Pub Date : 2024-08-05DOI: 10.1038/s41537-024-00486-w
Carlos A Larrauri
{"title":"Messiah or pariah? Psychosis, science, and finding meaning in lived experience.","authors":"Carlos A Larrauri","doi":"10.1038/s41537-024-00486-w","DOIUrl":"10.1038/s41537-024-00486-w","url":null,"abstract":"","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1038/s41537-024-00475-z
Reetta-Liina Armio, Heikki Laurikainen, Tuula Ilonen, Maija Walta, Elina Sormunen, Arvi Tolvanen, Raimo K R Salokangas, Nikolaos Koutsouleris, Lauri Tuominen, Jarmo Hietala
Altered hippocampal morphology and metabolic pathology, but also hippocampal circuit dysfunction, are established phenomena seen in psychotic disorders. Thus, we tested whether hippocampal subfield volume deficits link with deviations in glucose metabolism commonly seen in early psychosis, and whether the glucose parameters or subfield volumes change during follow-up period using one-year longitudinal study design of 78 first-episode psychosis patients (FEP), 48 clinical high-risk patients (CHR) and 83 controls (CTR). We also tested whether hippocampal morphology and glucose metabolism relate to clinical outcome. Hippocampus subfields were segmented with Freesurfer from 3T MRI images and parameters of glucose metabolism were determined in fasting plasma samples. Hippocampal subfield volumes were consistently lower in FEPs, and findings were more robust in non-affective psychoses, with strongest decreases in CA1, molecular layer and hippocampal tail, and in hippocampal tail of CHRs, compared to CTRs. These morphometric differences remained stable at one-year follow-up. Both non-diabetic CHRs and FEPs had worse glucose parameters compared to CTRs at baseline. We found that, insulin levels and insulin resistance increased during the follow-up period only in CHR, effect being largest in the CHRs converting to psychosis, independent of exposure to antipsychotics. The worsening of insulin resistance was associated with deterioration of function and symptoms in CHR. The smaller volume of hippocampal tail was associated with higher plasma insulin and insulin resistance in FEPs, at the one-year follow-up. Our longitudinal study supports the view that temporospatial hippocampal subfield volume deficits are stable near the onset of first psychosis, being more robust in non-affective psychoses, but less prominent in the CHR group. Specific subfield defects were related to worsening glucose metabolism during the progression of psychosis, suggesting that hippocampus is part of the circuits regulating aberrant glucose metabolism in early psychosis. Worsening of glucose metabolism in CHR group was associated with worse clinical outcome measures indicating a need for heightened clinical attention to metabolic problems already in CHR.
{"title":"Longitudinal study on hippocampal subfields and glucose metabolism in early psychosis.","authors":"Reetta-Liina Armio, Heikki Laurikainen, Tuula Ilonen, Maija Walta, Elina Sormunen, Arvi Tolvanen, Raimo K R Salokangas, Nikolaos Koutsouleris, Lauri Tuominen, Jarmo Hietala","doi":"10.1038/s41537-024-00475-z","DOIUrl":"10.1038/s41537-024-00475-z","url":null,"abstract":"<p><p>Altered hippocampal morphology and metabolic pathology, but also hippocampal circuit dysfunction, are established phenomena seen in psychotic disorders. Thus, we tested whether hippocampal subfield volume deficits link with deviations in glucose metabolism commonly seen in early psychosis, and whether the glucose parameters or subfield volumes change during follow-up period using one-year longitudinal study design of 78 first-episode psychosis patients (FEP), 48 clinical high-risk patients (CHR) and 83 controls (CTR). We also tested whether hippocampal morphology and glucose metabolism relate to clinical outcome. Hippocampus subfields were segmented with Freesurfer from 3T MRI images and parameters of glucose metabolism were determined in fasting plasma samples. Hippocampal subfield volumes were consistently lower in FEPs, and findings were more robust in non-affective psychoses, with strongest decreases in CA1, molecular layer and hippocampal tail, and in hippocampal tail of CHRs, compared to CTRs. These morphometric differences remained stable at one-year follow-up. Both non-diabetic CHRs and FEPs had worse glucose parameters compared to CTRs at baseline. We found that, insulin levels and insulin resistance increased during the follow-up period only in CHR, effect being largest in the CHRs converting to psychosis, independent of exposure to antipsychotics. The worsening of insulin resistance was associated with deterioration of function and symptoms in CHR. The smaller volume of hippocampal tail was associated with higher plasma insulin and insulin resistance in FEPs, at the one-year follow-up. Our longitudinal study supports the view that temporospatial hippocampal subfield volume deficits are stable near the onset of first psychosis, being more robust in non-affective psychoses, but less prominent in the CHR group. Specific subfield defects were related to worsening glucose metabolism during the progression of psychosis, suggesting that hippocampus is part of the circuits regulating aberrant glucose metabolism in early psychosis. Worsening of glucose metabolism in CHR group was associated with worse clinical outcome measures indicating a need for heightened clinical attention to metabolic problems already in CHR.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-23DOI: 10.1038/s41537-024-00485-x
