Activity In Schizophrenia Research Articles

Peripheral complement is increased in schizophrenia and inversely related to cortical thickness

BackgroundThere is growing evidence for complement system involvement in the pathophysiology of schizophrenia, although the extent and magnitude of complement factor disturbances has not been fully reported. It also remains unclear whether complement abnormalities are characteristic of all patients with schizophrenia or whether they are representative of a subgroup of patients who show signs of heightened inflammation. The aim of the present study was to quantify and compare the levels of a range of complement factors, receptors and regulators in healthy controls and people with schizophrenia and to determine the extent to which the levels of these peripheral molecules relate to measures of brain structure, particularly cortical thickness. MethodSeventy-five healthy controls and 90 patients with schizophrenia or schizoaffective disorder were included in the study. Peripheral blood samples were collected from all participants and mRNA expression was quantified in 20 complement related genes, four complement proteins, as well as for four cytokines. T1-weighted structural MRI scans were acquired and analysed to determine cortical thickness measures. ResultsThere were significant increases in peripheral mRNA encoding receptors (C5ar1, CR1, CR3a), regulators (CD55, C59) and protein concentrations (C3, C3b, C4) in people with schizophrenia relative to healthy controls. C4a expression was significantly increased in a subgroup of patients displaying elevated peripheral cytokine levels. A higher inflammation index score derived from mRNA expression patterns predicted reductions in cortical thickness in the temporal lobe (superior temporal gyrus, transverse temporal gyrus, fusiform gyrus, insula) in patients with schizophrenia and healthy controls. ConclusionsAnalysis of all three major complement pathways supports increased complement activity in schizophrenia and also shows that peripheral C4a up-regulation is related to increased peripheral pro-inflammatory cytokines in healthy controls. Our region-specific, neuroimaging findings linked to an increased peripheral complement mRNA expression pattern suggests a role for complement in cortical thinning. Further studies are required to further clarify clinical and neurobiological consequences of aberrant complement levels in schizophrenia and related psychoses.

Current findings and perspectives on aberrant neural oscillations in schizophrenia.

There is now consistent evidence that neural oscillation at low- and high-frequencies constitute an important aspect of the pathophysiology of schizophrenia. Specifically, impaired rhythmic activity may underlie the deficit to generate coherent cognition and behavior, leading to the characteristic symptoms of psychosis and cognitive deficits. Importantly, the generating mechanisms of neural oscillations are relatively well-understood and thus enable the targeted search for the underlying circuit impairments and novel treatment targets. In the following review, we will summarize and assess the evidence for aberrant rhythmic activity in schizophrenia through evaluating studies that have utilized Electro/Magnetoencephalography to examine neural oscillations during sensory and cognitive tasks as well as during resting-state measurements. These data will be linked to current evidence from post-mortem, neuroimaging, genetics, and animal models that have implicated deficits in GABAergic interneurons and glutamatergic neurotransmission in oscillatory deficits in schizophrenia. Finally, we will highlight methodological and analytical challenges as well as provide recommendations for future research.

Effect of mGluR2 positive allosteric modulation on frontostriatal working memory activation in schizophrenia.

Negative symptoms and cognitive deficits contribute strongly to disability in schizophrenia, and are resistant to existing medications. Recent drug development has targeted enhanced NMDA function by increasing mGluR2/3 signaling. However, the clinical utility of such agents remains uncertain, and markers of brain circuit function are critical for clarifying mechanisms and understanding individual differences in efficacy. We conducted a double-blind, placebo-controlled, randomized cross-over (14 day washout) pilot study evaluating adjunctive use of the mGluR2 positive allosteric modulator AZD8529 (80mg daily for 3 days), in chronic stable patients with schizophrenia (n=26 analyzed). We focused on 3T fMRI response in frontostriatal regions during an n-back working memory task, testing the hypothesis that AZD8529 produces fMRI changes that correlate with improvement in negative symptoms and cognition. We found that AZD8529 did not produce significant group-average effects on symptoms or cognitive accuracy. However, AZD8529 did increase n-back fMRI activation in striatum (p<0.0001) and anterior cingulate/paracingulate (p=0.002). Greater drug-versus-placebo effects on caudate activation significantly correlated with greater reductions in PANSS negative symptom scores (r=−0.42, p=0.031), and exploratory correlations suggested broader effects across multiple symptom domains and regions of interest. These findings demonstrate that fMRI responses to mGluR2 positive modulation relate to individual differences in symptom reduction, and could be pursued for future biomarker development. Negative clinical results at the group level should not lead to premature termination of investigation of this mechanism which may benefit an important subset of individuals with schizophrenia. Imaging biomarkers may reveal therapeutic mechanisms, and help guide treatment towards specific populations.

