bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Menarche and Depression in Adolescence
Authors: Born Leslie , Steiner Meir
Published: August 2016

Prior to adolescence, the rates of depression are similar in girls and boys, or are slightly higher in boys. However, with the onset of puberty, the gender proportion of depression dramatically shifts to a 2:1 female to male ratio. What is the relationship between menarche and the onset of major depression in early adolescence? A recent theoretical model proposes that vulnerability to depression may be rooted in normal female hormonal maturational processes and gender socialization. Information regarding the management of depression in adolescent and young adult women is provided, including gender differences in the presentation of depressive symptoms, instruments to facilitate assessment, and treatment options. Pubertal and other hormonal changes should be monitored prospectively along with individual, genetic, constitutional, and psychological characteristics. The burden of illness associated with onset of depression following menarche reinforces the importance of expeditious recognition and intervention.
Long-Term Treatment Goals: Enhancing Healthy Outcomes
Authors: Casey Daniel E.
Published: August 2016

The long-term management of schizophrenia with a goal of functional rehabilitation remains an enormous challenge to clinicians despite improvements in drug therapy, psychosocial treatments, and family and community interventions. The goals of long-term therapy are to preserve the gains made during acute treatment, prevent symptom exacerbation, enhance psychosocial functioning, and improve quality of life. Schizophrenia is an illness that disrupts broad areas of mental function, including thought, cognition, affect, and motor performance. The new antipsychotics should aid physicians in meeting higher treatment goals for persons with schizophrenia. These agents combine high efficacy with improved tolerability, mainly through a low liability for extrapyramidal symptoms and probably improve cognitive affect. Recent studies have demonstrated efficacy of these new antipsychotics in improving psychopathology and symptoms and in preventing relapse during long-term use. These drugs are likely to provide physicians with an increasingly viable option in the long-term treatment and rehabilitation of patients with schizophrenia.
Achieving Long-Term Optimal Outcomes in Geriatric Depression and Anxiety
Authors: Mulsant Benoit H. , Whyte Ellen , Lenze Eric J. , Lotrich Francis , Karp Jordan F. , Pollock Bruce G. , Reynolds Charles F.
Published: August 2016

Depression and anxiety disorders are very common in the elderly. Data accumulated over the past 2 decades have shown that most older patients can tolerate and respond to acute treatment with serotonergic antidepressants, other psychotropic agents, or manual-based psychotherapy. However, outcomes under usual-care conditions remain poor. This review proposes that clinicians may significantly improve the long-term outcomes of their older patients with depression and anxiety by focusing on four key factors: (1) identification and treatment of comorbid conditions; (2) full remission of acute symptoms; (3) education of patients, families, and professional colleagues about the need for long-term treatment; and (4) prevention and management of medication side-effects.
Pharmacologic Advances in the Treatment of ADHD
Authors: Spencer Thomas J. , Wigal Sharon B. , Newcorn Jeffrey H.
Published: August 2016

Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that affects many domains of life. Studies have shown that adequate treatment of ADHD can affect the course of the disorder in a fundamental manner. While nonpharmacologic treatments such as education and various psycho-social interventions are used in the management of ADHD, pharmacotherapy is the mainstay of treatment for this disorder. Psychostimulants are the only group of agents that have been approved for the ADHD indication and are considered to be first-line treatment for the disorder. Methylphenidate, amphetamines, andpemoline are the most commonly used agents in this group. The stimulants have been successfully used for many years and their efficacy has been confirmed by a large number of clinical studies. Recent pharmacological advances have been made with longer-acting stimulants, new isomers, and more advanced drug delivery systems that enable more convenient dosing schedules with drug effects lasting throughout the day. Other nonstimulant medications have been shown to have anti-ADHD activity as well, although more research is needed on the efficacy and utility of these treatments. Antihypertensive medications and antidepressants, such as tricyclics and bupropion, have been studied and may have applications in the treatment of specific subgroups of patients with comorbid conditions or for patients who do not respond to stimulant treatment.
Diagnosis and Treatment of Depression During Pregnancy
Authors: Cohen Lee S. , Nonacs Ruta , Viguera Adele C. , Reminick Alison
Published: August 2016

Pregnancy has frequently been described as a time of affective well-being. However, a growing literature suggests that women are neither “protected” against new-onset or recurrence of depression during this time. Diagnosis and effective treatment of depression during pregnancy requires a careful weighing of risk of treatment which may include psychotropic medications against the risks associated with failure to adequately manage affective distress and its potential impact of maternal and fetal well-being. Treatment options during pregnancy are reviewed in the context of developing the most appropriate risk/benefit decision for individual patients with past or current depression who either anticipate pregnancy or who become pregnant.
Functional Neuroimaging Studies of Human Emotions
Authors: Phan K. Luan , Wager Tor D. , Taylor Stephan F. , Liberzon Israel
Published: August 2016

