Choline, myo-inositol and mood in bipolar disorder: a proton magnetic resonance spectroscopic imaging study of the anterior cingulate cortex

Objectives: Alterations in choline and myo-inositol metabolism have been noted in bipolar disorder, and the therapeutic efficacy of lithium in mania may be related to these effects. We wished to determine the relationship between anterior cingulate cortex choline and myo-inositol levels, assessed using proton magnetic resonance spectroscopic imaging (MRSI), and mood state in subjects with bipolar disorder.

Methods: Serial assessments of anterior cingulate cortex choline and myo-inositol metabolism were performed in nine subjects with bipolar disorder, taking either lithium or valproate, and 14 controls. Each bipolar subject was examined between one and four times (3.1±1.3). On the occasion of each examination, standardized ratings of both depression and mania were recorded.

Results: In the left cingulate cortex, the bipolar subjects' depression ratings correlated positively with MRSI measures of Cho/Cr-PCr. In the right cingulate cortex, the Cho/Cr-PCr ratio was significantly higher in subjects with bipolar disorder compared with control subjects. In addition, bipolar subjects not taking antidepressants had a significantly higher right cingulate cortex Cho/Cr-PCr ratio compared with patients taking antidepressants or controls. No clinical or drug-related changes were observed for the Ino/Cr-PCr ratio.

Conclusions: The results of this study suggest that bipolar disorder is associated with alterations in the metabolism of cytosolic, choline-containing compounds in the anterior cingulate cortex. As this resonance arises primarily from phosphocholine and glycerophosphocholine, both of which are metabolites of phosphatidylcholine, these results are consistent with impaired intraneuronal signaling mechanisms.     

Volume reduction of ventromedial prefrontal cortex in bipolar II patients with rapid cycling: a voxel-based morphometric study

Although rapid cycling (RC), a course specifier of bipolar I or II disorder, is particularly common among bipolar II patients compared with bipolar I patients, the pathophysiological lines of evidence regarding bipolar II with RC are still limited. In this preliminary study with a cross-sectional design, we examined the regional gray matter (GM) volume in 14 bipolar II patients with RC, 17 patients without RC and 84 healthy controls by whole-brain and region-of-interest (ROI) analysis methods, using magnetic resonance imaging with voxel-based morphometry. Whole-brain analysis in this study revealed that the bipolar II patients with RC showed GM volume reductions in the bilateral hemispheres of the medial orbital prefrontal cortex, ventromedial prefrontal cortex, anterior cingulate, insula and parahippocampus, in the left hemisphere of the inferior temporal cortex and cerebellum, and in the brainstem, compared with the healthy controls. Moreover, ROI analysis focusing on the ventral prefrontal cortex, i.e., Brodmann areas 10, 11 and 47, revealed that the bipolar II patients with RC showed GM volume reduction in the ventromedial prefrontal cortex, compared with the patients without RC. The findings of our pilot study suggest that the ventromedial prefrontal cortex is associated with the generation of RC in bipolar II disorder.     

Proton magnetic resonance spectroscopy of patients with parkinsonism

We studied cerebral metabolism in 82 patients with nonfamilial parkinsonism, including Parkinson's disease (PD; n = 23), progressive supranuclear palsy (PSP; n = 12), corticobasal degeneration (CBD; n = 19), multiple systemic atrophy (MSA; n = 18) and vascular parkinsonism (VP; n = 10) by using proton magnetic resonance spectroscopy ((1)H-MRS), which allowed noninvasive measurement of signal intensities from N-acetylasparate (NAA), choline-containing compounds (CHO) and creatine plus phosphocreatine (CRE). As compared to normal controls, patients with PSP, CBD, MSA and VP, but not PD, had significant reduction of the NAA/CRE ratio in the frontal cortex, whereas patients with PSP, CBD, MSA and PD, but not VP, had significant reduction of the NAA/CRE ratio in the putamen. Patients with CBD had significant reduction of the NAA/CRE ratio in the frontal cortex and putamen as compared to patients with PD, MSA and VP. Patients with PSP showed a significant reduction of the NAA/CRE ratio in the putamen as compared with patients with PD and MSA. Patients with CBD showed clear asymmetry in the putamen as compared to controls and other patients. The reduction of the NAA/CRE ratio in the putamen correlated well with the severity of parkinsonism. (1)H-MRS may be useful in monitoring patients with various types of parkinsonism.     

