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Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorders(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta-analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI -0.55-0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05-0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17-0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptoms severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdownand sex-related differences in SSDs clinical trials and treatment strategies.
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Transtornos Psicóticos , Esquizofrenia , Humanos , Transtornos Psicóticos/líquido cefalorraquidiano , Esquizofrenia/líquido cefalorraquidiano , Masculino , Feminino , Barreira Hematoencefálica/metabolismo , Adulto , Índice de Gravidade de Doença , Fatores Sexuais , Biomarcadores/líquido cefalorraquidianoRESUMO
PURPOSE: Human Borna disease virus (BoDV-1) encephalitis is an emerging disease in Germany. This study investigates the spectrum of human BoDV-1 infection, characterizes anti-BoDV-1-antibodies and kinetics, and compares laboratory test performances. METHODS: Three hundred four encephalitis cases, 308 nation-wide neuropsychiatric conditions, 127 well-defined psychiatric cases from Borna disease-endemic areas, and 20 persons with contact to BoDV-1 encephalitis patients or animals were tested for BoDV-1 infections by serology and PCR. RESULTS: BoDV-1 infections were only found in encephalitis patients with residence in, or recent travel to, virus-endemic areas. Antibodies were detected as early as 12 days after symptom onset. Serum antibody levels correlated with disease duration. Serology was ordered after 50% of the disease duration had elapsed, reflecting low awareness. BoDV-1-antibodies were of IgG1 subclass, and the epitope on BoDV-1 antigens was determined. Specificity of the indirect immunofluorescence antibody test (IFAT) and lineblot (LB) from serum and cerebrospinal fluid (CSF), as well as PCR testing from CSF, was 100%. Sensitivity, depending on first or all samples, reached 75-86% in serum and 92-94% in CSF for the IFAT, and 33-57% in serum and 18-24% in CSF for the LB. Sensitivity for PCR in CSF was 25-67%. Positive predictive values were 100% each, while negative predictive values were 99% (IFAT), 91-97% (LB), and 90% (PCR). CONCLUSIONS: There is no hint that BoDV-1 causes other diseases than encephalitis in humans. Awareness has to be increased in virus-endemic areas. Tests are robust but lack sensitivity. Detection of IgG1 against specific peptides may facilitate diagnosis. Screening of healthy individuals is likely not beneficial.
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Vírus da Doença de Borna , Bornaviridae , Encefalite , Vírus , Animais , Humanos , Vírus da Doença de Borna/genética , Bornaviridae/genética , Correlação de Dados , Vírus/genética , Anticorpos Antivirais , RNA Viral/genética , Imunoglobulina GRESUMO
Opioid addiction is a global problem, causing the greatest health burden among drug use disorders, with opioid overdose deaths topping the statistics of fatal overdoses. The multifunctional anterior insular cortex (AIC) is involved in inhibitory control, which is severely impaired in opioid addiction. GABAergic interneurons shape the output of the AIC, where abnormalities have been reported in individuals addicted to opioids. In these neurons, glutamate decarboxylase (GAD) with its isoforms GAD 65 and 67 is a key enzyme in the synthesis of GABA, and research data point to a dysregulation of GABAergic activity in the AIC in opioid addiction. Our study, which was performed on paraffin-embedded brains from the Magdeburg Brain Bank, aimed to investigate abnormalities in the GABAergic function of the AIC in opioid addiction by densitometric evaluation of GAD 65/67-immunostained neuropil. The study showed bilaterally increased neuropil density in layers III and V in 13 male heroin-addicted males compared to 12 healthy controls, with significant U-test P values for layer V bilaterally. Analysis of confounding variables showed that age, brain volume and duration of formalin fixation did not confound the results. Our findings suggest a dysregulation of GABAergic activity in the AIC in opioid addiction, which is consistent with experimental data from animal models and human neuroimaging studies.
