2016

What have you heard or read over the past 10 years that has improved you ability to assess and manage suicide risk in your patients?

There has been a paucity of data. What little data there is reviewed in this month's articles.They highlight findings that you should know about. Clinicians seem to cling to the familiar, unless some intense marketing is done.

For instance, are you aware that the current evidence shows that a denial of suicide thoughts, plans, or intent—even a contract for safety—means absolutely nothing in the absence of a full suicide risk assessment?

Yet clinicians seem to rely on these ’reassurances“ from their patients and are shocked when the patient later commits suicide. Why should a patient who is deciding that life is too painful to live tell you the truth? Robert I. Simon, MD, and Daniel W. Shuman, JD, review these facts.

Are you aware that severe psychic anxiety, panic attacks, agitation, and severe insomnia often precede suicide within hours, days, or weeks and can be rapidly modified with treatment?

On the other hand, standard risk factors for suicide such as suicidal ideation, hopelessness, and past suicidal attempts are not good predictors of suicide in the short term. A suicide plan, recent high intent attempt, or refusal to contract for safety may well indicate immediate risk, but a denial of suicidal ideation or intent and a contract for no harm mean absolutely nothing without a full suicide assessment that takes current clinical status, past suicidal tendencies, social support, and willingness to accept help into account.
Quetiapine Augmentation of Selective Serotonin Reuptake Inhibitors in Treatment-Resistant Obsessive-Compulsive Disorder: A Six-Month Follow-Up Case Series
Authors: Dell'Osso Bernardo , Mundo Emanuela , Altamura A. Carlo
Published: August 2016

Obsessive-compulsive disorder (OCD) is a relatively common, often chronic and disabling disorder with high rates of partial and/or absent response to standard, recommended treatments, such as selective serotonin reuptake inhibitors (SSRIs) and psychotherapy. This article presents the cases of four patients suffering from OCD and comorbid mood or anxiety disorders, who were treated with SSRIs at adequate doses for at least 12 weeks, showing a partial response. Quetiapine treatment was added to SSRIs at a dose of 25 mg/day and titrated up to 200 mg/day. Patients were followed up for 6 months. After 12 weeks, all the patients were classified as “much improved” on the Clinical Global Impression–Improvement scale and showed a Yale-Brown Obsessive-Compulsive Scale score reduction ≥35%. After 6 months of follow-up, all the patients maintained the same level of improvement. Although quetiapine augmentation to SSRIs has shown mixed results in published controlled trials in the acute treatment (12 weeks) of patients with treatment-resistant OCD, this case series indicates that patients who benefit from this pharmacologic regimen in the acute phase tend to maintain such an improvement. Larger follow-up studies are warranted to confirm our findings.
Bipolar Depression: Best Practices for the Hospitalized Patient
Authors: Keck Paul E. , Frye Mark A. , Thase Michael E.
Published: August 2016

One of the most challenging clinical topics in psychiatry is the diagnosis and treatment of bipolar depression. The term mood stabilizer is frequently employed in the treatment of the hospitalized bipolar patient, although clinicians do not universally agree on a consensus definition of this term. Most clinicians would agree that a mood stabilizer refers to a medication that is effective for the acute treatment of manic, mixed, hypomanic, or depressive episodes. Many experts agree that such treatment should offer efficacy against mania, should not worsen depression, and preferably should treat depression as well. In addition, the acute effectiveness in stabilization should not be at the expense of inducing alternate mood symptoms or switching the patient into the alternate phase of illness. From a maintenance standpoint, a mood stabilizer should also prevent against future relapse or recurrence of manic, mixed, hypomanic, or depressive symptoms or episodes (Slide 1).

In addition to use of mood stabilizers, there are other issues surrounding treatment of the hospitalized patient with bipolar depression, including the commonly comorbid issue of substance abuse. Hazardous drinking may more commonly occur in bipolar depression or depressive phase of illness, representing a more complex clinical picture. To facilitate understanding of this complex disorder and its appropriate treatment, this discussion centers around the case of a major depressive episode in a patient with a past history of of mania (ie, bipolar I depression or bipolar depression).
Beyond the “C” in MCI: Noncognitive Symptoms in Amnestic and Non-amnestic Mild Cognitive Impairment
Authors: Ellison James M. , Harper David G. , Berlow Yossi , Zeranski Lauren
Published: August 2016

Introduction:

How frequent and how clinically important are mood and behavioral symptoms among older adults with mild cognitive impairment (MCI)? Although these noncognitive behavioral symptoms (NCBS) are not represented in the diagnostic criteria for MCI, their clinical significance is increasingly recognized.

Methods:

To address this question, the authors identified a cohort of consecutively evaluated patients from a psychiatric hospital's outpatient memory clinic. These patients' records contained both a clinical assessment and a standardized set of evaluations including the Mini-Mental State Exam, the Neuropsychiatric Inventory (NPI), and the Geriatric Depression Scale. Using a standardized chart-review approach, the presence of any NPI-screened symptom was identified and the frequencies of specific NPI-screened symptoms were calculated for the Memory Clinic MCI cohort and for amnestic and non-amnestic MCI subgroups.

