Among all contaminants of emerging interest,drugs are the ones that give rise to the greatest concern.Any of the multiple stages of the drug's life cycle(production,consumption and waste management)is a possible e...Among all contaminants of emerging interest,drugs are the ones that give rise to the greatest concern.Any of the multiple stages of the drug's life cycle(production,consumption and waste management)is a possible entry point to the different environmental matrices.Psychiatric drugs have received special attention because of two reasons.First,their use is increasing.Second,many of them act on phylogenetically highly conserved neuroendocrine systems,so they have the potential to affect many non-target organisms.Currently,wastewater is considered the most important source of drugs to the environment.Furthermore,the currently available wastewater treatment plants are not specifically prepared to remove drugs,so they reach practically all environmental matrices,even tap water.As drugs are designed to produce pharmacological effects at low concentrations,they are capable of producing ecotoxicological effects on microorganisms,flora and fauna,even on human health.It has also been observed that certain antidepressants and antipsychotics can bioaccumulate along the food chain.Drug pollution is a complicated and diffuse problem characterized by scientific uncertainties,a large number of stakeholders with different values and interests,and enormous complexity.Possible solutions consist on acting at source,using medicines more rationally,eco-prescribing or prescribing greener drugs,designing pharmaceuticals that are more readily biodegraded,educating both health professionals and citizens,and improving coordination and collaboration between environmental and healthcare sciences.Besides,end of pipe measures like improving or developing new purification systems(biological,physical,chemical,combination)that eliminate these residues efficiently and at a sustainable cost should be a priority.Here,we describe and discuss the main aspects of drug pollution,highlighting the specific issues of psychiatric drugs.展开更多
Attachment style,which has been theorized to be rooted in childhood bonding experiences,influences adult cognitive,emotional and interpersonal functioning.Despite its relationship with early experiences,research indic...Attachment style,which has been theorized to be rooted in childhood bonding experiences,influences adult cognitive,emotional and interpersonal functioning.Despite its relationship with early experiences,research indicates that the continuity of attachment style across childhood and adulthood is only partial,being a malleable tendency that is shaped throughout development,with an increasing influence of genetics,as it occurs in other cognitive and behavioral phenotypes.Genetic research indicates that up to 45% of the variability in anxious and 39% in avoidant adult attachment style could be explained by genetic causes,but the precise mechanisms remain unclear.A narrative review is conducted analyzing the existing literature regarding the implication of candidate genes related to oxytocin,dopaminergic pathways,serotonergic pathways and brainderived neurotrophic factor in adult attachment,with both vulnerability and differential susceptibility approaches,yielding mixed results.We highlight the lack of genome-wide studies and the scarcity of epigenetic investigation.Based on the existing data,we conclude that the genetics of adult attachment is an area that requires further research to clarify its etiological role and that it should be preferably approached as an interaction between nature and nurture.展开更多
Depression is a common,recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide.Up to 15%-40%of cases do not respond to diverse pharmacological treatments and,thus,c...Depression is a common,recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide.Up to 15%-40%of cases do not respond to diverse pharmacological treatments and,thus,can be defined as treatment-resistant depression(TRD).The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment.Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD.Specifically,the N-methyl-D-aspartic acid receptor(NMDAR)andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR),which are targeted by ketamine and esketamine,are proposed as promising pathways.A literature search was performed to identify studies on the genetics of the glutamatergic system in depression,focused on variables related to NMDARs and AMPARs.Our review highlights GRIN2B,which encodes the NR2B subunit of NMDAR,as a candidate gene in the pathogenesis of TRD.In addition,several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation.These genes encoding glutamatergic receptors could,therefore,be candidate genes for understanding the etiopathogenesis of TRD,as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.展开更多
N6-methyladenosine(m6A)is the most abundant modification in eukaryotic messenger RNA.1 This modification is dynamic,reversible,and mediated by proteins characterized as methyltransferases and demethylases.Recent inves...N6-methyladenosine(m6A)is the most abundant modification in eukaryotic messenger RNA.1 This modification is dynamic,reversible,and mediated by proteins characterized as methyltransferases and demethylases.Recent investigations have found that aberrant expression of methyltransferases and demethylases results in m6A dysregulation and,in consequence,affects the biological functions in which this modification is involved.Indeed,m6A dysregulation affects the development and maintenance of various diseases,including cancer.2 For this reason,we explored the potential role that m6A modification has in invasive breast cancer of no special type(IBC-NST)and its molecular subtypes luminal A,luminal B HER2-,luminal B HER2+,HER2+,and triple-negative breast cancer(TNBC)whose degree of global m6A methylation has not yet been studied.展开更多
