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1.
Lisy ME, Jarvis KB, DelBello MP, Mills NP, Weber WA, Fleck D, Strakowski SM, Adler CM. Progressive neurostructural changes in adolescent and adult patients with bipolar disorder.
Bipolar Disord 2011: 13: 396–405. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Several lines of evidence suggest that bipolar disorder is associated with progressive changes in gray matter volume (GMV), particularly in brain structures involved in emotional regulation and expression. The majority of these studies however, have been cross‐sectional in nature. In this study we compared baseline and follow‐up scans in groups of bipolar disorder and healthy subjects. We hypothesized bipolar disorder subjects would demonstrate significant GMV changes over time. Methods: A total of 58 bipolar disorder and 48 healthy subjects participated in structural magnetic resonance imaging (MRI). Subjects were rescanned 3–34 months after their baseline MRI. MRI images were segmented, normalized to standard stereotactic space, and compared voxel‐by‐voxel using statistical parametrical mapping software (SPM2). A model was developed to investigate differences in GMV at baseline, and associated with time and episodes, as well as in comparison to healthy subjects. Results: We observed increases in GMV in bipolar disorder subjects across several brain regions at baseline and over time, including portions of the prefrontal cortex as well as limbic and subcortical structures. Time‐related changes differed to some degree between adolescent and adult bipolar disorder subjects. The interval between scans positively correlated with GMV increases in bipolar disorder subjects in portions of the prefrontal cortex, and both illness duration and number of depressive episodes were associated with increased GMV in subcortical and limbic structures. Conclusions: Our findings support suggestions that widely observed progressive neurofunctional changes in bipolar disorder patients may be related to structural brain abnormalities in anterior limbic structures. Abnormalities largely involve regions previously noted to be integral to emotional expression and regulation, and appear to vary by age.  相似文献   

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James A, Hough M, James S, Burge L, Winmill L, Nijhawan S, Matthews PM, Zarei M. Structural brain and neuropsychometric changes associated with pediatric bipolar disorder with psychosis.
Bipolar Disord 2011: 13: 16–27. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: To identify neuropsychological and structural brain changes using a combination of high‐resolution structural and diffusion tensor imaging in pediatric bipolar disorder (PBD) with psychosis (presence of delusions and or hallucinations). Methods: We recruited 15 patients and 20 euthymic age‐ and gender‐matched healthy controls. All subjects underwent high‐resolution structural and diffusion tensor imaging. Voxel‐based morphometry (VBM), tract‐based spatial statistics (TBSS), and probabilistic tractography were used to analyse magnetic resonance imaging data. Results: The PBD subjects had normal overall intelligence with specific impairments in working memory, executive function, language function, and verbal memory. Reduced gray matter (GM) density was found in the left orbitofrontal cortex, left pars triangularis, right premotor cortex, occipital cortex, right occipital fusiform gyrus, and right crus of the cerebellum. TBSS analysis showed reduced fractional anisotropy (FA) in the anterior corpus callosum. Probabilistic tractography from this cluster showed that this region of the corpus callosum is connected with the prefrontal cortices, including those regions whose density is decreased in PBD. In addition, FA change was correlated with verbal memory and working memory, while more widespread reductions in GM density correlated with working memory, executive function, language function, and verbal memory. Conclusions: The findings suggest widespread cortical changes as well as specific involvement of interhemispheric prefrontal tracts in PBD, which may reflect delayed myelination in these tracts.  相似文献   

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Objectives:  The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls.
Methods:  The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function.
Results:  The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory.
Conclusions:  BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.  相似文献   

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BACKGROUND: Morphometric magnetic resonance imaging (MRI) studies of pediatric bipolar disorder (BD) have not reported on gray matter volumes but have reported increased lateral ventricular size and presence of white matter hyperintensities (WMH). We studied gray matter volume, ventricular-to-brain ratios (VBR), and number of WMH in patients with familial, pediatric BD compared with control subjects. METHODS: Twenty subjects with BD (aged 14.6 +/- 2.8 years; 4 female) according to the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, each with a parent with BD, and 20 age-, gender-, and intelligence quotient-matched healthy control subjects (aged 14.1 +/- 2.8 years; 4 female) were scanned at 3 T. Most subjects were taking psychotropic medications. A high-resolution T1-weighted spoiled gradient echo three-dimensional MRI sequence was analyzed by BrainImage for volumetric measurements, and T2-weighted images were read by a neuroradiologist to determine presence of WMH. RESULTS: After covarying for age and total brain volume, there were no significant differences between subjects with BD and control subjects in volume of cerebral (p = .09) or prefrontal gray matter (p = .34). Subjects with BD did not have elevated numbers of WMH or greater VBR when compared with control subjects. CONCLUSIONS: Children and adolescents with familial BD do not seem to have decreased cerebral grey matter or increased numbers of WMH, dissimilar to findings in adults with BD. Gray matter decreases and development of WMH might be later sequelae of BD or unique to adult-onset BD.  相似文献   

