scholarly journals The neurobiology of treatment-resistant schizophrenia: paths to antipsychotic resistance and a roadmap for future research

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Steven G. Potkin ◽  
John M. Kane ◽  
Christoph U. Correll ◽  
Jean-Pierre Lindenmayer ◽  
Ofer Agid ◽  
...  
Keyword(s):  
Clinical Problem ◽  
Therapeutic Interventions ◽  
First Episode ◽  
Future Research ◽  
Treatment Resistant ◽  
Adequate Dose ◽  
Clinical Trial Designs ◽  
New Treatments ◽  
Dopamine Supersensitivity ◽  
And Oxidative Stress

AbstractTreatment-resistant schizophrenia (TRS), the persistence of positive symptoms despite ≥2 trials of adequate dose and duration of antipsychotic medication with documented adherence, is a serious clinical problem with heterogeneous presentations. TRS can vary in its onset (at the first episode of psychosis or upon relapse), in its severity, and in the response to subsequent therapeutic interventions (i.e., clozapine, electroconvulsive therapy). The heterogeneity of TRS indicates that the underlying neurobiology of TRS may differ not only from treatment-responsive schizophrenia but also among patients with TRS. Several hypotheses have been proposed for the neurobiological mechanisms underlying TRS, including dopamine supersensitivity, hyperdopaminergic and normodopaminergic subtypes, glutamate dysregulation, inflammation and oxidative stress, and serotonin dysregulation. Research supporting these hypotheses is limited in part by variations in the criteria used to define TRS, as well as by the biological and clinical heterogeneity of TRS. Clinical trial designs for new treatments should be informed by this heterogeneity, and further clinical research is needed to more clearly understand the underlying neurobiology of TRS and to optimize treatment for patients with TRS.

Differential predictors of critical comments and emotional over-involvement in first-episode psychosis

2008 ◽  
Vol 40 (1) ◽  
pp. 63-72 ◽  
Author(s):  
M. Álvarez-Jiménez ◽  
J. F. Gleeson ◽  
S. M. Cotton ◽  
D. Wade ◽  
K. Crisp ◽  
...  
Keyword(s):  
Family Stress ◽  
First Episode Psychosis ◽  
Therapeutic Interventions ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Future Research ◽  
Burden Of Care ◽  
Related Factors ◽  
Episode Psychosis

BackgroundLittle research has focused on delineating the specific predictors of emotional over-involvement (EOI) and critical comments (CC) in the early course of psychosis. The purpose of this study was to investigate the differential relationships of EOI and CC with relevant predictors in relatives of first-episode psychosis (FEP) patients.MethodBaseline patient-related factors including psychotic symptoms, depression and duration of untreated psychosis (DUP) and carer attributes comprising CC, EOI, burden of care and carers' stress and depression were assessed in a cohort of 63 remitted FEP patients and their relatives. Carers were reassessed at 7 months follow-up.ResultsBaseline analysis showed that EOI was more strongly correlated with family stress compared with CC, whereas CC yielded a stronger association with DUP than EOI. Carers' CC at follow-up was not significantly predicted by either baseline family stress, burden of care or patient-related variables. Conversely, baseline EOI predicted both family stress and burden of care at 7 months follow-up. Finally, family burden of care at follow-up was a function of baseline EOI and patients' depressive symptoms.ConclusionsThis study provides preliminary support to the postulate that EOI and CC may be influenced by separate factors early in the course of psychosis and warrant future research and therapeutic interventions as separate constructs. Implications for family interventions in the early phase of psychosis and the prevention of CC and EOI are discussed.

