Proton magnetic resonance spectroscopy investigation of the right frontal lobe in children with attention-deficit/hyperactivity disorder

OBJECTIVE: To investigate neurometabolite concentrations in right prefrontal white matter in children with attention-deficit/hyperactivity disorder (ADHD) and relations of neurometabolites with attention skill and frontal anatomy. METHOD: Single voxel proton magnetic resonance spectroscopy ( H-MRS), quantitative morphometric analysis of left and right dorsolateral frontal volumes, and assessment of attentional problems with the Conners Continuous Performance Test were undertaken in 23 children (17 male) with ADHD (with no comorbid learning disabilities) and 24 matched controls (16 male). RESULTS: No overall group differences were found for any neurometabolite. However, a group by sex interaction was noted for -acetylaspartate, such that girls with ADHD had especially low concentrations. Morphological analyses revealed smaller right (but not left) dorsolateral volumes in children with ADHD, and in the ADHD group this volume correlated with neurometabolite concentrations. In the ADHD group Continuous Performance Test performance was related to both dorsolateral volume and the creatine-phosphocreatine peak from H-MRS. CONCLUSIONS: These results add to a growing body of evidence suggesting sex-specific neurobiological differences in ADHD and draw attention to relationships between neurochemistry, neuroanatomy, and performance in children with ADHD. Study limitations include small sample size and clinical heterogeneity among the children with ADHD.     

Proton magnetic resonance spectroscopy of bipolar disorder versus intermittent explosive disorder in children and adolescents

OBJECTIVE: The diagnosis of bipolar disorder in juveniles is controversial. This study was designed to compare proton magnetic resonance spectroscopy ((1)H MRS) in patients with bipolar disorder or intermittent explosive disorder, two groups with symptomatic overlap but categorical distinction. Children with intermittent explosive disorder designate patients whose illness clinically resembles pediatric bipolar disorder but does not satisfy DSM-IV criteria for mania. Based on the authors' previous report of higher levels of (1)H MRS cingulate myo-inositol/creatine in youngsters with bipolar disorder than in normal comparison subjects, they hypothesized that patients with bipolar disorder would have higher cingulate myo-inositol/creatine-phosphocreatine measurements than patients with intermittent explosive disorder and normal comparison subjects. METHOD: Myo-inositol levels were measured with a 2x2x2 cm(3) voxel placed in the anterior cingulate for acquisition of (1)H MRS in 10 patients with bipolar disorder, 10 patients with intermittent explosive disorder, and 13 normal comparison subjects. N-Acetylaspartate, choline moieties, creatine-phosphocreatine, and glutamate-glutamine metabolite levels were also measured. RESULTS: The patients with bipolar disorder showed significantly higher anterior cingulate myo-inositol/creatine-phosphocreatine and myo-inositol (mmol/liter) levels than the patients with intermittent explosive disorder and the normal comparison subjects. No significant differences were found across groups for myo-inositol or other metabolites in the occipital cortex. CONCLUSIONS: These data provide evidence that differences in the concentration of myo-inositol (mmol/liter) in the anterior cingulate cortex in (1)H MRS may differentiate these two populations. Follow-up studies involving larger samples may conclusively estimate the biological specificity between pediatric bipolar disorder and other disorders, which overlap clinically.     

Proton magnetic resonance spectroscopy in children with temporal lobe epilepsy

We performed proton magnetic resonance spectroscopy of the mesial temporal regions in 20 children with intractable temporal lobe epilepsy and compared results with those from 13 normal subjects. Abnormalities of the ratio of N-acetylaspartate to choline plus creatine (NAAI[Cho+Cr]) were seen in 15 patients (75%). The ratio NAA/(Cho+Cr) was correctly lateralizing in 55% and incorrectly lateralizing in none. Bilateral abnormalities were seen in 45%. Overall there was a unilateral decrease in N-acetylaspartate on the side ipsilateral to the seizure focus (mean 19% decrease vs normals, with 5% decrease on the contralateral side), suggesting neuronal loss or dysfunction. There was also a bilateral increase in creatine and choline (mean l8%), consistent with reactive astrocytosis. We conclude that proton magnetic resonance spectroscopy can contribute to lateralization of the seizure focus, and by detection of bilateral abnormalities, can contribute to the understanding of the underlying pathophysiology in temporal lobe epilepsy.     

