Scholarlink

<p>Immune dysregulation is implicated in patient subgroups in major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SCZ), but the role of microglia across affective and psychotic illnesses remains unclear. We propose an integrative framework linking systemic immune drivers to microglia-related circuit engagement, cellular phenotype, and kynurenine pathway (KP) branch balance. We systematically reviewed human TSPO-PET, cerebrospinal fluid (CSF) KP metabolite, and postmortem microglial and KP studies. Quantitative synthesis focused on MDD versus SCZ. BD was integrated descriptively due to limited data. MDD showed the most reproducible in vivo signal, with increased TSPO binding in frontolimbic regions (cingulate cortex, hippocampus, prefrontal cortex), and had lower heterogeneity and higher precision than SCZ. Postmortem MDD findings were largely null for diagnosis-level increases in microglial density or classical activation markers, but suggested subtle homeostatic shifts. KP findings were localized and regionally dissociated, including cingulate QUIN-related microglial signals and reduced hippocampal QUIN immunoreactivity in single cohorts. BD evidence was sparse as&#xa0;TSPO-PET comprised a single study reporting hippocampal increases, and&#xa0;postmortem microglial markers were mostly unchanged at the diagnosis level, with suicide or psychosis stratification revealing subgroup effects. Also, BD KP data suggested anterior cingulate upstream activation with a psychosis-linked downstream signal (reduced prefrontal KMO) in a subgroup. In SCZ, TSPO-PET findings were heterogeneous with small decreases or no change, and&#xa0;postmortem studies indicated either activation-marker increases or loss of homeostatic microglial signatures. In addition, the most consistent biochemical signal in SCZ&#xa0;was a shift toward the KYNA branch (increased CSF KYNA and cortical KYNA), consistent with KP-linked glutamatergic dysregulation. Overall, microglia-related alterations appear better explained by biological subgroups and symptom dimensions than&#xa0;by categorical diagnoses, motivating future transdiagnostic studies with&#xa0;dimensional phenotyping, subgroup stratification, longitudinal designs, and microglia-specific biomarkers. Limitations include the&#xa0;limited cellular specificity&#xa0;of TSPO-PET, small sample sizes, and postmortem studies focusing on few cortical/limbic regions rather than whole-brain coverage.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Multimodal microglial and kynurenine pathway alterations across the affective-psychosis spectrum: a systematic review of patterns, heterogeneity, and dimensional implications

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月21日

查看全文
  • Madeleine Nussbaumer,
  • Paul C. Guest,
  • Kolja Schiltz,
  • Leon Dudeck,
  • Leila Shokati Asl,
  • Gabriela Meyer-Lotz,
  • Henrik Dobrowolny,
  • Stefan Leucht,
  • Hans-Gert Bernstein,
  • Thomas Nickl-Jockschat,
  • Brisa S. Fernandes,
  • Johann Steiner

摘要

Immune dysregulation is implicated in patient subgroups in major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SCZ), but the role of microglia across affective and psychotic illnesses remains unclear. We propose an integrative framework linking systemic immune drivers to microglia-related circuit engagement, cellular phenotype, and kynurenine pathway (KP) branch balance. We systematically reviewed human TSPO-PET, cerebrospinal fluid (CSF) KP metabolite, and postmortem microglial and KP studies. Quantitative synthesis focused on MDD versus SCZ. BD was integrated descriptively due to limited data. MDD showed the most reproducible in vivo signal, with increased TSPO binding in frontolimbic regions (cingulate cortex, hippocampus, prefrontal cortex), and had lower heterogeneity and higher precision than SCZ. Postmortem MDD findings were largely null for diagnosis-level increases in microglial density or classical activation markers, but suggested subtle homeostatic shifts. KP findings were localized and regionally dissociated, including cingulate QUIN-related microglial signals and reduced hippocampal QUIN immunoreactivity in single cohorts. BD evidence was sparse as TSPO-PET comprised a single study reporting hippocampal increases, and postmortem microglial markers were mostly unchanged at the diagnosis level, with suicide or psychosis stratification revealing subgroup effects. Also, BD KP data suggested anterior cingulate upstream activation with a psychosis-linked downstream signal (reduced prefrontal KMO) in a subgroup. In SCZ, TSPO-PET findings were heterogeneous with small decreases or no change, and postmortem studies indicated either activation-marker increases or loss of homeostatic microglial signatures. In addition, the most consistent biochemical signal in SCZ was a shift toward the KYNA branch (increased CSF KYNA and cortical KYNA), consistent with KP-linked glutamatergic dysregulation. Overall, microglia-related alterations appear better explained by biological subgroups and symptom dimensions than by categorical diagnoses, motivating future transdiagnostic studies with dimensional phenotyping, subgroup stratification, longitudinal designs, and microglia-specific biomarkers. Limitations include the limited cellular specificity of TSPO-PET, small sample sizes, and postmortem studies focusing on few cortical/limbic regions rather than whole-brain coverage.