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Background: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention‐deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off‐label ADHD therapies in BD. Methods: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. Results: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment‐related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro‐cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. Conclusions: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers. [ABSTRACT FROM AUTHOR]

Objectives: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE‐BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean ± standard deviation age 47.2 ± 13.5, 65% women, 49% aged over 50) dataset. Design/Methods: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601). Results: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p ≤ 0.001, depression p ≤ 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning. Conclusions: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning. Key points: With the global population of older adults increasing rapidly, it is important to understand how older adults with bipolar disorder (BD) differ from younger adults.This replication analysis using a large global dataset focused on older‐age bipolar disorder (OABD) and examined associations of older age, BD symptoms, somatic burden and functioning.Older age was associated with less severe mania and more somatic burden but there was no association of depression with age.Worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning. [ABSTRACT FROM AUTHOR]

Background: By 2030, over 50% of individuals living with bipolar disorder (BD) are expected to be aged ≥50 years. However, older age bipolar disorder (OABD) remains understudied. There are limited large-scale prospectively collected data organized in key dimensions capable of addressing several fundamental questions about BD affecting this subgroup of patients. Methods: We developed initial recommendations for the essential dimensions for OABD data collection, based on (1) a systematic review of measures used in OABD studies, (2) a Delphi consensus of international OABD experts, (3) experience with harmonizing OABD data in the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD, n ≥ 4500 participants), and (4) critical feedback from 34 global experts in geriatric mental health. Results: We identified 15 key dimensions and variables within each that are relevant for the investigation of OABD: (1) demographics, (2) core symptoms of depression and (3) mania, (4) cognition screening and subjective cognitive function, (5) elements for BD diagnosis, (6) descriptors of course of illness, (7) treatment, (8) suicidality, (9) current medication, (10) psychiatric comorbidity, (11) psychotic symptoms, (12) general medical comorbidities, (13) functioning, (14) family history, and (15) other. We also recommend particular instruments for capturing some of the dimensions and variables. Conclusion: The essential data dimensions we present should be of use to guide future international data collection in OABD and clinical practice. In the longer term, we aim to establish a prospective consortium using this core set of dimensions and associated variables to answer research questions relevant to OABD. [ABSTRACT FROM AUTHOR]

Objectives: Impaired emotion regulation is a key feature of bipolar disorder (BD) that presents during acute mood episodes and in remission. The neural correlates of voluntary emotion regulation seem to involve deficient prefrontal top‐down regulation already at BD illness onset. However, the trajectory of aberrant neuronal activity during emotion regulation in BD is unclear. Methods: We investigated neural activity during emotion regulation in response to aversive pictures from the International Affective Picture System in patients with recently diagnosed BD (n = 43) in full or partial remission and in healthy controls (HC) (n = 38) longitudinally at baseline and 16 months later. Results: Patients with BD exhibited stable hypo‐activity in the left dorsomedial prefrontal cortex (DMPFC) and right dorsolateral prefrontal cortex (DLPFC) and impaired emotion regulation compared to HC over the 16 months follow‐up time. More DLPFC hypo‐activity during emotion regulation correlated with less successful down‐regulation (r = 0.16, p = 0.045), more subsyndromal depression (r = −0.18, p = 0.02) and more functional impairment (r = −0.24, p = 0.002), while more DMPFC hypo‐activity correlated with less efficient emotion regulation (r = 0.16, p = 0.048). Finally, more DMPFC hypo‐activity during emotion regulation at baseline was associated with an increased likelihood of subsequent relapse during the 16 months follow‐up time (β = −2.26, 95% CI [0.01; 0.99], p = 0.048). Conclusion: The stable DLPFC and DMPFC hypo‐activity during emotion regulation represents a neuronal trait‐marker of persistent emotion regulation difficulties in BD. Hypo‐activity in the DMPFC may contribute to greater risk of relapse. [ABSTRACT FROM AUTHOR]

