Lithium prevents grey matter atrophy in patients with bipolar disorder: an international multicenter study

2020 ◽  
pp. 1-10
Author(s):  
Franz Hozer ◽  
Samuel Sarrazin ◽  
Charles Laidi ◽  
Pauline Favre ◽  
Melissa Pauling ◽  
...  

Abstract Background Lithium (Li) is the gold standard treatment for bipolar disorder (BD). However, its mechanisms of action remain unknown but include neurotrophic effects. We here investigated the influence of Li on cortical and local grey matter (GM) volumes in a large international sample of patients with BD and healthy controls (HC). Methods We analyzed high-resolution T1-weighted structural magnetic resonance imaging scans of 271 patients with BD type I (120 undergoing Li) and 316 HC. Cortical and local GM volumes were compared using voxel-wise approaches with voxel-based morphometry and SIENAX using FSL. We used multiple linear regression models to test the influence of Li on cortical and local GM volumes, taking into account potential confounding factors such as a history of alcohol misuse. Results Patients taking Li had greater cortical GM volume than patients without. Patients undergoing Li had greater regional GM volumes in the right middle frontal gyrus, the right anterior cingulate gyrus, and the left fusiform gyrus in comparison with patients not taking Li. Conclusions Our results in a large multicentric sample support the hypothesis that Li could exert neurotrophic and neuroprotective effects limiting pathological GM atrophy in key brain regions associated with BD.

2005 ◽  
Vol 39 (4) ◽  
pp. 222-226 ◽  
Author(s):  
E. Serap Monkul ◽  
Gin S. Malhi ◽  
Jair C. Soares

Aim: Morphometric brain imaging studies have revealed regional brain abnormalities in patients with bipolar disorder, which may play a role in illness pathophysiology. It is not known whether such changes are of neurodevelopmental, neurodegenerative, or combined origin. We reviewed the anatomical brain imaging literature in bipolar disorder, in an attempt to determine whether there is evidence to suggest that such abnormalities are progressive. Method: Literature searches were conducted using MEDLINE for the period from 1966 to June 2004, using specific key words; bipolar disorder and the names of the individual brain structures. Papers were selected according to their salience in relation to whether reported changes are progressive. Results: Available findings suggest reduced grey matter in prefrontal brain regions such as anterior cingulate and subgenual prefrontal cortex, and abnormalities in amygdala size in adult and paediatric bipolar patients. White matter hyperintensities, which are non-specific abnormalities, are also common in bipolar patients. Bipolar patients may lose more brain grey matter by ageing. There is also evidence for impaired myelination of the corpus callosum in bipolar disorder. Lithium may reverse or prevent grey matter prefrontal cortex abnormalities in bipolar patients by its neuroprotective effects. Conclusions: Both early developmental and later neurodegenerative processes may play a role in the pathophysiology of bipolar disorder. Findings from anatomical brain imaging studies implicate key regions involved in mood regulation. The evidence for the progressive nature of this illness is tentative, as no follow-up study with bipolar patients has been reported to this date.


2020 ◽  
Vol 20 (7) ◽  
pp. 518-523
Author(s):  
Rugül Köse Çinar

Objective: Neuroserpin is a serine protease inhibitor predominantly expressed in the nervous system functioning mainly in neuronal migration and axonal growth. Neuroprotective effects of neuroserpin were shown in animal models of stroke, brain, and spinal cord injury. Postmortem studies confirmed the involvement of neuroserpin in Alzheimer’s disease. Since altered adult neurogenesis was postulated as an aetiological mechanism for bipolar disorder, the possible effect of neuroserpin gene expression in the disorder was evaluated. Methods: Neuroserpin mRNA expression levels were examined in the peripheral blood of bipolar disorder type I manic and euthymic patients and healthy controls using the polymerase chain reaction method. The sample comprised of 60 physically healthy, middle-aged men as participants who had no substance use disorder. Results: The gene expression levels of neuroserpin were found lower in the bipolar disorder patients than the healthy controls (p=0.000). The neuroserpin levels did not differ between mania and euthymia (both 96% down-regulated compared to the controls). Conclusion: Since we detected differences between the patients and the controls, not the disease states, the dysregulation in the neuroserpin gene could be interpreted as a result of the disease itself.


2020 ◽  
Author(s):  
Mbemba Jabbi ◽  
Wade Weber ◽  
Jeffrey Welge ◽  
Fabiano Nery ◽  
Maxwell Tallman ◽  
...  

