Modern trends in pharmacopsychiatry最新文献

{"title":"The Link between Refractoriness and Neuroprogression in Treatment-Resistant Bipolar Disorder.","authors":"Isabelle E Bauer,&nbsp;Jair C Soares,&nbsp;Salih Selek,&nbsp;Thomas D Meyer","doi":"10.1159/000470803","DOIUrl":"https://doi.org/10.1159/000470803","url":null,"abstract":"<p><p>Treatment refractoriness remains one of the biggest challenges in the field of bipolar disorder (BD) as treatments are often suboptimal or unsatisfactory. Recent evidence points towards a potential link between the progressively evolving nature of BD, increased inflammation, and reduced treatment response. There are several medications and other somatic treatments available, but remission rates are low, and medication compliance is still problematic. Psychotherapeutic techniques appear to be promising in several disease states and in relapse prevention, but additional research is needed to determine who will benefit from what strategy the most. Current knowledge on the link between neuroprogression in BD and poor treatment response promotes the use of anti-inflammatory and neuroprotective strategies in the early phases of BD. In the later stages of BD, mood stabilization and medication adherence would be essential in preventing additional brain changes and loss of cognitive reserve. Additional large-scale, longitudinal, and methodologically robust studies are urgently needed to develop effective therapeutic interventions for treatment-resistant BD.</p>","PeriodicalId":74212,"journal":{"name":"Modern trends in pharmacopsychiatry","volume":" ","pages":"10-26"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000470803","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35193610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Contribution of Adult Hippocampal Neurogenesis to the Progression of Psychiatric Disorders.","authors":"Rachel A Kohman,&nbsp;Justin S Rhodes","doi":"10.1159/000470812","DOIUrl":"https://doi.org/10.1159/000470812","url":null,"abstract":"<p><p>New neurons are continuously formed in the adult hippocampus of the human, nonhuman primate, and rodent throughout life though rates of neurogenesis precipitously decline with age to near zero levels at the end of the natural life span. Since its discovery in the 1960s, a large number of studies have documented numerous environmental and genetic factors which regulate adult neurogenesis. Chief among the positive regulators of neurogenesis are exercise and antidepressant drugs. Chief among the negative regulators of neurogenesis besides age are stress and inflammation. To the extent that many psychiatric disorders are comorbid with or causally related to stress and inflammation, decreased neurogenesis could be a partial contributor to the pathophysiology of the disorders. However, the functional significance of new neurons in behavior has yet to be established and is currently a hotly debated topic. Therefore, it is not clear whether changes in neurogenesis that occur alongside psychiatric illnesses are a cause or a consequence of the mediating factors such as stress, drug abuse, and inflammation, which are complexly involved in the disorders. It will be important moving forward to use modern technologies capable of instantaneously inactivating cohorts of new neurons to test their functional significance in behavior and the etiology of mental illnesses.</p>","PeriodicalId":74212,"journal":{"name":"Modern trends in pharmacopsychiatry","volume":" ","pages":"124-151"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000470812","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35193618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprogression and Immune Activation in Major Depressive Disorder.","authors":"Jeffrey H Meyer","doi":"10.1159/000470804","DOIUrl":"https://doi.org/10.1159/000470804","url":null,"abstract":"<p><p>Traditionally, the neurobiology of major depressive disorder (MDD) has been largely considered from the perspective of the state of major depressive episodes (MDE) versus being in remission, but the current accumulation of disease markers, largely acquired cross-sectionally, is strongly suggestive of neuroprogressive aspects of MDD. This chapter focuses on the changes in disease markers involved in the reorganization of the nervous system in MDD, including the translocator protein (TSPO; an index of microglial activation), glial fibrillary acidic protein (GFAP; an index of astroglial activation), [11C]harmine (a marker of monoamine oxidase A; MAO-A), and several other indices (metabotropic glutamate receptor 5 [mGluR5], excitatory amino acid transporters, and magnetic resonance imaging spectroscopy measurements) of glutamate dysregulation. These are markers of processes involved in immune activation, oxidative stress, and chronic glucocorticoid exposure. Positron emission