Objectives: There is limited information on the characteristics of older adults with bipolar disorder (OABD) treated with lithium, along with safety concerns about its use by older adults. The aim of the present study is to describe the demographic and clinical characteristics of OABD receiving lithium therapy, using data from the Global Ageing & Geriatric Experiments in Bipolar Disorder (GAGE‐BD). Experimental Procedures: Cross‐sectional analysis of the GAGE‐BD dataset to determine differences and similarities between lithium users and non‐users. We analysed data from 986 participants aged 50 years or older (mean age 63.5 years; 57.5% females) from 12 study sites. Two subgroups ('Lithium'; 'Non‐lithium') were defined according to the current prescription of lithium. We compared several outcomes between these groups, controlling for age, gender, and study site. Results: OABD treated with lithium had lower scores on depression rating scales and were less likely to be categorised as with moderate or severe depression. There was a lower proportion of lithium users than non‐users among those with evidence of rapid cycling and non‐bipolar psychiatric diagnoses. Assessment of global cognitive state and functionality indicated better performance among lithium users. The current use of antipsychotics was less frequent among lithium users, who also reported fewer cardiovascular comorbidities than non‐users. Conclusion: We found several potentially relevant differences in the clinical profile of OABD treated with lithium compared with those treated with other mood stabilisers. However, the interpretation of the present results must take into account the methodological limitations inherent to the cross‐sectional approach and data harmonisation. [ABSTRACT FROM AUTHOR]

Background: Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain‐based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neuroimaging studies of pro‐cognitive interventions. Methods: We included magnetic resonance imaging (MRI) studies of candidate interventions in people with mood disorders or healthy individuals, following the procedures of the Preferred Reporting Items for Systematic reviews and Meta‐Analysis 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE, Cochrane Library, and Clinicaltrials.gov from inception to 30th April 2021. Two independent authors reviewed the studies using the National Heart, Lung, Blood Institutes of Health Quality Assessment Tool for Controlled Intervention Studies and the quality of neuroimaging methodology assessment checklist. Results: We identified 26 studies (N = 702). Six investigated cognitive remediation or pharmacological treatments in mood disorders (N = 190). In healthy individuals, 14 studies investigated pharmacological interventions (N = 319), 2 cognitive training (N = 73) and 4 neuromodulatory treatments (N = 120). Methodologies were mostly rated as 'fair'. 77% of studies investigated effects with task‐based fMRI. Findings varied but most consistently involved treatment‐associated cognitive control network (CCN) activity increases with cognitive improvements, or CCN activity decreases with no cognitive change, and increased functional connectivity. In mood disorders, treatment‐related default mode network suppression occurred. Conclusions: Modulation of CCN and DMN activity is a putative efficacy biomarker. Methodological recommendations are to pre‐declare intended analyses and use task‐based fMRI, paradigms probing the CCN, longitudinal assessments, mock scanning, and out‐of‐scanner tests. [ABSTRACT FROM AUTHOR]

Objectives: Whether parental age, i.e., paternal or maternal, at childbirth is associated with the risk of bipolar disorder (BD) in offspring remains unclear. We conducted a meta‐analysis of observational studies to address this gap. Methods: PubMed, PsycINFO, Embase, and Web of Science were searched up to June 2021. Studies investigating the associations between parental age at childbirth (exposure) and the risk of BD in offspring (outcome) were eligible for inclusion in our study. Paternal and maternal age were examined separately. Odds ratio (OR) was used as the effect size index. Data were pooled through random‐effects meta‐analyses. Results: Seven studies involving 3,183,539 participants and 23,253 individuals with BD were included in our meta‐analyses. Meta‐analyses indicated an increased risk of BD in the offspring of the older paternal age groups (35–44 years old [k = 5; OR = 1.09; 95% CI 1.05, 1.14; p < 0.0001] and ≥45 years old [k = 5; OR = 1.44; 95% CI 1.19, 1.14; p = 0.0001]) in comparison with the reference category (25–34 years old). Meta‐analysis also indicated an increased risk of BD in the offspring of the older maternal age group (≥40 years old [k = 3; OR = 1.20; 95% CI 1.10, 1.31; p < 0.0001]) in comparison with the reference category (20–29 years old). Conclusions: Advanced paternal and maternal age were both associated with an increased risk of BD in offspring. Further studies are needed to investigate the mechanisms behind this association. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence‐based pro‐cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations. Methods: The review included RCTs of candidate pro‐cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta‐Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials. Results: We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre‐screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking. Conclusions: Evidence for pro‐cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre‐screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real‐world functioning, investigate multimodal interventions and include neuroimaging. [ABSTRACT FROM AUTHOR]

