Glymphatic system dysfunction in mood disorders: Evaluation by diffusion magnetic resonance imaging.

The glymphatic system, an expansive cerebral waste-disposal network, harbors myriad enigmatic facets necessitating elucidation of their nexus with diverse pathologies. Murine investigations have revealed a relationship between the glymphatic system and affective disorders. This study aimed to illuminate the interplay between bipolar disorder and the glymphatic system. Fifty-eight individuals afflicted with bipolar disorder were identified through meticulous psychiatric assessment. These individuals were juxtaposed with a cohort of 66 comparably aged and sex-matched, mentally stable subjects. Subsequent analysis entailed the application of covariance analysis to evaluate along with the perivascular space (ALPS) index, a novel magnetic resonance imaging method for assessing brain interstitial fluid dynamics via diffusion tensor imaging within the bipolar and control cohorts. We also evaluated the correlation between the ALPS index and clinical parameters, which included the Hamilton Depression scale scores, disease duration, and other clinical assessments. Moreover, partial correlation analyses, incorporating age and sex as covariates, were performed to investigate the relationships between the ALPS index and clinical measures within the two cohorts. A noteworthy adverse correlation was observed between the ALPS index and illness duration. A free-water imaging analysis revealed a substantial elevation in the free-water index within the white-matter tracts, prominently centered on the corpus callosum, within the bipolar cohort relative to that in the control group. In analogous cerebral regions, a conspicuous affirmative correlation was observed between the free-water-corrected radial diffusivity and depression rating scales. Our results showed that the protracted course of bipolar disorder concomitantly exacerbated glymphatic system dysregulation.

A Selective Hand Posture Apraxia in an Individual With Posterior Cortical Atrophy and Probable Corticobasal Syndrome.

A selective impairment for making hand postures that are required to use specific tools has rarely been reported in individuals with acquired brain injury, and such an impairment has not been documented at all in individuals with degenerative disorders. We describe an individual with posterior cortical atrophy and probable corticobasal syndrome who was unable to use tools because of an inability to make the proper hand posture required for each tool. This individual was, however, able to use the tools properly once her hand postures were corrected, and her ability to manipulate the tools (ie, timing, arm posture, and amplitude) was intact. Also, she had no difficulty with a test of her manipulation knowledge. Areas of hypoperfusion observed by single-photon emission computerized tomography included the anterior intraparietal sulcus in the left parietal lobe, which is an area that has been proposed to control hand postures. This selective impairment might be explained by the reasoning-based hypothesis for apraxia, which attributes hand posture errors in the absence of manipulation errors to dysfunction in one of the three independent pathways that subserve tool use, rather than the manipulation-based hypothesis for apraxia, which attributes hand posture errors to impaired manipulation knowledge. This is the first case with a degenerative disorder that revealed a selective impairment for making hand postures for tool use, which might be explained mainly by apraxia of hand postures along with visuospatial dysfunction (simultanagnosia) and/or sensory disturbance.

Comparison of White Matter Structure of Drug-Naïve Patients With Bipolar Disorder and Major Depressive Disorder Using Diffusion Tensor Tractography.

BACKGROUND: The presence of microstructural white matter (WM) abnormalities in individuals with bipolar disorder (BD) has previously been reported. However, the interpretation of data is challenging because pharmacological treatment has a potential effect on WM integrity. To date, no study has compared the differences in WM structure among drug-naïve BD patients, drug-naïve major depression disorder (MDD) patients, and healthy controls (HC) using the visual evaluation method of diffusion tensor tractography (DTT). METHODS: This retrospective study included 12 drug-naïve patients with BD, 15 drug-naïve patients with MDD, and 27 age- and sex-matched HC individuals. Visual evaluation, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were analysed in the anterior thalamic radiation (ATR) as a tract of interest using the optimal follow-up truncation threshold. They were also analysed in the cingulate fasciculus, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, and fornix. RESULTS: No significant differences were found in the FA or ADC of any tract. However, visual evaluation revealed poorer depiction of ATR in patients with BD than in patients with MDD and HC individuals (p = 0.004). Our post-hoc analysis showed a significant difference between BD and HC patients (p = 0.018). CONCLUSIONS: The visual evaluation method of DTT revealed poor depiction of ATR in patients with BD compared with HC individuals and MDD patients, suggesting microstructural WM abnormalities of ATR in BD.

Regional brain volume reductions in major depressive disorder and bipolar disorder: An analysis by voxel-based morphometry.

