Neuroprotective Effect of Modified Electroconvulsive Therapy for Schizophrenia: A Proton Magnetic Resonance Spectroscopy Study.

The underlying mechanism of modified electroconvulsive therapy (MECT) treatment for drug-resistant and catatonic schizophrenia remains unclear. Here, we aim to investigate whether MECT exerts its antipsychotic effects through elevating N-acetylaspartate (NAA) concentration measured by proton magnetic resonance spectroscopy (H-MRS). Multiple-voxel H-MRS was acquired in the bilateral prefrontal cortex (PFC) and thalamus to obtain measures of neurochemistry in 32 MECT, 34 atypical antipsychotic-treated schizophrenic patients, and 34 healthy controls. We found that both MECT and atypical antipsychotic treatments showed significant antipsychotic efficacy. MECT and atypical antipsychotic treatments reversed the reduced NAA/creatine ratio (NAA/Cr) in the left PFC and left thalamus in schizophrenic patients compared with healthy controls. Furthermore, the NAA/Cr ratio after treatments was significant higher in the MECT group, but not in the medication group. Our findings demonstrate that eight times of MECT elevated the relative NAA concentration to display neuroprotective effect, which may be the underlying mechanism of rapid antipsychotic efficacy.

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.

Atypical antipsychotic drug treatment for 6 months restores N-acetylaspartate in left prefrontal cortex and left thalamus of first-episode patients with early onset schizophrenia: A magnetic resonance spectroscopy study.

Early onset schizophrenia (EOS) is often associated with poorer outcomes, including lack of school education, higher risk of mental disability and resistance to treatment. But the knowledge of the neurobiological mechanism of EOS is limited. Here, using proton magnetic resonance spectroscopy, we investigated the possible neurochemical abnormalities in prefrontal cortex (PFC) and thalamus of first-episode drug-naïve patients with EOS, and followed up the effects of atypical antipsychotic treatment for 6 months on neurochemical metabolites and clinical symptoms. We measured the ratios of N-acetylaspartate (NAA), choline (Cho) to creatine (Cr) in 41 adolescents with first episode of EOS and in 28 healthy controls matched for age, gender, and years of education. The EOS patients presented with abnormally low NAA/Cr values in the left PFC and left thalamus with a reduced tendency in the right PFC compared with healthy controls. No significant differences were detected between groups for Cho/Cr in PFC and thalamus in any hemisphere. After atypical antipsychotic treatment for 6 months, the reduced NAA/Cr in the left PFC and left thalamus in EOS patients was elevated to the normal level in healthy controls, without any alteration in Cho/Cr. We also found that there was no significant correlation between the neurochemical metabolite ratios in the PFC and thalamus in patients with EOS, and clinical characteristics. Our results suggest that there was neurochemical metabolite abnormalities in PFC and thalamus in EOS patients, atypical antipsychotic treatment can effectively relieve the symptoms and restore the reduced NAA in PFC and thalamus.

[Proton magnetic resonance spectroscopy study of prefrontal lobe and thalamus in schizophrenics on modified electroconvulsive therapy].

OBJECTIVE: To explore the potential effects of modified electroconvulsive therapy (MECT) in prefrontal lobe and thalamus in patients with schizophrenia by proton magnetic resonance spectroscopy ((1)H-MRS). METHODS: From November 2010 to June 2011, a total of 31 schizophrenics fulfilling the third edition of the Chinese Classification of Mental Disorders (CCMD-III) were recruited. And prefrontal lobe and thalamus were evaluated by multi-voxel (1)H-MRS before and after 8 sessions of MECT. The subjects were evaluated by the positive and negative syndrome scale (PANSS). And the N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine compounds (Cr) were measured and the ratios of NAA/Cr and Cho/Cr determined. RESULTS: (1) In left prefrontal lobe and bilateral thalamus, the NAA/Cr ratio at post-treatment demonstrated higher than that at pre-treatment (1.50 ± 0.31 vs 1.35 ± 0.30, t = 2.07, P < 0.05; 1.53 ± 0.31 vs 1.38 ± 0.27, t = 2.03, P < 0.05; 1.51 ± 0.29 vs 1.36 ± 0.26, t = 2.14, P < 0.05). (2) The major influencing factors of the changes of NAA/Cr in left prefrontal lobe were age of onset, decrease rate of PANSS, baseline PANSS total score and duration of illness. And the major influencing factors for left thalamus were age of onset and duration of illness while a major influencing factor for right thalamus was baseline PANSS total score. CONCLUSION: MECT may modify brain metabolism as measured by (1)H-MRS. The pattern of changes suggests possible neuroprotective effects in schizophrenics. And these effects are correlated with age of onset, duration and severity of illness.

