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Changes in patterns of age-related network connectivity are associated with risk for schizophrenia.

ABSTRACT: Alterations in fMRI-based brain functional network connectivity (FNC) are associated with schizophrenia (SCZ) and the genetic risk or subthreshold clinical symptoms preceding the onset of SCZ, which often occurs in early adulthood. Thus, age-sensitive FNC changes may be relevant to SCZ risk-related FNC. We used independent component analysis to estimate FNC from childhood to adulthood in 9,236 individuals. To capture individual brain features more accurately than single-session fMRI, we studied an average of three fMRI scans per individual. To identify potential familial risk-related FNC changes, we compared age-related FNC in first-degree relatives of SCZ patients mostly including unaffected siblings (SIB) with neurotypical controls (NC) at the same age stage. Then, we examined how polygenic risk scores for SCZ influenced risk-related FNC patterns. Finally, we investigated the same risk-related FNC patterns in adult SCZ patients (oSCZ) and young individuals with subclinical psychotic symptoms (PSY). Age-sensitive risk-related FNC patterns emerge during adolescence and early adulthood, but not before. Young SIB always followed older NC patterns, with decreased FNC in a cerebellar-occipitoparietal circuit and increased FNC in two prefrontal-sensorimotor circuits when compared to young NC. Two of these FNC alterations were also found in oSCZ, with one exhibiting reversed pattern. All were linked to polygenic risk for SCZ in unrelated individuals (R² varied from 0.02 to 0.05). Young PSY showed FNC alterations in the same direction as SIB when compared to NC. These results suggest that age-related neurotypical FNC correlates with genetic risk for SCZ and is detectable with MRI in young participants.

SUBMITTER: Passiatore R

PROVIDER: S-EPMC10410767 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Changes in patterns of age-related network connectivity are associated with risk for schizophrenia.

Passiatore Roberta R Antonucci Linda A LA DeRamus Thomas P TP Fazio Leonardo L Stolfa Giuseppe G Sportelli Leonardo L Kikidis Gianluca C GC Blasi Giuseppe G Chen Qiang Q Dukart Juergen J Goldman Aaron L AL Mattay Venkata S VS Popolizio Teresa T Rampino Antonio A Sambataro Fabio F Selvaggi Pierluigi P Ulrich William W Weinberger Daniel R DR Bertolino Alessandro A Calhoun Vince D VD Pergola Giulio G

Proceedings of the National Academy of Sciences of the United States of America 20230801 32

Alterations in fMRI-based brain functional network connectivity (FNC) are associated with schizophrenia (SCZ) and the genetic risk or subthreshold clinical symptoms preceding the onset of SCZ, which often occurs in early adulthood. Thus, age-sensitive FNC changes may be relevant to SCZ risk-related FNC. We used independent component analysis to estimate FNC from childhood to adulthood in 9,236 individuals. To capture individual brain features more accurately than single-session fMRI, we studied ...[more]

PMID: 37527347

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Project description:Aging affects pain experience and brain functioning. However, how aging leads to changes in pain perception and brain functional connectivity has not yet been completely understood. To investigate resting-state and pain perception changes in old and young participants, this study employed region of interest (ROI) to ROI resting-state functional connectivity (rsFC) analysis of imaging data by using regions implicated in sensory and affective dimensions of pain, descending pain modulation, and the default-mode networks (DMNs). Thirty-seven older (66.86 ± 4.04 years; 16 males) and 38 younger healthy participants (20.74 ± 4.15 years; 19 males) underwent 10 min' eyes-closed resting-state scanning. We examined the relationship between rsFC parameters with pressure pain thresholds. Older participants showed higher pain thresholds than younger. Regarding rsFC, older adults displayed increased connectivity of pain-related sensory brain regions in comparison to younger participants: increased rsFC between bilateral primary somatosensory area (SI) and anterior cingulate cortex (ACC), and between SI(L) and secondary somatosensory area (SII)-(R) and dorsolateral prefrontal cortex (PFC). Moreover, decreased connectivity in the older compared to the younger group was found among descending pain modulatory regions: between the amygdala(R) and bilateral insula(R), thalamus(R), ACC, and amygdala(L); between the amygdala(L) and insula(R) and bilateral thalamus; between ACC and bilateral insula, and between periaqueductal gray (PAG) and bilateral thalamus. Regarding the DMN, the posterior parietal cortex and lateral parietal (LP; R) were more strongly connected in the older group than in the younger group. Correlational analyses also showed that SI(L)-SII(R) rsFC was positively associated with pressure pain thresholds in older participants. In conclusion, these findings suggest a compensatory mechanism for the sensory changes that typically accompanies aging. Furthermore, older participants showed reduced functional connectivity between key nodes of the descending pain inhibitory pathway.

Project description:Background: Integrity of functional brain networks is closely associated with maintained cognitive performance at old age. Consistently, both carrier status of Apolipoprotein E ε4 allele (APOE4), and age-related aggregation of Alzheimer's disease (AD) pathology result in altered brain network connectivity. The posterior cingulate and precuneus (PCP) is a node of particular interest due to its role in crucial memory processes. Moreover, the PCP is subject to the early aggregation of AD pathology. The current study aimed at characterizing brain network properties associated with unimpaired cognition in old aged adults. To determine the effects of age-related brain change and genetic risk for AD, pathological proteins β-amyloid and tau were measured by Positron-emission tomography (PET), PCP connectivity as a proxy of cognitive network integrity, and genetic risk by APOE4 carrier status. Methods: Fifty-seven cognitively unimpaired old-aged adults (MMSE = 29.20 ± 1.11; 73 ± 8.32 years) were administered 11C Pittsburgh Compound B and 18F Flutemetamol PET for assessing β-amyloid, and 18F AV-1451 PET for tau. Individual functional connectivity seed maps of the PCP were obtained by resting-state multiband BOLD functional MRI at 3-Tesla for increased temporal resolution. Voxelwise correlations between functional connectivity, β-amyloid- and tau-PET were explored by Biological Parametric Mapping (BPM). Results: Local β-amyloid was associated with increased connectivity in frontal and parietal regions of the brain. Tau was linked to increased connectivity in more spatially distributed clusters in frontal, parietal, occipital, temporal, and cerebellar regions. A positive interaction was observable for APOE4 carrier status and functional connectivity with brain regions characterized by increased local β-amyloid and tau tracer retention. Conclusions: Our data suggest an association between spatially differing connectivity systems and local β-amyloid, and tau aggregates in cognitively normal, old-aged adults, which is moderated by APOE4. Additional longitudinal studies may determine protective connectivity patterns associated with healthy aging trajectories of AD-pathology aggregation.

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Changes in patterns of age-related network connectivity are associated with risk for schizophrenia.

Publications

Changes in patterns of age-related network connectivity are associated with risk for schizophrenia.

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