The current pandemic has directly affected individuals suffering from Bipolar Disorder, since they depend on a well-balanced routine, regular sleeping hours, and sparse psychological stress in order to prevent relapses. In this context, our hope is that incorporating such strategies in the clinical practice would not only help BD patients during the social distance/COVID-19 pandemic, but also perpetuate their use afterwards, improving ER patient's capabilities. Adjunctive therapies and protocols such as ISRT, DBT Skills Training, and GOAL should be considered to help teaching BD patients ER abilities. [Extracted from the article]

Background: Impairments in affective cognition are part of the neurocognitive profile and possible treatment targets in bipolar disorder (BD), but the findings are heterogeneous. The International Society of Bipolar Disorder (ISBD) Targeting Cognition Task Force conducted a systematic review to (i) identify the most consistent findings in affective cognition in BD, and (ii) provide suggestions for affective cognitive domains for future study and meta‐analyses. Methods: The review included original studies reporting behavioral measures of affective cognition in BD patients vs controls following the procedures of the Preferred Reporting Items for Systematic reviews and Meta‐Analysis (PRISMA) statement. Searches were conducted on PubMed/MEDLINE, EMBASE, and PsychInfo from inception until November 2018. Results: A total of 106 articles were included (of which nine included data for several affective domains); 41 studies assessed emotional face processing; 23 studies investigated reactivity to emotional words and images; 3 investigated explicit emotion regulation; 17 assessed implicit emotion regulation; 31 assessed reward processing and affective decision making. In general, findings were inconsistent. The most consistent findings were trait‐related difficulties in facial emotion recognition and implicit emotion regulation, and impairments in reward processing and affective decision making during mood episodes. Studies using eye‐tracking and facial emotion analysis revealed subtle trait‐related abnormalities in emotional reactivity. Conclusion: The ISBD Task Force recommends facial expression recognition, implicit emotion regulation, and reward processing as domains for future research and meta‐analyses. An important step to aid comparability between studies in the field would be to reach consensus on an affective cognition test battery for BD. [ABSTRACT FROM AUTHOR]

Objectives: Bipolar disorder is frequently associated with cognitive impairment even during euthymia. Previous studies have reported significant impairments in functional and quality of life outcomes and a possible relationship between these variables and cognitive performance. Cognitive rehabilitation interventions have been proposed to address these outcomes but positive results are still scarce. The objective of the present study is to evaluate the efficacy of a new intervention developed to address both cognitive and functional impairment. Methods: Thirty‐nine individuals were included in this randomized controlled trial. All participants were evaluated by the Cambridge Neuropsychological Test Automated Battery (CANTAB) and completed functional and quality of life (QOL) scales. Patients were randomized to either treatment as usual (TAU) or Cognitive Behavior Rehabilitation (CBR), an add‐on treatment delivered in 12 weekly group sessions. All individuals were revaluated after 12 weeks. Results: A total of 39 bipolar type I or II patients were included in the analysis, 19 in the TAU group and 20 in the CBR condition. At the entrance of the study, both groups were statistically similar regarding clinical, socio‐demographics and cognitive variables. After the end of the intervention, CBR individuals had significantly improved reaction time, visual memory and emotion recognition. In contrast, individuals in the CBR did not present a statistically change in functional and QOL scores after the 12‐week intervention. Conclusions: CBR intervention showed promising results in improving some of the commonly impaired cognitive domains in BD. A longer follow‐up period may be necessary to detect changes in functional and QOL domains. [ABSTRACT FROM AUTHOR]

The article offers information on causes of the cognitive deficits in Bipolar Disorder (BD), which is the fourth leading cause of disability worldwide among young people of age range between 10-24. It is noted that "The International Consortium Investigating Cognition in Bipolar Disorder" (ICONIC-BD) was organized to bring together an international team of experts in BD to analyze various issues.

