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Schizophrenia Bulletin Jan 2024Consistent with postmortem findings in patients, most animal models for schizophrenia (SCZ) present abnormal levels of parvalbumin (PV), a marker of fast-spiking... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Consistent with postmortem findings in patients, most animal models for schizophrenia (SCZ) present abnormal levels of parvalbumin (PV), a marker of fast-spiking GABAergic interneurons, in the prefrontal cortex (PFC) and hippocampus (HIP). However, there are discrepancies in the literature. PV reductions lead to a functional loss of PV interneurons, which is proposed to underly SCZ symptoms. Given its complex etiology, different categories of animal models have been developed to study SCZ, which may distinctly impact PV levels in rodent brain areas.
STUDY DESIGN
We performed a quantitative meta-analysis on PV-positive cell number/density and expression levels in the PFC and HIP of animal models for SCZ based on pharmacological, neurodevelopmental, and genetic manipulations.
RESULTS
Our results confirmed that PV levels are significantly reduced in the PFC and HIP regardless of the animal model. By categorizing into subgroups, we found that all pharmacological models based on NMDA receptor antagonism decreased PV-positive cell number/density or PV expression levels in both brain areas examined. In neurodevelopmental models, abnormal PV levels were confirmed in both brain areas in maternal immune activation models and HIP of the methylazoxymethanol acetate model. In genetic models, negative effects were found in neuregulin 1 and ERBB4 mutant mice in both brain regions and the PFC of dysbindin mutant mice. Regarding sex differences, male rodents exhibited PV reductions in both brain regions only in pharmacological models, while few studies have been conducted in females.
CONCLUSION
Overall, our findings support deficits in prefrontal and hippocampal PV interneurons in animal models for SCZ.
Topics: Humans; Mice; Male; Female; Animals; Schizophrenia; Parvalbumins; Disease Models, Animal; Interneurons; Prefrontal Cortex; Hippocampus
PubMed: 37584417
DOI: 10.1093/schbul/sbad123 -
Psychoneuroendocrinology Jun 2019Melatonin (MLT), the main hormone of the pineal gland (PG), is assumed to support initiation and maintenance of sleep, and a stable sleep-wake cycle, exerting... (Meta-Analysis)
Meta-Analysis
Melatonin (MLT), the main hormone of the pineal gland (PG), is assumed to support initiation and maintenance of sleep, and a stable sleep-wake cycle, exerting antioxidative and neuroprotective actions. Evidence demonstrates that sleep and circadian rhythm abnormalities are very common in schizophrenia patients. Some imaging studies suggest structural abnormalities of the PG in these patients as well. We aimed to critically appraise the literature on PG imaging and melatonin secretion in schizophrenia patients, in comparison to matched healthy controls, and to review placebo-controlled trials of add-on exogenous MLT treatment in schizophrenia patients. In this systematic review, twenty-nine studies were included. Meta-analytical evaluation of data was possible only for MLT secretion finding that midnight plasma levels were significantly reduced in individuals with schizophrenia as compared to healthy controls (Hedge`s g = 1.32, p < 0.01). Imaging studies demonstrated greater prevalence of enlarged calcifications (>1 cm) of the PG (2 out of 2 computed tomography studies) and smaller PG volume (2 out of 3 magnetic resonance studies) compared with healthy controls. Anatomic and functional abnormalities of the PG were not associated with duration of illness or with treatment factors, maybe suggesting them to be primary characteristics of the disease and genetically based. Add-on MLT treatment leads to a modest improvement of objective and subjective sleep quality, of metabolic adverse effects of antipsychotics, and of tardive dyskinesia symptoms in schizophrenia patients. It remains to be established whether MLT treatment in prodromal phases of the disease could prevent neurostructural abnormalities.
Topics: Circadian Rhythm; Female; Humans; Magnetic Resonance Imaging; Male; Melatonin; Pineal Gland; Schizophrenia; Schizophrenic Psychology; Sleep
PubMed: 30831343
DOI: 10.1016/j.psyneuen.2019.02.024 -
Epilepsia Jun 2024Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a widespread invasive procedure for treating drug-resistant epilepsy. Nonetheless, there is... (Meta-Analysis)
Meta-Analysis Review
Assessing short-term and long-term security and efficacy of anterior nucleus of the thalamus deep brain stimulation for treating drug-resistant epilepsy: A systematic review and single-arm meta-analysis.
Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a widespread invasive procedure for treating drug-resistant epilepsy. Nonetheless, there is a persistent debate regarding the short-term and long-term efficacy and safety of ANT-DBS. Thus we conducted a systematic review and meta-analysis. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we searched PubMed, Cochrane, Embase, and Web of Science for studies treating refractory epilepsy with ANT-DBS. Short-term analysis was considered for studies with a mean follow-up of 3 years or less. The following outcomes were assessed for data extraction: procedure responders and nonresponders, increased seizure frequency, complications, and procedure-related mortality. Of 650 studies, 25 fit our inclusion criteria, involving 427 patients. Previous surgical treatments have been reported in 214 patients (50.1%) and a median average baseline seizure frequency of 64.9 monthly seizures. In the short-term analysis, we observed a proportion of 67% (95% confidence interval [CI] 54%-79%) of responders and 33% (95% CI 21%-46%) of nonresponders. In addition, 4% (95% CI 0%-9%) of the patients presented increased seizure frequency. In the long-term analysis, we observed 72% (95% CI 66%-78%) responders and 27% (95% CI 21%-34%) nonresponders. Moreover, there was a 2% (95% CI 0%-5%) increase in seizure frequency. No procedure-related mortality was reported at any follow-up. ANT-DBS effectively treats refractory epilepsy, with lasting short-term and long-term benefits. It remains safe and efficient despite complications, showing no procedure-linked fatalities, high patient responsiveness, and minimal increased seizures. Consistent results over time and low morbidity/mortality rates emphasize its worth. Further research is necessary to diminish the discrepancy among results.
Topics: Humans; Deep Brain Stimulation; Drug Resistant Epilepsy; Anterior Thalamic Nuclei; Treatment Outcome
PubMed: 38506635
DOI: 10.1111/epi.17955 -
Neuroscience and Biobehavioral Reviews Sep 2023The dysregulation of excitatory and inhibitory neurotransmission is considered a pathological marker of Anorexia Nervosa (AN), however, no systematic evaluation of the... (Review)
Review
The dysregulation of excitatory and inhibitory neurotransmission is considered a pathological marker of Anorexia Nervosa (AN), however, no systematic evaluation of the proton Magnetic Resonance Spectroscopy (H-MRS) literature has been conducted to date. Accordingly, we conducted a systematic review of neurometabolite differences between individuals with AN and healthy controls (HC). A comprehensive database search (until June 2023) identified seven studies meeting inclusion criteria. Samples included adolescents and adults with similar mean age (AN: 22.20 HC: 22.60), and female percentages (AN: 98%; HC: 94%). The review found a considerable need for improving study design and the reporting of MRS sequence parameters and analysis. Reduced glutamate concentrations in the ACC and OCC, and reduced Glx concentrations in the ACC were reported by one and two studies, respectively. Lastly, only one study to date has quantified GABA concentrations, with no significant differences found. In conclusion, there is currently insufficient evidence of excitatory and inhibitory neurometabolites changes in AN. As the H-MRS literature in AN increases, the key questions herein proposed must be revisited.
Topics: Anorexia Nervosa; Proton Magnetic Resonance Spectroscopy; Gyrus Cinguli; Occipital Lobe; Humans; Glutamic Acid
PubMed: 37307945
DOI: 10.1016/j.neubiorev.2023.105279 -
Developmental Cognitive Neuroscience Dec 2023Resting-state functional connectivity (rsFC) has the potential to shed light on how childhood abuse and neglect relates to negative psychiatric outcomes. However, a... (Review)
Review
Resting-state functional connectivity (rsFC) has the potential to shed light on how childhood abuse and neglect relates to negative psychiatric outcomes. However, a comprehensive review of the impact of childhood maltreatment on the brain's resting state functional organization has not yet been undertaken. We systematically searched rsFC studies in children and youth exposed to maltreatment. Nineteen studies (total n = 3079) met our inclusion criteria. Two consistent findings were observed. Childhood maltreatment was linked to reduced connectivity between the anterior insula and dorsal anterior cingulate cortex, and with widespread heightened amygdala connectivity with key structures in the salience, default mode, and prefrontal regulatory networks. Other brain regions showing altered connectivity included the ventral anterior cingulate cortex, dorsolateral prefrontal cortex, and hippocampus. These patterns of altered functional connectivity associated with maltreatment exposure were independent of symptoms, yet comparable to those seen in individuals with overt clinical disorder. Summative findings indicate that rsFC alterations associated with maltreatment experience are related to poor cognitive and social functioning and are prognostic of future symptoms. In conclusion, maltreatment is associated with altered rsFC in emotional reactivity, regulation, learning, and salience detection brain circuits. This indicates patterns of recalibration of putative mechanisms implicated in maladaptive developmental outcomes.