Dabing Li, Qiangwen Pan, Yewei Xiao, Kehui Hu
Schizophrenia (SZ) is a chronic, severe mental disorder with heterogeneous clinical manifestations and unknown etiology. Research on SZ has long been limited by the low reliability of and ambiguous pathogenesis in schizophrenia animal models. Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, rapidly induces both positive and negative symptoms of SZ as well as stable SZ-related cognitive impairment in rodents. However, the neural mechanism underlying PCP-induced SZ-like symptoms is not fully understood. Nondopaminergic pathophysiology, particularly excessive glutamate release induced by NMDAR hypofunction in the prefrontal cortex (PFC), may play a key role in the development of PCP-induced SZ-like symptoms. In this review, we summarize studies on the behavioral and metabolic effects of PCP and the cellular and circuitary targets of PCP in the PFC and hippocampus (HIP). PCP is thought to target the ventral HIP-PFC pathway more strongly than the PFC-VTA pathway and thalamocortical pathway. Systemic PCP administration might preferentially inhibit gamma-aminobutyric acid (GABA) neurons in the vHIP and in turn lead to hippocampal pyramidal cell disinhibition. Excitatory inputs from the HIP may trigger sustained, excessive and pathological PFC pyramidal neuron activation to mediate various SZ-like symptoms. In addition, astrocyte and microglial activation and oxidative stress in the cerebral cortex or hippocampus have been observed in PCP-induced models of SZ. These findings perfect the hypoglutamatergic hypothesis of schizophrenia. However, whether these effects direct the consequences of PCP administration and how about the relationships between these changes induced by PCP remain further elucidation through rigorous, causal and direct experimental evidence.
{"title":"Advances in the study of phencyclidine-induced schizophrenia-like animal models and the underlying neural mechanisms.","authors":"Dabing Li, Qiangwen Pan, Yewei Xiao, Kehui Hu","doi":"10.1038/s41537-024-00485-x","DOIUrl":"10.1038/s41537-024-00485-x","url":null,"abstract":"<p><p>Schizophrenia (SZ) is a chronic, severe mental disorder with heterogeneous clinical manifestations and unknown etiology. Research on SZ has long been limited by the low reliability of and ambiguous pathogenesis in schizophrenia animal models. Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, rapidly induces both positive and negative symptoms of SZ as well as stable SZ-related cognitive impairment in rodents. However, the neural mechanism underlying PCP-induced SZ-like symptoms is not fully understood. Nondopaminergic pathophysiology, particularly excessive glutamate release induced by NMDAR hypofunction in the prefrontal cortex (PFC), may play a key role in the development of PCP-induced SZ-like symptoms. In this review, we summarize studies on the behavioral and metabolic effects of PCP and the cellular and circuitary targets of PCP in the PFC and hippocampus (HIP). PCP is thought to target the ventral HIP-PFC pathway more strongly than the PFC-VTA pathway and thalamocortical pathway. Systemic PCP administration might preferentially inhibit gamma-aminobutyric acid (GABA) neurons in the vHIP and in turn lead to hippocampal pyramidal cell disinhibition. Excitatory inputs from the HIP may trigger sustained, excessive and pathological PFC pyramidal neuron activation to mediate various SZ-like symptoms. In addition, astrocyte and microglial activation and oxidative stress in the cerebral cortex or hippocampus have been observed in PCP-induced models of SZ. These findings perfect the hypoglutamatergic hypothesis of schizophrenia. However, whether these effects direct the consequences of PCP administration and how about the relationships between these changes induced by PCP remain further elucidation through rigorous, causal and direct experimental evidence.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The etiological and therapeutic complexities of schizophrenia (SCZ) persist, prompting exploration of anti-inflammatory therapy as a potential treatment approach. Methyl salicylate glycosides (MSGs), possessing a structural parent nucleus akin to aspirin, are being investigated for their therapeutic potential in schizophrenia. Utilizing bioinformation mining, network pharmacology, molecular docking and dynamics simulation, the potential value and mechanism of MSGs (including MSTG-A, MSTG-B, and Gaultherin) in the treatment of SCZ, as well as the underlying pathogenesis of the disorder, were examined. 