bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of the Glutamatergic System in Posttraumatic Stress Disorder
Authors: Nair Jyotsna , Ajit Sarbjot Singh
Published: August 2016

Antiglutamatergic agents, such as lamotrigine, have been used successfully for the treatment of posttraumatic stress disorder (PTSD). They could be potentially acting through the stabilization of the corticotropin-releasing factor (CRF) systems. Glutamate mediates CRF release in various brain regions involved in the pathophysiology of PTSD, antiglutamatergic agents could stabilize the CRF system and, thereby, improve the symptom complex of PTSD (reexperiencing, hyperarousal, and avoidance). The role of glutamate and CRF in PTSD and other anxiety disorders are still being elucidated. However, it is clear that the glutamatergic systems play a role in the pathophysiology of PTSD.
Long-Term Improvement in Efficacy and Safety After Switching to Ziprasidone in Stable Outpatients with Schizophrenia
Authors: Simpson George M. , O'Gorman Cedric J. , Loebel Antony , Yang Ruoyong
Published: August 2016

Introduction:

The long-term efficacy and tolerability of treatment with ziprasidone following a switch from prior antipsychotics was evaluated in outpatients with schizophrenia or schizoaffective disorder in three open-label, flexible-dose, 1-year extension studies.

Methods:

These studies enrolled completers of 6-week trials in which subjects were switched to ziprasidone from conventional antipsychotics, olanzapine, or risperidone. Identical study designs and the small number of patients entering the extensions supported pooling of the data.

Results:

Of 185 pooled subjects entering the extension studies, 72 completed 58 weeks of treatment. Median treatment duration was 34.6 weeks; median dose was 120 mg/day at endpoint. The intent-to-treat population showed significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores (−4.3 [P≤.01]), PANSS negative scores (−2.4 [P≤.0001]), and Clinical Global Impression of severity score (−0.3 [P≤.001]). Completers showed significant improvement in mean PANSS total scores (−10.2 [P<.0001]), PANSS positive scores (−2.7 [P<.0001]), PANSS negative scores (−2.7 [P<.001]), and Clinical Global Impression of severity scores (−0.6 [P<.0001]).

Conclusion:

Ziprasidone was well tolerated, and patients demonstrated significant improvement in metabolic parameters and in all movement disorder assessments. Insomnia and somnolence were the only adverse events with an incidence >10% in pooled subjects. No subject had a corrected QT interval ≥500 msec.
Major Psychosis and Chromosome 22: Genetics Meets Epigenetics
Authors: Petronis Arturas , Popendikyte Violeta , Kan Peixiang , Sasaki Tsukasa
Published: August 2016

Elucidation of genetic factors in schizophrenia and bipolar disorder remains a challenging task to psychiatric researchers. As a rule, data from genetic linkage and association studies are quite controversial. In this article, we further explore the possibility that in addition to DNA sequence variation, a putative epigenetic dysregulation of brain genes plays an important role in the etiopathogenesis of major psychosis. We provide an epigenetic interpretation of unclear genetic findings specifically pertaining to chromosome 22 in schizophrenia and bipolar disorder. It is suggested that epigenetic strategies, when applied in conjunction with traditional genetic ones, may significantly expedite the uncovering of the molecular causes of major psychosis.
Diffusion Tensor MRI Methods: Historical Perspective and New Directions
Authors: Davis Timothy L. , Tuch David S.
Published: August 2016

This article will briefly review the history of diffusion physics and diffusion imaging beginning with Brown's initial observations of the diffusion phenomenon in the early part of the 19th century, through the development of diffusion-weighted imaging, and diffusion tensor imaging. The basic principles and limitations of diffusion tensor imaging are discussed. We conclude by reflecting on some of the open interpretative questions in diffusion imaging.
Novel Insights Into Neuropsychiatry
Authors: Trimble Michael
Published: August 2016

A centenary is often an excuse for reminding people of la fin des siècles, and there seems to be recurrent revivals of interest in the psychological, the mysterious, and their related medical syndromes. Only history will tell if the same occurred at the turn of the millennium, but to date there does not appear to be a flood of novels equivalent to, for example, Dr. Jekyll and Mr. Hyde, in which the two opposing poles of the human psyche are laid out with dramatic effect. At that time there was much interest in hypnosis, automatisms, sonambulism, and their relationship to human happenstance. However, there have been recent novels about Tourette syndrome, such as Johnathan Letham's Motherless Brooklyn. There may also be a revival of interest about epilepsy, and two recently published novels are of particular neuropsychiatric relevance. The first is Lauren Slater's Spasm, and the second Mark Salzman's Lying Awake.

