bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability in Response to Clozapine: Potential Role of Cytochrome P450 1A2 and the Dopamine D4Receptor Gene
Authors: Özdemir Vura , Masellis Mario , Basile Vincenzo S. , Kalow Werner , Meltzer Herbert Y. , Lieberman Jeffrey A. , Kennedy James L. 
Published: August 2016

ABSTRACTClozapine is a prototype atypical antipsychotic drug and displays efficacy in 30% to 60% of schizophrenia patients who do not respond to traditional antipsychotics. There is considerable evidence supporting a concentration-response relationship for clozapine. A plasma clozapine concentration >200 to 420 ng/mL increases the probability of antipsychotic effects. Approximately 70% to 80% of variability in clozapine plasma concentration can be attributed to variability in cytochrome P450 1A2 activity. Measurement of caffeine metabolites in plasma or urine can be used as an in vivo index of cytochrome P450 1A2 activity, since caffeine is primarily eliminated by oxidative metabolism through this cytochrome P450 enzyme. Caffeine-based tests may contribute to individualization of clozapine dosages and optimization of its antipsychotic effects in schizophrenia patieents There are several lines of evidence suggesting the potential involvement of the dopamine D4 receptor in pharmacodynamic effects of clozapine. Clozapine has a 10-fold higher affinity for the dopamine D4 receptor in comparison to the D2and the D3receptors. Moreover, the free plasma fluid concentration of clozapine is comparable to its binding affinity for the D4receptor in vitro. Blockade of the D4receptor in the mesocorticolimbic region, a brain area implicated in the pathogenesis of schizophrenia, may contribute to efficacy of clozapine in negative symptoms. Moreover, the dopamine D4receptor gene(DRD4)displays an unusual degree of genetic variation (polymorphism). In a recent preliminary study, investigated the (G)nmononucleotide repeat polymorphism within the first intron of the D4gene in 50 schizophrenia patients refractory to traditional antipsychotics. These patients were prospectively followed for antipsychotic response during clozapine treatment. Analysis of variance found significant differences in antipsychotic response as demonstrated by mean change in Brief Psychiatric Rating Scale scores among the genotype panels for this polymorphism F[3,49]=4.1(P=0.01).Future studies investigating the mechanistic basis of variability in response to clozapine should focus on both pharmacokinetic and pharmacodynamic factors.
Chronic Malignant Pain in Cancer Patients
Authors: Landolfi Joseph C. 
Published: August 2016

AbstractAlthough the incidence of cancer and cancer-related deaths has declined in recent years, undertreatment of cancer-related pain continues to be a significant problem. By thoroughly assessing chronic malignant pain (CMP) as it relates to cancer and achieving a more complete understanding of the CMP syndromes experienced by cancer patients, psychiatrists and neurologists can formulate accurate diagnoses of patients' clinical pain syndromes and construct well-defined, individual management plans for each patient.
Frontal Lobe Epilepsy Presenting as a Psychotic Disorder With Delusions and Hallucinations: A Case Study
Authors: Ramsey Bonnie J. 
Published: August 2016

AbstractAlthough psychotic symptoms are a recognized manifestation of epilepsy, these are more often associated with seizures of the temporal lobe type. While 10% of children with temporal lobe epilepsy develop a psychotic disorder by adulthood, the literature does not report any cases of psychotic disorders associated with frontal lobe seizures in children. This article presents a unique case of a girl whose frontal lobe seizures were associated with delusional psychotic symptoms. Once her seizure disorder was identified through electroencephalography (EEG) and appropriate anticonvulsant therapy was initiated, her associated psychotic symptoms resolved.
Opioid Antagonists and Alcoholism Treatment
Authors: Swift Robert M. 
Published: August 2016