Results:

A total of 116 patient records were reviewed. Thirty-eight patients with MCI were identified. Twenty-two of these met criteria for amnestic MCI by Mayo Clinic criteria while 16 met criteria for non-amnestic MCI. At least one NPI-screened mood or behavioral symptom was present in 86.8% of these MCI patients. Depression/dysphoria (63.3%), apathy (60.5%), anxiety (47.4%), irritability (44.7%), and nighttime behaviors (42.1%) were the most frequent. While depression/dysphoria was distributed similarly between amnestic and non-amnestic subgroups, apathy was significantly more frequently associated with the amnestic subtype of MCI, and nighttime behaviors were more frequently associated with the non-amnestic subtype.

Conclusion:

Although the presence of NCBS is not required for a diagnosis of MCI, these symptoms are frequently present and constitute an important source of morbidity. Apathy and depression may be difficult to differentiate, but targeted treatment of depression may fail to address apathy. Recognizing the limitations of this preliminary study, the authors suggest that apathy may be more characteristic of amnestic MCI while nighttime behaviors may be more characteristic of non-amnestic MCI.
Personalized Medicine, Pharmacogenomics, and the Practice of Psychiatry: On the Threshold of Predictive Therapeutics in Psychopharmacology?
Authors: Stahl Stephen M.
Published: August 2016

Personalizing medicine by understanding the unique properties of each patient's genome has the potential of predicting what drug to prescribe for that individual. This approach has already proven useful for several drugs in medicine and promises to become a strategy for selection of therapeutics in psychiatry soon. Understanding some of the key concepts, strategies, and advances in the field of pharmacogenomics can set the stage for adapting emerging findings to the practice of psychopharmacology.
Paradoxical Excitation on Diphenhydramine May Be Associated with Being a CYP2D6 Ultrarapid Metabolizer: Three Case Reports
Authors: de Leon Jose , Nikoloff D. Michele
Published: August 2016

Diphenhydramine is a widely used antihistaminic that is frequently included in over-the-counter medications. Due to its sedating properties, diphenhydramine is used in some hypnotic preparations. Occasionally, patients respond to diphenhydramine with paradoxical excitation. There are no studies on the prevalence of paradoxical excitation in healthy subjects. Diphenhydramine appears to cause mild inhibition of the cytochrome P450 (CYP) 2D6 enzyme. This can be interpreted as competitive inhibition, suggesting that diphenhydramine may be a CYP2D6 substrate. When subjects have at least three active copies of the CYP2D6 gene, they are called ultrarapid metabolizers (UMs) and present high metabolic capacity for CYP2D6 substrates. In the United States, CYP2D6 UMs may account for ∼1 % to 2% of the population. We describe three CYP2D6 UMs who reported paradoxical excitation on diphenhydramine. These cases suggest that in CYP2D6 UMs, diphenhydramine may be converted to a compound that causes excitation due to the abnormally high CYP2D6 activity. Therefore, such individuals may be at higher risk for excitation. Although these are onl y three anecdotal cases of paradoxical excitation from three CYP2D6 UMs, the reports illustrate the need for larger, more formal studies of diphenhydramine responses in CYP2D6 UMs and of diphenhydramine metabolism.
The Potential Role of a Corticotropin-Releasing Factor Receptor-1 Antagonist in Psychiatric Disorders
Authors: Stahl Stephen M. , Wise Dana D.
Published: August 2016

The hypothalamic-pituitary-adrenal axis is a key mediator of the stress response in humans. The corticotropin-releasing factor (CRF) type 1 receptor (CRFR-1) in the pituitary gland is a gatekeeper for that response, and the CRFR-1 receptor is also present in many other mood- and cognition-related neural structures. Behaviorally, a number of relationships between stress and psychiatric disorders can be observed: chronic or repeated stress is associated with onset of depression; stressors can cause a recovering alcoholic to relapse; overactive stress responses mark many anxiety disorders; and insomnia can arise from an overactive stress response. Thus, a CRFR-1 antagonist could be useful for treating or preventing the consequences of CRF-mediated stress in depression, anxiety, insomnia, and substance abuse.
Escitalopram in Obsessive-Compulsive Disorder:Response of Symptom Dimensions to Pharmacotherapy
Authors: Stein Dan J. , Carey Paul D. , Lochner Christine , Seedat Soraya , Fineberg Naomi , Andersen Elisabeth Wreford
Published: August 2016

Introduction:

There is a substantial body of evidence that obsessive-compulsive disorder (OCD) symptoms can be grouped into a series of discrete dimensions, and some evidence that not all OCD symptom dimensions respond equally well to pharmacologic or psychotherapeutic intervention. The response of OCD symptom dimensions to 12 weeks of treatment with escitalopram or placebo was investigated.

Methods:

Data from a randomized, double-blind, placebo-controlled study of escitalopram in 466 adults with OCD were analyzed. Exploratory factor analysis of individual items of the Yale-Brown Obsessive-Compulsive Scale checklist was performed and subscale scores based on the extracted factors were determined. Analyses of covariance were undertaken to determine whether inclusion of each subscale score in these models impacted on the efficacy of escitalopram versus placebo.