The subtitle of Spasm hints at what is to come. It is a “Memoir With Lies.” Chapter 1 begins with the words “I exaggerate.” The tale is an autobiographical account of the growing up of a young girl with seizures, diagnosed as epilepsy, and who is put through all the traumas associated with the disorder. With auras of strange smells and seizure descriptions that would be called partial and secondarily generalized seizures, she gets examined by her pediatrician, given phenobarbital (600 mg!), has psychotherapy, and goes to a special school run by nuns. However, her seizures are relentless, she sees a neurologist who stimulates her cortex and recommends that she has a corpus callosotomy, which she then undergoes.
A Review of Common Sleep Disorders
Authors: Richert Allen C. , Baran Alp Sinan
Published: August 2016

What should clinicians know about sleep disorders? This article briefly introduces the reader to sleep medicine and succinctly reviews common sleep disorders. First, the authors describe the diagnostic tools unique to sleep medicine: the over-night polysomnogram and the multiple sleep latency test. Next, the authors review essential features of a subset of the sleep, described in the International Classification of Sleep Disorders-Revised, that sleep disorder specialists commonly evaluate, diagnose, and treat. The disorders reviewed include the intrinsic and circadian rhythm subsets of the dyssomnias group and the parasomnia group of sleep disorders. The authors identify the core signs and symptoms, polysomnogram findings, multiple sleep latency test findings, and treatment of these disorders.
Venlafaxine Treatment of Obsessive-Compulsive Disorder: Case Reports
Authors: Marazziti Donatella
Published: August 2016

About one-third of patients affected by obsessive-compulsive disorder fail to respond to serotonergic drugs and different strategies have been proposed for these resistant cases. This article reports experiences with venlafaxine in patients with obsessive-compulsive disorder who did not respond or did not tolerate serotonergic drugs.
Mouse Genetic Approaches to Feeding Regulation: Serotonin 5-HT2C Receptor Mutant Mice
Authors: Tecott Laurence H. , Abdallah Luna
Published: August 2016

Neural mechanisms underlying the regulation of ingestive behavior and energy balance are well conserved among mammals. Many neural pathways, each reflecting the function of many genes, interact to regulate these processes. Systematic genetic perturbations are not feasible in humans—the examination of gene functions relevant to feeding regulation must be performed in other species. Many advances in this field have been made through molecular genetic studies of mice, the most genetically tractable of mammalian species. The relevance of mouse ingestive behavior to the mechanisms underlying the regulation of feeding in humans is discussed. Approaches for evaluating the contribution of genes to the regulation of energy balance and to the actions of anorectic drugs are described in the context of studies focused on a line of mice lacking the serotonin 5-HT2C receptor subtype. These animals display reduced responsiveness to serotonergic anorexic drugs and a late-onset obesity syndrome associated with features reminiscent of common forms of human obesity. Developmental studies of energy balance uncovered a novel age-dependent physiological process that may contribute generally to the predisposition of humans and other mammals to accumulate fat stores during “middle-age.” These findings are presented to illustrate considerations in the use of mouse molecular genetic technologies to investigate genetic influences on ingestive behavior and energy balance.
Methylphenidate-Induced Obsessive-Compulsive Symptoms in an Elderly Man
Authors: Serby Michael
Published: August 2016

An 82-year-old man with treatment-resistant depression and early Alzheimer's disease was started on methylphenidate. Significant obsessive-compulsive behavior ensued but diminished over several weeks when methylphenidate was replaced by fluvoxamine. The patient had no prior psychiatric history, but he had a sister with obsessive-compulsive disorder. It appears that methylphenidate precipitated the patient's pathological behavior.
The Diagnosis, Symptomatology, and Epidemiology of Seasonal Affective Disorder
Authors: Magnusson Andres , Partonen Timo
Published: August 2016

The operational criteria for seasonal affective disorder (SAD) have undergone several changes since first proposed in 1984. SAD is currently included as a specifier of either bipolar or recurrent major depressive disorder in theDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition.TheInternational Classification of Diseases, Tenth Editionhas provisional diagnostic criteria for SAD. The most characteristic quality of SAD is that the symptoms usually present during winter and remit in the spring. Furthermore, the symptoms tend to remit when the patients are exposed to daylight or bright light therapy. The cognitive and emotional symptoms are as in other types of depression but the vegetative symptoms are the reverse of classic depressive vegetative symptoms, namely increased sleep and increased appetite. SAD is a common condition, but the exact prevalence rates vary between different studies and countries and is consistently found to be more common in women and in youth. SAD probably possibly occurs in children although not as commonly as in young adults. Some studies have found that certain ethnic groups who live at high northern latitudes may have adapted to the long arctic winter.
Auditory Abnormalities in Autism: Toward Functional Distinctions Among Findings
Authors: Kellerman Gabriella R. , Fan Jin , Gorman Jack M.
Published: August 2016

Recently, findings on a wide range of auditory abnormalities among individuals with autism have been reported. To date, functional distinctions among these varied findings are poorly established. Such distinctions should be of interest to clinicians and researchers alike given their potential therapeutic and experimental applications. This review suggests three general trends among these findings as a starting point for future analyses. First, studies of auditory perception of linguistic and social auditory stimuli among individuals with autism generally have found impaired perception versus normal controls. Such findings may correlate with impaired language and communication skills and social isolation observed among individuals with autism. Second, studies of auditory perception of pitch and music among individuals with autism generally have found enhanced perception versus normal controls. These findings may correlate with the restrictive and highly focused behaviors observed among individuals with autism. Third, findings on the auditory perception of non-linguistic, non-musical stimuli among autism patients resist any generalized conclusions. Ultimately, as some researchers have already suggested, the distinction between impaired global processing and enhanced local processing may prove useful in making sense of apparently discordant findings on auditory abnormalities among individuals with autism.
Functional Disorders and Comorbidity
Authors: Gorman Jack M.
Published: August 2016

It seems obvious to most people that the brain and the rest of the body interact. Stress seems to worsen most general medical conditions, mortality is higher among widowers than married men, and almost everyone becomes moody when he or she has a viral infection. However, these are mostly anecdotal observations. The precise ways in which mind and body relate in health and disease is more elusive and, at times, controversial.