AbstractThe increasing evidence for a neurobiologic basis for alcoholism has spurred the search for pharmacologic agents to treat alcohol abuse. The complex set of symptoms and behaviors that characterizes alcoholism has been linked to dopaminergic and opioid neurotransmitter systems, suggesting that opioid antagonists, such as naltrexone, may alter the positive reinforcement effects and craving involved in alcoholism. Laboratory and clinical investigations of naltrexone have demonstrated the potential for this agent to reduce craving, increase the aversive effects of alcohol, decrease drinking days, and increase abstinence. While naltrexone and other opioid antagonists, such as nalmefene, may be effective components of an alcohol-treatment program, they should only be used in combination with psychosocial interventions, such as support groups and psychotherapy.
Central Nervous System Opportunistic Infections in HIV-1 Infection
Authors: Concha Mauricio , Rabinstein Alejandro 
Published: August 2016

AbstractNeurologic disease is commonly encountered in the population infected with human immunodeficiency virus type 1 (HIV-1). Although HIV-1 is responsible for many of these neurologic complications, other organisms will affect the nervous system as the immune deficiency state progresses. With the wide use of potent antiretroviral therapy, the mortality from and incidence of opportunistic infections (OIs) among persons with advanced HIV-1 infection has decreased. Nevertheless, these diseases are still seen frequently, especially among those with limited access to new antiretroviral therapies. Therefore, it remains important to recognize the most common OIs of the central nervous system (CNS) as well as primary CNS lymphoma, which will be the focus of this review.
Cognitive Effects of HIV-1 Infection
Authors: Wilkie Frances L. , Goodkin Karl , van Zuilen M. H. , Tyll Mary D. , Lecusay Robert , Edwin Tony 
Published: August 2016

AbstractThe major neurological complication of human immunodeficiency virus type 1 (HIV-1) infection is cognitive impairment, which can range in severity from a mild subclinical cognitive inefficiency to a severe dementing illness. Mild to moderate cognitive impairment is identified primarily by neuropsychological tests. The prevalence and severity of cognitive impairment associated with HIV-1 infection increases as the disease progresses. Deficits in attention, information processing speed, memory, and motor abilities can occur early in the course of HIV-1 infection, with deficits in abstraction and executive functions observed in later stages of infection. The nature of the cognitive impairment observed is thought to reflect the effects of HIV-1 infection on the integrity of subcortical or frontostriatal brain systems. Issues related to the detection of subclinical to severe cognitive impairment are discussed, along with the clinical significance of mild cognitive impairment as a significant risk factor for mortality in HIV-1 infection. The need to control for possible confounding factors that can influence test performance is also reviewed.
Lessons Learned in Deep Brain Stimulation for Movement and Neuropsychiatric Disorders
Authors: Skidmore Frank M. , Rodriguez Ramon L. , Fernandez Hubert H. , Goodman Wayne K. , Foote Kelly D. , Okun Michael S. 
Published: August 2016

ABSTRACTThe introduction of deep brain stimulation (DBS) as a treatment for medication-refractory essential tremor in the late 1980s revealed, for the first time, that “chronically” implanted brain hardware had the potential to modulate neurologic function with surprisingly low morbidity. Over time, the therapeutic promise of DBS has become evident in Parkinson's disease and dystonia. In some experienced centers, complex tremor disorders, such as posttraumatic Holmes tremor and the tremor of multiple sclerosis, are being increasingly targeted. More recently, other indications, including obsessive-compulsive disorder, Tourette's syndrome, major depression, and chronic pain, have been proposed. As the field has expanded, our knowledge about potential cognitive side effects of DBS has also expanded. This article reviews the current knowledge regarding the impact of stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's disease, and dystonia. Also discussed are the emerging targets, what is known about the cognitive sequelae of DBS, and what has been learned about the complications and therapeutic failures.
Non-Motor Aspects of Parkinson's Disease
Authors: Borek Leora L. , Amick Melissa M. , Friedman Joseph H. 
Published: August 2016