ABSTRACTOver 2.3 million people in the United States live with bipolar disorder. Sixty percent of those with a bipolar disorder diagnosis attempt suicide at least once in their lifetime, and up to 19% die by suicide. However, the neurobiology of suicide attempts in bipolar disorder remains unclear. Here, we studied the neuroanatomical basis for suicide attempt history in bipolar disorder by measuring gray matter volumes (GMV) to identify differences in brain-volumes in 121 participants with bipolar disorder type I, and healthy participants (n=40). The bipolar group consisted of individuals with suicide attempt history (n=23) and no suicide attempt history (n=58). All participants completed behavioral/diagnostic assessments and MRI measures of GMV. We focused on a predefined frontolimbic circuitry in bipolar disorder versus (vs.) healthy to first identify diagnostic GMV markers and to specifically identify markers for suicide attempt history. We found reduced GMV markers for bipolar diagnosis (i.e., bipolar<healthy) in the anterior cingulate cortex (ACC), and dorsolateral prefrontal cortices (DLPFC). Our observed frontolimbic GMV abnormalities were associated with suicide attempt history and measures of individual variations in current suicidal ideation at the time of scanning. These results identified a frontolimbic-GMV marker for bipolar diagnosis and suicidal behavioral risk tendencies.HighlightsSuicide is a major health problem especially in bipolar disorder but the neurobiological basis for suicide attempts remains obscure. We identified an anterior cingulate and dorsolateral prefrontal cortical volume correlate for suicide attempt history and suicidal ideation and thereby demonstrates a convergent brain marker for suicidal behaviors.


2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
M. G. Tana ◽  
E. Montin ◽  
S. Cerutti ◽  
A. M. Bianchi

Functional magnetic resonance imaging (fMRI) was performed in eight healthy subjects to identify the localization, magnitude, and volume extent of activation in brain regions that are involved in blood oxygen level-dependent (BOLD) response during the performance of Conners' Continuous Performance Test (CPT). An extensive brain network was activated during the task including frontal, temporal, and occipital cortical areas and left cerebellum. The more activated cluster in terms of volume extent and magnitude was located in the right anterior cingulate cortex (ACC). Analyzing the dynamic trend of the activation in the identified areas during the entire duration of the sustained attention test, we found a progressive decreasing of BOLD response probably due to a habituation effect without any deterioration of the performances. The observed brain network is consistent with existing models of visual object processing and attentional control and may serve as a basis for fMRI studies in clinical populations with neuropsychological deficits in Conners' CPT performance.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Nobuaki Mizuguchi ◽  
Shintaro Uehara ◽  
Satoshi Hirose ◽  
Shinji Yamamoto ◽  
Eiichi Naito

Motor performance fluctuates trial by trial even in a well-trained motor skill. Here we show neural substrates underlying such behavioral fluctuation in humans. We first scanned brain activity with functional magnetic resonance imaging while healthy participants repeatedly performed a 10 s skillful sequential finger-tapping task. Before starting the experiment, the participants had completed intensive training. We evaluated task performance per trial (number of correct sequences in 10 s) and depicted brain regions where the activity changes in association with the fluctuation of the task performance across trials. We found that the activity in a broader range of frontoparietocerebellar network, including the bilateral dorsolateral prefrontal cortex (DLPFC), anterior cingulate and anterior insular cortices, and left cerebellar hemisphere, was negatively correlated with the task performance. We further showed in another transcranial direct current stimulation (tDCS) experiment that task performance deteriorated, when we applied anodal tDCS to the right DLPFC. These results indicate that fluctuation of brain activity in the nonmotor frontoparietocerebellar network may underlie trial-by-trial performance variability even in a well-trained motor skill, and its neuromodulation with tDCS may affect the task performance.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V Probst ◽  
G Clerici ◽  
D Babuty ◽  
N Badenco ◽  
C Marquie ◽  
...  