Perhaps the hardest evidence we have for a mind-body connection comes from studies showing that depression is an independent—and, surprisingly, quite a robust—risk factor for cardiovascular disease. Following acute coronary syndrome depression significantly worsens outcome, including increasing all-cause mortality rates.

Another well-documented finding, going in the opposite direction, is the high rate of depression experienced by those receiving α-interferon for the treatment of hepatitis C or malignant melanoma. Less secure is whether depression increases risk or worsens prognosis for cancer; why patients with schizophrenia are at greater risk for heart disease and cancer than the general population; if it is true that stress plays a role in exacerbations of multiple sclerosis; and what is the relationship between depression and the risk for Alzheimer's disease. In each there are conflicting epidemiological data and difficulties understanding the neural mechanisms that would broker the relationship between brain and targeted peripheral organ.
Depression, Dementia, or Pseudodementia?
Authors: Dunner David L.
Published: August 2016

A 79-year-old woman is referred by her primary care physician for an evaluation regarding a possible psychiatric diagnosis. Until now, she has had an unremarkable medical and psychiatric history. For the past 4 months, the family has observed increasing confusion. She has been repeating statements that she has just made, evidences increasing forgetfulness, such as misplacing her keys and checkbook, and, on one occasion, went to the grocery store but could not remember which items she needed to purchase. There has also been a history of insomnia, some irritability, and she becomes agitated over trivial issues related to household activities. She has had a reduction in appetite and has lost 5 pounds. Furthermore, she has complained of fatigue and a decrease in energy. Her husband indicated that she rarely drinks alcohol. She has not mentioned suicidal ideation directly but she has become increasingly concerned that her affairs are in order. Two of her friends died in the previous year and one was admitted to a nursing home.
An Atypical Presentation of Anton Syndrome in a Patient with Preserved Cognition Despite Multiple Cerebral Infarcts: A Case Report
Authors: Davis Glen P. , Sewell R. Andrew , Levy Boaz , Price Bruce H. , Cunningham Miles G.
Published: August 2016

Visual anosognosia (Anton syndrome) is a rare complication of cortical blindness that results from injury to the visual association cortex, in which patients who are unable to see deny that they are blind. They sometimes confabulate explanations for their visual problems (“there is not enough light to see”), or endanger themselves in efforts to “prove” that they can see (eg, tripping or walking into walls). Without functioning visual-association centers, these patients lack the concept of sight and are unable to acknowledge their impairment. Usually, Anton syndrome is encountered in patients with bilateral occipital infarcts but no other cause for impaired vision. We present an atypical case of Anton syndrome in which the patient's underlying visual deficit was due to advanced glaucoma.
Attenuation of Apparent New-Onset Ocular Tics with Successful Treatment of PTSD
Authors: Hayes Patrick C. , Weber Charles L. , Gallagher Michael B. , Drouillard Gary J.
Published: August 2016

This case report describes a patient with reportedly new onset of tics, beginning at 21 years of age, in the context of posttraumatic stress disorder (PTSD) and comorbid alcohol abuse, with no known head injury. The setting is an American Society of Addiction Medicine intensive outpatient substance abuse rehabilitation program in an United States Army Medical Center. The patient is a 22-year-old male diagnosed with alcohol abuse and delayed PTSD who presented to the program's medical officer due to insomnia. We discovered he had a reportedly new ocular tic of ∼9 months duration, which he claimed developed at 21 years of age soon after returning from 1 year of combat duty. The patient was thoroughly evaluated, and we surmised the tic was a symptom of PTSD. After achieving full remission from alcohol, the tic persisted. However, as his PTSD symptoms remitted, so did his tic symptoms. At 6-month follow-up, the patient reported he was essentially free from PTSD symptoms, and his tic was significantly reduced.
Prevalence of Psychotic Disorders in Patients with Obsessive-Compulsive Disorder
Authors: de Haan Lieuwe , Dudek-Hodge Christine , Verhoeven Yolanda , Denys Damiaan
Published: August 2016

Introduction:The co-occurrence of obsessive-compulsive disorder (OCD) in patients with schizophrenia and related disorders has been increasingly recognized. However, the rate of psychosis comorbidity in OCD patients has yet to be systematically evaluated.

Methods:The prevalence of theDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition psychotic disorders was evaluated in 757 subjects consecutively referred to a specialised diagnostic and treatment facility for OCD. Demographic and clinical characteristics were assessed.