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Opioid addiction is a global problem that has been exacerbated in the USA and Europe by the COVID-19 pandemic. The globus pallidus (GP) plays a prominent neurobiological role in the regulation of behaviour as an output station of the striato-pallidal system. GABAergic large projection neurons are the main neuronal type in the external (EGP) and internal (IGP) parts of the GP, where addiction-specific molecular and functional abnormalities occur. In these neurons, glutamate decarboxylase (GAD) with isoforms GAD 65 and 67 is a key enzyme in GABA synthesis, and experimental studies suggest GAD dysregulation in the GP of heroin addicts. Our study, which was performed on paraffin-embedded brains from the Magdeburg Brain Bank, aimed to investigate abnormalities in the GABAergic function of large GP neurons by densitometric evaluation of their GAD 65/67-immunostained thick dendrites. The study revealed a bilaterally decreased fibres density in the EGP paralleled by the increase in the IGP in 11 male heroin addicts versus 11 healthy controls (significant U-test P values). The analysis of confounding variables found no interference of age, brain volume, and duration of formalin fixation with the results. Our findings suggest a dysregulation of GABAergic activity in the GP of heroin addicts, which is consistent with experimental data from animal models and plays potentially a role in the disturbed function of basal ganglia circuit in opioid addiction.
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Globo Pálido , Transtornos Relacionados ao Uso de Opioides , Animais , Masculino , Humanos , Heroína , Pandemias , Gânglios da BaseRESUMO
The role of the complement system in schizophrenia (Sz) is inconclusive due to heterogeneity of the disease and study designs. Here, we assessed the levels of complement activation products and functionality of the classical pathway in acutely ill unmedicated Sz patients at baseline and after 6 weeks of treatment versus matched controls. The study included analyses of the terminal complement complex (sTCC) and C5a in plasma from 96 patients and 96 controls by enzyme-linked immunosorbent assay. Sub-group analysis of serum was conducted for measurement of C4 component and activity of the classical pathway (28 and 24 cases per cohort, respectively). We found no differences in levels of C5a, C4 and classical pathway function in patients versus controls. Plasma sTCC was significantly higher in patients [486 (392-659) ng/mL, n = 96] compared to controls [389 (304-612) ng/mL, n = 96] (p = 0.027, δ = 0.185), but not associated with clinical symptom ratings or treatment. The differences in sTCC between Sz and controls were confirmed using an Aligned Rank Transformation model considering the covariates age and sex (p = 0.040). Additional analysis showed that sTCC was significantly associated with C-reactive protein (CRP; p = 0.006). These findings suggest that sTCC plays a role in Sz as a trait marker of non-specific chronic immune activation, as previously described for CRP. Future longitudinal analyses with more sampling time points from early recognition centres for psychoses may be helpful to better understand the temporal dynamics of innate immune system changes during psychosis development.
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Esquizofrenia , Humanos , Esquizofrenia/sangue , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Complemento C4/análise , Complemento C4/metabolismo , Complemento C5a , Adulto Jovem , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Complexo de Ataque à Membrana do Sistema Complemento/metabolismoRESUMO
Ethanol is metabolized by alcohol dehydrogenase to acetaldehyde and induces cytochrome P450 2E1 (CYP2E1), which generates reactive oxygen species that cause inflammatory liver damage. Clomethiazole, a drug approved for alcohol withdrawal treatment (AWT) in some European countries, inhibits CYP2E1. We hypothesized that clomethiazole would lead to a faster reduction in oxidative stress, inflammatory cytokines, and liver enzymes compared to diazepam treatment. We analysed respective biomarkers in 50 patients undergoing AWT and 25 healthy individuals but found no statistical difference between the two medication groups over 3-5 days. Hence, our hypothesis was not confirmed during this observation period.