To the study of higher nervous activity in schizophrenia in children

The current state of the theory of conditioned reflexes dictates the necessity of introducing a physiological method for studying higher "nervous activity" into the everyday life of clinical research.

Alteration of power law scaling of spontaneous brain activity in schizophrenia

Nonlinear dynamical analysis has been used to quantify the complexity of brain signal at temporal scales. Power law scaling is a well-validated method in physics that has been used to describe the dynamics of a system in the frequency domain, ranging from noisy oscillation to complex fluctuations. In this research, we investigated the power-law characteristics in a large-scale resting-state fMRI data of schizophrenia and healthy participants derived from Taiwan Aging and Mental Illness cohort. We extracted the power spectral density (PSD) of resting signal by Fourier transform. Power law scaling of PSD was estimated by determining the slope of the regression line fitting to the logarithm of PSD. t-Test was used to assess the statistical difference in power law scaling between schizophrenia and healthy participants. The significant differences in power law scaling were found in six brain regions. Schizophrenia patients have significantly more positive power law scaling (i.e., more homogenous frequency components) at four brain regions: left precuneus, left medial dorsal nucleus, right inferior frontal gyrus, and right middle temporal gyrus and less positive power law scaling (i.e., more dominant at lower frequency range) in bilateral putamen compared with healthy participants. Moreover, significant correlations of power law scaling with the severity of psychosis were found. These findings suggest that schizophrenia has abnormal brain signal complexity linked to psychotic symptoms. The power law scaling represents the dynamical properties of resting-state fMRI signal may serve as a novel functional brain imaging marker for evaluating patients with mental illness.

Target selection for deep brain stimulation in treatment resistant schizophrenia

The use of deep brain stimulation (DBS) in treatment resistant patients with schizophrenia is of considerable current interest, but where to site the electrodes is challenging. This article reviews rationales for electrode placement in schizophrenia based on evidence for localized brain abnormality in the disorder and the targets that have been proposed and employed to date. The nucleus accumbens and the subgenual anterior cingulate cortex are of interest on the grounds that they are sites of potential pathologically increased brain activity in schizophrenia and so susceptible to the local inhibitory effects of DBS; both sites have been employed in trials of DBS in schizophrenia. Based on other lines of reasoning, the ventral tegmental area, the substantia nigra pars reticulata and the habenula have also been proposed and in some cases employed. The dorsolateral prefrontal cortex has not been suggested, probably reflecting evidence that it is underactive rather than overactive in schizophrenia. The hippocampus is also of theoretical interest but there is no clear functional imaging evidence that it shows overactivity in schizophrenia. On current evidence, the nucleus accumbens may represent the strongest candidate for DBS electrode placement in schizophrenia, with the substantia nigra pars reticulata also showing promise in a single case report; the ventral tegmental area is also of potential interest, though it remains untried.

Neuronal and Astrocytic Regulations in Schizophrenia: A Computational Modelling Study.

According to the tripartite synapse model, astrocytes have a modulatory effect on neuronal signal transmission. More recently, astrocyte malfunction has been associated with psychiatric diseases such as schizophrenia. Several hypotheses have been proposed on the pathological mechanisms of astrocytes in schizophrenia. For example, post-mortem examinations have revealed a reduced astrocytic density in patients with schizophrenia. Another hypothesis suggests that disease symptoms are linked to an abnormality of glutamate transmission, which is also regulated by astrocytes (glutamate hypothesis of schizophrenia). Electrophysiological findings indicate a dispute over whether the disorder causes an increase or a decrease in neuronal and astrocytic activity. Moreover, there is no consensus as to which molecular pathways and network mechanisms are altered in schizophrenia. Computational models can aid the process in finding the underlying pathological malfunctions. The effect of astrocytes on the activity of neuron-astrocyte networks has been analysed with computational models. These can reproduce experimentally observed phenomena, such as astrocytic modulation of spike and burst signalling in neuron-astrocyte networks. Using an established computational neuron-astrocyte network model, we simulate experimental data of healthy and pathological networks by using different neuronal and astrocytic parameter configurations. In our simulations, the reduction of neuronal or astrocytic cell densities yields decreased glutamate levels and a statistically significant reduction in the network activity. Amplifications of the astrocytic ATP release toward postsynaptic terminals also reduced the network activity and resulted in temporarily increased glutamate levels. In contrast, reducing either the glutamate release or re-uptake in astrocytes resulted in higher network activities. Similarly, an increase in synaptic weights of excitatory or inhibitory neurons raises the excitability of individual cells and elevates the activation level of the network. To conclude, our simulations suggest that the impairment of both neurons and astrocytes disturbs the neuronal network activity in schizophrenia.