Results:Thirteen OCD patients (1.7%) also met theDSM-IVcriteria for a psychotic disorder. We found no significant differences in clinical characteristic between OCD patients with and without a psychotic disorder, although patients with OCD and a psychotic disorder more likely used illicit substances and more likely were male.

Conclusion:Relatively few patients referred to a specialized treatment OCD center suffer from a psychotic disorder.
Overview of Trends in Modern Psychopharmacology
Authors: Stahl Stephen M.
Published: August 2016

Beginning this month, CNS Spectrums will publish this column, “Trends in Psychopharmacology,” on a bi-monthly basis. Developments in psychopharmacology are proceeding at a fast pace, and this column will cover important and emerging areas from the field in a format that will be brief, and hopefully understandable. Topics will include what is new, “hot,” controversial, or informative in the field, and, of course, suggestions for future columns are always welcome.
Psychosocial Treatment of Depression and Suicidality in Adolescents
Authors: Klomek Anat Brunstein , Stanley Barbara
Published: August 2016

Depression is a common disorder among adolescents and is associated with a high risk of suicide. Suicide is the third leading cause of death among adolescents in the United States. Currently, there are only two evidence-based psychotherapies for adolescence depression: cognitive-behavioral therapy and interpersonal psychotherapy. Furthermore, psychosocial interventions that specifically target suicidal behavior in adolescents are even fewer in number than treatments for depression. This article will review the psychosocial interventions for depression and suicidality in adolescents and will describe a recently developed treatment that is under study for depressed suicidal adolescents.
What is the Self?A Psychobiological Perspective
Authors: Stein Dan J.
Published: August 2016

Philosophers have long struggled with questions about the nature of personal identity and of the self, with some viewing the self as a transcendent entity, and others arguing that the self is a constructed fiction. An approach based in cognitive-affective neuroscience emphasizes that self-related structures and processes are based in the brain-mind, and emerge within the social processes of human development. Alterations in such structures and processes are present in a wide range of neurological and psychiatric disorders, and neuropsychiatric lesion and functional brain imaging studies have led to more detailed awareness of the precise neuronal circuitry underlying self-representations. A cognitive-affective neuroscience approach provides a conceptual basis from which clinical research can further explore how best to assess and treat a wide range of disruptions to the self.
5-HT2A:Its Role in Frontally Mediated Executive Function and Related Psychopathology
Authors: Stein Dan J. , Hemmings Sian , Moolman-Smook Hanlie , Audenaert Kurt
Published: August 2016

Serotonin (5-HT)2Areceptors are widely distributed, with high levels in the frontal cortex, where postsynaptic activation may increase activity in pyramidal glutamatergic neurons and mediate various executive functions. More specifically, reciprocal cortical-raphe pathways may allow the ventral prefrontal cortex to inhibit stress-induced neural activity in the brainstem when stressors are perceived as controllable. However, early adversity and negative attitudes may be associated with higher frontal 5-HT2Areceptor levels and greater risk for stress-induced psychopathology, and certain 5-HT2Agene variants have been associated with increased risk for impulsive behavior. Conversely, many antidepressants result in decreased levels of 5-HT2Areceptor levels, and blockade of 5-HT2Areceptors has proven useful in the treatment of a number of psychiatric disorders.
The Precuneus and Consciousness
Authors: Cavanna Andrea E.
Published: August 2016

This article reviews the rapidly growing literature on the functional anatomy and behavioral correlates of the precuneus, with special reference to imaging neuroscience studies using hamodynamic techniques. The precuneus, along with adjacent areas within the posteromedial parietal cortex, is among the most active cortical regions according to the “default mode” of brain function during the conscious resting state, whereas it selectively deactivates in a number of pathophysiological conditions (ie, sleep, vegetative state, drug-induced anesthesia), and neuropsychiatric disorders (ie, epilepsy, Alzheimer's disease, and schizophrenia) characterized by impaired consciousness. These findings, along with the widespread connectivity pattern, suggest that the precuneus may play a central role in the neural network correlates of consciousness. Specifically, its activity seems to correlate with self-reflection processes, possibly involving mental imagery and episodic/autobiographical memory retrieval.
The PANDAS Subgroup: Recognition and Treatment
Authors: Swedo Susan E. , Garvey Marjorie , Snider Lisa , Hamilton Charlotte , Leonard Henrietta L.
Published: August 2016

A subgroup of patients with childhood-onset obsessive-compulsive disorder (OCD) has been identified who share a common clinical course characterized by dramatic symptom exacerbations following Group A beta-hemolytic streptococcal (GABHS) infections. The term PANDAS has been applied to the subgroup, to indicate the postulated etiology of their symptoms: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. Five clinical characteristics define the PANDAS subgroup: presence of OCD and/or tic disorder, prepubertal symptom onset, sudden onset or abrupt exacerbations (sawtooth course), association with neurological abnormalities (presence of adventitious movements or motoric hyperactivity during exacerbations), and temporal association between symptom exacerbations and GABHS infections. Post-streptococcal symptom exacerbations are typically quite dramatic, with patients reporting that their symptoms “…came on overnight” or “…appeared all of a sudden a few days after I had a sore throat.” The post-streptococcal inflammatory nature of the neuropsychiatric symptoms provides novel opportunities for treatment and prevention, including immunomodulatory therapies such as therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIG). A recently completed placebo-controlled trial revealed that both IVIG and TPE were effective in reducing neuropsychiatric symptom severity (40% to 55% reductions, respectively) for a group of severely ill children with OCD and/or tic disorders. Further research is required to determine why the treatments are helpful, as well as to ascertain whether or not antibiotic prophylaxis can help prevent post-streptococcal symptom exacerbations.
Neurosurgical Approaches to Intractable Obsessive-Compulsive Disorder
Authors: Rasmussen Steven , Greenberg Benjamin , Mindus Per , Friehs Gerhard , Noren George
Published: August 2016

