MRI study of thalamic volumes in bipolar and unipolar patients and healthy individuals

The thalamus is a key structure in brain anatomic circuits potentially involved in the pathophysiology of mood disorders. Available findings from studies that examined this brain region in mood disorder patients have been conflicting. To examine the hypothesis of anatomical abnormalities in the thalamus in patients with mood disorders, we conducted a magnetic resonance imaging (MRI) study in 25 bipolar patients (mean age±S.D.=34.4±9.8 years), 17 unipolar patients (mean age±S.D.=42.8±9.2 years), and 39 healthy control subjects (mean age±S.D.=36.6±9.7 years). Thalamic volumes Gray Matter were measured blindly with a semi-automated technique. Multivariate analysis of variance, with age and gender as covariates, revealed no significant differences in left or right thalamic volumes among bipolar patients, unipolar patients and healthy individuals. There were no significant effects of gender, age at illness onset, episode type, number of episodes, length of illness, or family history of mood disorders on thalamic measurements. Although functional abnormalities in the thalamus are likely to be implicated in the pathophysiology of mood disorders, no abnormalities in thalamic size appear present in bipolar or unipolar individuals.     

MRI study of posterior fossa structures and brain ventricles in bipolar patients

Previous brain imaging studies have suggested anatomical abnormalities in posterior fossa structures and brain ventricles in bipolar patients. Such abnormalities could possibly be implicated in the pathophysiology of bipolar disorder. Twenty-two DSM-IV bipolar outpatients (mean age±S.D.=36±10 years) and 22 healthy controls (mean age±S.D.=38±10 years) underwent an 1.5T MRI (3D-gradient echo-imaging SPGR), performed in the coronal plane (TR=25 ms, TE=5 ms, slice THICKNESS=1.5 mm). The brain structures of interest were traced blindly with a semi-automated software. No significant differences were found between bipolar patients and healthy controls for any posterior fossa measures, or for measures of third or lateral ventricles (MANOVA, age covariate, P>0.05). Age was directly correlated with 3rd ventricle volumes in bipolar patients (Pearson correlation COEFFICIENT=0.458, P=0.032), but not in healthy controls (Pearson correlation COEFFICIENT=0.313, P=0.155). There was a significant direct correlation between the number of prior illness episodes and right lateral ventricle volumes (Partial correlation COEFFICIENT=0.658, P=0.011). Familial patients had smaller left and right cerebellar hemispheres and total vermis volumes, and larger left lateral ventricle volumes compared with non-familial ones (MANOVA, age covariate, P<0.05). In this preliminary study, we were not able to replicate previous findings of abnormalities in cerebellum or brain ventricles in bipolar individuals. However, there were suggestions that abnormalities in cerebellum, vermis, and lateral ventricle sizes may be present in familial cases of the disorder, which should be further examined in future studies with larger patient samples.     

Neurodevelopmental basis of bipolar disorder: a critical appraisal

Neurodevelopmental factors have been implicated in the pathophysiology of mental disorders. However, the evidence regarding their role in bipolar disorder is controversial. We reviewed the pertinent literature searching for evidence regarding a neurodevelopmental origin of bipolar disorder. Findings from clinical, epidemiological, neuroimaging, and post-mortem studies are discussed, as well as the implications of the available data for a better understanding of the mechanisms involved in the genesis of bipolar disorder. While some evidence exists for developmental risk factors in bipolar disorder, further research is needed to determine the precise extent of their contribution to pathogenesis. The timing and course of such developmentally mediated neurobiological alterations also need to be determined. Of particular importance for further study is the possibility that bipolar disorder may be mediated by an abnormal maturation of brain structures involved in affect regulation.     

Voxel-based morphometric analysis on the volume of gray matter in bipolar I disorder

A number of previous studies have found that bipolar disorder is associated with abnormalities of brain structure. In this study we used optimized voxel-based morphometry (VBM) to compare gray matter volume between patients with bipolar I disorder and healthy controls. Twenty-four bipolar I patients (15 males and nine females) and 36 healthy controls (21 males and 15 females), who were well matched for age and gender, were scanned using structural magnetic resonance imaging. Gray matter volume was assessed and compared using optimized VBM, and the correlation between duration of illness/number of episodes and regional volumes was analyzed. There was no difference in whole-brain gray matter volume between the two groups. Optimized vVBM showed that subjects with bipolar I disorder had smaller volumes in the left inferior parietal lobule, right superior temporal gyrus, right middle frontal gyrus and left caudate. Only the volume of the right middle frontal gyrus was correlated with duration of illness and number of episodes in patients. These results suggest widespread gray matter defects in bipolar I disorder, which may play an important role in onset of the illness.     