OBJECTIVES: The present study investigated the usefulness of evaluating the existence of volume reduction in brain regions using voxel-based morphometry (VBM) to dissociate major depressive disorder (MDD) from bipolar disorder (BD). METHODS/DESIGN: This study enrolled 92 individuals with MDD, 32 individuals with BD, and 43 healthy controls (HCs). We focused on gray matter volume (GMV) of the subgenual anterior cingulate cortex (sgACC), subcallosal area (SCA), and hippocampus. The degree of volume reduction in these brain regions was calculated as the z score, and the differences of z scores in these regions were investigated among the MDD, BD, and HC groups. We then performed a receiver operating characteristic curve analysis to dissociate the individuals with MDD and BD from the HCs based on the z scores in the GMV of these brain regions. RESULTS: While there were no significant differences in the z scores of the hippocampus among the three groups, the z score of the sgACC was significantly higher in the MDD group than in the BD and HC groups, and the SCA z score was significantly higher in the MDD and BD groups than in the HC group. CONCLUSIONS: Our findings suggest that VBM evaluation of GMV reduction in the sgACC may be useful as an objective adjunctive tool to distinguish between MDD and BD.

Aberrant Anterior Thalamic Radiation Structure in Bipolar Disorder: A Diffusion Tensor Tractography Study.

Disrupted white matter (WM) integrity in the anterior thalamic radiation (ATR) has been identified in individuals with bipolar disorder (BD). We explored whether structural WM aberration in the ATR could be visually evaluated by diffusion tensor tractography (DTT). The study comprised 114 participants, including 57 patients with BD and 57 healthy controls (HCs). A poorly visualized ATR reflects an abnormal WM structure. We defined a poorly visualized ATR as one in which at least one ATR fiber bundle failed to reach to the boundary between gray and white matter. Poor ATR visualization occurred significantly more frequently in the left ATR of those with BD than in HCs (P = 0.042). Furthermore, we adjusted the fractional anisotropy (FA) value and when evaluation of a given ATR changed from good to poor, we defined that value as the optimal FA threshold. In the right ATR, we successfully classified BD and HCs with 71.1% accuracy (sensitivity = 89.5% and specificity = 52.6%) and an area under the curve of 0.76 using the optimal FA threshold of 0.28. The present results suggest that the optimal FA threshold can serve as a biological marker that distinguishes individuals with BD from HCs. Thus, visual evaluation of the ATR by DTT may prove to be a useful adjunctive diagnostic tool for BD in clinical practice.

[The Center of Sadness, Pain, and Recognition].

The posterior cingulate cortex (Brodmann area, BA 23) is the hub of the default mode network (DMN). Moreover, its network connectivity decreases early in Alzheimer disease. The anterior cingulate cortex (BA 24) is connected to networks such as the DMN, working memory network (WMN), and salience network (SN) and plays a role in network coordination. The subgenual anterior cingulate cortex (sgACC) on the rostral region of the anterior cingulated cortex is suggested to be associated with depression.

Analysis of the presence or absence of atrophy of the subgenual and subcallosal cingulate cortices using voxel-based morphometry on MRI is useful to select prescriptions for patients with depressive symptoms.

OBJECTIVE: We objectively evaluated the presence or absence of atrophy of the subgenual anterior cingulate cortex (sgACC) and the subcallosal anterior cingulate cortex (scACC), using new voxel-based morphometry (VBM) software employing Statistical Parametric Mapping software v8 and diffeomorphic anatomic registration through an exponentiated lie algebra. We prepared a database covering young-mature adulthood and investigated the clinical usefulness of the evaluation. SUBJECTS AND METHODS: One hundred seven patients with major depressive disorder (MDD), 74 patients with bipolar disorder (BD), and 240 healthy control subjects underwent 1.5T magnetic resonance imaging scanning. Using new VBM software and databases covering young-mature adults and the elderly, target volumes of interest were set in the sgACC and scACC, four indicators (severity, extent, ratio, and whole-brain extent) were determined, and the presence or absence of atrophy of the sgACC and scACC was evaluated on the basis of the indicators. In addition, the relationships between the presence or absence of atrophy of the sgACC and scACC and performance of diagnosing MDD and BD and therapeutic drugs were investigated. RESULTS: It was clarified that the disease is likely to be MDD when atrophy is detected in the sgACC, and likely to be BD when no atrophy is detected in the sgACC but is detected in the scACC. Regarding the relationship with therapeutic drugs, it was clarified that, when atrophy is detected in both the sgACC and the scACC, concomitant administration of mood stabilizers and atypical antipsychotics acting as dopamine-system stabilizers is necessary in many cases. CONCLUSION: VBM on magnetic resonance imaging enabled automatic analysis of atrophy in the sgACC and scACC, and findings obtained by this procedure are useful not only for differentiation of MDD and BD patients but also for selection of prescriptions.

Usefulness of visual evaluation of the anterior thalamic radiation by diffusion tensor tractography for differentiating between Alzheimer's disease and elderly major depressive disorder patients.

