Magnetic resonance spectroscopy of limbic structures displays metabolite differences in young unaffected relatives of schizophrenia probands

Abstract

Imaging studies of schizophrenia patients showed fronto-temporal brain volume deficits, while magnetic resonance spectroscopy (MRS) studies of patients and unaffected biological relatives have found a decrement of the neuronal marker N-acetyl-aspartate (NAA) in the hippocampus and frontal lobes, and increased choline-containing phospholipids. Using a 3 T MR scanner, we determined the metabolite profile within limbic regions (anterior cingulate cortex (ACC) and left hippocampus) of 36 unaffected, adolescent/young adult relatives of schizophrenia probands (first-degree=16, second-degree=20) and 25 healthy controls with no family history of schizophrenia. Significant main effects of group were found on NAA/Cho ratios for both the left hippocampus (F=6.11, p≤0.02) and ACC (F=4.89, p≤0.03) as well as for the left hippocampus Cho/Cr ratio (F=5.55, p≤0.02). Compared to age and sex matched healthy controls without a family history of schizophrenia, first-degree relatives of probands had greater MRS metabolite deviations than second-degree relatives. Greater familial proximity to the schizophrenia proband (or higher schizophrenia susceptibility) among biological relatives was associated with stepwise lowering of NAA/Cho and elevations in Cho/Cr ratios. The observed limbic metabolite changes among young, nonpsychotic biological relatives are likely related to shared genetic vulnerability factors, and may assist in the early identification of schizophrenia for primary and secondary prevention.

Transitive inference deficits in unaffected biological relatives of schizophrenia patients

“…In general, second-degree biological relatives performed better than their first-degree counterparts, and were more similar to HC in relational memory performance. These observations are consistent with a previous finding by our group (Capizzano et al, 2011); where we found that first-degree relatives of schizophrenia patients had more severe abnormal magnetic resonance spectroscopy (MRS) metabolite levels in limbic brain regions than second-degree relatives. Thus, our current study provides additional evidence that deviations in endophenotypic features of schizophrenia among unaffected biological relatives increase with greater familial proximity to the schizophrenia proband.…”

“…Prior studies have reported similar, but less severe neurocognitive, neuroanatomical, electrophysiological and behavioral abnormalities in non-psychotic biological relatives of schizophrenia patients (Boos, Aleman, Cahn, Pol, & Kahn, 2007; Capizzano, Toscano, & Ho, 2011; Ho, 2007; Ho & Magnotta, 2010; Keshavan et al, 2002; Lawrie et al, 1999; McDonald et al, 2004; Steel et al, 2002). Such intermediate phenotypes are likely related to genetic vulnerability factors that biological relatives have in common with schizophrenia patients.…”

Neurochemical effects of oxytocin in people at clinical high risk for psychosis

“…Metabolite alterations have also been observed in other brain regions in CHR-P and other (i.e. familial) high-risk groups, such as reduced N-acetylaspartate in the thalamus Tandon et al, 2013;Yoo et al, 2009), ACC (Capizzano et al, 2011;Jessen et al, 2006), and caudate (Keshavan et al, 2009)-although increases are also observed in the caudate (de la Fuente-Sandoval et al, 2011). Increased Glx has been reported in the thalamus and caudate, as well as increased (de la or decreased (Menschikov et al, 2016) medial prefrontal GABA-although differences are not always found (Modinos et al, 2018b;Wang et al, 2016).…”

A review of neuroimaging studies of young relatives of individuals with schizophrenia: A developmental perspective from schizotaxia to schizophrenia

“…In a later report, HR subjects showed NAA, PCr + Cr, and GPC + PC reductions in the caudate, and NAA increases in PFC white matter [Keshavan et al, ]. In the Iowa HRS, HR had reduced NAA/Cho ratios for both the left hippocampus and ACC and increased left hippocampus Cho/Cr ratio compared to controls [Capizzano et al, ]. Greater familial proximity to SZ probands among HR was associated with stepwise lowering of NAA/Cho and elevations in Cho/Cr ratios.…”