MRI investigation of temporal lobe structures in bipolar patients

Previous anatomical MRI studies have suggested abnormalities in amygdala volumes in bipolar disorder, whereas hippocampus, temporal lobe (TL), and superior temporal gyri (STG) measures have been reported to be normal. This study further investigated the existence of anatomical abnormalities in these brain structures in bipolar subjects, to attempt to replicate previously reported findings. Twenty-four DSM-IV bipolar patients (mean age+/-S.D.=35+/-10 years) and 36 healthy controls (mean age+/-S.D.=37+/-10 years) were studied. 3D SPGR images were obtained with a 1.5T-GE Signa magnet (TR=25 ms, TE=5 ms, FOV=24 cm, slice-thickness=1.5 mm, matrix-size=256 x 192). Volumetric measurements of TL, hippocampus, amygdala, and STG were performed blindly, with a semi-automated software. Bipolar patients had significantly larger left amygdala volumes compared with controls (mean volumes+/-S.D.=2.57+/-0.69 vs. 2.17+/-0.58 ml, respectively; ANCOVA, age, gender, ICV as covariates; F=4.42, df=1/55, P=0.04). The volumes of the other temporal lobe structures did not differ significantly between the two groups (ANCOVA, age, gender, and ICV as covariates, P>0.05). Our findings of enlarged left amygdala in bipolar patients are in agreement with prior MRI studies, suggesting that abnormalities in this brain structure may be implicated in pathophysiology of the illness. Longitudinal studies in high-risk offspring and first-episode patients will be needed to examine whether such abnormalities precede the appearance of symptoms, or whether they may appear subsequently as a result of illness course.     

Decreased brain intracellular pH measured by 31P-MRS in bipolar disorder: a confirmation in drug-free patients and correlation with white matter hyperintensity

The authors have previously reported decreased intracellular pH (pHi) in the frontal lobes in euthymic bipolar patients treated with lithium using ³¹P-MRS. White matter hyperintensity (WMHI) is frequently seen in bipolar disorder. To examine a possible effect of lithium on pHi and the relationship between pHi and WMHI, seven drug-free euthymic bipolar patients were examined, and T₂-weighted MRI were examined in 14 previously reported bipolar patients. Drug-free patients showed significantly lower pHi than controls. WMHI was associated with low pHi and increased phosphodiester peak. These results suggest that decrease of pHi is not an effect of lithium but is instead related to the pathophysiology of illness. Decrease of pHi and increase of the PDE peak may be the biochemical basis of WMHI in bipolar disorder. Received: 7 January 1998 / Accepted: 15 September 1998     

Anatomical MRI study of corpus callosum in unipolar depression

Previous studies have suggested abnormal cerebral lateralization in major depressive disorder (MDD). Few controlled MRI studies have investigated the corpus callosum (CC), the largest commissura connecting the two cerebral hemispheres, in MDD. This study investigated anatomical abnormalities in the CC and its subdivisions in MDD patients. Twenty-two unmedicated MDD patients and 39 healthy subjects underwent brain magnetic resonance imaging (MRI). Measurements of the CC and its sub-regions were performed with a semi-automated software (NIH Image, version 1.62). ANCOVA with age, gender, and intra-cranial volume (ICV) as covariates showed no significant differences in CC measurements between patients and controls (df=1,56; p>0.05). However, patients with familial MDD had a significantly larger middle genu area (F(1,45)=4.252; p=0.045) compared to healthy controls, and significantly larger middle genu (F(1,13)=5.366; p=0.037), anterior splenium (F(1,13)=6.27; p=0.026), and middle splenium areas (F(1,13)=4.706; p=0.049) compared to patients with non-familial MDD. Although preliminary, our findings suggest that anatomical abnormalities in CC may be restricted to patients with familial MDD, with possible enlargement of CC in this particular sub-group. The possible role of callosal abnormalities in the pathogenesis of mood disorders should be further examined.     

