Cognition in older adults with bipolar disorder versus major depressive disorder

Gildengers AG, Butters MA, Chisholm D, Anderson SJ, Begley A, Holm M, Rogers JC, Reynolds CF III, Mulsant BH. Cognition in older adults with bipolar disorder versus major depressive disorder. Bipolar Disord 2012: 14: 198–205. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Bipolar disorder (BD) and major depressive disorder (MDD) are associated with cognitive dysfunction in older age during both acute mood episodes and remitted states. The purpose of this study was to investigate for the first time the similarities and differences in the cognitive function of older adults with BD and MDD that may shed light on mechanisms of cognitive decline. Methods: A total of 165 subjects with BD (n = 43) or MDD (n = 122), ages ≥ 65 years [mean (SD) 74.2 (6.2)], were assessed when euthymic, using comprehensive measures of cognitive function and cognitive–instrumental activities of daily living (C‐IADLs). Test results were standardized using a group of mentally healthy individuals (n = 92) of comparable age and education level. Results: Subjects with BD and MDD were impaired across all cognitive domains compared with controls, most prominently in Information Processing Speed/Executive Function. Despite the protective effects of having higher education and lower vascular burden, BD subjects were more impaired across all cognitive domains compared with MDD subjects. Subjects with BD and MDD did not differ significantly in C‐IADLs. Conclusion: In older age, patients with BD have worse overall cognitive function than patients with MDD. Our findings suggest that factors intrinsic to BD appear to be related to cognitive deterioration and support the understanding that BD is associated with cognitive decline.     

Higher serum VGF protein levels discriminate bipolar depression from major depressive disorder

Misdiagnosis between major depressive disorder (MDD) and bipolar depression (BD) is quite common. Our previous study found significantly lower serum VGF (non-acronymic) in MDD patients. However, it is unclear whether same changes occur in BD patients. Therefore, we aimed to investigate the relationship between serum VGF levels in BD and MDD patients. General information, scores of 17-item Hamilton Depression Rating Scale (HDRS), and fasting blood samples of all participants including 30 MDD patients, 20 BD patients, and 30 healthy controls (HC) were collected. Serum VGF levels were measured by Enzyme-linked immunosorbent assay kits. Pearson correlation analysis was used to analyze correlations between serum VGF levels and clinical information. Receiver operating characteristic (ROC) curve and likelihood ratios (LRs) were used to analyze the differential potential of serum VGF. Serum VGF levels were significantly lower in MDD patients but higher in BD patients compared with HC (both P_Tukey < 0.01). No correlation was found between serum VGF levels and any data of subjects. The optimal cutoff for serum VGF in discriminating BD patients from MDD patients was ≥1093.85 pg/ml (AUC = 0.990, sensitivity of 95%, specificity of 100% and accuracy of 95%). LRs further confirmed the differential efficiency of serum VGF in distinguishing BD and MDD patients with +LR of infinity and –LR of 0. The results suggest that serum VGF level changed significantly in MDD and BD patients and serum VGF may be an indicator for differentiating BD patients from MDD patients.     

重性抑郁障碍与双相障碍患者躯体疾病共病调查

目的:了解重性抑郁障碍(MDD)与双相障碍(BD)患者躯体疾病共病情况。方法:对141例MDD和52例BD患者进行一般情况、躯体疾病调查及精神疾病评估。结果:MDD和BD患者躯体疾病的共病率分别为68.1%、46.2%,共病的躯体疾病以慢性病为主,依次为高血压、慢性胃炎、腰椎间盘突出、糖尿病。与非共病患者比较,共病患者年龄及起病年龄大,精神疾病复发次数多(P0.05或P0.01)。MDD共病患者自杀意念风险明显增加(P0.01)。结论:较高龄及较高龄起病的MDD、BD患者更易共病慢性躯体疾病。     

Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder

BACKGROUND: As patients with mood disorders manifest heterogeneity in phenomenology, pathophysiology, etiology, and treatment response, a biological classification of mental disease is urgently needed to advance research. Patient and methodological variability complicates the comparison of neuroimaging study results and limits heuristic model development and a biologically-based diagnostic schema. OBJECTIVE: We have critically reviewed and compared the magnetic resonance neuroimaging literature to determine the degree and directionality of volumetric changes in brain regions putatively implicated in the pathophysiology of major depressive disorder (MDD) versus bipolar disorder (BD). METHODS: A total of 140 published magnetic resonance imaging investigations evaluating subjects with BD or MDD were selected to provide a summary and interpretation of volumetric neuroimaging results in MDD and BD. Further commentary on the pathophysiological implications, and putative cellular and pharmacological mechanisms, is also provided. RESULTS: While whole brain volumes of patients with mood disorders do not differ from those of healthy controls, regional deficits in the frontal lobe, particularly in the anterior cingulate and the orbitofrontal cortex, appear to consistently differentiate subjects with mood disorders from the general population. Preliminary findings also suggest that subcortical structures, particularly the striatum, amygdala, and hippocampus, may be differentially affected in MDD and BD. CONCLUSIONS: Structural neuroimaging studies have consistently identified regional abnormalities in subjects with mood disorders. Future studies should strive to definitively establish the influence of age and medication.     

