Shared effects of electroconvulsive shocks and ketamine on neuroplasticity: A systematic review of animal models of depression.

Electroconvulsive shocks (ECS) and ketamine are antidepressant treatments with a relatively fast onset of therapeutic effects compared to conventional medication and psychotherapy. While the exact neurobiological mechanisms underlying the antidepressant response of ECS and ketamine are unknown, both interventions are associated with neuroplasticity. Restoration of neuroplasticity may be a shared mechanism underlying the antidepressant efficacy of these interventions. In this systematic review, literature of animal models of depression is summarized to examine the possible role of neuroplasticity in ECS and ketamine on a molecular, neuronal, synaptic and functional level, and specifically to what extent these mechanisms are shared between both interventions. The results highlight that hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) levels are consistently increased after ECS and ketamine. Moreover, both interventions positively affect glutamatergic neurotransmission, astrocyte and neuronal morphology, synaptic density, vasculature and functional plasticity. However, a small number of studies investigated these processes after ECS. Understanding the shared fundamental mechanisms of fast-acting antidepressants can contribute to the development of novel therapeutic approaches for patients with severe depression.

Reproducible gut microbial signatures in bipolar and schizophrenia spectrum disorders: A metagenome-wide study.

BACKGROUND: Numerous studies report gut microbiome variations in bipolar disorder (BD) and schizophrenia spectrum disorders (SSD) compared to healthy individuals, though, there is limited consensus on which specific bacteria are associated with these disorders. METHODS: In this study, we performed a comprehensive metagenomic shotgun sequencing analysis in 103 Dutch patients with BD/SSD and 128 healthy controls matched for age, sex, body mass index and income, while accounting for diet quality, transit time and technical confounders. To assess the replicability of the findings, we used two validation cohorts (total n = 203), including participants from a distinct population with a different metagenomic isolation protocol. RESULTS: The gut microbiome of the patients had a significantly different ß-diversity, but not α-diversity nor neuroactive potential compared to healthy controls. Initially, twenty-six bacterial taxa were identified as differentially abundant in patients. Among these, the previously reported genera Lachnoclostridium and Eggerthella were replicated in the validation cohorts. Employing the CoDaCoRe learning algorithm, we identified two bacterial balances specific to BD/SSD, which demonstrated an area under the receiver operating characteristic curve (AUC) of 0.77 in the test dataset. These balances were replicated in the validation cohorts and showed a positive association with the severity of psychiatric symptoms and antipsychotic use. Last, we showed a positive association between the relative abundance of Klebsiella and Klebsiella pneumoniae with antipsychotic use and between the Anaeromassilibacillus and lithium use. CONCLUSIONS: Our findings suggest that microbial balances could be a reproducible method for identifying BD/SSD-specific microbial signatures, with potential diagnostic and prognostic applications. Notably, Lachnoclostridium and Eggerthella emerge as frequently occurring bacteria in BD/SSD. Last, our study reaffirms the previously established link between Klebsiella and antipsychotic medication use and identifies a novel association between Anaeromassilibacillus and lithium use.

The association of prolactin and gonadal hormones with cognition and symptoms in men with schizophrenia spectrum disorder: Divergent effects of testosterone and estrogen.

BACKGROUND: Certain antipsychotics elevate prolactin levels in patients with schizophrenia spectrum disorders (SSD), potentially affecting cognition, symptoms, and hormone levels. This study examines the association between prolactin, testosterone, and estrogen and cognition and symptoms in men with SSD, considering antipsychotic medication. METHODS: This cross-sectional study included 128 men with SSD and 44 healthy men from two trials. Patients were divided into a prolactin-sparing (n = 53) and prolactin-raising group (n = 75) based on antipsychotic medication. We examined the association between hormones (testosterone, estrogen and prolactin), and cognition and symptoms using backward linear regression. Three domains of cognition were assessed including: processing speed, verbal fluency, and working memory, while symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Prolactin levels were highest in the prolactin-raising group, followed by the control group, and lowest in the prolactin-sparing group (H = 45.279, p < .001). Testosterone and estrogen levels did not differ significantly between groups. In the prolactin-raising group, prolactin negatively correlated with testosterone (r(73) = -0.32, p = .005). Higher testosterone predicted better cognitive functioning (working memory: ß = 0.20, p = .007, verbal fluency: ß = 0.30, p = .001) and lower symptom scores (total: ß = -0.21, p = .001; negative: ß = -0.24, p = .002) in men with SSD. Conversely, higher estrogen levels related to slower processing speed (ß = -0.22, p < .001) and higher symptoms scores (ß = 0.23, p = .010) in men with SSD. CONCLUSION: The results suggest positive associations between testosterone and cognition and symptoms in men with SSD, while suggesting that high prolactin levels could relate to lower testosterone levels, possibly worsening cognition and symptoms in men with SSD.

The experience of felt presence in a general population sample.

Felt presence is a widely occurring experience, but remains under-recognised in clinical and research practice. To contribute to a wider recognition of the phenomenon, we aimed to assess the presentation of felt presence in a large population sample (n = 10 447) and explore its relation to key risk factors for psychosis. In our sample 1.6% reported experiencing felt presence in the past month. Felt presence was associated with visual and tactile hallucinations and delusion-like thinking; it was also associated with past occurrence of adverse events, loneliness and poor sleep. The occurrence of felt presence may function as a marker for general hallucination proneness.

