BackgroundSeveral recent studies have investigated the role of C-reactive protein (CRP) in bipolar disorder (BD), but few studies have directly investigated the interaction between CRP genetic variants and peripheral CRP concentration across different phases of BD. In this study, we aimed to replicate previous findings that demonstrated altered CRP levels in BD, and to investigate whether there is an association of peripheral protein expression with genetic variants in the CRP gene.Methods221 patients were included in the study, of which 183 (all episodes, 46 not medicated, 174 medicated) were genotyped for CRP single-nucleotide polymorphisms (SNPs) shown to influence peripheral CRP protein expression (rs1800947, rs2808630, rs1417938, rs1205).ResultsThere were no differences in CRP levels associated with the genotypes, only regarding the rs1205 SNP there were significantly different CRP protein expression between the genotypes when taking body mass index, age, BD polarity, subtype and leukocyte number into account. However, we could show significantly elevated CRP protein expression in manic patients compared to euthymic and depressed patients, independent from genotype. Medication was found to have no effect on CRP protein expression.ConclusionsThese results indicate that low grade inflammation might play a role in mania and might be rather a state than a trait marker of bipolar disorder.

BackgroundIn previous studies we found mild deficiencies of circulating T cells in patients with bipolar disorder (BD) and children at risk for BD, correlating to a higher inflammatory state. The genetic and environmental influences on these T cell deficiencies in association with BD development are unknown.ObjectivesThe aim is to quantify genetic and environmental factors that contribute to the association between the liability to develop BD and T cell deficiencies.MethodsParticipants of a Dutch bipolar twin study (11 monozygotic BD twin pairs, 15 dizygotic BD twin pairs, 15 monozygotic and 12 dizygotic healthy twin pairs) were included. A detailed FACS analysis of frozen stored leukocytes was carried out to determine the percentages of T cells and various other leukocyte and lymphocyte subsets. A bivariate liability threshold twin model was used to determine genetic and environmental (common and unique) influences on the correlation between BD and the various subsets.ResultsLower percentages of T cells and higher percentages of NK cells were associated with the familial liability to develop BD. Neither genetic nor shared or unique environmental factors could explain the associations. Lithium usage explained part of the association for T cells, smoking in part that for NK cells.ConclusionsOur results confirm that BD is the result of a complex interaction between various genetic and environmental risk factors, in which T and NK cells act as important intermediate immune players.

BackgroundSchizophrenia shares some genetic risk and clinical symptoms with bipolar disorder. Clinical heterogeneity across subjects is thought to contribute to variable structural imaging findings across studies. The current study investigates cortical thickness in young adults diagnosed with schizophrenia or bipolar I disorder with a history of hyperthymic mania. We hypothesize that cortical thickness will be most similar between SCZ and the psychotic bipolar 1 disorder subtype.MethodsPatients with schizophrenia (n = 52), psychotic bipolar I disorder (PBD; n = 49) and non-psychotic bipolar I disorder (NPBD; n = 24) and healthy controls (n = 40) were scanned in a 3T Trio MRI. The thickness of 34 cortical regions was estimated with FreeSurfer, and analyzed using univariate analyses of variance. Relationships to psychotic (SAPS) and negative (SANS) symptoms were investigated using linear regression.ResultsCortical thickness showed significant group effects, after covarying for sex, age, and intracranial volume (p = 0.001). SCZ subjects had thinner paracentral, inferior parietal, supramarginal and fusiform cortices compared to CON. Caudal anterior cingulate cortical thickness was increased in SCZ, PBD and NPBD. Cortical thickness in PBD and NPBD were not significantly different from controls. Significant partial correlations were observed for SAPS severity with middle temporal (r = − 0.26; p = 0.001) and fusiform (− 0.26; p = 0.001) cortical thickness.ConclusionsIndividuals with SCZ displayed significantly reduced cortical thickness in several cortical regions compared to both CON and bipolar. We found that SCZ participants had significant cortical thinning relative to CON and bipolar disorder most significantly in the frontal (i.e. paracentral), parietal (i.e. inferior parietal, supramarginal), and temporal (i.e. middle temporal, fusiform) cortices.

