A longitudinal study on intrinsic connectivity of hippocampus associated with positive symptom in first-episode schizophrenia.

Hippocampal pathology has been considered to underlie clinical, functional and cognitive impairments in schizophrenia. While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the hippocampus during the early phases of schizophrenia (SCZ), very little is known about whether functional connectivity (FC) between the hippocampus and other brain regions also exhibit progressive changes. In this study, resting state functional MRI (fMRI) was used to examine changes in hippocampal connectivity at baseline and follow-up scans comparing 68 patients with first episode SCZ and 62 matched controls. At baseline and follow-up, in the bilateral hippocampal network, SCZ mainly showed decreased FC with bilateral cerebellum posterior lobe, frontal gyrus temporal gyrus, precuneus, and cingulate cortex compared to controls. Furthermore, in the bilateral hippocampus, there was a significant interaction effect of group and time for FC with cerebellum posterior lobe, temporal gyrus, frontal gyrus, and posterior cingulate cortex. Interestingly, longitudinal changes of bilateral hippocampal connectivity with right middle frontal gyrus negatively correlated with positive symptom scores in SCZ. These results provide novel evidence for the progressive changes of FC between hippocampus and other brain regions in SCZ. It further suggests that longitudinal changes of bilateral hippocampal connectivity with right middle frontal gyrus can contribute to the formation and emergence of positive symptom of SCZ.

[Proton magnetic resonance spectroscopy of prefrontal lobe and thalamus in schizophrenics: correlation with clinical characteristics].

OBJECTIVE: To explore the characteristics of different subtypes of schizophrenics on prefrontal lobe and thalamus by proton magnetic resonance spectroscopy ((1)H-MRS) and its relationship. METHODS: From August 2007 to April 2010 at our center, a total of 159 schizophrenics fulfilling the third edition criteria of Chinese Classification of Mental Disorders (CCMD-III) were recruited. And prefrontal lobe and thalamus were evaluated by multi-voxel (1)H-MRS. There were 88 males and 71 females. There were first-episode (n = 54) and not-first-episode (n = 105), negative subtype (n = 125) and positive subtype (n = 34), medicated (n = 96) and non-medicated (n = 63) by different criteria. The levels of N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine compounds (Cr) were measured and the ratios of NAA/Cr and Cho/Cr determined. Positive and negative syndrome scale (PANSS) and Wisconsin card sorting test (WCST) were also assessed. Only 45 normal controls received (1)H-MRS. RESULTS: On left prefrontal lobe and left thalamus, the NAA/Cr ratios in different subtypes of patients were lower than those in normal controls (P < 0.05 or 0.01). The NAA/Cr ratios in patients of non-first-episode (1.48 ± 0.34), negative subtype (1.40 ± 0.35) and medicated (1.47 ± 0.36) on right thalamus were also lower than those in normal controls (1.62 ± 0.37, t = 2.25, 3.56, 2.28, P < 0.05 or P < 0.01). Compared with positive subtype schizophrenics, the NAA/Cr ratios in those of negative subtype on right thalamus were lower (1.40 ± 0.35 vs 1.60 ± 0.37, t = 2.92, P < 0.01). On right thalamus of non-medicated schizophrenics, there was a negative correlation between the duration of illness and the ratio of NAA/Cr (r = -0.38, P < 0.05) and a positive correlation between the duration of illness and the ratio of Cho/Cr (r = 0.43, P < 0.01). On right thalamus of negative subtype schizophrenics, the ratios of NAA/Cr were negatively correlated with the total score of PANSS and the score of negative factor respectively (r = -0.36, -0.40, P < 0.05). On left prefrontal lobe of different subtypes, the ratios of NAA/Cr were negatively correlated with the total score of PANSS, the score of negative factor, responses errors and persistent errors (P < 0.01) and positively correlated with completed categories and conceptual level responses (P < 0.05 or P < 0.01). CONCLUSION: Abnormalities in neuronal function and/or integrity are present on left prefrontal lobe and left thalamus in schizophrenics. And right thalamus is probably involved in non-first-episode subtype, negative subtype and non-medicated subtype. Different subtypes of schizophrenics may have different characteristics of (1)H-MRS due to the duration of illness and their clinical symptoms.