1 H-MR spectroscopy in ultra-high risk and first episode stages of schizophrenia

Using proton magnetic resonance spectroscopy biochemical characteristics in early stages of schizophrenia were examined. N-acetylaspartate, choline and creatine were measured in hippocampus, anterior cingulate gyrus (ACC) and medial prefrontal cortex (mPFC) of 24 first episode and 30 ultra-high risk patients. Careful LCModel analyses revealed no differences between the patient groups and 31 healthy controls, casting doubt upon the idea of metabolic changes in early stages of psychosis.     

Medial Frontal Cortex GABA Concentrations in Psychosis Spectrum and Mood Disorders: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies

BackgroundAbnormalities of GABAergic (gamma-aminobutyric acidergic) systems may play a role in schizophrenia and mood disorders. Magnetic resonance spectroscopy allows for noninvasive in vivo quantification of GABA; however, studies of GABA in schizophrenia have yielded inconsistent findings. This may stem from grouping together disparate voxels from functionally heterogeneous regions.MethodsWe searched PubMed for magnetic resonance spectroscopy studies of GABA in the medial frontal cortex (MFC) in patients with schizophrenia, bipolar disorder, and depression and in individuals meeting criteria for ultra-high risk for psychosis. Voxel placements were classified as rostral-, rostral-mid-, mid-, or posterior MFC, and meta-analyses were conducted for each group for each subregion.ResultsOf 341 screened articles, 23 studies of schizophrenia, 6 studies of bipolar disorder, 20 studies of depression, and 7 studies of ultra-high risk met the inclusion criteria. Meta-analysis revealed lower mid- (standardized mean difference [SMD] = ?0.28, 95% CI, ?0.48 to ?0.07, p < .01) and posterior (SMD = ?0.29, 95% CI, ?0.49 to ?0.09, p < .01) MFC GABA in schizophrenia and increased rostral MFC GABA in bipolar disorder (SMD = 0.76, 95% CI, 0.25 to –1.25, p < .01). In depression, reduced rostral MFC GABA (SMD = ?0.36, 95% CI, ?0.64 to ?0.08, p = .01) did not survive correction for multiple comparisons. We found no evidence for GABA differences in individuals at ultra-high risk for psychosis.ConclusionsWhile limited by small numbers of published studies, these results substantiate the relevance of GABA in the pathophysiology of psychosis spectrum and mood disorders and underline the importance of voxel placement.     

Posterior Cingulate and Lateral Parietal Gray Matter Volume in Older Adults with Depressive Symptoms

Depressive symptoms occurring late in life are an important risk factor for Alzheimer’s disease (AD). The latest research finds that onset of depressive symptoms in late life may herald the development of AD, not only for amnestic Mild Cognitive Impairment (aMCI) patients, but also for cognitively-normal older adults. Neuroimaging of brain structure, blood flow, and glucose metabolism indicates that depressive symptoms in late life are accompanied by structural and functional changes in limbic brain regions vulnerable to AD. The present cross-sectional study was guided by the hypothesis that compared to their non-depressed counterparts, older adults with mild to moderate depressive symptoms have less volume in limbic structures vulnerable to changes in AD—specifically, cortical midline structures such as anterior cingulate and posterior cingulate cortex as well as mesial temporal regions such as bilateral hippocampi and amygdalae. Consistent with our hypothesis, results of a voxel-based morphometry analysis revealed smaller retrosplenial, posterior cingulate, and precuneus gray matter volumes in depressed individuals relative to healthy controls. Right lateral parietal cortex—another region vulnerable to change in AD—was also smaller in the group with depressive symptoms. Contrary to our hypothesis, no volumetric differences were found in the anterior cingulate cortex or mesial temporal lobe. Results of this study show a relationship between geriatric depressive symptoms and brain volume in regions vulnerable to AD. Follow-up of participants over time will tell if brain changes detected here predict development of AD.     