Although significant progress has been made over the last decade in the treatment of obsessive-compulsive disorder (OCD), approximately 20% of OCD patients remain refractory to nonsurgical therapies, including pharmacologic and cognitive-behavioral therapy. Because a number of neural circuits involving the basal ganglia, thalamus, limbic system, and frontal lobes have been implicated in the pathophysiology of OCD, the need for an effective intervention in these patients has brought the focus on surgical approaches, including cingulotomy and capsulotomy procedures. Unlike free-hand surgical approaches used in the past, current neurosurgical interventions have been greatly enhanced by advances in technology, which allow lesioning to an accuracy of 1 mm. Today's neurosurgical approaches have shown significant benefit in as many as 60% of refractory patients, while preserving personality and cognitive functioning and limiting morbidity. A study of gamma knife capsulotomy conducted at Brown University School of Medicine showed that 40% of patients undergoing two lesioning procedures were much or very much improved 2 years postsurgery. The inherent obstacles to conducting placebo-controlled studies in these severely ill patients mean that further study is required to identify optimal candidates for surgical intervention.
Remission-Oriented Treatment of Depression
Authors: Howland Robert H. , Trivedi Madhukar H. , Ninan Philip T. , Ginsberg David L.
Published: August 2016

Given the wide variety of available antidepressant therapies, an important question is how effective are we in treating depression? In clinical research trials of antidepressants, a treatment response is defined as a 50% or greater improvement in depressive symptoms, whereas remission is defined as having minimal or absent symptoms at the end of treatment. Approximately 50% of patients treated with antidepressants have a treatment response, but only about 25% have a complete remission. Many treatment responders therefore have residual symptoms despite adequate treatment. This is critically important because depressed patients with residual symptoms, even though mild in severity, still have significant functional impairment, have a high risk of relapsing into a more severe episode, and may have a more chronic course of illness. Such patients also do not show a full functional recovery from their depression. Recent comparative studies have found that remission rates are significantly higher with venlafaxine (Effexor) compared to serotonin reuptake inhibitors, which might be due to their different effects on neurotransmitter systems. The use of medication combinations, having additive and/or synergistic antidepressant effects, or adding psychotherapy following a course of pharmacotherapy also can be used to treat residual symptoms and lead to a more complete remission.
Affect Regulation, Brain Development, and Behavioral/Emotional Health in Adolescence
Authors: Dahl Ronald E.
Published: August 2016

This paper addresses the importance of affect regulation (AR) in relation to a broad range of behavioral and emotional health problems that emerge during adolescence. AR is defined as the adaptive modulation of emotional experience to serve a goal or purpose. This conceptualization of AR emphasizes the use of cognitive skills to guide, inhibit, or modify emotion and behavior, including the expression of emotional responses, in learned, strategic ways—skills that ultimately underpin adult levels of social maturity and the ability to show “responsible” behavior across a range of emotional situations. Neurobehavioral systems that subserve these AR skills include areas of the inferior and orbital prefrontal cortex (PFC), with rich interconnections to several limbic structures and other cortical areas, including the dorsolateral PFC. Adolescence represents an important developmental period in the functional maturation of adult AR skills; it is also a critical time in the development of clinical disorders of AR (eg, rates of depression increase dramatically and gender differences in depression emerge). Maturational changes in AR that occur during adolescence—particularly with respect to the role of emotions influencing responsible decision making—are also relevant to understanding key aspects of the developmental pathways of some behavioral health problems, such as alcohol use and nicotine dependence. A strong case is made for developmental research in affective neuroscience aimed at this important maturational period, particularly the kind of transdisciplinary research leading toward mechanistic understanding of the development of adolescent-onset disorders. Improving understanding in these areas could ultimately lead to the development of early interventions in targeted high-risk populations, and has enormous clinical and social policy relevance.
Borderline Personality Disorder:Toward Integration
Authors: Stein Dan J.
Published: August 2016

