European Archives of Psychiatry and Clinical Neuroscience最新文献

Schizophrenia (SCZ) is a severe psychotic disorder associated with premature mortality and aging. Moreover, the symptoms and progression of psychiatric disorders in general are associated with decreased lifespan, biological aging, and poorer medical outcomes. In this study, we investigated the relationship between several epigenetic clocks and scanned the entire genome for association in a cohort of SCZ individuals (n = 107). Biological age was computed from blood DNA methylation (DNAm) and tested for association against  common  variants across the genome using general linear models. Genes affecting epigenetic age acceleration in our cohort were found mainly when using the telomeric length clock rather than the other biological clocks. These findings pair with existing evidence that there are some genes associated with longevity and suggest further investigations of  putative biological mechanisms for morbidity and premature mortality, not only in patients with SCZ but also in the general population.

Unipolar depression is a prevalent and disabling condition, often left untreated. In the outpatient setting, general practitioners fail to recognize depression in about 50% of cases mainly due to somatic comorbidities. Given the significant economic, social, and interpersonal impact of depression and its increasing prevalence, there is a need to improve its diagnosis and treatment in outpatient care. Various efforts have been made to isolate individual biological markers for depression to streamline diagnostic and therapeutic approaches. However, the intricate and dynamic interplay between neuroinflammation, metabolic abnormalities, and relevant neurobiological correlates of depression is not yet fully understood. To address this issue, we propose a naturalistic prospective study involving outpatients with unipolar depression, individuals without depression or comorbidities, and healthy controls. In addition to clinical assessments, cardiovascular parameters, metabolic factors, and inflammatory parameters are collected. For analysis we will use conventional statistics as well as machine learning algorithms. We aim to detect relevant participant subgroups by data-driven cluster algorithms and their impact on the subjects' long-term prognosis. The POKAL-PSY study is a subproject of the research network POKAL (Predictors and Clinical Outcomes in Depressive Disorders; GRK 2621).

Objectives: Emerging evidence indicates a connection between oxidative stress, immune-inflammatory processes, and the negative symptoms of schizophrenia. In addition to possessing potent antioxidant and anti-inflammatory properties, sulforaphane (SFN) has shown promise in enhancing cognitive function among individuals with schizophrenia. This study aims to investigate the efficacy of combined treatment with SFN in patients with schizophrenia who experience negative symptoms and its effect on the levels of superoxide dismutase (SOD) and the inflammatory marker, high-sensitivity C-reactive protein (HsCRP).

Design: Forty-five patients with schizophrenia were recruited, who mainly experienced negative symptoms during a stable period. In addition to the original treatments, the patients received SFN tablets at a daily dose of 90 mg for 24 weeks. At baseline, 12 weeks, and 24 weeks, the participants were interviewed and evaluated. The reduction rate of the Positive and Negative Syndrome Scale (PANSS) was used to assess each participant. The side effects scale of Treatment Emergent Symptom Scale (TESS) was applied to assess the adverse reactions. Additionally, the levels of the SOD, HsCRP, and other indicators were examined.

Results: The study findings revealed a significant decrease in PANSS negative subscale scores (P < 0.001). Furthermore, there was a significant increase in SOD activity and HsCRP levels (P < 0.001 and P < 0.05). Notably, the group of participants who exhibited a reduction in PANSS negative subscale scores demonstrated a significant improvement in HsCRP levels (P < 0.05).

Conclusions: Our study suggests that SFN may potentially serve as a safe adjunctive intervention to improve the negative symptoms of schizophrenia. The potential mechanism by which SFN improves negative symptoms in schizophrenia patients may involve its anti-inflammatory properties, specifically its ability to reduce HsCRP levels. Trial registration ClinicalTrial.gov (ID: NCT03451734).