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Nicotinic acetylcholine receptors (nAChRs) are widely expressed in many and diverse cell types, participating in various functions of cells, tissues and systems. In this review, we focus on the autoimmunity against neuronal nAChRs, the specific autoantibodies and their mechanisms of pathological action in selected autoimmune diseases. We summarize the current relevant knowledge from human diseases as well as from experimental models of autoimmune neurological disorders related to antibodies against neuronal nAChR subunits. Despite the well-studied high immunogenicity of the muscle nAChRs where autoantibodies are the main pathogen of myasthenia gravis, autoimmunity to neuronal nAChRs seems infrequent, except for the autoantibodies to the ganglionic receptor, the α3 subunit containing nAChR (α3-nAChR), which are detected and are likely pathogenic in Autoimmune Autonomic Ganglionopathy (AAG). We describe the detection, presence and function of these antibodies and especially the recent development of a cell-based assay (CBA) which, contrary to until recently available assays, is highly specific for AAG. Rare reports of autoantibodies to the other neuronal nAChR subtypes include a few cases of antibodies to α7 and/or α4ß2 nAChRs in Rasmussen encephalitis, schizophrenia, autoimmune meningoencephalomyelitis, and in some myasthenia gravis patients with concurrent CNS symptoms. Neuronal-type nAChRs are also present in several non-excitable tissues, however the presence and possible role of antibodies against them needs further verification. It is likely that the future development of more sensitive and disease-specific assays would reveal that neuronal nAChR autoantibodies are much more frequent and may explain the mechanisms of some seronegative autoimmune diseases.
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Doenças Autoimunes do Sistema Nervoso , Miastenia Gravis , Receptores Nicotínicos , Humanos , Autoimunidade , Receptores Nicotínicos/metabolismo , Doenças Autoimunes do Sistema Nervoso/diagnóstico , AutoanticorposRESUMO
Patients with major depression (MD) are at high-risk for insulin resistance (IR), type-2 diabetes, metabolic syndrome, cardiovascular morbidity and mortality. However, our recent study published in this journal [Eur Arch Psychiatry Clin Neurosci. 2019 Jun;269(4):373-377], found no evidence of IR in acutely-ill drug-naive first-episode MD (FEMD) using the homeostatic model assessment of insulin resistance (HOMA-IR). We concluded, that MD may be related to impaired glucose/insulin homeostasis in the long-term but not in early disease stages. Now, we performed a complementary analysis of the canonical insulin signalling pathway containing the set of control and FEMD samples from the study mentioned above. The first node (pS312-IRS-1, pY-IRS-1) and downstream pathway which affects glucose and lipid homeostasis (phosphorylated proteins: pS473-AKT, pS9-GSK3ß, pS2448-mTOR, pT389-p70S6K; total proteins AKT, GSK3ß, mTOR, p70S6K) were analyzed by electrochemiluminescence (ECL) in neuronal extracellular vesicles (nEVs) enriched for L1 neural cell adhesion molecule (L1CAM) expression. No significant diagnosis-related differences were observed for the pS312-IRS-1 / pYIRS-1 ratio (P = 0.093), but the mean ratio was reduced by ~ 70% in FEMD versus controls. Moreover, omnibus analysis of downstream phosphorylated / total signaling protein ratios and respective post-hoc analyses revealed no significant changes in FEMD patients versus controls (P = 0.734). HAMD-21 scores were not correlated with pS312-IRS-1 / pY-IRS-1 or downstream phosphorylated/total signaling protein ratios. In summary, we did not find evidence for altered neuronal insulin signaling in early disease stages of MD. This is in contrast to schizophrenia, where we and other researchers have seen evidence of IR in first-episode patients.