ABSTRACTParkinson's disease is primarily considered to be a movement disorder and is defined by its motor signs. Yet, the behavioral manifestations of the disease are often more debilitating than its motor complications. This review will focus on the non-motor aspects of Parkinson's disease, including mood, psychosis, cognitive, sleep, fatigue, apathy, delirium, and repetitive disorders, that may occur. The phenomenology, pathology, and treatment of the behavioral symptoms of Parkinson's disease will be discussed.
Impulse-Control Disorders in Parkinson's Disease
Authors: Ferrara Joseph M. , Stacy Mark 
Published: August 2016

ABSTRACTParkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.
Behavioral and Psychological Symptoms of Dementia and Bipolar Spectrum Disorders: Review of the Evidence of a Relationship and Treatment Implications
Authors: Dorey Jean-Michel , Beauchet Olivier , Anterion Catherine Thomas , Rouch Isabelle , Krolak-Salmon Pierre , Gaucher Jacques , Gonthier Régis , Akiskal Hagop S. 
Published: August 2016

AbstractDementia is a neuropsychiatric disorder characterized by cognitive impairment and behavioral disturbances. The behavioral and psychological symptoms of dementia (BPSD) are common, contributing to caregiver burden and premature institutionalization. Management of BPSD is complex and often needs recourse to psychotropic drugs. Though widely prescribed, there is a lack of consensus concerning their use, and serious side effects are frequent. This is particularly the case with antidepressant treatment based on the assumption that BPSD is depressive in nature. A better understanding of BPSD etiology could lead to better management strategies. We submit that some BPSD could be the consequence of both dementia and an undiagnosed comorbid bipolar spectrum disorder, or a pre-existing bipolar diathesis pathoplastically altering the clinical expression of dementia. The existence of such a relationship is based on clinical observation, as far as the high frequency of bipolar spectrum disorders in the general population, with a prevalence estimated to be between 5.4% and 8.3%, and the psychopathological similarities between BPSD and mood disorder episodes in bipolar illness. We will review the concept of the bipolar spectrum and explain BPSD before proposing clinical pointers of a possible bipolar spectrum contaminating the phenomenology of dementia, which could lead to the targeted prescription of mood-stabilizing agents in lieu of antidepressant monotherapy. These considerations are of heuristic interest in reconceptualizing the origin of the behavioral manifestations of dementia, with important implications for geriatric practice.
Muscarinic Agonists for the Treatment of Cognition in Schizophrenia
Authors: Sellin Angela K. , Shad Mujeeb , Tamminga Carol 
Published: August 2016

ABSTRACTIt is widely accepted that cholinergic activity at muscarinic receptors is required to maintain cognitive functions, including learning and memory. Memory domains are especially impaired in schizophrenia, which may explain difficulties in psychosocial rehabilitation of individuals with this illness. However, little is known about the mechanism of this impairment. To understand our current knowledge, we reviewed the literature since 1990 via a PubMed search for the terms “muscarinic”, “schizophrenia” “cognition,” “memory,” “learning,” and “agonist” in combination. We found 89 basic science/laboratory studies, case reports/series, case-control studies, cross-sectional studies, standardized controlled animal trials, standardized controlled human trials, and reviews. Although further research is required to fully understand the neuropharmacology of the cholinergic system in cognitive function in schizophrenia, we have examined the data currently available. In general, these data suggest that agonist activity at acetylcholine muscarinic type 1 (M1) receptors would enhance memory and learning in schizophrenia. We present an overview of likely side effects of muscarinic agonists. We outline the anticholinergic activity of several available antipsychotics and review the available M1muscarinic agonists.
Rationalizing Therapeutic Approaches in Alzheimer's Disease
Authors: Grossberg George T. 
Published: August 2016

