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1.
Anal Chem ; 96(12): 4835-4844, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38488022

RESUMO

The rapid proliferation of new psychoactive substances (NPS) poses significant challenges to conventional mass-spectrometry-based identification methods due to the absence of reference spectra for these emerging substances. This paper introduces PS2MS, an AI-powered predictive system designed specifically to address the limitations of identifying the emergence of unidentified novel illicit drugs. PS2MS builds a synthetic NPS database by enumerating feasible derivatives of known substances and uses deep learning to generate mass spectra and chemical fingerprints. When the mass spectrum of an analyte does not match any known reference, PS2MS simultaneously examines the chemical fingerprint and mass spectrum against the putative NPS database using integrated metrics to deduce possible identities. Experimental results affirm the effectiveness of PS2MS in identifying cathinone derivatives within real evidence specimens, signifying its potential for practical use in identifying emerging drugs of abuse for researchers and forensic experts.


Assuntos
Aprendizado Profundo , Drogas Ilícitas , Cromatografia Líquida/métodos , Psicotrópicos/análise , Espectrometria de Massas/métodos , Drogas Ilícitas/análise , Detecção do Abuso de Substâncias/métodos
3.
Lancet Psychiatry ; 11(4): 274-284, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490760

RESUMO

BACKGROUND: Little information is available on the clinical trajectories of children and adolescents who attend general practice (GP) with psychiatric symptoms. We aimed to examine 5-year service use in English primary care for children and adolescents with neurodevelopmental or mental health symptoms or diagnoses. METHODS: In this retrospective cohort study, we used anonymised primary care health records from the Clinical Practice Research Datalink Aurum database (CPRD-Aurum). We identified children and adolescents (aged 3-18 years) presenting to primary care in England between Jan 1, 2000, and May 9, 2016, with a symptom or diagnosis of a mental health, behavioural, or neurodevelopmental condition. Participants were excluded if they had less than 1 year of follow-up. We followed up participants from their index date until either death, transfer out of the practice, or the end of data collection on May 5, 2021, and for trajectory analysis we limited follow-up to 5 years. We used group-based multi-trajectory models to identify clusters with similar trajectories over 5 years of follow-up for three primary outcomes: mental health-related GP contacts, psychotropic medication prescriptions, and specialist mental health-care contact. We did survival analysis to examine the associations between trajectory-group membership and hospital admission for self-harm or death by suicide, as indicators of severe psychiatric distress. FINDINGS: We included 369 340 children and adolescents, of whom 180 863 (49·0%) were girls, 188 438 (51·0%) were boys, 39 (<0·1%) were of indeterminate gender, 290 125 (78·6%) were White, 9161 (2·5%) were South Asian, 10 418 (2·8%) were Black, 8115 (2·2%) were of mixed ethnicity, and 8587 (2·3%) were other ethnicities, and the median age at index presentation was 13·6 years (IQR 8·4-16·7). In the best-fitting, seven-group, group-based multi-trajectory model, over a 5-year period, the largest group (low contact; 207 985 [51·2%]) had low rates of additional service contact or psychotropic prescriptions. The other trajectory groups were moderate, non-pharmacological contact (43 836 [13·0%]); declining contact (25 469 [8·7%]); year-4 escalating contact (18 277 [6·9%]); year-5 escalating contact (18 139; 5·2%); prolonged GP contact (32 147 [8·6%]); and prolonged specialist contact (23 487 [6·5%]). Non-White ethnicity and presentation in earlier study years (eg, 2000-2004) were associated with low-contact group membership. The prolonged specialist-contact group had the highest risk of hospital admission for self-harm (hazard ratio vs low-contact group 2·19 [95% CI 2·03-2·36]) and suicide (2·67 [1·72-4·14]). INTERPRETATION: Most children and adolescents presenting to primary care with psychiatric symptoms or diagnoses have low or declining rates of ongoing contact. If these trajectories reflect symptomatic improvement, these findings provide reassurance for children and adolescents and their caregivers. However, these trajectories might reflect an unmet need for some children and adolescents. FUNDING: National Institute for Health and Care Research and the Wellcome Trust.