581 differentially expressed genes related to SCZ were identified in patients and healthy individuals, with 349 up-regulated genes and 232 down-regulated genes. 29 core targets were characterized by protein-protein interaction (PPI) network, with the top 10 core targets being BDNF, VEGFA, PVALB, KCNA1, GRIN2A, ATP2B2, KCNA2, APOE, PPARGC1A and SCN1A. The pathogenesis of SCZ primarily involves cAMP signaling, neurodegenerative diseases and other pathways, as well as regulation of ion transmembrane transport. Molecular docking analysis revealed that the three candidates exhibited binding activity with certain targets with binding affinities ranging from -4.7 to -109.2 kcal/mol. MSTG-A, MSTG-B and Gaultherin show promise for use in the treatment of SCZ, potentially through their ability to modulate the expression of multiple genes involved in synaptic structure and function, ion transport, energy metabolism. Molecular dynamics simulation revealed good binding abilities between MSTG-A, MSTG-B, Gaultherin and ATP2B2. It suggests new avenues for further investigation in this area.
{"title":"Exploration on the potential efficacy and mechanism of methyl salicylate glycosides in the treatment of schizophrenia based on bioinformatics, molecular docking and dynamics simulation.","authors":"Xiuhuan Wang, Jiamu Ma, Ying Dong, Xueyang Ren, Ruoming Li, Guigang Yang, Gaimei She, Yunlong Tan, Song Chen","doi":"10.1038/s41537-024-00484-y","DOIUrl":"10.1038/s41537-024-00484-y","url":null,"abstract":"<p><p>The etiological and therapeutic complexities of schizophrenia (SCZ) persist, prompting exploration of anti-inflammatory therapy as a potential treatment approach. Methyl salicylate glycosides (MSGs), possessing a structural parent nucleus akin to aspirin, are being investigated for their therapeutic potential in schizophrenia. Utilizing bioinformation mining, network pharmacology, molecular docking and dynamics simulation, the potential value and mechanism of MSGs (including MSTG-A, MSTG-B, and Gaultherin) in the treatment of SCZ, as well as the underlying pathogenesis of the disorder, were examined. 581 differentially expressed genes related to SCZ were identified in patients and healthy individuals, with 349 up-regulated genes and 232 down-regulated genes. 29 core targets were characterized by protein-protein interaction (PPI) network, with the top 10 core targets being BDNF, VEGFA, PVALB, KCNA1, GRIN2A, ATP2B2, KCNA2, APOE, PPARGC1A and SCN1A. The pathogenesis of SCZ primarily involves cAMP signaling, neurodegenerative diseases and other pathways, as well as regulation of ion transmembrane transport. Molecular docking analysis revealed that the three candidates exhibited binding activity with certain targets with binding affinities ranging from -4.7 to -109.2 kcal/mol. MSTG-A, MSTG-B and Gaultherin show promise for use in the treatment of SCZ, potentially through their ability to modulate the expression of multiple genes involved in synaptic structure and function, ion transport, energy metabolism. Molecular dynamics simulation revealed good binding abilities between MSTG-A, MSTG-B, Gaultherin and ATP2B2. It suggests new avenues for further investigation in this area.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patients with schizophrenia exhibit abnormalities in spatial frequency sensitivity, and it is believed that these abnormalities indicate more widespread dysfunction and dysregulation of bottom-up processing. The early visual system, including the first-order Lateral Geniculate Nucleus of the thalamus (LGN) and the primary visual cortex (V1), are key contributors to spatial frequency sensitivity. Medicated and unmedicated patients with schizophrenia exhibit contrasting changes in spatial frequency sensitivity, thus making it a useful probe for examining potential effects of the disorder and antipsychotic medications in neural processing. We constructed a parameterized, rate-based neural model of on-center/off-surround neurons in the early visual system to investigate the impacts of changes to the excitatory and inhibitory receptive field subfields. By incorporating changes in both the excitatory and inhibitory subfields that are associated with pathophysiological findings in schizophrenia, the model successfully replicated perceptual data from behavioral/functional studies involving medicated and unmedicated patients. Among several plausible mechanisms, our results highlight the dampening of excitation and/or increase in the spread and strength of the inhibitory subfield in medicated patients and the contrasting decreased spread and strength of inhibition in unmedicated patients. Given that the model was successful at replicating results from perceptual data under a variety of conditions, these elements of the receptive field may be useful markers for the imbalances seen in patients with schizophrenia.