Prevalence of Depressive Symptoms and Related Risk Factors for Depressive Symptoms among Elderly Persons Living in a Rural Japanese Community: a Cross-Sectional Study

To clarify the prevalence of depression in a rural community in Japan and to evaluate the social and familial risk factors for depression, with the goal of suicide prevention, a questionnaire survey was conducted on a total of 2,763 elderly persons. The determined prevalence of depressive symptoms (Zung’s self-rated depression scale score of 50 points or more) was 10.4%. Logistic regression analysis showed associations between depressive symptoms and age, absence of a friendly companion, irritation with one’s family, frequent loneliness, the opinion that stress has a large impact on one’s life, suicide ideation, and poor subjective physical and mental health. Y. Kaneko, Y. Motohashi and H. Sasaki are affiliated with the Department of Public Health, Akita, Japan. M. Yamaji is an Assistant Professor in the Faculty of Health and Medical Care, Saitama, Japan.     

Impact of Comorbid Affective Disorders on Longitudinal Clinical Outcomes in Individuals at Ultra-high Risk for Psychosis

IntroductionDiagnoses of anxiety and/or depression are common in subjects at Ultra-High Risk for Psychosis (UHR) and associated with extensive functional impairment. Less is known about the impact of affective comorbidities on the prospective course of attenuated psychotic symptoms (APS).MethodLatent class mixed modelling identified APS trajectories in 331 UHR subjects assessed at baseline, 6, 12, and 24 months follow-up. The prognostic value of past, baseline, and one-year DSM-IV depressive or anxiety disorders on trajectories was investigated using logistic regression, controlling for confounders. Cox proportional hazard analyses investigated associations with transition risk.Results46.8% of participants fulfilled the criteria for a past depressive disorder, 33.2% at baseline, and 15.1% at one-year follow-up. Any past, baseline, or one-year anxiety disorder was diagnosed in 42.9%, 37.2%, and 27.0%, respectively. Participants were classified into one of three latent APS trajectory groups: (1) persistently low, (2) increasing, and (3) decreasing. Past depression was associated with a higher risk of belonging to the increasing trajectory group, compared to the persistently low (OR = 3.149, [95%CI: 1.298–7.642]) or decreasing group (OR = 3.137, [1.165–8.450]). In contrast, past (OR = .443, [.179–1.094]) or current (OR = .414, [.156–1.094]) anxiety disorders showed a trend-level association with a lower risk of belonging to the increasing group compared to the persistently low group. Past depression was significantly associated with a higher risk of transitioning to psychosis (HR = 2.123, [1.178–3.828]).ConclusionA past depressive episode might be a particularly relevant risk factor for an unfavorable course of APS in UHR individuals. Early affective disturbances may be used to advance detection, prognostic, and clinical strategies.     

男性精神分裂症患者海马磁共振质子波谱成像的研究

目的 探讨精神分裂症患者双侧海马的磁共振质子波谱(MRS)的特点,以期对此疾病的临床诊断提供代谢方面依据,为精神分裂症的病因学探讨提供线索。方法 应用MRS成像技术,对20例男性精神分裂症患者和20名男性正常人检测双侧海马的氮-乙酰天门冬氨酸复合物(NAA)、胆碱复合物(CHO)和肌酸-磷酸肌酸复合物(Cr)含量,对NAA/Cr和CHO/Cr的比值进行计算。以重复测量方差分析的方法进行统计分析,其中组别作为组间差异,左右侧作为组内差异。结果 CHO/Cr的比值在精神分裂症患者双侧海马(左侧为1.03±0.22,右侧为1.00±0.23)高于正常人(左侧为0.95±0.16,右侧为0.97±0.16),差异有显著性(F=6.896,P=0.013);而NAA/Cr的比值在精神分裂症患者与正常人间的差异无显著性(患者左侧为1.29±0.16,右侧为1.25±0.13;正常人左侧为1.41±0.20,右侧为1.36±0.17)。结论 男性精神分裂症患者的海马可能存在膜的磷脂代谢异常。     

Obsessive-Compulsive Symptoms and Other Symptoms of the At-risk Mental State for Psychosis: A Network Perspective