Neuroimaging studies with positron emission tomography and functional magnetic resonance imaging have begun to describe the functional neuroanatomy of human emotion. Taken separately, specific studies vary in task dimensions and in type(s) of emotion studied, and are limited by statistical power and sensitivity. By examining findings across studies in a meta-analysis, we sought to determine if common or segregated patterns of activations exist in different emotions and across various emotional tasks. We surveyed over 55 positron emission tomography and functional magnetic resonance imaging activation studies, which investigated emotion in healthy subjects. This paper will review observations in several regions of interest in limbic (eg, amygdala, anterior cingulate cortex) and paralimbic (eg, medial prefrontal cortex, insula) brain regions in emotional responding.
Nonparametric Linkage Analysis Between Schizophrenia and Candidate Genes of Dopaminergic and Serotonergic Systems
Authors: Ambrósio Alda M. , Kennedy James L. , Macciardi Fabio , Coelho Isabel , Soares Maria J. , Oliveira Catarina R. , Pato Michele T. , Pato Carlos N.
Published: August 2016

Background:

Alterations in dopaminergic and serotonergic systems have been implicated in the pathophysiology of schizophrenia for many years. This study was performed to assess the possible involvement of the dopamine receptor genes D2 (DRD2), D3, D4, serotonin receptor genes 1Dα, 1Dβ, and 2A in the etiology of schizophrenia.

Methods:

We examined 33 multiplex schizophrenic families from Portugal.

Results:

Linkage analysis performed by GENE-HUNTER showed nonsignificant linkage for these genes. A maximum nonparametric linkage score of 1.635 (P=.032) at DRD2 gene was observed, and this finding suggests DRD2 gene for further studies.

Conclusion:

the polymorphisms studied at dopamine receptor genes D3, D4, serotonin receptor genes 1Dα, 1Dβ, and 2A do not have a major effect in susceptibility to schizophrenia in a Portuguese population.
Social Stress in Tree Shrews as an Animal Model of Depression: An Example of a Behavioral Model of a CNS Disorder
Authors: Fuchs Eberhard
Published: August 2016

Animal models are invaluable in preclinical research on human psychopathology. Valid animal models to study the pathophysiology of depression and specific biological and behavioral responses to antidepressant drug treatments are of prime interest. In order to improve our knowledge of the causal mechanisms of stress-related disorders such as depression, we need animal models that mirror the situation seen in patients. One promising model is the chronic psychosocial stress paradigm in male tree shrews. Coexistence of two males in visual and olfactory contact leads to a stable dominant/subordinate relationship, with the subordinates showing obvious changes in behavioral, neuroendocrine, and central nervous activity that are similar to the signs and symptoms observed during episodes of depression in patients.
Viral Vector Mediated Overexpression of Human α-Synuclein in the Nigrostriatal Dopaminergic Neurons: A New Model for Parkinson's Disease
Authors: Maingay Matthew , Romero-Ramos Marina , Kirik Deniz
Published: August 2016

Parkinson's disease is predominantly a dopamine deficiency syndrome, which is produced in the brain by the loss of cells located in a small area in the ventral midbrain called the substantia nigra. Complete unilateral dopamine lesions, based on the administration of toxic substances (ie, 6-hydroxy-dopamine in rats and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice and primates) have been extremely useful in testing strategies of replacement. For example, the functional and biochemical impact of the transplanted ventral mesencephalic dopaminergic progenitors has been characterized to a large extent, using the complete lesion model in rats. Over the last decade, however, studies addressing the ability of neurotrophic factors to protect injured dopamine cells prompted researchers to make available partial and progressive lesion models to allow a window of opportunity to interfere the disease progression. Recent findings relating a-synuclein with Parkinson's disease pathology have opened new possibilities to develop alternative models based on the overexpression of this protein using recombinant adeno-associated viral vectors, which is valuable not only for helping to better understand its involvement in the disease process, but also to more closely resemble the neurodegeneration found in Parkinson's disease.
Thrombolytic Treatment of Acute Cerebral Infarction
Authors: Burger Kathleen M. , Horowitz Deborah R.
Published: August 2016

Stroke is a common cause of death and disability throughout the world. Acute neurologic deficits due to ischemic injury deserve rapid recognition and diagnosis in order to provide effective therapy. Intravenous tissue plasminogen activator (t-PA) provided to carefully selected patients that can be treated within 3 hours of stroke onset results in improved outcome in these patients. Intra-arterial administration of t-PA within a 6-hour window is performed at several academic centers in patients with middle cerebral and other intracranial artery occlusions based on results of one randomized clinical trial and numerous case reports. Although acute therapy of ischemic stroke has received much attention since the approval of intravenous t-PA, only a small percentage of individuals suffering a stroke actually receive t-PA. This article will review the optimal management of the acute stroke patient and discuss thrombolytic clinical trials that have been completed as well as those that are in progress.
Beyond Monoamines: Glutamatergic Function in Mood Disorders
Authors: Kugaya Akira , Sanacora Gerard
Published: August 2016