Assuntos
Clínicos Gerais , Transtornos Mentais , Masculino , Criança , Feminino , Humanos , Adolescente , Estudos Retrospectivos , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Inglaterra/epidemiologia , Psicotrópicos , Avaliação de Resultados em Cuidados de Saúde
5.
Tidsskr Nor Laegeforen ; 144(4)2024 Mar 19.
Artigo em Norueguês | MEDLINE | ID: mdl-38506014

RESUMO

Background: The knowledge base on new psychoactive substances (NPS) is generally limited. This introduces new challenges and increased unpredictability in substance abuse treatment. Case presentation: A man in his thirties was submitted to detoxification after reportedly using flubromazolam, a high potency designer benzodiazepine, which he had purchased on the dark web. Extensive drug testing of serum, urine and hair, and the remains in a dropper bottle delivered by the patient, did not reveal flubromazolam or possible metabolites, but did reveal several common drugs of abuse, and 8-aminoclonazolam, a metabolite of clonazolam, another designer benzodiazepine sold on the dark web. The detoxification was uncomplicated. An excessive treatment protocol based on the patient's information, involving high preparedness and increased resources, both clinically and analytically, turned out to be unnecessary. Interpretation: The drug use and clinical course in this case proved to be more common than the unit prepared for. The case history illustrates both the challenges with users of NPS and the general unpredictability in substance abuse treatment.


Assuntos
Drogas Desenhadas , Transtornos Relacionados ao Uso de Substâncias , Masculino , Humanos , Benzodiazepinas/efeitos adversos , Detecção do Abuso de Substâncias/métodos , Psicotrópicos
6.
Angiol. (Barcelona) ; 76(1): 38-42, ene.-feb. 2024. ilus
Artigo em Espanhol | IBECS | ID: ibc-231197

RESUMO

Introducción: la isquemia aguda se caracteriza por una disminución repentina de la perfusión arterial de la extremidad, con una amenaza potencial para su supervivencia, que requiere evaluación y manejo urgentes. Es una enfermedad causada por varias etiologías, incluida la aterotrombosis y la embolización periférica. Sin embargo, se han presentado casos raros en adultos jóvenes en los que también deben considerarse otras etiologías. Caso clínico: presentamos dos casos raros de pacientes que desarrollaron isquemia aguda de las extremidades debido a vasoespasmo prolongado secundario al consumo de sustancias psicoactivas. Discusión: el vasoespasmo es una causa rara de isquemia aguda de las extremidades. Nuestro reporte de casos documenta la complejidad y la importancia de las consideraciones diagnósticas diferenciales que deben realizarse en pacientes con estos antecedentes personales y con dichas características clínicas, en los que no hay causas ateroscleróticas de isquemia en las extremidades. (AU)


Introduction: acute ischemia is characterized by a sudden decrease in arterial perfusion of the extremity, with a potential threat to its survival, which requires urgent evaluation and management. It is a disease caused by various etiologies, including atherothrombosis and peripheral embolization. However, rare cases have occurred in young adults where other etiologies must also be considered. Case report: we present two rare cases of patients who developed acute limb ischemia due to prolonged vasospasm secondary to psychoactive substance use. Discussion: vasospasm is a rare cause of acute limb ischemia. Our case report documents the complexity and importance of the differential diagnostic considerations that must be made in patients with these personal backgrounds and with these clinical characteristics, in whom there are no atherosclerotic causes of ischemia in the extremities. (AU)


Assuntos
Humanos , Masculino , Adulto , Isquemia , Extremidades , Transtornos Relacionados ao Uso de Substâncias , Psicotrópicos
7.
CNS Drugs ; 38(3): 193-204, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38386200

RESUMO

Psychodermatology, the multidisciplinary field that explores the intricate interplay between the mind and the skin, has gained increasing recognition over the past decade. However, several knowledge gaps and unmet needs persist in the field. The objective of this narrative review was to investigate the unmet needs in the field of psychodermatology as they pertain to medical training, treatment, research, and care access. PubMed was searched from inception through December 2023 to identify articles related to psychodermatology. Findings revealed several unmet needs within the field of psychodermatology. First, there is a need for further investigation into the pathophysiology that links psychological stress to cutaneous disease including the development of novel therapies targeting key neuropeptides. Second, the existing literature focuses primarily on the pharmacologic treatment of body dysmorphic disorder and body-focused repetitive behaviors, as well as delusional parasitosis, for which the first-line agents are selective serotonin reuptake inhibitors and atypical antipsychotics, respectively. However, additional research into the efficacy and safety of the remaining psychotropic medications and the treatment of other common psychocutaneous diseases is required. Finally, there exists a significant gap in knowledge amongst clinicians tasked with treating psychocutaneous diseases. Dermatologists report low rates of training in psychodermatology and discomfort with prescribing psychotropic medications. In conclusion, increasing resources for dermatologist education on psychotropic agent use, development of new drugs targeting stress-induced skin conditions, and research on the psychocutaneous applications of current medications may greatly improve the quality and access of psychodermatology care.


