Journal of Psychiatry & Neuroscience最新文献

Background: The nucleus accumbens (NAcc) is a crucial brain region for emotionally relevant behaviours. The NAcc is mainly composed of medium spiny neurons (MSNs) expressing either dopamine receptor D1 (D1-MSNs) or D2 (D2-MSNs). The D1-MSNs project to the ventral tegmental area (VTA) and the ventral pallidum (VP), whereas the D2-MSNs project only to the VP. The D1- and D2-MSNs have been associated with depression-like behaviours, but their contribution to anxiety remains to be determined.

Methods: We used optogenetic tools to selectively manipulate D1-MSN projections from the NAcc core to the VP or VTA and D2-MSN projections to the VP during validated anxiety-producing behavioural procedures in naive mice. In addition, we assessed the effects of optical stimulation on neuronal activity using in vivo electrophysiologic recordings in anesthetized animals.

Results: Optogenetic activation of D1-MSN projections to the VTA or VP did not trigger anxiety-like behaviour. However, optical activation of D2-MSN projections to the VP significantly increased anxiety-like behaviour. This phenotype was associated with a decrease in the neuronal activity of putative GABAergic neurons in the VP. Importantly, pretreating D2-MSN-VP animals with the γ-aminobutyric acid modulator diazepam prevented the optically triggered anxiety-like behaviour.

Limitations: The exclusive use of males in the behavioural tests limits broader interpretation of the findings. Although we used optogenetic conditions that trigger quasi-physiologic changes, there are caveats associated with the artificial manipulation of neuronal activity.

Conclusion: The D2-MSN-VP projections contributed to the development of anxiety-like behaviour, through modulation of GABAergic activity in the VP.

Background: Decreased affective flexibility is associated with depression symptoms, and it has been suggested that common interventions may target this mechanism. To explore this hypothesis, we evaluated whether real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training to increase the amygdala responses during positive memory recall resulted in both symptom improvements, as has been observed previously, and flexibility to decrease amygdala reactivity in response to a cognitive task among patients with major depressive disorder (MDD).

Methods: In a double-blind, placebo-controlled, randomized clinical trial, adults with MDD received 2 sessions of rtfMRI-nf training to increase their amygdala (experimental group) or parietal (control group) responses during positive autobiographical memory recall. We evaluated signal changes in the amygdala during both the positive memory neurofeedback and a subsequent counting condition.

Results: We included 38 adults with MDD, including 16 in the experimental group and 22 in the control group. In the experimental group, amygdala activity increased (t > 2.01, df < 27, p < 0.05, d > 0.5) and depressive symptoms decreased (-8.57, 95 % confidence interval [CI] -15.12 to -2.59; t ₁₃ = -3.06, p = 0.009, d = 1). Amygdala activity during the count condition decreased after rtfMRI-nf (-0.16, 95 % CI -0.23 to -0.09; t ₃₉₆ = 4.73, p < 0.001, d = 0.48) and was correlated with decreased depression scores (r = 0.46, p = 0.01). We replicated previous results and extended them to show decreased amygdala reactivity to a cognitive task during which no neurofeedback was provided.

Limitations: The count condition was reported by participants as negative, but emotionality or accuracy during this condition was not assessed.

Conclusion: These results suggest that nominally targeting unidimensional change in neural mechanisms could have implications for bidirectional control, increasing the likely reach and explanatory framework for how common depression interventions work.Trial registration: ClinicalTrials.gov NCT02709161.

Background: Decision-making under approach-avoidance conflict (AAC; e.g., sacrificing quality of life to avoid feared outcomes) may be affected in multiple psychiatric disorders. Recently, we used a computational (active inference) model to characterize information processing differences during AAC in individuals with depression, anxiety and/or substance use disorders. Individuals with psychiatric disorders exhibited increased decision uncertainty (DU) and reduced sensitivity to unpleasant stimuli. This preregistered study aimed to determine the replicability of this processing dysfunction.