Results:

Exploratory factor analysis of individual Yale-Brown Obsessive-Compulsive Scale items yielded 5 factors (contamination/cleaning, harm/checking, hoarding/symmetry, religious/sexual, and somatic/hypochondriacal). Analyses of covariance including all the subscales demonstrated that escitalopram was more effective than placebo. There was a significant interaction for the hoarding/symmetry factor, which was associated with a poor treatment response.

Conclusion:

Escitalopram shows good efficacy across the range of OCD symptom dimensions. Nevertheless, hoarding/symmetry was associated with a poorer treatment response. Hoarding/symmetry may be particularly characteristic of an early-onset group of OCD patients, with the involvement of neurotransmitters other than serotonin. Further work is needed to delineate fully the subtypes of OCD, and their correlates with underlying psychobiology and treatment responsivity.
The Effects of Testosterone on Cognition in Elderly Men: A Review
Authors: Warren Matthew F. , Serby Michael J. , Roane David M.
Published: August 2016

In this article, the literature examining the relationship between testosterone and various cognitive domains in elderly men is reviewed. The review focuses on the role of endogenous testosterone levels and the effects of androgen depletion and replacement. The cognitive domains most commonly linked to testosterone include memory and visuospatial function. Indeed, the literature suggests that in certain conditions (ie, hypogonadism, cognitive impairment) testosterone levels may be significantly associated with memory and visuospatial function, but not other cognitive functions. Studies with larger sample sizes and more sensitive cognitive measures are indicated, as questions remain about the potential role of testosterone as a cognitive enhancer.
Introduction: The Prevalence of Alzheimer's Disease — A Growing Crisis
Authors: Salloway Stephen
Published: August 2016

In 1906, the German physician Alois Alzheimer provided the first description of the “serious and peculiar disease” of mental deterioration that would later on take his name. Alzheimer described the classic pathology of neuritic plaques and neurofibrillary tangles in an affected patient. Since that time, understanding of Alzheimer's disease (AD) has progressed substantially, although the ability to influence disease progression has not progressed as rapidly. It is likely that over the next decade these advances will lead to earlier diagnosis and development of disease-modifying treatments for AD.

It is known that two variants of AD exist: a rare hereditary form and a more prevalent sporadic form. As with many neurodegenerative diseases, early clues to the pathology of AD came from the inherited form of the disease. Hereditary links include mutations of the amyloid precursor protein (APP) and the presenilins, both of which are integrally involved in the cascade of events that leads to the deposition of the 42-amino-acid amyloid β protein and the eventual cell death responsible for AD.
Course, Prognosis, and Management of Psychosis in Parkinson's Disease: Are Current Treatments Really Effective?
Authors: Zahodne Laura B. , Fernandez Hubert H.
Published: August 2016

It is essential to recognize and treat psychosis in Parkinson's disease for several reasons. Studies have shown that psychosis in Parkinson's disease patients is a strong risk factor for nursing home placement. Psychosis may be the greatest source of stress for caretakers of Parkinson's patients; it is often persistent, and its presence markedly increases mortality. Treatment of psychotic symptoms should occur only after potential medical and environmental causes of delirium have been eliminated or addressed. Initial pharmacologic changes should include limiting the patient's antiparkinsonian medications to those that are necessary to preserve motor function. Should that fail, an atypical antipsychotic is presently the treatment of choice. An emerging treatment option is acetylcholinesterase inhibitors. This article reviews what is currently known about the course, prognosis, and treatment strategies in Parkinson's disease psychosis.
Disaster Mental Health Services Following The 1995 Oklahoma City Bombing: Modifying Approaches to Address Terrorism
Authors: Pfefferbaum Betty , North Carol S. , Flynn Brian W. , Norris Fran H. , DeMartino Robert
Published: August 2016

How did the 1995 Oklahoma City bombing differ from prior disasters and what implications did it have for disaster mental health services and service delivery? The federal disaster mental health approach in this country developed largely out of experiences with natural disasters. The 1995 Oklahoma City bombing differed in several important ways, including the large number of human casualties, higher rates of psychopathology, and an extended period of concern due to the criminal investigation and trials, which suggested the need to consider modifications in the program. Outreach was extensive, but psychiatric morbidity of direct victims was greater than that of victims of natural disasters, emphasizing the need for attention to the triage and referral process. Other concerns that warrant consideration include practices related to record keeping and program evaluation.
An Investigation of the Psychological Effects of the September 11, 2001, Attacks on New York City: Developing and Implementing Research in the Acute Postdisaster Period
Authors: Galea Sandro , Vlahov David , Resnick Heidi , Kilpatrick Dean , Bucuvalas Michael J. , Morgan Mark D. , Gold Joel
Published: August 2016

The September 11, 2001, attack on New York City was the largest human-made disaster in United States history. In the first few days after the attack, it became clear that the scope of the attacks (including loss of life, property damage, and financial strain) was unprecedented and that the attacks could result in substantial psychological sequelae in the city population. Researchers at the Center for Urban Epidemiologic Studies at the New York Academy of Medicine designed and implemented an assessment of the mental health of New Yorkers 5—8 weeks after the attacks. To implement this research in the immediate postdisaster period, researchers at the center had to develop, in a compressed time interval, new academic collaborations, links with potential funders, and unique safeguards for study respondents who may have been suffering from acute psychological distress. Results of the assessment contributed to a New York state mental health needs assessment that secured Federal Emergency Management Agency funding for mental health programs in New York City. This experience suggests that mechanisms should be in place for rapid implementation of mental health assessments after disasters.
Long-Term Efficacy of Exposure and Ritual Prevention Therapy and Serotonergic Medications for Obsessive-Compulsive Disorder
Authors: Hembree Elizabeth A. , Riggs David S. , Kozak Michael J. , Franklin Martin E. , Foa Edna B.
Published: August 2016