BackgroundBipolar disorder is associated with heightened and persistent positive emotion (Gruber in Curr Dir Psychol Sci 20:217–221, 2011; Johnson in Clin Psychol Rev 25:241–262, 2005). Yet little is known about information processing biases that may influence these patterns of emotion responding.MethodsThe current study adopted eye-tracking methodology as a continuous measure of sustained overt attention to monitor gaze preferences during passive viewing of positive, negative, and neutral standardized photo stimuli among remitted bipolar adults and healthy controls. Percentage fixation durations were recorded for predetermined areas of interest across the entire image presentation, and exploratory analyses were conducted to examine early versus late temporal phases of image processing.ResultsResults suggest that the bipolar and healthy control groups did not differ in patterns of attention bias.ConclusionsFindings provide insight into apparently intact attention processing despite disrupted emotional responding in bipolar disorder.

Over recent decades, the field of psychiatry has allocated a vast amount of resources and efforts to make available more accurate and objective methods to diagnose, assess and monitor treatment outcomes in psychiatric disorders. Despite the optimism and some significant progress in biological markers, it has become increasingly evident that they are failing to meet initial expectations due to their lack of specificity, inconsistent reliability and limited availability. On the other hand, there is an increasingly emerging evidence of mobile technologies’ feasibility to measure mental illness activity. Moreover, taking into account its widespread use, availability and potential to capture behavioural markers, mobile-connected technologies could be strong candidates to fill and complement—at least at some degree—the gaps that biological markers couldn’t. This represents an especially interesting opportunity to reform our current diagnostic system using a bottom-up research methodology based on digital and biological markers data instead of the classical traditional top-down approach. Therefore, the field might benefit of further exploring this promising –and increasingly evidence-based- pathway as well as other auspicious alternatives in order to attain a more holistic and integrative approach in research, which could ultimately impact real-world clinical practice.

BackgroundConcerns about the adverse effects of long-term treatment with lithium include reduced renal function. In the present study, we examined comorbidities which may be associated with chronic kidney disease in a cohort of patients treated with lithium for up to 41 years.MethodsWe studied 394 patients who were treated with lithium for ≥ 5 years. The potential role of comorbidities (diabetes, concurrent antihypertensive medication, treatment with l-thyroxine, and presence of antithyroid peroxidase/microsomes, anti-thyroglobulin, and/or anti-thyrotropin-receptor antibodies) was analysed. We focused on the categories of patients with an estimated glomerular filtration rate (eGFR) lower than 60 or 45 mL/min/1.73 m2 as calculated from serum creatinine according to the Modification of Diet in Renal Disease Study Group. We applied multivariate regression analysis and Cox survival analysis to study the effects exerted by sex, age, duration of lithium treatment, and comorbidities using eGFR categories as the dependent variable. Kaplan–Meier curves were generated to measure the time to decline to an eGFR lower than 45 mL/min/1.73 m2 in patients with positive or negative thyroid antibodies.ResultsAge was associated with a decline to an eGFR lower than 60 mL/min/1.73 m2 after controlling for sex, duration of lithium treatment, and comorbidities. Circulating thyroid antibodies were associated with a decline to an eGFR lower than 45 mL/min/1.73 m2.ConclusionsThe present study is the first to suggest a potential role of circulating thyroid antibodies in the severe decline of eGFR in lithium-treated patients.

BackgroundA number of studies in bipolar patients have shown a deficit in mentalization (theory of mind), one of the main aspects of social cognition. The aim of current study was to assess both cognitive and affective mentalization in well-defined groups of depressed and manic bipolar patients, compared to healthy control subjects, using a battery of tests measuring mentalization processes. The second aim was to investigate a possible relationship between cognitive and affective mentalization and cognitive functions in bipolar patients during a depressive and manic episode.MethodsThe study involved 25 bipolar disorder type I patients (10 male, 15 female) during a depressive episode (mean 24 ± 2 points in the 17-item Hamilton Depression Rating Scale) and 25 patients (10 male, 15 female) during a manic episode (mean 27 ± 4 points in the Young Mania Rating Scale). The control group consisted of 25 healthy subjects (10 male, 15 female) without psychiatric disorders. To measure mentalization, a revised version of the Reading the Mind in the Eyes (R-MET), the Strange Stories (SS), the Faux Pas Recognition (FPR), and the Moving Shapes Paradigm (MSP) tests were used. Assessment of cognitive functioning was made using the Digit Span, Trail Making, and Wisconsin Card Sorting Tests.ResultsIn bipolar patients significant deficits in both cognitive and affective mentalization were demonstrated during both acute depressive and manic episodes. The impairment in FPR in manic patients was more severe than that in the depressive ones. On the other hand, in MSP, manic patients showed significantly increased intentionality for non-mentalization animations, compared with depressive patients and for “cause and effect” animations compared with control subjects. A significant relationship was found between the decrease in cognitive and affective mentalization and deficits of cognitive functions during both the depressive and manic episodes.ConclusionsThe results obtained confirm the deficits of mentalization in bipolar I patients, during both acute depressive and manic episodes. We found that in such patients mentalization deficits significantly correlated with cognitive dysfunctions more so during depressive episodes.