Exploring peripheral biomarkers of response to simvastatin supplementation in schizophrenia.

Schizophrenia is one of the most debilitating mental disorders, and its diagnosis and treatment present significant challenges. Several clinical trials have previously evaluated the effectiveness of simvastatin, a lipid-lowering medication, as a novel add-on treatment for schizophrenia. However, treatment effects varied highly between patients and over time. In the present study, we aimed to identify biomarkers of response to simvastatin in recent-onset schizophrenia patients. To this end, we profiled relevant immune and metabolic markers in patient blood samples collected in a previous clinical trial (ClinicalTrials.gov: NCT01999309) before simvastatin add-on treatment was initiated. Analysed sample types included serum, plasma, resting-state peripheral blood mononuclear cells (PBMCs), as well as PBMC samples treated ex vivo with immune stimulants and simvastatin. Associations between the blood readouts and clinical endpoints were evaluated using multivariable linear regression. This revealed that changes in insulin receptor (IR) levels induced in B-cells by ex vivo simvastatin treatment inversely correlated with in vivo effects on cognition at the primary endpoint of 12 months, as measured using the Brief Assessment of Cognition in Schizophrenia scale total score (standardised ß ± SE = -0.75 ± 0.16, P = 2.2 × 10-4, Q = 0.029; n = 21 patients). This correlation was not observed in the placebo group (ß ± SE = 0.62 ± 0.39, P = 0.17, Q = 0.49; n = 14 patients). The candidate biomarker explained 53.4 % of the variation in cognitive outcomes after simvastatin supplementation. Despite the small sample size, these findings suggest a possible interaction between the insulin signalling pathway and cognitive effects during simvastatin therapy. They also point to opportunities for personalized schizophrenia treatment through patient stratification.

Short-latency afferent inhibition as a biomarker of cholinergic degeneration compared to PET imaging in Parkinson's disease.

INTRODUCTION: Short-latency afferent inhibition (SAI) is a relatively cheap and non-invasive method that has been proposed as a cholinergic marker in Parkinson's disease (PD). We aim to verify the clinical feasibility of SAI as a cholinergic marker in PD using positron emission tomography (PET) with the tracer (2R,3R)-5-(2-[18F]fluoroethoxy)benzovesamicol ([18F]FEOBV) as a reference. METHODS: We examined relations between SAI and [18F]FEOBV PET using linear regression analysis, with the primary motor cortex (M1) as primary region of interest. Additionally, we examined relations of both measures with clinical features. RESULTS: 30 PD patients with varying degrees of cognitive dysfunction and 10 healthy controls (HC) were included in the analysis. SAI was not related to tracer uptake in M1 in the PD group (p = .291) or the HC group (p = .206). We could not replicate the previously published relations between SAI and cholinergic symptoms, such as cognition, psychotic experiences and olfactory function. CONCLUSION: SAI was not related to [18F]FEOBV imaging parameters, nor to clinical measures of cholinergic dysfunction. Therefore, SAI may not be feasible as a clinically applied cholinergic marker in PD.

Multisensory hallucinations and other unusual sensory experiences in the context of migraine: a systematic review.

OBJECTIVE AND BACKGROUND: Visual auras in migraine have been extensively studied, but less is known about multisensory hallucinations or other unusual sensory experiences, including whether these should be diagnostically considered as part of aura symptoms. The current study aimed to conduct a systematic review and synthesis to bring together existing empirical evidence on these non-visual perceptual experiences, focusing on their phenomenological descriptions and clinical correlates. METHODS: Forty-eight relevant studies were included based on a systematic search across PsycINFO APA and Web of Science, for peer-reviewed publications in the English language, from 1980 to the present. These comprised a mix of case reports/series (n = 19) and group design studies (n = 29). RESULTS: Reports of complex multisensory hallucinations, beyond typical established aura symptoms, were numerous and varied in nature. Yet there were limited data on how this related to patient distress and functional interference. Other sensory distortions or hypersensitivities across non-visual domains were also evident, and generally more common in those with established aura symptoms. CONCLUSION: Our findings provide preliminary evidence that multisensory hallucinations and other unusual perceptual experiences in migraine are likely more common than previously believed. Further investigations are needed to appropriately account for these symptoms within current nosological systems. Increased clinician-patient awareness is important for managing distress (where necessary), and potentially for offering a holistic therapeutic approach to migraine management.

[Antipsychotic medication after a first episode of psychosis: taper or continue?] / Antipsychotica na een eerste psychose.

In this paper we discuss the risks and benefits of discontinuing antipsychotic medication within one year after remission of a first episode of psychosis. We start with a fictional case report of a 21-year-old man, who was diagnosed with schizophreniform disorder four months earlier. While symptoms responded well to a daily dose of 10 mg ariprazole, he experienced side effects (tiredness and mild hypersomnia). Three months after symptom remission, he expressed the wish to discontinue his medication. How should psychiatrists respond to his wish? To answer that, we briefly summarize relevant evidence and discuss arguments for the different therapeutic approaches, i.e., maintaining vs. tapering antipsychotic medication, based on specific patient characteristics. Recommendations from the current Dutch guidelines are complemented with personal experience and considerations in finding the optimal balance between side effects, relapse risk, stigma and acceptance of mental health problems, while incorporating the principles of shared decision-making.