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BACKGROUND: Decreased caudate volumes have been noted in unipolar depressed subjects, especially in the elderly and those with cognitive impairment. No differences have been noted in initial studies of multi-aged bipolar subjects; however, this region has not been examined in older bipolar subjects. METHODS: We examined the caudate nuclei volumes of 36 older bipolar subjects (mean age 58) and 35 older controls (mean age 62) using logistic regression analyses to control for age and gender differences. Differences between late- and early-onset (age-of-onset before age 45) bipolar subjects were also examined, as well as the effect of length of illness. RESULTS: The right caudate was noted to be smaller in older bipolar subjects compared with older controls when controlled for sex and age (p = 0.0448). No differences were noted in overall brain volume nor lateral ventricular volume between the bipolar and control subjects. Late-onset bipolar subjects had a decrease in brain volume (p = 0.035) compared with early-onset bipolar subjects. Late-onset bipolar subjects had a decrease in the right (p = 0.044) and total (p = 0.04) caudate size compared with older controls. CONCLUSIONS: Right caudate volume is decreased in older bipolar subjects compared to controls. Bipolar subjects with late-onset illness have significantly decreased right and total caudate volumes compared to controls. This is affected by neither the length of illness nor the age of onset. Late-onset bipolar subjects have decreased total brain volume compared with early-onset bipolar subjects.  相似文献   

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Background. Religiousness and spirituality (R/S) are often neglected features among psychiatric patients but important both for quality of life and coping strategies for mental disorders. In patients affected by bipolar disorder (BD), R/S can sometimes be confused with symptoms related to the psychiatric disorder. This study aimed to perform a clinical review of the relationship between R/S and BD. Methods. Data sources included Medline (OvidSP), CINAHL (Ebsco), EMBASE (Ovid), PsychINFO (Ebsco), Angeline, Cochrane Database of Systematic Reviews and Database of Abstract of Reviews of Effects, searching for pertinent Keywords: ‘religiousness’, ‘spirituality’ and ‘bipolar disorder’. Results. Nine works were found but only five used homogeneous samples with BD patients. R/S were important when facing symptoms and relapses in the lifeworld. These beliefs influenced the relationship with psychiatrists and spiritual figures of reference. Conclusions. R/S play a role as a psychosocial variable in the course of BD. However, the hypothesis that the R/S factor can be relevant both in terms of providing a protective effect as well as a provocative element in depressive or hypomanic phases was not fully supported at the moment.  相似文献   

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OBJECTIVES: An increased incidence in white matter abnormalities is among the most frequently reported brain change in patients with bipolar disorder. The objective of the present study was to examine white matter tract integrity, using diffusion tensor imaging (DTI), in bipolar patients and healthy comparison subjects. METHODS: Eleven DSM-IV bipolar I patients and 10 healthy age- and sex-matched controls were studied. DTI data were acquired on a 1.5 Tesla scanner. Fractional anisotropy (FA) and diffusivity (trace) were determined from axial images using region of interest (ROI) analyses. The ROIs were manually placed in the midline and forward projecting arms of the genu (anterior) and the midline of the splenium (posterior) of the corpus callosum. RESULTS: Bipolar patients had significantly higher FA in the midline of the genu compared with healthy controls. Regional white matter differences were also observed, with significantly lower FA in the genu than forward projecting regions in both groups and lower FA in the genu than the splenium in controls. CONCLUSIONS: Diffusion tensor imaging revealed significant microstructural differences in the genu, as measured by elevated FA in bipolar patients compared with healthy controls. These preliminary findings further support the hypothesis that anomalous frontal brain mechanisms may be associated with bipolar disorder.  相似文献   