BackgroundThe high prevalence of obsessive-compulsive symptoms (OCS) among subjects at Ultra-High Risk (UHR) for psychosis is well documented. However, the network structure spanning the relations between OCS and symptoms of the at risk mental state for psychosis as assessed with the Comprehensive Assessment of At Risk Mental States (CAARMS) has not yet been investigated. This article aimed to use a network approach to investigate the associations between OCS and CAARMS symptoms in a large sample of individuals with different levels of risk for psychosis. MethodThree hundred and forty-one UHR and 66 healthy participants were included, who participated in the EU-GEI study. Data analysis consisted of constructing a network of CAARMS symptoms, investigating central items in the network, and identifying the shortest pathways between OCS and positive symptoms. ResultsStrong associations between OCS and anxiety, social isolation and blunted affect were identified. Depression was the most central symptom in terms of the number of connections, and anxiety was a key item in bridging OCS to other symptoms. Shortest paths between OCS and positive symptoms revealed that unusual thought content and perceptual abnormalities were connected mainly via anxiety, while disorganized speech was connected via blunted affect and cognitive change. ConclusionsFindings provide valuable insight into the central role of depression and the potential connective component of anxiety between OCS and other symptoms of the network. Interventions specifically aimed to reduce affective symptoms might be crucial for the development and prospective course of symptom co-occurrence.     

抑郁症首次发病患者海马磁共振质子波谱成像的研究

目的 探讨抑郁症首次发病患者海马的磁共振质子波谱(1H-MRS)代谢物质的变化.方法 对99例首次发病的抑郁症患者和26例健康对照组行磁共振常规扫描及1H-MRS检查,测量双侧海马N-乙酰天门冬氨酸(NAA)、胆碱复合物(Cho)和肌酸(Cr)三种代谢物质,计算NAA/Cr和Cho/Cr比值.结果 抑郁症患者海马NAA/Cr左右侧比值(1.23±0.16;1.16±0.16)低于对照组NAA/Cr左右侧比值(1.38±0.23;1.31±0.26),差异有显著性(P<0.05);抑郁症患者海马体部Cho/Cr左右侧比值(1.19±0.14;1.18±0.12)高于对照组Cho/Cr左右侧比值(1.14±0.12;1.11±0.14),差异有显著性(P<0.05).对照组左右侧NAA/Cr和Cho/Cr比较差异无显著性(P>0.05).抑郁症组右侧NAA/Cr低于左侧,差异显著(P<0.05);左侧Cho/Cr高于右侧,差异不明显(P>0.05).结论 抑郁症患者可能存在双侧海马神经细胞代谢功能障碍,右侧神经细胞功能障碍较左侧明显.     

Cognitive Behavioral Therapy for Subjects at Ultrahigh Risk for Developing Psychosis: A Randomized Controlled Clinical Trial

Background

: Evidence for the effectiveness of treatments for subjects at ultrahigh risk (UHR) for developing psychosis remains inconclusive. Objective : A new cognitive behavioral intervention specifically targeted at cognitive biases (ie, Cognitive Behavioral Therapy [CBT] for UHR patients plus treatment as usual [TAU] called CBTuhr) is compared with TAU in a group of young help-seeking UHR subjects. Methods : A total of 201 patients were recruited at 4 sites and randomized. In most cases, CBTuhr was an add-on therapy because most people were seeking help for a comorbid disorder. The CBT was provided for 6 months, and the follow-up period was 18 months. Results : In the CBTuhr condition, 10 patients transitioned to psychosis compared with 22 in the TAU condition (χ ² (1) = 5.575, P = .03). The number needed to treat (NNT) was 9 (95% confidence interval [CI]: 4.7–89.9). At 18-month follow-up the CBTuhr group was significantly more often remitted from an at-risk mental state, with a NNT of 7 (95% CI: 3.7–71.2). Intention-to-treat analysis, including 5 violations against exclusion criteria, showed a statistical tendency (χ ² (1) = 3.338, P = .06). Conclusions : Compared with TAU, this new CBT (focusing on normalization and awareness of cognitive biases) showed a favorable effect on the transition to psychosis and reduction of subclinical psychotic symptoms in subjects at UHR to develop psychosis. Key words: cognitive behavioral therapy, ultrahigh risk, cognitive biases, prevention, psychosis, schizophrenia     