Objective: We examined brain volume and atrophy in individuals with major depressive disorder (MDD) without dementia that were referred to a large autopsy service. We also examined potential risk factors for brain atrophy, including demographics and clinical variables.Methods: In this study, 1373 participants (787 male) aged 50 years or older who died from natural causes were included. Participants with no reliable informant, with cognitive impairment or dementia, with a medical history of severe chronic disease, or with prolonged agonal state were excluded. Presence of MDD at least once in their lifetime was defined according to the Structured Clinical Interview for DSM. Brain volume was measured immediately after removal from the skull.Results: Mean age at death was 68.6 ± 11.6, and MDD was present in 185 (14%) individuals. Smaller brain volume was associated with older age (p < 0.001), lower education (years; p < 0.001), hypertension (p = 0.001), diabetes (p = 0.006), and female gender (p < 0.001). In the multivariate analysis adjusted for sociodemographics and cardiovascular risk factors, smaller brain volume was not associated with major depression (β = -0.86, 95% CI = -26.50 to 24.77, p = 0.95).Conclusions: In this large autopsy study of older adults, MDD was not associated with smaller brain volumes. Regardless of the presence of MDD, in this sample of older adults without dementia, we found that smaller brain volumes were associated with risk factors for brain neurodegeneration such as older age, diabetes, hypertension, and lower education. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background There are few studies addressing caregivers of bipolar disorder (BD) patients, especially patients who are older adults with an increased need for care, often given by a relative. The aim of this study was to describe which factors increase caregiver burden among caregivers of elderly BD outpatients. Methods Patients were older than 60 years and met the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, criteria for BD. They were evaluated for current mood, cognitive and other neuropsychiatric symptoms, functionality, medical comorbidities, quality of life, years since BD diagnosis, and number of psychiatric admissions. The caregiver who spent the greatest time with each patient was evaluated with the Zarit Caregiver Burden Interview. The caregivers' global health, mood symptoms, quality of life, and tasks performed for the patient were also assessed. Results Thirty-six BD patients and their caregivers were assessed. The Zarit Caregiver Burden Interview was positively correlated with patients' neuropsychiatric symptoms ( r = 0.508, P = 0.002) and functional impairment ( r = 0.466, P = 0.004). The Zarit Caregiver Burden Interview was also correlated with caregivers' own depression ( r = 0.576, P < 0.001), anxiety ( r = 0.360, P = 0.031), quality of life ( r = −0.406, P = 0.014), medical comorbidities ( r = 0.387, P = 0.020), and number of tasks that they completed for the patient ( r = 0.480, P = 0.003). Conclusions In this group of elderly BD patients, caregiver burden was more associated with symptoms frequently seen in others diseases as in dementia than with depressive, manic, or anxiety symptoms, which are often used as treatment outcomes measures goals in BD. Potential treatable and modifiable factors associated with caregiver burden could be caregivers' depression, anxiety, and medical comorbidities, as well as support for caregivers in terms of services and social relationships. [ABSTRACT FROM AUTHOR]

Thus, it is necessary to explore the possible mechanisms involved in the improvements provided by PE intervention in people with BD and if fundamental to apply randomized clinical trials design to verify the potential benefits of PE in BD. Bipolar disorder (BD) is associated with higher rates of sedentarism, metabolic syndrome, obesity, and early onset cardiovascular disease, leading to premature mortality. Furthermore, the relationships among PGC-1 alpha, inflammation, and PE are relevant to BD due to the relationship between BD and high inflammatory markers, metabolic syndrome, and cardiovascular disease. [Extracted from the article]

The article presents a case study related to 35-year-old woman, who came to our hospital at the age of 25. Topics include the retrospective information was taken from the patient and her family, maternal aunt suffered from severe depression and had attempted suicide several times, and the aternal uncle and grandfather were alcohol abusers.