伴有自杀意念的双相情感障碍患者前额叶 磁共振波谱研究

目的 借助氢质子磁共振波谱检测手段探讨双相情感障碍患者自杀意念与前额叶各代谢 物之间的关系。方法 2017 年 4 月至 2019 年 8 月收集新疆维吾尔自治区人民医院临床心理科 21 例 1 个 月内未经治疗的双相情感障碍患者,按有无自杀意念分为有自杀意念组（12 例）与无自杀意念组（9 例）, 应用氢质子磁共振波谱技术分别检测两组左右侧前额叶 N- 乙酰天门冬氨酸 / 肌酸（NAA/Cr）、胆碱 / 肌 酸（Cho/Cr）、谷氨酸和谷氨酰胺复合物 / 肌酸（Glx/Cr）、肌醇 / 肌酸（mI/Cr）的比值。结果 有自杀意念的 双相情感障碍患者组右侧前额叶 mI/Cr 值高于无自杀意念的双相情感障碍患者组,差异有统计学意义 （P＜ 0.05）;两组在左右侧前额叶 NAA/Cr 值、Cho/Cr 值、Glx/Cr 值及左侧前额叶 mI/Cr 值的比较中差异均 无统计学意义（P＞ 0.05）;有自杀意念的双相情感障碍患者组左侧前额叶 mI/Cr 值与发病年龄呈正相关 （r=0.661,P＜ 0.05）。结论 有自杀意念的双相情感障碍患者右侧前额叶肌醇代谢水平增高;有自杀意 念的双相情感障碍患者发病年龄越大,左侧前额叶肌醇代谢水平就会越高     

Proton magnetic resonance spectroscopy of the lenticular nuclei in bipolar I affective disorder

Proton magnetic resonance spectroscopy (1H-NMS) was used to examine the ratio of choline-containing compound (Cho) to creatine (Cr) in the basal ganglia. Subjects comprised 10 bipolar I affective disorder patients and 10 healthy control subjects. No significant difference was found in the Cho/Cr, N-acetyl-aspartate (NAA)/Cr, or NAA/Cho ratios between bipolar patients and control subjects. Within the bipolar group, negative correlations emerged between the NAA/Cr ratio in the right lenticular nuclei and both age at onset and age at the time of study. The results suggest that a late onset of illness and older age are associated with neuronal cell loss in the right lenticular nuclei in bipolar patients.     

Proton magnetic resonance spectroscopic imaging in patients with frontal lobe epilepsy

Proton magnetic resonance spectroscopic imaging (¹H MRSI) has demonstrated decreased N-acetyl compounds (NA) in the epileptogenic hippocampus in patients with temporal lobe epilepsy. We studied 8 patients with frontal lobe epilepsy and found mean NA/creatine (Cr) in the epileptogenic frontal lobe decreased by 27% compared with that of the contralateral homologous region (1.81 ±0.36 vs 2.49 ± 0.60, p < 0.008). In every patient, NA/Cr was decreased in the epileptogenic region by at least 5%. These findings suggest that ¹H MRSI may be useful in the presurgical evaluation of patients with frontal lobe epilepsy.     

Proton magnetic resonance spectroscopy in youth with severe mood dysregulation

Increasing numbers of youth are presenting for psychiatric evaluation with markedly irritable mood plus "hyperarousal" symptoms. Diagnostically homeless in current nosology, the syndrome (as well as its underlying neurobiology) is little understood. To address this problem, we conducted an exploratory proton magnetic resonance spectroscopy (MRS) study in a large sample of youth with chronic, functionally disabling irritability accompanied by hyperarousal, a clinical syndrome known as "severe mood dysregulation" (SMD), which may represent a broad phenotype of pediatric bipolar disorder. Medication-free SMD youth (N=36) and controls (N=48) underwent 1.5 Tesla MRS in four regions of interest. The following three neurometabolites, relative to creatine (Cr), were quantified with LCModel Software: (a) myo-inositol (mI), a marker of intra-cellular second messengers linked to the neurobiology of bipolar disorder; (b) glutamate/glutamine (GLX), a marker of the major excitatory neurotransmitter glutamate; and (c) N-acetyl aspartate (NAA), a marker of neuronal energetics. SMD subjects had significantly lower temporal mI/Cr versus controls. However, this difference did not survive correction for multiple comparisons. Given studies implicating mI in lithium's action in BD adults and youth, further work is necessary to determine potential therapeutic implications of our present finding and how SMD youth differ pathophysiologically from those with strictly defined BD.     