{"title":"A neural modeling approach to study mechanisms underlying the heterogeneity of visual spatial frequency sensitivity in schizophrenia.","authors":"Caroline Dugan, Basilis Zikopoulos, Arash Yazdanbakhsh","doi":"10.1038/s41537-024-00480-2","DOIUrl":"10.1038/s41537-024-00480-2","url":null,"abstract":"<p><p>Patients with schizophrenia exhibit abnormalities in spatial frequency sensitivity, and it is believed that these abnormalities indicate more widespread dysfunction and dysregulation of bottom-up processing. The early visual system, including the first-order Lateral Geniculate Nucleus of the thalamus (LGN) and the primary visual cortex (V1), are key contributors to spatial frequency sensitivity. Medicated and unmedicated patients with schizophrenia exhibit contrasting changes in spatial frequency sensitivity, thus making it a useful probe for examining potential effects of the disorder and antipsychotic medications in neural processing. We constructed a parameterized, rate-based neural model of on-center/off-surround neurons in the early visual system to investigate the impacts of changes to the excitatory and inhibitory receptive field subfields. By incorporating changes in both the excitatory and inhibitory subfields that are associated with pathophysiological findings in schizophrenia, the model successfully replicated perceptual data from behavioral/functional studies involving medicated and unmedicated patients. Among several plausible mechanisms, our results highlight the dampening of excitation and/or increase in the spread and strength of the inhibitory subfield in medicated patients and the contrasting decreased spread and strength of inhibition in unmedicated patients. Given that the model was successful at replicating results from perceptual data under a variety of conditions, these elements of the receptive field may be useful markers for the imbalances seen in patients with schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.1038/s41537-024-00483-z
Alex Hatzimanolis, Stefania Foteli, Lida-Alkisti Xenaki, Mirjana Selakovic, Stefanos Dimitrakopoulos, Ilias Vlachos, Ioannis Kosteletos, Rigas-Filippos Soldatos, Maria Gazouli, Stylianos Chatzipanagiotou, Nikos Stefanis
The tryptophan-metabolizing kynurenine pathway (KP) can be activated by enhanced inflammatory responses and has been implicated in the pathophysiology of schizophrenia. However, there is little evidence for KP dysregulation in the early course of psychotic illness. We aimed to investigate the potential immune-mediated hyperactivity of KP in individuals with first-episode psychosis (FEP) and the relationship with symptom severity and treatment response outcomes. Serum immunoassays were performed to measure peripheral levels of inflammatory cytokines (IL-1β, IL-10, TNF-a), KP rate-limiting enzymes (IDO/TDO), and kynurenic acid (KYNA) metabolite in 104 antipsychotic-naïve patients with FEP and 80 healthy controls (HC). The Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning Scale (GAF) were administered to assess psychopathology and functioning status at admission and following 4-week treatment with antipsychotics. Cytokine and KP components levels were substantially increased in FEP patients compared to HC, before and after antipsychotic treatment. A significant positive correlation between pro-inflammatory IL-1β and KYNA levels was observed among FEP patients, but not in HC. Importantly, within-patient analysis revealed that those with higher baseline KYNA experienced more severe negative symptoms and poorer clinical improvement at follow-up. These findings suggest that KP is upregulated in early psychosis, likely through the induction of IL-1β-dependent pathways, and raised peripheral KYNA might represent a promising indicator of non-response to antipsychotic medication in patients with FEP.