Unfortunately, the diagnosis of BD still relies solely on clinical evaluation, in contrast with a wide range of biomarkers available for detecting neurodegenerative disorders, including LBD and FTD. Despite being the third most frequent cause of dementia confirmed by neuropathological studies,2 LBD can be often overlooked by psychiatrists, as Khosravi's study also pointed out, because some of its core symptoms may be attributable as either symptoms of BD or side effects of BD treatments to which patients can be more susceptible as they get older. LBD includes dementia with Lewy bodies in which dementia develops early in the course of the disease and Parkinson's disease dementia, a dementia that has later developed in someone with established Parkinson's disease. [Extracted from the article]

In the literature, guidelines for BD prioritize the level of evidence and based on the strength of the studies rank the treatments as first, second and third line accordingly, for both acute episodes and maintenance treatments. Clinical practice guidelines for bipolar disorder should lead to better treatment outcomes by providing evidence-based and easy to use recommendations for clinicians regarding diagnosis and treatment. Evidence-based versus clinical expertise guidelines for Bipolar Disorders. [Extracted from the article]

OBJECTIVES: We aimed to investigate the association of depression with cardiovascular risk factors and diseases (CVRFD) in a large population-based sample. METHODS: This cross-sectional study included 1012 deceased individuals greater than 50 years of age from a general autopsy service located in Sao Paulo, Brazil. Demographics, socioeconomic profile, and CVRFD information were collected by caregivers from the deceased individuals from the Brain Bank of the Brazilian Aging Brain Study Group. Depression diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Mental Disorders was the main outcome. RESULTS: Depression was associated with female gender (odds ratio (OR) = 1.86; 95% confidence interval (CI) = 1.28-2.71, p = 0.001), widowhood (OR = 1.54; 95% CI = 1.03-2.32, p = 0.04), physical inactivity (OR = 1.61; 95% CI = 1.15-2.26, p = 0.006), and smoking (OR = 2.03; 95% CI = 1.40-2.95, p < 0.001) after multivariate logistic regression analysis. Other CVRFD were not associated with the presence of depression. CONCLUSIONS: In our cross-sectional study, sedentary individuals and smokers showed a higher chance of depression during lifetime. Measures to control these common risk factors could decrease the incidence of depression. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O'Donovan C, MacQueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI, Lafer B, Birmaher B, Ha K, Nolen WA, Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord 2012: 00: 000-000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009. This third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunction with the previous publications.The recommendations for the management of acute mania remain largely unchanged. Lithium, valproate, and several atypical antipsychotic agents continue to be first-line treatments for acute mania. Monotherapy with asenapine, paliperidone extended release (ER), and divalproex ER, as well as adjunctive asenapine, have been added as first-line options.For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, as well as olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. Lurasidone monotherapy and the combination of lurasidone or lamotrigine plus lithium or divalproex have been added as a second-line options. Ziprasidone alone or as adjunctive therapy, and adjunctive levetiracetam have been added as not-recommended options for the treatment of bipolar depression. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone long-acting injection, and adjunctive ziprasidone continue to be first-line options for maintenance treatment of bipolar disorder. Asenapine alone or as adjunctive therapy have been added as third-line options. [ABSTRACT FROM AUTHOR]

Bauer M, Glenn T, Alda M, Andreassen OA, Ardau R, Bellivier F, Berk M, Bjella TD, Bossini L, Del Zompo M, Dodd S, Fagiolini A, Frye MA, Gonzalez-Pinto A, Henry C, Kapczinski F, Kliwicki S, König B, Kunz M, Lafer B, Lopez-Jaramillo C, Manchia M, Marsh W, Martinez-Cengotitabengoa M, Melle I, Morken G, Munoz R, Nery FG, O'Donovan C, Pfennig A, Quiroz D, Rasgon N, Reif A, Rybakowski J, Sagduyu K, Simhandl C, Torrent C, Vieta E, Zetin M, Whybrow PC. Impact of sunlight on the age of onset of bipolar disorder. Bipolar Disord 2012: 14: 654-663. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Although bipolar disorder has high heritability, the onset occurs during several decades of life, suggesting that social and environmental factors may have considerable influence on disease onset. This study examined the association between the age of onset and sunlight at the location of onset. Method: Data were obtained from 2414 patients with a diagnosis of bipolar I disorder, according to DSM-IV criteria. Data were collected at 24 sites in 13 countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data from both hemispheres. The age of onset and location of onset were obtained retrospectively, from patient records and/or direct interviews. Solar insolation data, or the amount of electromagnetic energy striking the surface of the earth, were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database for each location of onset. Results: The larger the maximum monthly increase in solar insolation at the location of onset, the younger the age of onset (coefficient= −4.724, 95% CI: −8.124 to −1.323, p = 0.006), controlling for each country's median age. The maximum monthly increase in solar insolation occurred in springtime. No relationships were found between the age of onset and latitude, yearly total solar insolation, and the maximum monthly decrease in solar insolation. The largest maximum monthly increases in solar insolation occurred in diverse environments, including Norway, arid areas in California, and Chile. Conclusion: The large maximum monthly increase in sunlight in springtime may have an important influence on the onset of bipolar disorder. [ABSTRACT FROM AUTHOR]