Interaction of the DRD3 and BDNF gene variants in subtyped bipolar disorder

Objectives

Bipolar disorder is a severe mental disorder with prominent genetic etiologic factors. Dopaminergic dysfunction has been implicated in the pathogenesis of bipolar disorder, which suggests that the dopamine D3 receptor gene (DRD3) is a strong candidate gene. The brain-derived neurotrophic factor (BDNF) gene has been implicated in the etiology of bipolar disorder. We examined the association between the BDNF Val66Met and DRD3 Ser9Gly polymorphisms with two subtypes of bipolar disorder: bipolar-I and -II. Because BDNF regulates DRD3 expression (1), we also examined possible interactions between these genes.

Methods

We recruited 964 participants: 268 with bipolar-I, 436 with bipolar-II, and 260 healthy controls. The genotypes of the BDNF Val66Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis.

Results

Logistic regression analysis showed a significant main effect for the Val/Val genotype of the BDNF Val66Met polymorphism (P = 0.020), which predicted bipolar-II patients. Significant interaction effects for the BDNF Val66Met Val/Val genotype and both DRD3 Ser9Gly Ser/Ser and Ser/Gly genotypes were found only in bipolar-II patients (P = 0.027 and 0.006, respectively).

Conclusion

We provide initial evidence that the BDNF Val66Met and DRD3 Ser9Gly genotypes interact only in bipolar-II disorder and that bipolar-I and bipolar-II may be genetically distinct.     

重复经颅磁刺激对抑郁症患者磁共振波谱和疗效的影响

目的 探讨重复经颅磁刺激(rTMS)治疗抑郁症患者的疗效及可能机制. 方法 选择自2012年8月至2014年7月在全军精神疾病防治研究所住院的抑郁症患者70例,所有患者均符合美国精神障碍诊断与统计手册第4版诊断标准.按照随机数字表法将患者随机分为研究组(n=36)和对照组(n=34),2组患者均接受盐酸文拉法辛缓释片(75 mg/片)治疗.研究组同时联合10Hz rTMS作用于左侧背外侧前额叶(DLPFC)治疗4周,对照组给予rTMS伪刺激.治疗前后采用多体素磁共振质子波谱(1H-MRS)检测患者前额叶和丘脑N-乙酰基天门冬氨酸(NAA)、胆碱复合物(Cho)与肌酸复合物(Cr)含量.采用汉密尔顿抑郁量表(HAMD)于治疗前、治疗4周评估临床症状和疗效. 结果 (1)研究组治疗前左侧前额叶、左侧丘脑NAA/Cr值分别为1.51±0.34、1.36±0.29,治疗后分别升高至1.71±0.42、1.54±0.34,差异有统计学意义(P＜0.05).对照组双侧前额叶、双侧丘脑的NAA/Cr值、Cho/Cr值治疗前后差异均无统计学意义(P＞0.05).(2)研究组、对照组治疗前HAMD评分分别为32.3±8.8、31.8±8.5,治疗后降低为12.3±4.7、15.2±5.0,差异均有统计学意义(P＜0.05).研究组治疗前后的HAMD评分差值大于对照组,差异有统计学意义(P＜0.05).(3)治疗后,研究组显效率为80.6％(29/36)、治愈率为27.8％(10/36),对照组显效率为50.0％(17/34)、治愈率为5.9％(2/34),2组间显效率和治愈率的差异均有统计学意义(P＜0.05).(4)研究组盐酸文拉法辛缓释片平均治疗剂量为(136.6±28.4)mg/d、最大剂量为(175.0±35.6)mg/d;对照组平均治疗剂量为(162.4±32.2)mg/d、最大剂量为(216.2±40.3)mg/d;组间差异均有统计学意义(P＜0.05). 结论 10 Hz rTMS联合盐酸文拉法辛缓释片可以调节抑郁症患者前额叶和丘脑的神经生化代谢,进而改善抑郁症状,降低抗抑郁药物使用剂量.     

