[CACNA1C rs58619945 genotype influences the cortical thickness of attention network among patients with Bipolar â disorder].

OBJECTIVE: To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). METHODS: From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. RESULTS: Compared with the HC group, the BD-I patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex. A significant interaction between the CACNA1C genotype and the cortical thickness of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted. Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex predominantly among carriers of the BD-I G allele. CONCLUSION: The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Distinct global brain connectivity alterations in depressed adolescents with subthreshold mania and the relationship with processing speed: Evidence from sBEAD Cohort.

BACKGROUND: Bipolar disorder (BD) is a progressive condition. Investigating the neuroimaging mechanisms in depressed adolescents with subthreshold mania (SubMD) facilitates the early identification of BD. However, the global brain connectivity (GBC) patterns in SubMD patients, as well as the relationship with processing speed before the onset of full-blown BD, remain unclear. METHODS: The study involved 72 SubMD, 77 depressed adolescents without subthreshold mania (nSubMD), and 69 gender- and age-matched healthy adolescents (HCs). All patients underwent a clinical follow-up ranging from six to twelve months. We calculated the voxel-based graph theory analysis of the GBC map and conducted the TMT-A test to measure the processing speed. RESULTS: Compared to HCs and nSubMD, SubMD patients displayed distinctive GBC index patterns: GBC index decreased in the right Medial Superior Frontal Gyrus (SFGmed.R)/Superior Frontal Gyrus (SFG) while increased in the right Precuneus and left Postcentral Gyrus. Both patient groups showed increased GBC index in the right Inferior Temporal Gyrus. An increased GBC value in the right Supplementary Motor Area was exclusively observed in the nSubMD-group. There were opposite changes in the GBC index in SFGmed.R/SFG between two patient groups, with an AUC of 0.727. Additionally, GBC values in SFGmed.R/SFG exhibited a positive correlation with TMT-A scores in SubMD-group. LIMITATIONS: Relatively shorter follow-up duration, medications confounding, and modest sample size. CONCLUSION: These findings suggest that adolescents with subthreshold BD have specific impairments patterns at the whole brain connectivity level associated with processing speed impairments, providing insights into early identification and intervention strategies for BD.

Alterations in resting-state global brain connectivity in bipolar I disorder patients with prior suicide attempt.

BACKGROUND: Bipolar I disorder (BD-I) is associated with a high risk of suicide attempt; however, the neural circuit dysfunction that confers suicidal vulnerability in individuals with this disorder remains largely unknown. Resting-state functional magnetic resonance imaging (rs-fMRI) allows non-invasive mapping of brain functional connectivity. The current study used an unbiased voxel-based graph theory analysis of rs-fMRI to investigate the intrinsic brain networks of BD-I patients with and without suicide attempt. METHODS: A total of 30 BD-I patients with suicide attempt (attempter group), 82 patients without suicide attempt (non-attempter group), and 67 healthy controls underwent rs-fMRI scan, and then global brain connectivity (GBC) was computed as the sum of connections of each voxel with all other gray matter voxels in the brain. RESULTS: Compared with the non-attempter group, we found regional differences in GBC values in emotion-encoding circuits, including the left superior temporal gyrus, bilateral insula/rolandic operculum, and right precuneus (PCu)/cuneus in the bipolar disorder (BD) attempter group, and these disrupted hub-like regions displayed fair to good power in distinguishing attempters from non-attempters among BD-I patients. GBC values of the right PCu/cuneus were positively correlated with illness duration and education in the attempter group. CONCLUSIONS: Our results indicate that abnormal connectivity patterns in emotion-encoding circuits are associated with the increasing risk of vulnerability to suicide attempt in BD patients, and global dysconnectivity across these emotion-encoding circuits might serve as potential biomarkers for classification of suicide attempt in BD patients.

Effectiveness of electroconvulsive therapy in patients with "less treatment-resistant" depression by the Maudsley Staging Model.

