1,721,004 research outputs found
Leukocytosis associated with clozapine treatment: A case series and systematic review of the literature
Background and Objectives: Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia. Despite its superior efficacy profile as compared with other antipsychotics, clozapine remains underutilized. Clozapine monitoring systems clearly describe the proposed management of clozapine-induced neutropenia; however, no specific mention is made of how to interpret neutrophilic leukocytosis, despite that being a relatively frequent finding. Prescribers unfamiliar with this molecule may misjudge its clinical significance, potentially leading to untimely treatment interruption. Here, we systematically review the literature on the risk of neutrophilic leukocytosis during clozapine treatment, and describe eight additional cases among our patient cohort. Materials and Methods: We performed a systematic review of the literature on PubMed and Embase using the PRISMA 2020 guidelines, and selected all original reports describing either (1) the prevalence of neutrophilic leukocytosis during clozapine treatment, or (2) the clinical significance of neutrophilic leukocytosis. We described eight additional cases of neutrophilic leukocytosis during clozapine treatment while attending an outpatient psychiatric clinic. Results: Our research ultimately yielded the selection of 13 articles included in this systematic review. The case series highlighted the presence of stable and clinically unremarkable neutrophilia during a follow-up ranging from one to ten years. Conclusions: Existing evidence indicates that leukocytosis associated with clozapine treatment can be considered as an asymptomatic and benign condition, suggesting that no change in clozapine treatment is needed upon its detection
Pharmacogenomics and response to lithium in bipolar disorder
Aims: The present review explores the existing evidence on pharmacogenomic tests for prediction of lithium response in the treatment of bipolar disorder. We focused our research article on reports describing findings from genome-wide association studies, polygenic risk scores, and gene expression analyses associated with lithium response. Methods: We conducted a non-systematic review of studies from PubMed/Medline by using terms such as “pharmacogenomics,” “GWAS,” “gene expression,” and “lithium response.” Inclusion criteria focused on original research involving human subjects and assessing lithium response outcomes as well as in vitro studies. An extensive pearl-growing strategy was employed to further enlarge the scope of the piece by capitalizing on the knowledge of study authors on the subject. Results: The observed results, albeit promising, remain preliminary in terms of clinical relevance. Machine learning combining genetic and clinical data appears associated with moderate success in predicting lithium responsiveness. Gene expression studies and genome-wide association studies have helped identify possible targets of lithium and have the potential to support target-specific drug research. Conclusions: Pharmacogenomics may support further discoveries in precision medicine further enlarging our understanding of the underlying mechanisms of lithium for its efficacy. However, clinical applications currently appear out of reach in the near future
Current pharmacotherapeutic approaches for dysthymic disorder and persistent depressive disorder
Introduction: Persistent Depressive Disorder (PDD) is a nosological entity introduced with DSM–5, encompassing numerous different conditions including Dysthymia, recurrent Major Depressive Disorder, Double Depression and Chronic Major Depression. PDD is a particularly significant cause of disease burden in the general population. Areas covered: In the present paper, the authors explore the controversies surrounding the definition of PDD, the current approach to its treatment endorsed by the major scientific bodies, along with the available evidence on the efficacy of said treatments. Expert opinion: Clinicians need to be particularly vigilant and always gather a thorough history. In this diagnostic group, there is a relevant risk of having an undiagnosed Bipolar Disorder as affected individuals typically fail to recognize the pathological components of hypomanic episodes. In this setting, it is crucial to reconsider the diagnosis and to frequently verify compliance with the treatment plan. Numerous technological advances, particularly in the neuroimaging field, offer new insight and new challenges in defining the pathophysiological mechanisms of depressive syndromes. In the future, these advances may offer guidance towards an improved treatment approach and diagnostic process
Impulsivity, aggressivity and mood disorders: a narrative review
Aggressiveness and Impulsivity represent clinically significant elements in the context of coexisting mental disorders and have been extensively studied in the context of mood disorders. Considering their significant impact on prognostic trajectories, accruing evidence suggests the need to consider these elements in the development of specific treatment strategies tailored to the specific requirements at the individual patient level and in the specific context where care is delivered. In the present narrative review, we propose to the reader a selection of study articles deemed relevant to the discussion of this complex subject, with a critical analysis of the available evidence regarding empiric evidence for the association of aggressiveness and impulsivity with a focus on bipolar disorder and major depressive disorder. A brief overview of reports deemed relevant to the discussion for some of the possible biological basis for this phenomena is also outlined, offering a selection of studies based on the study authors' judgement
Pharmacological management of depression in patients with multiple sclerosis