A proton magnetic resonance spectroscopic study in autism spectrum disorders: Amygdala and orbito-frontal cortex

We previously reported neural dysfunction in the anterior cingulate cortex and dorsolateral prefrontal cortex in autistic patients using proton magnetic resonance spectroscopy (¹H-MRS). In this investigation, we measured chemical metabolites in the left amygdala and the bilateral orbito-frontal cortex (OFC), which are the main components of the social brain. We also examined the association between these metabolic findings and social abilities in subjects with autism. The study group included 77 autistic patients (3–6 years old; mean age 4.1; 57 boys and 20 girls). The control subjects were 31 children (3–6 years old; mean age 4.0; 23 boys and 8 girls). Conventional proton MR spectra were obtained using the STEAM sequence with parameters of TR = 5 sec and TE = 15 msec by a 1.5-tesla clinical MRI system. We analyzed the concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr), and choline-containing compounds (Cho) using LCModel (Ver. 6.1). The concentrations of NAA in the left amygdala and the bilateral OFC in autistic patients were significantly decreased compared to those in the control group. In the autistic patients, the NAA concentrations in these regions correlated with their social quotient. These findings suggest the presence of neuronal dysfunction in the amygdala and OFC in autism. Dysfunction in the amygdala and OFC may contribute to the pathogenesis of autism.     

Usefulness of long-acting injectable risperidone during 12-month maintenance therapy of bipolar disorder

This study aimed to assess the safety, tolerability, efficacy, and compliance of a risperidone long-acting injection (RLAI) formulation for the maintenance treatment of stabilized bipolar patients. A prospective, open-label trial of RLAI was conducted for 12 months. Stable bipolar patients (n=11) were switched from their existing oral antipsychotic agents to RLAI, and injections were given every 2 weeks. The assessments were performed at baseline and at 6 and 12 months of treatment by using the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Severity of Illness (CGI-S) scale, 17-item Hamilton Rating Scale for Depression (HAM-D), Brief Psychiatric Rating Scale (BPRS), and Extrapyramidal Symptom Rating Scale (ESRS). The satisfaction levels of subjects were evaluated at the end of the study period using a 10-point visual analog scale. Ten patients (90.9%) completed the trial, and no significant changes were seen in the YMRS, HAM-D, and BPRS scores throughout the study. CGI-S and ESRS scores were significantly decreased from the baseline to the post-12-month treatment score. Relapses were not reported by any of the participants. This result indicates that RLAI may be beneficial in the maintenance therapy of stable bipolar patients; however, an adequately powered, randomized, placebo-controlled trial is necessary to draw a definite conclusion about the role of RLAI in the maintenance treatment of bipolar patients.     

A proton magnetic resonance spectroscopy study in schizoaffective disorder: Comparison of bipolar disorder and schziophrenia