The monoamine theory has implicated abnormalities in serotonin and norepinephrine in the pathophysiology of major depression and bipolar illness and contributed greatly to our understanding of mood disorders and their treatment. Nevertheless, some limitations of this model still exist that require researchers and clinicians to seek further explanation and develop novel interventions that reach beyond the confines of the monoaminergic systems. Recent studies have provided strong evidence that glutamate and other amino acid neurotransmitters are involved in the pathophysiology and treatment of mood disorders. Studies employing in vivo magnetic resonance spectroscopy have revealed altered cortical glutamate levels in depressed subjects. Consistent with a model of excessive glutamate-induced excitation in mood disorders, several antiglutamatergic agents, such as riluzole and lamotrigine, have demonstrated potential antidepressant efficacy. Glial cell abnormalities commonly associated with mood disorders may at least partly account for the impairment in glutamate action since glial cells play a primary role in synaptic glutamate removal. A hypothetical model of altered glutamatergic function in mood disorders is proposed in conjunction with potential antidepressant mechanisms of antiglutamatergic agents. Further studies elucidating the role of the glutamatergic system in the pathophysiology of mood and anxiety disorders and studies exploring the efficacy and mechanism of action of antiglutamatergic agents in these disorders, are likely to provide new targets for the development of novel antidepressant agents.
Posttraumatic Stress Disorder:A Missed Link Between Psychiatric and Cardiovascular Morbidity?
Authors: Cotter Gad , Milo-Cotter Olga , Rubinstein David , Shemesh Eyal
Published: August 2016

Posttraumatic stress disorder (PTSD) symptoms may develop as a result of an acute, life-threatening traumatic event. Such acute events are quite common in patients with cardiovascular illnesses (ie, a myocardial infarction, acute exacerbations of heart failure or edema). Indeed, PTSD symptoms have been described in a substantial minority of patients who had such events (10% to 25%), and have been shown to be associated with medical morbidity and with non-adherence to medications. This review summarizes available information about these symptoms in patients with cardiovascular illnesses. It also describes the importance of recognizing PTSD as a distinct psychiatric disorder (that can be addressed by specific treatments) and as an important compounding factor in studies of psychopathology in cardiovascular patients. In particular, an argument is made that the understanding of depressive disorders in patients with cardiovascular illnesses should incorporate conceptual and treatment information from the emotional trauma literature if indeed depressive and anxiety disorders are to be successfully treated in these patients. The authors conclude with a description of the challenges and promise of an effort to implement a clinical program to screen for PTSD symptoms in patients with cardiovascular illnesses, and with recommendations for future efforts.
Vagus Nerve Stimulation Therapy in a Patient with Treatment-Resistant Depression: A Case Report of Long-Term Follow-up and Battery End-of-Service
Authors: Martinez James M. , Zboyan Holly A.
Published: August 2016

This is the first case report of a patient who received long-term (69-month) adjunctive vagus nerve stimulation (VNS) therapy for treatment-resistant depression (TRD) and reached VNS battery end-of-service (EOS).The patient is a 41-year-old female with depression who entered a study of adjunctive VNS therapy for TRD. Her Hamilton Rating Scale for Depression (HAM-D) scores dropped from a mean of 33.5 (pre-implantation baseline period) to 16 at the end of the 12-week acute-phase treatment period, and then fluctuated from <7 (normal range) to scores in the moderately depressed range (∼20) during long-term follow-up. Three and one-half years after VNS implantation, the patient's HAM-D scores began to increase from a score of 18 to a peak score of 27 ∼ 16 months later (5-years post-implantation). The patient subsequently reported that she could no longer feel stimulation from the device and device interrogation 2 weeks later indicated battery EOS. The patient was hospitalized due to worsened depression, the pulse generator was replaced, and medication adjusted. HAM-D scores through the subsequent 9 months of followup returned to a pattern of fluctuations within the range noted during the long-term follow-up period prior to VNS battery EOS.
Neuroscience and Psychopharmacology into the Next Millennium
Authors: Birnbaum Robert J.
Published: August 2016

The end of the millennium provides an opportunity to review some of the common practices that were present in psychopharmacology during the 20th century. The author focuses on two approaches that have dominated research and guided the clinical application of psychopharmacologic therapeutics: the unitary clinically-based and single-lesion perspectives. The author expands upon these older formulations of neuropsychiatric disease pathogenesis and describes how the approach to psychopharmacologic research and therapeutics has changed in light of advances in the basic neurosciences. Relevant recent advances in the basic neurosciences that shed light on the pathophysiology of neuropsychiatric disease states and that guide psychopharmacologic practices are described. The use of atypical antipsychotic agents to treat schizophrenia is given as one example of the clinical applications of the approach to psychopharmacology in the next century.
Management and Pharmacotherapy of Chronic Pain Syndromes Including Opioid Pharmacotherapy
Authors: Greenfield Daniel P. , Narcessian Elizabeth
Published: August 2016