Topics: Adolescent; Humans; Child; Brain; Amygdala; Brain Mapping; Gyrus Cinguli; Child Abuse; Magnetic Resonance Imaging
PubMed: 37952287
DOI: 10.1016/j.dcn.2023.101322 -
Frontiers in Immunology 2024Recent evidence supports the contribution of gut microbiota dysbiosis to the pathophysiology of rheumatic diseases, neuropathic pain, and neurodegenerative disorders.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Recent evidence supports the contribution of gut microbiota dysbiosis to the pathophysiology of rheumatic diseases, neuropathic pain, and neurodegenerative disorders. The bidirectional gut-brain communication network and the occurrence of chronic pain both involve contributions of the autonomic nervous system and the hypothalamic pituitary adrenal axis. Nevertheless, the current understanding of the association between gut microbiota and chronic pain is still not clear. Therefore, the aim of this study is to systematically evaluate the existing knowledge about gut microbiota alterations in chronic pain conditions.
METHODS
Four databases were consulted for this systematic literature review: PubMed, Web of Science, Scopus, and Embase. The Newcastle-Ottawa Scale was used to assess the risk of bias. The study protocol was prospectively registered at the International prospective register of systematic reviews (PROSPERO, CRD42023430115). Alpha-diversity, β-diversity, and relative abundance at different taxonomic levels were summarized qualitatively, and quantitatively if possible.
RESULTS
The initial database search identified a total of 3544 unique studies, of which 21 studies were eventually included in the systematic review and 11 in the meta-analysis. Decreases in alpha-diversity were revealed in chronic pain patients compared to controls for several metrics: observed species (SMD= -0.201, 95% CI from -0.04 to -0.36, p=0.01), Shannon index (SMD= -0.27, 95% CI from -0.11 to -0.43, p<0.001), and faith phylogenetic diversity (SMD -0.35, 95% CI from -0.08 to -0.61, p=0.01). Inconsistent results were revealed for beta-diversity. A decrease in the relative abundance of the Lachnospiraceae family, genus and , and species of and , as well as an increase in spp., was revealed in chronic pain patients compared to controls.
DISCUSSION
Indications for gut microbiota dysbiosis were revealed in chronic pain patients, with non-specific disease alterations of microbes.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023430115.
Topics: Humans; Chronic Pain; Dysbiosis; Hypothalamo-Hypophyseal System; Phylogeny; Pituitary-Adrenal System; Clostridiales
PubMed: 38352865
DOI: 10.3389/fimmu.2024.1342833 -
Journal of Neurosurgery Feb 2023The nucleus accumbens (NAcc) of the ventral striatum is critically involved in goal- and reward-based behavior. Structural and functional abnormalities of the NAcc or... (Review)
Review
OBJECTIVE
The nucleus accumbens (NAcc) of the ventral striatum is critically involved in goal- and reward-based behavior. Structural and functional abnormalities of the NAcc or its associated neural systems are involved in neurological and psychiatric disorders. Studies of neural circuitry have shed light on the subtleties of the structural and functional derangements of the NAcc across various diseases. In this systematic review, the authors sought to identify human studies involving the NAcc and provide a synthesis of the literature on the known circuity of the NAcc in healthy and diseased states, as well as the clinical outcomes following neuromodulation.
METHODS
A systematic review was conducted using the PubMed, Embase, and Scopus databases. Neuroimaging studies that reported on neural circuitry related to the human NAcc with sample sizes greater than 5 patients were included. Demographic data, aim, design and duration, participants, and clinical and neurocircuitry details and outcomes of the studies were extracted.
RESULTS
Of 3591 resultant articles, 123 were included. The NAcc and its corticolimbic connections to other brain regions, such as the prefrontal cortex, are largely involved in reward and pain processes, with distinct functional circuitry between the shell and core in healthy patients. There is heterogeneity between clinical studies with regard to the NAcc indirect targeting coordinates, methods for postoperative confirmation, and blinded trial design. Neuromodulation studies provided promising clinical results in the context of addiction and substance misuse, obsessive-compulsive disorder, and mood disorders. The most common complications were impaired memory or concentration, and a notable serious complication was hypomania.
CONCLUSIONS
The functional diversity of the NAcc highlights the importance of studying the NAcc in healthy and pathological states. The results of this review suggest that NAcc neuromodulation has been attempted in the management of diverse psychiatric indications. There is promising, emerging evidence that the NAcc may be an effective target for specific reward- or pain-based pathologies with a reasonable risk profile.