Assuntos
Antipsicóticos , Dermatopatias , Humanos , Dermatopatias/tratamento farmacológico , Dermatopatias/psicologia , Psicotrópicos/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina
8.
Pharmacoepidemiol Drug Saf ; 33(2): e5754, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38362653

RESUMO

PURPOSE: Patients with cancer may be prescribed psychotropic medications to address their psychiatric symptoms and disorders. This study examined the patterns and factors associated with the prescription of psychotropics after cancer diagnosis using a population-based database in Hong Kong. METHODS: Patients who were diagnosed with malignant cancer and had no documented psychiatric diagnosis or psychotropic medications prior to cancer diagnosis, were included. Multivariable log-binomial models were used to explore the associations between predictive factors and psychotropic medications use. RESULTS: Among 9337 patients, 1868 patients (20.0%) were newly prescribed with psychotropic medications after cancer diagnoses, most commonly hypnotics (50.3%) and antidepressants (32.8%). About one-third (31.4%) were prescribed chronic psychotropics (≥90 days). Approximately 48.3% of patients who were prescribed psychotropic medications received their prescriptions within 1 year after diagnosed with cancer. Only 18.6% of those prescribed psychotropic medications had a registered psychiatric diagnosis. Patients with multiple comorbidities (adjusted risk ratio[aRR] = 2.74; CI = 2.46-3.05) and diagnosed with oral (aRR = 1.89; CI = 1.52-2.35) or respiratory cancers (aRR = 1.62; CI = 1.36-1.93) were more likely to be prescribed psychotropics. CONCLUSIONS: The use of psychotropic medication is common (20%) among patients with cancer. Our findings highlight the importance of identification and documentation of psychiatric needs among patients with cancer.


Assuntos
Neoplasias , Psicotrópicos , Humanos , Estudos de Coortes , Psicotrópicos/uso terapêutico , Prescrições , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , China/epidemiologia
9.
JAMA Netw Open ; 7(2): e2356404, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38363573

RESUMO

This cross-sectional study aims to identify temporal changes and characteristics associated with psychotropic polypharmacy among youths aged 17 years or younger who were enrolled in Medicaid in Maryland.


Assuntos
Medicaid , Transtornos Mentais , Humanos , Adolescente , Estados Unidos , Polimedicação , Psicotrópicos/uso terapêutico , Transtornos Mentais/tratamento farmacológico
10.
BMC Psychiatry ; 24(1): 127, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365662

RESUMO

BACKGROUND: A focus on patient's and service user's perspectives regarding long-term antipsychotic treatment led to a declaration from the Norwegian Ministry of Health in 2015 to offer treatment without psychotropic medication in mental health as a voluntary option in all four health care regions. In the northernmost region, a 6-bed inpatient ward unit was established, uniquely designed to give people with severe mental illness the possibility to choose such treatment. Only voluntary admissions were accepted. The aim of the present study was to explore the motivation for applying for medication free treatment among patients with several years of treatment history due to psychosis. METHOD: We performed nineteen semi-structured, in-depth interviews with persons having at least one admission at the medication free treatment ward during the period 01.01.17 - 17.10.2021. The interviews were recorded, transcribed and analysed using computer-assisted qualitative data analysis software (NVivo). Systematic Text Condensation was applied, with analysis of data from the first interview. Exploration of connections, similarities and nuances was performed through axial coding with continuous comparison of data and memo writing, followed by focused coding identifying core concepts. RESULTS: All participants had a diagnosis of severe mental illness and a history of use of antipsychotics throughout many years. The motivation to apply for medication free treatment was complex. Negative experiences with medication were described, but also positive. Many had tried to taper off before, but described this as a lonely and difficult process. Five core concepts were formed and developed from the participants' narratives: 1) Medication experiences, 2) Developing illness, 3) Treatment in general, 4) Social life and 4) Growing up. CONCLUSION: The concept of medication free treatment represents a salutogenetic hope for change, closely linked to self-efficacy and an experience of mastery. Potential conflicts concerning guidelines or evidence on medication does not come forward as important. Support from family and professionals is crucial, in contrast to the feeling of being alone when hoping for change. Motivational factors are closely linked to the concept of recovery, where interaction happens on both an individual and a structural level.


