Neuroimaging Studies Of Bipolar Disorder Research Articles

Neural underpinnings of emotion regulation subgroups in remitted patients with recently diagnosed bipolar disorder

Neuroimaging studies of bipolar disorder (BD) generally involve comparison with healthy controls (HC), which may mask neurobiological variability within the disorder. This study aims to assess the neural underpinnings of potential subgroups of BD patients based on functional activity in the emotion regulation network and its relation to illness characteristics and relapse risk. Eighty-seven remitted patients with recently diagnosed BD and 66 HC underwent functional magnetic resonance imaging (fMRI) while performing an emotion regulation task. Patients were re-assessed with clinical interviews after 16 (±5) months. Data-driven hierarchical cluster analysis was employed to investigate ‘neuronal subgroups’ of patients based on their neuronal activity in a pre-defined emotion regulation network. Relations between neuronal subgroups and illness characteristics and relapse rates were examined. Patients were allocated into two subgroups. Subgroup 1 (n=62, 75%) was characterized by exaggerated bilateral amygdala reactivity but normal prefrontal and temporo-parietal activation. Subgroup 2 (n= 22, 25%) showed widespread hypo-activity within all emotion regulation regions. Both subgroups were less successful at down-regulating their emotions than HC (F(2,146)=5.33, p=.006, ηp2=.07). Patients in subgroup 2 had a history of more and longer mixed episodes (ps≤.01). Importantly, heightened amygdala activity across all patients was associated with increased risk of relapse during a 16-month follow-up period (β=3.36, 95% CI [1.49;550.35], N=60, p=.03). The identified neuronal subgroups of patients with either amygdala hyper-activity or broad network hypo-activity during emotion regulation points to neurobiological heterogeneity among remitted patients with BD. Heightened amygdala reactivity may be a neuronal target for personalized treatments to prevent relapse.

In vivo human brain expression of histone deacetylases in bipolar disorder

The etiology of bipolar disorder (BD) is unknown and the neurobiological underpinnings are not fully understood. Both genetic and environmental factors contribute to the risk of BD, which may be linked through epigenetic mechanisms, including those regulated by histone deacetylase (HDAC) enzymes. This study measures in vivo HDAC expression in individuals with BD for the first time using the HDAC-specific radiotracer [11C]Martinostat. Eleven participants with BD and 11 age- and sex-matched control participants (CON) completed a simultaneous magnetic resonance – positron emission tomography (MR-PET) scan with [11C]Martinostat. Lower [11C]Martinostat uptake was found in the right amygdala of BD compared to CON. We assessed uptake in the dorsolateral prefrontal cortex (DLPFC) to compare previous findings of lower uptake in the DLPFC in schizophrenia and found no group differences in BD. Exploratory whole-brain voxelwise analysis showed lower [11C]Martinostat uptake in the bilateral thalamus, orbitofrontal cortex, right hippocampus, and right amygdala in BD compared to CON. Furthermore, regional [11C]Martinostat uptake was associated with emotion regulation in BD in fronto-limbic areas, which aligns with findings from previous structural, functional, and molecular neuroimaging studies in BD. Regional [11C]Martinostat uptake was associated with attention in BD in fronto-parietal and temporal regions. These findings indicate a potential role of HDACs in BD pathophysiology. In particular, HDAC expression levels may modulate attention and emotion regulation, which represent two core clinical features of BD.

Gray matter bases of psychotic features in adult bipolar disorder: A systematic review and voxel-based meta-analysis of neuroimaging studies.

Psychotic bipolar disorder (P-BD) is a specific subset that presents greater risk of relapse and worse outcomes than nonpsychotic bipolar disorder (NP-BD). To explore the neuroanatomical bases of psychotic dimension in bipolar disorder (BD), a systematic review was carried out based on the gray matter volume (GMV) among P-BD and NP-BD patients and healthy controls (HC). Further, we conducted a meta-analysis of GMV differences between P-BD patients and HC using a whole-brain imaging approach. Our review revealed that P-BD patients exhibited smaller GMVs mainly in the prefronto-temporal and cingulate cortices, the precentral gyrus, and insula relative to HC both qualitatively and quantitatively. Qualitatively the comparison between P-BD and NP-BD patients suggested inconsistent GMV alterations mainly involving the prefrontal cortex, while NP-BD patients showed GMV deficits in local regions compared with HC. The higher proportions of female patients and patients taking psychotropic medication in P-BD and P-BD type I were associated with smaller GMV in the right precentral gyrus, and the right insula, respectively. In conclusions, psychosis in BD might be associated with specific cortical GMV deficits. Gender and psychotropic medication might have effects on the regional GMVs in P-BD patients. It is necessary to distinguish psychotic dimension in neuroimaging studies of BD.

Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen’s d=−0.293; P=1.71 × 10−21), left fusiform gyrus (d=−0.288; P=8.25 × 10−21) and left rostral middle frontal cortex (d=−0.276; P=2.99 × 10−19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Body mass index associates with white matter microstructure in bipolar depression.

Obesity has been reported in over 60% of bipolar disorder (BD) patients. It worsens the severity of illness, and influences cognition and functional outcomes. White matter (WM) abnormalities are one of the most consistently reported findings in neuroimaging studies of BD. We hypothesized that body mass index (BMI) could correlate with WM integrity in bipolar patients. We evaluated BMI in a sample of 164 depressed patients affected by BD. We performed whole-brain tract-based spatial statistics with threshold-free cluster enhancement for the diffusion tensor imaging (DTI) measures of WM integrity: fractional anisotropy; axial, radial, and mean diffusivity. We observed that BMI was associated with DTI measures of WM integrity in several fiber tracts: anterior corona radiata, anterior thalamic radiation, inferior fronto-occipital fasciculus and corpus callosum. The association of BMI in key WM tracts that are crucial to mood regulation and neurocognitive functioning suggests that BMI might contribute to the pathophysiology of BD through a detrimental action on structural connectivity in critical cortico-limbic networks.

Structural brain changes in first episode mania with and without psychosis: Data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM)

Objectives: The neurobiological underpinnings of bipolar I disorder are not yet understood. Previous structural neuroimaging studies of bipolar disorder have produced rather conflicting results. We hypothesise that clinical sub-phenotypes of bipolar I disorder defined by their psychotic symptoms, especially those with mood-incongruent psychotic features, may have more extensive structural brain abnormalities.Methods: We investigated structural brain alterations in patients with first-episode mania (n = 55) with mood-congruent (n = 16) and mood-incongruent (n = 32) psychotic features, as well as those without psychotic symptoms (n = 7), relative to healthy subjects (n = 56).Results: Total intracranial volume was significantly reduced in patients with mood-incongruent psychosis compared to healthy subjects while cerebrospinal fluid (CSF) volume was significantly increased. Patients with mood-congruent psychosis showed significant reduction in total white matter volume and significant CSF volume increase. Patients with psychosis had significant volume reduction in anterior cingulate and medial prefrontal cortices. Relative to mood-congruent psychotic features, mood-incongruent psychotic features were associated with volume reduction in the left middle temporal gyrus, right inferior parietal gyrus, right fusiform gyrus, left middle orbitofrontal gyrus and cerebellum.Conclusions: While preliminary, our findings suggest that the presence and type of psychosis in first-episode mania may be phenotypic markers of underlying biological variants of bipolar disorder.

Cognitive performances associate with measures of white matter integrity in bipolar disorder

BackgroundNeuropsychological deficits constitute enduring trait-like features in bipolar disorder (BD), and persist in euthymia. White matter (WM) abnormalities are one of the most consistently reported findings in neuroimaging studies of BD. We hypothesized that neuropsychological performances could correlate with WM integrity in a sample of bipolar patients in core WM tracts. MethodsSeventy-eight patients affected by BD were evaluated for verbal memory, working memory, psychomotor coordination, executive functions, attention and information processing, and verbal fluency through the Brief Assessment of Cognition in Schizophrenia. White matter integrity was evaluated using DTI and tract-based spatial statistics with threshold free cluster enhancement (p>0.949). ResultsWe observed that cognitive performances in attention and information processing, working memory, executive functions and psychomotor coordination were associated with DTI measures of WM integrity in several association fibres: inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, cingulum bundle, corpus callosum, and corona radiata. LimitationThe drug treatments administered during the course of the illness could have influenced DTI measures and neurocognitive function. Other limitations include issues such as generalizability due to the lack of a control group, possible undetected past comorbidities, population stratification, and the presence of a 28% of patients which previously experienced delusions. ConclusionsThis is the first study to use a validated cognitive battery to investigate the principal cognitive domains in BD. Our data confirm the importance of WM integrity as a neurobiological underpinning of cognitive deficits.