Abstract Background Brugada syndrome (BrS) is an inherited arrhythmia syndrome with an increased risk of SCD. While Subcutaneous ICD (S-ICD) is a seductive approach to treat these patients, questions raised on the risk of inappropriate shock in this specific population. Objective The aim of this study was to evaluate the safety and the effectiveness of the S-ICD in BrS patients. Methods We prospectively enrolled 112 BrS patients implanted with S-ICD in 17 European centers. During the screening at least 2 vectors must be suitable but it was not necessary to check for the suitability of the ECG during sodium channel blocker or exercise test. S-ICD indications follow the current guidelines. Results Mean age of patients was 45±13 years, with 95 (85%) males. Implantation was performed in 91 (83%) patients for primary prevention and in 18 (16%) patients for secondary prevention. There is an indication of ICD replacement for 16 patients (14%): 13 lead defect (81%), 1 infection (6%) and 2 ICD end of life (13%). In this cohort, 57 patients (51%) had spontaneous type I BrS, 60 patients (55%) were symptomatic: 10 resuscitated SCD (17%) and 48 (83%) syncope. Implantation was performed under general anesthesia in 79 patients (71%). The mean operation time was 56±19 min. The lead was placed at the left side of the sternum in 102 patients (92%) and at the right side in 9 (8%). Sensing configuration was the primary vector for 46 patients (41%), secondary vector for 57 (51%) and alternative vector for 9 (8%). No complications occurred during implantation. During a mean follow-up of 15.6 months (0–39 months), 6 patients (5%) had at least one appropriate shock (n=9). The rate of appropriate shock was 4.5%/y. All the VF episodes were successfully treated with the first shock. One patient had VF ablation for recurrent VF. Among the 6 patients who received an appropriate shock, 3 (50%) were implanted for secondary prevention and 3 (50%) were implanted for primary prevention including 2 patients with a history of syncope and one asymptomatic patient. Twelve patients (11%) had at least one inappropriate shock (n=22) including 2 patients with respectively 8 and 4 inappropriate shocks due to T-wave oversensing. With the SMART pass system the first patient had no more inappropriate shock for now 2 years. The rate of inappropriate shock was 9%/y. One patient died of myocardial infarction. Five patients (4%) were hospitalized for complications (4 pocket or scar infections and 1 electrode failure). Conclusion Our initial experience showed that S-ICD is efficient to treat VF episode in BrS patients. In this population, the rate of inappropriate shock was 9%/y. In view of these results, S-ICD implantation seems to be efficient to protect BrS patients against SCD. Acknowledgement/Funding Investigator-Sponsored Research program, Boston Scientific


2020 ◽  
Vol 11 (02) ◽  
pp. 291-298
Author(s):  
Karthick Subramanian ◽  
Vikas Menon ◽  
Siddharth Sarkar ◽  
Vigneshvar Chandrasekaran ◽  
Nivedhitha Selvakumar

Abstract Background Suicide is the leading contributor to mortality in bipolar disorder (BD). A history of suicidal attempt is a robust predictive marker for future suicide attempts. Personality profiles and coping strategies are the areas of contemporary research in bipolar suicides apart from clinical and demographic risk factors. However, similar research in developing countries is rarer. Objectives The present study aimed to identify the risk factors associated with suicidal attempts in BD type I (BD-I). Materials and Methods Patients with BD-I currently in clinical remission (N = 102) were recruited. Sociodemographic details and the clinical data were collected using a semistructured pro forma. The psychiatric diagnoses were confirmed using the Mini-International Neuropsychiatric Interview 5.0. The National Institute of Mental Health–Life Chart Methodology Clinician Retrospective Chart was used to chart the illness course. Presumptive Stressful Life Events Scale, Coping Strategies Inventory Short Form, Buss–Perry aggression questionnaire, Past Feelings and Acts of Violence, and Barratt Impulsivity scale were used to assess the patient’s stress scores, coping skills, aggression, violence, and impulsivity, respectively. Statistical Analysis Descriptive statistics were used for demographic details and characteristics of the illness course. Binary logistic regression analyses were performed to identify the predictors for lifetime suicide attempt in BD-I. Results A total of 102 patients (males = 49 and females = 53) with BD-I were included. Thirty-seven subjects (36.3%) had a history of suicide attempt. The illness course in suicide attempters more frequently had an index episode of depression, was encumbered with frequent mood episodes, especially in depression, and had a higher propensity for psychiatric comorbidities. On binary logistic regression analysis, the odds ratios (ORs) for predicting a suicide attempt were highest for positive family history of suicide (OR: 13.65, 95% confidence interval [CI]: 1.28–145.38, p = 0.030), followed by the presence of an index depressive episode (OR: 6.88, 95% CI: 1.70–27.91, p = 0.007), and lower scores on problem-focused disengagement (OR: 0.72, 95% CI: 0.56–0.92, p = 0.009). Conclusion BD-I patients with lifetime suicide attempt differ from non-attempters on various course-related and temperamental factors. However, an index episode depression, family history of suicide, and lower problem-focused engagement can predict lifetime suicide attempt in patients with BD-I.


2018 ◽  
Vol 49 (3) ◽  
pp. 412-420 ◽  
Author(s):  
Lena Palaniyappan ◽  
Olha Hodgson ◽  
Vijender Balain ◽  
Sarina Iwabuchi ◽  
Penny Gowland ◽  
...  