Age at onset in 3014 Sardinian bipolar and major depressive disorder patients

Tondo L, Lepri B, Cruz N, Baldessarini RJ. Age at onset in 3014 Sardinian bipolar and major depressive disorder patients. Objective: To test if onset age in major affective illnesses is younger in bipolar disorder (BPD) than unipolar‐major depressive disorder (UP‐MDD), and is a useful measure. Method: We evaluated onset‐age for DSM‐IV‐TR major illnesses in 3014 adults (18.5% BP‐I, 12.5% BP‐II, 69.0% UP‐MDD; 64% women) at a mood‐disorders center. Results: Median and interquartile range (IQR) onset‐age ranked: BP‐I = 24 (19–32) < BP‐II = 29 (20–40) < UP‐MDD = 32 (23–47) years (P < 0.0001), and has remained stable since the 1970s. In BP‐I patients, onset was latest for hypomania, and depression presented earlier than in BP‐II or UP‐MDD cases. Factors associated with younger onset included: i) being unmarried, ii) more education, iii) BPD‐diagnosis, iv) family‐history, v) being employed, vi) ever‐suicidal, vii) substance‐abuse and viii) ever‐hospitalized. Onset‐age distinguished BP‐I from UP‐MDD depressive onsets with weak sensitivity and specificity. Conclusion: Onset age was younger among BPD than MDD patients, and very early onset may distinguish BPD vs. UP‐MDD with depressive‐onset.     

The tryptophan hydroxylase gene influences risk for bipolar disorder but not major depressive disorder: results of meta-analyses

Objective: Tryptophan hydroxylase is the rate-limiting enzyme in the synthesis of serotonin, and thus its gene, TPH, has been extensively studied as a risk factor for both bipolar disorder and major depressive disorder. The purpose of the present report is to synthesize the available data on these putative associations and derive best estimates of the nature and magnitude of the influence of TPH on risk for mood disorders. Methods: We identified studies that examined the TPH A218C polymorphism in relation to major depressive disorder or bipolar disorder using the PubMed online search engine, ultimately including 10 case-control studies in two meta-analyses. Results: The AA genotype had a significant effect on risk for bipolar disorder in comparison to either the CC or AC genotypes, suggesting that the A allele may increase risk for bipolar disorder in a recessive manner. None of the three genotypes significantly increased risk for major depressive disorder relative to any of the other genotypes. Conclusion: The homozygous recessive genotype of the TPH A218C polymorphism has a significant effect on risk for bipolar disorder but not major depressive disorder. A possible explanation for these results is that the A allele influences mood by permitting or facilitating mania while having no effect on depression. Further replication of these findings in additional large case-control and family-based association is needed before TPH can be designated a risk gene for bipolar disorder.     

High-sensitivity C-reactive protein levels in patients with major depressive disorder and bipolar mania

The serum high-sensitivity C-reactive protein (hsCRP) levels in patients with major depressive disorder and bipolar I disorder in acute phases were investigated. During a 1-year period, a total of 67 participants including 23 patients with major depressive disorder, 13 patients with bipolar I disorder (manic episode) and 31 healthy controls were recruited in this study. The diagnoses of mental disorders in participants were made by one psychiatrist according to the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). Both patient groups with major depression and bipolar disorder had higher mean serum hsCRP levels than the healthy control group. Using analysis of covariance with age adjustment, patients with bipolar I disorders still had significantly higher hsCRP levels than healthy controls (P=0.043). However, patients with major depression did not have significantly higher hsCRP levels than healthy controls (P=0.172). These results suggest that patients with bipolar I disorder might have a more severe inflammation reaction than patients without major depression. However, larger samples and adequate statistical methods are needed to prove these results.     

Changes in cortical protein markers of iron transport with gender,major depressive disorder and suicide

Abstract

Objectives: The objective of this study was to determine whether a breakdown in proteins regulating cortical iron homeostasis could be involved in the pathophysiology of mood disorders.

Methods: Levels of select proteins responsible for cortical iron transport were quantitated by Western blotting of Brodmann’s (BA) areas 6 and 10 from patients with major depressive disorder (n?=?13), bipolar disorder (n?=?12) and age/sex matched controls (n?=?13).

Results: We found the inactive form of ceruloplasmin was lower in BA 6 from males compared to females. Levels of copper containing ceruloplasmin was lower in BA 6 from suicide completers whilst levels of amyloid precursor protein, TAU and transferrin were higher in BA 10 from those individuals. The level of prion protein was lower in BA 6 from subjects with major depressive disorder.

Conclusions: Our data suggests that perturbation in cortical iron transport proteins is not prevalent in mood disorders. By contrast, our data suggests changes in iron transport proteins in BA 6 and BA 10 are present after suicide completion. If these changes were present before death, they could have had a role in the genesis of the contemplation and completion of suicide.     

HTR2A−1438A/G polymorphism influences the risk of schizophrenia but not bipolar disorder or major depressive disorder: A meta‐analysis

The incidence of psychiatric disorders has been shown to have a strong genetic component, and we conducted this study to investigate whether the ?1438A/G polymorphism of the HTR2A gene was associated with susceptibility to schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using data obtained from a total 27 studies that investigated an association between the HTR2A ?1438A/G polymorphism and SZ (15), BD (7), and MDD (4). We failed to observe an association between the HTR2A ?1438A/G polymorphism and BD and MDD, and we found contrary results with regard to SZ. Our results showed that the ?1438A/G polymorphism was a risk factor for SZ, especially in Caucasians (allele model: OR, 1.12; 95% CI, 1.05–1.20; I² = 17.3%; dominant model: OR, 1.14; 95% CI, 1.03–1.27; I² = 15.3%; recessive model: OR, 1.20; 95% CI, 1.06–1.37; I² = 0.0%; codominant model 1: OR, 1.16; 95% CI, 1.01–1.32; I² = 0.0%). We found that the association of the HTR2A ?1438A/G polymorphism with SZ depends on the ethnic origin of the study population, and this genetic variant does not modify the susceptibility to BD or MDD. © 2013 Wiley Periodicals, Inc.