Regional Homogeneity Brain Alterations in Schizophrenia: An Activation Likelihood Estimation Meta-Analysis.

ObjectiveResting state functional magnetic resonance imaging (rsfMRI) provides a lot of evidence for local abnormal brain activity in schizophrenia, but the results are not consistent. Our aim is to find out the consistent abnormal brain regions of the patients with schizophrenia by using regional homogeneity (ReHo), and indirectly understand the degree of brain damage of the patients with drug-naive first episode schizophrenia (Dn-FES) and chronic schizophrenia. MethodsWe performed the experiment by activation likelihood estimation (ALE) software to analysis the differences between people with schizophrenia group (all schizophrenia group and chronic schizophrenia group) and healthy controls. ResultsThirteen functional imaging studies were included in quantitative meta-analysis. All schizophrenia group showed decreased ReHo in bilateral precentral gyrus (PreCG) and left middle occipital gyrus (MOG), and increased ReHo in bilateral superior frontal gyrus (SFG) and right insula. Chronic schizophrenia group showed decreased ReHo in bilateral MOG, right fusiform gyrus, left PreCG, left cerebellum, right precuneus, left medial frontal gyrus and left anterior cingulate cortex (ACC). No significant increased brain areas were found in patients with chronic schizophrenia. ConclusionOur findings suggest that patients with chronic schizophrenia have more extensive brain damage than FES, which may contribute to our understanding of the progressive pathophysiology of schizophrenia.

Altered Complexity of Spontaneous Brain Activity in Schizophrenia and Bipolar Disorder Patients

Slice images of the brain regions with significant difference Slice images showed the differences of (a) the effect of group and (b) the effect of interaction between the control and patient groups after adjusting for age, sex, and education (P &lt; 0.05, GRF corrected). CAL.L: Calcarine fissure, DCG.L: Median Cingulate, LING.L: Lingual Gyrus, PCUN.L: Precuneus, IOG.R: Inferior Occipital Gyrus, MTG.R: Middle Temporal Gyrus, HIP.R: Hippocampus, THA.R: Thalamus, MFG.R: Middle Frontal Gyrus, MTG.L: Middle Temporal Gyrus by N. Zhang et al (586–595)image

Levels of lymphocyte-associated regulators of complement system CD55 and CD59 are changed in schizophrenia patients

Objective Although pathological mechanisms of schizophrenia are unknown, evidence in the literature suggests that the immune system might be involved in the pathogenesis. Complement is an important part of the immune system and it has been suggested to play role in the pathogenesis of schizophrenia. We aimed to investigate the potential involvement of the complement system in schizophrenia by the determination of peripheral concentrations of certain complement proteins and their regulators in patients. Methods Plasma concentrations of complement C3, C4, and C1 inhibitory protein were measured by chemiluminescence in 41 schizophrenia patients and 39 healthy controls. Expression of CD55, CD59, and CD46 proteins on peripheral blood mononuclear cells were determined by flow cytometry in the same groups. Results Frequencies of peripheral immune cells expressing CD55 were determined to be significantly higher in schizophrenia patients than in healthy people (p = 0.020). Frequencies of peripheral immune cells expressing CD59 was determined to be significantly higher in healthy people than in schizophrenia patients (p = 0.012). The expression level of CD55 per cell was measured to be significantly elevated in patients compared to healthy controls (p = 0.026). Conclusions Our data clearly demonstrate an elevated complement activity in schizophrenia and points to a possible complement association in the pathogenesis. Key points Increased the expression level, and frequency of CD55 in schizophrenia patients. Decreased frequency of CD59 in schizophrenia patients. No difference in the expression level of CD59; the expression level, and frequency of CD46; frequency of complement C3, C4, and C1 inhibitory protein.

Predicting individual variability in task-evoked brain activity in schizophrenia.

