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Reduced cortical thickness related to single nucleotide polymorphisms in the major histocompatibility complex region in antipsychotic-naive schizophrenia.

ABSTRACT: INSTRUCTIONS:The aim of this study was to explore the relationships between changes in cortical thickness and single nucleotide polymorphisms (SNPs) in the major histocompatibility complex (MHC) region in a group of antipsychotic-naive schizophrenia (AN-SCZ) patients. Methods Twenty-five AN-SCZ patients and 51 healthy controls (HCs) participated in this study. General linear models were used to identify associations between the average cortical thicknesses of each brain region (N = 68) and each of the 11 SNPs in the MHC region in the AN-SCZ patients and HCs. Next, we performed independent-sample t tests to investigate whether cortical thickness was significantly lower in the AN-SCZ patients than in HCs in the brain regions that were significantly associated with the SNPs. Finally, we examined the correlations between clinical symptoms and cortical thickness in the above brain areas in the whole AN-SCZ group using Pearson correlation tests. Results Seven of the 11 SNPs within the MHC region were significantly associated with cortical thickness only in the AN-SCZ patients; these included rs1635, rs1736913, rs2021722, rs204999, rs2523722, rs3131296, and rs9272105. The AN-SCZ patients had significantly thinner cortical thicknesses in the above brain regions, especially the prefrontal cortex. Furthermore, the left entorhinal region was negatively correlated with Positive and Negative Symptom Scale (PANSS) activation scores in the AN-SCZ group (r = -0.601, p = 0.03). Conclusions This study provides evidence demonstrating the potential effects of MHC risk variants in cortical thickness deficits in AN-SCZ. These data also support the notion that the immune system plays critical roles in the pathology of schizophrenia, which is mediated via the modulation of the development of cerebral cortical structures.

SUBMITTER: Tao B

PROVIDER: S-EPMC6598395 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Reduced cortical thickness related to single nucleotide polymorphisms in the major histocompatibility complex region in antipsychotic-naive schizophrenia.

Tao Bo B Xiao Yuan Y Hu Na N Shah Chandan C Liu Lu L Gao Xin X Liu Jieke J Zhang Wenjing W Yao Li L Xu Heng H Hua Jun J Lui Su S

Brain and behavior 20190328 5

<h4>Instructions</h4>The aim of this study was to explore the relationships between changes in cortical thickness and single nucleotide polymorphisms (SNPs) in the major histocompatibility complex (MHC) region in a group of antipsychotic-naive schizophrenia (AN-SCZ) patients. Methods Twenty-five AN-SCZ patients and 51 healthy controls (HCs) participated in this study. General linear models were used to identify associations between the average cortical thicknesses of each brain region (N = 68) a ...[more]

PMID: 30924326

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Project description:Background: Major Depressive Disorder (MDD) is highly prevalent in patients with mesial temporal lobe epilepsy (MTLE), especially in women, carrying significant morbidity. This study aimed to investigate the cortical thickness (CT) abnormalities associated with MDD in women with MTLE and hippocampal atrophy (HA). Also, we investigated the impact of MDD upon the volumes of the hippocampus and amygdala in these patients. Methods: We included 50 women with MTLE and HA (20 left, LMTLE; 30 right, RMTLE), 41 healthy women in the control group, and 15 women with MDD without epilepsy. MTLE patients were subdivided into three groups: MTLE-without-MDD (23 MTLE patients without MDD), MTLE-mild-MDD (nine MTLE patients with mild symptoms of MDD), and MTLE-severe-MDD (18 MTLE patients with moderate to severe symptoms of MDD). The five groups were balanced for age (p = 0.56). All participants had high-resolution 3D T1-weighted images in a 3T scanner. We used FreeSurfer 6.0 for volumetry and CT parcellation. All participants were submitted to a clinical psychological evaluation through the Structured Clinical Interview for DSM-IV (SCID-IV) and completed the Beck Depression Inventory (BDI-II). Results: We identified a smaller ipsilateral amygdala volume (p = 0.04) in the MTLE-severe-MDD group when compared to the control group. Our results presented a reduced ipsilateral lateral orbitofrontal cortex (p = 0.02) in the MTLE-severe-MDD in comparison to the MTLE-mild-MDD group. We also identified a thinner ipsilateral fusiform gyrus (p < 0.01) in the MTLE-severe-MDD compared to both MTLE-without-MDD and control groups. A reduced CT of the contralateral superior frontal gyrus (p = 0.02) was observed in the MTLE-severe-MDD in comparison to the MTLE-mild-MDD group. Conclusions: The identification of areas with reduced CT and atrophy of the ipsilateral amygdala in women with MTLE and MDD suggest that the cortical thinning in the network of the paralimbic system is related to the co-occurrence and intensity of depressive symptoms in this group.

