Amygdala astrocyte reduction in subjects with major depressive disorder but not bipolar disorder

Altshuler LL, Abulseoud OA, Foland‐Ross L, Bartzokis G, Chang S, Mintz J, Hellemann G, Vinters HV. Amygdala astrocyte reduction in subjects with major depressive disorder but not bipolar disorder.
Bipolar Disord 2010: 12: 541–549. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Several magnetic resonance imaging studies have found changes in amygdala volumes in adults with mood disorders. The cellular basis for these changes has not been explored in detail. Specifically, it is not known whether differences in the density and/or volume of neurons or glial cells contribute to tissue volume changes seen on magnetic resonance images. Methods: Postmortem amygdala samples were obtained from the Stanley Foundation Neuropathology Consortium from subjects diagnosed with bipolar disorder (n = 10), major depressive disorder (n = 11), and schizophrenia (n = 9), and from normal controls (n = 14). Samples were first stained with glial fibrillary acidic protein (GFAP) and counter‐stained with hematoxylin to ascertain neuron and glia (astrocyte) densities. Results: No significant differences in neuronal densities were found between groups. However, a reduction in the density of GFAP immunoreactive astrocytes was observed in the amygdala of subjects with major depressive disorder compared to the bipolar disorder, schizophrenia, and normal control postmortem samples. Conclusions: A decrease in density of GFAP immunoreactive astrocytes in the amygdala of depressed subjects is consistent with prior histologic reports and might contribute to amygdala volume reductions reported in several in vivo neuroimaging studies.     

Human leukocyte antigen alleles in patients with bipolar disorder in the Korean population

We performed an association study between human leukocyte antigen (HLA) alleles and bipolar disorder to evaluate the potentiality of HLA as a genetic marker in bipolar disorder. HLA class I and class II allele frequencies were assessed in 87 bipolar patients and were compared with those of 206 normal controls in the Korean population. HLA class I typing was performed using the microlymphocytotoxicity method, whereas class II (DRB1 and DQB1) genotyping was performed with polymerase chain reaction-sequence specific oligonucleotide probes. When the allele frequency of HLA in bipolar patients was compared with that in normal controls, there were some significant differences. Bipolar patients showed statistically significant increased allele frequencies of HLA-A29 and B54. Allele frequencies of HLA-B51 and DRB1*02 were significantly higher in normal controls. However, these results were no longer significant after correcting for the number of alleles. The results of the present study suggest that HLA alleles may not confer susceptibility to bipolar disorder in the Korean population. To clarify the genetic influence of HLA on bipolar disorder, we should conduct a consecutive study with a larger cohort of subjects.     

Low glial numbers in the amygdala in major depressive disorder.

BACKGROUND: Functional imaging studies implicate the prefrontal cortex and amygdala in major depressive disorder and bipolar disorder, and glial decreases have been reported in the prefrontal cortex. Here, glia and neurons were counted in the amygdala and entorhinal cortex in major depressive disorder, bipolar disorder, and control cases. METHODS: Tissue blocks from major depressive disorder (7), bipolar disorder (10), and control (12) cases, equally divided between right and left, were cut into 50 microm sections and stained with the Nissl method. One major depressive disorder and all but two bipolar disorder cases had been treated with lithium or valproate. Neurons and glia were counted using stereological methods. RESULTS: Glial density and the glia/neuron ratio were substantially reduced in the amygdala in major depressive disorder cases. The reduction was mainly accounted for by counts in the left hemisphere. No change was found in neurons. Average glia measures were not reduced in bipolar disorder cases; however, bipolar disorder cases not treated with lithium or valproate had significant glial reduction. Similar but smaller changes were found in the entorhinal cortex. CONCLUSIONS: Glia are reduced in the amygdala in major depressive disorder, especially on the left side. The results suggest that lithium and valproate may moderate the glial reduction.     

抑郁症门诊患者中未识别出的双相障碍者的临床特征（英文）

背景双相障碍常未被识别或被误诊为单相抑郁。明确未被识别或被误诊的双相障碍者的临床特征有助于减少错误分类。目的调查门诊抑郁症患者中未被识别的双相障碍者的比例,并分析未被识别的双相障碍者的临床特征。方法使用32项轻躁狂症状清单（Hypomania Checklist-32,HCL-32）、心境障碍问卷（Mood Disorder Questionnaire,MDQ）和简明国际神经精神访谈（Mini International Neuropsychiatric Interview,MINI）对目前被诊断为抑郁症的100例门诊患者进行调查。对被重新诊断为双相障碍与仍然被诊断为抑郁症的患者的临床特征进行比较分析。结果共有29例（29%）抑郁症门诊患者被诊断为双相障碍;其中双相Ⅰ型6例,双相Ⅱ型23例。与未更改诊断的抑郁症者相比,被重新诊断为双相障碍者年龄轻、起病早、发病次数多、受教育程度高,多为复发性抑郁且多伴精神病性症状。多因素Logistic回归分析显示年龄（OR=0.55,95%CI=0.34~0.89）和精神病性症状（OR=9.12,95%CI=1.56~53.26）是双相障碍的独立危险因素。结论在门诊抑郁症患者中未被识别的双相障碍比例较高,尤其是双相Ⅱ型。与单相抑郁相比,诊断为抑郁症而为未被识别的双相障碍者年龄轻,更可能伴有精神病性症状。     

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.     