[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.

[Effects of risperidone on polysomnography in patients with first-episode schizophrenia].

OBJECTIVE: To investigate the effects of risperidone on the polysomnography (PSG) in the patients with first-episode schizophrenia. METHODS: Twenty-five patients with first-episode schizophrenia, 13 males and 12 females, aged 29 +/- 8, underwent polysomnographic recording for 4 consecutive nights, the first night being used for acclimatization, and on the 3 rd and 4 th nights risperidone in the dose of 1.2 mg was administered before going to bed. Forty-four healthy persons, 23 males and 21 females, aged 28 +/- 8, underwent polysomnographic recording for 2 consecutive nights, the first night being used for acclimatization. RESULTS: The baseline PSG recording showed that in comparison with the normal control group the total sleep time of the schizophrenia patients was shorter (378 min +/- 30 min vs 462 min +/- 21 min), sleep latency was longer (30 min +/- 14 min vs 18 min +/- 8 min), rapid eye movement (REM) sleep latency was shorter (59 min +/- 20 min vs 88 min +/- 10 min), REM sleep time was shorter (61 min +/- 17 min vs 84 min +/- 12 min), awakening time was longer (34 min +/- 17 min vs 15 min +/- 5 min), stage 1 (S1) time was longer (22% +/- 10% vs 9.0% +/- 1.7%), S3 time and S4 time were shorter, and the sleep efficacy was lower (86% +/- 10%) (P < 0.05 approximately P < 0.01); however, there was no significant difference in the S2 time between these 2 groups (54% +/- 16% vs 56% +/- 4%, P > 0.05). In the schizophrenia group, in comparison with the baseline levels in the third and fourth nights the total sleep times were significantly increased (406 min +/- 34 min and 428 min +/- 31 min respectively), the awakening times were significantly decreased (23 min +/- 15 min and 19 min +/- 8 min respectively), and S1 times were significantly decreased (14 min +/- 9 min and 10 min +/- 9 min respectively), with such changes time-dependently; and in the 4 th night the REM sleep time was significantly increased (87 min +/- 20 min) and the sleep efficacy was significantly improved (93% +/- 12%) (P < 0.05 approximately P < 0.01), however, there were no significant differences in the sleep latency and slow wave sleep (both P > 0.05). CONCLUSION: Risperidone significantly improves the quality of sleep.

[Sensory gating of patients with first-episode schizophrenia].

OBJECTIVE: To investigate the characteristics of sensory gating P50 of patients with first-episode schizophrenia. METHODS: The auditory evoked potentials P50 were recorded in 66 patients (Group Sch) with first-episode schizophrenia and 92 normal controls (Group NC) by using conditioning/testing paradigm presented with auditory double click stimuli. RESULTS: The value of S1-P50 of Group Sch was 3 microV +/- 2 microV, significantly lower than that of Group NC (6 microV +/- 3 microV, P <0.01). The value of S2-P50 of Group Sch was 4 microV +/- 2 microV, significantly higher than that of Group NC (2 microV +/- 1 microV, P < 0.01). The S2/S1 ratio of Group Sc was 81% +/- 40%, significantly higher than that of Group NC (42% +/- 21%, P < 0.01). The value of S2 - S1 of Group Sch was 2 microV +/- 1 mciroV, significantly lower than that of Group Sch (3 mciroV +/- 2 microV). The value of 100 (1-S2/S1) of Group Sch was 19% +/- 17%, significantly lower than that of Group NC (58% +/- 21% , P < 0.01). CONCLUSION: Sensory gating deficit exists in the patients with first-episode schizophrenia, manifested in deficiency of inhibition that can be quantitatively observed by measuring auditory evoked potential P50.