Emphasizing the importance of an interdisciplinary approach in the treatment and management of patients with chronic pain syndromes (CPS), this article reviews, first, non-pharmacologic approaches and modalities for CPS patients, and next, pharmacologic approaches for CPS patients. Flexibility and the use of multiple modalities are emphasized. The article concludes with the controversial subject of the use of long-term analgesic opioid pharmacotherapy in patients with chronic benign pain syndromes.
Neuropsychiatry of Hypersexuality
Authors: Stein Dan J. , Hugo Frans , Oosthuizen Piet , Hawkridge Susan M. , van Heerden Ben
Published: August 2016

Relatively few studies of the psychobiology of hypersexuality have been undertaken. Nevertheless, the literature does suggest the possibility of a neurobiology of hypersexuality. Three cases of hypersexual behavior are presented in the context of neuropsychiatric disorders, and the literature on this phenomenon is briefly reviewed. These case studies and the literature provide evidence that different brain systems may play a role in this disorder. Frontal lesions may be accompanied by disinhibition, including impulsive hypersexual response to external cues, while striatal lesions may be accompanied by repetitive triggering of internally generated response patterns. Temporal-limbic lesions may be accompanied by disturbances in sexual appetite itself, including change in the direction of sexual drive. These case studies demonstrate that a neurobiology of hypersexuality may prove of some heuristic value in the clinic. However, further research is required to consolidate the literature in this area.
Nutritional Contributions to the CNS Pathophysiology of HIV-1 Infection and Implications for Treatment
Authors: Baldewicz Teri T. , Brouwers Pim , Goodkin Karl , Kumar Adarsh M. , Kumar Mahendra
Published: August 2016

Nutritional deficiencies are commonplace in patients with human immunodeficiency virus type 1 (HIV-1) infection, and recent research has indicated that nutritional factors may play an important role in the pathogenesis of HIV-1 disease. Although nutritional deficiencies are unlikely to be the primary causative factor in disease progression, they may contribute to cognitive dysfunction, neurologic abnormalities, mood disturbance, and immune dysregulation associated with HIV-1 infection. Furthermore, deficiencies of specific micronutrients have been associated with increased risk of HIV-1–associated mortality. This article will briefly summarize the role of macronutrient deficiency, the interactions of specific micronutrient deficiencies with neuropsychiatrie functioning, and the role of these factors in HIV-1 disease progression. Since recent research has shown that normalization of many nutritional deficits and supplementation beyond normal levels are associated with improvements in neuropsychiatrie functioning, potential treatment implications will also be discussed.
The Cognitive-Affective Neuroscience of the Unconscious
Authors: Stein Dan J. , Solms Mark , van Honk Jack
Published: August 2016

There is an ongoing debate about how best to conceptualize the unconscious. Early psychodynamic views employed theories influenced by physics to explain clinical material, while subsequent cognitivist views relied on computational models of the mind to explain laboratory data. More recently, advances in cognitive-affective neuroscience have provided new insights into the workings of unconscious cognition and affect. We briefly review some of this recent work and its clinical implications.
Injury Increases the Risk for PTSD: An Examination of Potential Neurobiological and Psychological Mediators
Authors: Koren Danny , Hemel Deborah , Klein Ehud
Published: August 2016

A growing number of common traumatic events involve both physical and emotional injuries. In contrast to previously held beliefs, the rapidly growing body of literature shows quite convincingly that physical injury, over and above exposure to the traumatic event itself, increases rather than decreases the risk for posttraumatic stress disorder (PTSD). A pertinent question becomes how bodily injury contributes to the risk of developing PTSD. In this article, we review contemporary findings regarding the neurobiological and psychological mechanisms by which bodily injury may augment or independently contribute to chronic posttraumatic stress. In addition, we propose three theoretical pathways through which physical injury can increase the risk for PTSD. These pathways are: additive, unique, and recovery impeding. Finally, we highlight unresolved issues pertaining to each one of these pathways and propose directions for future research to address them.
The Subgenual Anterior Cingulate Cortex in Mood Disorders
Authors: Drevets Wayne C. , Savitz Jonathan , Trimble Michael
Published: August 2016

The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this “subgenual” ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended “visceromotor network” of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.
Switching, Induction of Rapid Cycling, and Increased Suicidality With Antidepressants in Bipolar Patients: Fact or Overinterpretation?
Authors: Grunze Heinz C.R.
Published: August 2016

Antidepressants constitute a central cornerstone in the treatment of depressive syndromes. In bipolar patients, however, there is an ongoing controversy about their usefulness for at least 3 decades. Early reports, mainly concerning tricyclic antidepressants, have repeatedly pointed toward unfavorable side effects on the course of the disorder, namely switching into (hypo)mania, induction of rapid cycling, and increased risk of suicide. Most evidence for both unfavorable and favorable effects has been deducted, thus far, from small studies with methodological flaws. More substantiated evidence only recently became available. From this it appears that, at least, the switch risk, and perhaps also the risk for rapid cycling and new-onset suicidality have been overinterpreted. At the same time, these new data raise doubt about the efficacy of anti-depressants as a primary-treatment choice in bipolar depression.
Brain-Derived Neurotrophic Factor: The Neurotrophin Hypothesis of Psychopathology
Authors: Stein Dan J. , Daniels Willie M.U. , Savitz Jonathan , Harvey Brian H.
Published: August 2016