AbstractDeficits in cholinergic and glutamatergic neurotransmission have been linked to the symptomatology of Alzheimer's disease, and current therapies for Alzheimer's, including cholinesterase inhibitors (ChEIs) and the N-methyl-D-aspartate receptor antagonist memantine, have been developed to compensate for these deficits. This article reviews the results of clinical trials involving agents approved by the United States Food and Drug Administration for use in the treatment of Alzheimer's disease (namely, ChEIs for mild to moderate Alzheimer's and memantine for moderate to severe Alzheimer's). In particular, the efficacy of current monotherapy strategies in the treatment of cognitive and functional symptoms of Alzheimer's disease will be addressed. In addition, data from a clinical trial examining the use of a ChEI in combination with memantine will also be discussed, as it has been hypothesized that ChEIs and memantine may offer synergistic benefits due to their distinct mechanisms of action.
An Open-Label Trial of OROS Methylphenidate in Adults with Late-Onset ADHD
Authors: Biederman Joseph , Mick Eric , Spencer Thomas , Surman Craig , Hammerness Paul , Doyle Robert , Dougherty Megan , Aleardi Megan , Schweitzer Karl 
Published: August 2016

ABSTRACTIntroductionMany adults with current impairing symptoms of attention-deficit/hyperactivity disorder (ADHD) do not report an age at onset before 7 years of age and cannot, therefore, be assigned the fullDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)diagnosis of ADHD. We hypothesized that treatment with oral-release osmotic system (OROS) methylphenidate (MPH) will be safe and efficacious for the treatment of adults with late-onset ADHD.MethodThis was a 6-week, open-label, prospective treatment study of OROS MPH monotherapy in 36 adult patients with late-onset ADHD (onset later than the required 7 years of age) using standardized instruments for diagnosis and a robust oral daily dose of up to 1.3 mg/kg/day. Symptom severity was assessed with the Adult ADHD Investigator Symptom Report Scale (AISRS) and the Clinical Global Impression (CGI) scale.ResultsSubjects reported robust current symptoms of ADHD at pre-treatment baseline (11.1±2.8DSM-IVsymptoms), but had an atypical mean age at onset of 14.2±8.6 years. Treatment with OROS MPH at an average daily dose of 78.2±29.4 mg was associated with a statistically and clinically significant reduction in ADHD symptoms relative to baseline as assessed through the AISRS (−16.4±10.5;P<.001). Using a categorical definition of response (CGI-I much or very much improved), a majority (n=26; 72%) of subjects were rated as improved at endpoint.ConclusionThese results extend previous findings in adults with full ADHD to adults meeting criteria for late-onset ADHD and support the need for further controlled clinical trials in this population.
Borderline Personality Disorder and Traits in Veterans: Psychiatric Comorbidity, Healthcare Utilization, and Quality of Life Along a Continuum of Severity
Authors: Black Donald W. , Blum Nancee , Letuchy Elena , Doebbeling Caroline Carney , Forman-Hoffman Valerie L. , Doebbeling Bradley N. 
Published: August 2016

ABSTRACTObjective:To examine the presence of borderline personality disorder (BPD) traits in Gulf War veterans, and to assess psychiatric comorbidity, health status, healthcare utilization, and quality of life (QOL) along a continuum of BPD trait severity.Method:BPD and traits were evaluated using the Schedule for Non-Adaptive and Adaptive Personality in 576 veterans who were either deployed to the Persian Gulf (1990–1991) or were on active duty though not deployed to the Gulf. Demographic and military characteristics, personal and family history, psychiatric comorbidity, and QOL were also assessed.Results:One or more BPD traits were present in 247 subjects (43%), and BPD (≥5 traits) was identified in 15 subjects (3%).The number of traits was significantly associated with age and level of education. Lifetime psychiatric comorbidity was significantly associated with the number of BPD traits present, and level of functioning, health status, healthcare utilization, social functioning, self-injurious tendencies, and military/behavioral problems.Conclusion:BPD and traits identified in Gulf War veterans were associated with significant psychiatric morbidity, poorer QOL, and increased utilization of healthcare resources. Early recognition and treatment of veterans with BPD symptoms may be warranted to minimize the burden on the healthcare system.
A Poor Metabolizer for Cytochromes P450 2D6 and 2C19: A Case Report on Antidepressant Treatment
Authors: Johnson Maria , Markham-Abedi Courtney , Susce Margaret T. , Murray-Carmichael Elaina , McCollum Stuart , de Leon Jose 
Published: August 2016

