Increased white matter connectivity in euthymic bipolar patients: diffusion tensor tractography between the subgenual cingulate and the amygdalo-hippocampal complex

Bipolar disorder has been associated with anatomical as well as functional abnormalities in a brain network that mediates normal and impaired emotion regulation. Previous brain imaging studies have highlighted the subgenual cingulate (SC) and the amygdalo-hippocampal (AH) complex as core regions of this network. Thus we investigated white matter (WM) fiber tracts between the SC and the AH region, the uncinate fasciculus, as well as between two control regions (pons and cerebellum), using diffusion tensor imaging tractography in 16 euthymic bipolar patients (BP) and 16 sex-, age- and handedness-matched controls. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the reconstructed fiber bundle and the number of virtual reconstructed fibers were compared between groups. The tractography results revealed a significantly increased number of reconstructed fibers between the left SC and left AH in BP as compared to healthy controls. FA and ADC of the reconstructed fiber tract did not differ significantly between the groups. Furthermore, no significant group differences were observed neither for reconstructed fiber tracts between the right SC and right AH nor between the control regions. The present results suggest an altered WM pathway between the left SC and AH region and thus extend previous findings of anatomical and functional modifications in these structures in BP.     

Cognitive functioning in euthymic bipolar I and bipolar II patients

Objective: There is growing evidence of cognitive impairment as a trait factor in bipolar disorder. The generalizability of this finding is limited because previous studies have either focussed exclusively on bipolar I disorder or have analysed mixed patient groups. Thus, it is still largely unknown whether bipolar II patients perform differently from bipolar I patients on measures of cognitive functioning. Methodology: A total of 65 patients with bipolar I disorder, 38 with bipolar II disorder, and 62 healthy controls participated in the study. Patients had to be euthymic for at least one month. Clinical and demographic variables were collected in a clinical interview and with the Structured Clinical Interview for DSM‐IV. Cognitive functioning was assessed using a neuropsychological battery. Univariate and multivariate analyses of variance were conducted for analyzing possible differences between the groups. Results: The multivariate analysis of covariance (MANCOVA) indicated overall differences in neuropsychological performance between the three groups (Pillai Spur: F 1.96, p = 0.003). Post hoc comparisons revealed that patients with bipolar I disorder showed significantly lower scores in psychomotor speed, working memory, verbal learning, delayed memory, and executive functions than healthy controls. Patients with bipolar II disorder showed significant deficits in psychomotor speed, working memory, visual/constructional abilities, and executive functions compared to controls, but not on verbal learning and delayed memory. The two patient groups did not differ significantly from each other on any domain tested. Conclusion: These results support a similar pattern of cognitive deficits in both subtypes of bipolar disorder.     

白质纤维束示踪成像技术在高血压脑出血中的初步应用

目的探讨白质纤维束示踪成像技术在高血压脑出血中的临床应用价值。方法对我院8例急性期情况稳定的高血压脑出血患者进行磁共振弥散张量成像,应用日本东京大学的Volume-one1.72和Diffusion Ten-sor Visualizer(dTV)软件进行三维白质纤维束示踪成像,观察以内囊为主的白质纤维束的压迫、推移、破坏情况。结果8例患者均行磁共振弥散张量成像并行内囊白质纤维束示踪成像,可清楚看到内囊白质纤维束受血肿压迫、推移、破坏情况,由患侧内囊追踪到的相对纤维束条目数少于健侧内囊(P<0.005)。结论白质纤维束示踪成像技术可以清楚显示高血压脑出血后内囊白质纤维束的受累情况。     

Microstructural white matter changes in euthymic bipolar patients: a whole-brain diffusion tensor imaging study

Objectives:  Brain structures of a distributed ventral-limbic and dorsal brain network have been associated with altered mood states and emotion regulation in affective disorders. So far, diffusion tensor imaging studies in bipolar patients have focused on frontal/prefrontal brain regions and found alterations in white matter integrity in manic, depressed, and euthymic bipolar patients, observed as changes in fractional anisotropy and mean diffusivity. To extend previous findings, we investigated whole-brain modifications in white matter integrity in euthymic bipolar patients with minimal manic and depressive symptoms.
Methods:  Twenty-two patients with a DSM-IV-TR diagnosis of bipolar I and II disorder in remission, with no lifetime or present comorbidities of substance abuse, and 21 sex- and age-matched healthy controls underwent diffusion tensor imaging with diffusion gradients applied along 41 directions. Fractional anisotropy and mean diffusivity group differences were explored using two voxel-based, whole-brain analyses that differ in their normalization approaches.
Results:  Fractional anisotropy was significantly increased in bipolar patients relative to healthy controls in medial frontal, precentral, inferior parietal, and occipital white matter. No group differences in mean diffusivity were found.
Conclusions:  The result of increased fractional anisotropy in euthymic bipolar patients in the present study suggests increased directional coherence of white matter fibers in bipolar patients during remission.     

