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1.
Mol Psychiatry ; 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39304742

RESUMO

Immunological aetiology is supported for a subgroup with obsessive compulsive disorder (OCD) and conceptualized as autoimmune OCD. The longitudinal clinical course is detailed for three severely ill cases with OCD and indications of immunological involvement with off-label rituximab treatment every six months. All cases showed clear and sustained gains regarding symptom burden and function for over 2.5 years. Brief Psychiatric Rating Scale and Yale-Brown Obsessive-Compulsive Inventory Scale scores decreased 67-100% and 44-92%, respectively. These complex cases, prior to rituximab, had very low functioning and disease duration has been eight, nine and 16 years respectively. All three patients had been unsuccessfully treated with at least two antidepressants or anxiolytics, one neuroleptic and cognitive behavioural therapy. Clinical phenotypes and findings were suggestive of possible autoimmune OCD. Indirect immunohistochemistry detected cerebral spinal fluid (CSF) antibodies in all three cases including a novel anti-neuronal staining pattern against mouse thalamic cells. Exploratory analyses of CSF markers and proteomics identified elevated levels of sCD27 and markers indicative of complement pathway activation when compared to CSF from healthy controls. Multidisciplinary collaboration, advanced clinical investigations and rituximab treatment are feasible in a psychiatric setting. The case histories provide a proof of principle for the newly proposed criteria for autoimmune OCD. The findings suggest that clinical red flags and biological measures may predict rituximab response in chronic treatment-resistant OCD. The report provides orientation that may inform the hypotheses and design of future treatment trials.

2.
Dev Neurosci ; : 1-33, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39396515

RESUMO

Acute onset of severe psychiatric symptoms or regression may occur in children with premorbid neurodevelopmental disorders, although typically developing children can also be affected. Infections or other stressors are likely triggers. The underlying causes are unclear, but a current hypothesis suggests the convergence of genes that influence neuronal and immunological function. We previously identified 11 genes in Pediatric Acute-Onset Neuropsychiatry Syndrome (PANS), in which two classes of genes related to either synaptic function or the immune system were found. Among the latter, three affect the DNA damage response (DDR): PPM1D, CHK2, and RAG1. We now report an additional 17 cases with mutations in PPM1D and other DDR genes in patients with acute onset of psychiatric symptoms and/or regression that their clinicians classified as PANS or another inflammatory brain condition. The genes include clusters affecting p53 DNA repair (PPM1D, ATM, ATR, 53BP1, and RMRP), and the Fanconi Anemia Complex (FANCE, SLX4/FANCP, FANCA, FANCI, and FANCC). We hypothesize that defects in DNA repair genes, in the context of infection or other stressors, could contribute to decompensated states through an increase in genomic instability with a concomitant accumulation of cytosolic DNA in immune cells triggering DNA sensors, such as cGAS-STING and AIM2 inflammasomes, as well as central deficits on neuroplasticity. In addition, increased senescence and defective apoptosis affecting immunological responses could be playing a role. These compelling preliminary findings motivate further genetic and functional characterization as the downstream impact of DDR deficits may point to novel treatment strategies.

3.
BMC Psychiatry ; 24(1): 687, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39407178

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) is an important treatment for several severe psychiatric conditions, yet its precise mechanism of action remains unknown. Increased inhibition in the brain after ECT seizures, mediated by γ-aminobutyric acid (GABA), has been linked to clinical effectiveness. Case series on epileptic patients report a postictal serum concentration increase of the GABAA receptor agonist allopregnanolone. Serum allopregnanolone remains unchanged after a full ECT series, but possible transient effects directly after a single ECT seizure remain unexplored. The primary aim was to measure serum concentrations of allopregnanolone and its substrate progesterone after one ECT seizure. Secondary aims were to examine whether concentrations at baseline, or postictal changes, either correlate with seizure generalization or predict clinical outcome ratings after ECT. METHODS: A total of 130 participants (18-85 years) were included. Generalization parameters comprised peak ictal heart rate, electroencephalographic (EEG) seizure duration, and prolactin increase. Outcome measures were ratings of clinical global improvement, perceived health status and subjective memory impairment. Non-parametric tests were used for group comparisons and correlations. The prediction analyses were conducted with binary logistic and simple linear regression analyses. RESULTS: Allopregnanolone and progesterone remained unchanged and correlated neither with seizure generalization nor with clinical outcome. In men (n = 50), progesterone increased and allopregnanolone change correlated negatively with EEG seizure duration. In a subgroup analysis (n = 62), higher baseline allopregnanolone and progesterone correlated with postictal EEG suppression. CONCLUSIONS: ECT seizures have different physiologic effects than generalized seizures in epilepsy. Progesterone might have implications for psychiatric illness in men.