Proton magnetic resonance spectroscopy in youth with severe mood dysregulation

Increasing numbers of youth are presenting for psychiatric evaluation with markedly irritable mood plus “hyperarousal” symptoms. Diagnostically homeless in current nosology, the syndrome (as well as its underlying neurobiology) is little understood. To address this problem, we conducted an exploratory proton magnetic resonance spectroscopy (MRS) study in a large sample of youth with chronic, functionally disabling irritability accompanied by hyperarousal, a clinical syndrome known as “severe mood dysregulation” (SMD), which may represent a broad phenotype of pediatric bipolar disorder. Medication-free SMD youth (N = 36) and controls (N = 48) underwent 1.5 Tesla MRS in four regions of interest. The following three neurometabolites, relative to creatine (Cr), were quantified with LCModel Software: (a) myo-inositol (mI), a marker of intra-cellular second messengers linked to the neurobiology of bipolar disorder; (b) glutamate/glutamine (GLX), a marker of the major excitatory neurotransmitter glutamate; and (c) N-acetyl aspartate (NAA), a marker of neuronal energetics. SMD subjects had significantly lower temporal mI/Cr versus controls. However, this difference did not survive correction for multiple comparisons. Given studies implicating mI in lithium's action in BD adults and youth, further work is necessary to determine potential therapeutic implications of our present finding and how SMD youth differ pathophysiologically from those with strictly defined BD.     

Review of magnetic resonance imaging and spectroscopy studies in children with bipolar disorder

Pediatric bipolar disorder is a serious condition that affects a child's ability to function normally during important developmental stages. Pediatric bipolar disorder often presents with a different symptom complex than adult-onset bipolar disorder, including higher rates of irritability and rapid cycling. Due to these differences, it is important to understand the neural substrates of the disease as it presents in children, especially when compared with adults. Understanding the brain abnormalities associated with pediatric bipolar disorder may provide much needed markers useful in diagnosing childhood-onset bipolar disorder, give insight into the neurobiological etiology of the disorder and lead to more effective treatments. Currently, there has been little neuroimaging research into pediatric bipolar disorder, specifically with regards to brain function. This review summarizes the neurobiological research that has been conducted on childhood- and adolescent-onset bipolar disorder using magnetic resonance technology. Future directions of research needed in this area also are discussed in the context of the existing literature.     

Association of rapid mood switching with panic disorder and familial panic risk in familial bipolar disorder

OBJECTIVE: Comorbid bipolar and panic disorders aggregate in families. A phenotypic trait shared by both disorders is the sudden shift in affect observed in panic attacks and some rapid cycling states. The authors investigated whether comorbidity of bipolar disorder and panic disorder is associated with rapid mood switching in families with a high rate of bipolar disorder. METHOD: Six hundred six subjects with bipolar disorder from the NIMH Bipolar Disorder Genetics Initiative were included in the study. Logistic regression analysis was used to analyze rapid mood switching as a function of panic disorder diagnosis, sex, and familial risk for panic. RESULTS: Familial panic and the diagnosis of panic disorder in an individual subject increased the odds for rapid mood switching. The familial effect persisted when individuals with panic disorder were excluded from the analysis. CONCLUSIONS: Panic and rapid mood switching occurring together in familial bipolar disorder may define a useful subphenotype for future studies.     

Frontal lobe bioenergetic metabolism in depressed adolescents with bipolar disorder: a phosphorus-31 magnetic resonance spectroscopy study

Shi X‐F, Kondo DG, Sung Y‐H, Hellem TL, Fiedler KK, Jeong E‐K, Huber RS, Renshaw PF. Frontal lobe bioenergetic metabolism in depressed adolescents with bipolar disorder: a phosphorus‐31 magnetic resonance spectroscopy study. Bipolar Disord 2012: 14: 607–617. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: To compare the concentrations of high‐energy phosphorus metabolites associated with mitochondrial function in the frontal lobe of depressed adolescents with bipolar disorder (BD) and healthy controls (HC). Methods: We used in vivo phosphorus‐31 magnetic resonance spectroscopy (³¹P‐MRS) at 3 Tesla to measure phosphocreatine (PCr), beta‐nucleoside triphosphate (β‐NTP), inorganic phosphate (Pi), and other neurometabolites in the frontal lobe of eight unmedicated and six medicated adolescents with bipolar depression and 24 adolescent HCs. Results: Analysis of covariance, including age as a covariate, revealed differences in PCr (p = 0.037), Pi (p = 0.017), and PCr/Pi (p = 0.002) between participant groups. Percentage neurochemical differences were calculated with respect to mean metabolite concentrations in the HC group. Post‐hoc Tukey–Kramer analysis showed that unmedicated BD participants had decreased Pi compared with both HC (17%; p = 0.038) and medicated BD (24%; p = 0.022). The unmedicated BD group had increased PCr compared with medicated BD (11%; p = 0.032). The PCr/Pi ratio was increased in unmedicated BD compared with HC (24%; p = 0.013) and with medicated BD (39%; p = 0.002). No differences in β‐NTP or pH were observed. Conclusions: Our results support the view that frontal lobe mitochondrial function is altered in adolescent BD and may have implications for the use of Pi as a biomarker. These findings join volumetric studies of the amygdala, and proton MRS studies of n‐acetyl aspartate in pointing to potential differences in neurobiology between pediatric and adult BD.     