{"title":"Elevated serum kynurenic acid in individuals with first-episode psychosis and insufficient response to antipsychotics.","authors":"Alex Hatzimanolis, Stefania Foteli, Lida-Alkisti Xenaki, Mirjana Selakovic, Stefanos Dimitrakopoulos, Ilias Vlachos, Ioannis Kosteletos, Rigas-Filippos Soldatos, Maria Gazouli, Stylianos Chatzipanagiotou, Nikos Stefanis","doi":"10.1038/s41537-024-00483-z","DOIUrl":"10.1038/s41537-024-00483-z","url":null,"abstract":"<p><p>The tryptophan-metabolizing kynurenine pathway (KP) can be activated by enhanced inflammatory responses and has been implicated in the pathophysiology of schizophrenia. However, there is little evidence for KP dysregulation in the early course of psychotic illness. We aimed to investigate the potential immune-mediated hyperactivity of KP in individuals with first-episode psychosis (FEP) and the relationship with symptom severity and treatment response outcomes. Serum immunoassays were performed to measure peripheral levels of inflammatory cytokines (IL-1β, IL-10, TNF-a), KP rate-limiting enzymes (IDO/TDO), and kynurenic acid (KYNA) metabolite in 104 antipsychotic-naïve patients with FEP and 80 healthy controls (HC). The Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning Scale (GAF) were administered to assess psychopathology and functioning status at admission and following 4-week treatment with antipsychotics. Cytokine and KP components levels were substantially increased in FEP patients compared to HC, before and after antipsychotic treatment. A significant positive correlation between pro-inflammatory IL-1β and KYNA levels was observed among FEP patients, but not in HC. Importantly, within-patient analysis revealed that those with higher baseline KYNA experienced more severe negative symptoms and poorer clinical improvement at follow-up. These findings suggest that KP is upregulated in early psychosis, likely through the induction of IL-1β-dependent pathways, and raised peripheral KYNA might represent a promising indicator of non-response to antipsychotic medication in patients with FEP.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1038/s41537-024-00478-w
Julia Gallucci, Maria T Secara, Oliver Chen, Lindsay D Oliver, Brett D M Jones, Tulip Marawi, George Foussias, Aristotle N Voineskos, Colin Hawco
Depressive symptoms in Schizophrenia Spectrum Disorders (SSDs) negatively impact suicidality, prognosis, and quality of life. Despite this, efficacious treatments are limited, largely because the neural mechanisms underlying depressive symptoms in SSDs remain poorly understood. We conducted a systematic review to provide an overview of studies that investigated the neural correlates of depressive symptoms in SSDs using neuroimaging techniques. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases from inception through June 19, 2023. Specifically, we focused on structural and functional magnetic resonance imaging (MRI), encompassing: (1) T1-weighted imaging measuring brain morphology; (2) diffusion-weighted imaging assessing white matter integrity; or (3) T2*-weighted imaging measures of brain function. Our search yielded 33 articles; 14 structural MRI studies, 18 functional (f)MRI studies, and 1 multimodal fMRI/MRI study. Reviewed studies indicate potential commonalities in the neurobiology of depressive symptoms between SSDs and major depressive disorders, particularly in subcortical and frontal brain regions, though confidence in this interpretation is limited. The review underscores a notable knowledge gap in our understanding of the neurobiology of depression in SSDs, marked by inconsistent approaches and few studies examining imaging metrics of depressive symptoms. Inconsistencies across studies' findings emphasize the necessity for more direct and comprehensive research focusing on the neurobiology of depression in SSDs. Future studies should go beyond "total score" depression metrics and adopt more nuanced assessment approaches considering distinct subdomains. This could reveal unique neurobiological profiles and inform investigations of targeted treatments for depression in SSDs.