Several psychiatric disorders, including borderline personality disorder (BPD), are characterized by emotional dysregulation and impulse dyscontrol. More specifically, symptoms in patients with BPD often occur within the context of disruptions in attachment and related distortions in cognitive-affective processing of the self and others. From a neurocircuitry perspective, findings include prefrontal hypoactivity, amygdala hyperreactivity, and alterations in prefrontal-limbic interaction. Molecular pathways relevant to these circuits include the serotonergic, noradrenergic, and dopaminergic systems, and there is some evidence that pharmacotherapy with agents that act on these systems may be useful. Given the disruptions in attachment and schemas of the self and others in BPD, establishing a therapeutic alliance is crucial while psychotherapy remains the cornerstone of an integrated approach to management.
Nail-Biting Stuff? The Effect of N-acetyl Cysteine on Nail-Biting
Authors: Berk Michael , Jeavons Sue , Dean Olivia M. , Dodd Seetal , Moss Kirsteen , Gama Clarissa S. , Malhi Gin S.
Published: August 2016

N-acetyl cysteine (NAC) is a widely available nutraceutical with a variety of actions. As a precursor of cysteine and glutathione, it has antioxidant properties that may impact on mood and contribute to an effect on impulsivity and obsessive behaviour. Via its additional effect on glutamate via the cystine-glutamate exchange system, NAC has been shown to mediate impulsivity in preclinical models of addiction, reduce craving, and cue extinction. Further, by boosting glutathione, NAC acts as a potent antioxidant and has been shown in two positive, large-scale randomized placebo-controlled trials to affect negative symptoms in schizophrenia and depression in bipolar disorder. We describe three cases in which its actions specifically on nail-biting and associated anxiety may offer a potential treatment. The spontaneous findings are reported as part of an ongoing treatment trial examining the utility of NAC in bipolar disorder. Its actions, if robustly replicated, also point to potential treatment targets in glutathione or glutamate pathways in the brain.
Neuropsychopharmacologic Treatment of Depression and Other Neuropsychiatric Disorders in HIV-Infected Individuals
Authors: Repetto Martin J. , Evans Dwight L. , Cruess Dean G. , Gettes David R. , Douglas Steven D. , Petitto John M.
Published: August 2016

How can neuropsychiatric disorders and syndromes be underdiagnosed and inadequately treated in individuals infected with human immunodeficiency virus? Depression in particular is among the most prevalent diagnoses and there is a solid foundation of data from controlled clinical studies that has begun to examine the efficacy of various antidepressants in HIV-infected persons. This article summarizes essential findings pertaining to the use of psychotropic medications to treat depression and other neuropsychiatric disorders in the context of immunodeficiency. This includes discussion of clinically significant treatment considerations (eg, efficacy, side effects, drug-drug interactions) derived from the existing literature. Taken together, there is compelling evidence that psychopharmacologic intervention can improve the quality of life of mentally ill HIV-infected individuals.
Oxytocin and Vasopressin: Social Neuropeptides
Authors: Stein Dan J.
Published: August 2016

Oxytocin and vasopressin are highly conserved neuropeptides that play a key role in social attachment and affiliation, including parental care and pair-bonding. Oxytocin attenuates neural responses to aversive pictures and has been associated with reduced coupling of amygdala to brainstem regions involved in the fear response. Differential activation of the amygdala has been found to be associated with different genetic variants of the vasopressin receptor. There is growing evidence that oxytocin and vasopressin receptor variants are associated with individual differences in prosocial behavior. It is humbling that differences in complex human behaviors may be partially explicable on the basis of relatively simple neuropeptide systems. Nevertheless, such findings potentially allow for targeted interventions for a range of psychiatric disorders in which such systems play a role.
Low-dose Transdermal Testosterone Augmentation Therapy Improves Depression Severity in Women
Authors: Miller Karen K. , Perlis Roy H. , Papakostas George I. , Mischoulon David , Iosifescu Dan V. , Brick Danielle J. , Fava Maurizio
Published: August 2016

Background: Inadequate response to antidepressant monotherapy in women with major depressive disorder is common. Testosterone administration has been shown to be an effective augmentation therapy in depressed hypogonadal men with selective serotonin reuptake inhibitor-resistant depression. However, the effects of low-dose testosterone as augmentation therapy in women with treatment-resistant depression have not been studied.

Methods: Low-dose transdermal testosterone (300 mcg/day, Intrinsa, Procter and Gamble Pharmaceuticals) was administered to nine women with treatment-resistant depression in an 8 week open-label pilot protocol.

Results: There was a statistically significant improvement in mean Montgomery-Asberg Depression Rating Scale (MADRS) scores at 2 weeks, sustained through the 8 week period. Two-thirds of subjects achieved a response to the treatment (decrease in MADRS score of ≥50%) and 33% achieved remission (final MADRS score <10) after 8 weeks of therapy. Mean levels of fatigue, as measured by the MADRS lassitude item, significantly decreased at all time points with a mean 38% decrease from baseline to 8 weeks.

Conclusion: These preliminary pilot data suggest that low-dose transdermal testosterone may be an effective augmentation therapy in women with treatment-resistant depression. Further studies are warranted.
Association of OCD with a History of Traumatic Events Among Patients in Methadone Maintenance Treatment
Authors: Peles Einat , Adelson Miriam , Schreiber Shaul
Published: August 2016

Introduction: We studied the relationship between obsessive-compulsive disorder (OCD) and lifetime history of any traumatic events among methadone maintenance treatment (MMT) patients.

Methods: In a cross-sectional sample of 167 patients, we clinically assessed for OCD using the Yale-Brown Obsessive Compulsive Scale and interviewed for their lifetime history of traumas.

