BackgroundDepression is a highly prevalent disorder that is one of the leading causes of disability worldwide. Despite an unknown aetiology, evidence suggests that the innate and adaptive immune systems play a significant role in the development and maintenance of major depressive disorder (MDD). The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), has demonstrated rapid and robust efficacy as an antidepressant when administered at sub-anaesthetic doses.MethodsOur goal was to characterize the pro-inflammatory profile of patients with MDD by measuring pro-inflammatory cytokines in plasma and circulating monocyte subsets and to understand how ketamine induces an anti-inflammatory program in monocyte and macrophages in vitro and vivo.FindingOur results show that patients with MDD without other comorbidities (N = 33) exhibited significantly higher levels of pro-inflammatory IL-12 and IL-6 in plasma and that these cytokines were associated with increased numbers of non-classical (CD11b+CD16brightCD14neg) monocytes and increased activation state (CD40+CD86+) of classical monocytes in circulation. Remarkably, we have demonstrated that sub-anaesthetic doses of ketamine programs human monocytes into M2c-like macrophages by inducing high levels of CD163 and MERTK with intermediate levels of CD64 and stimulating mTOR-associated gene expression in vitro. The NMDAR antagonist MK-801, but not the α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonist, NBQX, also polarizes macrophages to an M2c-like phenotype, but this phenotype disappears upon mTOR pathway inhibition. Sub-anaesthetic doses (10 mg/kg) of ketamine administration in mice both promote reduction of circulating classical pro-inflammatory monocytes and increase of alternative M2 macrophage subtypes in the spleen and CNS.InterpretationOur results suggest an anti-inflammatory property of ketamine that can skew macrophages to an M2-like phenotype, highlighting potential therapeutic implications not only for patients with MDD but also other inflammatory-based diseases.FundingThis study was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT-FONCYT).

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Hallucination-like experiences (HLEs) are typically defined as sensory perceptions in the absence of external stimuli. Multidimensional tools, able to assess different facets of HLEs, are helpful for a better characterization of hallucination proneness and to investigate the cross-national variation in the frequencies of HLEs. The current study set out to establish the validity, factor structure, and measurement invariance of the Launay-Slade Hallucinations Scale-Extended (LSHS-E), a tool to assess HLEs. A total of 4419 respondents from 10 countries were enrolled. Network analyses between the LSHS-E and the 3 dimensions of the Community Assessment of Psychic Experiences (CAPE) were performed to assess convergent and divergent validity of the LSHS-E. Confirmatory factor analysis was used to test its measurement invariance. The best fit was a 4-factor model, which proved invariant by country and clinical status, indicating cross-national stability of the hallucination-proneness construct. Among the different components of hallucination-proneness, auditory-visual HLEs had the strongest association with the positive dimension of the CAPE, compared with the depression and negative dimensions. Participants who reported a diagnosis of a mental disorder scored higher on the 4 LSHS-E factors. Small effect size differences by country were found in the scores of the 4 LSHS-E factors even after taking into account the role of socio-demographic and clinical variables. Due to its good psychometric properties, the LSHS-E is a strong candidate tool for large investigations of HLEs.

Objective To evaluate the incidence of suicidal outcomes and risk factors for short‐ and long‐term recurrence of suicidal behavior (SB) among high‐risk borderline personality disorder (BPD) patients during a 24‐month prospective follow‐up period. Methods A multicenter prospective cohort study was designed to compare data obtained from 136 patients admitted to the emergency department for current suicidal ideation (SI) or a recent suicide attempt (SA). Subjects were clinically evaluated and monitored for a new SA or suicide. Results The incidence of a new SA was 25.63 events/100 persons‐year, and one patient died by suicide. Child sexual abuse (CSA) was the only significant predictor throughout the complete follow‐up period. The absence of prior psychiatric treatment predicts the recurrence of SB in the first 6 months of follow‐up. Patient age, poor psychosocial functioning before hospitalization, age at first SA, and having multiple suicide attempts increased risk of SB recurrence at the long‐term period (24th months). In addition, there was an interaction between CSA and poor psychosocial functioning that increased risk of SB. Conclusion The risk of recurrence was higher during the first 6 months. Risk factors at 6 and 24 months vary. These findings are important for implementing suicide strategies.