Hippocampal 1H MRS in first-episode bipolar I patients

Based on earlier structural and functional neuroimaging studies, we specifically wanted to assess N-acetylaspartate (NAA), choline-containing compounds (CHO), and creatine+phosphocreatine (CRE) levels in brain hippocampus previously demonstrated to be involved in the pathophysiology of bipolar disorder which have not been evaluated in first-episode patients. Twelve patients meeting DSM-IV criteria for bipolar disorder who consecutively applied to our department and 12 healthy controls were studied. The patients and controls underwent proton magnetic resonance spectroscopy ((1)H MRS), and measures of NAA, CHO, and CRE in hippocampal regions were obtained. ANOVA revealed in the hippocampus a significant effect of diagnosis for NAA/CRE and for NAA/CHO but not for CHO/CRE. Post hoc analysis showed that patients had a significant bilateral reduction of NAA/CRE and of NAA/CHO. No significant correlation was found between hippocampus volume and ratio measures. Correlation analyses exhibited significant correlation between NAA values and the YMRS for both side of the hippocampus, but not any other clinical variables (age, age at onset, and duration of illness). In summary, hippocampal neuronal abnormalities seem to be present at the onset of bipolar I disorder. These data suggest that neuronal abnormalities in hippocampus may be associated with the severity of bipolar I disorder. As these data were obtained in patients in their first-episode (all the patients were manic), they cannot be explained by chronicity of illness or pharmacological treatment.     

Neurochemistry of the hippocampus in patients with obsessive–compulsive disorder

Aim:  To date, despite possible neuroanatomical importance, no magnetic resonance spectroscopy (MRS) study on hippocampus has been performed in obsessive–compulsive disorder (OCD). The purpose of the present study was therefore to compare hippocampal chemicals in patients with OCD with those in healthy subjects with no psychopathology.
Methods:  Eighteen patients meeting DSM-IV criteria for OCD and 18 healthy controls were studied. The patients and controls underwent proton magnetic resonance spectroscopy (¹H-MRS), and measures of N -acetyl-l-aspartate (NAA), choline (CHO), and creatine (CRE) in hippocampal regions were obtained.
Results:  Both NAA/CRE and NAA/CHO ratios in the hippocampus in patients with OCD were reduced relative to healthy controls. The anova showed a near-significant effect of diagnosis for NAA/CRE and a significant effect for NAA/CHO, but the anova did not show any significant effect even at a trend level for CHO/CRE. No main effect of hemisphere was found for any metabolite ratio.
Conclusions:  The presence of neuronal degeneration is suggested in OCD. Future longitudinal neuroimaging and neuropsychological studies with larger patient samples are warranted in order to confirm these preliminary findings to better characterize the relevance of neurochemical abnormalities in hippocampus in the pathophysiology of OCD.     

Hippocampal neurochemical pathology in patients at first episode of affective psychosis: a proton magnetic resonance spectroscopic imaging study

While several studies have suggested a relationship between the hippocampus and psychosis in schizophrenia, fewer studies have specifically investigated the presence of psychosis in mood disorders from a neurobiological perspective. Moreover, a limitation of these earlier studies is that the majority of them were performed in chronic patients. The present proton magnetic resonance spectroscopic imaging (1H-MRSI) study assessed neuronal integrity (as assessed with N-acetylaspartate, NAA) in the hippocampus of patients with a first episode of mood disorders with psychotic symptoms. We studied 17 patients and 17 healthy subjects matched for age and sex. Subjects underwent 1H-MRSI, and measures of NAA, choline-containing compounds (CHO), and creatine+phosphocreatine (CRE) in 11 brain regions were obtained, i.e. hippocampus (HIPPO), dorsolateral prefrontal cortex, superior temporal gyrus, inferior frontal gyrus, occipital cortex, anterior and posterior cingulate, centrum semiovale, prefrontal white matter, thalamus and putamen. NAA/CRE ratios in HIPPO of patients were significantly lower than in controls. Sporadic and non-hypothesis-driven results were found in occipital cortex and prefrontal white matter as a main effect of diagnosis, and in superior temporal gyrus as a hemisphere by diagnosis interaction. These results would not survive a Bonferroni correction for the number of ROIs. No correlations were found with the available demographic and clinical data. Therefore, hippocampal neuronal abnormalities are present at the onset of mood disorders with psychotic symptoms. These data suggest that neuronal abnormalities in HIPPO may be associated with psychosis in mood disorders. Since these data were obtained in patients at first episode, they cannot be explained by chronicity of illness or pharmacological treatment.     