A Critical Appraisal of Neuroimaging Studies of Bipolar Disorder: Toward a New Conceptualization of Underlying Neural Circuitry and a Road Map for Future Research

In this critical review, the authors appraise neuroimaging findings in bipolar disorder in emotion-processing, emotion-regulation, and reward-processing neural circuitry in order to synthesize the current knowledge of the neural underpinnings of bipolar disorder and provide a neuroimaging research road map for future studies. The authors examined findings from all major studies in bipolar disorder that used functional MRI, volumetric analysis, diffusion imaging, and resting-state techniques, integrating findings to provide a better understanding of larger-scale neural circuitry abnormalities in bipolar disorder. Bipolar disorder can be conceptualized, in neural circuitry terms, as parallel dysfunction in prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion-processing and emotion-regulation circuits bilaterally, together with an "overactive" left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward-processing circuitry, resulting in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation, and heightened reward sensitivity. A potential structural basis for these functional abnormalities is gray matter volume decreases in the prefrontal and temporal cortices, the amygdala, and the hippocampus and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuits supporting emotion processing, emotion regulation, and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in youths with bipolar disorder or at risk for bipolar disorder; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful individual-level data. Such studies will help identify clinically relevant biomarkers to guide diagnosis and treatment decision making for individuals with bipolar disorder.

Neurobiology of Mood-State Shifts in Bipolar Disorder

Neuroimaging techniques have begun to elucidate the neurophysiology of bipolar disorder (BPD). Several features of BPD have hindered understanding of how mood-state changes are reflected in changes in brain physiology. Longitudinal studies have advantages in isolating state-related changes and in studying the instability, inherent in these disorders, that gives rise to pathological mood states. To assess the state of the art in longitudinal neuroimaging studies in BPD, we conducted a literature review, searching MEDLINE for articles that included the key words bipolar disorder and magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI), or emission tomography. The search was limited to studies with multiple subjects at two distinct and defined mood states. This search yielded eight MRS studies, four functional MRI studies, and three positron emission tomography studies. Although longitudinally designed studies allow for the isolation of biomarkers of mood state (including euthymia), the current literature is hampered by a lack of replication between studies. The current body of longitudinal BPD imaging studies is heterogeneous and incomplete, and does not lend itself to the construction of an explanatory model of mood-state transitions. Drawing on extant studies, we propose a hypothetical framework for future experiments combining multimodal imaging with a longitudinal study design.

États mixtes et neuroimagerie

Despite the growing number of neuroimaging studies in bipolar disorder over the past years, the brain regions involved in mood dysregulation in this disease are still poorly understood. If some neurofunctional abnormalities seem to be independent of mood state, others were preferentially associated with mania or depression, involving the amygdala and other limbic regions as well as ventral frontal regions, with a likely hemispheric lateralization of these abnormalities according to the thymic state that was examined. Very few imaging studies became interested in bipolar patients in a mixed state, making it harder to connect brain malfunction to a given mood state. However, data obtained so far support the hypothesis of a lateralization of brain abnormalities in relation to bipolar symptomatology, suggesting that neurofonctional abnormalities preferentially located in the right ventral frontal and limbic areas may underlie the depressive component, associated with abnormalities of the left similar regions for the manic component. Identification of brain dysfunctions that may explain the emergence of mixed symptoms will likely provide useful information to better understand the respective roles of each hemisphere in the pathophysiology of bipolar disorder.