Results: OCD was defined among 40.1% patients. Sixteen percent of patients reported having been victims of sexual abuse or rape, 21.6% had self-inflicted physical injuries, 34.1% attempted suicide, 44.9% sustained other physical violence or abuse, 28.7% were involved in a car accident as drivers and 6% as passengers, and 16.8% had significant falls. Patients with OCD compared with patients without OCD included more rape victims (28.4% vs. 9%), had more self-inflicted physical injuries (31.3% vs. 15%), and had more suicide attempts (46.3% vs. 26%), with no differences in other traumatic events exposure. The OCD group was characterized as being female (OR=4.0 [95% CI 1.7-9.3]), having a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text-Revision Axis I psychiatric disorder (OR=2.6 [95% CI 1.2-5.5]), being Israeli born (OR=2.9 [95% CI 1.2-6.9]), abusing benzodiazepines (OR=2.2 [95% CI 1.02-4.6]), having attempted suicide (OR=2.5 [95% CI 1.1-5.4]), and having longer duration of opiate abuse before admission to MMT (OR=1.06 [95% CI 1.01-1.1]).
Prevalence of Irritable Bowel Syndrome in Obsessive–Compulsive Disorder
Authors: Masand Prakash S. , Keuthen Nancy J. , Gupta Sanjay , Virk Subhdeep , Yu-Siao Barbara , Kaplan David
Published: August 2016

Introduction:

Irritable bowel syndrome (IBS) occurs more frequently in psychiatric patients, especially those with anxiety and mood disorders.

Methods:

We sought to determine the prevalence and phenomenology of IBS in patients diagnosed with obsessive-compulsive disorder (OCD). A semi-structured diagnostic interview was administered to patients seeking treatment for OCD in outpatient settings. Structured questions regarding gastrointestinal functioning and IBS symptoms were administered. IBS was diagnosed by a gastroenterologist using Rome I criteria.

Results:

Thirty-seven patients (35.1%) with OCD met criteria for IBS. Of these, 53.8% had IBS with both diarrhea and constipation, 30.8% had diarrhea-predominant IBS, and 15.4% had constipation-predominant IBS.The prevalence rate of IBS in an age- and sex-matched control group (n=40) of medical patients in a family practice was 2.5%. IBS prevalence rates were significantly higher for OCD patients than control subjects (P=.0002).

Conclusion:

IBS and psychiatric illness have high rates of bi-directional comorbidity. This study shows that 35.1% of patients with OCD satisfied criteria for IBS in contrast to 2.5% of the controlled subjects. In most patients the IBS was characterized by both diarrhea and constipation. While taking the initial history clinicians should inquire about bowel symptoms in patients presenting with psychiatric illnesses, including OCD. SSRIs could potentially worsen such symptoms and lead to non-adherence.
Recognition and Treatment of Depression with or Without Comorbid Anxiety Disorders
Authors: Zimmerman Mark , Chelminski Iwona , Zisook Sidney , Ginsberg David L.
Published: August 2016

Anxiety disorders are common in depressed patients. Several studies of the full range of Diagnostic and Statistical Manual of Mental Disorders-defined anxiety disorders in depressed psychiatric outpatients each found that when diagnoses are based on semi-structured diagnostic interviews >40% of the patients had a comorbid anxiety disorder. The recognition of comorbidity is not simply of academic interest, but it has important clinical significance. Epidemiological studies, such as the National Comorbidity Study, have demonstrated that depressed individuals with a history of anxiety disorders are at increased risk for hospitalization, suicide attempt, and greater impairment from the depression. The co-occurrence of anxiety disorders in depressed patients has been associated with a more chronic course of depression in psychiatric patients, primary care patients, and epidemiological samples. Recent research has suggested that clinicians underrecognize anxiety disorder comorbidity in depressed patients. The clinical significance of this underrecognition is highlighted by the finding that patients often want treatment to address their anxiety disorder comorbidity. When anxiety disorders are detected they often influence clinicians' selection of antidepressant medication, though some of clinicians' prescribing biases are not supported by empirical data.

In this monograph, Iwona Chelminski, PhD, reviews the significance of anxiety in patients with depression as well as diagnostic instruments for recognizing this comorbidity. Next, Mark Zimmerman, MD, addresses the factors that affect the clinician's choice of antidepressant, focusing on the influence of comorbid anxiety. Finally, Sidney Zisook, MD, discusses the differential efficacy of antidepressants as well as the role of psychotherapy in patients with comorbid anxiety and depression.
Reassessing Carbamazepine in Bipolar Disorders
Authors: Ketter Terence A.
Published: August 2016

This discussion focuses on the historical trends of carbamazepine in the treatment of acute mania, acute bipolar depression, and as maintenance treatment for bipolar disorder. Clinical implications of efficacy, safety, tolerability, and drug interactions associated with carbamazepine are discussed as well.