BackgroundThe efficacy and utility of long-term prophylactic treatment in patients with bipolar disorders (BDs) have not been fully explored. This study aims to estimate the long-term clinical response of patients with BDs to mood stabilizer treatment and to identify the clinical factors associated with that response.MethodsThe study subjects consisted of 80 patients with bipolar I or bipolar II disorder who had been receiving treatment with lithium and/or valproate for more than 2 years at a single bipolar disorder clinic. The long-term response to the best treatment option based on treatment algorithms was evaluated using the Alda scale. Clinical characteristics were evaluated on a lifetime basis. Patients were classified into two response groups based on frequentist mixture analysis using the total Alda scale score.ResultsThirty-four percent of the patients were good responders, with a total Alda score of 5 or higher. The treatment response rate did not differ between the lithium and valproate groups, but lithium and valproate combination therapy was associated with poorer response. The number of previous mixed episodes was associated with a worse response (p = 0.026). Of individual symptoms, delusions during manic episodes (p = 0.008) and increased appetite (p = 0.035) during depressive episodes were more common in moderate/poor responders than in good responders. Co-morbid anxiety disorders were more frequently observed in the moderate/poor response group (p = 0.008).ConclusionsPsychotic, mixed, and atypical features of BDs were found to be correlated with long-term treatment outcomes. Lithium and valproate showed similar efficacy but moderate/poor responders preferred to use polypharmacy.

BackgroundThis study explores the association of demographic and clinical features with quality of life and functioning in individuals with bipolar disorder.MethodsAdult participants (N = 482) with bipolar I or II disorder were enrolled in a comparative effectiveness study across eleven study sites and completed baseline measures of medical and psychiatric history, current mood, quality of life, and functioning. Participants with at least mildly depressive or manic/hypomanic symptomatic severity were randomized to receive lithium or quetiapine in addition to adjunctive personalized treatment for 6 months.ResultsParticipants with more severe depressive and irritability symptoms had lower quality of life and higher functional impairment. All psychiatric comorbid conditions except substance use disorder were associated with worse quality of life. On average, females had lower quality of life than males. Patients who were married, living as married, divorced, or separated had worse functional impairment compared with patients who were single or never married. A composite score of social disadvantage was associated with worse functioning and marginally associated with worse quality of life. Symptom severity did not moderate the effect of social disadvantage on quality of life or functioning.ConclusionsOur findings highlight that depression, irritability, and psychiatric comorbid conditions negatively impact quality of life and functioning in bipolar disorder. The study suggests that individuals with social disadvantage are at risk for functional impairment.Trial Registration This study is registered with ClinicalTrials.gov. Identification number: NCT01331304

BackgroundBipolar disorder is a chronic illness that impairs functioning and affects the quality of life of patients. The onset of this illness usually occurs at an early age, and the risk of relapse remains high for decades. Thus, due to the great clinical relevance of identifying long-term predictors of functioning in bipolar disorder, Strauss and Carpenter developed a scale composed of items known to have prognostic value.Methods To determine the clinical usefulness of the four-item Strauss–Carpenter scale in bipolar disorder, a 1-year prospective follow-up study was carried out. The internal consistency, convergent and discriminant validity, and test–retest reliability of the scale were assessed. We also compared the Strauss–Carpenter scale with the reference scales Global Assessment Functioning (GAF), Clinical Global Impression for Bipolar Disorder, the Modified Version (CGI-BIP-M) and the Sheehan Disability Scale (Sheehan). Additionally, a cut-off point for remission was established.ResultsThe total sample was composed of 98 patients with a diagnosis of bipolar disorder. The four-item version of the Strauss–Carpenter scale showed to have appropriate psychometric properties, comparable to those of reference scales. The best cut-off point for remission was 14.ConclusionsThe four-item version of the Strauss–Carpenter scale has suitable validity and reliability for the assessment of functioning in patients with bipolar disorder.