White matter lesions in euthymic patients with bipolar disorder

Objective: We aimed to quantify both load and regional distributions of hyperintensities on magnetic resonance imaging (MRI) in prospectively verified euthymic bipolar patients and matched controls. Method: Cerebral hyperintensities on T2, proton density and fluid‐attenuated inversion recovery (FLAIR) MRI were compared between 48 bipolar and 47 control subjects using semi‐quantitative rating scales. Results: Bipolar subjects had more severe frontal deep white matter lesions (DWML). Hyperintensity load was independent of age in bipolar patients but increased with age in controls. Global prevalence and severity of hyperintensities did not differ between groups. Exploratory analysis showed DWML in excess in the left hemisphere in bipolar subjects but not in controls. Conclusion: Findings are consistent with clinical, particularly some neurocognitive, features of bipolar disorder and implicate fronto‐subcortical circuits in its neurobiology. They more probably reflect a trait abnormality or illness scar rather than a mood state‐dependent finding. Processes other than ageing and vascular factors may underlie their development.     

Deep white matter hyperintensities in patients with bipolar depression,unipolar depression and age-matched control subjects

Objective:  Hyperintensities in the white matter of the brain (DWH) and in the periventricular area (PVH) seen on magnetic resonance imaging (MRI) have been reported to be more frequent in patients with bipolar disorder (BP) than in normal subjects. To examine this further we compared MRI of patients with BP with age-matched patients with major depressive disorder (unipolar depression, UP) and healthy control subjects.
Methods:  T2 weighted axial and coronal brain MRI scans were obtained from 13 patients in the depressive phase of BP, 11 with current UP and 19 age-matched control subjects. The degree of DWH and PVH present in each scan was determined using a standardized scoring method.
Results:  The PVH ratings were similar in the three groups of subjects. However, proportionately more BP patients had higher DWH scores than either UP patients or controls. Although this difference did attain statistical significant, a main effect of age was noted. Further, subjects over the age of 50 were under-represented in the UP group.
Conclusions:  Notwithstanding the small total sample size and relative lack of older subjects in the UP group, the fact that almost twice as many BP patients showed more severe DWH suggests that patients with BP may be more vulnerable to develop these changes than UP patients and healthy controls.     

Total white matter hyperintensity volume in bipolar disorder patients and their healthy relatives

Tighe SK, Reading SA, Rivkin P, Caffo B, Schweizer B, Pearlson G, Potash JB, DePaulo J Raymond, Bassett SS.
Total white matter hyperintensity volume in bipolar disorder patients and their healthy relatives.
Bipolar Disord 2012: 14: 888–893. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: White matter hyperintensities (WMH) are more common in subjects with bipolar disorder (BP) than in healthy subjects (HS). Few studies have examined the effect of the diagnostic type of bipolar illness on WMH burden, and none have approached this question through a direct measurement of the volume of affected white matter in relationship to familiality. In this pilot study, we utilized a volumetric measurement of WMH to investigate the relationship between the total volume of WMH and the familiality and type of BP. Methods: Forty‐five individuals with bipolar I disorder (BP‐I) with psychotic features, BP‐I without psychotic features, or bipolar II disorder (BP‐II), seven of their unaffected relatives, and 32 HS were recruited for participation. T‐2 weighted magnetic resonance imaging scans were obtained on all subjects, and the total volume of all WMH for each subject was measured in cubic centimeters. The significance of difference between groups was tested using ANOVA with post‐hoc adjustment for multiple comparisons. Further, we used logistic regression to test for trends between symptom load and total WMH volume. Results: The mean total volume of WMH in BP‐I patients with psychotic features was significantly higher (p < 0.05) than that of HS. Further, we observed a positive linear trend by familiality and type of affectedness when comparing mean total WMH volume of HS, unaffected family members, subjects with BP‐II, and BP‐I with and without a history of psychosis (p < 0.05). Conclusions: Based on a quantitative technique, WMH burden appears to be associated with familiality and type of BP. The significance of these findings remains to be fully elucidated.     

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.     