Proton magnetic resonance spectroscopy in brain white matter disorders

The advent of magnetic resonance imaging (MRI) has revolutionized the clinical approach to the evaluation of brain white matter disorders and has contributed significantly to expansion of the concept of these diseases. MRI is very sensitive at detecting white matter lesions, but conventional T1 and T2-weighted images do not provide specific pathological information about the lesions, and correlation between MRI lesion load and clinical disability is often weak. Proton magnetic resonance spectroscopy can provide chemical-pathological information of a given tissue invivo. The use of this MR technique in brain white matter disorders has shown to improve diagnostic classification and to provide surrogate measures useful for monitoring disease evolution and response to therapeutic intervention.The study was supported in part by grants from the Multiple Sclerosis Society of Canada and from the Progetto Sclerosi Multipla of the Istituto Superiore di Sanità, Rome, Italy.     

Proton magnetic resonance spectroscopy in subjects at risk for schizophrenia

We used proton magnetic resonance spectroscopy (1H MRS) to examine biochemical characteristics of the brain tissue in subjects at risk for schizophrenia. Nineteen participants fulfilling research criteria for an early (n=10) or a late (n=9) at-risk syndrome, 21 patients with full disease according to DSM IV and 31 healthy control subjects were included in the study. Single-voxel 1H MRS was performed in the left frontal lobe, the anterior cingulate gyrus and the left superior temporal lobe. Subjects were followed longitudinally to detect conversion to schizophrenia. We observed a significant reduction of the metabolic ratios NAA/Cr and NAA/Cho in the left frontal lobe and of NAA/Cr in the anterior cingulate gyrus in both at-risk groups and in the schizophrenic patients compared with healthy controls. Those at-risk subjects, who converted to schizophrenia within the observation period, had a higher Cho/Cr and a lower NAA/Cho ratio in the anterior cingulate gyrus compared with non-converters. NAA/Cr did not differ between converters and non-converters. Six at-risk subjects were taking antidepressants, two were taking antipsychotics. There was no difference in any metabolic ratio in any region between at-risk subjects with and without medication. We conclude that the reduction of the neuronal marker NAA in the left prefrontal lobe and the anterior cingulate gyrus may represent a vulnerability indicator for schizophrenia in at-risk subjects, while elevated Cho in the anterior cingulate gyrus may be a predictor for conversion from the prodromal state to the full disease.     

Proton magnetic resonance spectroscopy of lenticular nuclei in obsessive-compulsive disorder

Magnetic resonance spectroscopy (MRS) is a safe and non-invasive technique for the in vivo study of brain chemistry and metabolism. As such, it is highly applicable to the study of living brain tissue in psychiatric diseases. Several neuropathological and neuroimaging studies have suggested that abnormalities of the basal ganglia nuclei might be implicated in patients with obsessive-compulsive disorder (OCD). In the present study, we performed proton [1H]MRS of the lenticular nuclei in 12 patients with OCD and 12 healthy normal comparison subjects. The peaks of N-acetyl-aspartate (NAA), creatine (Cr), and choline-containing compounds (Cho) were measured. No differences between OCD patients and normal subjects were found in the NAA/Cr, Cho/Cr and NAA/Cho ratios. Our results suggest the normal viability of neuronal cells, as indicated by the quantification of NAA, Cr and Cho in the lenticular nuclei of patients with OCD.     

Neurochemical deficits in the cerebellar vermis in child offspring of parents with bipolar disorder

Singh MK, Spielman D, Libby A, Adams E, Acquaye T, Howe M, Kelley R, Reiss A, Chang KD. Neurochemical deficits in the cerebellar vermis in child offspring of parents with bipolar disorder.
Bipolar Disord 2011: 13: 189–197. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: We aimed to compare concentrations of N‐acetyl aspartate, myo‐inositol, and other neurometabolites in the cerebellar vermis of offspring at risk for bipolar disorder (BD) and healthy controls to examine whether changes in these neuronal metabolite concentrations occur in at‐risk offspring prior to the onset of mania. Methods: A total of 22 children and adolescents aged 9–17 years with a familial risk for bipolar I or II disorder [at‐risk offspring with non‐bipolar I disorder mood symptoms (AR)], and 25 healthy controls (HC) were examined using proton magnetic resonance spectroscopy at 3T to study metabolite concentrations in an 8‐cc voxel in the cerebellar vermis. Results: Decreased myo‐inositol and choline concentrations in the vermis were seen in the AR group compared to HC (p < 0.01). Conclusions: Decreased cellular metabolism and interference with second messenger pathways may be present in the cerebellar vermis in youth at risk for BD as evident by decreased myo‐inositol and choline concentrations in this region. These results may be limited by a cross‐sectional design, co‐occurring diagnoses, and medication exposure. Longitudinal studies are necessary to determine whether early neurochemical changes can predict the development of mania. Improved methods for identifying children with certain neurochemical vulnerabilities may inform preventive and early intervention strategies prior to the onset of mania.     