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BACKGROUND: Relatively low levels of brain N-acetylaspartate, as measured by magnetic resonance spectroscopy, may indicate decreased neuronal density or viability. Dorsolateral prefrontal levels of N-acetylaspartate have been reported to be decreased in adults with bipolar disorder. We used proton magnetic resonance spectroscopy to investigate dorsolateral prefrontal N-acetylaspartate levels in children with familial bipolar disorder. METHODS: Subjects were 15 children and adolescents with bipolar disorder, who each had at least one parent with bipolar disorder, and 11 healthy controls. Mean age was 12.6 years for subjects and controls. Subjects were allowed to continue current medications. Proton magnetic resonance spectroscopy at 3-Tesla was used to study 8 cm(3) voxels placed in left and right dorsolateral prefrontal cortex. RESULTS: Bipolar subjects had lower N-acetylaspartate/Creatine ratios only in the right dorsolateral prefrontal cortex (p <.02). No differences in myoinositol or choline levels were found. CONCLUSIONS: Children and adolescents with bipolar disorder may have decreased dorsolateral prefrontal N-acetylaspartate, similar to adults with BD, indicating a common neuropathophysiology. Longitudinal studies of at-risk children before the onset and during the early course of bipolar disorder are needed to determine the role of prefrontal N-acetylaspartate as a possible risk marker and/or indication of early bipolar illness progression.  相似文献   

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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.  相似文献   

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BACKGROUND: This study sought to assess white matter density in patients and relatives with histories of bipolar disorder and/or schizophrenia. METHODS: Subjects included those with schizophrenia from families affected by schizophrenia alone, those with bipolar disorder from families affected by bipolar disorder alone and those with bipolar disorder from families affected by both bipolar disorder and schizophrenia. Unaffected relatives of the three patient groups were also recruited. Subjects underwent an MRI brain scan which was analyzed using a white-matter optimized technique. RESULTS: Subjects with schizophrenia and bipolar disorder showed reduced white matter density in the anterior limb of the internal capsule which was not found in unaffected relatives. Reductions were found in frontal subgyral white matter density in affected subjects with a family history of schizophrenia only. CONCLUSIONS: Abnormal anterior internal capsule white matter may provide a structural substrate for both disorders.  相似文献   

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Objectives: Rapidly alternating or mixed mood states in bipolar disorder are associated with a particularly high risk for suicidal behavior. Are individuals with these patterns of illness more likely to develop suicidal intentions, or are they less able to resist them? This analysis examines the specific contribution of rapid switching and other variables to the relative likelihood of having or acting on self‐reported suicidal thought and action, in a large group of individuals with bipolar disorder. Methods: The analysis included 1574 family members with bipolar disorder interviewed for a multi‐site bipolar disorder genetic linkage study. Two models were tested, using the same set of demographic and clinical data points as independent variables. One model tested the influence of rapid switching and other variables on self‐reported suicidal thought or action (i.e., suicidality), while the other tested the influences on suicidal action only among those who reported a history of suicidality. Results: Over 75% of subjects had contemplated suicide and 38% reported a history of suicidal behavior. A history of rapid switching was associated with higher likelihood of a history of suicidality, as was panic disorder. Familial suicidal behavior, as well as drug abuse, increased the likelihood of suicidal action among suicidal individuals, but did not increase the likelihood of becoming suicidal. Female sex, early age at onset, and several demographic factors were associated with both facets of suicidality. Conclusions: Factors associated with high acuity of distress, such as panic attacks and unstable moods, appear to enhance the risk of suicidality in general. Factors that affected the threshold for action without increasing suicidality overall can also be seen as markers of impulsive decision‐making. Of the two distinct kinds of suicidal risk, the latter – the likelihood of action given intent – appears to be the more familial.  相似文献   

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Objectives

The subgenual prefrontal cortex (SGPFC) is an important brain region involved in emotional regulation and reward mechanisms. Volumetric abnormalities in this region have been identified in adults with bipolar disorder but thus far not in pediatric cases. We examined the volume of this brain region in subjects with pediatric bipolar disorder (PBD) and compared them to healthy controls.

