JOURNAL OF PSYCHIATRY & NEUROSCIENCE

Glutamate levels and symptom burden in high-risk and first-episode schizophrenia: a dual-voxel study of the anterior cingulate cortex
Fan L, Zhang Z, Ma X, Liang L, Wang Y, Yuan L, Ouyang L, Li Z, Chen X, He Y and Palaniyappan L
Reduced glutamatergic excitability of the anterior cingulate cortex (ACC) has been long suspected in schizophrenia; recent observations support low glutamatergic tone as the primary pathophysiology contributing to subtle early features of this illness, with a secondary disinhibition (higher glutamate tone) resulting in more prominent clinical symptoms later in its course. We sought to investigate whether people with genetic high risk (GHR) for schizophrenia have lower glutamate levels in the ACC than those at later stages of clinical high risk (CHR) and those with first-episode schizophrenia (FES), among whom symptoms are already prominent.
Public discourse on mental health: a critical view
Malla A and Gold I
Intracranial self-stimulation reverses impaired spatial learning and regulates serum microRNA levels in a streptozotocin-induced rat model of Alzheimer disease
Riberas-Sánchez A, Puig-Parnau I, Vila-Solés L, Garcia-Brito S, Aldavert-Vera L, Segura-Torres P, Huguet G and Kádár E
The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is ongoing. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs.
Correction to "Improving causality perception judgments in schizophrenia spectrum disorder via transcranial direct current stimulation"
Neuroimaging alterations and relapse in early-stage psychosis
Mihaljevic M, Nagpal A, Etyemez S, Narita Z, Ross A, Schaub R, Cascella NG, Coughlin JM, Nestadt G, Nucifora FC, Sedlak TW, Calhoun VD, Faria AV, Yang K and Sawa A
Recent reports have indicated that symptom exacerbation after a period of improvement, referred to as relapse, in early-stage psychosis could result in brain changes and poor disease outcomes. We hypothesized that substantial neuroimaging alterations may exist among patients who experience relapse in early-stage psychosis.
Widespread reductions in cortical thickness following ketamine abuse
Tang J, Wu Q, Qi C, Xie A, Liu J, Sun Y, Yuan T, Chen W, Liu T, Hao W, Shao X and Liao Y
Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine.
Disproportionate neuroanatomical effects of haploinsufficiency in adolescence compared with adulthood: links to dopamine, connectivity, covariance, and gene expression brain maps in mice
Hoops D, Yee Y, Hammill C, Wong S, Manitt C, Bedell BJ, Cahill L, Lerch JP, Flores C and Sled JG
Critical adolescent neural refinement is controlled by the DCC (deleted in colorectal cancer) protein, a receptor for the netrin-1 guidance cue. We sought to describe the effects of reduced on neuroanatomy in the adolescent and adult mouse brain.
Interaction of the gut microbiota and brain functional connectivity in late-life depression
Tsai CF, Chuang CH, Tu PC, Chang WC, Wang YP, Liu PY, Wu PS, Lin CY and Lu CL
Increasing evidence suggests an important role of the gut microbiome in the pathogenesis of mental disorders, including depression, along the microbiota-gut-brain axis. We sought to explore the interactions between gut microbe composition and neural circuits in late-life depression (LLD).
Perspective on adolescent psychiatric illness and emerging role of microRNAs as biomarkers of risk
Morgunova A, Teixeira M and Flores C
Spatial transcriptomic analysis of adult hippocampal neurogenesis in the human brain
Simard S, Rahimian R, Davoli MA, Théberge S, Matosin N, Turecki G, Nagy C and Mechawar N
Adult hippocampal neurogenesis has been extensively characterized in rodent models, but its existence in humans remains controversial. We sought to assess the phenomenon in postmortem human hippocampal samples by combining spatial transcriptomics and multiplexed fluorescent in situ hybridization.
CCNP Innovations in Neuropsychopharmacology Award: The psychopharmacology of psychedelics: where the brain meets spirituality
Gobbi G
For 3000 years, psychedelics have been used in religious contexts to enhance spiritual thinking, well-being, and a sense of community. In the last few years, a renaissance in the use of psychedelic drugs for mental disorders has occurred in Western society; consequently, a pressing scientific need to elucidate the intricate mechanisms underlying their actions has arisen. Psychedelics mainly bind to serotonin (5-HT) receptors, particularly 5-HT receptors, but may also bind to other receptors. Unlike conventional psychotropic drugs used in psychiatry, psychedelics introduce a distinctive complexity. They not only engage in receptor activation, but also exert influence over specific neural circuits, thereby facilitating transformative cognitive experiences and fostering what many have identified as a spiritual contemplation or mystical experience. This comprehensive review describes clinical studies that have examined the propensity of psychedelics to enhance spiritual, mystical, and transcendent cognitive states. This multifaceted nature, encompassing diverse components and paradigms, necessitates careful consideration during the investigation of psychedelic mechanisms of action to avoid oversimplification. The present review endeavours to elucidate the mechanisms underlying the actions of 2 principal psychedelic substances, psilocybin and lysergic acid diethylamide (LSD), with a focus on monoamine and glutamate receptor mechanisms; molecular aspects, such as neuroplasticity and epigenetics; as well as the impact of psychedelics on brain circuits, including the default mode network and the cortico-striato-thalamo-cortical network. Given their distinctive and intricate mechanisms of action, psychedelics necessitate a novel conceptual framework in psychiatry, offering insight into the treatment of mental health disorders and facilitating the integration of the realms of brain, mind, and spirituality.