What is the long-term outcome of patients with obsessive-compulsive disorder (OCD) who are treatred with exposure and response (ritual) prevention (EX/RP) alone, serotonergic medications alone, or their combination? How is the long-term outcome of these patients affected by the discontinuation? Follow-up assessments were conducted with 62 patients treated for OCD an average of 17 months posttreatment (range: 6–43 months). Patients received one of three treatments: serotonergic medications (fluvoxamine or clomipramine), intensive behavior therapy involving EX/RP, or intensive EX/RP with concurrent antidepressant medication. At follow-up, no differences in OCD symptom severity were found among the three treatment groups. However, when current medication use was taken into consideration, differences among the three treatment groups emerged. Among patients who were medication-free at the time of follow-up assessment (n=37), those in the EX/RP-alone and EX/RP-with-medication groups had lower symptom severity ratings than those in the medication-only group on 4 out of 6 measures. There were no differences in OCD severity ratings among patients taking medications at follow-up (n=25). Although these findings are interpreted with caution due to the uncontrolled nature of the study, results suggested that long-term outcome may be superior following EX/RP than following serotonergic medications, after discontinuation. For patients who remain on medications, the treatment produced benefits equivalent to EX/RP.
Gut Feelings: Irritable Bowel Syndrome and Psychiatric Disorders
Authors: Lydiard R. Bruce
Published: August 2016

Irritable bowel syndrome (IBS) is one of over 20 functional gastrointestinal disorders. There is considerable overlap of IBS with panic disorder as well as other anxiety disorders and depression. It has been proposed that the high prevalence of psychiatric disorders in clinical samples of IBS patients is a result of self-selection of individuals with anxiety and depression, which drives treatment-seeking behavior. Over the past several years, data from some community studies have shown that there is a high prevalence of psychiatric disorders in individuals with IBS who never sought treatment. This suggests that there may be a more fundamental linnk between IBS, anxiety and mood disorders, such as shared pathophysiology.

This month's issue of CNS Spectrums brings together reviews on the brain-gut axis, each of which provides a unique perspective, which is complementary to the other reviews.

Kirsten Tillisch, MD, and Emeran A. Mayer, MD, review the neurobiology of visceral sensation, focusing on visceral hyperalgesia in IBS. In their paper, the importance of expectancy, comorbidity, gender, and other issues on pain perception is discussed. One of the most fascinating points the authors make is that extra-intestinal functional disorders, such as fibromyalgia, which often coexists with IBS, may affect somatic perception and pain thresholds. The observation that these disorders not only co-exist, but can affect each other raises an important and often overlooked issue for researchers. Comorbid disorders should be assessed and taken into account when conducting studies in patients with IBS. The authors highlight advances in methodology and new conceptual frameworks for understanding the functional gastrointestinal disorders (FGIDs) as well as remaining gaps in our knowledge about visceral hyperalgesia.
From Clinical Research to Clinical Practice: A 4-Year Review of Ziprasidone
Authors: Masand Prakash S. , Nemeroff Charles B. , Newcomer John W. , Lieberman Jeffrey A. , Schatzberg Alan F. , Weiden Peter J. , Kilts Clinton D. , Harvey Philip D. , Daniel David G.
Published: August 2016

Ziprasidone is a second-generation antipsychotic that received Food and Drug Administration approval in February 2001. It has a unique receptor profile that includes high-affinity antagonist activity at dopamine D2receptors, inverse agonist activity at serotonin (5-HT)2Areceptors, agonist activity at 5-HT1Areceptors, and a relatively high affinity for the serotonin and norepinephrine transporters. The 5-HT1Aaffinity, together with the inhibitory effect on monoamine reuptake, may underlie the hypothesized beneficial effects on comorbid affective and cognitive abnormalities in schizophrenia and schizoaffective disorder. The short-term efficacy of ziprasidone for core positive symptoms of schizophrenia appears to be comparable to other conventional and atypical antipsychotics. The short-term efficacy of ziprasidone in acute mania has been established based on two 3-week, double-blind, placebo-controlled trials. Open-label treatment for up to 52 weeks confirms the sustained efficacy and safety of ziprasidone in bipolar disorder. Maintenance studies in schizophrenia and schizoaffective disorder indicate that long-term ziprasidone therapy is effective in preventing relapse, while maintaining cognitive and psychosocial benefits. The safety database suggests that the overall cardiovascular and cerebrovascular risk associated with ziprasidone is lower than with other atypicals, with notably lower risk of drug-related increases in weight, glucose, or lipids. The data also suggest a modestly increased risk of QTc prolongation that is not dose related or linked to torsades de pointes. Switching to ziprasidone from other atypicals appears to improve both clinical symptoms and metabolic parameters, though more studies are needed to fully characterize these benefits. This monograph summarizes the efficacy, tolerability, and safety of oral ziprasidone in the treatment of schizophrenia, schizoaffective disorder, and bipolar mania.
Caffeine-Induced Psychosis
Authors: Hedges Dawson W. , Woon Fu Lye , Hoopes Scott P.
Published: August 2016