Effects of medication on neuroimaging findings in bipolar disorder: an updated review

Neuroimaging is an important tool for better understanding the neurobiological underpinnings of bipolar disorder (BD). However, potential study participants are often receiving psychotropic medications which can possibly confound imaging data. To better interpret the results of neuroimaging studies in BD, it is important to understand the impact of medications on structural magnetic resonance imaging (sMRI), functional MRI (fMRI), and diffusion tensor imaging (DTI). To better understand the impact of medications on imaging data, we conducted a literature review and searched MEDLINE for papers that included the key words bipolar disorder and fMRI, sMRI, or DTI. The search was limited to papers that assessed medication effects and had not been included in a previous review by Phillips et al. (Medication effects in neuroimaging studies of bipolar disorder. Am J Psychiatry 2008; 165: 313-320). This search yielded 74 sMRI studies, 46 fMRI studies, and 15 DTI studies. Medication appeared to influence many sMRI studies, but had limited impact on fMRI and DTI findings. From the structural studies, the most robust finding (20/45 studies) was that lithium was associated with increased volumes in areas important for mood regulation, while antipsychotic agents and anticonvulsants were generally not. Regarding secondary analysis of the medication effects of fMRI and DTI studies, few showed significant effects of medication, although rigorous analyses were typically not possible when the majority of subjects were medicated. Medication effects were more frequently observed in longitudinal studies designed to assess the impact of particular medications on the blood oxygen level-dependent (BOLD) signal. With a few exceptions, the observed effects were normalizing, meaning that the medicated individuals with BD were more similar than their unmedicated counterparts to healthy subjects. The effects of psychotropic medications, when present, are predominantly normalizing and thus do not seem to provide an alternative explanation for differences in volume, white matter tracts, or BOLD signal between BD participants and healthy subjects. However, the normalizing effects of medication could obfuscate differences between BD and healthy subjects, and thus might lead to type II errors.

Increased hippocampal volumes in lithium treated adolescents with bipolar disorders: A structural MRI study

Structural neuroimaging studies in bipolar disorder (BD) have consistently identified several anatomical abnormalities in many brain areas related to mood regulation. Hippocampus is one of the key components of emotional regulatory networks in the brain. Evidence about hippocampal changes in BD is quite limited and inconsistent particularly for adolescent onset BD. It is aimed to compare hippocampus volumes of euthymic BD-I adolescents with healthy controls using structural MRI. Hippocampal volumes of seventeen youths between 13 and 19 age period with DSM-IV BD (seven boys) and twelve healthy comparison subjects (five boys) were compared using structural MRI. Differences in hippocampal volumes between groups were tested. There was no significant difference between the right and left hippocampus volumes of patients with BD and the control group. However boys tended to have significantly larger right hippocampal volumes than girls both in BD and control group. Right hippocampal volumes were enlarged in lithium treated bipolar patients. This enlargement is not related to sex. Future, longitudinal follow-up studies need large enough sample sizes of both sexes and a sex-matched healthy comparison group to sort out developmental, gender and medication influences on brain structures over time in BD. Lithium treatment in adolescent-onset BD has a significant effect on hippocampus volumes.

A meta-analysis of whole-brain diffusion tensor imaging studies in bipolar disorder

White matter abnormalities are one of the most consistently reported findings in neuroimaging studies of bipolar disorder (BD). We conducted an anatomical likelihood estimation meta-analysis of BD whole-brain diffusion tensor imaging (DTI) studies, with the aim of identifying statistically consistent fractional anisotropy (FA) changes reflecting microstructural modifications to white matter in BD. We performed online searches of the PUBMED and EMBASE databases in January 2011. Studies were considered for inclusion if they used diffusion tensor MRI, compared a group of subjects with BD with healthy controls and involved whole-brain white matter analysis of FA. The analyses were conducted in Talairach space, using the activation likelihood estimation technique. We carried out a meta-analysis restricted to studies reporting a lower FA in patients with BD than in healthy controls. Ten studies were included. We identified two significant clusters of decreased FA on the right side of the brain. The first was located in the right white matter, close to the parahippocampal gyrus. Four of the ten studies included contributed to this cluster. The second cluster was located close to the right anterior and subgenual cingulate cortex. These two clusters of decreased FA in BD are crossed by several white matter tracts. These two clusters of altered FA may underlie the abnormal emotional processing and altered functional limbic connectivity in BD. Explorations based on DTI-based tractography are required to identify the tracts involved in the pathophysiology of BD.