INTRODUCTION: Electroconvulsive therapy (ECT) is an effective treatment for patients with mood disorders and is most often used for treatment-resistant cases. This study aimed to examine the effectiveness of ECT in a real-world treatment sample in a Chinese psychiatric hospital which included both treatment-resistant and nontreatment-resistant patients. METHODS: An observational study of symptom outcomes from admission to the time of discharge was conducted with 37 inpatients diagnosed with unipolar or bipolar depression treated with ECT. Symptom severity was assessed with the 17-item Hamilton Rating Scales for Depression (HRSD-17) and treatment-resistance with the Maudsley Staging Model (MSM). Stratifying at the MSM median admission characteristics and symptom change was compared between patients who were treatment-resistant (n = 18) and who were not (n = 19). The outcome difference between groups was compared using analyses of covariance adjusted for baseline characteristics including symptom severity, followed by linear regression to identify factors associated symptom improvement in the entire sample. RESULTS: The sample (n = 37) showed moderate treatment-resistance (MSM = 7.30 ± 1.13) at admission and both groups received 8.3 ± 2 ECT sessions. The treatment-resistant group had a smaller proportion of bipolar patients and more severe symptoms, but showed no significant difference from the nontreatment-resistant group in HDRS-17 scores at the time of discharge (adjusted means = 6.23 ± 1.00 vs. 5.94 ± 0.97, Partial η2  = 0.001, p = .845). Baseline symptom severity was the strongest correlate of reduction in HDRS-17 scores (ß = 0.891, p < .001). CONCLUSIONS: Symptom change with ECT in depression did not differ by level of treatment-resistance but was greatest among those with more severe baseline symptoms. Correlates of ECT effectiveness should be further evaluated in stratified randomized trials.

Are existing self-ratings of acute manic symptoms in adults reliable and valid?-A systematic review.

BACKGROUND: Depression research historically uses both self- and clinician ratings of symptoms with significant and substantial correlations. It is often assumed that manic patients lack insight and cannot accurately report their symptoms. This delayed the development of self-rating scales for mania, but several scales now exist and are used in research. Our objective is to systematically review the literature to identify existing self-ratings of symptoms of (hypo)mania and to evaluate their psychometric properties. METHODS: PubMed, Web of Knowledge, and Ovid were searched up until June 2018 using the keywords: "(hypo)mania," "self-report," and "mood disorder" to identify papers which included data on the validity and reliability of self-rating scales for (hypo)mania in samples including patients with bipolar disorder. RESULTS: We identified 55 papers reporting on 16 different self-rating scales claiming to assess (hypo)manic symptoms or states. This included single item scales, but also some with over 40 items. Three of the scales, the Internal State Scale (ISS), Altman Self-Rating Mania Scale (ASRM), and Self-Report Manic Inventory (SRMI), provided data about reliability and/or validity in more than three independent studies. Validity was mostly assessed by comparing group means from individuals in different mood states and sometimes by correlation to clinician ratings of mania. CONCLUSIONS: ASRM, ISS, and SRMI are promising self-rating tools for (hypo)mania to be used in clinical contexts. Future studies are, however, needed to further validate these measures; for example, their associations between each other and sensitivity to change, especially if they are meant to be outcome measures in studies.

CACNB2 rs11013860 polymorphism correlates of prefrontal cortex thickness in bipolar patients with first-episode mania.