BACKGROUND AND OBJECTIVE: Many surveys of neural integrity of the cerebral white matter with psychiatric diseases on diffusion tensor imaging have recently been performed, but these mainly utilize fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) values, and the results were inconsistent and not fully applied clinically. In this study, we investigated the possibility of differentiating between Alzheimer's disease (AD) and elderly major depressive disorder (MDD) patients in whom early-stage symptoms are difficult to diagnose, by visually evaluating cerebral nerve fascicles utilizing diffusion tensor tractography. We also measured and evaluated FA and ADC values at the same time. SUBJECTS AND METHODS: The subjects included 13 AD patients (age: 69.5 ± 5.1 years), 19 MDD patients (65.8 ± 5.7 years), and 22 healthy control (HC) subjects (67.4 ± 4.8 years). Images were acquired using a 1.5T magnetic resonance imaging device and analyzed by diffusion tensor tractography analysis software. RESULTS: Depiction of the anterior thalamic radiation (ATR) tended to be poor in AD patients unlike in MDD patients and HC subjects. The FA values in the left superior longitudinal fasciculus and fornix (FX) in AD patients were significantly different from those in MDD patients and HC subjects. The ADC values in the bilateral ATR and left superior and inferior longitudinal fasciculi, left inferior fronto-occipital fasciculus, and FX in AD patients were significantly different from those in MDD patients and HC subjects. CONCLUSION: Visual evaluation of the ATR in combination with the FA values of the left superior longitudinal fasciculus and FX and ADC values of the bilateral ATR, left superior and inferior longitudinal fasciculi, left inferior fronto-occipital fasciculus, and FX is useful for differentiating between AD and MDD patients, which further suggests that it may become a useful auxiliary diagnostic tool.

Identification of atrophy of the subgenual anterior cingulate cortex, in particular the subcallosal area, as an effective auxiliary means of diagnosis for major depressive disorder.

BACKGROUND: Despite being a very common psychiatric disorder, physicians often have difficulty making a diagnosis of major depressive disorder (MDD) because, without established diagnostic criteria, they have to depend on interviews with patients and observation to assess psychiatric symptoms. However, previous researchers have reported that magnetic resonance imaging (MRI) scans identify morphological changes in the brains of patients with MDD, which inspired us to hypothesize that assessment of local changes in the brain using voxel-based morphometry would serve as an auxiliary diagnostic method for MDD. Therefore, we focused on the VSRAD(®) plus (voxel-based specific regional analysis system for Alzheimer's disease), a diagnostic support system for use in early Alzheimer's disease, which allowed us to identify regional atrophy in the brain easily based on images obtained from MRI scans. METHODS: The subjects were 75 patients with MDD, 15 with bipolar disorder, and 30 healthy subjects, aged 54-82 years. First, 1.5 T MRI equipment was used to scan three-dimensional T(1)-weighted images for the individual subjects, and the imaged data were analyzed by VSRAD advance (voxel-based morphometric software developed for diagnosis of early Alzheimer's disease). The efficacy of the equipment for diagnosis of MDD was evaluated based on the distribution of atrophy in the subgenual anterior cingulate cortex (sACC) on the z-score map obtained. RESULTS: No significant difference in atrophy was noted between the left and right sACCs. The VSRAD advance used in the present study was more effective than the VSRAD plus for diagnosis of MDD, with a sensitivity of 90.7%, specificity of 86.7%, accuracy of 89.5%, a positive predictive value of 94.4%, and a negative predictive value of 78.8%. In particular, atrophy was observed in the subcallosal area of the sACC. CONCLUSION: The identification of atrophy in the sACC, in particular of the subcallosal area, with the use of updated voxel-based morphometric software proved to be effective as an auxiliary diagnostic method for MDD.

Diagnosis of depression by MRI scans with the use of VSRAD - a promising auxiliary means of diagnosis: a report of 10 years research.

OBJECTIVES: This study was designed to evaluate the usefulness of assessing subgenual anterior cingulate cortex (sACC) volume reduction by magnetic resonance imaging (MRI) as an objective auxiliary means of diagnosis of depression. The study was additionally designed to analyze the association of sACC volume reduction with the effectiveness of treatments for depression and other diseases presenting with similar symptoms, and to examine the possibility of using sACC volume reduction in the distinction between depression and bipolar disorder and determining optimum medication for these conditions. METHODS: Three-dimensional T1-weighted sagittal images, taken with Achieva 1.5T NOVA (Philips), were analyzed with VSRAD plus(®) to evaluate a reduction in sACC volume. The finding from this analysis was compared with the clinical data, including the longitudinal course follow-up data based on the treatment algorithm. SUBJECTS: The study involved 88 patients aged over 54 who received MRI during 2010, ie, 71 patients with major depressive disorder (MDD), 11 patients bipolar disorder, and 6 patients in whom the initial diagnosis (MDD) was later modified. Thirty-three normal individuals served as controls. RESULTS: sACC volume reduction was noted in 66 of the 71 patients receiving treatment of MDD, with sensitivity of 93%, specificity of 85%, and accuracy of 90%. In the 66 patients diagnosed as having MDD and exhibiting sACC volume reduction, the disease showed remission in response to treatment with antidepressants, but medication needed to be continued after achievement of remission. In cases initially diagnosed as having MDD but not exhibiting sACC volume reduction, the necessity of modifying the diagnosis was considered. Typical cases of bipolar disorder did not exhibit sACC volume reduction. CONCLUSION: That patients receiving treatment of MDD often showed reduction in sACC volume suggests the usefulness of this parameter as an objective auxiliary means of diagnosis for MDD.