AbstractBackgroundIn patients with schizophrenia, distributed abnormalities are observed in grey matter volume. A recent hypothesis posits that these distributed changes are indicative of a plastic reorganisation process occurring in response to a functional defect in neuronal information transmission. We investigated the structural covariance across various brain regions in early-stage schizophrenia to determine if indeed the observed patterns of volumetric loss conform to a coordinated pattern of structural reorganisation.MethodsStructural magnetic resonance imaging scans were obtained from 40 healthy adults and 41 age, gender and parental socioeconomic status matched patients with schizophrenia. Volumes of grey matter tissue were estimated at the regional level across 90 atlas-based parcellations. Group-level structural covariance was studied using a graph theoretical framework.ResultsPatients had distributed reduction in grey matter volume, with high degree of localised covariance (clustering) compared with controls. Patients with schizophrenia had reduced centrality of anterior cingulate and insula but increased centrality of the fusiform cortex, compared with controls. Simulating targeted removal of highly central nodes resulted in significant loss of the overall covariance patterns in patients compared with controls.ConclusionRegional volumetric deficits in schizophrenia are not a result of random, mutually independent processes. Our observations support the occurrence of a spatially interconnected reorganisation with the systematic de-escalation of conventional ‘hub’ regions. This raises the question of whether the morphological architecture in schizophrenia is primed for compensatory functions, albeit with a high risk of inefficiency.


CNS Spectrums ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 609-615 ◽  
Author(s):  
Jon E. Grant ◽  
Masanori Isobe ◽  
Samuel R. Chamberlain

ObjectiveThe clinical phenotype of gambling disorder (GD) is suggestive of changes in brain regions involved in reward and impulse suppression, notably the striatum. Studies have yet to characterize striatal morphology (shape) in GD and whether this may be a vulnerability marker.AimsTo characterize the morphology of the striatum in those with disordered gambling (at-risk gambling and GD) versus controls.MethodIndividuals aged 18–29 years were classified a priori into those with some degree of GD symptoms (at-risk gambling and GD) or controls. Exclusion criteria were a current mental disorder (apart from GD), history of brain injury, or taking psychoactive medication within 6 weeks of enrollment. History of any substance use disorder was exclusionary. Participants completed an impulsivity questionnaire and structural brain scan. Group differences in volumes and morphology were characterized in subcortical regions of interest, focusing on the striatum.ResultsThirty-two people with GD symptoms (14 at-risk and 18 GD participants) and 22 controls completed the study. GD symptoms were significantly associated with higher impulsivity and morphological alterations in the bilateral pallidum and left putamen. Localized contraction in the right pallidum strongly correlated with trait impulsivity in those with GD symptoms.ConclusionsMorphologic abnormalities of the striatum appear to exist early in the disease trajectory from subsyndromal gambling to GD and thus constitute candidate biological vulnerability markers, which may reflect differences in brain development associated with trait impulsivity. Striatal morphology and associated impulsivity might predispose to a range of problematic repetitive behaviors.


2019 ◽  
Vol 62 ◽  
pp. 107-115 ◽  
Author(s):  
Irina Filippi ◽  
Nicolas Hoertel ◽  
Eric Artiges ◽  
Guillaume Airagnes ◽  
Christophe Guérin-Langlois ◽  
...  

Abstract Background: Neuroimaging studies of vulnerability to Alcohol Use Disorder (AUD) have identified structural and functional variations which might reflect inheritable features in alcohol-naïve relatives of AUD individuals (FH+) compared to controls having no such family history (FH-). However, prior research did not simultaneously account for childhood maltreatment, any clinically significant disorder and maternal AUD. Therefore, we mainly aimed to investigate the brain structure and reward-related neural activations (fMRI), using whole-brain analysis in FH+ young adults with no prevalent confounders. Methods: 46 FH+ and 45 FH- male and female participants had no severe childhood maltreatment exposure, neither any psychiatric disorder or AUD, nor a prenatal exposure to maternal AUD. We used a 3 T MRI coupled with a whole brain voxel-based method to compare between groups the grey matter volumes and activations in response to big versus small wins during a Monetary Incentive Delay task. The Childhood Trauma Questionnaire score was used as confounding variable in the analyses to account for the remaining variance between groups. Results: Compared to FH- controls, FH+ participants had smaller grey matter volumes in the frontal and cingulate regions as well as in the bilateral nucleus accumbens and right insula. The FH+ participants’ fMRI datasets denoted a blunted activation in the middle cingulum with respect to FH- controls’ during the processing of reward magnitude, and a greater activation in the anterior cingulum in response to anticipation of a small win. Conclusions: Family history of alcohol use disorder is linked to structural and functional variations including brain regions involved in reward processes.


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