文摘Among all contaminants of emerging interest,drugs are the ones that give rise to the greatest concern.Any of the multiple stages of the drug's life cycle(production,consumption and waste management)is a possible entry point to the different environmental matrices.Psychiatric drugs have received special attention because of two reasons.First,their use is increasing.Second,many of them act on phylogenetically highly conserved neuroendocrine systems,so they have the potential to affect many non-target organisms.Currently,wastewater is considered the most important source of drugs to the environment.Furthermore,the currently available wastewater treatment plants are not specifically prepared to remove drugs,so they reach practically all environmental matrices,even tap water.As drugs are designed to produce pharmacological effects at low concentrations,they are capable of producing ecotoxicological effects on microorganisms,flora and fauna,even on human health.It has also been observed that certain antidepressants and antipsychotics can bioaccumulate along the food chain.Drug pollution is a complicated and diffuse problem characterized by scientific uncertainties,a large number of stakeholders with different values and interests,and enormous complexity.Possible solutions consist on acting at source,using medicines more rationally,eco-prescribing or prescribing greener drugs,designing pharmaceuticals that are more readily biodegraded,educating both health professionals and citizens,and improving coordination and collaboration between environmental and healthcare sciences.Besides,end of pipe measures like improving or developing new purification systems(biological,physical,chemical,combination)that eliminate these residues efficiently and at a sustainable cost should be a priority.Here,we describe and discuss the main aspects of drug pollution,highlighting the specific issues of psychiatric drugs.
文摘Attachment style,which has been theorized to be rooted in childhood bonding experiences,influences adult cognitive,emotional and interpersonal functioning.Despite its relationship with early experiences,research indicates that the continuity of attachment style across childhood and adulthood is only partial,being a malleable tendency that is shaped throughout development,with an increasing influence of genetics,as it occurs in other cognitive and behavioral phenotypes.Genetic research indicates that up to 45% of the variability in anxious and 39% in avoidant adult attachment style could be explained by genetic causes,but the precise mechanisms remain unclear.A narrative review is conducted analyzing the existing literature regarding the implication of candidate genes related to oxytocin,dopaminergic pathways,serotonergic pathways and brainderived neurotrophic factor in adult attachment,with both vulnerability and differential susceptibility approaches,yielding mixed results.We highlight the lack of genome-wide studies and the scarcity of epigenetic investigation.Based on the existing data,we conclude that the genetics of adult attachment is an area that requires further research to clarify its etiological role and that it should be preferably approached as an interaction between nature and nurture.
文摘Depression is a common,recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide.Up to 15%-40%of cases do not respond to diverse pharmacological treatments and,thus,can be defined as treatment-resistant depression(TRD).The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment.Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD.Specifically,the N-methyl-D-aspartic acid receptor(NMDAR)andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR),which are targeted by ketamine and esketamine,are proposed as promising pathways.A literature search was performed to identify studies on the genetics of the glutamatergic system in depression,focused on variables related to NMDARs and AMPARs.Our review highlights GRIN2B,which encodes the NR2B subunit of NMDAR,as a candidate gene in the pathogenesis of TRD.In addition,several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation.These genes encoding glutamatergic receptors could,therefore,be candidate genes for understanding the etiopathogenesis of TRD,as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.
基金supported by the Basque Government,Spain(IT1633-22 and predoctoral fellowship PRE_2019_2_0005 to TK).
文摘N6-methyladenosine(m6A)is the most abundant modification in eukaryotic messenger RNA.1 This modification is dynamic,reversible,and mediated by proteins characterized as methyltransferases and demethylases.Recent investigations have found that aberrant expression of methyltransferases and demethylases results in m6A dysregulation and,in consequence,affects the biological functions in which this modification is involved.Indeed,m6A dysregulation affects the development and maintenance of various diseases,including cancer.2 For this reason,we explored the potential role that m6A modification has in invasive breast cancer of no special type(IBC-NST)and its molecular subtypes luminal A,luminal B HER2-,luminal B HER2+,HER2+,and triple-negative breast cancer(TNBC)whose degree of global m6A methylation has not yet been studied.