As a competitive adenosine antagonist, caffeine affects dopamine transmission and has been reported to worsen psychosis in people with schizophrenia and to cause psychosis in otherwise healthy people. We report of case of apparent chronic caffeine-induced psychosis characterized by delusions and paranoia in a 47-year-old man with high caffeine intake. The psychosis resolved within 7 weeks after lowering caffeine intake without use of antipsychotic medication. Clinicians might consider the possibility of caffeinism when evaluating chronic psychosis.
Validation of the University of São Paulo Sensory Phenomena Scale:Initial Psychometric Properties
Authors: Rosario Maria Conceição , Prado Helena Silva , Borcato Sonia , Diniz Juliana Belo , Shavitt Roseli Gedanki , Hounie Ana Gabriela , Mathis Maria Eugênia , Mastrorosa Rosana Savio , Velloso Patricia , Perin Eduardo Alliende , Fossaluza Victor , Pereira Carlos Alberto , Geller Daniel , Leckman James , Miguel Euripedes
Published: August 2016

Introduction:Although obsessions and compulsions comprise the main features of obsessive-compulsive disorder (OCD), many patients report that their compulsions are preceded by a sense of “incompleteness” or other unpleasant feelings such as premonitory urges or a need perform actions until feeling “just right.” These manifestations have been characterized as Sensory Phenomena (SP). The current study presents initial psychometric data for a new scale designed to measure SP.

Methods:Seventy-six adult OCD subjects were probed twice. Patients were assessed with an open clinical interview (considered as the “gold standard”) and with the following standardized instruments: Structured Clinical Interview forDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders, Yale-Brown Obsessive-Compulsive Scale, Dimensional Yale-Brown Obsessive-Compulsive Scale, Yale Global Tic Severity Scale, Beck Anxiety Inventory, and Beck Depression Inventory.

Results:SP were present in 51 OCD patients (67.1%). Tics were present in 16 (21.1%) of the overall sample. The presence of SP was significantly higher in early-onset OCD patients. There were no significant differences in the presence of SP according to comorbidity with tics or gender. The comparison between the results from the open clinical interviews and the University of São Paulo Sensory Phenomena Scale (USP-SPS) showed an excellent concordance between them, with no significant differences between interviewers. The inter-rater reliability between the expert raters for the USP-SPS was high, with K=.92. The Pearson correlation coefficient between the SP severity scores given by the two raters was .89.

Conclusion:Preliminary results suggest that the USP-SPS is a valid and reliable instrument for assessing the presence and severity of SP in OCD subjects.
Mind and Muscle:The Cognitive-Affective Neuroscience of Exercise
Authors: Stein Dan J. , Collins Malcolm , Daniels Willie , Noakes Timothy D. , Zigmond Michael
Published: August 2016

There is growing basic-science interest in the mechanisms underpinning the positive effects of exercise on brain function and cognitive-affective performance. There is also increasing clinical evidence that exercise may prevent and treat various neuropsychiatric disorders. At the same time, there is growing awareness that athletic performance is mediated in crucial ways by central nervous system mechanisms. The relevant mechanisms in all these cases requires further exploration, but likely includes neurotrophic, neuroendocrine, and neurotransmitter systems, which in turn are crucial mediators of psychopathology and resilience. The hypothesis that Homo sapiens evolved as a specialist endurance runner provides an intriguing context against which to research the proximal mechanisms relevant to a cognitive-affective neuroscience of exercise.
Specific Phobia: A Disorder of Fear Conditioning and Extinction
Authors: Stein Dan J. , Matsunaga Hisato
Published: August 2016

Specific phobia is the most prevalent of the anxiety disorders. Although there have been relatively few studies of its psychobiology and pharmacotherapy, there is a rich laboratory of literature on fear conditioning and extinction and a clear evolutionary perspective. Advances in the cognitive-affective neuroscience of fear processing may ultimately lead to new approaches to the clinical management of phobias.
The Neurophysiology of Childhood and Adolescent Bipolar Disorder
Authors: DelBello Melissa P. , Adler Caleb M. , Strakowski Stephen M.
Published: August 2016

Introduction:Children and adolescents with bipolar disorder often present with higher rates of mixed episodes, rapid cycling, and co-occurring attention-deficit/hyperactivity disorder than adults with bipolar disorder. It is unclear whether the differences in clinical presentation between youth and adults with bipolar disorder are due to differences in underlying etiologies or developmental differences in symptom manifestation. Neuroimaging studies of children and adolescents with bipolar disorder may clarify whether neurobiological abnormalities associated with early-and adult-onset bipolar disorder are distinct. Moreover, children and adolescents with bipolar disorder are typically closer to their illness onset than bipolar adults, providing a window of opportunity for identifying core neurobiological characteristics of the illness (ie, disease biomarkers) that are independent of repeated affective episodes and other confounding factors associated with illness course.

Methods:Peer-reviewed publications of neuroimaging studies of bipolar children and adolescents were reviewed.