What goes wrong in a schizophrenia patient's brain that makes it so different from a healthy brain? In this study, we tested the hypothesis that the abnormal brain activity in schizophrenia is tightly related to alterations in brain connectivity. Using functional magnetic resonance imaging (fMRI), we demonstrated that both resting‐state functional connectivity and brain activity during the well‐validated N‐back task differed significantly between schizophrenia patients and healthy controls. Nevertheless, using a machine‐learning approach we were able to use resting‐state functional connectivity measures extracted from healthy controls to accurately predict individual variability in the task‐evoked brain activation in the schizophrenia patients. The predictions were highly accurate, sensitive, and specific, offering novel insights regarding the strong coupling between brain connectivity and activity in schizophrenia. On a practical perspective, these findings may allow to generate task activity maps for clinical populations without the need to actually perform any tasks, thereby reducing patients inconvenience while saving time and money.

Altered Resting-State Brain Activity in Schizophrenia and Obsessive-Compulsive Disorder Compared With Non-psychiatric Controls: Commonalities and Distinctions Across Disorders.

Backgrounds: Schizophrenia (SCZ) and obsessive-compulsive disorder (OCD) are classified as two chronic psychiatric disorders with high comorbidity rate and shared clinical symptoms. Abnormal spontaneous brain activity within the cortical–striatal neural circuits has been observed in both disorders. However, it is unclear if the common or distinct neural abnormalities underlie the neurobiological substrates in the resting state.Methods: Resting-state fMRI data were collected from 88 patients with SCZ, 58 patients with OCD, and 72 healthy control subjects. First, we examined differences in amplitude of low-frequency fluctuations (ALFF) among three groups. Resting-state functional connectivity (rsFC) analysis with the brain region that showed different ALFF as the seed was then conducted to identify the changes in brain networks. Finally, we examined the correlation between the altered activities and clinical symptoms.Results: Both the patients with SCZ and OCD showed increased ALFF in the right hippocampus and decreased ALFF in the left posterior cingulate cortex (PCC). SCZ patients exhibited increased ALFF in the left caudate [voxel-level family-wise error (FWE) P < 0.05] and decreased rsFC between the left caudate and right cerebellum, which correlated with positive symptoms. The left caudate showed increased rsFC with the right thalamus and bilateral supplementary motor complex (SMC) in OCD patients (cluster-level FWE P < 0.05).Conclusions: The hippocampus and PCC are common regions presenting abnormal local spontaneous neuronal activities in both SCZ and OCD, while the abnormality of the striatum can reflect the differences. Increased ALFF in the striatum and symptom-related weakened rsFC between the caudate and cerebellum showed SCZ specificity. Enhanced rsFC between the caudate and SMC may be a key characteristic in OCD. Our research shows the similarities and differences between the two diseases from the perspective of resting-state fMRI, which provides clues to understand the disease and find methods for treatment.

MTOR kinase activity disrupts a phosphorylation signaling network in schizophrenia brain.

The AKT-mTOR signaling transduction pathway plays an important role in neurodevelopment and synaptic plasticity. mTOR is a serine/threonine kinase that modulates signals from multiple neurotransmitters and phosphorylates specific proteins to regulate protein synthesis and cytoskeletal organization. There is substantial evidence demonstrating abnormalities in AKT expression and activity in different schizophrenia (SZ) models. However, direct evidence for dysregulated mTOR kinase activity and its consequences on downstream effector proteins in SZ pathophysiology is lacking. Recently, we reported reduced phosphorylation of mTOR at an activating site and abnormal mTOR complex formation in the SZ dorsolateral prefrontal cortex (DLPFC). Here, we expand on our hypothesis of disrupted mTOR signaling in the SZ brain and studied the expression and activity of downstream effector proteins of mTOR complexes and the kinase activity profiles of SZ subjects. We found that S6RP phosphorylation, downstream of mTOR complex I, is reduced, whereas PKCα phosphorylation, downstream of mTOR complex II, is increased in SZ DLPFC. In rats chronically treated with haloperidol, we showed that S6RP phosphorylation is increased in the rat frontal cortex, suggesting a potential novel mechanism of action for antipsychotics. We also demonstrated key differences in kinase signaling networks between SZ and comparison subjects for both males and females using kinome peptide arrays. We further investigated the role of mTOR kinase activity by inhibiting it with rapamycin in postmortem tissue and compared the impact of mTOR inhibition in SZ and comparison subjects using kinome arrays. We found that SZ subjects are globally more sensitive to rapamycin treatment and AMP-activated protein kinase (AMPK) contributes to this differential kinase activity. Together, our findings provide new insights into the role of mTOR as a master regulator of kinase activity in SZ and suggest potential targets for therapeutic intervention.