No change to grey and white matter volumes in bipolar I disorder patients

BACKGROUND: Structural brain imaging is assumed to be a key method to elucidate the underlying neuropathology of bipolar disorder. However, magnetic resonance imaging studies using region of interest analysis and voxel-based morphometry (VBM) revealed quite inconsistent findings. Hence, there is no clear evidence so far for core regions of cortical or subcortical structural abnormalities in bipolar disorder. The aim of this study was to investigate grey and white matter volumes in a large sample of patients with bipolar I disorder. METHODS: Thirty-five patients with bipolar I disorder and 32 healthy controls matched with respect to gender, handedness and education participated in the study. MRI scanning was performed and an optimized VBM analysis was conducted. RESULTS: We could not observe any significant differences of grey or white matter volumes between patients with bipolar disorder and healthy control subjects. Additional analyses did not reveal significant correlations between grey or white matter volume with number of manic or depressive episodes, duration of illness, existence of psychotic symptoms, and treatment with lithium or antipsychotics. CONCLUSIONS: With this VBM study we were not able to identify core regions of structural abnormalities in bipolar disorder.     

Neurocircuitry of emotion and cognition in alcoholism: contributions from white matter fiber tractography

Chronic alcoholism is characterized by impaired control over emotionally motivated actions towards alcohol use. Neuropathologically, it is associated with widespread brain structural compromise marked by gray matter shrinkage, ventricular enlargement, and white matter degradation. The extent to which cortical damage itself or cortical disconnection by white matter fiber pathway disruption contribute to deficits in emotion, cognition, and behavior can be investigated with in vivo structural neuroimaging and diffusion tensor imaging (DTI)-based quantitative fiber tracking. Tractography in alcoholism has revealed abnormalities in selective white matter fiber bundles involving limbic fiber tracts (fornix and cingulum) that connect cortico-limbic-striatal nodes of emotion and reward circuits. Studies documenting brain-behavior relationships support the role of alcoholism-related white matter fiber degradation as a substrate of clinical impairment. An understanding of the role of cortico-limbic fiber degradation in emotional dysregulation in alcoholism is now emerging.     

State-dependent microstructural white matter changes in bipolar I depression

Abnormalities in fronto-limbic-striatal white matter (WM) have been reported in bipolar disorder (BD), but results have been inconsistent across studies. Furthermore, there have been no detailed investigations as to whether acute mood states contribute to microstructural changes in WM tracts. In order to compare fiber density and structural integrity within WM tracts between BD depression and remission, whole-brain fractional anisotropy (FA) and mean diffusivity (MD) were assessed in 37 bipolar I disorder (BD-I) patients (16 depressed and 21 remitted), and 26 healthy individuals with diffusion tensor imaging. Significantly decreased FA and increased MD in bilateral prefronto-limbic-striatal white matter and right inferior fronto-occipital, superior and inferior longitudinal fasciculi were shown in all BD-I patients versus controls, as well as in depressed BD-I patients compared to both controls and remitted BD-I patients. Depressed BD-I patients also exhibited increased FA in the ventromedial prefrontal cortex. Remitted BD-I patients did not differ from controls in FA or MD. These findings suggest that BD-I depression may be associated with acute microstructural WM changes.     

Cognitive function in euthymic bipolar patients, stabilized schizophrenic patients, and healthy controls

Studies on cognitive function in bipolar disorder have led to contrasting results and few data are available on affected subjects during the euthymic phase. In the present study we investigated the cognitive function of a cohort of bipolar (n=40) and schizophrenic (n=66) patients compared to healthy controls (n=64). Patients were evaluated in the outpatient setting over at least 3 months using a computerized version of Wisconsin Card Sorting Test. Schizophrenic patients showed the worst performance while that of the bipolar patients was somewhere between schizophrenic and controls. A discriminant analysis was able to classify correctly 60.59% of the subjects (schizophrenics 48.5%, bipolars 40%; healthy controls 85. 9%). The scores of the Wisconsin Card Sorting Test were entered into a principal component analysis, which yielded a 2-factor solution. Even in that analysis bipolar patients showed intermediate features in comparison with the other groups. These data indicate that bipolar patients have subtle neurocognitive deficits even after the resolution of an affective disorder. As well as observing quantitative differences between groups, the results show different dimensions of cognitive performance within groups suggesting that the deficit of euthymic bipolars could be a dishomogeneous entity, probably more heterogeneous than that in schizophrenia. Studies administering a more complete neuropsychological battery could further clarify the nature and meaning of the cognitive deficits in schizophrenia and bipolar disorder.     

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.     

Cognitive function in euthymic bipolar I disorder

Recent reports have suggested the presence of persistent cognitive impairments in patients diagnosed with Bipolar Disorder even after prolonged euthymic phases. In this work, various domains of cognitive function were examined in asymptomatic patients diagnosed with Bipolar I Disorder (BDI) in comparison with healthy subjects. Fifteen otherwise healthy BDI patients with a prior history of psychosis during mania completed a neuropsychological testing battery after a prolonged asymptomatic remission. Their scores were compared to those of individually matched healthy subjects with unpaired two-tailed t-tests at P<0.01. Relationships between cognitive performance measures and clinical variables related to illness severity were also examined with Pearson correlations, P<0.05. We detected poorer performance on measures of verbal learning, executive functioning and motor coordination in BDI patients compared to control volunteers. Scores on tests of executive functioning were negatively correlated with the number of episodes of mania and depression. Social and occupational scores were also associated with a poorer performance on measures of verbal learning and executive function. Euthymic BDI patients, therefore, demonstrate reductions in specific cognitive domains even after prolonged asymptomatic phases. Some of these deficits appear to be associated with a more severe course of illness and poorer social and occupational functioning.     