BACKGROUND: The ß2 subunit of the voltage-gated l-type calcium channel gene(CACNB2) rs11013860 polymorphism is a putative genetic susceptibility marker for bipolar disorder (BD). However, the neural effects of CACNB2 rs11013860 in BD are largely unknown. METHODS: Forty-six bipolar patients with first-episode mania and eighty-three healthy controls (HC) were genotyped for CACNB2 rs11013860 and were scanned with a 3.0 Tesla structural magnetic resonance imaging system to measure cortical thickness of prefrontal cortex (PFC) components (superior frontal cortex, orbitofrontal cortex, middle and inferior frontal gyri). RESULTS: Cortical thickness was thinner in patients on all PFC measurements compared to HC (p < 0.050). Moreover, we found a significant interaction between CACNB2 genotype and diagnosis for the right superior frontal cortical thickness (F = 8.190, p = 0.040). Bonferroni corrected post-hoc tests revealed that, in CACNB2 A-allele carriers, patients displayed thinner superior frontal thickness compared to HC (p < 0.001). In patients, CACNB2 A-allele carriers also exhibited reduced superior frontal thickness compared to CACNB2 CC-allele carriers (p = 0.016). LIMITATIONS: Lithium treatment may influence our results, and the sample size in our study is relatively small. CONCLUSIONS: Our results suggest that the CACNB2 rs11013860 might impact PFC thickness in patients with first-episode mania. These findings provide evidence to support CACNB2 rs11013860 involvement in the emotion-processing neural circuitry abnormality in the early stage of BD, which will ultimately contribute to revealing the link between the variation in calcium channel genes and the neuropathological mechanism of BD.

Abnormal Degree Centrality Associated With Cognitive Dysfunctions in Early Bipolar Disorder.

Delayed diagnosis of bipolar disorder (BD) is common. However, diagnostic validity may be enhanced using reliable neurobiological markers for BD. Degree centrality (DC) is one such potential marker that enables researchers to visualize neuronal network abnormalities in the early stages of some neuropsychiatric disorders. In the present study, we measured resting-state DC abnormalities and cognitive deficits in order to identify early neurobiological markers for BD. We recruited 23 patients with BD who had recently experienced manic episodes (duration of illness <2 years) and 46 matched healthy controls. Our findings indicated that patients with BD exhibited DC abnormalities in frontal areas, temporal areas, the right postcentral gyrus, and the posterior lobe of the cerebellum. Moreover, correlation analysis revealed that psychomotor speed indicators were associated with DC in the superior temporal and inferior temporal gyri, while attention indicators were associated with DC in the inferior temporal gyrus, in patients with early BD. Our findings suggest that DC abnormalities in neural emotion regulation circuits are present in patients with early BD, and that correlations between attention/psychomotor speed deficits and temporal DC abnormalities may represent early markers of BD.

Effectiveness of cognitive behavioral therapy in treating bipolar disorder: An updated meta-analysis with randomized controlled trials.

AIM: The aim of this updated meta-analysis was to further assess the effectiveness of cognitive behavioral therapy (CBT) in treating bipolar disorder (BD). METHODS: We carried out a literature search on PubMed, Embase, and the Cochrane Library up to October 2015. We calculated the pooled relative risk of relapse rate and standard mean difference (SMD) of mean change (data at a follow-up time-point - baseline) of the Beck Depression Inventory, Beck Hopelessness Scale, Hamilton Rating Scale for Depression, Young Mania Rating Scale (YMRS) and Mania Rating Scale scores with their 95% confidence interval (95%CI). Subgroup analyses based on follow-up time were performed. RESULTS: Nine randomized controlled trials with 520 bipolar I or II disorder patients were reanalyzed. Overall analysis showed that CBT did not significantly reduce the relapse rate of BD or improve the level of depression. However, significant efficacy of CBT in improving severity of mania was proved based on the YMRS (SMD = -0.54, 95%CI, -1.03 to -0.06, P = 0.03) but not based on MRS. Subgroup analyses showed that CBT had short-term efficacy in reducing relapse rate of BD (at 6 months' follow-up: relative risk = 0.49, 95%CI: 0.29-0.81, P = 0.006) and improving severity of mania based on YMRS score (post-treatment: SMD = -0.30, 95%CI, -0.59 to -0.01, P = 0.04). CONCLUSION: Short-term efficacy of CBT in reducing relapse rate of BD and improving the severity of mania was proved. But these effects could be weakened by time. In addition, there was no effect of CBT on level of depression in BD.