Assuntos
Eletroconvulsoterapia , Pregnanolona , Progesterona , Convulsões , Humanos , Pregnanolona/sangue , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Eletroconvulsoterapia/métodos , Convulsões/sangue , Convulsões/terapia , Progesterona/sangue , Adolescente , Adulto Jovem , Idoso de 80 Anos ou mais , Resultado do Tratamento , Eletroencefalografia , Estudos de Coortes
4.
Eur J Neurol ; 30(10): 3142-3148, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37392418

RESUMO

BACKGROUND AND PURPOSE: COVID-19 is associated with multiple neurological manifestations. The clinical presentation, trajectory, and treatment response for three cases of myoclonus during COVID-19 infection, with no previous neurological disease, are decsribed. METODS: Analysis of cerebrospinal fluid from the cases using indirect immunohistochemistry. RESULTS: Antibodies against rodent brain tissue, and similarities in staining patterns were observed, indicating the presence of antineuronal immunoglobulin G autoantibodies targeting astrocytes in the hippocampus. CONCLUSION: Our results demontrate cerebrospinal fluid antineuronal antibodies indicating an an autoimmune involvment in the pathogenesis in COVID-19 associated myoclonus.


Assuntos
COVID-19 , Mioclonia , Doenças do Sistema Nervoso , Humanos , Autoanticorpos , Mioclonia/etiologia , COVID-19/complicações , Encéfalo
5.
Nord J Psychiatry ; 77(3): 312-318, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35968653

RESUMO

OBJECTIVE: Physiological parameters that predict electroconvulsive therapy (ECT) effectiveness may reflect propagation of the induced epileptic seizure. As an indication of seizure propagation to the diencephalon, we here examined the correlation between prolactin increase after ECT and clinical seizure evaluation parameters, focusing on peak heart rate. As a proxy for peripheral endocrine stress response, we examined the correlation to postictal cortisol increase. METHODS: Participants were consecutively recruited from clinical ECT patients (n = 131, age 18-85 years). The first ECT session in a series was examined. For each participant, blood serum concentrations of prolactin and cortisol were measured immediately before and within 30 min after the seizure. Physiological parameters were extracted from clinical records: peak heart rate (HR) during seizure, electroencephalography (EEG) seizure duration, and motor seizure duration. Correlations were calculated using non-parametric tests. RESULTS: Serum prolactin increased after ECT and correlated with peak HR, EEG seizure duration, and motor seizure duration. Peak HR during seizure also correlated positively with both EEG seizure duration and motor seizure duration. Correlations were unaffected by age, sex, baseline prolactin levels, antipsychotics, or beta-blocking agents. Serum cortisol increased after ECT but did not correlate with the seizure evaluation parameters, nor with prolactin concentrations. CONCLUSIONS: Our findings of a positive correlation between peak HR and prolactin that was independent from the peripheral endocrine stress response might be in line with the idea that tachycardia during ECT seizures reflects seizure propagation to the diencephalon. This supports the practice of monitoring cardiovascular response for ECT seizure evaluation.