Smartphone-Based Markers of Social Activity in Schizophrenia and Bipolar Disorder

Social impairment and isolation are indicators of progression and predictors of relapse in psychiatric disorders. Little research has been done to measure these constructs using digital technologies in this population. We investigate the feasibility of collecting active and passive information about the social activity phenotype, in the long-term, using the Beiwe smartphone application.

DNA hydrolysing IgG catalytic antibodies: an emerging link between psychoses and autoimmunity

It is not uncommon to observe autoimmune comorbidities in a significant subset of patients with psychotic disorders, namely schizophrenia (SCZ) and bipolar disorder (BPD). To understand the autoimmune basis, the DNA abyzme activity mediated by serum polyclonal IgG Abs were examined in psychoses patients, quantitatively, by an in-house optimized DNase assay. A similar activity exhibited by IgG Abs from neuropsychiatric-systemic lupus erythematosus (NP-SLE) patients was used as a comparator. Our data revealed that the IgG DNase activity of SCZ was close to that of NP-SLE and it was twofold higher than the healthy controls. Interestingly, the association between DNase activity with PANSS (positive, general and total scores) and MADRS were noted in a subgroup of SCZ and BPD patients, respectively. In our study group, the levels of IL-6 and total IgG in BPD patients were higher than SCZ and healthy controls, indicating a relatively inflammatory nature in BPD, while autoimmune comorbidity was mainly observed in SCZ patients.

Altered Complexity of Spontaneous Brain Activity in Schizophrenia and Bipolar Disorder Patients.

Schizophrenia (SC) and bipolar disorder (BP) share elements of symptoms and the underlying neural mechanisms for both remain unclear. Recently, the complexity of spontaneous functional MRI (fMRI) signals in brain activity has been investigated in SC and BP using multiscale sample entropy (MSE) with inconsistent results. To perform MSE analysis across five time scales to assess differences in resting-state fMRI signal complexity in SC, BP, and normal controls (NC). Retrospective. Fifty SC, 49 BP, and 49 NC. A 3 T, T2* weighted echo planar imaging (EPI) sequence. The mean MSEs of all gray matter (GM) and of 12 regions of interest (ROIs) were extracted using masks across the five scales. The regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) in these ROIs were also determined and the relationship between the three measures was investigated. The correlations between cognitive assessment scores and MSE values were also explored. Bonferroni correction, One-way ANOVA, Spearman rank correlation coefficient (r), Gaussian random field (GRF) correction. There were decreased GM MSE values in the patient groups (F=9.629, P < 0.05). SC and BP patients demonstrated lower complexity than NCs in the calcarine fissure, precuneus, inferior occipital gyrus, lingual gyrus and cerebellum, and higher complexity in the median cingulate, thalamus, hippocampus, middle temporal gyrus and middle frontal gyrus. There were significant differences between SC and BP patients in the precuneus (F=4.890, P < 0.05) and inferior occipital gyrus (F=5.820, P < 0.05). Calcarine fissure, cingulate, temporal gyrus, occipital gyrus, hippocampus, precuneus, frontal gyrus, and lingual gyrus MSE values were significantly correlated with both ReHo (r > 0.282, P < 0.05) and ALFF (r > 0.278, P < 0.05). Furthermore, median temporal MSE (r=-0.321, P < 0.05) on scale 3 and (r=-0.307, P < 0.05) on scale 4 and median cingulate MSE (r=-0.337, P < 0.05) on scale 5 was significantly negatively correlated with cognitive assessment scores. These data highlight different patterns of brain signal intensity complexity in SC and BP. 1 TECHNICAL EFFICACY: Stage 1.

Separating scale-free and oscillatory components of neural activity in schizophrenia.