Risk factors associated with treatment-resistant schizophrenia in first-episode psychosis

2017 ◽  
Vol Ano 7 ◽  
pp. 8-12
Author(s):  
Ana Beatriz de Oliveira Assis ◽  
Jayse Gimenez Pereira Brandão ◽  
Pedro Otávio Piva Espósito ◽  
Osmar Tessari Junior ◽  
Bruno Berlucci Ortiz
Keyword(s):  
Risk Factors ◽  
First Episode Psychosis ◽  
First Episode ◽  
Treatment Resistant ◽  
Factors Associated ◽  
Syndrome Scale ◽  
Episode Psychosis ◽  
Negative Syndrome

Objetivo: Ainda não está claro quais são os fatores de risco para a esquizofrenia resistente ao tratamento (ERT) em primeiro episódio psicótico (PEP). O objetivo deste trabalho é investigar indicadores de risco para ERT em PEP. Métodos: Foram selecionados 53 pacientes em primeiro episódio psicótico, com diagnóstico de esquizofrenia, que deram entrada à enfermaria de psiquiatria do Hospital das Clínicas Luzia de Pinho Melo entre 2011 e 2015. Ao ser admitido na enfermaria, o paciente era avaliado com a Escala de Sintomas para as Síndromes Positiva e Negativa (Positive and Negative Syndrome Scale – PANSS) e recebia tratamento inicial por 4 semanas. Caso sua resposta fosse inferior a 40% de redução na PANSS, o antipsicótico era trocado, e as escalas eram aplicadas novamente após mais 4 semanas. Após a falha com dois antipsicóticos, em doses plenas, por 4 semanas cada, a clozapina era introduzida, e o paciente era considerado ERT. Uma regressão logística foi aplicada onde sexo, idade de início, tempo de doença não tratada, uso de substâncias, avaliação global do funcionamento inicial e PANSS inicial total foram inseridos como variáveis independentes, e ERT foi inserida como variável dependente. Resultados: Tempo de doença não tratada apresentou significância de p = 0,038 e Exp (B) = 4,29, enquanto que PANSS total apresentou p = 0,012 e Exp (B) = 1,06. Conclusão: Identificar os fatores associados à resistência precoce ao tratamento poderia permitir aos clínicos evitar o atraso na introdução da clozapina e prevenir um pior prognóstico para esses pacientes.

The Role of Resilience in Sexual and Gender Minority Mental Health

2020 ◽  
pp. 428-442
Author(s):  
Dawn M. Szymanski ◽  
Kirsten A. Gonzalez
Keyword(s):  
Mental Health ◽  
Minority Stress ◽  
Quantitative Research ◽  
Social Stigma ◽  
Therapeutic Interventions ◽  
Future Research ◽  
Minority Mental Health ◽  
And Gender ◽  
Structural Levels

Many lesbian, gay, bisexual, transgender, and queer (LGBTQ) persons are able to persevere and flourish despite pervasive social stigma and minority stress based on their sexual orientation and gender identity. This chapter reviews the research on LGBTQ resilience that can occur at individual, interpersonal/family, community, and contextual/structural levels. The authors describe qualitative research that has examined pathways to resilience and positive LGBTQ identity. The authors also review quantitative research on LGBTQ resilience via mediator, moderator, and moderated mediation models. Variables are described that have been found to explain or buffer the links between external and internalized minority stressors and mental health outcomes. The authors review the small but growing body of research that has begun to examine the efficacy of therapeutic interventions aimed at promoting LGBTQ resilience. Limitations are discussed and directions for future research are suggested.

scholarly journals Efficacy of Phytocannabinoids in Epilepsy Treatment: Novel Approaches and Recent Advances

2021 ◽  
Vol 18 (8) ◽  
pp. 3993
Author(s):  
Aaron M. Farrelly ◽  
Styliani Vlachou ◽  
Konstantinos Grintzalis
Keyword(s):  
Therapeutic Potential ◽  
Significant Proportion ◽  
Future Research ◽  
Specific Reference ◽  
Undesirable Side Effect ◽  
Treatment Resistant ◽  
Current Review ◽  
Epilepsy Treatment ◽  
Clinical Environments