Results:Structural, neurochemical, and neurofunctional abnormalities in prefrontal and medical temporal and subcortical limbic structures, including the striatum, amygdala, and possibly hippocampus, are present in children and adolescents with bipolar disorder.

Conclusion:Differences between neurobiological abnormalities in bipolar youth and adults as well as recommendations for future research directions are discussed.
Brain Network Dysfunction in Bipolar Disorder
Authors: Adler Caleb M. , DelBello Melissa P. , Strakowski Stephen M.
Published: August 2016

Bipolar disorder is a common psychiatric condition with significant associated morbidity and mortality. Despite its significance, the neurophysiology and neuropathology of this illness is incompletely understood. Recent advances in neuroimaging techniques have helped to begin clarifying these areas. Specifically, bipolar disorder appears to arise from abnormalities within discrete brain networks (eg, the anterior limbic network). The expression of the symptoms of bipolar disorder does not appear to result from single, localized brain lesions, but rather are emergent properties of dysfunction of these brain networks. As neuroimaging techniques continue to improve, the underlying neural basis of bipolar disorder will be clarified.
Balancing Short-Term Symptom Control and Long-Term Functional Outcomes in Patients with Parkinson's Disease
Authors: Tetrud James W.
Published: August 2016

Levodopa has played a central role in the treatment of Parkinson's disease for nearly 40 years and remains the single most effective symptomatic treatment for the disease. However, the response to levodopa therapy changes over time, and its long-term use is commonly associated with disabling motor complications. For this reason, the appropriate role of levodopa in the treatment of Parkinson's disease—in particular, the question of when to initiate therapy with the drug—has been a matter of controversy. Because levodopa is the most effective treatment for Parkinson's disease, the management of this disease becomes a matter of balancing short-term symptom control with long-term functional outcomes. This article provides an overview of the basis for levodopa-associated motor complications and their impact on patients' clinical function and quality of life, followed by a discussion of strategies for managing these complications to achieve optimum symptom control while minimizing the adverse effects of long-term therapy.
Obsessive-Compulsive Disorder:Boundary Issues
Authors: Fineberg Naomi A. , Saxena Sanjaya , Zohar Joseph , Craig Kevin J.
Published: August 2016

The boundaries between obsessive-compulsive disorder (OCD) and other neuropsychiatric disorders remain unresolved and may well differ from one disorder to another. Endophenotypes are heritable, quantitative traits hypothesized to more closely represent genetic risk for complex polygenic mental disorders than overt symptoms and behaviors. They may have a role in identifying how closely these disorders are associated with another and with other mental disorders with which they share major comorbidity. This review maps the nosological relationships of OCD to other neuropsychiatric disorders, using OCD as the prototype disorder and endophenotype markers, such as cognitive, imaging, and molecular data as well as results from demographic, comorbidity, family, and treatment studies. Despite high comorbidity rates, emerging evidence suggests substantial endophenotypic differences between OCD and anxiety disorders, depression, schizophrenia, and addictions, though comparative data is lacking and the picture is far from clear. On the other hand, strong relationships between OCD, Tourette syndrome, body dysmorphic disorder, hypochondriasis, grooming disorders, obsessive-compulsive personality disorder, and pediatric autoimmune neuropsychiatric disorders associated with streptococcus are likely. Studies designed to delineate the cause, consequences, and common factors are a challenging but essential goal for future research in this area.
Symptom Dimensions in Obsessive-Compulsive Disorder:Implications for theDSM-V
Authors: Leckman James F. , Rauch Scott L. , Mataix-Cols David
Published: August 2016

In the absence of definitive etiological markers of vulnerability or a unitary profile of pathophysiology for obsessive-compulsive disorder (OCD), obsessive-compulsive (OC) symptom dimensions seem to offer a fruitful point of orientation.The complex clinical presentation of OCD can be summarized using a few consistent and temporally stable symptom dimensions. These can be understood as a spectrum of potentially overlapping features that are likely to be continuous with “normal” worries and extend beyond the traditional nosological boundaries of OCD. Although the understanding of the dimensional structure of obsessive-compulsive symptoms (OCS) is still imperfect, this quantitative approach to phenotypic traits has the potential to advance our understanding of OCD and may aid in the identification of more robust endophenotypes. Preliminary data suggest that these dimensional phenotypes may be useful in studies of the natural history, genetics, neurobiology, and treatment outcome of OCD. A dimensional approach is not mutually exclusive of other methods to parse the larger spectrum of disorders related to OCD. Thus far, age-of-onset of OCS and the individual's “tic-related” status seem to be particularly useful categorical distinctions. Finally, existing assessment methods are inadequate and new dimensional scales are needed to take full advantage of a dimensional approach in clinical and population-based studies.
D-cycloserine Inhibits Amygdala Responses During Repeated Presentations of Faces
Authors: Britton Jennifer C. , Gold Andrea L. , Feczko Eric J. , Rauch Scott L. , Williams Danielle , Wright Christopher I.
Published: August 2016

Introduction: Recently, human studies using exposure therapy to treat anxiety have demonstrated that pretreatment with D-cycloserine (DCS) enhances fear reduction in anxiety disorders. However, the underlying brain mechanisms mediating this fear reduction have yet to be determined.