Neuroimaging-based markers of bipolar disorder: Evidence from two meta-analyses

Bipolar disorder (BD) is often misdiagnosed or tardily detected, leading to inadequate treatment and devastating consequences. The identification of objective biomarkers, such as functional and structural brain abnormalities of BD might improve diagnosis and help elucidate its pathophysiology. To identify neurobiological markers of BD, two meta-analyses, one of functional neuroimaging studies related to emotional processing and a second of structural whole-brain neuroimaging studies in BD were conducted in the present study. Conducting a literature search on studies published up to September 2009 we identified 28 studies that were eligible for the meta-analyses: 13 functional magnetic resonance imaging studies, related to emotional processing and 15 structural imaging studies using whole-brain voxel-based morphometry. Only studies comparing patients with bipolar disorder to healthy controls were considered. Data were extracted or converted to a single anatomical reference (Talairach space). The activation likelihood estimation technique was used to assess the voxel-wise correspondence of results between studies. In patients with BD, decreased activation and diminution of gray matter were identified in a cortical-cognitive brain network that has been associated with the regulation of emotions. By contrast, patients with BD exhibited increased activation in ventral limbic brain regions that mediate the experience of emotions and generation of emotional responses. The present study provides evidence for functional and anatomical alterations in BD in brain networks associated with the experience and regulation of emotions. These alterations support previously proposed neurobiological models of BD and might represent valid neurobiological markers of the disorder. The specificity of these results to unipolar depression remains to be explored.

Remission from mania is associated with a decrease in amygdala activation during motor response inhibition

Neuroimaging studies of bipolar disorder (BD) have provided evidence of brain functional abnormalities during both the states of mania and remission. However, the differences in brain function between these two states are still poorly known. In the current study, we aimed to use a longitudinal design to examine the functional changes associated with symptomatic remission from mania within the brain network underlying motor response inhibition. Using event-related functional magnetic resonance imaging (fMRI), 10 BD patients and 10 healthy subjects were imaged twice while performing a Go/NoGo task. Patients were in a manic state when they underwent the first scan and fully remitted during the second scan. A mixed-effect ANOVA was used to identify brain regions showing differences in activation change over time between the two groups. The left amygdala was the only brain region to show a time-dependent change in activation that was significantly different between BD patients and healthy subjects. Further analyses revealed that this difference arose from the patient group, in which amygdala activation was decreased between mania and subsequent remission. This finding suggests that a decrease in left amygdala responsiveness is a critical phenomenon associated with remission from mania. It emphasizes the relevance of longitudinal approaches for identifying neurofunctional modifications associated with mood changes in BD.

Functional neuroimaging studies of bipolar disorder: Examining the wide clinical spectrum in the search for disease endophenotypes

Bipolar disorder (BP) is among the top ten most disabling illnesses worldwide. This review includes findings from recent studies employing functional neuroimaging to examine functional abnormalities in neural systems underlying core domains of the psychopathology in BP: emotion processing, emotion regulation and executive control, and common comorbid features of BP, that are relevant to the wide spectrum of BP rather than focused on the more traditional BPI subtype, and that may facilitate future identification of diagnostically-relevant biomarkers of the disorder. In addition, an emerging number of studies are reviewed that demonstrate the use of neuroimaging to elucidate biomarkers whose identification may help to (1) identify at-risk individuals who will subsequently develop the illness to facilitate early intervention, (2) identify targets for treatment and markers of treatment response. The use of newer neuroimaging techniques and potential confounds of psychotropic medication upon neuroimaging findings in BP are also examined. These approaches will help to improve diagnosis and the mental well-being of all individuals with BP.

Medication Effects in Neuroimaging Studies of Bipolar Disorder

Neuroimaging studies are promising components for a new diagnostic framework for bipolar disorder, but a major issue is the potential confound of psychotropic medication upon experimental measures. Withdrawing all individuals from medication and examining only unmedicated individuals may be clinically unfeasible, and examining only unmedicated individuals may render findings less generalizable. The authors review structural and functional neuroimaging studies of medicated and unmedicated patients with bipolar disorder to discern the possible confounding effect of medication. Findings from studies identified on MEDLINE that included medicated individuals with bipolar disorder indicated either no significant effect or ameliorative effects of psychotropic medications on abnormal structural and functional neuroimaging measures relevant to pathophysiologic mechanisms of the disorder. Different strategies for assessing medication effects are compared. Neuroimaging studies of bipolar disorder ideally should recruit both unmedicated and medicated individuals. Individuals who are unable to tolerate medication withdrawal likely have more severe illness and are especially informative for research examining biomarkers of illness and treatment response.