The aim of this study was to compare schizoaffective disorder, bipolar disorder and schizophrenia based on (1)H-MRS metabolite values in dorsolateral prefrontal cortex and executive functions. The subjects comprised 15 patients with bipolar disorder type I (BD), 15 with schizophrenia (SCH), 15 with schizoaffective disorder (SAD) and 15 healthy controls. We performed proton magnetic resonance spectroscopy ((1)H-MRS) of the dorsolateral prefrontal cortex (DLPFC) bilaterally. Levels of N-acetyl aspartate (NAA), choline-containing compounds (Cho) and creatine-containing compounds (Cr) were measured in the DLPFC using (1)H-MRS. We administered the Wisconsin Card Sorting Test (WCST) and the Stroop Test (ST) to evaluate executive functions. The SAD, BD and SCH patients had lower levels of NAA than the control group. The SAD and BD patients had low levels of Cho compared to the control group. The left DLPFC Cr levels in all of the patient groups and the right DLPFC Cr levels in the BD and SAD groups were lower than in the control group. The levels of NAA Cho and Cr were not related to executive functions and attention performance. Cr level were related to attention processes, only in SCH. Our results indicate that NAA levels are reduced in schizoaffective disorder, bipolar disorder and schizophrenia, but the reduction in the levels of NAA is not a distinctive feature among these three illnesses. Schizoaffective and bipolar disorders have similar features related to the levels of compounds containing Cho and Cr. This similarity may be related to these illnesses both having an affective basis.     

Metabolic changes of prefrontal cerebral lobe ,white matter and cerebellum in patients with post-stroke depression A proton magnetic resonance spectroscopy study

BACKGROUND:Proton magnetic resonance spectroscopy(1H-MRS)non-invasively detects changes in chemical substances in the brain,which reflects the pathological metabolism.OBJECTIVE:To investigate changes in N-acetyl-aspartate(NAA),choline(Cho),creatine(Cr),and myoinositol(MI)in the gray and white matter of cerebral prefrontal lobe and cerebellum of patients with differential degrees of post-stroke depression(PSD)using 1H-MRS.DESIGN:A case control study.SETTING:The First Affiliated Hospital of the Dalian Medical University.PARTICIPANTS:A total of 38 patients with stroke(28 male and 10 female patients,aged 40 to 79 years)were selected from the Department of Neurology,1st Atfiliated Hospital,Dalian Medical University,from February to October in 2004.All subjects met the DSM-IV criteria for cerebrovascular disease and depression.The degree of depression was defined according to Hamilton criteria.38 patients with PSD were divided into two groups according to the time after ischemia,20 patients in the acute group with less than 10 days after ischemic attack(mild:16 patients,moderate/severe:4 patients)and 18 patients in the chronic group with more than 11 days after ischemic attack(mild:15 patients,moderate/severe:3 patients).Seventeen healthy volunteers with matching age from 41 to 80 years were examined as a control group.The study was approved by the Medical Ethics Committee of the University Medical Center Utrecht,and each participant signed an informed consent form.METHODS:Spectra were acquired by multi-voxel point-resolved spectroscopy(PRESS)sequence with GE signal.ST MP-di,localized in prefrontal cerebral lobe and cerebellum.Values of NAA,Cho,MI,and Cr ere compared between different graded PSD patients and control subjects with one-way analysis of variance in software SPSS11.5.MAIN OUTCOME MEASURES:Metabolite concentration in different brain regions of interest.Difference in metabolites between distinctly graded PSD patients and control subjects.Exclusion of age-effects on metabolites. RESULTS:Metabolite concentrations of different brain regions:A significant rise in the Cho/Cr ratio was detected in the acute and chronic group compared to the control group.The ratio change was more significant in the acute group(P＜0.05).There was no significant difference between these three groups for other metabolites detected by 1H-MRS in the right frontal white matter,bilateral frontal grey matter,and cerebellum(P＞0.05).Comparison of metabolite levels among differently graded PSD patients and control subjects:a significant increase in the Cho/Cr ratio was detected in the left frontal white matter compared to the control group(P＜0.05).There was no significant difference in age between patients in the stroke groups and the control group(P＞0.05),and similarly,there was no significant correlation between age and absolute or relative values in the control group(P＞0.05).CONCLUSION:Abnormalities of frontal lobe in PSD were located in the white matter.There was early abnormality of metabolic substance in PSD.     