Epilepsy is a neurological disorder mainly characterised by recurrent seizures that affect the entire population diagnosed with the condition. Currently, there is no cure for the disease and a significant proportion of patients have been deemed to have treatment-resistant epilepsy (TRE). A patient is deemed to have TRE if two or more antiepileptic drugs (AEDs) fail to bring about seizure remission. This inefficacy of traditional AEDs, coupled with their undesirable side effect profile, has led to researchers considering alternative forms of treatment. Phytocannabinoids have long served as therapeutics with delta-9-THC (Δ9-THC) receiving extensive focus to determine its therapeutic potential. This focus on Δ9-THC has been to the detriment of analysing the plethora of other phytocannabinoids found in the cannabis plant. The overall aim of this review is to explore other novel phytocannabinoids and their place in epilepsy treatment. The current review intends to achieve this aim via an exploration of the molecular targets underlying the anticonvulsant capabilities of cannabidiol (CBD), cannabidavarin (CBDV), delta-9-tetrahydrocannabivarin (Δ9-THCV) and cannabigerol (CBG). Further, this review will provide an exploration of current pre-clinical and clinical data as it relates to the aforementioned phytocannabinoids and the treatment of epilepsy symptoms. With specific reference to epilepsy in young adult and adolescent populations, the exploration of CBD, CBDV, Δ9-THCV and CBG in both preclinical and clinical environments can guide future research and aid in the further understanding of the role of phytocannabinoids in epilepsy treatment. Currently, much more research is warranted in this area to be conclusive.

scholarly journals Ketamine-Assisted Psychotherapy for PTSD Related to Racial Discrimination

2021 ◽  
pp. 153465012199089
Author(s):  
Mailae Halstead ◽  
Sara Reed ◽  
Robert Krause ◽  
Monnica T. Williams
Keyword(s):  
Therapeutic Interventions ◽  
Traumatic Experiences ◽  
Social Avoidance ◽  
Functional Analytic Psychotherapy ◽  
Treatment Resistant ◽  
Psychotherapeutic Treatment ◽  
Presenting Symptoms ◽  
Self Talk ◽  
Effective Use

Current research suggests that ketamine-assisted psychotherapy has benefit for the treatment of mental disorders. We report on the results of ketamine-assisted intensive outpatient psychotherapeutic treatment of a client with treatment-resistant, posttraumatic stress disorder (PTSD) as a result of experiences of racism and childhood sexual abuse. The client’s presenting symptoms included hypervigilance, social avoidance, feelings of hopelessness, and intense recollections. These symptoms impacted all areas of daily functioning. Psychoeducation was provided on how untreated intergenerational trauma, compounded by additional traumatic experiences, potentiated the client’s experience of PTSD and subsequent maladaptive coping mechanisms. Ketamine was administered four times over a 13-day span as an off-label, adjunct to psychotherapy. Therapeutic interventions and orientations utilized were mindfulness-based cognitive therapy (MBCT) and functional analytic psychotherapy (FAP). New skills were obtained in helping the client respond effectively to negative self-talk, catastrophic thinking, and feelings of helplessness. Treatment led to a significant reduction in symptoms after completion of the program, with gains maintained 4 months post-treatment. This case study demonstrates the effective use of ketamine as an adjunct to psychotherapy in treatment-resistant PTSD.

scholarly journals Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma

2021 ◽  
Author(s):  
Sinan Xiong ◽  
Wee-Joo Chng ◽  
Jianbiao Zhou
Keyword(s):  
Oxidative Stress ◽  
Multiple Myeloma ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Fate ◽  
Stress Responses ◽  
Plasma Cells ◽  
Reactive Oxygen Species Generation ◽  
Future Research ◽  
And Oxidative Stress

AbstractUnder physiological and pathological conditions, cells activate the unfolded protein response (UPR) to deal with the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. Multiple myeloma (MM) is a hematological malignancy arising from immunoglobulin-secreting plasma cells. MM cells are subject to continual ER stress and highly dependent on the UPR signaling activation due to overproduction of paraproteins. Mounting evidence suggests the close linkage between ER stress and oxidative stress, demonstrated by overlapping signaling pathways and inter-organelle communication pivotal to cell fate decision. Imbalance of intracellular homeostasis can lead to deranged control of cellular functions and engage apoptosis due to mutual activation between ER stress and reactive oxygen species generation through a self-perpetuating cycle. Here, we present accumulating evidence showing the interactive roles of redox homeostasis and proteostasis in MM pathogenesis and drug resistance, which would be helpful in elucidating the still underdefined molecular pathways linking ER stress and oxidative stress in MM. Lastly, we highlight future research directions in the development of anti-myeloma therapy, focusing particularly on targeting redox signaling and ER stress responses.