While monoaminergic hypotheses of psychopathology remain popular, there has been growing interest in the role of neurotrophins in neuropsychiatric disorders. Basic laboratory work has documented the importance of neurotrophins in neuronal survival and synaptic plasticity, and a range of clinical studies has provided analogous evidence of their role in neuropathology. Work on gene variants in brain-derived neurotrophic factor, and associated changes in structural and function brain imaging, have further contributed to our understanding of this area. Much remains to be done to delineate fully the relevant mechanisms by which brain-derived neurotrophic factor and other neurotrophins contribute to psychopathology, and to develop targeted therapeutic interventions. Nevertheless, the neurotrophin hypothesis has already given impetus to a range of valuable research.
The Interplay of Neurotransmitters in Alzheimer's Disease
Authors: Francis Paul T.
Published: August 2016

Evidence exists for both cholinergic and glutamatergic involvement in the etiology of Alzheimer's disease. Acetylcholine (ACh), a neurotransmitter essential for processing memory and learning, is decreased in both concentration and function in patients with Alzheimer's disease. This deficit and other presynaptic cholinergic deficits, including loss of cholinergic neurons and decreased acetylcholinesterase activity, underscore the cholinergic hypothesis of Alzheimer's disease. The glutamatergic hypothesis links cognitive decline in patients with Alzheimer's to neuronal damage resulting from overactivation of N-methyl-D-aspartate (NMDA) receptors by glutamate. The sustained low-level activation of NMDA receptors, which are pivotal in learning and memory, may result from deficiencies in glutamate reuptake by astroglial cells in the synaptic cleft. This article reviews the roles of ACh and glutamate in Alzheimer's disease, with particular attention given to the overlap between cholinergic and glutamatergic pathways. In addition, the potential synergy between cholinesterase inhibitors and the NMDA receptor antagonist memantine in correcting neurologic abnormalities associated with Alzheimer's disease is addressed.
Formulating a Clinical Practice Care Plan for the Diagnosis and Assessment of Alzheimer's Disease
Authors: Faison Warachal Eileen
Published: August 2016

Alzheimer's disease is a devastating neurological disorder characterized by cognitive deficits, functional impairment, and often troublesome behavioral symptoms. Unfortunately, Alzheimer's disease can be difficult to diagnose at early and even moderate stages of the disease. This article outlines simple, efficient strategies for identifying patients with potential dementia. The discussion focuses on the key components of a comprehensive assessment plan, which typically involves taking the patient's history, as well as conducting cognitive testing, laboratory testing, neurologic examination, and neuroimaging to evaluate patients for Alzheimer's disease. Finally, opportunities for the improvement of care are discussed, with an emphasis on overcoming barriers to diagnosis such as time limitations and reimbursement issues.
Utilizing Advanced Imaging and Surrogate Markers Across the Spectrum of Alzheimer's Disease
Authors: Mintun Mark A.
Published: August 2016

Alzheimer's disease is a degenerative neurological condition characterized by the presence of β-amyloid plaques and neurofibrillary tangles in the limbic and neocortical regions of the brain. Pittsburgh Compound-B (PIB), a benzothiazole analog, has recently been found to specifically label amyloid deposits in positron emission tomography (PET) studies of the brain, opening the door for a wide range of applications related to Alzheimer's disease. In this article, data demonstrating the specificity of PIB as a PET tracer for β-amyloid lesions are reviewed, and the potential clinical applications of PIB PET imaging is discussed. Because amyloid plaques are common even in elderly individuals who are not suffering from dementia, the primary diagnostic function of PIB PET imaging presumably would be to rule out, rather than definitively confirm, Alzheimer's diagnoses in elderly patients. Other possible uses include monitoring plaque loads in patients receiving anti-amyloid therapy for Alzheimer's disease, as well as assessing plaque formation in unaffected individuals as a means of evaluating future Alzheimer's disease.
Idiopathic Physical Symptoms: A Common Manifestation of Psychiatric Disorders in Primary Care
Authors: Escobar Javier I. , Dìaz-Martínez Angelica , Gara Michael
Published: August 2016

Worldwide, patients with common mental disorders, such as depression and anxiety, have a tendency to present first to primary care exhibiting idiopathic physical symptoms. Typically, these symptoms consist of pain and other physical complaints that remain medically unexplained. While in the past, traditional psychopathology emphasized the relevance of somatic presentations for disorders, such as depression, in the last few decades, the “somatic component” has been neglected in the assessment and treatment of psychiatric patients. Medical specialties have come up with a variety of “fashionable” labels to characterize these patients and the new psychiatric nomenclatures, such as the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, attempt to classify these patients into a separate “somatoform disorders” category. These efforts fall short, and revisionists are asking altogether for the elimination of “somatoform disorders” from future nomenclatures.