Neurochemical pathology in hippocampus in euthymic patients with bipolar I disorder

Objective: Subcortical regions such as hippocampus, thalamus and ventral putamen are assumed to be involved in the pathophysiology of mood regulation. Disturbed hippocampal neuronal function indicated by reduced N‐acetyl‐aspartate (NAA) levels in bipolar patients was shown by several studies. Results in thalamus and putamen are inconsistent. Method: N‐acetyl‐aspartate, choline (Cho), creatine (Cr) and myo‐inositol (Ins) were measured in left hippocampus, left thalamus and left putamen using proton magnetic resonance spectroscopy in 13 euthymic patients with bipolar I disorder and 13 pairwise matched healthy control subjects. Metabolic ratios NAA/Cr, NAA/Cho, Cho/Cr and Ins/Cr were calculated. Results: Patients with bipolar I disorder demonstrated significantly reduced NAA/Cr in the left hippocampus compared with healthy control subjects. No alterations were found in thalamus or putamen. Conclusion: We hypothesize that this NAA/Cr reduction might reflect neuronal dysfunction in the left hippocampus in patients with bipolar disorder.     

双相抑郁患者前额叶及海马磁共振质子波谱成像研究

目的探讨双相抑郁患者前额叶及海马磁共振质子波谱(proton magnetic resonance spectroscopy,1H-MRS)的代谢物变化特点,为其神经生物学研究提供线索。方法应用磁共振质子波谱成像技术检测26例双相抑郁患者(患者组)和26例单相抑郁患者及13例健康志愿者(对照组)双侧前额叶白质、前扣带回皮质、海马N-乙酰天门冬氨酸(N-Acetylaspartate,NAA)、胆碱(choline,Cho)、肌酸(creatine,Cr)3种代谢物,以Cr为参照物,分别计算双侧NAA/Cr和Cho/Cr比值。采用SPSS 13.0进行统计处理。结果患者组左侧前额叶白质NAA/Cr(1.65±0.31)低于对照组(2.37±0.36),左侧前额叶白质Cho/Cr(1.35±0.27)低于对照组(1.65±0.21),差异有统计学意义(P<0.05);右侧前额叶白质NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组双侧前扣带回NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组双侧海马NAA/Cr、Cho/Cr值与正常对照组差异无统计学意义;患者组与单相抑郁组的双侧额叶白质、双侧前扣带回皮质、双侧海马NAA/Cr、Cho/Cr值差异均无统计学意义。结论双相抑郁患者可能存在左侧前额叶神经元功能下降和膜磷脂代谢异常,其代谢物特点存在偏侧化。     

Cortical neurochemistry in euthymic patients with bipolar I disorder

Objective. Prefrontal and anterior cingulate cortical regions are assumed to be involved in the pathophysiology of mood regulation. Reduced prefrontal and anterior cingulate function indicated by decreased N-acetyl-aspartate (NAA) levels in patients with bipolar disorder has been reported inconsistently. A positive correlation between lithium serum level and NAA concentrations has been found previously. The aim of this study was to re-investigate prefrontal and anterior cingulate neurochemistry in a sample of euthymic patients with bipolar I disorder. Methods. NAA, choline (Cho), creatine (Cr) and myo-inositol (Ins) in left dorsolateral prefrontal cortex and left anterior cingulate cortex were measured in 33 euthymic patients with bipolar I disorder and 29 healthy comparison subjects by using proton magnetic resonance spectroscopy ([¹H]MRS). Results. Metabolic ratios did not differ between patients with bipolar I disorder and comparison subjects in prefrontal and anterior cingulate cortex neither in the total sample nor in the pairwise matched sub-sample. We could not observe an association between lithium level and NAA ratios. Lithium treated patients demonstrated unchanged NAA or myo-inositol ratios compared to alternatively treated patients. Conclusion. In contrast to prior findings, we could not observe any metabolic alterations in euthymic patients with bipolar disorder.     

Neurochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: a systematic review of the in vivo proton magnetic resonance spectroscopy findings

OBJECTIVE: To perform systematic analysis of current proton magnetic resonance spectroscopy ((1)H MRS) findings in bipolar disorder (BD). METHOD: We grouped the (1)H MRS studies documenting data on the metabolites of N-acetylaspartate (NAA), Choline (Cho), myo-inositol (mI), Glutamate (Glu)/Glutamine (Gln) and Creatine (Cr) separately, for each of the euthymic, manic, depressed adult and child/adolescent bipolar patients. RESULTS: For NAA resonance, 22 studies involving 328 adult bipolar and 349 control subjects were identified. NAA levels were lower in euthymic bipolar patients in the frontal lobe structures and hippocampus. Lithium seems to have an increasing effect on NAA in those brain regions. Available data in children indicates lower NAA levels in euthymic bipolar patients in dorsolateral prefrontal cortex (DLPFC) and cerebellar vermis. Existing data over 25 studies on 366 adult bipolar and 393 control subjects, although inconsistent, may suggest higher Cho/Cr ratios in the basal ganglia (BG) of euthymic bipolar patients. The metabolite mI seems to be increased both in euthymic and manic bipolar children, while most of the available data does not support such alteration in adults. Glu/Gln levels in adult bipolar patients were higher in all mood states compared to controls. Limited data in children supports such an alteration only in the euthymic state. CONCLUSION: The studies reviewed in this paper suggest regional abnormalities of NAA, Cho and Glu/Gln in BD, with the DLPFC, prefrontal and anterior cingulate cortices, hippocampus, and BG being specifically implicated. Systematic analysis of (1)H MRS findings so far helps to define future strategies in this field for delineation of actual neurochemical framework in BD.     

Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder.

BACKGROUND: N-acetyl aspartate (NAA) is an amino acid present in high concentrations in neurons and is thus a putative neuronal marker. In vivo proton magnetic resonance spectroscopy ((1)H MRS) studies have shown lower NAA concentrations in patients with various neurodegenerative disorders, suggesting decreased neuronal number, size, or function. Dorsolateral prefrontal (DLPF) NAA has not been extensively assessed in bipolar disorder patients, but it could be decreased in view of consistent reports of decreased DLPF cerebral blood flow and metabolism in mood disorders. We measured DLPF NAA in patients with bipolar disorder and healthy control subjects using in vivo (1)H MRS. METHODS: We obtained ratios of NAA, choline, and myoinositol (mI) to creatine-phosphocreatine (Cr-PCr) in bilateral DLPF 8-mL voxels of 20 bipolar patients (10 Bipolar I, 10 Bipolar II) and 20 age- and gender-matched healthy control subjects using (1)H MRS. RESULTS: DLPF NAA/Cr-PCr ratios were lower on the right hemisphere (p<.03) and the left hemisphere (p<.003) in bipolar disorder patients compared with healthy control subjects. CONCLUSIONS: These preliminary data suggest that bipolar disorder patients have decreased DLPF NAA/Cr-PCr. This finding could represent decreased neuronal density or neuronal dysfunction in the DLPF region.     

Proton magnetic resonance spectroscopy of the frontal lobe and cerebellar vermis in children with a mood disorder and a familial risk for bipolar disorders

OBJECTIVE: Few studies have examined the neurochemical abnormalities that might be associated with pediatric bipolar disorder. The aim of this study was to use magnetic resonance spectroscopy to evaluate several brain regions implicated in bipolar disorder in children with a mood disorder and a familial risk for bipolar disorder. We hypothesized that these children would exhibit neurochemical differences compared with healthy children of parents without a psychiatric disorder. Specifically, decreased N-acetylaspartate (NAA) and creatine and phosphocreatine (Cr) of the prefrontal cortex and cerebellar vermis would reflect impairments in neuronal function and cellular metabolism, and elevated myo-inositol (mI) would reflect impaired phosphoinositide metabolism, potentially representing early markers of neurophysiologic changes that might underlie the development of bipolar disorder. METHODS: Children with a mood disorder and at least one parent with bipolar disorder (n = 9) and healthy children (n = 10) group matched for age (8-12 years), race, sex, education, and Tanner stage were evaluated using the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia. Proton magnetic resonance spectroscopy was acquired using 8-cc volumes within the frontal cortex, frontal white matter, and the cerebellar vermis. Metabolite ratios (NAA/Cr, cholines (Cho)/Cr, mI/Cr, NAA/Cho, NAA/mI, and Cho/mI) and concentrations (NAA, Cr, Cho, and mI) were calculated and compared between groups. RESULTS: The trend in concentration levels of NAA and Cr was approximately 8% lower for children with a mood disorder than healthy children within the cerebellar vermis. The frontal cortex in children with a mood disorder revealed elevated mI concentration levels, approximately 16% increased, compared with healthy children. CONCLUSIONS: Similar to findings in adults with bipolar disorders, neurochemical abnormalities within the frontal cortex and the cerebellar vermis were present in this preliminary comparison of children with a mood disorder and a familial risk for bipolar disorder. Larger sample sizes are needed to replicate these findings.     

Temporal change in N-acetyl-aspartate concentrations in adolescents with bipolar depression treated with lithium

OBJECTIVE: This proton magnetic resonance spectroscopy (1H MRS) study identified the in vivo effects of lithium on N-acetyl-aspartate (NAA) concentrations in adolescent bipolar depression. METHOD: Twenty eight adolescents with bipolar I disorder in a depressive episode received open-label lithium 30 mg/kg, adjusted to achieve serum levels of 1.0-1.2 mEq/L. Medial ventral and ventral lateral prefrontal NAA concentrations were measured at baseline, day 7, and day 42 of treatment. Temporal changes in NAA concentrations were analyzed and effect sizes (Cohen's d) were calculated. RESULTS: Medial ventral prefrontal NAA concentrations decreased over time (p = 0.03), with day-42 concentrations significantly lower than baseline concentrations (p = 0.01, d = 0.7). No significant time effects on NAA concentrations were observed in the left (p = 0.2) or right ventral lateral (p = 0.3) prefrontal cortices. CONCLUSIONS: In contrast with prior studies of bipolar adults, this study observes that ventral prefrontal NAA concentrations do not significantly increase from baseline following lithium treatment in adolescent bipolar depression. The results should be viewed in the context of the study's limitations, including the lack of a matched healthy control group. Additional longitudinal magnetic resonance imaging studies are warranted to understand better the role of NAA in the pathophysiology of bipolar disorder and neurochemical mechanisms by which lithium stabilizes mood.