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In proton magnetic resonance spectroscopy (¹H MRS) studies, aberrant levels of choline-containing compounds that include glycerophosphocholine plus phosphocholine (GPC+PC), can signify alterations in the metabolism of cellular membrane phospholipids (MPLs) from a healthy baseline. In a recent ¹H MRS study, we reported increased GPC+PC in cortical and subcortical areas of adult patients with bipolar disorder I (BP-I). Post-traumatic stress disorder (PTSD) can worsen the severity of BP-I, but it is unclear whether the effect of a PTSD comorbidity in BP-I is associated with altered MPL metabolism. The purpose of this study was to re-investigate the ¹H MRS data to determine whether the regional extent of elevated GPC+PC was greater in BP-I patients with PTSD (BP-I /wPTSD ) compared to BP-I without comorbid PTSD (BP-I /woPTSD ) patients and healthy controls. GPC+PC levels from four brain areas [the anterior cingulate cortex (ACC), anterior-dorsal ACC, caudate, and putamen] were measured in 14 BP-I /wPTSD , 36 BP-I /woPTSD , and 44 healthy controls using a multi-voxel 1 H MRS approach on a 3 Tesla system with high spatial resolution and absolute quantification. Results show a significant increase in GPC+PC levels from the caudate and putamen of BP-I /wPTSD patients compared to healthy controls (P<0.05) and in the putamen compared to BP-I /woPTSD patients (P<0.05). These findings are consistent with evidence of elevated degradation of MPLs in the neuropil that is more pronounced in BP-I patients with comorbid PTSD., (Copyright © 2021. Published by Elsevier B.V.)

Background: Cognitive deficits have been consistently reported in individuals with bipolar disorder (BD). The cognitive profile of siblings of individuals with BD is, however, less clearly established possibly due to the heterogeneity of neuropsychological measures used in previous studies. The aim of this exploratory study was to assess the cognitive function of siblings of individuals with BD and compare it with that of their first-degree relatives suffering with BD, and healthy controls (HC) using the Cambridge Neuropsychological Test Automated Battery (CANTAB) - a comprehensive and validated computerized cognitive battery., Methods: We recruited 23 HC (33.52±10.29 years, 8 males), 27 individuals with BD (34.26±10.19 years, 9 males, 25 BDI, 1BDII and 1 BD-NOS), and 15 of their biologically related siblings (37.47±13.15 years, 4 males). Siblings had no current or lifetime history of mental disorders. Participants performed the CANTAB and completed questionnaires assessing mood and global functioning. Multivariate analyses compared CANTAB measures across the three participant groups., Results: Individuals with BD and their siblings were less accurate in a task of sustained attention (Rapid Visual Processing) when compared to HC. Further, individuals with BD displayed pronounced deficits in affective processing (Affective Go/No-Go) compared to HC. There were no cognitive differences between siblings and individuals with BD. After correcting for current depressive symptoms, these results did not reach statistical significance., Conclusions: Subthreshold depressive symptoms may be associated with reduced sustained attention in healthy siblings of BD patients. This preliminary result needs to be corroborated by large-scale, longitudinal studies assessing the relationship between cognition and mood in vulnerable individuals., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Previous studies investigated the impact of brain-derived neurotrophic factor (BDNF) val66met (rs6265) on hippocampus volumes and neurocognition in bipolar disorders (BD), but the results were not consistent. This study aimed to investigate the effect of BDNF polymorphism on hippocampus volumes and memory performance in well-characterized adult populations diagnosed with type I BD (BD-I) and major depressive disorder (MDD) compared with healthy controls (HC)., Methods: 48 BD-I patients, 33 MDD patients and 60 HC were genotyped for BDNF rs6265 using DNA isolated from white blood cells. Individuals with val/met and met/met genotypes were grouped as met carriers and compared to those with the val/val. Brain segmentations were obtained from structural magnetic resonance imaging (MRI) using the Freesurfer. Memory performance was assessed with the California Verbal Learning Task (CVLT)., Results: We found a significant diagnosis effect and marginal interaction between diagnosis and BDNF genotype group for both hippocampus volumes and memory performance. BDNF met allele