This review emphasizes the importance of idiopathic physical symptoms to the clinical phenomenology of many psychiatric disorders, offers suggestions to the diagnostic conundrum, and provides some hints for the proper assessment and management of patients with these common syndromes.
Presidential Stroke: United States Presidents and Cerebrovascular Disease
Authors: Jones Jeffrey M. , Jones Joni L.
Published: August 2016

In the United States, more individuals suffer disability from stroke than from any other disease, and as many as 11 of the 43 presidents have been affected. In this article, the authors review the cases of the United States presidents who have had strokes, some of which have occurred while the president was in office, having a direct effect on the country.
The Efficacy and Safety of Lower Doses of Aripiprazole for the Treatment of Patients with Acute Exacerbation of Schizophrenia
Authors: Cutler Andrew J. , Marcus Ronald N. , Hardy Sterling A. , O'Donnell Amy , Carson William H. , McQuade Robert D.
Published: August 2016

Introduction

Efficacy and safety of aripiprazole administered at doses lower than those previously studied systematically were investigated in patients with acute exacerbation of schizophrenia.

Methods

In this double-blind, multicenter study, 367 patients requiring inpatient hospitalization for acute relapse of schizophrenia were randomized to one of three fixed doses of aripiprazole (2, 5, or 10 mg/day) or placebo for 6 weeks. Efficacy and safety parameters were assessed weekly. Primary outcome measure was mean change from baseline in Positive and Negative Syndrome Scale (PANSS)Total score at endpoint.

Results

Aripiprazole 10 mg/day produced statistically significantly greater improvements from baseline compared with placebo for PANSS Total at endpoint (−11.3 vs −5.3; P=.03) and at weeks 2–5. Aripiprazole 5 mg/day did not produce significantly greater improvement in PANSS Total compared with placebo at endpoint, although significant differences were seen at weeks 3–5. No statistically significant improvements compared with placebo were achieved with aripiprazole 2 mg/day at any time points. All aripiprazole doses were well tolerated. Aripiprazole was not associated with significant extrapyramidal symptoms.

Conclusion

While aripiprazole 5 mg/day warrants further study, the 10 mg/day dose provides effective and well-tolerated therapy for management of acute psychosis in patients with schizophrenia.
What is the Optimal Way to Subdivide Obsessive-Compulsive Disorder?
Authors: de Mathis Maria Alice , Diniz Juliana Belo , do Rosário Maria Conceição , Torres Albina R. , Hoexter Marcelo , Hasler Gregor , Miguel Eurípedes C.
Published: August 2016

The clinical presentation of obsessive-compulsive disorder (OCD) varies not only across patients but over the course of the disorder. This diversity indicates that OCD is a heterogeneous disorder, which may have an important impact on psychopathological, longitudinal, genetic, and treatment research. To better understand OCD heterogeneity, more homogeneous phenotypic descriptions are necessary to delimiting clinically meaningful subgroups of patients. Besides phenotypic descriptions, another method of delimiting OCD patient subgroups includes the search for endophenotypes (extended phenotypes) based on neurophysiological, immunological, genetic, neuropsychological, or neuroanatomic (neuroimaging) paradigms. This article will describe some strategies that deal with OCD heterogeneity, including the identification of more homogeneous phenotypical categories, an improved understanding of obsessive-compulsive symptom dimensions and how to use them as quantitative traits, and broadening the diagnostic boundaries of OCD to include other related conditions. The relevance and limitations of each approach are also discussed. Since the etiological mechanisms associated with the expressions of OCD are unknown, there is probably not one but several heuristic strategies to search for more homogeneous OCD subgroup, that combined may provide the most fruitful results.
The Use of Antiepileptic Drugs in Bipolar Disorders: A Review Based on Evidence From Controlled Trials
Authors: Weisler Richard H. , Cutler Andrew J. , Ballenger James C. , Post Robert M. , Ketter Terence A.
Published: August 2016

Antiepileptic drugs (AEDs) have diverse psychotropic profiles. Some AEDs have proven to be efficacious in the treatment of mood disorders, especially bipolar disorder. Others are ineffective as primary treatments but may be useful adjuncts for mood disorders or comorbid conditions. Valproate (acute mania and mixed episodes), carbamazepine (acute mania and mixed episodes), and lamotrigine (maintenance to delay recurrence) have United States Food and Drug Administration indications for the treatment of bipolar disorder. This article provides an overview of data on the use of AEDs in bipolar disorder, including acute mania and depression, prophylaxis, and rapid cycling.
The Genetics of Gambling and Behavioral Addictions
Authors: Lobo Daniela S.S. , Kennedy James L.
Published: August 2016