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Resistência à Insulina , Insulina , Humanos , Resistência à Insulina/fisiologia , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Depressão , Fosforilação , Serina-Treonina Quinases TOR , Glucose/metabolismoRESUMO
The anterior cingulate cortex (AC) as a part of prefrontal cortex plays a crucial role in behavioural regulation, which is profoundly disturbed in suicide. Citrate synthase (CS) is a key enzyme of tricarboxylic acid cycle fundamental for brain energetics and neurotransmitter synthesis, which are deteriorated in suicidal behaviour. However, CS activity has not been yet studied in brain structures of suicide victims. CS activity assay was performed bilaterally on frozen samples of the rostral part of the AC of 24 violent suicide completers (21 males and 3 females) with unknown psychiatric diagnosis and 24 non-suicidal controls (20 males and 4 females). Compared to controls, suicide victims revealed decreased CS activity in the right AC, however, insignificant. Further statistical analysis of laterality index revealed the left-lateralisation of CS activity in the AC in male suicides compared to male controls (U-test P = 0.0003, corrected for multiple comparisons). The results were not confounded by postmortem interval, blood alcohol concentration, age, and brain weight. Our findings suggest that disturbed CS activity in the AC plays a role in suicide pathogenesis and correspond with our previous morphological and molecular studies of prefrontal regions in suicide.
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Suicídio , Feminino , Humanos , Masculino , Suicídio/psicologia , Giro do Cíngulo/patologia , Citrato (si)-Sintase , Concentração Alcoólica no Sangue , Encéfalo/patologia , Córtex Pré-Frontal/patologiaRESUMO
The paper, which is a continuation of our previous epidemiological studies on the phenomenon of suicide in the Tri-City metropolitan area, presents the results of statistical analyses of suicides in the autopsy material of the Department of Forensic Medicine of the Medical University of Gdansk in the years 2010-2019. The purpose of the study was to analyse in detail demographic data of suicides (age, sex, place of death), as well as to assess suicide methods and the impact of alcohol on suicides in the study area. During the 10-year study period, 8495 autopsies were performed, of which 1261 were suicides (14.8%). Statistical analyses were conducted using the statistical data analysis software system STATISTICA, version 13 (StatSoft, Tulsa, Oklahoma, USA). The results of the study indicate a continuing downward trend in the number of suicides since the beginning of the 21th century, with the number of suicides in rural areas increasing over the same period. In the analysed cohort, suicides were committed in particular by middle-aged men and the number of suicides among older people (65 +) increased at the same time. The increase in suicide occurred in late autumn and early spring. The most common method of suicide was hanging. There was a high percentage of inebriated victims (45%), and a comparison of the present studies with previous ones indicates the increasing impact of alcohol on suicide.
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Suicídio , Pessoa de Meia-Idade , Masculino , Humanos , Idoso , Polônia/epidemiologia , Autopsia , Medicina Legal/métodos , EtanolRESUMO
We determined cytokine levels in paired serum/CSF samples from first-episode schizophrenia (FES) participants (n = 20) and controls (n = 21) using a 13-plex immunoassay. Applying strictly-determined detection limits, 12 cytokines were found in serum and two in CSF. Higher serum MCP-1 levels (p = 0.007) were present in FES versus controls, which correlated with serum IgG (R = - 0.750; p = 0.013). Finally, IL-18 levels correlated with body weight in FES (R = 0.691; p = 0.041). This study demonstrates potential limitations in the sensitivity of multiplex cytokine assays for CSF studies in mental disorders and suggests that some published studies in this area should be re-evaluated.
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Citocinas , Esquizofrenia , HumanosRESUMO
We and others have observed reduced volumes of brain regions, including the nucleus accumbens, globus pallidus, hypothalamus, and habenula in opioid addiction. Notably, the insular cortex has been under increasing study in addiction, and a smaller anterior insula has been found in alcohol-addicted cases. Here, we have investigated whether similar effects occur in heroin addicts compared to healthy controls. Volumes of the anterior and posterior insula in heroin addicts (n = 14) and controls (n = 13) were assessed by morphometry of Nissl-myelin-stained serial whole-brain coronal sections. The mean relative volume of the anterior insular cortex was smaller than in non-addicted controls (3010 ± 614 *10-6 versus 3970 ± 1306 *10-6; p = 0.021). However, no significant differences in neuronal cell counts were observed. Therefore, the observed volume reduction appears to be a consequence of damaged connecting structures such as neuropil and glial cells. The findings were not confounded by age or duration of autolysis. Our results provide further evidence of structural deficits in key hubs of the addiction circuitry in heroin-dependent individuals and warrant further research in this area.