Assuntos
Eletroconvulsoterapia , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Prolactina , Hidrocortisona , Convulsões/terapia , Eletroencefalografia
6.
J Infect Dis ; 225(6): 965-970, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33744954

RESUMO

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/diagnóstico , Imunoglobulina G/sangue , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/líquido cefalorraquidiano , SARS-CoV-2/isolamento & purificação , Idoso , Anticorpos Neutralizantes/sangue , Formação de Anticorpos , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , COVID-19/sangue , COVID-19/líquido cefalorraquidiano , COVID-19/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/etiologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus
7.
J Neurosci Res ; 99(1): 407-418, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32729199

RESUMO

Lithium is widely used to treat bipolar disorder. However, the efficacy and vulnerability as to its side effects are known to differ. Although the specific biochemical mechanism of action is still elusive, lithium may influence mitochondrial function, and consequently, metabolism. Lithium exposure in this study was conducted on a unique set of mito-nuclear introgression lines of Drosophila subobscura to disentangle the independent effects of mitochondrial DNA (mtDNA) against a common nuclear DNA background. The study addressed three issues: (a) whether lithium has a dose-dependent effect on whole-organism metabolic rate, (b) whether mtDNA haplotypes show divergent metabolic efficiency measured by metabolic rate to lithium exposure and (c) whether lithium influences the whole-organism metabolic rate across sexes. The results confirm that lithium influenced the whole-organism metabolic rate, showing a subtle balance between efficacy and adverse effects within a narrow dose range. In addition, lithium exposure was found to influence metabolism differently based on mtDNA haplotypes and sex. This preliminary research may have a range of biological implications for the role of mitochondrial variability in psychiatric disease and treatment by contributing to the understanding and predicting of the lithium treatment response and risk for toxic side effects.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Compostos de Lítio/toxicidade , Mitocôndrias/efeitos dos fármacos , Sulfatos/toxicidade , Animais , Drosophila , Feminino , Masculino
8.
Psychosom Med ; 83(7): 693-699, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34267089

RESUMO

OBJECTIVE: Short-chain fatty acids (SCFAs) are produced by the gut microbiota and may reflect health. Gut symptoms are common in individuals with depressive disorders, and recent data indicate relationships between gut microbiota and psychiatric health. We aimed to investigate potential associations between SCFAs and self-reported depressive and gut symptoms in young adults. METHODS: Fecal samples from 164 individuals (125 were patients with psychiatric disorders: mean [standard deviation] age = 21.9 [2.6] years, 14% men; 39 nonpsychiatric controls: age = 28.5 [9.5] years, 38% men) were analyzed for the SCFA acetate, butyrate, and propionate by nuclear magnetic resonance spectroscopy. We then compared SCFA ratios with dimensional measures of self-reported depressive and gut symptoms. RESULTS: Depressive symptoms showed a positive association with acetate levels (ρ = 0.235, p = .003) and negative associations with both butyrate (ρ = -0.195, p = .014) and propionate levels (ρ = -0.201, p = .009) in relation to total SCFA levels. Furthermore, symptoms of diarrhea showed positive associations with acetate (ρ = 0.217, p = .010) and negative associations with propionate in relation to total SCFA levels (ρ = 0.229, p = 0-007). Cluster analysis revealed a heterogeneous pattern where shifts in SCFA ratios were observed in individuals with elevated levels of depressive symptoms, elevated levels of gut symptoms, or both. CONCLUSIONS: Shifts in SCFAs are associated with both depressive symptoms and gut symptoms in young adults and may have of relevance for treatment.


Assuntos
Depressão , Microbioma Gastrointestinal , Adulto , Ácidos Graxos Voláteis , Fezes , Feminino , Humanos , Masculino , Adulto Jovem
9.
Eur J Neurol ; 28(10): 3324-3331, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33369818

RESUMO

BACKGROUND AND PURPOSE: Neurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID-19), and biomarkers of central nervous system (CNS) injury are reported to be increased in plasma but not extensively studied in cerebrospinal fluid (CSF). This study examined CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and disease severity in patients with neurological manifestations of COVID-19. METHODS: Nineteen patients with neurological symptoms and mild to critical COVID-19 were prospectively included. Extensive analysis of CSF, including measurement of biomarkers of CNS injury (neurofilament light chain [NfL] protein, glial fibrillary acidic protein [GFAp], and total tau), was performed and compared to neurological features and disease severity. RESULTS: Neurological symptoms included altered mental status (42%), headache (42%), and central (21%) and peripheral weakness (32%). Two patients demonstrated minor pleocytosis, and four patients had increased immunoglobulin G levels in CSF. Neuronal autoantibody testing using commercial tests was negative in all patients. Increased CSF levels of NfL protein, total tau, and GFAp were seen in 63%, 37%, and 16% of patients, respectively. Increased NfL protein correlated with disease severity, time in intensive care, and level of consciousness. NfL protein in CSF was higher in patients with central neurological symptoms. CONCLUSIONS: Although limited by the small sample size, our data suggest that levels of NfL protein, GFAp, and total tau in CSF are commonly elevated in patients with COVID-19 with neurological symptoms. This is in contrast to the standard CSF workup where pathological findings are scarce. NfL protein, in particular, is associated with central neurological symptoms and disease severity.