Phosphorus-31 magnetic resonance brain spectroscopy of children at risk for a substance use disorder: Preliminary results

The purpose of this exploratory investigation was to evaluate the heuristic potential of ³¹P magnetic resonance spectroscopy (MRS) in elucidating a neurobiologic component of the liability for a substance use disorder (SUD). We investigated ³¹P MRS spectra employing chemical shift imaging (CSI) derived from four distinct anatomic brain locations (i.e. frontal, occipital, right parietal, left parietal) in three groups of peripubertal children who are hypothesized to be at increasing levels of familial SUD risk. Specifically, we studied children with a positive paternal family history of SUD and a disruptive behavior disorder (DBD) diagnosis (SUD+/DBD+; n=10), in contrast to those with a positive paternal SUD history in the absence of other psychopathology (SUD+/DBD−; n=13) and matched control children from normal families (SUD−/DBD−; n=13). In addition, we examined neurocognitive tests of our subjects to determine any associations between cognitive capacities with regional ³¹P MRS spectra. The highest-risk sample (SUD+/DBD+) demonstrated a diminished proportion of phosphodiesters confined to the right parietal voxel. This right parietal phosphodiester proportion correlated only with the Information Scale score on a standard intelligence test for children. This suggested a relationship between general learning ability and motivation for academic achievement and right parietal physiology in the highest-risk sample. Variations in synaptic pruning could account for this observation.     

抑郁症首次发病患者额叶三维磁共振氢质子波谱分析研究

目的探讨抑郁症首次发病患者额叶灰、白质可能存在的神经生化异常。方法对24例首次发病抑郁症患者(抑郁症20例,双相障碍抑郁发作者4例;抑郁症组)进行磁共振常规扫描及应用三维磁共振氢质子波谱(1HMRS)检查,测量双侧额叶背外侧白质和前部扣带回皮质的N-乙酰天门冬氨酸(NAA)、胆碱复合物(CHO)、肌醇(MI)和肌酸(CR)的绝对值,计算NAA、CHO、MI与CR的比值,并与21名正常对照者(对照组)作比较。结果(1)抑郁症组患者前额叶扣带回皮质CHO[(772±59)MMOL/L]、MI[(131±39)MMOL/L]的绝对值及CHO/CR(2·3±0·4)、MI/CR(0·39±0·14)均高于对照组[分别为(663±70)MMOL/L,(99±26)MMOL/L,2·0±0·4,0·30±0·01],差异均有统计学意义(P均<0·01);而NAA的绝对值及NAA/CR与对照组的差异无统计学意义(P>0·05)。(2)抑郁症组患者额叶背外侧白质内NAA、CHO、MI的绝对值以及NAA/CR、CHO/CR、MI/CR的比值与对照组的差异均无统计学意义(P均>0·05)。结论抑郁症患者额叶扣带回皮质的CHO、MI绝对值以及CHO/CR、MI/CR比值均增高。     

阳性症状为主型精神分裂症首次发病患者前额叶和海马磁共振质子波谱成像研究

目的 探讨阳性症状为主型精神分裂症首次发病患者前额叶和海马的磁共振质子波谱(1H-MRS)变化特点,为其病因学探讨提供线索.方法 对22例首次发病精神分裂症阳性症状为主型患者(患者组)和11名年龄、性别、受教育时间均匹配的正常对照者(对照组),应用2D 1H-MRS成像技术检测2组双侧前额叶白质、前扣带回皮质、海马N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)3种代谢物,分别计算NAA/Cr和Cho/Cr的比值;采用配对t检验、独立样本t检验进行统计分析.结果 (1)患者组左侧额叶白质NAA/Cr和Cho/Cr分别为(1.63±0.30)和(1.23±0.26),均低于对照组[(2.10±0.30)、(1.54±0.25)],右侧额叶白质NAA/Cr(1.70±0.34)低于对照组(1.97±0.34),差异有统计学意义(P<0.01和P<0.05);(2)双侧前扣带回皮质NAA/Cr、Cho/Cr值与对照组差异无统计学意义(P>0.05);(3)患者组右侧海马NAA/Cr(1.59±0.27)高于对照组(1.24±0.17),差异有统计学意义(P<0.01);(4)对照组内左侧额叶白质Cho/Cr(1.54±0.25)高于右侧(1.35±0.18),左侧海马NAA/Cr(1.45±0.28)高于右侧(1.24±0.17),差异均有统计学意义(P<0.05);(5)患者组内左侧海马NAA/Cr和Cho/Cr分别为(1.43±0.27)和(1.39±0.38),均低于右侧[(1.59±0.27)、(1.56±0.39)],差异有统计学意义(P<0.05).结论 首发精神分裂症阳性症状为主型患者的1H-MRS代谢物与正常人存在差异,提示阳性症状为主型患者存在双侧前额叶白质、海马的神经功能障碍.