Behavioral addictions are considered as the repetitive occurrence of impulsive behaviors without consideration of their potential negative consequences. These addictions represent an increasing cost to society and are an important new field of research in psychiatric genetics. There has been a growing body of evidence on the familial aggregation and genetic influences on the development of behavioral addictions and mainly on pathological gambling. The aim of this article is to critically review findings of family and molecular genetic studies on behavioral addictions, focusing on pathological gambling and commenting on other disorders where appropriate. This review provides a comprehensive approach to genetic studies on behavioral addiction and points out the necessity of expanding the genetic research in this field. Future directions for genetic studies in this field are also discussed.
Problematic Internet Use: Clinical Implications
Authors: Liu Timothy , Potenza Marc N.
Published: August 2016

Impulse-control disorders have received relatively little attention from the mental health community. An increasing awareness of the prevalence and impact of these disorders is emerging. Among impulse control disorders, problematic Internet use has been considered and examined. Prevalence estimate studies indicate that problematic Internet use is experienced across geographic locations by many individuals of diverse backgrounds. This review examines problematic Internet use from epidemiological and clinical perspectives. Clinicians should be familiar with the extent of problematic Internet use and the data regarding the efficacies and tolerabilities of available treatments.
Does Obsessive-Compulsive Personality Disorder Belong Within the Obsessive-Compulsive Spectrum?
Authors: Fineberg Naomi A. , Sharma Punita , Sivakumaran Thanusha , Sahakian Barbara , Chamberlain Sam
Published: August 2016

It has been proposed that certainDiagnostic and Statistical Manual of Mental Disorders, Fourth EditionAxis I disorders share overlapping clinical features, genetic contributions, and treatment response and fall within an “obsessive-compulsive” spectrum. Obsessive-compulsive personality disorder (OCPD) resembles obsessive-compulsive disorder (OCD) and other spectrum disorders in terms of phenomenology, comorbidity, neurocognition, and treatment response.This article critically examines the nosological profile of OCPD with special reference to OCD and related disorders. By viewing OCPD as a candidate member of the obsessive-compulsive spectrum, we gain a fresh approach to understanding its neurobiology, etiology, and potential treatments.
Novel Therapeutics for Depression:L-methylfolate as a Trimonoamine Modulator and Antidepressant-Augmenting Agent
Authors: Stahl Stephen M.
Published: August 2016

Folate deficiency may increase the risk of depression and reduce the action of antidepressants. Individuals with an inherited polymorphism that reduces the efficiency of folate formation may be at high risk for folate deficiency and for major depression. Antidepressant effects have been reported when antidepressants are augmented with folic acid, folinic acid, or the centrally active L-methylfolate (known formally as (6(S)-5-methyltetrahydrofolate [MTHF]), particularly in depressed patients with folate deficiency whose major depressive episodes have failed to respond to antidepressants. The putative mechanism of action of MTHF as an augmenting agent to antidepressants is that it acts as a trimonoamine modulator (TMM), enhancing the synthesis of the three monoamines: dopamine (DA), norepinephrine (NE), and serotonin (5-HT), resulting in a boost to the efficacy of antidepressants.
Risperidone-lnduced Polydipsia and Polyphagia Associated with Galactorrhea, Abdominal Pain, and Rapid Weight Gain in an Adolescent Hispanic Female
Authors: Afzal Khalid I. , Briones David F. , DeVargas Cecilia
Published: August 2016

A 15-year-old Hispanic female was started on risperidone for new-onset psychosis. The patient responded well to the gradual dose increase but developed rapid weight gain secondary to polydipsia and polyphagia. She also begain complaining of nipple discharge and griping abdominal pain on the left lower quadrant by the third week of treatment. Her prolactin level escalated to three times normal with a weight gain of 12 pounds in 16 days. Risperidone was switched to another antipsychotic. Her prolactin level then dropped to a normal level within 7 days and she lost 7 pounds in the next 2 weeks. Her abdominal pain, galactorrhea, polydipsia, and polyphagia subsided within the first few days of the cessation of risperdione.
Hypersexuality in Inpatient Children and Adolescents: Recognition, Differential Diagnosis, and Evaluation
Authors: El-Gabalawi Fayez , Johnson Robert Arnold
Published: August 2016

We describe a 17-year-old girl with hypersexuality resulting from virilization, the latter a consequence of polycystic ovary syndrome, and we review the literature pertinent to hypersexuality in children and adults. Inappropriate sexual behavior (a common cause of disruption among children who are hospitalized for psychiatric disorders) may be caused either by hypersexuality or by simply ill-regulated behavior: a definition of hypersexuality is proposed that can be applied at the bedside (namely, sexual behaviors or fantasies that have abruptly increased in frequency by comparison with a previous baseline, are of sufficient excessiveness to disrupt expected or usual social, academic, or occupational functioning, or constitute a source of distress), so that this distinction can be made promptly, and we present a differential diagnosis for hypersexuality to direct its evaluation. Virilization does not seem to be a common cause of hypersexuality in children and adolescents, but it should not be overlooked when it does exist.The differential diagnosis of hypersexuality in adults, which we present for comparison, is much larger than it is in children.
Comorbidity with Axis I Anxiety Disorders in Remitted Psychotic Patients 1 Year After Hospitalization
Authors: Ciapparelli Antonio , Paggini Rosemma , Marazziti Donatella , Carmassi Claudia , Bianchi Maria , Taponecco Claudia , Consoli Giorgio , Lombardi Valentina , Massimetti Gabriele , Dell'Osso Liliana
Published: August 2016

Introduction

Comorbid anxiety disorders are frequently encountered in psychoses and mainly assessed during the hospitalization.

