Psychiatry and Clinical Neurosciences最新文献

Aim: Neuroinflammation is an important causal factor for a variety of psychiatric disorders. We previously reported increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and major depressive disorder. The present study aimed to examine the possible association of interleukin-6 levels with anxiety and frustration, negative valence symptoms shared in various psychiatric disorders.

Methods: We included 129 patients with psychiatric disorders and 70 controls. CSF and plasma interleukin-6 levels were measured by immunoassay kits, and psychological symptoms were assessed with the State-Trait Anxiety Inventory, and the Basic Psychological Need Satisfaction and Frustration Scale. To examine regional cerebral blood flow, patients underwent arterial spin labeling analysis using magnetic resonance imaging.

Results: Cerebrospinal fluid interleukin-6 levels were significantly correlated with State-Trait Anxiety Inventory-trait anxiety (r = 0.25, P = 0.046) and Basic Psychological Need Satisfaction and Frustration Scale-autonomy frustration scores (r = 0.29, P = 0.018). Patients with abnormally high cerebrospinal fluid interleukin-6 levels (defined >97.5 percentile of the controls) had higher scores for trait anxiety (P = 0.035) and autonomy frustration (P = 0.026), and significantly increased regional cerebral blood flow in the left superior temporal gyrus, bilateral nucleus accumbens, and cerebellum than the remaining patients.

Conclusion: Patients with elevated cerebrospinal fluid interleukin-6 constitute a subpopulation of psychiatric disorders associated with anxiety and autonomy frustration, which may be related to altered functions in specific brain areas.

Aim: Empirical research investigating hyperorality in syndromes associated with frontotemporal lobar degeneration (FTLD) is limited. The present study aims to assess and describe hyperorality and its clinical and imaging correlates in patients with FTLD-associated syndromes.

Methods: This retrospective longitudinal study included consecutive patients with FTLD who underwent a clinical, cognitive, and behavioral assessment. The presence and severity of hyperorality was assessed using the Frontal Behavior Inventory.

Results: A total of 712 patients with FTLD were included in the study. Hyperorality was reported by 29% (204 of 712 [95% CI: 25-32%]) of patients; was more frequent in those with severe dementia than in those with prodromal or mild to moderate dementia (P < 0.05); was associated with younger age (odds ratio [OR] = 0.96 [95% CI: 0.94-0.99]), (P = 0.003) and positive family history for dementia (OR = 2.03 [95% CI: 1.18-3.49], P = 0.010); was overall more probable in the behavioral variant of frontotemporal dementia (bvFTD) and frontotemporal dementia with amyotrophic lateral sclerosis phenotypes, and less probable in other language or motor phenotypes; and was associated with higher severity of neuropsychiatric symptoms (OR = 1.08 [95% CI: 1.06-1.10], P < 0.001) and with the presence of several behavioral symptoms (P < 0.05). Moreover, hyperorality severity increased over time only in patients with bvFTD (β = +0.15, P = 0.011) or semantic variant of primary progressive aphasia (β = +0.34, P = 0.010). Finally, the presence of hyperorality was significantly associated with greater atrophy in the right anterior insula and right orbitofrontal region (false discovery rate-corrected P < 0.05).

Conclusion: Hyperorality is common in certain FTLD-associated syndromes. Understanding its correlates can help clinicians define pharmacological and educational interventions and clarify related anatomical circuits.

Aim: Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous neurodevelopmental disorder with a strong genetic basis. Conducting the first comprehensive whole-genome sequencing (WGS) analysis of Japanese ASD trios, this study aimed to elucidate the clinical significance of pathogenic variants and enhance the understanding of ASD pathogenesis.

Methods: WGS was performed on 57 Japanese patients with ASD and their parents, investigating variants ranging from single-nucleotide variants to structural variants (SVs), short tandem repeats (STRs), mitochondrial variants, and polygenic risk score (PRS).

Results: Potentially pathogenic variants that could explain observed phenotypes were identified in 18 patients (31.6%) overall and in 10 of 23 patients (43.5%) with comorbid intellectual developmental disorder (IDD). De novo variants in PTEN, CHD7, and HNRNPH2 were identified in patients referred for genetic counseling who exhibited previously reported phenotypes, including one patient with ASD who had profound IDD and macrocephaly with PTEN L320S. Analysis of the AlphaFold3 protein structure indicated potential inhibition of intramolecular interactions within PTEN. SV analysis identified deletions in ARHGAP11B and TMLHE. A pathogenic de novo mitochondrial variant was identified in a patient with ASD who had a history of encephalitis and cognitive decline. GO enrichment analysis of genes with nonsense variants and missense variants (Missense badness, PolyPhen-2, and Constraint >1) showed associations with regulation of growth and ATP-dependent chromatin remodeler activity. No reportable results were obtained in the analysis of STR and PRS.

Conclusion: Characterizing the comprehensive genetic architecture and phenotypes of ASD is a fundamental step towards unraveling its complex biology.

Sleep and biological rhythms are integral to mood regulation across the lifespan, particularly in bipolar disorder (BD), where alterations in sleep phase, structure, and duration occur in all mood states. These disruptions are linked to poorer quality of life, heightened suicide risk, impaired cognitive function, and increased relapse rates. This review highlights the pathophysiology of sleep disturbances in BD and aims to consolidate understanding and clinical applications of these phenomena. It also summarizes the evolution of sleep and biological rhythms assessment methods, including ecological momentary assessment (EMA) and digital phenotyping. It underscores the importance of recognizing circadian rhythm involvement in mood regulation, suggesting potential therapeutic targets. Future research directions include elucidating circadian clock gene mechanisms, understanding environmental impacts on circadian rhythms, and investigating the bidirectional relationship between sleep disturbances and mood regulation in BD. Standardizing assessment methods and addressing privacy concerns related to EMA technology and digital phenotyping are essential for advancing research. Collaborative efforts are crucial for enhancing clinical applicability and understanding the broader implications of biological rhythms in BD diagnosis and treatment. Overall, recognizing the significance of sleep and biological rhythms in BD offers promise for improved outcomes through targeted interventions and a deeper understanding of the disorder's underlying mechanisms.

Aim: The extent to which recent potentially traumatic events (PTEs) hinder the recovery from pre-existing mental health problems is largely unknown. The same applies to the extent to which non-recovery from pre-existing mental health problems increases the risk of posttraumatic stress disorder (PTSD). The aim of the present study is to gain insight in these effects.

Methods: Data were extracted from six annual surveys of the Dutch population-based Victims in Modern Society (VICTIMS) study. Of the adult respondents who participated in two subsequent surveys (labeled T1 and T2, n = 6942), those with severe anxiety and depression symptoms (ADS) at T1 (n = 487) were selected. We distinguished respondents exposed to PTEs (PTE-group, n = 162) and not exposed to PTEs (comparison group, n = 325) between T1 and T2. We applied five indicators of recovery [based on the Reliable Change Index (RCI), degrees of symptom reduction, and the cut-off score at T2]. Differences in the recovery from ADS and probable PTSD at T2 were examined using multivariate logistic regression.

Results: The PTE group less often recovered from severe ADS between T1 and T2 than the comparison group according to all five indicators of recovery, while controlling for 11 different variables (0.40 ≤ adjusted OR's ≤ 0.66). Those in the PTE group who did not recover, considerably more often suffered from probable PTSD at T2 (63%-82%) than those who did recover (0%-29%; 8.96 ≤ adjusted OR ≤ 26.33).

Conclusion: Recent potentially traumatic events hinder the recovery from pre-existing anxiety and depression symptomatology and thereby increase the risk of probable PTSD.