Gigante AD, Bond DJ, Lafer B, Lam RW, Young LT, Yatham LN. Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis. Bipolar Disord 2012: 14: 478-487. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Bipolar disorder (BD) is a common and highly disabling disease characterized by substantial cognitive and functional impairment. The exact neurobiological mechanisms underlying the expression of symptoms in this condition remain unknown but there is growing evidence that glutamate might play an important role. Using proton magnetic resonance spectroscopy (1H-MRS), a number of studies have examined brain glutamate/glutamine levels in patients with bipolar disorder, but they have produced conflicting results. The objective of this paper was to conduct a systematic review and meta-analysis of the literature on brain glutamate/glutamine in BD as measured by 1H-MRS. Methods: A Medline search for the period January 1980-April 2010 was conducted to identify published studies that used 1H-MRS to measure glutamate + glutamine (Glx), the Glx/creatine (Cr) ratio, glutamate (Glu), or the Glu/Cr ratio in any brain region in adult or child/adolescent patients with BD and healthy subjects. A meta-analysis of the pooled data was conducted. Results: BD patients were found to have increased Glx compared to healthy subjects when all brain areas were combined. This finding remained true in medicated and non-medicated patients, and in frontal brain areas in adults. There was a non-significant trend (p = 0.09) for an increase in whole-brain Glx/Cr and Glu in patients compared with healthy subjects. No significant difference was found in Glu/Cr. Conclusions: The results of this meta-analysis suggest that brain Glx levels are elevated in BD patients and support the idea that glutamate might play an important role in the pathophysiology of BD. [ABSTRACT FROM AUTHOR]

SUMMARY This paper reviews the association between bipolar disorder (BD) and metabolic syndrome (MetS), focusing on the etiopathogenetic and pathophysiological aspects of this association and on the recommendations for preventing and managing MetS in patients with BD. We conducted a nonsystematic literature review by means of a MEDLINE search. The exact causal relationship between MetS and BD is still uncertain. The side effects of psychotropic medications may be a major contributor to the increased rates of MetS in patients with BD. Other factors such as unhealthy lifestyles, common neuroendocrine and immuno-inflammatory abnormalities, and genetic vulnerability may also play a role in explaining the high rates of MetS in BD. Strategies to prevent and treat the MetS and its cardiovascular consequences in patients with BD include accurate screening and monitoring of the patient and appropriate psychoeducation on weight control, healthy nutrition, and increased physical activity. When deciding on pharmacological therapy for the treatment of the components of the MetS, drug interactions and the effects of the medications on mood must be taken into account. [ABSTRACT FROM AUTHOR]