The pharmacotherapeutic management of depression in patients with multiple sclerosis (MS) is a matter of debate that cannot be decided from the evidence available in the current literature. Therefore, its management essentially relies on the clinical experience of the prescribing clinician rather than on evidence-based approaches. Areas covered: This review provides a clinically oriented critical perspective on the connection between MS and major depressive disorder (MDD) or depression associated with bipolar disorder (BD), focusing on its optimal pharmacotherapy. Both clinical and pharmacological considerations are accounted in order to promote rational pharmacotherapy, both in terms of efficacy and tolerability. Expert opinion: Despite its clinical burden and relatively frequent occurrence, the interplay of MS and depression still requires further controlled trials to better clarify the appropriate pharmacotherapy across varying 'diseases categories' of MS itself, as well as discriminating between depressive symptoms that do not necessarily reach the threshold of either MDD or BD. Additional insight into new mood-tolerated neurological pharmacotherapy for MS is likewise warranted toward a more effective, immune- and patient-tailored pharmacotherapy, while promoting innovation in drug design, with the ultimate goal of enhancing the overall quality life of the affected individual, his/her caregivers, and to reduce the associated economic and social burden
Psychiatric assessment in image-based sexual abuse case: a case report on imputability in personality disorder with narcissistic traits
Objectives: Crimes committed on the Internet and social networks are rising, and the phenomenon is complex. Knowledge of context would be useful for professionals in cases that need psychiatric assessment. We report on a case of a 27-year-old young adult who is accused of image-based sexual abuse and other crimes, for whom the examining judge requested psychiatric assessment. Methods: We conducted anamnestic collection (family, physiological and pathological, psychiatric, and toxicological), direct evaluation of the examinee, assessment of acquired health records, psychodiagnostic tests (i.e. graphic tests: Machover test, Koch test), Montreal Cognitive Assessment, Minnesota Multiphasic Personality Inventory 2, Pathological Narcissism Inventory, State-Trait Anger Expression Inventory 2, Toronto Alexithymia Scale, Thematic Apperception Test. Results: The clinical forensic assessment led to a diagnosis of Unspecified Personality Disorder (predominantly narcissistic traits) according to the DSM-5 criteria. Direct assessment showed a tendency to simulate or exaggerate symptoms, confirmed by the invalidation of the MMPI-2. In addition, the psychodiagnostic test showed a tendency to aggressive behavior and difficulty in identifying and describing emotions and feelings (alexithymia). Conclusions: This case highlights the importance of being familiar with the context of the Internet and social networks, where a rising number of crimes are committed. Forensic psychiatrists will be increasingly involved in evaluating cases related to the online world, which requires a basic knowledge of its characteristics and dynamics
Anatomical distribution and expression of CYP in humans: Neuropharmacological implications
The cytochrome P450 (CYP450) superfamily is responsible for the metabolism of most xenobiotics and pharmacological treatments generally used in clinical settings. Genetic factors as well as environmental determinants acting through fine epigenetic mechanisms modulate the expression of CYP over the lifespan (fetal vs. infancy vs. adult phases) and in diverse organs. In addition, pathological processes might alter the expression of CYP. In this selective review, we sought to summarize the evidence on the expression of CYP focusing on three specific aspects: (a) the anatomical distribution of the expression in body districts relevant in terms of drug pharmacokinetics (liver, gut, and kidney) and pharmacodynamics, focusing for the latter on the brain, since this is the target organ of psychopharmacological agents; (b) the patterns of expression during developmental phases; and (c) the expression of CYP450 enzymes during pathological processes such as cancer. We showed that CYP isoforms show distinct patterns of expression depending on the body district and the specific developmental phases. Of particular relevance for neuropsychopharmacology is the complex regulatory mechanisms that significantly modulate the complexity of the pharmacokinetic regulation, including the concentration of specific CYP isoforms in distinct areas of the brain, where they could greatly affect local substrate and metabolite concentrations of drugs
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The Role of Gut Microbiota in the High-Risk Construct of Severe Mental Disorders: A Mini Review
Severe mental disorders (SMD) are highly prevalent psychiatric conditions exerting an enormous toll on society. Therefore, prevention of SMD has received enormous attention in the last two decades. Preventative approaches are based on the knowledge and detailed characterization of the developmental stages of SMD and on risk prediction. One relevant biological component, so far neglected in high risk research, is microbiota. The human microbiota consists in the ensemble of microbes, including viruses, bacteria, and eukaryotes, that inhabit several ecological niches of the organism. Due to its demonstrated role in modulating illness and health, as well in influencing behavior, much interest has focused on the characterization of the microbiota inhabiting the gut. Several studies in animal models have shown the early modifications in the gut microbiota might impact on neurodevelopment and the onset of deficits in social behavior corresponding to distinct neurosignaling alterations. However, despite this evidence, only one study investigated the effect of altered microbiome and risk of developing mental disorders in humans, showing that individuals at risk for SMD had significantly different global microbiome composition than healthy controls. We then offer a developmental perspective and provided mechanistic insights on how changes in the microbiota could influence the risk of SMD. We suggest that the analysis of microbiota should be included in the comprehensive assessment generally performed in populations at high risk for SMD as it can inform predictive models and ultimately preventative strategies
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