Project description:Schizophrenia is a severe psychiatric illness with widespread impairments of cognitive functioning; however, a certain percentage of subjects are known to perform in the normal range on neuropsychological measures. While the cognitive profiles of these individuals have been examined, there has been relatively little attention to the neuroanatomical characteristics of this important subgroup. The aims of this study were to statistically identify schizophrenia subjects with relatively normal cognition, examine their neuroanatomical characteristics relative to their more impaired counterparts using cortical thickness mapping, and to investigate relationships between these characteristics and demographic variables to better understand the nature of cognitive heterogeneity in schizophrenia. Clinical, neuropsychological, and MRI data were collected from schizophrenia (n = 79) and healthy subjects (n = 65). A series of clustering algorithms on neuropsychological scores was examined, and a 2-cluster solution that separated subjects into neuropsychologically near-normal (NPNN) and neuropsychologically impaired (NPI) groups was determined most appropriate. Surface-based cortical thickness mapping was utilized to examine differences in thinning among schizophrenia subtypes compared with the healthy participants. A widespread cortical thinning pattern characteristic of schizophrenia emerged in the NPI group, while NPNN subjects demonstrated very limited thinning relative to healthy comparison subjects. Analysis of illness duration indicated minimal effects on subtype classification and cortical thickness results. Findings suggest a strong link between cognitive impairment and cortical thinning in schizophrenia, where subjects with near-normal cognitive abilities also demonstrate near-normal cortical thickness patterns. While generally supportive of distinct etiological processes for cognitive subtypes, results provide direction for further examination of additional neuroanatomical differences.

Project description:BACKGROUND:Enlarged ventricles and reduced hippocampal volume are consistently found in patients with first-episode schizophrenia. Studies investigating brain structure in antipsychotic-naive patients have generally focused on the striatum. In this study, we examined whether ventricular enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia. METHODS:We obtained high-resolution 3-dimensional T1-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use of a false discovery rate correction (p < 0.05) to control for multiple comparisons. We derived and analyzed estimates of brain structure volumes. We grouped patients as those with (n = 9) or without (n = 29) any lifetime substance abuse to examine the possible effects of substance abuse. RESULTS:We found that hippocampal and caudate volumes were decreased in patients with first-episode schizophrenia. We found no ventricular enlargement, differences in global volume or significant associations between tissue volume and duration of untreated illness or psychopathology. The hippocampal volume reductions appeared to be influenced by a history of substance abuse. Exploratory analyses indicated reduced volume of the nucleus accumbens in patients with first-episode schizophrenia. LIMITATIONS:This study was not a priori designed to test for differences between schizophrenia patients with or without lifetime substance abuse, and this subgroup was small. CONCLUSION:Reductions in hippocampal and caudate volume may constitute morphological traits in antipsychotic-naive first-episode schizophrenia patients. However, the clinical implications of these findings are unclear. Moreover, past substance abuse may accentuate hippocampal volume reduction. Magnetic resonance imaging studies addressing the potential effects of substance abuse in antipsychotic-naive first-episode schizophrenia patients are warranted.

Dataset Information

Reduced cortical thickness related to single nucleotide polymorphisms in the major histocompatibility complex region in antipsychotic-naive schizophrenia.

Publications

Reduced cortical thickness related to single nucleotide polymorphisms in the major histocompatibility complex region in antipsychotic-naive schizophrenia.

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