Abstract：

Objective To identify the possible alteration of brain functioning in prefrontal lobes and hippocampus in the first-episode positive symptoms of schizophrenia using proton magnetic resonance spectroscopy (1H-MRS). Methods 1H-MRS was performed on prefrontal white matter, anterior cingulated cortex and hippocampus in 22 patients and 11 age-, sex-, and education-matched right-handed healthy controls. The ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline-containing compounds (Cho)/Cr were calculated. Results The NAA/Cr and Cho/Cr ratios in the left prefrontal white matter in patients were lower than that in normal controls (patients, NAA/Cr 1. 63 ±0. 30; Cho/Cr 1. 23 ±0. 26; controls, NAA/Cr 2. 10 ±0. 30; Cho/Cr 1. 54 ± 0. 25, P<0. 01) , and NAA/Cr in the right prefrontal white matter was lower in patients than in controls (patients 1. 70 ± 0. 34; controls 1. 97 ± 0. 34, P<0. 05). There were no significant difference in NAA/Cr, Cho/Cr for the bilateral anterior cingulated cortex between patients and controls (P>0. 05). The ratio of NAA/Cr in the right hippocampus was significantly higher in patients than that in controls (patients 1. 59 ± 0. 27; controls 1. 24 ± 0. 17, P<0. 01). In addition, in healthy controls,Cho/Cr was significantly higher in the left prefrontal white matter than in the right (left 1. 54 ± 0. 25; right 1. 35 ±0. 18, P<0. 05) , and NAA/Cr in the left hippocampus was significantly higher than in the right (left 1. 45 ± 0. 28; right 1. 24 ± 0. 17, P<0. 05). While NAA/Cr and Cho/Cr in the left hippocampus were significantly lower than in the right hippocampus in schizophrenia patients (left, NAA/Cr 1.43 ± 0. 27;Cho/Cr 1.39 ±0.38; right, NAA/Cr 1.59 ±0.27; Cho/Cr 1.56 ±0.39, P<0.05). Conclusion There is the significant difference of manifestation of 1H-MRS between schizophrenia patients with positive symptoms and normal controls, which reflects neuronal dysfunction in the prefrontal lobes and hippocampus.     

男性首次发病精神分裂症患者治疗前后额叶的质子波谱研究

目的在体研究精神分裂症症状发生的神经生物学基础,探讨抗精神病药对额叶代谢物质的潜在影响。方法应用磁共振质子波谱(MRS)技术对10例男性首发精神分裂症患者(患者组)和10名男性正常对照者(对照组)检测额叶氮-乙酰天门冬氨酸(NAA)、胆碱复合物(CHO)、肌酸(Cr)。患者组入组后均予以第二代抗精神病药治疗,治疗第2个月时复查额叶~1H-MRS。每次~1H-MRS检查的同时,患者组各接受1次阳性和阴性症状量表(PANSS)评定、威斯康星卡片分类测试(WCST)评定。对照组仅进行1次WCST评定。结果多因素方差分析表明,治疗前患者组左、右侧额叶灰白质NAA/Cr均低于对照组[左侧白质：患者组1.87±0.30；对照组2.13±0.43。左侧灰质：患者组1.44±0.20；对照组1.67±0.32。右侧白质：患者组1.60±0.28；对照组2.09±0.41。右侧灰质：患者组1.35±0.25；对照组1.56±0.30],差异均有统计学意义(P均＜0.05)。患者组治疗前后NAA/Cr、CHO/Cr的差异均无统计学意义(P均＞0.05)。结论精神分裂症患者可能存在额叶神经元的损害。第二代抗精神病药短期治疗对精神分裂症患者额叶~1H-MRS代谢物水平无明显影响。     