carrier BD patients had smaller hippocampus volumes and reduced performance on multiple CVLT scores compared to MDD patients and HC., Conclusions: We provide strong evidence for the BDNF val66met polymorphism as a putative biological signature for the neuroanatomical and cognitive abnormalities commonly observed in BD patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: A growing body of evidence has put forward clinical risk factors associated with patients with mood disorders that attempt suicide. However, what is not known is how to integrate clinical variables into a clinically useful tool in order to estimate the probability of an individual patient attempting suicide., Method: A total of 144 patients with mood disorders were included. Clinical variables associated with suicide attempts among patients with mood disorders and demographic variables were used to 'train' a machine learning algorithm. The resulting algorithm was utilized in identifying novel or 'unseen' individual subjects as either suicide attempters or non-attempters. Three machine learning algorithms were implemented and evaluated., Results: All algorithms distinguished individual suicide attempters from non-attempters with prediction accuracy ranging between 65% and 72% (p<0.05). In particular, the relevance vector machine (RVM) algorithm correctly predicted 103 out of 144 subjects translating into 72% accuracy (72.1% sensitivity and 71.3% specificity) and an area under the curve of 0.77 (p<0.0001). The most relevant predictor variables in distinguishing attempters from non-attempters included previous hospitalizations for depression, a history of psychosis, cocaine dependence and post-traumatic stress disorder (PTSD) comorbidity., Conclusion: Risk for suicide attempt among patients with mood disorders can be estimated at an individual subject level by incorporating both demographic and clinical variables. Future studies should examine the performance of this model in other populations and its subsequent utility in facilitating selection of interventions to prevent suicide., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Previous studies have reported that patients with bipolar disorder (BD) present with cognitive impairments during mood episodes as well as euthymic phase. However, it is still unknown whether reported neurocognitive abnormalities can objectively identify individual BD patients from healthy controls (HC)., Methods: A total of 21 euthymic BD patients and 21 demographically matched HC were included in the current study. Participants performed the computerized Cambridge Neurocognitive Test Automated Battery (CANTAB) to assess cognitive performance. The least absolute shrinkage selection operator (LASSO) machine learning algorithm was implemented to identify neurocognitive signatures to distinguish individual BD patients from HC., Results: The LASSO machine learning algorithm identified individual BD patients from HC with an accuracy of 71%, area under receiver operating characteristic curve of 0.7143 and significant at p=0.0053. The LASSO algorithm assigned individual subjects with a probability score (0-healthy, 1-patient). Patients with rapid cycling (RC) were assigned increased probability scores as compared to patients without RC. A multivariate pattern of neurocognitive abnormalities comprising of affective Go/No-go and the Cambridge gambling task was relevant in distinguishing individual patients from HC., Limitations: Our study sample was small as we only considered euthymic BD patients and demographically matched HC., Conclusion: Neurocognitive abnormalities can distinguish individual euthymic BD patients from HC with relatively high accuracy. In addition, patients with RC had more cognitive impairments compared to patients without RC. The predictive neurocognitive signature identified in the current study can potentially be used to provide individualized clinical inferences on BD patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Previous studies have reported abnormalities of white-matter diffusivity in pediatric bipolar disorder. However, it has not been established whether these abnormalities are able to distinguish individual subjects with pediatric bipolar disorder from healthy controls with a high specificity and sensitivity. Diffusion-weighted imaging scans were acquired from 16 youths diagnosed with DSM-IV bipolar disorder and 16 demographically matched healthy controls. Regional white matter tissue microstructural measurements such as fractional anisotropy, axial diffusivity and radial diffusivity were computed using an