We investigated the differences in the resting state corticolimbic blood flow between 20 unmedicated depressed patients and 21 healthy comparisons. Resting state cerebral blood flow (CBF) was measured with H215O PET. Anatomical MRI scans were performed on an Elscint 1.9 T Prestige system for PET-MRI coregistration. Significant changes in cerebral blood flow indicating neural activity were detected using an ROI-free image subtraction strategy. In addition, the resting blood flow in patients was correlated with the severity of depression as measured by HAM-D scores. Depressed patients showed decreases in blood flow in right anterior cingulate (Brodmann areas 24 and 32) and increased blood flow in left and right posterior cingulate (Brodmann areas 23, 29, 30), left parahippocampal gyrus (Brodmann area 36), and right caudate compared with healthy volunteers. The severity of depression was inversely correlated with the left middle and inferior frontal gyri (Brodmann areas 9 and 47) and right medial frontal gyrus (Brodmann area 10) and right anterior cingulate (Brodmann areas 24, 32) blood flow, and directly correlated with the right thalamus blood flow. These findings support previous reports of abnormalities in the resting state blood flow in the limbic-frontal structures in depressed patients compared to healthy volunteers. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Almeida KM, Nery FG, Moreno RA, Gorenstein C, Lafer B. Personality traits in bipolar disorder type I: a sib-pair analysis. Bipolar Disord 2011: 13: 662-669. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objective: The aim of this study was to compare temperament and character traits among patients with bipolar disorder (BD), their siblings, and healthy controls (HCs) in order to examine whether personality traits are related to the genetic vulnerability to develop BD. Methods: Using the Temperament and Character Inventory, we assessed 204 subjects: 67 euthymic outpatients with bipolar disorder type I, 67 siblings without BD, and 70 HCs. Results: Scores on harm avoidance, novelty seeking, and self-transcendence were significantly higher among patients with BD than among HCs, whereas those on self-directedness and cooperativeness were significantly lower. Siblings showed higher scores on harm avoidance and lower scores on self-directedness than did HCs. As some of the siblings presented at least one lifetime psychiatric disorder other than BD (n = 35), we examined the subset of siblings who had no lifetime psychiatric disorder (n = 32). This group showed statistically higher harm avoidance scores than HCs. Conclusions: Our results suggest that the harm avoidance temperament trait and, to a lesser extent, the self-directedness character trait may represent vulnerability factors for BD. [ABSTRACT FROM AUTHOR]

Objectives: This paper reviews the literature to examine the DSM-IV diagnostic criteria for rapid cycling in bipolar disorder. Methods: Studies on the clinical characteristics of rapid cycling bipolar disorder were reviewed. To identify relevant papers, literature searches using PubMed and MEDLINE were undertaken. Results: First observed in the prepharmacologic era, rapid cycling subsequently has been associated with a relatively poor response to pharmacologic treatment. Rapid cycling can be conceptualized as either a high frequency of episodes of any polarity or as a temporal sequence of episodes of opposite polarity. The DSM-IV defines rapid cycling as a course specifier, signifying at least four episodes of major depression, mania, mixed mania, or hypomania in the past year, occurring in any combination or order. It is estimated that rapid cycling is present in about 12–24% of patients at specialized mood disorder clinics. However, apart from episode frequency, studies over the past 30 years have been unable to determine clinical characteristics that define patients with rapid cycling as a specific subgroup. Furthermore, rapid cycling is a transient phenomenon in many patients. Conclusions: While a dimensional approach to episode frequency as a continuum between the extremes of no cycling and continuous cycling may be more appropriate and provide a framework to include ultra-rapid and ultradian cycling, the evidence does not exist today to refine the DSM-IV definition in a less arbitrary manner. Continued use of the DSM-IV definition also enables comparisons between past and future studies, and it should be included in the next release of the ICD. Further scientific investigation into rapid cycling is needed. In addition to improving the diagnostic criteria, insight into neurophysiologic mechanisms of mood switching and episode frequency may have important implications for clinical care. [ABSTRACT FROM AUTHOR]