Metabolic changes of prefrontal cerebral lobe, white matter and cerebellum in patients with post-stroke depression*☆ A proton magnetic resonance spectroscopy study

BACKGROUND： Proton magnetic resonance spectroscopy （IH-MRS） non-invasively detects changes in chemical substances in the brain, which reflects the pathological metabolism.
OBJECTIVE： To investigate changes in N-acetyl-aspartate （NAA）, choline （Cho）, creatine （Cr）, and myoinositol （MI） in the gray and white matter of cerebral prefrontal lobe and cerebellum of patients with differential degrees of post-stroke depression （PSD） using ^1H-MRS.
DESIGN： A case control study.
SETTING： The First Affiliated Hospital of the Dalian Medical University.
PARTICIPANTS： A total of 38 patients with stroke （28 male and l0 female patients, aged 40 to 79 years） were selected from the Department of Neurology, 1st Affiliated Hospital, Dalian Medical University, from February to October in 2004. All subjects met the DSM-IV criteria for cerebrovascular disease and depression. The degree of depression was defined according to Hamilton criteria. 38 patients with PSD were divided into two groups according to the time after ischemia, 20 patients in the acute group with less than 10 days after ischemic attack （mild： 16 patients, moderate/severe： 4 patients） and 18 patients in the chronic group with more than l l days after ischemic attack （mild： 15 patients, moderate/severe： 3 patients）. Seventeen healthy volunteers with matching age from 41 to 80 years were examined as a control group. The study was approved by the Medical Ethics Committee of the University Medical Center Utrecht, and each participant signed an informed consent form.
METHODS： Spectra were acquired by multi-voxel point-resolved spectroscopy （PRESS） sequence with GE signal.5T MR/i, localized in prefrontal cerebral lobe and cerebellum. Values of NAA, Cho, MI, and Cr ere compared between different graded PSD patients and control subjects with one-way analysis of variance in software SPSS 11.5.
MAIN OUTCOME MEASURES： Metabolite concentration in different brain regions of interest. Difference in metabolites b     

精神分裂症阳性症状与脑质子波谱及事件相关电位的相关性

目的:探讨阳性症状为主型精神分裂症患者前额叶和丘脑氢质子磁共振波谱(1H-MRS)与事件相关电位的相关性。方法:78例7d内未使用抗精神病药及影响脑内乙酰胆碱神经递质药阳性症状为主型精神分裂症患者(研究组)及56名正常对照(对照组)。研究组在入组24h内采用多体素1H-MRS检测前额叶和丘脑生化代谢物N-乙酰基天门冬氨酸(NAA)、胆碱复合物(Cho)与肌酸复合物(Cr),计算NAA/Cr和Cho/Cr值;同时检测事件相关电位P300(P300)和听觉诱发电位(AEP),并与对照组进行比较。结果:研究组NAA/Cr值左侧前额叶、左侧丘脑均低于对照组,差异有统计学意义[(1.40±0.35)vs(1.60±0.39),t=3.11,P<0.01;(1.48±0.33)vs(1.64±0.36),t=2.50,P<0.05]。研究组P300靶刺激P3(Cz、FPz)、非靶刺激NP3(Cz、FPz)与AEPP2(FPz)的潜伏期均高于对照组,靶刺激P3(Cz、FPz)、非靶刺激NP3(Cz、FPz)及AEPN1-P2(Cz、FPz)波幅均低于对照组,差异均有统计学意义(P<0.05或P<0.01)。研究组左侧前额叶NAA/Cr值与Cz点的P3潜伏期呈负相关(r=-0.32,P<0.05),与P3、N1-P2波幅呈正相关(r=0.32、0.34,P均<0.05);与FPz点P3、NP3、P2潜伏期呈负相关(r=-0.37、-0.40、-0.41,P均<0.01),与P3、NP3、N1-P2波幅呈正相关(r=0.33、0.33、0.35,P均<0.05)。结论:阳性症状为主型精神分裂症患者左侧前额叶NAA代谢失衡与认知功能损害有关,低水平的NAA浓度可能是认知功能损害的发病机制之一。     