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Dependência de Heroína , Heroína , Humanos , Masculino , Córtex Insular , Encéfalo , Núcleo Accumbens , Imageamento por Ressonância Magnética/métodos , Córtex Cerebral/diagnóstico por imagemRESUMO
BACKGROUND: The global pandemic of the coronavirus disease 2019 (COVID-19) has presented many unique challenges to health systems. The hidden impact of COVID-19 and its associated lockdown have been an increased prevalence of domestic violence. OBJECTIVE: To increase our understanding of the connection between COVID-19 containment measures, domestic violence, and mental health in Germany, we conducted an online self-assessment survey of 98 domestic violence victims and 276 controls. All participants answered questions concerning domestic violence, emotional regulation skills, limitations due to and acceptance of containment measures, and quality of their contact experiences. RESULTS: There was no significant effect of "gender" x "domestic violence." Among victims of domestic violence, the number of women was considerably higher than the number of men. In addition, the factors "negative contact quality," "emotional regulation," and "resilience" differed significantly between the victims of domestic violence and the control group. CONCLUSIONS: The COVID-19 outbreak and associated containment and quarantine measures resulted in a "hidden pandemic" of domestic violence for which prevention programs and early victim assistance through the expansion of digital technologies are urgently needed. Prospective studies should expand empirical data to focus on the long-term psychological effects of domestic violence and biomarkers that can serve as warning signs of stress-related disorders.
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COVID-19 , Violência Doméstica , Masculino , Humanos , Feminino , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , SARS-CoV-2 , Estudos Prospectivos , Controle de Doenças Transmissíveis , Violência Doméstica/psicologiaRESUMO
Approximately 30% of COVID-19 cases may experience chronic symptoms, known as post-COVID-19 syndrome (PCS). Common PCS symptoms can include fatigue, cognitive impairment, and persistent physical, neurological, and neuropsychiatric complaints. To improve healthcare and management of the current and future pandemics, we highlight the need for establishing interdisciplinary post-viral outpatient clinics comprised of specialists in fields such as psychiatry, psychotherapy, neurology, cardiology, pneumology, and immunology. In this way, PCS patients with a high health burden can receive modern diagnostics and targeted therapeutic recommendations. A key objective is to distinguish the "sick recovered" from the "healthy recovered." Our hypothesis is that there is a PCS subgroup with autoimmune-mediated systemic and brain-vascular dysregulation, which may lead to circulatory disorders, fatigue, cognitive impairment, depression, and anxiety. This can be clarified using a combination of specific antibody diagnostics and precise clinical, psychological, and apparative testing.