Methods: The effects of orally administered DCS on amygdala activity during the processing of repeated facial expressions were examined in this double-blind study. Fourteen healthy males (30.0±8.7 years of age) randomly received DCS 500 mg or placebo prior to 3.0 Tesla functional magnetic resonance imaging acquisition. All participants viewed four separate runs, consisting of a single block of a repeated facial expression (happy or fearful) bracketed by fixation blocks.

Results: Anatomic region-of-interest analyses showed that the placebo group exhibited amygdala activation and response habituation, while the DCS group displayed blunted amygdala responses to emotional faces across the experiment, whereby habituation was not detected.

Conclusion: This finding may have relevance for testing treatments of anxiety and depression.
An Abbreviated Review of Immune Abnormalities in Schizophrenia
Authors: Rapaport Mark H. , Delrahim Katia K.
Published: August 2016

Initial investigations of the possible interaction between schizophrenia and the immune system began in the early 1900s and have proceeded in a rather halting fashion because of the methodological challenges faced by investigators. However, a confluence of recent data suggests that activation of the inflammatory response system, the cellular immune system, and the humoral immune system may be present in some patients with schizophrenia. Some of the most compelling data support the hypothesis that minor levels of immune activation may be associated with acute psychotic exacerbations. However, a second body of evidence suggests that some individuals with schizophrenia may have chronic, evolving autoimmune processes. This article is an overview of the history, rationale, and some of the recent findings on the interaction between schizophrenia and the immune system.
Stiff-Person Syndrome: Autoimmunity and the Central Nervous System
Authors: Murinson Beth Brianna , Vincent Angela
Published: August 2016

Stiff-person syndrome (SPS) is a rare disease of severe progressive muscle stiffness in the spine and lower extremities with superimposed muscle spasms triggered by external stimuli. Patients with SPS are often referred for psychiatric evaluation and the psychiatrist may be the first to diagnosis SPS. Psychosocial stressors often precede the first manifestations of the disease; depression, anxiety, and alcohol abuse are comorbid illnesses. The identification of an association with antibodies to glutamic acid decarboxylase (GAD) was invaluable for definitively establishing a pathological basis for the disease; antibodies to amphiphysin and gephyrin are also found in cases of SPS but at much lower frequencies. Whether the antibodies inhibit GAD activity in vivo, target GAD-expressing neurons for immune-mediated destruction, are part of a wider immune process, or are merely a marker for destruction of GAD-expressing neurons by an independent neurodegenerative process is not yet clear. Both electromyography and the detection of GAD antibodies are useful in establishing a diagnosis of SPS. Treatment of SPS includes the use of immunomodulating therapies (plasmapheresis and intravenous immunoglobulins) and symptomatic treatment with benzodiazepines and baclofen. The use of tricyclic antidepressants and rapid withdrawal from therapy should be avoided.
Implications of the cAMP Signaling Pathway in Psychiatric Disorders: A Systematic Review of the Evidence
Authors: Perez Jorge , Tardito Daniela
Published: August 2016

The last decade has seen a shift in the theoretical framework addressing the pathophysiology of psychiatric disorders. During this period, research endeavors have been directed toward investigating the biochemical mechanisms involved in the transduction of information from the cell surface to the cell interior. The emerging picture, supported by growing evidence, is that in addition to neurotransmitters and their receptors, various signal transduction pathways may be linked to the pathophysiology of major psychiatric disorders. In this review, the role of one such pathway—the cyclic adenosine monophosphate (cAMP) signaling pathway—will be highlighted. We review data suggesting the involvement of the upstream and downstream components of this system in the pathophysiology of psychiatric disorders.
An Unusual Case of Motor and Vocal Tics With Obsessive-Compulsive Symptoms in a Young Adult With Behçet's Disease
Authors: Budman Cathy , Sarcevic Adnan
Published: August 2016

Behçet's disease is a chronic relapsing-remitting, multi-system inflammatory disorder of unknown etiology, characterized by recurrent oral and genital ulcers, uveitis, and skin lesions. The most common central nervous system findings are demyelization and perivascular cell infiltration; menin-goencephalitis, cerebral atrophy, and vascular thrombosis may also occur. Neuropsychiatric symptoms may include: paroxysmal dystonia, parkinsonism, delirium, hallucinations, and behavioral disturbances. We report an unusual case of explosive onset of motor and vocal tics with obsessive-compulsive symptoms in a 22-year-old male with Behçet's disease. The putative roles of infection and autoimmune mechanisms in the pathogenesis of tics and obsessive-compulsive symptoms are explored.
Global Benefit-risk Evaluation of Antidepressant Action: Comparison of Pooled Data for Venlafaxine, SSRIs, and Placebo
Authors: Entsuah Richard , Gao Bo
Published: August 2016