Assuntos
COVID-19 , Proteínas de Neurofilamentos , Biomarcadores , Sistema Nervoso Central , Proteína Glial Fibrilar Ácida , Humanos , SARS-CoV-2 , Índice de Gravidade de Doença
10.
Acta Neurol Scand ; 143(6): 602-607, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33626181

RESUMO

OBJECTIVE: To identify serum proteins associated with MS and affected by interferon beta treatment. METHODS: Plasma samples from 29 untreated relapsing-remitting MS patients and 15 healthy controls were investigated with a multiplexed panel containing 92 proteins related to inflammation. Follow-up samples were available from 13 patients at 1 and 3 months after initiation of treatment with interferon beta-1a. RESULTS: Ten proteins were differentially expressed in MS patients. Five of these were altered by treatment with IFN-ß 1a: uPA, CX3CL1, CCL2, TRAIL and IL18. CONCLUSION: CCL2 and TRAIL were confirmed to be modulated with interferon beta treatment in MS. As novel findings, we now report that uPA and CX3CL1 were differentially expressed in MS and increased after IFN-beta-1a treatment. Conflicting results have been reported on how interferon beta affects IL-18.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Citocinas/sangue , Citocinas/efeitos dos fármacos , Interferon beta-1a/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Quimiocina CCL2/sangue , Quimiocina CCL2/efeitos dos fármacos , Quimiocina CX3CL1/sangue , Quimiocina CX3CL1/efeitos dos fármacos , Feminino , Humanos , Interleucina-18/sangue , Masculino , Proteínas de Membrana/sangue , Proteínas de Membrana/efeitos dos fármacos , Pessoa de Meia-Idade , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Ligante Indutor de Apoptose Relacionado a TNF/efeitos dos fármacos
11.
Health Expect ; 24 Suppl 1: 20-29, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-31605443

RESUMO

BACKGROUND: Meaningful and generalizable research depends on patients' willingness to participate. Studies often fail to reach satisfactory representativeness. OBJECTIVE: This paper aims to investigate reasons for not participating in research among young adult patients with psychiatric illness. METHOD: A quantitative cross-sectional study was performed based on questionnaires reported on by 51 psychiatric patients (14 males, 35 females and two unspecified) who had previously declined participation in an ongoing research project. Thereafter, a qualitative interview with subsequent content analysis was conducted with ten additional patients (five males, five females). RESULTS: The questionnaires indicate being 'too tired/too sick to participate' as the most common barrier. Lack of time and fear of needles were other common barriers. Lack of trust or belief in the value of research was less inhibitive. In the interviews, disabling psychiatric symptoms were confirmed as the main reason for not participating. Several potential ways to increase participation were identified, such as simplification of procedures and information as well as providing rewards and feedback, and building relationships before asking. CONCLUSION: This study is unusual as it focuses on the group of young people attending psychiatry outpatient clinics we know very little about - those who do not partake in research. Our results indicate that fatigue and sickness reduce research participation and identify factors that may facilitate enrolment of this important group.


Assuntos
Transtornos Mentais , Adolescente , Estudos Transversais , Fadiga , Feminino , Humanos , Masculino , Inquéritos e Questionários , Confiança , Adulto Jovem
12.
J Neurosci Res ; 98(7): 1309-1321, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-30252150

RESUMO

Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.