Altered neural activities during emotion regulation in depression: a meta-analysis
Wu D, Li J and Wang J
Deficient neural activities during emotion regulation have been reported in depression. We sought to conduct a meta-analysis to provide a comprehensive description of these neural alterations during use of emotion regulation strategies among patients with depression, including major depressive disorder (MDD) and bipolar disorder (BD).
Structural-informed functional MRI analysis of patients with empathy impairment following stroke
Qu JF, Liu XW, Wang MZ, Luo YS, Gao T, Shi L and Chen YK
The underlying functional alterations of brain structural changes among patients with empathy impairment following stroke remain unclear. We sought to investigate functional connectivity changes informed by brain structural abnormalities in multimodal magnetic resonance imaging (MRI) among patients with empathy impairment following stroke.
Beyond mood - depression as a speed disorder: biomarkers for abnormal slowness
Northoff G
Emotions related to threatening events are mainly linked to the right hemisphere
Gainotti G
A recent meta-analysis of functional neuroimaging contrasts between emotional and neutral face processing has shown that the processing of facial emotions can be better classified according to threat detection than emotional valence, with the authors suggesting that their data are inconsistent with both the right-hemisphere and valence models of emotional laterality. I report empirical and theoretical data indicating that facial expressions are better classified according to threat detection than to the distinction between positive and negative emotions. I challenge, however, the claim that laterality effects provide little support to the right-hemisphere model of emotional laterality. This claim contrasts with neuropsychological and psychophysiological investigations that have shown that the right hemisphere has a graded prevalence for emotions provoked by threatening events. A reanalysis of data obtained in the target study suggests that the reported data are not necessarily inconsistent with a model assuming a graded, right-hemisphere dominance for emotions. I present a model of hemispheric asymmetries that could be consistent with the assumption that the right hemisphere's dominance for emotions may mainly be concerned with threatening events.
Plasma exosomes carrying mmu-miR-146a-5p and Notch signalling pathway-mediated synaptic activity in schizophrenia
Wang Z, Wu T, Hu H, Alabed AAA, Cui G, Sun L, Sun Z, Wang Y and Li P
Schizophrenia is characterized by a complex interplay of genetic and environmental factors, leading to alterations in various molecular pathways that may contribute to its pathogenesis. Recent studies have shown that exosomal microRNAs could play essential roles in various brain disorders; thus, we sought to explore the potential molecular mechanisms through which microRNAs in plasma exosomes are involved in schizophrenia.
Oxytocin neurons in the paraventricular nucleus and fear empathy among male mice
Zhang L, Chen HC, Li B, Cao JX, Su XM, Kang YT, Gao LP and Jing YH
Recent studies have identified empathy deficit as a core impairment and diagnostic criterion for people with autism spectrum disorders; however, the improvement of empathy focuses primarily on behavioural interventions without the target regulation. We sought to compare brain regions associated with empathy-like behaviours of fear and pain, and to explore the role of the oxytocin-oxytocin receptor system in fear empathy.
Clozapine-induced priapism in a man with schizoaffective disorder
Woo J and Eisa M
Effects of repetitive transcranial magnetic stimulation on individual variability of resting-state functional connectivity in major depressive disorder
Tan V, Downar J, Nestor S, Vila-Rodriguez F, Daskalakis ZJ, Blumberger DM and Hawco C
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), but substantial heterogeneity in outcomes remains. We examined a potential mechanism of action of rTMS to normalize individual variability in resting-state functional connectivity (rs-fc) before and after a course of treatment.
Perplexity of utterances in untreated first-episode psychosis: an ultra-high field MRI dynamic causal modelling study of the semantic network
Alonso-Sánchez MF, Hinzen W, He R, Gati J and Palaniyappan L
Psychosis involves a distortion of thought content, which is partly reflected in anomalous ways in which words are semantically connected into utterances in speech. We sought to explore how these linguistic anomalies are realized through putative circuit-level abnormalities in the brain's semantic network.