Regional Cerebral Glucose Metabolic Abnormalities in Bipolar II Depression

Functional neuroimaging studies of bipolar disorder (BD) performed in conjunction with antidepressant treatment trials generally require that patients remain on mood stabilizers to reduce the risk of inducing mania; yet, it is unknown whether the metabolic abnormalities evident in unmedicated BD depressives remain detectable in patients receiving mood stabilizers. This study investigated whether cerebral metabolic abnormalities previously reported in unmedicated BD subjects are evident in depressed bipolar disorder type II (BD II) subjects receiving lithium or divalproex. Using [18F]-fluorodeoxyglucose-positron-emission tomography, cerebral glucose metabolism was compared between 13 depressed BD II subjects on therapeutic doses of lithium or divalproex and 18 healthy control subjects. Regional metabolism was compared between groups in predefined regions of interest. Metabolism was increased in the bilateral amygdala, accumbens area, and anteroventral putamen, left orbitofrontal cortex and right pregenual anterior cingulate cortex in depressives versus control subjects. Post hoc exploratory analysis additionally revealed increased metabolism in left parahippocampal, posterior cingulate, and right anterior insular cortices in depressives versus control subjects. Correlational analyses showed multiple limbic-cortical-striatal interactions in the BD sample not evident in the control sample, permitting sensitive and specific classification of subjects by discriminant analysis. These results confirm previous reports that bipolar depression is associated with abnormally increased metabolism in the amygdala, ventral striatum, orbitofrontal cortex, anterior cingulate, and anterior insula, and extend these results to bipolar disorder type II depressives on lithium or divalproex. They also implicate an extended functional anatomical network known to modulate visceromotor function in the pathophysiology of BD II depression.

Les anomalies structurales observées en imagerie cérébrale dans le trouble bipolaire

The number of structural neuroimaging studies of bipolar disorder have increased during recent years, expanding the literature on the nature of cerebral abnormalities underlying this disorder. The purpose of this paper is to provide a selective review on the main issues concerning this literature. Consistent findings are higher rate of periventricular and deep subcortical white matter hyperintensites seen on MRI. Although there is strong evidence for links between hyper-intense lesions and age or cardio-vascular risk factors, some authors have observed the presence of these abnormalities early in the course of the illness. There are also frequent reports on ventricular enlargement, which has been described as mild and predominant in the right lateral ventricle. Total cerebral volume appears to be preserved. Whereas changes in total grey matter volume are uncertain, evidence suggests that reduced white matter volume reflects genetic factors predisposing to the disorder. Recent studies have reported volume changes in several cortical areas including the subgenual cingular, frontal and temporal cortices. Additionally, a number of reports described morphometric abnormalities in various subcortical structures, such as amygdala, basal ganglia and thalamus. Part of the variability in the morphometric abnormalities might be attributable to differences in clinical status and demographic characteristics of patient groups. Despite some inconsistencies across the studies, it emerges that abnormalities are asymmetrically distributed throughout the two cerebral hemispheres. When increase in volume is reported, it is preferentially localised in the left cerebral hemi-sphere and more specifically in prefrontal and temporal cortices and in amygdala. By contrast, when structural abnormalities concern the right cerebral hemisphere, they are identified as deficits. These latter results are in direct line with those of studies of mania following brain injuries, which report that these secondary mania result mainly from right cerebral lesions. It is also important to notice that most of the abnormalities concern both the cortical and subcortical level, ie frontal, striatal, thalamic and limbic regions. These abnormalities highlight the role in the pathophysiology of bipolar disorder of the loops involved in emotional information processing. The particular role of fronto-limbic loops in the phenomenology of bipolar disorder have been emphasised by recent data from functional neuroimaging studies.

Bipolar Disorder: Imaging State Versus Trait

Bipolar Disorder: Imaging State Versus Trait