Assuntos
Quimiocina CXCL1/sangue , Depressão Pós-Parto/sangue , Fatores de Crescimento de Fibroblastos/sangue , Fator de Crescimento de Hepatócito/sangue , Interleucina-18/sangue , Ligante RANK/sangue , Adulto , Biomarcadores/sangue , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Inflamação/sangue
13.
BMC Psychiatry ; 20(1): 535, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176747

RESUMO

BACKGROUND: >Patients with functional gastrointestinal disorders have a high psychiatric co-morbidity. This study aimed to investigate and characterise gastrointestinal symptoms in relation to depressive symptoms and trait anxiety in a well-defined population of young adult psychiatric outpatients and healthy controls. METHODS: Gastrointestinal symptoms were assessed with the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS). Depressive symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale- Self assessment (MADRS-S). Trait anxiety was estimated with three of the Swedish universities of Personality (SSP) scales: Somatic trait anxiety, Psychic trait anxiety and Stress susceptibility. Self-ratings were collected from 491 young adult psychiatric outpatients and 85 healthy controls. Gastrointestinal symptom severity was compared between patients with and without current psychotropic medication and controls. Associations between gastrointestinal symptoms, depressive symptoms and trait anxiety were assessed using Spearman's coefficients and generalized linear models adjusting for possible confounders (sex, body mass index, bulimia nervosa). RESULTS: Patients, with and without current psychotropic medication, reported significantly more gastrointestinal symptoms than controls. In the generalized linear models, total MADRS-S score (p < 0.001), Somatic trait anxiety (p < 0.001), Psychic trait anxiety (p = 0.002) and Stress susceptibility (p = 0.002) were independent predictors of the total GSRS-IBS score. Further exploratory analysis using unsupervised learning revealed a diverse spectrum of symptoms that clustered into six groups. CONCLUSION: Gastrointestinal symptoms are both highly prevalent and diverse in young adult psychiatric outpatients, regardless of current psychotropic medication. Depressive symptom severity and degree of trait anxiety are independently related to the total gastrointestinal symptom burden.


Assuntos
Depressão , Gastroenteropatias , Ansiedade/complicações , Ansiedade/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Gastroenteropatias/complicações , Gastroenteropatias/epidemiologia , Humanos , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Suécia , Adulto Jovem
14.
Psychosom Med ; 81(1): 51-56, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30299401

RESUMO

OBJECTIVE: The pathophysiology of irritable bowel syndrome (IBS) is not completely understood, although we do know that patients with IBS have a high prevalence of psychiatric comorbidity (mainly depression and anxiety disorders). Melatonin, produced in the gastrointestinal tract, influences gut motility. Psychiatric conditions are associated with circadian disturbances in peripheral melatonin levels. This study aimed to investigate associations between daytime salivary melatonin and gastrointestinal symptoms in young adult psychiatric patients. METHODS: Ninety-six patients (86% women), aged 18-25 years (M (SD) = 21 (2)), seeking psychiatric care with primarily anxiety disorders, affective disorders, or both were included in the study. Total scores from the Gastrointestinal Symptoms Rating Scale - IBS were compared with salivary melatonin measured at three time points (30 minutes after waking up, at 11:00 hours and 30 minutes after lunch) during the waking hours of 1 day. RESULTS: After adjustment for potential confounders, melatonin levels in saliva 30 minutes after lunch remained significantly correlated to the total Gastrointestinal Symptoms Rating Scale - IBS score after correction for multiple testing (B = 0.016, SE = 0.006, p = .015, q = 0.045). In a post hoc analysis, symptoms of gastrointestinal pain and bloating contributed most to this association. CONCLUSIONS: In young adult psychiatric patients, salivary melatonin levels after lunch are associated with gastrointestinal symptoms, which is consistent with the proposed effect of elevated levels of gastrointestinal melatonin on gut motility. This result suggests a link between IBS symptoms and regulation of melatonin in patients with psychiatric disorders.


Assuntos
Transtornos de Ansiedade/metabolismo , Síndrome do Intestino Irritável/metabolismo , Melatonina/metabolismo , Transtornos do Humor/metabolismo , Adolescente , Adulto , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/fisiopatologia , Ritmo Circadiano/fisiologia , Comorbidade , Feminino , Humanos , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Transtornos do Humor/epidemiologia , Transtornos do Humor/fisiopatologia , Saliva , Adulto Jovem
15.
Int J Mol Sci ; 20(24)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817800

