Euthymic patients with predominantly manic polarity avoid happy faces in a dot probe task.

BACKGROUND: Some studies suggest a mood-congruent attentional bias in bipolar patients. However, for euthymic patients, especially in dependence on the predominant polarity, there is little and inconsistent data. A clearer understanding of emotion-related attentional biases and their relationship to dysfunctional emotion regulation could help improving the diagnostics and treatment of bipolar disorder (BD). Twenty bipolar patients in a depressive state (BP-acute-D), 32 euthymic patients with manic (BP-euth-M) or depressive (BP-euth-D) predominant polarity, and 20 healthy control participants (HC) performed a dot-probe task (DPT) with happy and sad faces presented for 250 ms or 1250 ms in two different runs. Emotion regulation strategies were assessed with two questionnaires. RESULTS: In the short presentation condition of the DPT, BP-euth-M showed less attention for happy faces than HC (p = .03, r = - 0.48). BP-acute-D scored lower in cognitive reappraisal and putting into perspective and higher in suppression, catastrophizing, and rumination than HC. BP-euth-M scored higher in rumination and BP-euth-D lower in putting into perspective and higher in catastrophizing than HC. In BP-euth-D and HC, bias scores for sad faces in the longer presentation condition and reappraisal scores correlated positively. CONCLUSIONS: Results of the DPT suggest an avoidance of happy faces for BP-euth-M which we interpret as a protection mechanism for triggers of mania. That individuals who apply more reappraisal show more selective attention to sad faces could on the one hand reflect a mental effort in reevaluating the sad emotional input and on the other hand a greater tolerance for it.

Prediction of lithium response using genomic data.

Predicting lithium response prior to treatment could both expedite therapy and avoid exposure to side effects. Since lithium responsiveness may be heritable, its predictability based on genomic data is of interest. We thus evaluate the degree to which lithium response can be predicted with a machine learning (ML) approach using genomic data. Using the largest existing genomic dataset in the lithium response literature (n = 2210 across 14 international sites; 29% responders), we evaluated the degree to which lithium response could be predicted based on 47,465 genotyped single nucleotide polymorphisms using a supervised ML approach. Under appropriate cross-validation procedures, lithium response could be predicted to above-chance levels in two constituent sites (Halifax, Cohen's kappa 0.15, 95% confidence interval, CI [0.07, 0.24]; and Würzburg, kappa 0.2 [0.1, 0.3]). Variants with shared importance in these models showed over-representation of postsynaptic membrane related genes. Lithium response was not predictable in the pooled dataset (kappa 0.02 [- 0.01, 0.04]), although non-trivial performance was achieved within a restricted dataset including only those patients followed prospectively (kappa 0.09 [0.04, 0.14]). Genomic classification of lithium response remains a promising but difficult task. Classification performance could potentially be improved by further harmonization of data collection procedures.

C-reactive protein concentration in bipolar disorder: association with genetic variants.

BACKGROUND: Several 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. METHODS: 221 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). RESULTS: There 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. CONCLUSIONS: These 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.

Neural correlates of response inhibition in patients with bipolar disorder during acute versus remitted phase.

Objectives: Elevated behavioural impulsivity has been shown to be a core feature of bipolar disorder. However, no study has so far investigated impulsivity-related brain activation in patients with BD during acute versus remitted phase. To address the question whether elevated behavioural impulsivity and its differential neural pathways is a state or trait marker of BD, we employed a combined stop signal-go/no-go task in 30 controls, and 37 depressed and 15 remitted patients who were retested.Methods: Frontal brain activation was recorded using near-infrared spectroscopy.Results: Behaviourally, we found increased impulsivity as indexed by higher stop signal reaction time for patients in their depressed phase while remitted patients did not differ from controls in any measure. In contrast, brain activation measurements revealed an opposite pattern: compared to controls, depressed patients did not show significant differences, while the remitted group displayed significantly decreased activation in bilateral prefrontal cortex during successful inhibition. Analysis of the remaining conditions (go, no-go, unsuccessful inhibition) did not reveal significant differences.Conclusions: Therefore, behavioural impulsivity and prefrontal hypoactivation do not seem to be a trait marker of BD. As only successful inhibition differentiated between groups, a specific dysfunction of this inhibitory process and its neural pathway may be postulated in BD.

Long-term lithium treatment in bipolar disorder: effects on glomerular filtration rate and other metabolic parameters.

BACKGROUND: Concerns about potential adverse effects of long-term exposure to lithium as a mood-stabilizing treatment notably include altered renal function. However, the incidence of severe renal dysfunction; rate of decline over time; effects of lithium dose, serum concentration, and duration of treatment; relative effects of lithium exposure vs. aging; and contributions of sex and other factors all remain unclear. METHODS: Accordingly, we acquired data from 12 collaborating international sites and 312 bipolar disorder patients (6142 person-years, 2669 assays) treated with lithium carbonate for 8-48 (mean 18) years and aged 20-89 (mean 56) years. We evaluated changes of estimated glomerular filtration rate (eGFR) as well as serum creatinine, urea-nitrogen, and glucose concentrations, white blood cell count, and body-mass index, and tested associations of eGFR with selected factors, using standard bivariate contrasts and regression modeling. RESULTS: Overall, 29.5% of subjects experienced at least one low value of eGFR (<60 mL/min/1.73 m2), most after ≥15 years of treatment and age > 55; risk of ≥2 low values was 18.1%; none experienced end-stage renal failure. eGFR declined by 0.71%/year of age and 0.92%/year of treatment, both by 19% more among women than men. Mean serum creatinine increased from 0.87 to 1.17 mg/dL, BUN from 23.7 to 33.1 mg/dL, glucose from 88 to 122 mg/dL, and BMI from 25.9 to 26.6 kg/m2. By multivariate regression, risk factors for declining eGFR ranked: longer lithium treatment, lower lithium dose, higher serum lithium concentration, older age, and medical comorbidity. Later low eGFR was also predicted by lower initial eGFR, and starting lithium at age ≥ 40 years. LIMITATIONS: Control data for age-matched subjects not exposed to lithium were lacking. CONCLUSIONS: Long-term lithium treatment was associated with gradual decline of renal functioning (eGFR) by about 30% more than that was associated with aging alone. Risk of subnormal eGFR was from 18.1% (≥2 low values) to 29.5% (≥1 low value), requiring about 30 years of exposure. Additional risk factors for low eGFR were higher serum lithium level, longer lithium treatment, lower initial eGFR, and medical comorbidity, as well as older age.