scholarly journals Treatment-resistant schizophrenia characterised by dopamine supersensitivity psychosis and efficacy of asenapine

2021 ◽  
Vol 14 (4) ◽  
pp. e242495
Author(s):  
Nagara Takao ◽  
Toshiya Murai ◽  
Hironobu Fujiwara
Keyword(s):  
Animal Studies ◽  
Significant Proportion ◽  
Antipsychotic Treatment ◽  
High Dose ◽  
Receptor Density ◽  
Treatment Resistant ◽  
Psychomotor Activity ◽  
Receptor Blockers ◽  
Dopamine Supersensitivity

Dopamine supersensitivity psychosis (DSP) frequently arises with long-term antipsychotic treatment and accounts for a significant proportion of treatment-resistant schizophrenia. The mechanism underlying DSP is thought to be a compensatory increase in dopamine receptor density in the striatum caused by long-term antipsychotic treatment. Previous animal studies have reported that antipsychotics increase serotonin 5-HT2A receptor density in the striatum and that 5-HT2A receptor blockers suppress dopamine-sensitive psychomotor activity, which may be linked to the pathophysiology of DSP. In this paper, we describe a patient who was hospitalised with treatment-resistant schizophrenia. Following treatment with high-dose antipsychotic polypharmacy for 10 weeks, the patient experienced worsening of psychotic and extrapyramidal symptoms. The patient was then started on second-generation antipsychotic asenapine while other antipsychotics were tapered off, resulting in improvement of these symptoms. Retrospectively, we presumed that the high-dose antipsychotic polypharmacy caused DSP, which was effectively treated by the potent 5-HT2A receptor antagonism of asenapine.

scholarly journals Docosahexaenoic Acid-Acylated Astaxanthin Esters Exhibit Superior Renal Protective Effect to Recombination of Astaxanthin with DHA via Alleviating Oxidative Stress Coupled with Apoptosis in Vancomycin-Treated Mice with Nephrotoxicity

Marine Drugs ◽  
2021 ◽  
Vol 19 (9) ◽  
pp. 499
Author(s):  
Hao-Hao Shi ◽  
Ying Guo ◽  
Li-Pin Chen ◽  
Cheng-Cheng Wang ◽  
Qing-Rong Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Fatty Acid ◽  
Docosahexaenoic Acid ◽  
Kidney Injury ◽  
Clinical Problem ◽  
Kidney Dysfunction ◽  
Serum Biochemical ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

Prevention of acute kidney injury caused by drugs is still a clinical problem to be solved urgently. Astaxanthin (AST) and docosahexaenoic acid (DHA) are important marine-derived active ingredients, and they are reported to exhibit renal protective activity. It is noteworthy that the existing forms of AST in nature are mainly fatty acid-acylated AST monoesters and diesters, as well as unesterified AST, in which DHA is an esterified fatty acid. However, no reports focus on the different bioactivities of unesterified AST, monoesters and diesters, as well as the recombination of DHA and unesterified AST on nephrotoxicity. In the present study, vancomycin-treated mice were used to evaluate the effects of DHA-acylated AST monoesters, DHA-acylated AST diesters, unesterified AST, and the recombination of AST and DHA in alleviating nephrotoxicity by determining serum biochemical index, histopathological changes, and the enzyme activity related to oxidative stress. Results found that the intervention of DHA-acylated AST diesters significantly ameliorated kidney dysfunction by decreasing the levels of urea nitrogen and creatinine, alleviating pathological damage and oxidative stress compared to AST monoester, unesterified AST, and the recombination of AST and DHA. Further studies revealed that dietary DHA-acylated AST esters could inhibit the activation of the caspase cascade and MAPKs signaling pathway, and reduce the levels of pro-inflammatory cytokines. These findings indicated that the administration of DHA-acylated AST esters could alleviate vancomycin-induced nephrotoxicity, which represented a potentially novel candidate or therapeutic adjuvant for alleviating acute kidney injury.