Methods: A new sample of participants completed the AAC task. Individual-level computational parameter estimates, reflecting decision uncertainty and sensitivity to unpleasant stimuli ("emotion conflict"; EC), were obtained and compared between groups. Subsequent analyses combining the prior and current samples allowed assessment of narrower disorder categories.

Results: The sample in the present study included 480 participants: 97 healthy controls, 175 individuals with substance use disorders and 208 individuals with depression and/or anxiety disorders. Individuals with substance use disorders showed higher DU and lower EC values than healthy controls. The EC values were lower in females, but not males, with depression and/or anxiety disorders than in healthy controls. However, the previously observed difference in DU between participants with depression and/or anxiety disorders and healthy controls did not replicate. Analyses of specific disorders in the combined samples indicated that effects were common across different substance use disorders and affective disorders.

Limitations: There were differences, although with small effect size, in age and baseline intellectual functioning between the previous and current sample, which may have affected replication of DU differences in participants with depression and/or anxiety disorders.

Conclusion: The now robust evidence base for these clinical group differences motivates specific questions that should be addressed in future research: can DU and EC become behavioural treatment targets, and can we identify neural substrates of DU and EC that could be used to measure severity of dysfunction or as neuromodulatory treatment targets?

Environment is known to substantially alter mental state and behaviour across the lifespan. Biological barriers such as the blood-brain barrier (BBB) and gut barrier (GB) are major hubs for communication of environmental information. Alterations in the structural, social and motor environment at different stages of life can influence function of the BBB and GB and their integrity to exert behavioural consequences. Importantly, each of these environmental components is associated with a distinct immune profile, glucocorticoid response and gut microbiome composition, creating unique effects on the BBB and GB. These barrier-environment interactions are sensitive to change throughout life, and positive or negative alterations at critical stages of development can exert long-lasting cognitive and behavioural consequences. Furthermore, because loss of barrier integrity is implicated in pathogenesis of mental disorders, the pathways of environmental influence represent important areas for understanding these diseases. Positive environments can be protective against stress- and age-related damage, raising the possibility of novel pharmacological targets. This review summarizes known mechanisms of environmental influence - such as social interactions, structural complexity and physical exercise - on barrier composition, morphology and development, and considers the outcomes and implications of these interactions in the context of psychiatric disorders.

Background: Tourette syndrome is a developmental neuropsychiatric disorder. Its etiology is complex and elusive, although an important role of genetic factors has been established. The aim of the present study was to identify the genomic basis of Tourette syndrome in a group of families with affected members in 2 or 3 generations.

Methods: Whole-genome sequencing was performed followed by co-segregation and bioinformatic analyses. Identified variants were used to select candidate genes, which were then subjected to gene ontology and pathway enrichment analysis.

Results: The study group included 17 families comprising 80 patients with Tourette syndrome and 44 healthy family members. Co-segregation analysis and subsequent prioritization of variants pinpointed 37 rare and possibly pathogenic variants shared among affected individuals within a single family. Three such variants, in the ALDH2, DLD and ALDH1B1 genes, could influence oxidoreductase activity in the brain. Two variants, in SLC17A8 and BSN genes, were involved in sensory processing of sound by inner hair cells of the cochlea. Enrichment analysis of genes whose rare variants were present in all patients from at least 2 families identified significant gene sets implicated in cell-cell adhesion, cell junction assembly and organization, processing of sound, synapse assembly, and synaptic signalling processes.

Limitations: We did not examine intergenic variants, but they still could influence clinical phenotype.

Conclusion: Our results provide a further argument for a role of adhesion molecules and synaptic transmission in neuropsychiatric diseases. Moreover, an involvement of processes related to oxidative stress response and sound-sensing in the pathology of Tourette syndrome seems likely.

Background: Electrophysiological impairments in the magnocellular visual system have been reported among patients with schizophrenia, but previous theories proposed that these deficits may begin in the retina. We therefore sought to evaluate the potential contribution of the retina by comparing retinal and cortical visual electrophysiological impairments between patients with schizophrenia and healthy controls.