Brainstem function in rapid eye movement sleep behavior disorder: the evaluation of brainstem function by proton MR spectroscopy (1H-MRS)

Brainstem function was evaluated by proton magnetic resonance (MR) spectroscopy (1H-MRS) in a 69-year-old man with idiopathic rapid eye movement (REM) sleep behavior disorder. An analysis of spectral peak area ratios revealed an increase in the choline/creatine ratio. This change suggests that brainstem neurons have functional impairment at the cell membrane level. Further, our results suggest that 1H-MRS may provide for non-invasive, metabolic evaluation of brainstem neuronal function in REM sleep behavior disorder and find application in the differentiation of secondary REM sleep behavior disorders with neurodegenerative disorders from idiopathic disorders.     

Altered chemical metabolites in the amygdala-hippocampus region contribute to autistic symptoms of autism spectrum disorders.

BACKGROUND: Although several previous studies have been conducted, the neural basis of autism spectrum disorder (ASD) is poorly understood. The objective of the present study was to determine whether individuals with ASD have altered brain chemical metabolites and whether such alterations are related to their autistic symptoms. METHODS: N-acetylaspartate (NAA)/creatine (Cr) and choline/Cr ratios in the right medial temporal lobe (MTL), medial prefrontal cortex, and cerebellar vermis were measured in 38 individuals with ASD (mean age = 12.9 years), including 12 with autism, 15 with Asperger's Disorder, and 11 with pervasive developmental disorder not otherwise specified (PDD-NOS), and 16 matched healthy control subjects (mean age = 11.5 years) with proton magnetic resonance spectroscopy. Autistic symptoms were assessed by the Childhood Autistic Rating Scale-Tokyo Version. RESULTS: There was a significant group difference for NAA/Cr ratio in the right MTL between the autism, Asperger's Disorder, PDD-NOS, and control groups (p < .001), and the autism group had a significantly lower NAA/Cr ratio compared with the PDD-NOS (p < .001) and control (p < .001) groups. In the ASD group, there was a significant negative correlation between NAA/Cr ratio in the right MTL and their Childhood Autistic Rating Scale-Tokyo Version total scores (r = -.44, p = .01) and subscales of emotional response (r = -.38, p = .02) and listening response (r = -.54, p = .001). CONCLUSIONS: The results of the present study suggest that subjects with ASD have abnormalities of neural integrity in the amygdala-hippocampus region that are related to their severity and social impairments.     

Cognitive impairment and in vivo metabolites in first-episode neuroleptic-naive and chronic medicated schizophrenic patients: a proton magnetic resonance spectroscopy study

Involvement of the prefrontal cortex in schizophrenia has been implicated by neuropsychological, as well as neuropathological and imaging studies. Reductions of N-acetylaspartate (NAA), an in vivo marker of neuronal integrity, have repeatedly been detected in the frontal lobes of patients with schizophrenia by proton magnetic resonance spectroscopy (1H-MRS). In chronic medicated patients, a positive correlation between NAA levels of the prefrontal cortex and cognitive functioning has been observed, but to date, there have been no studies in first-episode neuroleptic-naive patients. In this study, single-voxel 1H-MRS was used to investigate neuronal function of the dorsolateral prefrontal cortex in 15 first-episode and 20 chronic schizophrenic patients. Outcomes were compared to 20 age-matched healthy controls to assess the relationship between prefrontal metabolism and neuropsychological performance. Patients with chronic schizophrenia had significant reductions of NAA, glutamate/glutamine, and choline levels compared to first-episode patients and healthy controls. Furthermore, creatine and phosphocreatine were significantly reduced in both patient groups compared to healthy controls. In the neuropsychological tests, chronic schizophrenic patients performed significantly poorer in the Auditory Verbal Learning Task (AVLT) compared to first-episode patients. In both patient groups, NAA levels of the left frontal lobe significantly correlated with performances in verbal learning and memory. These results corroborate data from recent structural and spectroscopic imaging studies of the frontal lobes in schizophrenia, in which cortical gray matter reductions after onset of symptoms as well as reduced levels of NAA in chronic, but not in first-episode schizophrenic patients have been reported.     