RESUMO

Immunomodulation is increasingly being recognised as a part of mental diseases. Here, we examined whether levels of immunological protein markers changed with depression, age, or the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). An analysis of plasma samples from patients with a major depressive episode and control blood donors (CBD) revealed the expression of 67 inflammatory markers. Thirteen of these markers displayed augmented levels in patients compared to CBD. Twenty-one markers correlated with the age of the patients, whereas 10 markers correlated with the age of CBD. Interestingly, CST5 and CDCP1 showed the strongest correlation with age in the patients and CBD, respectively. IL-18 was the only marker that correlated with the MADRS-S scores of the patients. Neuronal growth factors (NGFs) were significantly enhanced in plasma from the patients, as was the average plasma GABA concentration. GABA modulated the release of seven cytokines in anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) from the patients. The study reveals significant changes in the plasma composition of small molecules during depression and identifies potential peripheral biomarkers of the disease.


Assuntos
Biomarcadores/sangue , Biomarcadores/metabolismo , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/metabolismo , Inflamação/sangue , Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Ácido gama-Aminobutírico/metabolismo , Adulto , Fatores Etários , Idoso , Depressão , Transtorno Depressivo Maior/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
BMC Psychiatry ; 18(1): 157, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29843679

RESUMO

BACKGROUND: Treatment of Hepatitis C virus (HCV) infection has evolved from interferon (IFN)-based treatments to direct-acting antivirals (DAAs). Patients with HCV have an elevated psychiatric morbidity (including substance abuse) and patients with such comorbidity have often been excluded from treatment with IFN. To date, little is known about psychiatric adverse effects of DAA-based regimens. We therefore aimed to study the psychiatric side effects of new IFN-free treatment for HCV (including depressive symptoms and sleep) in real world patients also including those with a history of psychiatric diagnosis, substance abuse or drug dependence. METHODS: Consecutive patients were monitored during treatment with three of the latest DAA agents (sofosbuvir, simeprevir and daclatasvir). Repeated expert psychiatric assessments from baseline to 12 weeks post-treatment were performed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) clinical version and the self-report versions of the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Pittsburgh Sleep Quality Index (PSQI). Friedman's test was performed to calculate differences in the MADRS-S and PSQI over time. In a post-hoc analysis Wilcoxon's test was used to compare baseline depressive symptoms with those at post-treatment. Spearman's rank correlation test was conducted in another post-hoc analysis to evaluate the correlation between symptoms of depression and HCV viral load at baseline. RESULTS: At baseline, 15/17 patients (88%) had a history of any psychiatric diagnosis; 11 (65%) had a history of substance abuse or dependence; and 11 (65%) had previously been treated with IFN and six of those had experienced psychiatric side effects. There was no correlation between depressive symptoms and HCV viral load at baseline. Symptoms of depression did not increase during DAA treatment and were lower 12 weeks post-treatment compared with baseline: MADRS-S 10.7 vs. 8.3 (p = 0.01). This observation held when excluding patients taking antidepressant medication. Sleep quality did not significantly change during treatment. Adherence to treatment was estimated to 95% and sustained virological response was 88%. CONCLUSIONS: Despite high psychiatric morbidity, including previous substance abuse, patients successfully completed DAA treatment without increasing depressive symptoms or sleep disturbance. Symptoms of depression were significantly reduced 12 weeks after DAA treatment.


Assuntos
Antivirais/efeitos adversos , Depressão , Hepatite C , Sono/efeitos dos fármacos , Transtornos Relacionados ao Uso de Substâncias , Adulto , Antivirais/classificação , Antivirais/uso terapêutico , Correlação de Dados , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Hepacivirus/fisiologia , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Suécia/epidemiologia , Carga Viral/métodos
17.
Cephalalgia ; 37(5): 435-441, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27165492