Creativity in familial bipolar disorder

Studies have demonstrated relationships between creativity and bipolar disorder (BD) in individuals, and suggested familial transmission of both creativity and BD. However, to date, there have been no studies specifically examining creativity in offspring of bipolar parents and clarifying mechanisms of intergenerational transmission of creativity. We compared creativity in bipolar parents and their offspring with BD and bipolar offspring with attention-deficit/hyperactivity disorder (ADHD) with healthy control adults and their children. 40 adults with BD, 20 bipolar offspring with BD, 20 bipolar offspring with ADHD, and 18 healthy control parents and their healthy control children completed the Barron–Welsh Art Scale (BWAS), an objective measure of creativity. Adults with BD compared to controls scored significantly (120%) higher on the BWAS Dislike subscale, and non-significantly (32%) higher on the BWAS Total scale. Mean BWAS Dislike subscale scores were also significantly higher in offspring with BD (107% higher) and offspring with ADHD (91% higher) than in healthy control children. Compared to healthy control children, offspring with BD had 67% higher and offspring with ADHD had 40% higher BWAS Total scores, but these differences failed to reach statistical significance when adjusted for age. In the bipolar offspring with BD, BWAS Total scores were negatively correlated with duration of illness. The results of this study support an association between BD and creativity and contribute to a better understanding of possible mechanisms of transmission of creativity in families with genetic susceptibility for BD. This is the first study to show that children with and at high risk for BD have higher creativity than healthy control children. The finding in children and in adults was related to an enhanced ability to experience and express dislike of simple and symmetric images. This could reflect increased access to negative affect, which could yield both benefits with respect to providing affective energy for creative achievement, but also yield liabilities with respect to quality of interpersonal relationships or susceptibility to depression.     

Effects of comorbid anxiety disorders on the course of bipolar disorder-I

Abstract

Background and aims: Although comorbid anxiety disorders (AD) are quite frequent in bipolar disorders (BD), data on how this comorbidity affects BD are limited. In the present study, we aimed to investigate the frequency of comorbid AD in Turkish patients with bipolar disorder-I (BD-I) and the effects of comorbid AD on the course of BD-I. Methods: 114 patients with BD-I were included in the study. All patients were diagnosed by a psychiatrist. The patients were divided into two groups as BD-I patients with lifetime comorbid AD (BDI-CAD) or those without comorbid AD (BDI). Results: 37 (32.46%) patients had one or more comorbid lifetime AD. The numbers of admissions to the outpatient clinic within calendar year 2013 (P = 0.014), the number of lifetime mood episodes (P = 0.019) and the duration of BD (P = 0.007) were higher in the BDI-CAD group compared with the BDI group. There was a strong relationship between the duration of the disorder and the number of episodes (r = 0.583, P < 0.001). Partial correlation analyses showed that the number of admission to the outpatient clinic correlated significantly with the frequency of episodes (P = 0.007, r = 0.282). Conclusion: We found that the patients with BDI-CAD use the healthcare system more frequently than the BDI patients. This suggests that AD comorbidity may have a negative influence on the course of BD-I and it is a factor that should be considered in the clinical follow-up.     

Increased pituitary volume in patients with established bipolar affective disorder

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been demonstrated in bipolar disorder (BD), but previous magnetic resonance imaging (MRI) studies of pituitary gland volume in BD have reported variable findings. In this MRI study we investigated pituitary volume in 26 patients with established bipolar I disorder (8 males and 18 females, mean age = 38.4 years) and 24 matched controls (7 males and 17 females, mean age = 38.7 years). The BD patients had a significantly larger pituitary volume as compared with controls, but there was no association between pituitary volume and illness duration, number of manic/depressive episodes, daily medication dosage, family history, or clinical subtype (i.e., psychotic and nonpsychotic). Pituitary volume was larger in females than in males for both groups. These results support previous neuroendocrine findings that implicate HPA axis dysfunction in the core pathophysiological process of BD.     