{"title":"A systematic review of structural and functional magnetic resonance imaging studies on the neurobiology of depressive symptoms in schizophrenia spectrum disorders.","authors":"Julia Gallucci, Maria T Secara, Oliver Chen, Lindsay D Oliver, Brett D M Jones, Tulip Marawi, George Foussias, Aristotle N Voineskos, Colin Hawco","doi":"10.1038/s41537-024-00478-w","DOIUrl":"10.1038/s41537-024-00478-w","url":null,"abstract":"<p><p>Depressive symptoms in Schizophrenia Spectrum Disorders (SSDs) negatively impact suicidality, prognosis, and quality of life. Despite this, efficacious treatments are limited, largely because the neural mechanisms underlying depressive symptoms in SSDs remain poorly understood. We conducted a systematic review to provide an overview of studies that investigated the neural correlates of depressive symptoms in SSDs using neuroimaging techniques. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases from inception through June 19, 2023. Specifically, we focused on structural and functional magnetic resonance imaging (MRI), encompassing: (1) T1-weighted imaging measuring brain morphology; (2) diffusion-weighted imaging assessing white matter integrity; or (3) T2*-weighted imaging measures of brain function. Our search yielded 33 articles; 14 structural MRI studies, 18 functional (f)MRI studies, and 1 multimodal fMRI/MRI study. Reviewed studies indicate potential commonalities in the neurobiology of depressive symptoms between SSDs and major depressive disorders, particularly in subcortical and frontal brain regions, though confidence in this interpretation is limited. The review underscores a notable knowledge gap in our understanding of the neurobiology of depression in SSDs, marked by inconsistent approaches and few studies examining imaging metrics of depressive symptoms. Inconsistencies across studies' findings emphasize the necessity for more direct and comprehensive research focusing on the neurobiology of depression in SSDs. Future studies should go beyond \"total score\" depression metrics and adopt more nuanced assessment approaches considering distinct subdomains. This could reveal unique neurobiological profiles and inform investigations of targeted treatments for depression in SSDs.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1038/s41537-024-00481-1
Laurin Plank, Armin Zlomuzica
The extraction of linguistic markers from social media posts, which are indicative of the onset and course of mental disorders, offers great potential for mental healthcare. In the present study, we extracted over one million posts from the popular social media platform Reddit to analyze speech coherence, which reflects formal thought disorder and is a characteristic feature of schizophrenia and associated psychotic disorders. Natural language processing (NLP) models were used to perform an automated quantification of speech coherence. We could demonstrate that users who are active on forums geared towards disorders with a higher degree of psychotic symptoms tend to show a lower level of coherence. The lowest coherence scores were found in users of forums on dissociative identity disorder, schizophrenia, and bipolar disorder. In contrast, a relatively high level of coherence was detected in users of forums related to obsessive-compulsive disorder, anxiety, and depression. Users of forums on posttraumatic stress disorder, autism, and attention-deficit hyperactivity disorder exhibited medium-level coherence. Our findings provide promising first evidence for the possible utility of NLP-based coherence analyses for the early detection and prevention of psychosis on the basis of posts gathered from publicly available social media data. This opens new avenues for large-scale prevention programs aimed at high-risk populations.
{"title":"Reduced speech coherence in psychosis-related social media forum posts.","authors":"Laurin Plank, Armin Zlomuzica","doi":"10.1038/s41537-024-00481-1","DOIUrl":"10.1038/s41537-024-00481-1","url":null,"abstract":"<p><p>The extraction of linguistic markers from social media posts, which are indicative of the onset and course of mental disorders, offers great potential for mental healthcare. In the present study, we extracted over one million posts from the popular social media platform Reddit to analyze speech coherence, which reflects formal thought disorder and is a characteristic feature of schizophrenia and associated psychotic disorders. Natural language processing (NLP) models were used to perform an automated quantification of speech coherence. We could demonstrate that users who are active on forums geared towards disorders with a higher degree of psychotic symptoms tend to show a lower level of coherence. The lowest coherence scores were found in users of forums on dissociative identity disorder, schizophrenia, and bipolar disorder. In contrast, a relatively high level of coherence was detected in users of forums related to obsessive-compulsive disorder, anxiety, and depression. Users of forums on posttraumatic stress disorder, autism, and attention-deficit hyperactivity disorder exhibited medium-level coherence. Our findings provide promising first evidence for the possible utility of NLP-based coherence analyses for the early detection and prevention of psychosis on the basis of posts gathered from publicly available social media data. This opens new avenues for large-scale prevention programs aimed at high-risk populations.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-24DOI: 10.1038/s41537-024-00479-9
Sunny X Tang, Katrin Hänsel, Lindsay D Oliver, Erin W Dickie, Colin Hawco, Majnu John, Aristotle Voineskos, James M Gold, Robert W Buchanan, Anil K Malhotra
Functional impairments contribute to poor quality of life in schizophrenia spectrum disorders (SSD). We sought to (Objective I) define the main functional phenotypes in SSD, then (Objective II) identify key biopsychosocial correlates, emphasizing interpretable data-driven methods. Objective I was tested on independent samples: Dataset I (N = 282) and Dataset II (N = 317), with SSD participants who underwent assessment of multiple functioning areas. Participants were clustered based on functioning. Objective II was evaluated in Dataset I by identifying key features for classifying functional phenotype clusters from among 65 sociodemographic, psychological, clinical, cognitive, and brain volume measures. Findings were replicated across latent discriminant analyses (LDA) and one-vs.-rest binomial regularized regressions to identify key predictors. We identified three clusters of participants in each dataset, demonstrating replicable functional phenotypes: Cluster 1-poor functioning across domains; Cluster 2-impaired Role Functioning, but partially preserved Independent and Social Functioning; Cluster 3-good functioning across domains. Key correlates were Avolition, anhedonia, left hippocampal volume, and measures of emotional intelligence and subjective social experience. Avolition appeared more closely tied to role functioning, and anhedonia to independent and social functioning. Thus, we found three replicable functional phenotypes with evidence that recovery may not be uniform across domains. Avolition and anhedonia were both critical but played different roles for different functional domains. It may be important to identify critical functional areas for individual patients and target interventions accordingly.