Lithium effects on brain glutamatergic and GABAergic systems of healthy volunteers as measured by proton magnetic resonance spectroscopy

Lithium is a first-line medicinal treatment for acute bipolar disorder and is also used prophylactically in manic depressive illnesses; however, its mechanism of action is still largely unknown. Animal and human studies have suggested that lithium modulates glutamatergic and GABAergic neurotransmissions. The aim of this study is to investigate the effects of lithium on brain glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA) levels in healthy individuals using proton magnetic resonance spectroscopy (1H-MRS). In vivo 3 Tesla 1H-MRS was performed on the anterior cingulate cortex and bilateral basal ganglia initially and after two weeks of lithium administration on 8 healthy male subjects who had a mean age of 34.9 years. After two weeks of lithium administration, Gln significantly decreased in the left basal ganglia and showed a decreasing trend in the right basal ganglia. Additionally, Glu+Gln (Glx) significantly decreased in the right basal ganglia and showed a decreasing trend in the left basal ganglia. Glu did not significantly change in any of the three tested areas, and GABA exhibited no significant change after the lithium administration when measured in the anterior cingulate cortex and left basal ganglia. This study is the first to demonstrate that subchronic lithium treatment decreases Gln and Glx levels in the bilateral basal ganglia of healthy individuals. Our finding might suggest that the decrease of Glx levels is associated with the pharmacological actions of subchronic lithium treatment.     

癫痫复杂部分性发作患者认知功能与海马质子磁共振波谱改变相关性分析

目的 探讨癫痫复杂部分性发作(CPS)患者认知功能损害的特点以及磁共振波谱(MRS)检查与认知功能的相关性.方法 对45例癫痫CPS患者和16例健康对照组进行临床记忆量表、瑞文标准推理测验的测评,~1H-MRS检测双侧海马,比较2组间2项测验分值及~1H-MRS结果,并对记忆商、智商与海马~1H-MRS结果进行相关性分析.结果 CPS组多项量表分值、记忆商、智商明显低于对照组,差异有统计学意义(P<0.05),CPS组N-乙酰天门冬氨酸(NAA)及NAA/[胆碱(Cho)+肌酸(Cr)]明显低于对照组,Cr、Cho明显高于对照组,差异有统计学意义(P<0.05).CPS组记忆商、智商与NAA浓度、NAA/(Cho+Cr)均呈正相关(P<0.05),与Cho浓度呈负相关(P<0.05),与Cr浓度无明显相关性(P>0.05).结论 CPS患者存在短时记忆功能障碍和抽象思维、判断推理能力的下降,其认知功能障碍与海马NAA、Cho浓度及NAA/(Cho+Cr)的相关性表明~1H-MRS检查可成为早期发现CPS患者认知功能情况的一项重要检查,其与神经心理学测验联合应用可早期、准确地发现CPS患者的认知功能障碍.     

Systemic illness moderates the impact of N-acetyl cysteine in bipolar disorder

Objectives

Bipolar disorder (BD) is intricately associated with chronic clinical conditions. Medical comorbidity is not only more prevalent in mood disorders, but is associated with increased costs, cognitive impairment and, ultimately, premature mortality. Oxidative stress and inflammation may mediate part of this association. To further investigate the association between medical comorbidity status and clinical improvement with adjuvant N acetyl cysteine (NAC) in the context of a placebo-controlled trial.

Methods

Placebo-controlled randomized clinical trial assessing the effect of NAC over 24 weeks. Symptomatic and functional outcomes were collected over the study period. Medical comorbidities were self-reported, and we took special interest in cardiovascular and endocrine conditions. We evaluated change from baseline to endpoint and the interaction between change and reported medical comorbidities.