IntroductionAlterations in narrow‐band spectral power of electroencephalography (EEG) recordings are commonly reported in patients with schizophrenia (SZ). It is well established however that electrophysiological signals comprise a broadband scale‐free (or fractal) component generated by mechanisms different from those producing oscillatory neural activity. Despite this known feature, it has not yet been investigated if spectral abnormalities found in SZ could be attributed to scale‐free or oscillatory brain function.MethodsIn this study, we analyzed resting‐state EEG recordings of 14 SZ patients and 14 healthy controls. Scale‐free and oscillatory components of the power spectral density (PSD) were separated, and band‐limited power (BLP) of the original (mixed) PSD, as well as its fractal and oscillatory components, was estimated in five frequency bands. The scaling property of the fractal component was characterized by its spectral exponent in two distinct frequency ranges (1–13 and 13–30 Hz).ResultsAnalysis of the mixed PSD revealed a decrease of BLP in the delta band in SZ over the central regions; however, this difference could be attributed almost exclusively to a shift of power toward higher frequencies in the fractal component. Broadband neural activity expressed a true bimodal nature in all except frontal regions. Furthermore, both low‐ and high‐range spectral exponents exhibited a characteristic topology over the cortex in both groups.ConclusionOur results imply strong functional significance of scale‐free neural activity in SZ and suggest that abnormalities in PSD may emerge from alterations of the fractal and not only the oscillatory components of neural activity.

EHealth tools for assessing psychomotor activity in schizophrenia: a systematic review.

Objective:Psychomotor abnormalities are relevant symptoms in the clinical presentation of schizophrenia, and assessing them could facilitate monitoring. New technologies can measure psychomotor activity objectively and continuously, but evidence on the topic is scarce. Our aim is to systematically review the existing evidence about eHealth tools for assessing psychomotor activity in patients diagnosed with schizophrenia.Method:We performed a systematic search of the PubMed and Embase databases and identified 15 relevant articles on eHealth tools for assessing psychomotor activity in schizophrenia.Results:eHealth devices accurately assessed psychomotor activity and were well accepted. Abnormalities in psychomotor activity helped differentiate between different subtypes of schizophrenia. Abnormal increases in psychomotor activity were correlated with acute presentations, while lower activity was associated with relapses, deterioration, and negative symptoms.Conclusion:Actigraphy is still the preferred eHealth device in research settings, but mobile applications have great potential. Further studies are needed to explore the possibilities of psychomotor monitoring and mobile health applications for preventing relapses in schizophrenia. eHealth could be useful for monitoring psychomotor activity, which might help prevent relapses.

A loss of mature microglial markers without immune activation in schizophrenia.

Microglia, the immune cells of the brain, are important for neurodevelopment and have been hypothesized to play a role in the pathogenesis of schizophrenia (SCZ). Although previous postmortem studies pointed toward presence of microglial activation, this view has been challenged by more recent hypothesis‐driven and hypothesis‐free analyses. The aim of the present study is to further understand the observed microglial changes in SCZ. We first performed a detailed meta‐analysis on studies that analyzed microglial cell density, microglial morphology, and expression of microglial‐specific markers. We then further explored findings from the temporal cortex by performing immunostainings and qPCRs on an additional dataset. A random effect meta‐analysis showed that the density of microglial cells was unaltered in SCZ (ES: 0.144 95% CI: 0.102 to 0.390, p = .250), and clear changes in microglial morphology were also absent. The expression of several microglial specific genes, such as CX3CR1, CSF1R, IRF8, OLR1, and TMEM119 was decreased in SCZ (ES: −0.417 95% CI: −0.417 to −0.546, p < .0001), consistent with genome‐wide transcriptome meta‐analysis results. These results indicate a change in microglial phenotype rather than density, which was validated with the use of TMEM119/Iba1 immunostainings on temporal cortex of a separate cohort. Changes in microglial gene expression were overlapping between SCZ and other psychiatric disorders, but largely opposite from changes reported in Alzheimer's disease. This distinct microglial phenotype provides a crucial molecular hallmark for future research into the role of microglia in SCZ and other psychiatric disorders.

Astrocytes in schizophrenia.

Schizophrenia is a severe and clinically heterogenous mental disorder affecting approximately 1% of the population worldwide. Despite tremendous achievements in the field of schizophrenia research, its precise aetiology remains elusive. Besides dysfunctional neuronal signalling, the pathophysiology of schizophrenia appears to involve molecular and functional abnormalities in glial cells, including astrocytes. This article provides a concise overview of the current evidence supporting altered astrocyte activity in schizophrenia, which ranges from findings obtained from post-mortem immunohistochemical analyses, genetic association studies and transcriptomic investigations, as well as from experimental investigations of astrocyte functions in animal models. Integrating the existing data from these research areas strongly suggests that astrocytes have the capacity to critically affect key neurodevelopmental and homeostatic processes pertaining to schizophrenia pathogenesis, including glutamatergic signalling, synaptogenesis, synaptic pruning and myelination. The further elucidation of astrocytes functions in health and disease may, therefore, offer new insights into how these glial cells contribute to abnormal brain development and functioning underlying this debilitating mental disorder.