Important progress in bipolar disorders therapeutics began in the 1970s with lithium and the conventional antipsychotics, and continued in the 1980s with carbamazepine, in the 1990s with divalproex, and in the 2000s with lamotrigine and the introduction of the atypical antipsychotics. Electroconvulsive therapy (ECT) has been used throughout these periods and still has a place in bipolar disorder, especially for severe, treatment-resistant, and very acute cases.
Introduction: Assessing Current Practice in Alzheimer's Disease
Authors: Mintzer Jacobo E.
Published: August 2016

Alzheimer's disease (AD) is a debilitating condition currently affecting 4.5 million elderly citizens in the United States alone. It is the most common form of dementia and is associated with significant disability. For many years the prognosis of the disease has remained largely unchanged. Those patients who develop AD face progressive cognitive and functional decline that ultimately shortens their life expectancy and destroys their quality of life. At the same time, the disease has a significant adverse impact on the lives of those family members who serve as caregivers. With the aging of the baby-boomer generation and the expected associated increase in the number of patients with AD, clinicians who treat the elderly will clearly be in need of some new answers. Recent advances in assessment, diagnosis, and treatment offer some hope for relief from this bleak prognosis.

Advances in AD include the establishment of clear diagnostic criteria, the validation of disease-specific assessment instruments, and pharmacologic and behavioral therapies for management of symptoms. A handful of medications that enhance cognition have obtained the approval of the Food and Drug Administration, and more are currently in development. Trials of existing medications have demonstrated benefit in the management of the psychiatric symptoms (eg, psychosis and agitation) typically associated with the disease. But much still remains to be done.

In the first article in this supplement, Michael A. Rogawski, MD, PhD, explains what is known about the pathogenesis and the behavioral and psychological symptoms of AD. He discusses the scientific basis for empirical therapies currently being used to relieve the symptoms of this disease, focusing on drug therapies approved by the FDA, including the newest AD medication to market memantine.
The Fourth IOCDC
Authors: Hollander Eric , Zohar Joseph , Marazziti Donatella
Published: August 2016

The Fourth International Obsessive Compulsive Disorder Conference (IOCDC) was held February 10–12, 2000, on the beautiful island of St. Thomas. The IOCDC is an annual meeting which brings together the world's leading experts in obsessive-compulsive disorder (OCD) and related disorders in a small workshop setting to present recent research advances, discuss gaps in our current knowledge, and plan or international approaches that address these knowledge gaps. The IOCDC meetings have been held on islands on both sides of the Atlantic—Capri, Guadeloupe, Madeira, and now St. Thomas.

The International Organizing Committee consists of Eric Hollander, MD (USA), Joseph Zohar, MD (Israel), and Donatella Marazziti, MD (Italy). The proceedings are generously supported by an unrestricted educational grant from Solvay Pharmaceuticals Inc. and Solvay Pharmaceuticals, and we would like to acknowledge the very important contributions of Chantal Vekens and Mary Blangiardo of Solvay. Also, an mportant part of the success of these meetings stems from the very active role of the chairpersons and cochairpersons of the workshops who lead the discussions, who synthesize the future directions and prepare the manuscripts that result from these discussions that appear in this academic supplement.

The meeting led off with a state-of-the-art plenary address by Mark George, MD (USA), describing how new methods of brain stimulation are improving research and therapy in OCD and promise to revolutionize neuropsychiatric research and herapy over the next decade. He describes how transcranial magnetic stimulation (TMS) is used to test the circuits in OCD and test electrophysiologic evaluations of cortical inhibition n OCD. Newer techniques that are less invasive than ablative surgery and appear promising in OCD therapy include vagus nerve stimulation and deep brain stimulation.
Are All Atypical Antipsychotics Equal for the Treatment of Cognition and Affect in Schizophrenia?
Authors: Zohar Joseph
Published: August 2016

One of the major developments in psychiatry in the last decade is the development and widespread use of the new antipsychotics. The field has moved from the typical dopamine D2-blocking neuroleptics into the new era of antipsychotics with the addition of the serotonin 5-HT2A properties to the classical D2 antagonism. These “atypical” antipsychotic drugs (APDs) provide us with new tools with which to treat our patients. However, do we really know how to make the most of these new medications? Are we equipped with the knowledge to do the best matching between the different APDs and the patients that we will see in an hour's time?

One potential way to get the maximum therapeutic effect of a specific medication is to improve the matching between the compound and the patient that we are seeing, ie, to try and get the best medication for the patient. For example, the medication one would choose for a patient with cognitive decline and a tendency to be overweight, would likely be different from an antipsychotic one would select for a patient with the same diagnosis, but who is slim and has paranoid delusions. It is also intuitively clear to us that we should treat first-episode patients differently from those with a 20-year history of social decline. Similarly, a patient with pronounced affective component would receive a different treatment regimen from a patient who is affectively “flat.”

Although we have been hearing and reading a lot about all the different APDs, it would be quite accurate to postulate that a concise updated summary of the different APDs, examining them around four different critical axes, might be welcomed by our readers.

The topics covered in this supplement are: the differential receptor's profile of APDs and their clinical implications, the issue of cognitive impairment in schizophrenia and APDs, monitoring guidelines to assess metabolic abnormalities that may occur with APDs, and an update on treatment after first-episode psychosis.