Quantitative proton magnetic resonance spectroscopy of the basal ganglia in patients with affective disorders

Proton magnetic resonance spectra were recorded from a subcortical region containing the basal ganglia in 40 patients with affective disorders (18 with bipolar disorder and 22 with major depression) and in 20 normal controls. The absolute concentration of the choline-containing compounds (Cho) in the patients with bipolar disorder in the depressive state was significantly higher than that in the normal controls. The patients with bipolar disorder had significantly higher levels of the Cho/creatine + phosphocreatine (Cr) and Cho/N-acetly-l-aspartate (NAA) peak ratio compared with the normal controls in both the depressive and euthymic states, with a tendency to higher levels in the depressive state. The Cho/NAA peak ratio was also significantly higher in the patients with major depression compared with the normal controls. These results suggest that the membrane phospholipid metabolism in the basal ganglia is altered in affective disorders. Received: 26 June 1997 / Accepted: 5 August 1997     

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。     

A study of genetic and environmental contributions to structural brain changes over time in twins concordant and discordant for bipolar disorder

This is the first longitudinal twin study examining genetic and environmental contributions to the association between liability to bipolar disorder (BD) and changes over time in global brain volumes, and global and regional measures of cortical surface area, cortical thickness and cortical volume.A total of 50 twins from pairs discordant or concordant for BD (monozygotic: 8 discordant and 3 concordant pairs, and 1 patient and 3 co-twins from incomplete pairs; dizygotic: 6 discordant and 2 concordant pairs, and 1 patient and 7 co-twins from incomplete pairs) underwent magnetic resonance imaging twice. In addition, 57 twins from healthy twin pairs (15 monozygotic and 10 dizygotic pairs, and 4 monozygotic and 3 dizygotic subjects from incomplete pairs) were also scanned twice. Mean follow-up duration for all twins was 7.5 years (standard deviation: 1.5 years). Data were analyzed using structural equation modeling software OpenMx.The liability to BD was not associated with global or regional structural brain changes over time. Although we observed a subtle increase in cerebral white matter in BD patients, this effect disappeared after correction for multiple comparisons. Heritability of brain changes over time was generally low to moderate.Structural brain changes appear to follow similar trajectories in BD patients and healthy controls. Existing brain abnormalities in BD do not appear to progressively change over time, but this requires additional confirmation. Further study with large cohorts is recommended to assess genetic and environmental influences on structural brain abnormalities in BD, while taking into account the influence of lithium on the brain.     

Metabolic syndrome in subjects with bipolar disorder and major depressive disorder in a current depressive episode: Population-based study: Metabolic syndrome in current depressive episode

ObjectiveTo assess the differences in the prevalence of the metabolic syndrome (MetS) and their components in young adults with bipolar disorder (BD) and major depressive disorder (MDD) in a current depressive episode.MethodsThis was a cross-sectional study with young adults aged 24–30 years old. Depressive episode (bipolar or unipolar) was assessed using the Mini International Neuropsychiatric Interview – Plus version (MINI Plus). The MetS was assessed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III).ResultsThe sample included 972 subjects with a mean age of 25.81 (±2.17) years. Both BD and MDD patients showed higher prevalence of MetS compared to the population sample (BD = 46.9%, MDD = 35.1%, population = 22.1%, p < 0.001). Higher levels of glucose, total cholesterol and LDL cholesterol, Body Mass Index, low levels of HDL cholesterol, and a higher prevalence of abdominal obesity were observed in both BD and MDD individuals with current depressive episode compared to the general population. Moreover, there was a significant difference on BMI values in the case of BD and MDD subjects (p = 0.016).ConclusionMetabolic components were significantly associated with the presence of depressive symptoms, independently of the diagnosis.     