tomography studies of the TSPO distribution volume, a marker of microglial activation, provide strong evidence for microglial activation throughout the gray matter of the brain during MDE of MDD. In postmortem studies, GFAP reductions in the orbitofrontal cortex, anterior cingulate cortex, and hippocampus indicate a deficit in reactive astroglia. Elevated MAO-A levels are present throughout the gray matter of the brain, including affect-modulating brain regions, starting in high-risk states for MDE such as the early postpartum period, perimenopause, heavy cigarette smoking, heavy alcohol intake, and prior to MDE recurrence. Evidence is accumulating for glutamate dysregulation, with some findings of reduced glutamate transporter density in the orbitofrontal cortex, and decreased mGluR5 density. Collectively, these changes suggest an imbalance in the immune system with increased microglial activation and decreased astroglial activation, continued elevations of the MAO-A level, and, likely, the development of extracellular glutamate dysregulation. Many of these imbalances involve processes implicated in increased oxidative stress, apoptosis, and neurodegeneration. Future studies are required to assess potential therapeutics targeting these processes to ameliorate progression of MDD.</p>","PeriodicalId":74212,"journal":{"name":"Modern trends in pharmacopsychiatry","volume":" ","pages":"27-36"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000470804","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35194020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprogression in Schizophrenia and Psychotic Disorders: The Possible Role of Inflammation.","authors":"Norbert Müller","doi":"10.1159/000470802","DOIUrl":"https://doi.org/10.1159/000470802","url":null,"abstract":"<p><p>Schizophrenia is a disorder that shows a progressive course in 30-50% of the people concerned. The biology of chronification and progression is unclear. Genetic aspects may play a role, but details are unresolved. The fact that immune-mediated and autoimmune disorders such as rheumatoid arthritis or multiple sclerosis have a very similar course as schizophrenia has focused the interest on the immunopathogenesis of schizophrenia. A clear immune marker for neuroprogression in schizophrenia or psychosis could not be identified up to now, but a proinflammatory immune state (increased markers of cellular immunity) is regularly found in schizophrenia, e.g., increased levels of cytokines such as interleukin-6 (IL-6). Moreover, the tryptophan/kynurenine metabolism is regulated via pro- and anti-inflammatory cytokines and is closely related to the glutamatergic neurotransmission. Certain molecules of this metabolism, such as quinolinic acid or 3OH-kynurenine, have neurotoxic effects and seem to play a role in chronification. Studies with immune/anti-inflammatory-based therapeutic approaches show that acuity or chronicity of the inflammation influence the outcome of therapeutic interventions.</p>","PeriodicalId":74212,"journal":{"name":"Modern trends in pharmacopsychiatry","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000470802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35194196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodegeneration, Neuroregeneration, and Neuroprotection in Psychiatric Disorders.","authors":"Siu W Tang,&nbsp;Daiga M Helmeste,&nbsp;Brian E Leonard","doi":"10.1159/000470811","DOIUrl":"https://doi.org/10.1159/000470811","url":null,"abstract":"<p><p>Prevention of deterioration of brain function over time is important in the long-term management of chronic brain disorders such as dementia, schizophrenia, and mood disorders. Although the possibility of neurogenesis in the adult human brain is attractive, and there are psychiatric drugs proven to be effective inducers of neurogenesis in animals, we have yet to see their utility in clinical practice. The terms neurodegeneration and neuroregeneration are often used in a nonspecific manner. Neuroregeneration may mean neurogenesis, dendritogenesis, spinogenesis, or axonogenesis. The term \"neuroprotection\" is attractive clinically and may involve different mechanisms. Many causative and protective factors of neurodegeneration and neuroregeneration have been proposed. However, the specificity of these factors and agents and differential neuronal vulnerability factors have generally been ignored in past studies. It is also hard to separate disease-modifying from \"neuroprotective\" effects of a drug. The application of stringent long-term neuroanatomical, neurochemical, neurophysiological, and therapeutic efficacy criteria should improve future research in this important area.