Patients with autoimmune encephalitis (AE) often developed psychiatric features during the disease course. Many studies focused on the psychiatric characteristic in anti-NMDAR encephalitis (NMDAR-E), but anti-LGI1 encephalitis (LGI1-E) had received less attention regarding the analysis of psychiatric features, and no study compared psychiatric characteristic between these two groups. The clinical data of AE patients (62 NMDAR-E and 20 LGI1-E) who developed psychiatric symptoms were analyzed in this study. In NMDAR-E, the most common higher-level feature was "behavior changes" (60/62, 96.8%) and the lower-level feature "incoherent speech" was observed in 33 patients (33/62, 53.2%), followed by "agitation" (29/62, 46.8%) and "incongruent laughter/crying" (20/62, 32.3%). Similar to NMDAR-E, "behavior changes" was most common in LGI1-E (17/20, 85.0%), but the features of suicidality, eating, and obsessive-compulsive were not reported. The top three lower-level features were visual hallucinations (9/20, 45.0%), incoherent speech (8/20, 40.0%), and mood instability (7/20, 35.0%). The comparative study found that "incongruent laughter/crying", in lower-level features, was more frequently observed in NMDAR-E (32.3% vs. 0%, p = 0.002). Moreover, the Bush Francis Catatonia Rating Scale (BFCRS) assessing the catatonic symptoms in NMDAR-E were higher than LGI1-E, but the 18 item-Brief Psychiatric Rating Scale (BPRS-18) showed no difference in the two groups. In summary, both NMDAR-E and LGI1-E often developed psychiatric symptoms. In contrast with LGI1-E, the psychiatric feature "incongruent laughter/crying" was more frequently associated with NMDAR-E, and catatonic symptoms were more severe in NMDAR-E.

Emerging studies indicate that oxidative stress may contribute to deficit syndrome (DS) in patients with schizophrenia. Homocysteine (Hcy) is a well-known marker and mediator of oxidative stress that exhibits tight associations with schizophrenia. However, no previous studies have assessed the relationship of DS with Hcy. This study evaluated the prevalence, clinical characteristics, and association of DS with Hcy in 491 patients with schizophrenia. Plasma levels of Hcy and other metabolic parameters were measured. Positive and Negative Syndrome Scale and the proxy scale for deficit syndrome were employed to assess psychiatric symptoms and DS. The logistic regression model was conducted to assess independent factors associated with DS, and the Area Under the Curve (AUC) was used to assess the performance of our model. There was a high incidence of hyperhomocysteinemia (58.8%) and DS (24.4%). Plasma Hcy levels were significantly higher in patients with DS. Age, Hcy levels, and psychiatric symptoms were independently associated with DS. The combination of these variables perfectly differentiated DS and non-DS patients with an AUC value of 0.89. Our study suggests that elevated Hcy levels may be related to DS. Routine monitoring of Hcy is essential and may facilitate early detection of DS in patients with schizophrenia.

Objective: To investigate differences in social adjustment during adulthood between adoptees with high genetic risk (HR) and low genetic risk (LR) for schizophrenia spectrum disorders.

Methods: This study is a subsample of the Finnish Adoptive Family Study of Schizophrenia. The study sample consisted of 120  adoptees whose biological mothers had DSM-III-R verified schizophrenia spectrum disorders, and 142 socio-demographically matched control adoptees. The social adjustment of the adoptees was assessed using the interview-based Adult Adjustment Scale (AAS).

Results: A lower proportion of the HR adoptees (61.7%) fell into the category of good adaptation compared to LR adoptees (74.6%) (p = 0.024). In addition, the median AAS score among HR adoptees was lower compared to LR adoptees (p = 0.023). Poorer results among HR adoptees were also found regarding some individual items and the social health -domain within the AAS. The psychiatric morbidity, excluding schizophrenia spectrum disorders, was higher among HR adoptees. Psychiatric morbidity was shown to mediate the association of genetic status to total AAS, and, also to the domain of social health.

Conclusion: According to our results, genetic susceptibility to schizophrenia is associated with weakened social adjustment during adulthood. Although our results demonstrated that psychiatric morbidity has notable effect on the association of genetic status to adult adjustment scores, the impact of other determinants, like psychosocial factors or health-related behaviour, cannot be ruled out. The comparable rearing environment provided by the adoption design in conjunction with reliable diagnostics provide new information on the relation of genetic susceptibility and social adjustment.

In the last two decades, numerous magnetic resonance imaging (MRI) studies have examined differences in cortical structure between individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) and healthy controls. These studies primarily emphasized alterations in gray matter volume (GMV) and cortical thickness (CT). Still, the scientific literature is notably scarce in regard to investigating associations of cortical structure with ADHD psychopathology, specifically inattention within adults with ADHD. The present study aimed to elucidate neurobiological underpinnings of inattention beyond GMV and CT by including cortical gyrification, sulcal depth, and fractal dimension. Building upon the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), cortical structure parameters were investigated using 141 T1-weighted anatomical scans of adult patients with ADHD. All brain structural analyses were performed using the threshold-free cluster enhancement (TFCE) approach and the Computational Anatomy Toolbox (CAT12) integrated into the Statistical Parametric Mapping Software (Matlab Version R2021a). Results revealed significant correlations of inattention in multiple brain regions. Cortical gyrification was negatively correlated, whereas cortical thickness and fractal dimension were positively associated with inattention. The clusters showed widespread distribution across the cerebral cortex, with both hemispheres affected. The cortical regions most prominently affected included the precuneus, para-, pre-, and postcentral gyri, superior parietal lobe, and posterior cingulate cortex. This study highlights the importance of cortical alterations in attentional processes in adults with ADHD. Further research in this area is warranted to elucidate intricacies of inattention in adults with ADHD to potentially enhance diagnostic accuracy and inform personalized treatment strategies.