atlas-based approach. These measurements were used to 'train' a support vector machine (SVM) algorithm to predict new or 'unseen' subjects' diagnostic labels. The SVM algorithm predicted individual subjects with specificity=87.5%, sensitivity=68.75%, accuracy=78.12%, positive predictive value=84.62%, negative predictive value=73.68%, area under receiver operating characteristic curve (AUROC)=0.7812 and chi-square p-value=0.0012. A pattern of reduced regional white matter fractional anisotropy was observed in pediatric bipolar disorder patients. These results suggest that atlas-based diffusion weighted imaging measurements can distinguish individual pediatric bipolar disorder patients from healthy controls. Notably, from a clinical perspective these findings will contribute to the pathophysiological understanding of pediatric bipolar disorder., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The "spectrum" model has advantages for the conceptualization of mental disorders, representing a complementary approach to the currently available categorical systems. We carried out a study in order to assess lifetime mood symptoms among patients with bipolar disorder (BD) and healthy controls from a dimensional perspective., Methods: The Mood Spectrum Self-Report instrument (MOODS-SR) was administered to 101 bipolar patients (52 BD I, 32 BD II, and 17 BD NOS, 36 males/65 females, mean age+SD=36.10±13.34 years) and 38 healthy controls (16 males/22females, mean age+SD=35.18±13.70 years). The scores of the different MOOD-SR scales and subscales among patients and controls were compared using non-parametric tests (Mann-Whitney and Kruskal-Wallis)., Results: Bipolar patients scored significantly higher than healthy controls on the total MOOD-SR scores (BD: mean±SD=98.65±22.17; HC: mean±SD=12.92±10.72; p<0.01) and all subdomains. Multiple comparisons revealed lower scores among controls when compared to each one of the subtypes of BD, also regarding the total scores and all subdomains (p<0.01). Comparisons across the different subtypes of BD revealed statistically significant higher scores among BD I patients when compared to BD II and BD NOS patients, only in regard to the total MOOD-SR scores (BD I: mean±SD=102.94±22.79; BD II: mean±SD=93.53±21.97; BD NOS: mean±SD= 94.88±18.68; p=0.03) and two subdomains: mood mania and energy mania., Conclusions: These results, although preliminary, suggest that even though the MOODS-SR seems effective in distinguishing BD patients from HC, it is not as good in discriminating different subtypes of BD, especially in respect to lifetime depressive symptoms., Limitations: Our sample size was small, and comprised by outpatients. The MOOD-SR measures only lifetime symptoms and does not take into account the progression of mood symptoms or the current mood state of patients., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In order to assess the association between therapeutic response to lithium treatment and fronto-limbic brain structures' volumes in bipolar I patients (BPI) 24 BPI and 11 healthy comparisons underwent MRI scans at baseline and 4 weeks later. The BPIs received lithium during the 4 week period with a goal of achieving therapeutic blood levels of >0.5 mEq/L (mean level 0.67 mEq/L). Mood symptoms were rated with the Hamilton Depression and the Young Mania Rating Scales at baseline and after 4 weeks, and response was defined as >50% decrease on either scale. Hippocampus, amygdala, prefrontal (PFC), dorsolateral prefrontal (DLPFC), and anterior cingulate cortex (ACC) volumes were obtained by Freesurfer image analysis suite. According to baseline symptoms and treatment response, patients were assigned to three groups: euthymics (n=6), responders (n=12) and non-responders (n=6). Taken over both time periods, non-responders had smaller right amygdala than healthy comparisons and euthymic BPI (p=0.035 and p=0.003, respectively). When baseline and after treatment volumes were compared, there was a significant enlargement in left PFC and left DLPFC in BPI who responded to treatment (p=0.002 and p=0.006, respectively). Left hippocampus and right ACC volumes decreased in non-responders (p=0.02 and p=0.0001, respectively). According to the findings decreased left hippocampus and right ACC volumes may be markers of non-response to lithium amongst BPI. Smaller right amygdala may reflect symptomatic remission and be a marker of treatment non-response. Increases in left PFC and left DLPFC as a result of lithium treatment may relate to lithium's neurotrophic effects., (Copyright © 2013 Elsevier B.V. All rights reserved.)