Assuntos
Antipsicóticos , Transtornos Psicóticos , Humanos , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/psicologia , Saúde Mental , Antipsicóticos/uso terapêutico , Psicotrópicos/uso terapêutico , Pacientes Internados
11.
BMC Health Serv Res ; 24(1): 217, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365679

RESUMO

BACKGROUND: Promoting appropriate pharmacotherapy requires understanding the factors that influence how clinicians prescribe medications. While prior work has focused on patient and clinician factors, features of the organizational setting have received less attention, though identifying sources of variation in prescribing may help identify opportunities to improve patient safety and outcomes. OBJECTIVE: To evaluate the relationship between the number of clinicians who prescribe medications in a facility and facility prescribing intensity of six individual medication classes by clinician specialty: benzodiazepines, antipsychotics, antiepileptics, and antidepressants by psychiatrists and antibiotics, opioids, antiepileptics, and antidepressants by primary care clinicians (PCPs). DESIGN: We used 2017 Veterans Health Administration (VHA) administrative data. SUBJECTS: We included patient-clinician dyads of older patients (> 55 years) with an outpatient encounter with a clinician in 2017. Patient-clinician data from 140 VHA facilities were included (n = 13,347,658). Analysis was repeated for years 2014 to 2016. MAIN MEASURES: For each medication, facility prescribing intensity measures were calculated as clinician prescribing intensity averaged over all clinicians at each facility. Clinician prescribing intensity measures included percentage of each clinician's patients prescribed the medication and mean number of days supply per patient among all patients of each clinician. KEY RESULTS: As the number of prescribing clinicians in a facility increased, the intensity of prescribing decreased. Every increase of 10 facility clinicians was associated with a significant decline in prescribing intensity for both specialties for different medication classes: for psychiatrists, declines ranged from 6 to 11%, and for PCPs, from 2 to 3%. The pattern of more clinicians less prescribing was significant across all years. CONCLUSION: Future work should explore the mechanisms that link the number of facility clinicians with prescribing intensity for benzodiazepines, antipsychotics, antiepileptics, antidepressants, antibiotics, and opioids. Facilities with fewer clinicians may need additional resources to avoid unwanted prescribing of potentially harmful or unnecessary medications.


Assuntos
Analgésicos Opioides , Anticonvulsivantes , Humanos , Analgésicos Opioides/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antibacterianos/uso terapêutico , Psicotrópicos/uso terapêutico , Benzodiazepinas/uso terapêutico , Antidepressivos , Padrões de Prática Médica
12.
Molecules ; 29(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38398513

RESUMO

The intensive development of extraction methods based on µ-SPE extraction contributes to the increased interest in the synthesis of new sorption materials. This work presents the characterization of polystyrene fibers and polystyrene fibers blended with ZrO2 particles or polyaniline obtained by electrospinning and their use in the extraction of selected psychoactive drugs from biological samples. The characteristic of produced fibers is made by performing SEM images, measuring average fiber diameter, and examining their sorption abilities. Among the fibers based on pure polystyrene, tested in the first stage, the best sorption properties are demonstrated for the fibers obtained from a polystyrene solution in DMF with a concentration of 17.5 wt%. In the next stage, this material was modified with synthesized ZrO2 particles and polyaniline. Among the tested materials, the sorbent based on polystyrene with polyaniline shows the best sorption properties of the tested substances. The use of this material in the µ-SPE in a needle enables the extraction of selected compounds from aqueous and biological samples such as urine and human plasma.


Assuntos
Poliestirenos , Extração em Fase Sólida , Humanos , Extração em Fase Sólida/métodos , Compostos de Anilina , Psicotrópicos
13.
J Child Adolesc Psychopharmacol ; 34(1): 52-60, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38377527