Increasing evidence implicates compromised myelin integrity and oligodendrocyte abnormalities in the dysfunction of neuronal networks in schizophrenia. We previously reported a deficiency of myelinating oligodendrocytes (OL), oligodendrocyte progenitors (OP) and satellite oligodendrocytes of neurons (Sat-OL) in the prefrontal cortex and the inferior parietal cortex - cortical hubs of the frontoparietal cognitive network and default mode network (DMN) altered in schizophrenia. Deficiency of OL and OP was also detected in the head of the caudate nucleus (HCN), which accumulates cortical projections from the associative cortex and is the central node of these networks. However, the number of Sat-Ol per neuron in schizophrenia has not been studied in the HCN. In the current study we estimated the number of Sat-Ol per neuron in the rostral part of the HCN in schizophrenia (n = 18) compared to healthy controls (n = 18) in the same section collection that was previously used to study the number Ol and OP. We found a significant decrease of the number of Sat-Ol per neuron (- 50%, p < 0.001) in schizophrenia as compared to normal controls. Considering that the rostral part of the HCN is an individual network-specific projection zone of the DMN, the deficit of Sat-Ol found in schizophrenia may be related to the dysfunctional DMN-HCN connections, which has been repeatedly described in schizophrenia. The dramatic decrease of the number of Sat-Ol per neuron may be partially related to a pronounced excess of dopamine concentration in the rostral part of the HCN in schizophrenia.

Background: Childhood trauma experiences and inflammation are pivotal factors in the onset and perpetuation of major depressive disorder (MDD). However, research on brain mechanisms linking childhood trauma experiences and inflammation to depression remains insufficient and inconclusive.

Methods: Resting-state fMRI scans were performed on fifty-six first-episode, drug-naive MDD patients and sixty healthy controls (HCs). A whole-brain functional network was constructed by thresholding 246 brain regions, and connectivity and network properties were calculated. Plasma interleukin-6 (IL-6) levels were assessed using enzyme-linked immunosorbent assays in MDD patients, and childhood trauma experiences were evaluated through the Childhood Trauma Questionnaire (CTQ).

Results: Negative correlations were observed between CTQ total (r = -0.28, p = 0.047), emotional neglect (r = -0.286, p = 0.042) scores, as well as plasma IL-6 levels (r = -0.294, p = 0.036), with mean decreased functional connectivity (FC) in MDD patients. Additionally, physical abuse exhibited a positive correlation with the nodal clustering coefficient of the left thalamus in patients (r = 0.306, p = 0.029). Exploratory analysis indicated negative correlations between CTQ total and emotional neglect scores and mean decreased FC in MDD patients with lower plasma IL-6 levels (n = 28), while these correlations were nonsignificant in MDD patients with higher plasma IL-6 levels (n = 28).

Conclusions: This finding enhances our understanding of the correlation between childhood trauma experiences, inflammation, and brain activity in MDD, suggesting potential variations in their underlying pathophysiological mechanisms.

Post-COVID syndrome (PCS) describes a persistent complex of symptoms following a COVID-19 episode, lasting at least 4 to 12 weeks, depending on the specific criteria used for its definition. It is often associated with moderate to severe impairments of daily life and represents a major burden for many people worldwide. However, especially during the first two years of the COVID-19 pandemic, therapeutic and diagnostic uncertainties were prominent due to the novelty of the disease and non-specific definitions that overlooked functional deficits and lacked objective assessment. The present work comprehensively examines the status of PCS definitions as depicted in recent reviews and meta-analyses, alongside exploring associated symptoms and functional impairments. We searched the database Pubmed for reviews and meta-analysis evaluating PCS in the period between May 31, 2022, to December 31, 2023. Out of 95 studies, 33 were selected for inclusion in our analyses. Furthermore, we extended upon prior research by systematically recording the symptoms linked with PCS as identified in the studies. We found that fatigue, neurological complaints, and exercise intolerance were the most frequently reported symptoms. In conclusion, over the past eighteen months, there has been a notable increase in quantity and quality of research studies on PCS. However, there still remains a clear need for improvement, particularly with regard to the definition of the symptoms necessary for diagnosing this syndrome. Enhancing this aspect will render future research more comparable and precise, thereby advancing and understanding PCS.