scholarly journals Victims and Perpetrators of Child Sexual Abuse: Abusive Contact and Penetration Experiences

2021 ◽  
Vol 18 (18) ◽  
pp. 9593
Author(s):  
Marta Ferragut ◽  
Margarita Ortiz-Tallo ◽  
Maria J. Blanca
Keyword(s):  
Gender Differences ◽  
Sexual Abuse ◽  
Child Sexual Abuse ◽  
Early Detection ◽  
Physical Contact ◽  
First Episode ◽  
Future Research ◽  
Male Victims ◽  
Research And Practice ◽  
Female Perpetrator

Child sexual abuse (CSA) includes abusive contact experiences, which habitually impact the victim’s whole life. This study aims to analyze the characteristics of six CSA experiences with physical contact, including penetration, in a representative sample of the Spanish population. Participants were 1071 Spanish adults (53% males; Mage: 45.37) who completed the Child Sexual Abuse Experiences Questionnaire. The victim’s age at the first episode, the perpetrator’s characteristics, and the number of times that each experience occurred were analyzed, taking into account gender differences. Results were reported for every experience independently. The most prevalent age at the first experience was from 6 years old onwards, but with differences in some experiences. The abuses usually happened more than once, committed by the same person. The most prevalent perpetrator is a male, although a female perpetrator is more prevalent in male victims. Most of the abuses were committed by an adult acquaintance, a strange adult, and other minors, with some gender differences. The implications of the results concerning every CSA experience are discussed, highlighting their value for future research and practice, the design of preventive programs, and early detection of CSA.

scholarly journals Monocytic Subsets and Their Signature Genes Differentially Impact Cortex and Cognition in First-Episode Schizophrenia

2021 ◽  
Author(s):  
Song Chen ◽  
Keerthana Chithanathan ◽  
Fengmei Fan ◽  
Meihong Xiu ◽  
Hongzhen Fan ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Transmembrane Protein ◽  
Visual Learning ◽  
Protein A ◽  
Occipital Cortex ◽  
First Episode ◽  
Future Research ◽  
Cross Sectional ◽  
Signature Genes ◽  
First Episode Schizophrenia

Accumulating evidence supports involvement of innate immunity in the pathophysiology of schizophrenia. Monocytes are a highly heterogeneous population, subcategorized into classical (CD14++CD16-), intermediate (CD14++CD16+) and nonclassical subsets (CD14+CD16++). How monocytic subsets may shape brain structures and functions remains unclear. The primary goal of this cross-sectional study was to investigate the inter-relationships among monocytic subsets and their specific transcriptomic profiles, cerebral cortical thickness, and cognitive functions in first-episode schizophrenia (FES) patients. We performed whole-blood RNA sequencing (RNAseq) in 128 FES patients and 111 healthy controls (HCs) along with MATRICS Consensus Cognitive Battery (MCCB) measurement, as well as neuroimaging and flow cytometry among partial participants. RNAseq revealed significantly changed expressions of 54 monocytic signature genes in FES patients compared to HCs, especially for intermediate and nonclassical monocytic subsets, with the most outstanding alterations being downregulated S100 Calcium Binding Protein A (S100A) and upregulated Interferon Induced Transmembrane Protein (IFITM) family members, respectively. The percentage of nonclassical monocytes was decreased in FES patients. Cortical thicknesses and MCCB performance were expectantly reduced in FES patients too. Interestingly, negative inter-relationships of monocytic signature genes with both cortical thicknesses and cognition were found in HCs, which were weakened or even reversed in FES patients. Furthermore, the lateral occipital cortex fully mediated the negative effect of a classical monocytic gene Ribonuclease A Family Member 2 (RNASE2) on visual learning in patient group. This study suggests that monocytic dysfunctions play an essential role in cognitive deficit of schizophrenia, and their subtypes should be considered in future research.

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