RESUMO

Background Migraine is a prevalent disorder characterised by recurrent headache attacks preceded or accompanied by aura in a subgroup of patients. Migraine often occurs together with major depressive disorder (MDD). Alterations of adipokine levels have been reported both in migraine and in MDD. In this cross-sectional study, we aimed to assess the associations between serum leptin and adiponectin levels and migraine or migraine subtypes. Analyses were adjusted for a lifetime history of MDD in order to investigate the association between adipokines and migraine under consideration of depression status. Methods We included 3025 participants from the CoLaus/PsyCoLaus study. The impact of leptin and adiponectin levels on a diagnosis of migraine was analysed by binary regression analyses, adjusting for variables known to influence adipokine levels. Subgroup analyses were conducted based on the presence of aura. Results Crude leptin levels were significantly higher in subjects with migraine than controls (Mann-Whitney U = 515,102, p = 6 × 10-7). When performing adjusted analyses, leptin levels were found to be significantly higher in subjects with migraine (odds ratio = 1.22, p = 0.024) and migraine with aura (odds ratio = 1.34, p = 0.004). Conclusion High leptin levels might play a role in the pathogenesis of migraine and migraine with aura.


Assuntos
Leptina/sangue , Enxaqueca com Aura/sangue , Enxaqueca com Aura/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enxaqueca com Aura/epidemiologia , Distribuição Aleatória , Suíça/epidemiologia
18.
BMC Psychiatry ; 17(1): 21, 2017 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-28095825

RESUMO

BACKGROUND: Research in vulnerable individuals must insure voluntariness and minimize negative reactions caused by participation. This study aimed to describe consent and completion rate in young psychiatric patients in relation to study components, degree of disability and to compare response to research participation in patients and controls. METHODS: Between 2012 and 2015, 463 patients with psychiatric disorders between the ages of 18-25 from the Dept. of General Psychiatry at Uppsala University Hospital and 105 controls were recruited to donate data and samples to a biobank. Consent and completion in relation to questionnaires, biological sampling of blood, saliva or feces, were monitored. Both groups were also asked about their perceived disability and how research participation affected them. RESULTS: Most patients who participated consented to and completed questionnaires and blood sampling. The majority also consented to saliva sampling, while less than half consented to collect feces. Of those who gave consent to saliva and feces only half completed the sampling. Both patients and controls reported high voluntariness and were positive to research participation. Within the patient group, those with greater perceived disability reported greater distress while participating in research, but there was no difference in consent or completion rates or level of regret. CONCLUSIONS: With the described information procedures, psychiatric patients, regardless of perceived disability, reported high voluntariness and did not regret participation in biobanking. Compared to questionnaires and blood sampling, given consent was reduced for feces and completion was lower for both saliva and feces sampling.


Assuntos
Bancos de Espécimes Biológicos , Emoções , Consentimento Livre e Esclarecido/psicologia , Transtornos Mentais/psicologia , Participação do Paciente/psicologia , Unidade Hospitalar de Psiquiatria , Adolescente , Adulto , Bancos de Espécimes Biológicos/tendências , Feminino , Humanos , Masculino , Participação do Paciente/métodos , Participação do Paciente/tendências , Unidade Hospitalar de Psiquiatria/tendências , Inquéritos e Questionários , Adulto Jovem
20.
Sci Rep ; 14(1): 11635, 2024 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773198

RESUMO

Evidence links immune system alterations to major psychiatric disorders. The few previous studies on personality traits or personality disorders (PDs) indicate that immunometabolic dysregulation may be prevalent in this population. This study aimed to investigate relationships between personality traits, PDs, and immunometabolic markers in peripheral blood. We hypothesized that neuroticism would be correlated with elevated leptin. Participants were recruited as young adults seeking care for general psychiatric disorders. They responded to a personality inventory and were assessed for PDs, and reevaluated again at a 12 years follow-up. Blood samples were collected at the follow-up and analyzed for 29 immunometabolic markers. A positive correlation was found between the personality trait neuroticism and leptin (ρ = 0.31, p = 0.02). An exploratory analysis also revealed a positive correlation between brain-derived neurotrophic factor (ρ = 0.36, p < 0.01) and neuroticism. These findings remained after adjusting for other variables in general linear models. There were no relationships between PDs and any immunometabolic markers. Results both confirm previous findings of correlations between the immunometabolic system and personality traits and suggest directions for future research.


Assuntos
Biomarcadores , Neuroticismo , Transtornos da Personalidade , Personalidade , Humanos , Feminino , Masculino , Transtornos da Personalidade/sangue , Transtornos da Personalidade/psicologia , Biomarcadores/sangue , Adulto , Adulto Jovem , Leptina/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Inventário de Personalidade , Adolescente
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