Methods

Fifty one children and adolescents (mean age ± SD; 13.2 ± 2.9 y) with DSM-IV PBD and 41 (mean age ± SD; 13.7 ± 2.7 y) healthy comparison subjects (HC) underwent 1.5 T structural magnetic resonance imaging (MRI) brain scans. We traced the SGPFC manually and compared SGPFC gray matter volumes using analysis of covariance with age, gender, and intracranial volume as covariates. We also examined the relationship of family history of affective disorders and medication status to SGPFC volumes.

Results

SGPFC volumes were not significantly different in PBD and HC subjects. However, exploratory analysis showed PBD subjects who had one or more first degree relatives with mood disorders (n = 33) had significantly smaller left hemisphere SGPFC compared to HC (p = 0.03 Sidak corrected). Current usage of a mood stabilizer was significantly associated with larger right SGPFC volume in PBD (F = 4.82, df = 1/41, p = 0.03).

Conclusion

Subjects with PBD and a close family history of mood disorders may have smaller left SGPFC volumes than HC. Mood stabilizing medication may also impact SGPFC size and could have masked more subtle abnormalities overall.  相似文献   

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Usher J, Menzel P, Schneider‐Axmann T, Kemmer C, Reith W, Falkai P, Gruber O, Scherk H. Increased right amygdala volume in lithium‐treated patients with bipolar I disorder. Objective: The amygdala plays a major role in processing emotional stimuli. Fourteen studies using structural magnetic resonance imaging (MRI) have examined the amygdala volume in paediatric and adult patients with bipolar disorder (BD) compared with healthy controls (HC) and reported inconsistent findings. Lithium has been found to increase grey matter volume, and first evidence points towards an effect on regional brain volume such as the amygdala. Method: We examined the amygdala volume of euthymic patients with BD treated with lithium (n = 15), without lithium (n = 24) and HC (n = 41) using structural MRI. Results: Patients treated with lithium exhibited in comparison to HC a larger right absolute (+17.9%, P = 0.015) and relative (+18%, P = 0.017) amygdala volume. There was no significant difference in amygdala volume between patients without lithium treatment and HC. Conclusion: Lithium appears to have a sustained effect on a central core region of emotional processing and should therefore be considered in studies examining BD.  相似文献   

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OBJECTIVES: The purpose of this study was to investigate the increased risk for pulmonary embolism (PE) in patients with manic-depressive psychosis/bipolar disorder (BD). Affective patients show increased mortality compared with the background population. METHODS: A register study was carried out in which somatic and psychiatric information in 25,834 BD patients and 117,815 controls was extracted from The Danish Psychiatric Central Research Register, The National Register of Patients, The Danish Central Person Register and The Danish Register of Causes of Death, with similar information about patients with schizophrenia and anxiety for comparison. RESULTS: Patients with BD had a significantly increased occurrence of PE [increased incidence rate ratio (IRR)=1.61; 95% confidence interval (CI) (1.38, 1.88)]. An association was also found in schizophrenic patients [IRR=1.78; 95% CI (1.27, 2.51)] and in anxiety patients [IRR=1.49; 95% CI (1.10, 2.02)]. CONCLUSIONS: Increased occurrence of PE in patients with BD is one of the explanations of increased mortality in the affective patient group. A similar finding in females with schizophrenia and females with anxiety suggests 'mental disorder' as the risk factor for PE. The causes for the increased occurrence of PE in BD patients (and other diagnostic groups) need further investigation.  相似文献   

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In vivo imaging studies suggest functional abnormalities of the thalamus in adult patients with bipolar disorder, but the presence of anatomical abnormalities is controversial. Our objective in this study was to compare the thalamus volumes of children and adolescents with bipolar disorder versus healthy controls to determine whether any morphological abnormalities exist early in illness course. We studied 16 patients with bipolar disorder according to DSM-IV criteria (mean age+/-SD=15.5+/-3.4 years) and 21 healthy control subjects (mean age+/-SD=16.9+/-3.8 years). Blinded examiners measured thalamic gray matter volumes with a semiautomated technique. Analysis of covariance, with age, gender, and intracranial brain volume as covariates, revealed no significant differences in left and right thalamic volumes between patients with bipolar disorder and healthy controls. Our findings indicate there are no significant differences in thalamus size between children and adolescents with bipolar disorder and healthy comparison subjects, in contrast to available findings for schizophrenia and first-break psychosis. Any differences in thalamus size that may exist between patients with bipolar disorder and healthy controls must amount to small effect sizes.  相似文献   

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