</p>","PeriodicalId":74212,"journal":{"name":"Modern trends in pharmacopsychiatry","volume":" ","pages":"107-123"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000470811","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35193693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards an Integrated View of Early Molecular Changes Underlying Vulnerability to Social Stress in Psychosis.","authors":"Henry Barron,&nbsp;Sina Hafizi,&nbsp;Romina Mizrahi","doi":"10.1159/000470810","DOIUrl":"https://doi.org/10.1159/000470810","url":null,"abstract":"<p><p>Psychotic disorders are heterogeneous and complex, involving many putative causal factors interacting along the course of disease development. Many of the factors implicated in the pathogenesis of psychosis also appear to be involved in disease onset and subsequent neuroprogression. Herein, we highlight the pertinent literature implicating inflammation and oxidative stress in the pathogenesis of psychosis, and the potential contribution of N-methyl-D-aspartate receptors (NMDARs). We also emphasize the role of peripubertal social stress in psychosis, and the ways in which hippocampal dysfunction can mediate dysregulation of the hypothalamic-pituitary-adrenal axis and cortisol release. Finally, we propose a model wherein inflammation and oxidative stress act as a first hit, producing altered parvalbumin interneuron development, NMDAR hypofunction, microglial priming, and sensitivity to a second hit of peripubertal social stress. With a greater understanding of how these factors interact, it may be possible to detect, prevent, and treat psychosis more effectively.</p>","PeriodicalId":74212,"journal":{"name":"Modern trends in pharmacopsychiatry","volume":" ","pages":"96-106"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000470810","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35194416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate Immune Memory: Implications for Microglial Function and Neuroprogression.","authors":"Alex P Salam,&nbsp;Carmine M Pariante,&nbsp;Patricia Zunszain","doi":"10.1159/000470808","DOIUrl":"https://doi.org/10.1159/000470808","url":null,"abstract":"<p><p>Immunostimulatory insults such as stress and infection are risk factors for the development of several neuropsychiatric disorders characterized by neuroprogression. Inflammatory and neurotoxic molecules in the brain can cause disruptions in neurogenesis, neuronal excitability, synaptic transmission, synaptic plasticity, and neuronal survival - changes that characterize neuroprogression. We draw on recent findings in the immunology literature that peripheral innate immune cells are capable of retaining long-term memory of infectious insults and displaying long-lasting upregulated proinflammatory function in response to repeated infectious insults - a concept known as \"innate immune memory.\" In turn, we hypothesize that microglia, the resident innate immune cells of the brain, are also capable of retaining long-term memory of infectious and noninfectious insults, including stress. Microglia are capable of producing a variety of proinflammatory neurotoxic cytokines and chemokines. Persistent upregulation of microglial proinflammatory function as a result of memory for immunostimulatory insults may therefore contribute to persistent and progressive inflammation in neuropsychiatric illnesses and be an important driver of neuroprogression.</p>","PeriodicalId":74212,"journal":{"name":"Modern trends in pharmacopsychiatry","volume":" ","pages":"67-78"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000470808","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35196517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory and Innate Immune Markers of Neuroprogression in Depressed and Teenage Suicide Brain.","authors":"Ghanshyam N Pandey","doi":"10.1159/000470809","DOIUrl":"https://doi.org/10.1159/000470809","url":null,"abstract":"<p><p>Several studies suggest that major depressive disorder (MDD) and bipolar disorder (BPD) are neuroprogressive illnesses. Besides clinical features, neurobiological mechanisms have been suggested to contribute to the neuroprogression of mood disorders. Biological factors that have been shown to contribute significantly toward the neuroprogressive course of these disorders are inflammatory markers, such as cytokines. Cytokines have been extensively investigated, primarily in the serum of MDD and BPD patients, and these studies show cytokine abnormalities in both adolescent and adult patients with mood disorders. However, cytokine abnormalities in the brain may also contribute toward neuroprogression, but brain cytokines have not been adequately investigated. To examine the role of cytokines in neuroprogression, we have studied the markers of adaptive and innate immunity in postmortem brain obtained from teenage and adult suicide victims and gene expression of cytokines and their membrane-bound receptors in lymphocytes of MDD and BPD patients. Cytokines and Toll-like receptors (TLRs) were studied in 24 teenage suicide victims and 24 normal control (NC) subjects, and also in 22 adult depressed suicide victims and 20 adult NC subjects. We found that the protein and mRNA expression of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were significantly higher in the prefrontal cortex (PFC). We also found that the protein and mRNA expression of TLRs, which are major mediators of innate immunity, is increased in the PFC of adult depressed suicide victims and NC subjects. In patients, mRNA and protein expression of TNF-α, IL-1β, and IL-6 was significantly increased in both MDD and BPD patients. Similarly, mRNA expression of some specific membrane-bound receptors, such as IL1R1, TNFR1, IL1RA, were significantly increased in lymphocytes of MDD and BPD patients. These studies indicate the existence of abnormal cytokines and TLRs in the brain of teenage and adult suicide victims. Future studies, including both teenage and adult postmortem samples, will be needed to further clarify the role of cytokines and TLRs in neuroprogression.</p>","PeriodicalId":74212,"journal":{"name":"Modern trends in pharmacopsychiatry","volume":" ","pages":"79-95"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000470809","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35194192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Brain-Gut Axis Contributes to Neuroprogression in Stress-Related Disorders.","authors":"Kieran Rea,&nbsp;Timothy G Dinan,&nbsp;John F Cryan","doi":"10.1159/000470813","DOIUrl":"https://doi.org/10.1159/000470813","url":null,"abstract":"<p><p>There is a growing emphasis on the relationship between the complexity and diversity of the microorganisms that inhabit our gut (human gastrointestinal microbiota) and brain health. The microbiota-gut-brain axis is a dynamic matrix of tissues and organs including the brain, glands, gut, immune cells, and gastrointestinal microbiota that communicate in a complex multidirectional manner to maintain homeostasis. Changes in this environment may contribute to the neuroprogression of stress-related disorders by altering physiological processes including hypothalamic-pituitary-adrenal axis activation, neurotransmitter systems, immune function, and inflammatory responses. While appropriate, coordinated physiological responses, such as immune or stress responses, are necessary for survival, the contribution of repeated or chronic exposure to stress may predispose individuals to a more vulnerable state leaving them more susceptible to stress-related disorders. In this chapter, the involvement of the gastrointestinal microbiota in stress- and immune-mediated modulation of neuroendocrine, immune, and neurotransmitter systems and the consequential behavior is considered. We also focus on the mechanisms by which commensal gut microbiota can regulate neuroinflammation and further aim to exploit our understanding of their role in the effects of the microbiota-gut-brain axis on the neuroprogression of stress-related disorders as a consequence of neuroinflammatory processes.</p>","PeriodicalId":74212,"journal":{"name":"Modern trends in pharmacopsychiatry","volume":" ","pages":"152-161"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000470813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35194018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation Effects on Glutamate as a Pathway to Neuroprogression in Mood Disorders.","authors":"Ebrahim Haroon,&nbsp;Andrew H Miller","doi":"10.1159/000470805","DOIUrl":"https://doi.org/10.1159/000470805","url":null,"abstract":"<p><p>Neuroprogression is a term used to describe worsening psychopathology, poor treatment response, and declining cognitive and functional outcomes among patients with chronic mental disorders. Chronic inflammatory activation and glutamate-mediated excitotoxicity are two key etiological factors implicated in the development of neuroprogression. In this chapter, we hypothesize that the association between chronic inflammatory activation, neuroprogression, and glutamate dysregulation might be mediated by glial dysfunction. The role played by other mechanisms that increase glutamatergic activity, including oxidative stress and kynurenine pathway activation, will also be discussed, albeit briefly. We will conclude by providing a mechanistic model that draws upon our previous research, to link neuroimmune/neurotransmitter dysregulation to disrupted local neural activity and brain network connectivity eventually leading to a neuroprogressive course and associated clinical outcomes.</p>","PeriodicalId":74212,"journal":{"name":"Modern trends in pharmacopsychiatry","volume":"31 ","pages":"37-55"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000470805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10154057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}