RESUMO

Objective: Evidence for pharmacogenomic (PGx) guided treatment in child and adolescent psychiatry is growing. This study evaluated the impact of PGx testing on psychotropic medication prescribing in an ambulatory child and adolescent psychiatry and a developmental pediatrics clinic. Methods: This was a single-center, retrospective, descriptive analysis of patients who underwent PGx testing between January 2015 and October 2022 at a child and adolescent psychiatry clinic or developmental pediatrics clinic. The primary outcome was the proportion of patients with at least one psychotropic medication modification made 6-month posttesting that could be attributed to CYP2C19, CYP2D6, HLA-B*15:02, or HLA-A*31:01. Secondary outcomes included reason for testing, types of therapeutic modifications made, and whether the therapeutic modifications concorded with PGx guidelines. Results: A total of 193 patients were analyzed. The average age was 10 ± 4 years old, 60% were male, 78% were Caucasian. Sixty-eight percent had a primary diagnosis of a neurodevelopmental disorder, namely autism spectrum disorder (51%), and attention-deficit/hyperactivity disorder (14%). The reasons for PGx testing included medication inefficacy (34%), medication intolerance (20%), and family request (19%). At the time of PGx testing, 37% of patients were taking ≥1 psychotropic medication with PGx annotation. Overall, 35 PGx-related therapeutic modifications were made in 32 (17%) patients. These included continuing current PGx medication (6.2%) and starting PGx medication (5.2%). These modifications mainly involved antidepressants. Out of these 35 PGx-related therapeutic modifications, 94% were concordant with PGx guidelines. Among 29 patients who were prescribed at least one CYP2D6 inhibitor, 25 (86%) underwent CYP2D6 phenoconversion. Conclusions: It is critical to apply pediatric age-specific considerations when utilizing PGx testing in child and adolescent psychiatry. PGx testing stewardship could provide a framework to guide the clinical utility of PGx in a pediatric population with mental health conditions, including neurodevelopmental disorders.


Assuntos
Transtorno do Espectro Autista , Farmacogenética , Adolescente , Criança , Humanos , Masculino , Feminino , Citocromo P-450 CYP2D6/genética , Estudos Retrospectivos , Transtorno do Espectro Autista/tratamento farmacológico , Psicotrópicos/uso terapêutico , Assistência Ambulatorial
14.
J Child Adolesc Psychopharmacol ; 34(1): 4-20, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38377525

RESUMO

The efficacy and tolerability of psychotropic medications can vary significantly among children and adolescents, and some of this variability relates to pharmacogenetic factors. Pharmacogenetics (PGx) in child and adolescent psychiatry can potentially improve treatment outcomes and minimize adverse drug reactions. This article reviews key pharmacokinetic and pharmacodynamic genes and principles of pharmacogenetic testing and discusses the evidence base for clinical decision-making concerning PGx testing. This article reviews current guidelines from the United States Food and Drug Administration (FDA), the Clinical Pharmacogenetics Implementation Consortium (CPIC), and the Dutch Pharmacogenetics Working Group (DPWG) and explores potential future directions. This review discusses key clinical considerations for clinicians prescribing psychotropic medications in children and adolescents, focusing on antidepressants, antipsychotics, stimulants, norepinephrine reuptake inhibitors, and alpha-2 agonists. Finally, this review synthesizes the practical use of pharmacogenetic testing and clinical decision support systems.


Assuntos
Psiquiatria do Adolescente , Farmacogenética , Estados Unidos , Criança , Humanos , Adolescente , Psicotrópicos/uso terapêutico , Antidepressivos/uso terapêutico , Testes Farmacogenômicos
15.
Tijdschr Psychiatr ; 66(1): 30-35, 2024.
Artigo em Holandês | MEDLINE | ID: mdl-38380485

RESUMO

BACKGROUND: Sexual behavior disorders in intellectual disability form several challenges, despite evolutions in treatment options and risk assessment. The use of antilibidinal pharmacotherapy in this population is controversial and research is inconclusive about the most appropriate treatment strategy. AIM: To highlight pharmacotherapeutic management of sexual behavior disorders in intellectual disability, its medical and ethical considerations. METHOD: A literature review to provide an overview of the available literature, which was elaborated based on clinical experience. RESULTS: We found a lack of scientific evidence on the efficacy of pharmacotherapy specifically for sexual behavior disorders in people with intellectual disabilities. The routine use of antilibidinal medication is contraindicated. Medical and ethical guidelines have been published as well as contraindications for initiating androgen deprivation therapy in the general population. The necessity of pharmacotherapy should be closely monitored and supplemented with psychotherapeutic care to cultivate the patient’s sexual skills, attitudes and knowledge. A distinction should be made between sexual behavior disorders of the ‘paraphilic type’ and of the ‘sexually maladjusted or naive type’. CONCLUSION: Multidisciplinary evaluation, risk assessment and an individualized approach are the cornerstones of high-quality treatment of sexual behavior disorders in persons with intellectual disability.