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COVID-19 , Triagem , Humanos , Síndrome de COVID-19 Pós-Aguda , COVID-19/complicações , Biomarcadores , FadigaRESUMO
BACKGROUND: We recently reported increased levels of neutrophils, monocytes and C-reactive protein (CRP) correlated with symptom severity in acute schizophrenia. Here, we investigated if a similar pattern of innate immune system activation occurs in major depression (MD). METHODS: We assessed differential blood counts, CRP, depression symptoms (HAMD-21) and psychosocial functioning (GAF) in controls (n = 129) and patients with first (FEMD: n = 82) or recurrent (RMD: n = 47) disease episodes of MD at baseline (T0; hospital admission) and after 6-weeks treatment (T6). RESULTS: Considering smoking, BMI and gender as covariates, neutrophils (FEMD: p = 0.034, RMD: p = 0.034) and CRP (FEMD: p < 0.001, RMD: p = 0.021) were higher, and eosinophils (FEMD: p = 0.005, RMD: p = 0.004) lower in patients versus controls at T0. Baseline lymphocyte counts were elevated in RMD (p = 0.003) but not FEMD. Results were confirmed by analyses of nonsmokers. At follow-up, eosinophils rose significantly in FEMD (p = 0.011) but no significant changes were observed in RMD. Improvement in HAMD-21 correlated with T0-T6 changes of neutrophil counts in FEMD (r = 0.364, p = 0.024). Compared with our previous schizophrenia study, raised baseline neutrophil and reduced eosinophil counts in MD had smaller effect sizes and treatment had a weaker association with T0-T6 changes in neutrophils. In addition, lymphocytes were elevated at T0 in recurrent MD but not in schizophrenia patients. CONCLUSIONS: These findings suggest that innate immunity may be involved in early stages of MD, and adaptive immunity may be involved in chronic disease. Thus, further studies may lead to new disease stage-dependent MD treatment strategies targeting different aspects of immune system activation.
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Proteína C-Reativa , Transtorno Depressivo Maior , Proteína C-Reativa/metabolismo , Depressão , Humanos , Imunidade Inata , Leucócitos/metabolismo , Receptores ImunológicosRESUMO
Opioid addiction is a worldwide problem accentuated in the USA and European countries by the COVID-19 pandemic. The nucleus accumbens (NAc) plays an outstanding neurobiological role in opioid addiction as a part of the striatum and key component of brain reward system. The striatal GABAergic medium spiny projection neurons (MSNs) are the main neuronal type in the NAc where addiction-specific synaptic plasticity occurs. The activity of ribosomal DNA (rDNA) transcription is crucial for neural plasticity and molecular studies suggest its increase in the NAc of heroin addicts. Silver-stained argyrophilic nucleolar organizer region (AgNOR) areas visualised in neuronal nuclei in paraffin-embedded brain sections are reliable morphological estimators of rDNA transcription and thus surrogate markers for the activity of brain regions. Our study revealed increased AgNOR areas in MSNs of the left NAc in 11 heroin addicts versus 11 healthy controls from the Magdeburg Brain Bank (U-test P = 0.007). No differences were observed in another investigated part of the striatum, namely the head of caudate nucleus, which is located closely to the NAc. The results were not confounded by significant differences in the age, brain volume and time of formalin fixation existing between compared groups. Our findings suggest an increased NAc activity in heroin addicts, which is consistent with human and animal experimental data.
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COVID-19 , Dependência de Heroína , Masculino , Animais , Humanos , Núcleo Accumbens/fisiologia , Heroína , DNA Ribossômico , PandemiasRESUMO
This narrative review examines the possible role of microglial cells, first, in neuroinflammation and, second, in schizophrenia, depression, and suicide. Recent research on the interactions between microglia, astrocytes and neurons and their involvement in pathophysiological processes of neuropsychiatric disorders is presented. This review focuses on results from postmortem, positron emission tomography (PET) imaging studies, and animal models of schizophrenia and depression. Third, the effects of antipsychotic and antidepressant drug therapy, and of electroconvulsive therapy on microglial cells are explored and the upcoming development of therapeutic drugs targeting microglia is described. Finally, there is a discussion on the role of microglia in the evolutionary progression of human lineage. This view may contribute to a new understanding of neuropsychiatric disorders.
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Transtorno Depressivo Maior , Esquizofrenia , Suicídio , Animais , Humanos , Microglia , Tomografia por Emissão de Pósitrons/métodos , Esquizofrenia/terapia , Suicídio/psicologiaRESUMO
Approximately 30% of individuals with severe SARS-CoV-2 infections also develop neurological and psychiatric complaints. In rare cases, the occurrence of autoimmune encephalitis has been reported after SARS-CoV-2 infection. In this systematic review, we have identified eight SARS-CoV-2-associated cases of anti-NMDA receptor encephalitis. All had cerebrospinal fluid antibodies against the NMDA receptor and a recent onset of working memory deficits, altered mental status, or psychiatric symptoms, such as confusion, agitation, auditory hallucination, catatonia and speech dysfunction. All patients received high-dose steroid and immunoglobulin therapeutics and conditions improved in each case. These findings suggest that clinical attention should be paid to warning signs of autoimmune encephalitis in severe COVID-19 cases. If characteristic features of autoimmune encephalitis are present, autoantibody diagnostics should be performed and confirmed cases should be treated with immunotherapy to minimize neurological impairments.