Results

Fifty-one percent of patients reported have a cardiovascular or endocrine comorbidity. Although not found for depressive symptoms or quality of life, a significant interaction between medical comorbidity and change scores was consistently found for all functional outcomes. This indicated an advantage of NAC over placebo in those with a clinical comorbidity.

Conclusion

Systemic illness moderated only the effect of NAC on functioning, not on depression. Demonstrating an improvement in functional outcomes with an agent that modulates redox and inflammatory pathways, this study lends empirical support to the idea that medical and psychiatric comorbidity are additive in contributing to allostatic states. One intriguing possibility is that comorbid clinical illness could be a marker for more severe oxidative stress states – and thus guide antioxidant use – in BD.     

Residual symptoms in bipolar disorder: the effect of the last episode after remission

In this study it is aimed to assess interepisode residual symptoms in remitted bipolar disorder patients with a hypothesis that the last episode recovered has implications on residual symptomatology. The study was carried out with 23 bipolar patients diagnosed as mania (BP-M) and 20 bipolar patients diagnosed as depression (BP-D) in their last episode, and with 22 healthy controls in a university hospital clinic. All patients were in remission for at least 6 months. In the assessment Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale (YMRS), Stroop Test, Auditory Verbal Learning Test (AVLT), increased latency positive-evoked potentials (P300), Global Assessment of Functioning Scale (GAF), and Social Functioning Scale (SFS) were used cross-sectionally. In affective symptomatology, the BP-M group had higher YMRS scores, and the BP-D group had higher HAM-D scores compared to the controls. P300 test results revealed low amplitude in the BP-D group. In the AVLT, verbal learning and delayed recall were significantly lower in the two bipolar groups. The Stroop tasks were not different in the groups. Concerning the SFS, social withdrawal was impaired in the two bipolar groups, whereas dependency-competency was impaired in the BP-M and employment/occupation was impaired in the BP-D group. As a conclusion, bipolar patients recovering from depressive episode may experience more impairment in daily functioning due to residual depressive symptoms and impairment of attention and memory.     

Brain lithium, N-acetyl aspartate and myo-inositol levels in older adults with bipolar disorder treated with lithium: a lithium-7 and proton magnetic resonance spectroscopy study

Objectives:  We investigated the relationship between brain lithium levels and the metabolites N -acetyl aspartate (NAA) and myo -inositol ( myo -Ino) in the anterior cingulate cortex of a group of older adults with bipolar disorder (BD).
Methods:  This cross-sectional assessment included nine subjects (six males and three females) with bipolar I disorder and currently treated with lithium, who were examined at McLean Hospital's Geriatric Psychiatry Research Program and Brain Imaging Center. The subjects' ages ranged from 56 to 85 years (66.0 ± 9.7 years) and all subjects had measurements of serum and brain lithium levels. Brain lithium levels were assessed using lithium magnetic resonance spectroscopy. All subjects also had proton magnetic resonance spectroscopy to obtain measurements of NAA and myo -Ino.
Results:  Brain lithium levels were associated with higher NAA levels [df = (1, 8), Β = 12.53, t  =   4.09, p < 0.005] and higher myo -Ino levels [df = (1, 7), F  =   16.81, p < 0.006]. There were no significant effects of serum lithium levels on any of the metabolites.
Conclusion:  Our findings of a relationship between higher brain lithium levels and elevated NAA levels in older adult subjects with BD may support previous evidence of lithium's neuroprotective, neurotrophic, and mitochondrial function-enhancing effects. Elevated myo -Ino related to elevated brain lithium levels may reflect increased inositol monophosphatase (IMPase) activity, which would lead to an increase in myo -Ino levels. This is the first study to demonstrate alterations in NAA and myo -Ino in a sample of older adults with BD treated with lithium.