Altered effective connectivity among face-processing systems in major depressive disorder
Sheng F, Wang Y, Li R, Li X, Chen X, Zhang Z, Liu R, Zhang L, Zhou Y and Wang G
Neuroimaging studies have revealed abnormal functional interaction during the processing of emotional faces in patients with major depressive disorder (MDD), thereby enhancing our comprehension of the pathophysiology of MDD. However, it is unclear whether there is abnormal directional interaction among face-processing systems in patients with MDD.
Emotional dysregulation and stimulant medication in adult ADHD
Greenfield MS, Wang Y, Hamilton JP, Thunberg P and Msghina M
Emotional dysregulation affects up to two-thirds of adult patients with attention-deficit/hyperactivity disorder (ADHD) and is increasingly seen as a core ADHD symptom that is clinically associated with greater functional impairment and psychiatric comorbidity. We sought to investigate emotional dysregulation in ADHD and explored its neural underpinnings.
Correction to "Navigated and individual α-peak-frequency-guided transcranial magnetic stimulation in male patients with treatment-refractory schizophrenia"
Cerebellar network alterations in adult attention-deficit/hyperactivity disorder
Parkkinen S, Radua J, Andrews DS, Murphy D, Dell'Acqua F and Parlatini V
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that often persists into adulthood. Underlying alterations in brain connectivity have been identified but some relevant connections, such as the middle, superior, and inferior cerebellar peduncles (MCP, SCP, and ICP, respectively), have remained largely unexplored; thus, we sought to investigate whether the cerebellar peduncles contribute to ADHD pathophysiology among adults.
Making use of N-of-1 trials to treat ADHD in people with psychosis: a hypothetical case
Dalton K, Joober R, Karama S and Palaniyappan L
Aberrant functional connectivity of the globus pallidus in the modulation of the relationship between childhood trauma and major depressive disorder
Xia J, Lin X, Yu T, Yu H, Zou Y, Luo Q and Peng H
Childhood trauma plays a crucial role in the dysfunctional reward circuitry in major depressive disorder (MDD). We sought to explore the effect of abnormalities in the globus pallidus (GP)-centric reward circuitry on the relationship between childhood trauma and MDD.
Advances in the understanding of the pathophysiology of schizophrenia and bipolar disorder through induced pluripotent stem cell models
Perrottelli A, Marzocchi FF, Caporusso E, Giordano GM, Giuliani L, Melillo A, Pezzella P, Bucci P, Mucci A and Galderisi S
The pathophysiology of schizophrenia and bipolar disorder involves a complex interaction between genetic and environmental factors that begins in the early stages of neurodevelopment. Recent advancements in the field of induced pluripotent stem cells (iPSCs) offer a promising tool for understanding the neurobiological alterations involved in these disorders and, potentially, for developing new treatment options. In this review, we summarize the results of iPSC-based research on schizophrenia and bipolar disorder, showing disturbances in neurodevelopmental processes, imbalance in glutamatergic-GABAergic transmission and neuromorphological alterations. The limitations of the reviewed literature are also highlighted, particularly the methodological heterogeneity of the studies, the limited number of studies developing iPSC models of both diseases simultaneously, and the lack of in-depth clinical characterization of the included samples. Further studies are needed to advance knowledge on the common and disease-specific pathophysiological features of schizophrenia and bipolar disorder and to promote the development of new treatment options.
The : implications for human participant research with cannabis
Di Ciano P, Wickens C, Paul EM, Mahmood R, Crépault JF, Rueda S and Boileau I
Navigated and individual α-peak-frequency-guided transcranial magnetic stimulation in male patients with treatment-refractory schizophrenia
Tuppurainen H, Määttä S, Könönen M, Julkunen P, Kautiainen H, Hyvärinen S, Vaurio O, Joensuu M, Vanhanen M, Aho-Mustonen K, Mervaala E and Tiihonen J
Previous electroencephalography (EEG) studies have indicated altered brain oscillatory α-band activity in schizophrenia, and treatment with repetitive transcranial magnetic stimulation (rTMS) using individualized α-frequency has shown therapeutic effects. Magnetic resonance imaging-based neuronavigation methods allow stimulation of a specific cortical region and improve targeting of rTMS; therefore, we sought to study the efficacy of navigated, individual α-peak-frequency-guided rTMS (αTMS) on treatment-refractory schizophrenia.
Decreased temporal variabilities of functional connectivities in insula and lingual gyrus are associated with better early treatment response in patients with panic disorder
You L, Jiang W, Zhang X, Li Y, Wei J, Zhou Y, Chen S, Lu N, Yue Y, Kong Y and Yuan Y
Panic disorder is a common disabling condition with limited biomarkers. We aimed to explore the diagnostic and treatment response prediction value of functional temporal variability in people with panic disorder.