基于弥散张量成像技术的双相障碍患者脑白质纤维束异常分析

目的探讨抑郁期双相障碍患者脑白质纤维束的变化。方法选取42例未用药双相障碍抑郁期患者(患者组)和年龄、性别及右利手与之相匹配的59名对照者(对照组)进行DTI检查,根据约翰霍普金斯大学人类白质纤维束图谱,将大脑白质组织分割为20条公认存在的粗大纤维束,应用PANDA软件计算每个被试者每条白质纤维束的4项平均弥散属性,采用非参数置换检验比较2组在20条白质纤维束上弥散指标的差异,将差异有统计学意义的脑白质纤维束弥散指标与临床指标进行Pearson相关分析。结果患者组左侧钩束各向异性分数(fractional anisotropy,FA)值低于对照组(0.40±0.01与0.41±0.01,P=0.001);胼胝体辐射线额部FA值低于对照组(0.36±0.02与0.38±0.02,P<0.001);左侧钩束径向弥散率(radial diffusivity,RD)值高于对照组(6.57×10^-4±2.41×10^-5与6.40×10^-4±2.42×10^-5,P=0.0017)。Pearson相关分析显示,2组弥散指标差异有统计学意义的白质纤维束与临床指标之间均无相关性。结论抑郁期双相障碍患者钩束及胼胝体辐射线额部存在脑白质完整性破坏。     

多发性硬化患者MRI扩散张量成像脑白质束示踪的三维仿真定量研究

目的 研究多发性硬化(MS)患者脑白质束示踪的三维仿真影像表现,评价其定量结果与残疾状态扩展评分(EDSS)的相关性. 方法 对28例MS患者(MS组)和28名健康自愿者(对照组)通过MRI扩散张量成像扫描进行脑白质束示踪,测量示踪纤维数和示踪纤维密度,并应用配对t检验比较两组间差异;对MS组脱髓鞘斑块、正常表现脑白质和对照组感兴趣区的ADC值和FA值进行方差分析,使用线性回归模型计算MS组脑白质束示踪的定量结果与EDSS评分的相关性. 结果 在MS组脑白质束示踪三维仿真图像中可直接观察到脑白质束的受损和减少.MS组的示踪纤维数(2220±100)和示踪纤维密度(0.75±0.04)明显低予对照组(2750±70、0.93±0.02),差异有统计学意义(P＜0.05).MS组脱髓鞘斑块、正常表现脑白质和对照组感兴趣区的ADC值依次下降,分别为(1.23 ±0.13)× 10-3 mm2/s、(0.76±0.09)× 10-3 mm2/s、(0.63 ±0.10)×10-3 mm2/s; FA值依次升高,分别为0.24±0.04、0.42±0.07、0.48±0.06,差异均有统计学意义(P＜0.05).MS组示踪纤维数和示踪纤维密度都与EDSS评分呈负相关关系(r=-0.782,P=0.000;r=-0.771,P=0.000). 结论 通过MRI扩散张量成像扫描进行脑白质束示踪可以发现MS患者脑白质束的受损情况,其较常规MRI能提供更多的空间信息.     

Neurocognitive functions in euthymic bipolar patients

Objective: Meta‐analytic findings support the hypothesis of specific neurocognitive deficits for bipolar patients in the domains of attention, processing speed, memory and executive functions. This study aims to show neurocognitive impairment in euthymic patients with bipolar I disorder compared with healthy controls while detailing the impact of medication side‐effects or illness characteristics on neuropsychological test performance. Method: Forty euthymic patients with bipolar I disorder were compared with 40 healthy controls in a cross‐sectional design. Clinical features and neuropsychological measures of IQ, psychomotor speed, verbal fluency, learning and memory, executive functions and attention were assessed. Results: Patients without antipsychotic drug use did not differ significantly from healthy controls in any neuropsychological measure. Yet patients treated with antipsychotics showed significant underperformance in the domains of semantic fluency, verbal learning and recognition memory as well as executive functions related to planning abilities, even when clinical features were controlled for. Conclusion: The impact of antipsychotic medication needs to be further clarified for euthymic bipolar patients and should be considered when neuropsychological test performance is interpreted.