功能障碍导致精神分裂症谱系障碍(SSD)患者生活质量低下。我们试图(目标一)定义精神分裂症谱系障碍的主要功能表型,然后(目标二)确定关键的生物-心理-社会相关因素,强调可解释的数据驱动方法。目标 I 在独立样本上进行了测试:数据集 I(N = 282)和数据集 II(N = 317)中的 SSD 参与者接受了多个功能领域的评估。根据功能对参与者进行分组。目标 II 在数据集 I 中进行了评估,从 65 个社会人口、心理、临床、认知和脑容量测量指标中识别出功能表型集群分类的关键特征。研究结果在潜在判别分析(LDA)和一vs.-rest二项式正则回归中得到了重复,以确定关键的预测因素。我们在每个数据集中发现了三个参与者集群,展示了可复制的功能表型:第 1 组--各领域功能较差;第 2 组--角色功能受损,但独立和社交功能部分保留;第 3 组--各领域功能良好。与之相关的主要因素包括逃避、失乐症、左侧海马体积以及情商和主观社会体验的测量。逃避似乎与角色功能更密切相关,而失乐症则与独立和社会功能更密切相关。因此,我们发现了三种可复制的功能表型,有证据表明不同领域的恢复可能并不一致。逃避和失乐症都很关键,但在不同的功能领域发挥着不同的作用。确定个体患者的关键功能领域并有针对性地进行干预可能非常重要。
{"title":"Functional phenotypes in schizophrenia spectrum disorders: defining the constructs and identifying biopsychosocial correlates using data-driven methods.","authors":"Sunny X Tang, Katrin Hänsel, Lindsay D Oliver, Erin W Dickie, Colin Hawco, Majnu John, Aristotle Voineskos, James M Gold, Robert W Buchanan, Anil K Malhotra","doi":"10.1038/s41537-024-00479-9","DOIUrl":"10.1038/s41537-024-00479-9","url":null,"abstract":"<p><p>Functional impairments contribute to poor quality of life in schizophrenia spectrum disorders (SSD). We sought to (Objective I) define the main functional phenotypes in SSD, then (Objective II) identify key biopsychosocial correlates, emphasizing interpretable data-driven methods. Objective I was tested on independent samples: Dataset I (N = 282) and Dataset II (N = 317), with SSD participants who underwent assessment of multiple functioning areas. Participants were clustered based on functioning. Objective II was evaluated in Dataset I by identifying key features for classifying functional phenotype clusters from among 65 sociodemographic, psychological, clinical, cognitive, and brain volume measures. Findings were replicated across latent discriminant analyses (LDA) and one-vs.-rest binomial regularized regressions to identify key predictors. We identified three clusters of participants in each dataset, demonstrating replicable functional phenotypes: Cluster 1-poor functioning across domains; Cluster 2-impaired Role Functioning, but partially preserved Independent and Social Functioning; Cluster 3-good functioning across domains. Key correlates were Avolition, anhedonia, left hippocampal volume, and measures of emotional intelligence and subjective social experience. Avolition appeared more closely tied to role functioning, and anhedonia to independent and social functioning. Thus, we found three replicable functional phenotypes with evidence that recovery may not be uniform across domains. Avolition and anhedonia were both critical but played different roles for different functional domains. It may be important to identify critical functional areas for individual patients and target interventions accordingly.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-17DOI: 10.1038/s41537-024-00477-x
Sung Woo Joo, Young Tak Jo, Woohyeok Choi, Sun Min Kim, So Young Yoo, Soohyun Joe, Jungsun Lee
A morphometric similarity (MS) network can be constructed using multiple magnetic resonance imaging parameters of each cortical region. An MS network can be used to assess the similarity between cortical regions. Although MS networks can detect microstructural alterations and capture connections between histologically similar cortical areas, the influence of schizophrenia on the topological characteristics of MS networks remains unclear. We obtained T1- and diffusion-weighted images of 239 healthy controls and 190 individuals with schizophrenia to construct the MS network. Group comparisons of the mean MS of the cortical regions and subnetworks were performed. The strengths of the connections between the cortical regions and the global and