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Encefalite Antirreceptor de N-Metil-D-Aspartato/virologia , COVID-19/complicações , Transtornos Mentais/virologia , Receptores de N-Metil-D-Aspartato/imunologia , Adolescente , Adulto , Autoanticorpos/imunologia , COVID-19/imunologia , Criança , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mimetismo Molecular , SARS-CoV-2/imunologia , Adulto JovemRESUMO
Prefrontal cortical regions play a key role in behavioural regulation, which is profoundly disturbed in suicide. The study was carried out on frozen cortical samples from the anterior cingulate cortex (dorsal and ventral parts, ACd and ACv), the orbitofrontal cortex (OFC), and the dorsolateral cortex (DLC) obtained from 20 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 21 non-suicidal controls. The relative level of ribosomal RNA (rRNA) as a marker of the transcriptional activity of ribosomal DNA (rDNA) was evaluated bilaterally in prefrontal regions mentioned above (i.e. in eight regions of interest, ROIs) by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). The overall statistical analysis revealed a decrease in rDNA activity in suicide victims versus controls, particularly in male subjects. Further ROI-specific post hoc analyses revealed a significant decrease in this activity in suicides compared to non-suicides in five ROIs. This effect was accentuated in the ACv, where it was observed bilaterally. Our findings suggest that decreased rDNA transcription in the prefrontal cortex plays an important role in suicide pathogenesis and corresponds with our previous morphometric analyses of AgNOR-stained neurons.
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DNA Ribossômico/metabolismo , Giro do Cíngulo/metabolismo , Região Organizadora do Nucléolo/metabolismo , Córtex Pré-Frontal/metabolismo , Células Piramidais/metabolismo , Suicídio Consumado , Transcrição Gênica/genética , Adulto , Autopsia , Humanos , Coloração pela PrataRESUMO
The Habenula is increasingly being investigated in addiction. Reduced volumes of other relevant brain regions in addiction, such as nucleus accumbens, globus pallidus and hypothalamus have been reported. Reduced volumes of the habenula as well as reduced neuronal cell count in the habenula have also been reported in mood disorders and an overlap between mood disorders and addiction is clinically widely recognized. Thus, our aim was to investigate possible volume and neuronal cell count differences in heroin addicts compared to healthy controls. Volumes of the medial (MHB) and lateral habenula (LHB) in heroin addicts (n = 12) and healthy controls (n = 12) were assessed by morphometry of 20 µm serial whole brain sections. Total brain volume was larger in the heroin group (mean 1466.6 ± 58.5 cm3 vs. mean 1331.5 ± 98.8 cm3), possibly because the heroin group was about 15 years younger (p = 0.001). Despite larger mean whole brain volume, the mean relative volume of the MHB was smaller than in healthy non-addicted controls (6.94 ± 2.38 × 10-6 vs.10.64 ± 3.22 × 10-6; p = 0.004). A similar finding was observed regarding relative volumes of the LHB (46.62 ± 10.90 × 10-6 vs. 63.05 ± 16.42 × 10-6 p = 0.009). In parallel, neuronal cell numbers were reduced in the MHB of heroin-addicted subjects (395,966 ± 184,178 vs. 644,149 ± 131,140; p < 0.001). These findings were not significantly confounded by age and duration of autolysis. Our results provide further evidence for brain-structural deficits in heroin addiction.