Do antidepressants have an equivalent risk-benefit ratio? Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is an effective antidepressant for treating major depression. The results of some clinical studies have suggested that venlafaxine may have more potent efficacy in sustaining remission in patients with major depression. Comparative clinical studies, however, lack suitable power to discern treatment differences in safety and also lack a quantitative basis for comparing risk and benefit. A global benefit-risk analysis of pooled data from eight randomized, double-blind, clinical trials of the safety and efficacy of venlafaxine and selective serotonin reuptake inhibitors (SSRIs) was performed. By using the ratio measure of risk-benefit, patients treated with venlafaxine (n=851) for 6–8 weeks experienced a relative gain of 1.57 compared with SSRI-treated patients (n=743) and a relative gain of 2.27 compared with placebo-treated patients (n=439). Subgroup analyses showed a relative gain of 1.35 for venlafaxine-treated patients (n=538) compared with fluoxetine-treated patients (n=549) and a relative gain of 2.53 compared with placebo-treated patients (n=357). A dose-response relationship was apparent between low (<75 mg/day), medium (75–150 mg/day), and high (>150 mg/day) dosages of venlafaxine; r values were 0.758, 0.822, and 1.181, respectively (P=.023, high dosage versus placebo; P=.030, medium dosage versus placebo). Important differences in risk and benefit exist between venlafaxine and SSRIs as a group compared with fluoxetine alone. A significant gain in benefit-risk in the treatment of major depression was observed with an increase in venlafaxine dosage from 75–>150 mg/day.
Axons, Cells, and Depression: The Nexus of Neurology and Psychiatry in Multiple Sclerosis
Authors: Gorman Jack M. , Finkel Jennifer
Published: August 2016

In many ways, multiple sclerosis (MS) is among the most frustrating and vicious of human diseases. Although we can readily see the demyelinating effect of MS lesions on postmortem examination, the diagnosis during life is fraught with difficulty. Advances in cerebrospinal fluid analysis and neuroimaging techniques have contributed to a recent revision of diagnostic criteria for MS, yet the majority of patients still wait for years until a definitive diagnosis is reached. They then face a disease that is both highly unpredictable and, in most cases, severely debilitating.

The unpredictable nature of MS is particularly distressing and many patients exist in a persistent state of fear and anxiety about their next MS exacerbation. Despite improved treatments, MS leaves some of the most severely affected patients wheelchair-bound by their early twenties. The more fortunate ones learn to deal with sporadic functional impairments for the rest of their lives. The unpredictable nature of MS leaves its victims always wondering about the next phase of their illness. For some, a more negative but definitive prognosis would be easier to accept than one for which the outcome is so unclear.

To make matters worse, the cause of MS remains an elusive one. Research points to an infectious and/or autoimmune etiology. The disorder is more common among those living in northern hemispheres, afflicts women more often than men, and has a partial genetic basis as evidenced by a greater concordance rate for monozygotic than dizygotic twins that nevertheless, falls far short of what would be expected of an autosomal, Mendelian disease. Drugs that modulate the immune system, from steroids to interferons, are somewhat helpful. Yet despite this, the long-term prognosis for MS has not changed much in recent decades and no therapy exists that addresses the root pathophysiology of the disease—demyelination.
Detecting Cognitive Dysfunction in Multiple Sclerosis with a Magnetic Resonance Imaging Rating Scale: A Pilot Study
Authors: Chamelian Laury , Bocti Christian , Gao Fu-Qiang , Black Sandra E. , Feinstein Anthony
Published: August 2016

Objective: In multiple sclerosis (MS), magnetic resonance imaging (MRI) predictors of cognitive impairment are based on sophisticated computer-generated analyses that are difficult to apply in clinical settings. This study investigated the clinical usefulness of a new visual rating scale, the Cholinergic Pathways Hyperintensities Scale (CHIPS), in detecting cognitive dysfunction.

Methods: Forty clinically definite MS patients underwent a brain MRI. Based on the CHIPS, cholinergic pathway hyperintensities were rated in 10 regions on four axial slices. Computerized hyperintense lesion volumes were also obtained. For cognitive testing, The Neuropsychological Screening Battery for Multiple Sclerosis was used. “Low” and “High” lesion score groups were computed based on the mean of the total CHIPS score. Optimal sensitivity and specificity of the total CHIPS score in detecting cognitive impairment were determined using a receiver operator characteristic curve.

Results: Despite a similar demographic profile, subjects with a “High” lesion score performed significantly worse than the “Low” lesion score group on verbal (P=.007) and visuospatial (P=.02) memory, and on a global index of cognitive functioning (P=.001). Optimal sensitivity (82%) and specificity (83%) were reached with a threshold total CHIPS score of 18 points. Total CHIPS score and total hyperintense lesion load were correlated (σ=0.82, P<.0001).

Conclusion: CHIPS is helpful in clinically predicting cognitive impairment in MS.
Sex Steroids and Human Behavior: Implications for Developmental Psychopathology
Authors: Alexander Gerianne M. , Peterson Bradley S.
Published: August 2016

In a variety of mammalian species, prenatal androgens organize brain structures and functions that are later activated by steroid hormones in postnatal life. In humans, studies of individuals with typical and atypical development suggest that sex differences in reproductive and nonreproductive behavior derive in part from similar prenatal and postnatal steroid effects on brain development. This paper provides a summary of research investigating hormonal influences on human behavior and describes how sex differences in the prevalences and natural histories of developmental psychopathologies may be consistent with these steroid effects. An association between patterns of sexual differentiation and specific forms of psychopathology suggests novel avenues for assessing the effects of sex steroids on brain structure and function, which may in turn improve our understanding of typical and atypical development in women and men.