偏执型精神分裂症患者Stroop操作的功能磁共振研究

目的利用功能磁共振显像(fMRI)技术探讨精神分裂症患者注意障碍的脑功能基础。方法对14例精神分裂症患者(患者组)和16名正常人(对照组)检测Stroop测验刺激下的fMRI。结果(1)激活脑区计数(个)：Stroopl刺激下,患者组左侧额下回(11/3)、左侧颞上回(6/8)、左侧颞下回(6/8)脑区激活计数均多于对照组(分别为6/10、1/15、1/15),差异有统计学意义(P＜0.05)；Stroop2刺激下,患者组左侧前扣带皮质(ACC,4/10)、右侧额中回脑区激活计数(4/10)均少于对照组(分别为12/4、14/2),差异有统计学意义(P＜0.05),患者组左额上回激活计数(9/5)多于对照组(3/ 13),差异有统计学意义(P＜0.05)。(2)激活脑区体积(体素)：Stroop1刺激下,患者组右侧前额叶背外侧区(DLPFC,256±579)、左侧ACC(18±59)激活体积小于对照组(分别为298±597、67±87),差异有统计学意义(P＜0.05)；Stroop2刺激下,患者组两侧DLPFC(分别为73±190、80±245)、左侧ACC(17±28)激活体积小于对照组(分别为425±800、414±703、76±98),差异有统计学意义(P＜0.05)。结论精神分裂症患者的注意障碍可能与前额叶、ACC、颞叶神经回路功能障碍密切相关。     

抑郁症患者前额叶、海马磁共振质子波谱成像的研究

目的探讨抑郁症患者前额叶、海马的磁共振质子波谱(1H-MRS)变化特点。方法应用1H-MRS成像技术检测26例抑郁症患者(抑郁症组)和20名健康对照者(对照组)的前额叶、海马N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)3种代谢物,计算NAA/Cr和Cho/Cr比值。以抑郁症组年龄的中位数(38.5岁)为界将抑郁症组和对照组分为低年龄组[(28±7)岁,14例;(22±6)岁,9名]与高年龄组[(54±9)岁,12例;(53±7)岁,11名]。按病程分为首次发病组(19例,以下简称首发组)和复发组(7例)。采用方差分析进行统计比较。结果高年龄组患者左侧前额叶Cho/Cr(1.60±0.45)×10-6高于对照组(1.28±0.20)×10-6,差异有统计学意义(P<0.05);低年龄组患者右侧前额叶Cho/Cr(1.74±0.51)×10-6高于对照组(1.22±0.40)×10-6,差异有统计学意义(P<0.01)。高年龄组患者左侧海马NAA/Cr(1.16±0.31)×10-6低于对照组(2.21±0.83)×10-6,差异有统计学意义(P<0.01);低年龄组患者左侧海马Cho/Cr(1.54±0.44)×10-6高于对照组(1.08±0.35)×10-6,差异有统计学意义(P<0.05)。首发组患者左侧前额叶Cho/Cr(1.57±0.42)×10-6高于对照组(1.26±0.21)×10-6,复发组患者右侧前额叶Cho/Cr(1.77±0.50)×10-6高于对照组(1.29±0.32)×10-6,差异均有统计学意义(P均<0.01)。首发组患者左侧海马NAA/Cr(1.19±0.26)×10-6及复发组患者左侧海马NAA/Cr(1.10±0.29)×10-6均低于对照组(1.87±0.81)×10-6,复发组患者右侧海马Cho/Cr(2.13±0.51)×10-6高于对照组(1.51±0.52)×10-6,差异均有统计学意义(P均<0.01)。结论抑郁症患者可能存在前额叶、左侧海马细胞膜代谢异常,高年龄抑郁症患者的左侧海马神经元活力下降。