Topics: Humans; Nucleus Accumbens; Brain; Prefrontal Cortex; Reward; Pain; Magnetic Resonance Imaging
PubMed: 35901682
DOI: 10.3171/2022.5.JNS212548 -
Journal of Psychiatric Research Aug 2023Suicide behavior (SB) emerge from complex interactions among traumatic events and multiple genetic factors. We conducted the first systematic review to assess the... (Review)
Review
Suicide behavior (SB) emerge from complex interactions among traumatic events and multiple genetic factors. We conducted the first systematic review to assess the evidence of a link among trauma exposure, HPA-axis genes, and SB. A systematic search of PubMed, EBSCO, Science Direct, PsychInfo, and Scopus databases on gene-environment interaction, and susceptibility to SB was carried out until February 2022. Our study was prospectively registered in PROSPERO (CRD42022316141). A total of 13 epidemiological studies (11,756 subjects) were included: eight studies focused on traumatic experiences in the childhood and five studies on lifetime trauma exposure. All studies reported a positive association between the trauma exposure with SB. Gene-environment interaction was reported for CRHR1 (n = 6), CRHR2 (n = 2), FKBP5 (n = 2), and CRHBP (n = 1), however, for CRH, NR3C1, MC2R, and POMC genes no found gene-environment effects on SB. Trauma exposure could be one mechanism that links HPA-axis genes activity with the development of SB.
Topics: Humans; Child; Gene-Environment Interaction; Suicidal Ideation; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System
PubMed: 37352812
DOI: 10.1016/j.jpsychires.2023.06.011 -
Neuroscience and Biobehavioral Reviews Sep 2016The cortisol awakening response (CAR), defined as the increase in cortisol release in response to waking up, shows associations with social and environmental risk... (Meta-Analysis)
Meta-Analysis Review
The cortisol awakening response (CAR), defined as the increase in cortisol release in response to waking up, shows associations with social and environmental risk factors of schizophrenia and has been studied as a potential biomarker in schizophrenia. We report a systematic review and meta-analysis of 11 studies and 879 participants focusing on the CAR of patients with schizophrenia, first-episode psychosis, and at-risk mental states. Random-effects meta-analysis showed that CAR is attenuated in patients with psychosis compared to healthy controls (g=-0.426, 95% CI -0.585 to -0.267, p<0.001, 11 between-group comparisons, n=879). Subgroup analysis showed flattened CAR in patients with schizophrenia (g=-0.556, 95% CI -1.069 to -0.044, p<0.05, 2 between-group comparisons, n=114) and first-episode psychosis (g=-0.544, 95% CI -0.731 to -0.358, p<0.001, 6 between-group comparisons, n=505), but not in individuals with at-risk mental states. These distinctive alterations of hypothalamic-pituitary-adrenal axis function may have important implications for CAR as a marker for transition risk. However, the lack of objective verification of sampling adherence in these studies may limit the interpretation of the results.
Topics: Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Psychotic Disorders; Saliva
PubMed: 27229759
DOI: 10.1016/j.neubiorev.2016.05.027 -
Journal of the International... Feb 2023Despite the importance of social cognitive functions to mental health and social adjustment, examination of these functions is absent in routine assessment of epilepsy... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Despite the importance of social cognitive functions to mental health and social adjustment, examination of these functions is absent in routine assessment of epilepsy patients. Thus, this review aims to provide a comprehensive overview of the literature on four major aspects of social cognition among temporal and frontal lobe epilepsy, which is a critical step toward designing new interventions.
METHOD
Papers from 1990 to 2021 were reviewed and examined for inclusion in this study. After the deduplication process, a systematic review and meta-analysis of 44 and 40 articles, respectively, involving 113 people with frontal lobe epilepsy and 1482 people with temporal lobe epilepsy were conducted.
RESULTS
Our results indicated that while patients with frontal or temporal lobe epilepsy have difficulties in all aspects of social cognition relative to nonclinical controls, the effect sizes were larger for theory of mind ( = .95), than for emotion recognition ( = .69) among temporal lobe epilepsy group. The frontal lobe epilepsy group exhibited significantly greater impairment in emotion recognition compared to temporal lobe. Additionally, people with right temporal lobe epilepsy ( = 1.10) performed more poorly than those with a left-sided ( = .90) seizure focus, specifically in the theory of mind domain.
CONCLUSIONS
These data point to a potentially important difference in the severity of deficits within the emotion recognition and theory of mind abilities depending on the laterlization of seizure side. We also suggest a guide for the assessment of impairments in social cognition that can be integrated into multidisciplinary clinical evaluation for people with epilepsy.
Topics: Humans; Epilepsy, Temporal Lobe; Epilepsy, Frontal Lobe; Social Cognition; Neuropsychological Tests; Cognition; Seizures; Frontal Lobe
PubMed: 35249578
DOI: 10.1017/S1355617722000066