Methods: We recruited patients with schizophrenia and age- and sex-matched healthy controls. We recorded the P100 amplitude and latency using electroencephalography (EEG) while projecting low (0.5 cycles/degree) or high (15 cycles/degree) spatial frequency gratings at a temporal frequency of 0 Hz or 8 Hz. We compared the P100 results with previous results for retinal ganglion cell activity (N95) in these participants. We analyzed data using repeated-measures analysis of variance and correlation analyses.

Results: We recruited 21 patients with schizophrenia and 29 age- and sex-matched healthy controls. Results showed decreased P100 amplitude and increased P100 latency among patients with schizophrenia compared with healthy controls (p < 0.05). Analyses reported the main effects of spatial and temporal frequency but no interaction effects of spatial or temporal frequency by group. Moreover, correlation analysis indicated a positive association between P100 latency and previous retinal results for N95 latency in the schizophrenia group (p < 0.05).

Discussion: Alterations in the P100 wave among patients with schizophrenia are consistent with the deficits in early visual cortical processing shown in the literature. These deficits do not seem to correspond to an isolated magnocellular deficit but appear to be associated with previous retinal measurements. Such an association emphasizes the role of the retina in the occurrence of visual cortical abnormalities in schizophrenia. Studies with coupled electroretinography-EEG measurements are now required to further explore these findings.

Clinical trials registration: https://clinicaltrials.gov/ct2/show/NCT02864680.

Background: The postpartum period is a complex time for females that affects health recovery. Stress during this period is one of the main risk factors for depression. Therefore, preventing stress-induced depression in the postpartum period is of great importance. Pup separation (PS) is a natural paradigm of postpartum care; however, the effect of different PS protocols during lactation on stress-induced depressive behaviours in dams is unknown.

Methods: Lactating C57BL/6J mice were subjected to no pup separation (NPS), brief PS (15 min/day, PS15) or long PS (180 min/day, PS180) from postpartum day 1 to postpartum day 21 and were then subjected to chronic restraint stress (CRS) for 21 days. Behavioural tests, specifically the open field test (OFT), elevated plus maze (EPM) test and tail suspension test (TST), were performed. The expression of mRNA and protein in the hippocampus and microbiota composition were also assessed.

Results: We observed CRS-induced anxiety- and depression-like behaviours in NPS dams. In addition, in NPS dams, microglial activation and the levels of NOD-like receptor pyrin domain containing 3, caspase-1 and interleukin-1β were increased, whereas expression levels of collapsing response mediator protein 2 (CRMP2) and α-tubulin were decreased. However, immobility time in the TST was lower in PS15+CRS dams than in NPS+CRS dams, and time spent in the centre during the OFT and in the open arms during the EPM test was higher in PS15+CRS dams, indicating resilience. Expression of hippocampal biomarkers of neuroinflammation was inhibited and levels of CRMP2-mediated neuroplasticity were increased in PS15+CRS dams. Notably, we observed taxonomic changes in the cecal microbiota across different PS groups, as well as relationships between gut microbiota composition and some biomarkers of hippocampal neuroinflammation and neuroplasticity.

Limitations: The sample size for gut microbiota analysis in this study was small.

Conclusion: Collectively, the results of this study confirm that brief PS confers stress resilience in CRS-induced behavioural deficits and reverses hippocampal neuroinflammation-neuroplasticity injury and gut microbiota imbalance.

Open science provides a compelling framework for accelerating global collaborations and enabling discoveries to understand and treat mental health disorders. Herein, we discuss the advantages and obstacles to adopting open science in mental health research, considering the particularities of sensitive and diverse data types, the potential of co-designing projects with research participants and the opportunity of amplifying open science by integration with mental health care. We present a practical example of how this landscape may be navigated to adopt open science across an entire research centre, in 5 steps, namely leadership committing to open science; finding models, resources and allies; identifying needs; defining open science principles; and putting principles into practice. We derive lessons learned that can be built upon by researchers and research organizations joining the open science movement in mental health.