Introduction The anterior cingulate region has been implicated in the pathophysiology of mood disorders. Studies have reported anatomical and functional abnormalities in this region in bipolar disorder patients. Few neurochemical studies have evaluated this region, especially on medicated bipolar patients. Lithium has been reported to increase NAA levels but not by all studies. We used proton magnetic spectroscopy (1HMRS) to measure the levels of N-acetyl-L-aspartate (NAA) and choline (Cho) relative to creatine (Cr) in the anterior cingulate of euthymic medicated bipolar subjects. Methods 1HMRS was performed using a GE Signa 1.5 Tesla scanner in 13 euthymic bipolar patients who were taking lithium for at least four weeks before the scan and in 15 normal controls. The 1HMRS signal was collected from an 8 cm3 voxel placed in the anterior cingulate. Data analysis was performed with the automated PROBE/SV quantification tool. Results NAA/Cr and Cho/Cr ratios were not significantly different between patients and controls (NAA/Cr: 1.60 ± 0.34 in patients, 1.68 ± 0.34 in controls; Cho/Cr: 1.13 ± 0.13 in patients, 1.11 ± 0.20 in controls). Conclusions We did not find a significant difference in the NAA/Cr and Cho/Cr ratio between bipolar patients and healthy controls. Chronic administration of psychotropic drugs could have had an effect on NAA/Cr levels of bipolar patients. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions This study aimed to investigate the neural underpinnings of emotional cognition subgroups in recently diagnosed patients with bipolar disorder (BD) and change over time over a 15‐month follow‐up period.Patients and healthy controls (HC) underwent emotional and nonemotional cognitive assessments and functional magnetic resonance imaging (fMRI) at the baseline (BD n = 87; HC n = 65) and at 15‐month follow‐up (BD n = 44; HC n = 38). Neural activity during emotion reactivity and regulation in response to aversive pictures was assessed during fMRI. Patients were clustered into subgroups based on their emotional cognition and, with HC, were compared longitudinally on cognition and neural activity during emotion reactivity and regulation.Patients were optimally clustered into two subgroups: Subgroup 1 (n = 40, 46%) was characterized by heightened emotional reactivity in negative social scenarios, which persisted over time, but were otherwise cognitively intact. This subgroup exhibited stable left amygdala hyper‐activity over time during emotion reactivity compared to subgroup 2. Subgroup 2 (n = 47, 54%) was characterized by global emotional cognitive impairments, including stable difficulties with emotion regulation over time. During emotion regulation across both time points, this group exhibited hypo‐activity in the left dorsolateral prefrontal cortex. Additionally, patients in subgroup 2 had poorer nonemotional cognition, had more psychiatric hospital admissions and history of psychotic episodes than those in subgroup 1.Broad impairments in emotional cognition in approximately half of BD patients and associated nonemotional cognitive deficits may originate from insufficient recruitment of prefrontal resources, contributing to poorer clinical outcomes. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about comorbidity of anorexia nervosa and bipolar disorder in early adolescence.

A letter to the editor is presented regarding the application of long-acting injectable risperidone to a 43-year-old woman who developed intolerance to mood stabilizers after she underwent bariatric surgery.

Objectives: Impaired emotion regulation is a key feature of bipolar disorder (BD) that presents during acute mood episodes and in remission. The neural correlates of voluntary emotion regulation seem to involve deficient prefrontal top-down regulation already at BD illness onset. However, the trajectory of aberrant neuronal activity during emotion regulation in BD is unclear., Methods: We investigated neural activity during emotion regulation in response to aversive pictures from the International Affective Picture System in patients with recently diagnosed BD (n = 43) in full or partial remission and in healthy controls (HC) (n = 38) longitudinally at baseline and 16 months later., Results: Patients with BD exhibited stable hypo-activity in the left dorsomedial prefrontal cortex (DMPFC) and right dorsolateral prefrontal cortex (DLPFC) and impaired emotion regulation compared to HC over the 16 months follow-up time. More DLPFC hypo-activity during emotion regulation correlated with less successful down-regulation (r = 0.16, p = 0.045), more subsyndromal depression (r = -0.18, p = 0.02) and more functional impairment (r = -0.24, p = 0.002), while more DMPFC hypo-activity correlated with less efficient emotion regulation (r = 0.16, p = 0.048). Finally, more DMPFC hypo-activity during emotion regulation at baseline was associated with an increased likelihood of subsequent relapse during the 16 months follow-up time (β = -2.26, 95% CI [0.01; 0.99], p = 0.048)., Conclusion: The stable DLPFC and DMPFC hypo-activity during emotion regulation represents a neuronal trait-marker of persistent emotion regulation difficulties in BD. Hypo-activity in the DMPFC may contribute to greater risk of relapse., (© 2022 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)