Methods

Comorbidity was investigated in 98 patients with schizophrenia, schizoaffective, or bipolar disorder, previously hospitalized for psychotic symptoms. Assessments, including Structured Clinical Interview for theDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Brief Psychiatric Rating Scale, and Clinical Global Impressions Scale, were performed during hospitalization (t0) and subsequently in a phase of remission (t1). Comorbidity was assessed at t1 only.

Results

One or more comorbid anxiety diagnoses were made in 46 (46.9%) patients. Of these, 15 (32.6%) received multiple anxiety diagnoses, while 31 (67.4%) single anxiety diagnoses. Schizophrenic patients had a rate of social anxiety disorder (SAD) higher (P<.05) than the others. Patients assessed with panic disorder or with obsessive-compulsive disorder at t1 showed significantly greater severity of illness at t0; patients with SAD demonstrated greater severity at t1. No significant differences in the rates of individual anxiety disorders were found in patients treated with typical or atypical antipsychotics or with both.

Conclusion

Anxiety disorders, particularly obsessive-compulsive disorder, panic disorder and SAD, seem to be frequently comorbid in remitted psychotic patients; SAD would be more prevalent in schizophrenia and might negatively impact the course of the illness.
The Dopaminergic Projection System, Basal Forebrain Macrosystems, and Conditioned Stimuli
Authors: Zahm Daniel S. , Trimble Michael
Published: August 2016

This review begins with a description of some problems that recently have beset an influential circuit model of fear conditioning and goes on to look at neuroanatomy that may subserve conditioning viewed in a broader perspective, including not only fear but also appetitive conditioning. The column will then focus on basal forebrain functional-anatomical systems, or macrosystems, as they have come to be called. Yet, more specific attention is then given to the relationships of the dorsal and ventral striatopallidal systems and extended amygdala with the dopaminergic mesotelencephalic projection systems, culminating with the hypothesis that all macrosystems contribute to behavioral conditioning.
Neuropsychiatric Morbidity in Adolescent and Adult Succinic Semialdehyde Dehydrogenase Deficiency Patients
Authors: Knerr Ina , Gibson K. Michael , Jakobs Cornelis , Pearl Phillip L.
Published: August 2016

Introduction:

Succinic semialdehyde dehydrogenase (SSADH) deficiency (γ-hydroxybutyric aciduria) is a rare neurometabolic disorder of γ-aminobutyric acid degradation. While neurological manifestations, such as developmental delay, are typical during infancy, limited data are available on adolescent and adult symptomatology.

Methods:

We overview the phenotype of 33 adolescents and adults (10.1–39.5 years of age, mean: 17.1 years, 48% females) with SSADH deficiency. For this purpose, we applied a database with systematic questionnaire-based follow-up data.

Results:

Sixty-six percent of patients (n=21) presented by 6 months of age, 14% from 6–12 months of age, 5% from 1–2 years of age, and 14% from 2–4 years of age, mean age at first symptoms was 11±12 months. However, mean age at diagnosis was 6.6±6.4 years of age. Presenting symptoms encompassed motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia. Eighty-two percent demonstrated behavioral problems, such as attention deficit, hyperactivity, anxiety, or aggression, and 33% had ≥3 behavior problems. Electroencephalograms showed background slowing or epileptiform discharges in 40% of patients. Treatment approaches are then summarized.

Conclusion:

The variable phenotype in SSADH deficiency suggests the likelihood that this disease may be under-diagnosed. Families of patients with SSADH deficiency should be counseled and supported regarding the anticipated persistence of various neuropsychiatric symptoms into adulthood.
Addressing Underserved Populations and Unmet Needs
Authors: Hollander Eric
Published: August 2016

In this issue of CNS Spectrums we examine some underserved populations who continue to have real unmet needs. For example, patients in forensic and correctional settings have serious psychopathology resulting in substantial morbidity and mortality, and yet human subjects concerns have led them to be very much understudied. Likewise, patients with treatment-resistant obsessive-compulsive disorder (OCD) are quite common, and yet, compared with other disorders such as schizophrenia, few resources have been devoted to addressing their substantial functional disability. Finally, cognitive dysfunction in the elderly is an enormous problem, yet little work has addressed the role of gonadal dysfunction, or male menopause, in specific cognitive deficits of the elderly.