nodal network indices were compared between the groups. Clinical associations with the network indices were tested using Spearman's rho. Compared with healthy controls, individuals with schizophrenia had significant group differences in the mean MS of several cortical regions and subnetworks. Individuals with schizophrenia had both superior and inferior strengths of connections between cortical regions compared with those of healthy controls. We observed regional abnormalities of the MS network in individuals with schizophrenia regarding lower centrality values of the pars opercularis, superior frontal, and superior temporal areas. Specific nodal network measures of the right pars opercularis and left superior temporal areas were associated with illness duration in individuals with schizophrenia. We identified regional abnormalities of the MS network in schizophrenia with the left superior temporal area possibly being a key region in topological organization and cortical connections.
利用每个皮层区域的多个磁共振成像参数,可以构建一个形态计量相似性(MS)网络。MS 网络可用于评估皮质区域之间的相似性。虽然MS网络可以检测微观结构的改变并捕捉组织学上相似的皮质区域之间的联系,但精神分裂症对MS网络拓扑特征的影响仍不清楚。我们获取了 239 名健康对照组和 190 名精神分裂症患者的 T1 和弥散加权图像来构建 MS 网络。我们对皮质区域和子网的平均 MS 进行了分组比较。比较了各组之间皮质区域之间的连接强度以及整体和节点网络指数。使用Spearman's rho检验了网络指数与临床的关联性。与健康对照组相比,精神分裂症患者在几个皮层区域和子网的平均MS方面存在显著的群体差异。与健康对照组相比,精神分裂症患者大脑皮层区域之间的连接强度有高有低。我们观察到精神分裂症患者的 MS 网络存在区域性异常,其中眼旁、额叶上部和颞叶上部区域的中心性值较低。在精神分裂症患者中,右侧眼旁和左侧颞上区的特定节点网络测量值与病程有关。我们发现精神分裂症患者的多发性硬化症网络存在区域性异常,而左侧颞上区可能是拓扑组织和皮层连接的关键区域。
{"title":"Topological abnormalities of the morphometric similarity network of the cerebral cortex in schizophrenia.","authors":"Sung Woo Joo, Young Tak Jo, Woohyeok Choi, Sun Min Kim, So Young Yoo, Soohyun Joe, Jungsun Lee","doi":"10.1038/s41537-024-00477-x","DOIUrl":"10.1038/s41537-024-00477-x","url":null,"abstract":"<p><p>A morphometric similarity (MS) network can be constructed using multiple magnetic resonance imaging parameters of each cortical region. An MS network can be used to assess the similarity between cortical regions. Although MS networks can detect microstructural alterations and capture connections between histologically similar cortical areas, the influence of schizophrenia on the topological characteristics of MS networks remains unclear. We obtained T1- and diffusion-weighted images of 239 healthy controls and 190 individuals with schizophrenia to construct the MS network. Group comparisons of the mean MS of the cortical regions and subnetworks were performed. The strengths of the connections between the cortical regions and the global and nodal network indices were compared between the groups. Clinical associations with the network indices were tested using Spearman's rho. Compared with healthy controls, individuals with schizophrenia had significant group differences in the mean MS of several cortical regions and subnetworks. Individuals with schizophrenia had both superior and inferior strengths of connections between cortical regions compared with those of healthy controls. We observed regional abnormalities of the MS network in individuals with schizophrenia regarding lower centrality values of the pars opercularis, superior frontal, and superior temporal areas. Specific nodal network measures of the right pars opercularis and left superior temporal areas were associated with illness duration in individuals with schizophrenia. We identified regional abnormalities of the MS network in schizophrenia with the left superior temporal area possibly being a key region in topological organization and cortical connections.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11183129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}