Assuntos
Deficiência Intelectual , Neoplasias da Próstata , Masculino , Humanos , Deficiência Intelectual/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Comportamento Sexual , Psicotrópicos/uso terapêutico
16.
J Neural Transm (Vienna) ; 131(3): 253-266, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38353811

RESUMO

Edema as an adverse drug reaction is a commonly underestimated yet potentially debilitating condition. This study analyzes the incidence of severe psychotropic drug-induced edema (e.g., edema affecting the face, legs, or multiple body parts and lasting for more than 1 week, or in any case necessitating subsequent diuretic use) among psychiatric inpatients. The cases under examination are derived from an observational pharmacovigilance program conducted in German-speaking countries ("Arzneimittelsicherheit in der Psychiatrie", AMSP) from 1993 to 2016. Among the 462,661 inpatients monitored, severe edema was reported in 231 cases, resulting in an incidence of 0.05%. Edema occurred more frequently in women (80% of all cases) and older patients (mean age 51.8 years). Pregabalin had the highest incidence of severe edema, affecting 1.46‰ of patients treated with pregabalin, followed by mirtazapine (0.8‰). The majority of edema cases showed a positive response to appropriate countermeasures, such as dose reduction and drug discontinuation, and resolved by the end of the observation period. While most instances of drug-induced edema are reversible, they can have a significant impact on patient well-being and potentially result in decreased treatment adherence. It is, therefore, crucial to remain vigilant regarding risk-increasing circumstances during treatment with psychotropic drugs.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Edema/induzido quimicamente , Edema/epidemiologia , Edema/tratamento farmacológico , Pregabalina , Psicotrópicos/efeitos adversos , Farmacovigilância
18.
Clin Epigenetics ; 16(1): 36, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419113

RESUMO

BACKGROUND: Metabolic side effects of psychotropic medications are a major drawback to patients' successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain inducing psychotropic treatment were selected from the PsyMetab study cohort. Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip. RESULTS: A global methylation increase was noted after the first month of treatment, which was more pronounced (p < 2.2 × 10-16) in patients whose weight remained stable (< 2.5% weight increase). Epigenome-wide significant methylation changes (p < 9 × 10-8) were observed at 52 loci in the whole cohort. When restricting the analysis to patients who underwent important early weight gain (≥ 5% weight increase), one locus (cg12209987) showed a significant increase in methylation levels (p = 3.8 × 10-8), which was also associated with increased weight gain in the whole cohort (p = 0.004). Epigenome-wide association analyses failed to identify a significant link between metabolic changes and methylation data. Nevertheless, among the strongest associations, a potential causal effect of the baseline methylation level of cg11622362 on glycemia was revealed by a two-sample Mendelian randomization analysis (n = 3841 for instrument-exposure association; n = 314,916 for instrument-outcome association). CONCLUSION: These findings provide new insights into the mechanisms of psychotropic drug-induced weight gain, revealing important epigenetic alterations upon treatment, some of which may play a mediatory role.


Assuntos
Metilação de DNA , Epigênese Genética , Humanos , Estudos Prospectivos , Estudo de Associação Genômica Ampla/métodos , Aumento de Peso/genética , Psicotrópicos/efeitos adversos
19.
Sci Rep ; 14(1): 3376, 2024 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336912

RESUMO

KPNA1 is a mediator of nucleocytoplasmic transport that is abundantly expressed in the mammalian brain and regulates neuronal differentiation and synaptic function. De novo mutations in Kpna1 have been identified using genome-wide association studies in humans with schizophrenia; however, it remains unclear how KPNA1 contributes to schizophrenia pathogenesis. Recent studies have suggested a complex combination of genetic and environmental factors that are closely related to psychiatric disorders. Here, we found that subchronic administration of phencyclidine, a psychotropic drug, induced vulnerability and behavioral abnormalities consistent with the symptoms of schizophrenia in Kpna1-deficient mice. Microarray assessment revealed that the expression levels of dopamine d1/d2 receptors, an RNA editing enzyme, and a cytoplasmic dynein component were significantly altered in the nucleus accumbens brain region in a gene-environment (G × E) interaction-dependent manner. Our findings demonstrate that Kpna1-deficient mice may be useful as a G × E interaction mouse model for psychiatric disorders and for further investigation into the pathogenesis of such diseases and disorders.


Assuntos
Esquizofrenia , Humanos , Camundongos , Animais , Esquizofrenia/induzido quimicamente , Esquizofrenia/genética , Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Psicotrópicos/farmacologia , Fenciclidina/farmacologia , Núcleo Accumbens/metabolismo , Mamíferos/metabolismo , alfa Carioferinas/genética , alfa Carioferinas/metabolismo
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