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The etiology of autism spectrum disorder (ASD) is complex, and its pathobiology is characterized by enhanced inflammatory activities; however, the precise pathobiology and underlying causes of ASD remain unclear. This study was performed to identify inflammatory indicators useful for diagnosing ASD. The mRNA expression of cytokines, including tumor necrosis factor-α (TNF-α), was measured in cultured M1 and M2 macrophages from patients with ASD (n = 29) and typically developed (TD) individuals (n = 30). Additionally, TNF-α expression in the monocytes of patients with ASD (n = 7), showing aberrations in TNF-α expression in M1/M2 macrophages and TD individuals (n = 6), was measured. TNF-α expression in M1 macrophages and the TNF-α expression ratio in M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals; however, this increase was not observed in M2 macrophages (M1: sensitivity = 34.5%, specificity = 96.7%, area under the curve = 0.74, positive likelihood ratio = 10.34; ratio of M1/M2: sensitivity = 55.2%, specificity = 96.7%, area under the curve = 0.79, positive likelihood ratio = 16.55). Additionally, TNF-α expression in monocytes did not significantly differ between patients with ASD and TD individuals. In conclusion, further studies on TNF-α expression in cultured macrophages may improve the understanding of ASD pathobiology. LAY SUMMARY: TNF-α expression in differentiated M1 macrophages and TNF-α expression ratio in differentiated M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals, while no difference in TNF-α expression was found in pre-differentiation cells such as monocytes. These measurements allow elucidation of the novel pathobiology of ASD and can contribute to biomarker implementation for the diagnosis of adult high-functioning ASD.

Background A few case series on psychiatric adverse reactions to COVID-19 vaccines have been reported despite the absence of a history of psychiatric disorders. Herein, we report a case of a first episode of acute mania with psychotic features receival of the third mRNA-1273 vaccine. Case presentation A 37-year-old man developed talkativeness, grandiose delusions, emotional instability, sleeplessness, excitement, hyperactivity and suicidal behavior 4 days after receiving the third mRNA-1273 COVID-19 vaccine. On the 9thdays after vaccination, he was diagnosed with first-episode acute mania with psychotic features and admitted to the psychiatric institute for the first time. After olanzapine administration, the psychiatric symptoms improved within 4 weeks. Conclusions To our knowledge, this is the first report of a first episode of acute mania with psychiatric features associated with the mRNA-1273 vaccine booster. Psychiatrists should be aware of this possibility and be attentive to such a rare and severe adverse effect that could occur within 10 days of vaccination.

Visuospatial working memory (vsWM), which is impaired in schizophrenia (SZ), is mediated by a distributed cortical network. In one node of this network, the dorsolateral prefrontal cortex (DLPFC), altered expression of transcripts for actin assembly and mitochondrial oxidative phosphorylation (OXPHOS) have been reported in SZ. To understand the relationship between these processes, and the extent to which similar alterations are present in other regions of vsWM network in SZ, a subset of actin- (CDC42, BAIAP2, ARPC3, and ARPC4) and OXPHOS-related (ATP5H, COX4I1, COX7B, and NDUFB3) transcripts were quantified in DLPFC by RNA sequencing in 139 SZ and unaffected comparison (UC) subjects, and in DLPFC and three other regions of the cortical vsWM network by qPCR in 20 pairs of SZ and UC subjects. By RNA sequencing, levels of actin- and OXPHOS-related transcripts were significantly altered in SZ, and robustly correlated in both UC and SZ subject groups. By qPCR, cross-regional expression patterns of these transcripts in UC subjects were consistent with greater actin assembly in DLPFC and higher OXPHOS activity in primary visual cortex (V1). In SZ, CDC42 and ARPC4 levels were lower in all regions, BAIAP2 levels higher only in V1, and ARPC3 levels unaltered across regions. All OXPHOS-related transcript levels were lower in SZ, with the disease effect decreasing from posterior to anterior regions. The differential alterations in markers of actin assembly and energy production across regions of the cortical vsWM network in SZ suggest that each region may make specific contributions to vsWM impairments in the illness.

Background The etiology of autism spectrum disorder (ASD) is complex. Its pathobiology is characterized by enhanced inflammatory activities; however, the exact ASD pathobiology remains unclear. Some cases of ASD are difficult to diagnose using existing psychological assessments because the careful exclusion of other psychiatric disorders is challenging. To distinguish between the appropriate targets for interventions and research, the demand for identifying efficient diagnostic biomarkers is increasing. This study aimed to find an inflammatory indicator beneficial for the diagnosis of ASD.Methods Cytokine mRNA expression, including tumor necrosis factor-α (TNF-α), was measured in the differentiated M1 and M2 macrophages of ASD patients (n = 29) and typically developed (TD) individuals (n = 30). TNF-α expression was also measured in the monocytes of ASD patients (n = 7) and TD individuals (n = 6).Results TNF-α expression in M1 macrophages and TNF-α expression ratio of M1/M2 macrophages were markedly higher in ASD patients than in TD subjects; however, this difference was not observed in M2 macrophages (M1: p < 0.01; ratio of M1/M2: p < 0.0001; M2: p > 0.05), suggesting that this indicator could be a useful tool for diagnosing ASD (M1: sensitivity = 34.5%, specificity = 96.7%, area under the curve (AUC) = 0.74, positive likelihood ratio (PLR) = 10.34; ratio of M1/M2: sensitivity = 55.2%, specificity = 96.7%, AUC = 0.79, PLR = 16.55). However, there was no significant difference in the TNF-α expression in monocytes between ASD and TD individuals (p > 0.05).Conclusion These findings suggest that TNF-α expression in differentiated macrophages represents a novel adjunctive tool for the diagnosis of ASD.

Yasunari Yamaguchi, Sohei Kimoto, Takeshi Nagahama, Toshifumi Kishimoto Department of Psychiatry, Nara Medical University School of Medicine, Kashihara, Japan Objective: Several studies have documented that treatment with various antidepressant agents can result in mood switching during major depressive episodes. Escitalopram, one of the newer selective serotonin reuptake inhibitors (SSRIs), is considered preferable due to its relatively high efficacy and acceptability. Although a few cases of escitalopram treatment-emergent mania have been reported, it remains unknown whether this effect is dose-related.Method: In the present report, we discuss three cases of treatment-emergent mania/hypomania in patients receiving escitalopram for major depressive episodes. No patients had a family or personal history of bipolar disorder.Results: In all three cases, manic or hypomanic symptoms emerged within 1month right after the dosage of escitalopram was increased to 20mg/day. Moreover, manic episodes subsided as the dosage of escitalopram was reduced. Mood switching was not observed after the cessation of escitalopram treatment.Conclusion: Our case series indicates that escitalopram may induce treatment-emergent mania/hypomania in a dose-related manner. Treatment at lower doses and with careful upward titration might be favorable in certain patients with bipolar depression and major depressive disorder in order to minimize the risk of mood switching. Keywords: selective serotonin reuptake inhibitor, SSRI, escitalopram, antidepressant treatment-emergent mania/hypomania, dosage-related, bipolar depression