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。     

Rapid switching of mood in families with familial bipolar disorder

Objective:  Rapid switching of moods in bipolar disorder has been associated with early age at onset, panic comorbidity, and suicidality. This study aims to confirm these associations and investigate other potential correlates of rapid switching of mood using families from a multisite bipolar linkage study.
Methods:  The subjects were comprised of 1,143 probands and relatives with diagnosis of bipolar disorder. All subjects were interviewed directly with a standard diagnostic instrument, and all subjects who met criteria for bipolar disorder were asked if their moods had ever switched rapidly.
Results:  Individuals with rapid mood switching had significantly earlier age at onset (18 versus 21 years, p < 0.00001), higher comorbid anxiety (47% versus 26%, p < 0.00001) and substance use disorders (52% versus 42%, p = 0.0006), higher rate of violent behavior (6% versus 3%, p < 0.004), suicidal behavior (46% versus 31%, p < 0.00001), and nonsuicidal self-harm (13% versus 6%, p < 0.0002). Multiple logistic regression analysis found significant net effects on rapid mood switching for early emergence of symptoms [odds ratio (OR) = 0.62; 95% confidence interval (CI): 0.45–0.85]; anxiety comorbidity (OR = 2.31; 95% CI: 1.34–3.98); and hypersensitivity to antidepressants (OR = 2.05; 95% CI: 1.49–2.83) as the strongest predictors.
Conclusions:  This confirms earlier reports associating rapid switching with a more complex clinical course, in particular early emergence of bipolar symptomatology, antidepressant activation, and anxiety comorbidity. These results support a clinical differentiation of bipolar disorder into subtypes based on symptom stability.     

Proton magnetic resonance spectroscopy for the diagnosis and management of cerebral disorders.

The use of magnetism in medicine has a long and colorful history since its legendary discovery in the Western world by the shepherd Magnes. More recent use of magnetism has centered on nuclear magnetic resonance. Magnetic resonance spectroscopy (MRS) provides chemical information on tissue metabolites. Both hydrogen 1 (1H) and phosphorus 31 resonances have been used to study brain tissue, but the magnetic resonance sensitivity for protons is far greater than it is for phosphorus. One of the most important contributions of 1H-MRS to clinical neurology is its ability to quantify neuronal loss and to demonstrate reversible neuronal damage. 1H-magnetic resonance spectroscopy has been found to be a useful research tool in elucidating the pathophysiology underlying certain diseases. This review focuses on the use of proton MRS to study various neurologic diseases, including epilepsy, multiple sclerosis, brain tumors, human immunodeficiency virus 1-associated neurologic disorders, as well as cerebrovascular, neurodegenerative, and metabolic diseases. It highlights the contributions of 1H-MRS to the diagnosis and the monitoring of these neurologic diseases that make it a useful adjunct in patient management.     

31P magnetic resonance spectroscopy in the frontal lobe of major depressed patients

Most research with ³¹P-magnetic resonance spectroscopy (³¹P-MRS) in affective disorders has been done in the field of bipolar disturbances. Reduced frontal and temporal lobe phosphomonoester (PME) concentrations were measured in the euthymic state, whereas increased values were found in the depressed state. In bipolar-II patients reduced phosphocreatine (PCr) concentrations were reported in the euthymic, depressed, and manic state. The aim of the present study was to explore whether PME and PCr were also altered in the frontal lobe of major depressed, unipolar patients. Therefore, we used ³¹P-MRS to investigate the relative phospholipid and high-energy phosphate concentrations in the frontal lobe of 14 unipolar patients, mostly medicated, and 8 age-matched controls. We found increased PME and decreased ATP values. Other ³¹P-MRS parameters were not different in both groups. Phosphomonoester percentages correlated negatively with the degree of depression. Thus, the main alterations found in bipolar depressed patients could also be demonstrated in unipolar depressed patients. The results are discussed with regard to disturbed phospholipid and intracellular high-energy phosphate metabolism in depressed patients. Received: 2 December 1997 / Accepted: 14 July 1998