Volume of cerebellar vermis in monozygotic twins discordant for combat exposure: Lack of relationship to post-traumatic stress disorder

Several functional neuroimaging studies have implicated the cerebellar vermis in post-traumatic stress disorder (PTSD), but there have been no structural neuroimaging studies of this brain structure in PTSD. We utilized magnetic resonance imaging (MRI) with manual tracing to quantify the volumes of three divisions of the mid-sagittal vermis, and their total, within an identical, co-twin control design that employed Vietnam veterans discordant for combat exposure in Vietnam. Each structure's volume was significantly correlated between twins, indicating a partial familial determination: for anterior superior vermis, r = 0.73; for posterior superior vermis, r = 0.47; for inferior posterior vermis, r = 0.51; and for total vermis, r = 0.57. There were no significant differences between the PTSD and non-PTSD veterans for any vermis volume, and no significant main effects or interactions when their non-combat-exposed co-twins were added to the analyses. Thus, the results do not support the structural abnormality of cerebellar vermis in combat-related PTSD.     

双相障碍患者代谢综合征风险研究

目的 调查双相障碍患者长期治疗中代谢综合征的风险发生率及分析可能的相关因素.方法 采用横断面研究.以单用心境稳定剂或联用抗精神病药连续6月以上的门诊双相障碍患者为调查对象.采用统一问卷及实验室检测.代谢综合征诊断标准采用2004年中华医学会糖尿病分会代谢综合征标准.结果 共入组128例,双相障碍患者中代谢综合征的发生率为36.7%(47例).药物类别及用药时间与代谢综合征的发病风险有关(回归系数B值分别为-0.614,-0.797;P值分别为0.028,0.001).结论 与普通人群相比,双相障碍患者有较高的代谢综合征发病风险.用药时间越长代谢综合征的发生风险越高.联用抗精神病药能增加代谢综合征的发生率.临床上应注意监测代谢指标及对代谢异常进行干预.     

Manic episode associated with mega cisterna magna

Mega cisterna magna is a part of "Dandy-Walker Complex" and it is characterized by the enlargement of the cisterna magna, morphologically intact vermis and cerebellar hemispheres. We report a case of manic attack in a 23-year-old man with mega cisterna magna. The patient was treated with quetiapine 1,000 mg/day and sodium valproate 1,500 mg/day and the symptoms were ameliorated within 2.5 months. In this case, mega cisterna magna and manic symptoms may be found together coincidentally or any cerebellar dysfunction due to mega cisterna magna may cause or contribute to the appearance of affective symptoms. To our knowledge, this is the first case reporting manic attack with psychotic symptoms associated with mega cisterna magna. This report suggests that any lesion in the cerebellum might contribute to the occurrences of some affective and psychotic symptoms seen in bipolar disorder.     

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.     

Greater cortical gray matter density in lithium-treated patients with bipolar disorder.

BACKGROUND: The neurobiological underpinnings of bipolar disorder are not well understood. Previous neuroimaging findings have been inconsistent; however, new methods for three-dimensional (3-D) computational image analysis may better characterize neuroanatomic changes than standard volumetric measures. METHODS: We used high-resolution magnetic resonance imaging and cortical pattern matching methods to map gray matter differences in 28 adults with bipolar disorder, 70% of whom were lithium-treated (mean age = 36.1 +/- 10.5; 13 female subject), and 28 healthy control subjects (mean age = 35.9 +/- 8.5; 11 female subjects). Detailed spatial analyses of gray matter density (GMD) were conducted by measuring local proportions of gray matter at thousands of homologous cortical locations. RESULTS: Gray matter density was significantly greater in bipolar patients relative to control subjects in diffuse cortical regions. Greatest differences were found in bilateral cingulate and paralimbic cortices, brain regions critical for attentional, motivational, and emotional modulation. Secondary region of interest (ROI) analyses indicated significantly greater GMD in the right anterior cingulate among lithium-treated bipolar patients (n = 20) relative to those not taking lithium (n = 8). CONCLUSIONS: These brain maps are consistent with previous voxel-based morphometry reports of greater GMD in portions of the anterior limbic network in bipolar patients and suggest neurotrophic effects of lithium as a possible etiology of these neuroanatomic differences.     

Preliminary evidence of within-subject changes in gray matter density associated with remission of bipolar depression

A preliminary within-subjects MRI study of seven patients with a diagnosis of bipolar I disorder revealed that, compared to remission, depression was associated with gray matter density increases in subgenual prefrontal cortex, parahippocampal gyrus, and inferior temporal gyri. Decreases were observed in superior and inferior frontal gyri and anterior cingulate.