ABSTRACTScientific literature has never described a poor metabolizer for both the cytochrome P450 (CYP) 2D6 and the CYP 2C19. They are expected to be rare (<1% in different ethnic groups) and prone to adverse drug reactions with many antidepressants. In an ongoing pharmacogenetic study, after genotyping 1,576 subjects in three Kentucky state hospitals we have found one poor metabolizer for both CYP 2D6 and CYP 2C19, which corresponds to a prevalence of 0.06% (95% Cl 0.01 to 0.36).The naturalistic antidepressant treatment of this poor metabolizer for both enzymes is described in this article. As genotyping reaches clinical practice, it will be interesting to prospectively establish whether mirtazapine is a reasonable choice as an antidepressant for these patients, as the data and this case suggest.
An A-B-C Model of Habit Disorders: Hair-Pulling, Skin-Picking, and Other Stereotypic Conditions
Authors: Stein Dan J. , Chamberlain Samuel R. , Fineberg Naomi 
Published: August 2016

ABSTRACTSevere hair-pulling is characteristic of trichotillomania, an impulse control disorder not otherwise classified. Other pathological habits, including severe nail-biting and skin-picking, are also prevalent and are potentially diagnosable as stereotypic movement disorder. There is increasing awareness of the morbidity associated with these kind of habit disorders but, to date, relatively few randomized controlled trials of pharmacotherapy or psychotherapy have been undertaken. Advances in the understanding of the underlying cognitive-affective mechanisms driving stereotypies in animals and humans may ultimately lead to new approaches. An affect regulation, behavioral addiction, and cognitive control (A-B-C) approach is outlined to conceptualizing and managing these conditions.
Lamotrigine Combined with Divalproex or Lithium for Bipolar Disorder: A Case Series
Authors: Redmond James R. , Jamison Katrina L. , Bowden Charles L. 
Published: August 2016

ABSTRACTObjectiveTo assess the efficacy of lamotrigine combined with either divalproex or lithium for the treatment of bipolar disorder.IntroductionLithium and divalproex seem to be predominantly effective for manic and mixed symptoms of bipolar disorder, whereas lamotrigine may be more effective for bipolar depression than for mania. Combination therapy may provide more efficacious treatment for many patients with bipolar disorder.MethodsData from charts of adult outpatients with bipolar disorder treated with lamotrigine plus divalproex or lithium during a 3-year period were retrospectively analyzed. The Clinical Global Impressions for Bipolar Disorder scale was used to assess severity of illness at baseline (adjunct-therapy initiation) and improvement after 3 months of treatment. The safety and tolerability of the medication combinations were assessed.ResultsAfter 3 months of treatment, 26 of 39 patients (67%) receiving lamotrigine plus divalproex had a depression rating of 1 (very much improved) or 2 (much improved) compared with seven of 16 (44%) taking lamotrigine plus lithium. The mania rating was 1 or 2 for 13 of 39 (39%) patients treated with lamotrigine plus divalproex and 7 of 16 (44%) patients receiving lamotrigine plus lithium. For overall illness severity, 26 of 39 (67%) patients given lamotrigine plus divalproex had scores of 1 or 2 compared with 10 of 16 (62%) patients taking lamotrigine plus lithium. Five of 39 patients (13%) taking lamotrigine plus divalproex and 5 of 16 (31%) receiving lamotrigine plus lithium discontinued at least one part of the combination in <3 months due to adverse events.ConclusionCombination therapy with lamotrigine plus divalproex or lithium may be a valuable option for managing symptoms of bipolar disorder. The combinations were generally well tolerated and apparently effective in improving depression as well as mania.The percentage of patients showing improvement in depression was somewhat larger. Tolerability was somewhat better for lamotrigine plus divalproex in combination than for lamotrigine plus lithium. Differences in tolerability are consistent with studies indicating poorer tolerability of lithium compared with divalproex.