Sustained unemployment in psychiatric outpatients with bipolar depression compared to major depressive disorder with comorbid borderline personality disorder

Zimmerman M, Martinez JH, Young D, Chelminski I, Dalrymple K. Sustained unemployment in psychiatric outpatients with bipolar depression compared to major depressive disorder with comorbid borderline personality disorder. Bipolar Disord 2012: 14: 856–862. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: The morbidity associated with bipolar disorder is, in part, responsible for repeated calls for improved detection and recognition. No such clinical commentary exists for improved detection of borderline personality disorder in depressed patients. Clinical experience suggests that borderline personality disorder is as disabling as bipolar disorder; however, no studies have directly compared the two disorders. For this reason we undertook the current analysis from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project comparing unemployment and disability rates in patients with bipolar disorder and borderline personality disorder. Methods: Patients were interviewed with semi‐structured interviews. We compared three non‐overlapping groups of depressed patients: (i) 181 patients with DSM–IV major depressive disorder and borderline personality disorder, (ii) 1068 patients with major depressive disorder without borderline personality disorder, and (iii) 84 patients with bipolar depression without borderline personality disorder. Results: Compared to depressed patients without borderline personality disorder, depressed patients with borderline personality disorder were significantly more likely to have been persistently unemployed. A similar difference was found between patients with bipolar depression and major depressive disorder without borderline personality disorder. No differences were found between patients with bipolar depression and depression with borderline personality disorder. Conclusions: Both bipolar disorder and borderline personality disorder were associated with impaired occupational functioning and thus carry a significant public health burden. Efforts to improve detection of borderline personality disorder in depressed patients might be as important as the recognition of bipolar disorder.     

Neurocognitive impairment in euthymic young adults with bipolar spectrum disorder and recurrent major depressive disorder

OBJECTIVE: Patients with remitted major depressive disorder (MDD) and bipolar disorder have persistent impairments in executive function and verbal memory that may represent endophenotypic abnormalities. In this study, we examine neurocognitive function in a sample of euthymic young adults with bipolar spectrum disorder (BSD) (Can J Psychiatry 2002; 47: 125-134) and compare this to well-matched samples of young adults with recurrent MDD and controls. METHOD: Twenty-one euthymic young adult patients with BSD were compared with 42 young adult patients with MDD and 33 controls on a neuropsychological battery assessing attention, executive function and verbal memory. RESULTS: Patients with BSD were significantly more impaired than MDD patients and controls on tests of executive function and verbal memory. MDD patients did not differ significantly from controls on verbal memory function but performed less well on a test of executive function. CONCLUSION: Euthymic young adults with BSD had greater impairment on neurocognitive measures associated with prefrontal and hippocampal function than MDD patients and controls. This is a reflection of a strong bipolar diathesis in the BSD group rather than being a consequence of a more severe unipolar illness.     

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。     

Resting state functional network switching rate is differently altered in bipolar disorder and major depressive disorder

The clinical misdiagnosis ratio of bipolar disorder (BD) patients to major depressive disorder (MDD) patients is high. Recent findings hypothesize that the ability to flexibly recruit functional neural networks is differently altered in BD and MDD patients. This study aimed to explore distinct aberrance of network flexibility during dynamic networks configuration in BD and MDD patients. Resting state functional magnetic resonance imaging of 40 BD patients, 61 MDD patients, and 61 matched healthy controls were recruited. Dynamic functional connectivity matrices for each subject were constructed with a sliding window method. Then, network switching rate of each node was calculated and compared among the three groups. BD and MDD patients shared decreased network switching rate of regions including left precuneus, bilateral parahippocampal gyrus, and bilateral dorsal medial prefrontal cortex. Apart from these regions, MDD patients presented specially decreased network switching rate in the bilateral anterior insula, left amygdala, and left striatum. Taken together, BD and MDD patients shared decreased network switching rate of key hubs in default mode network and MDD patients presented specially decreased switching rate in salience network and striatum. We found shared and distinct aberrance of network flexibility which revealed altered adaptive functions during dynamic networks configuration of BD and MDD.     

Late-onset bipolar disorder due to hyperthyroidism.

OBJECTIVE: Bipolar disorder starts typically in early age and late-onset cases are rare. Late-onset cases are more likely to have comorbid medical illnesses responsible for them. This case report highlights late-onset bipolar disorder due to hyperthyroidism. METHOD: A 65-year-old patient of bipolar disorder has been described. RESULT: Physical examination and laboratory investigations detected presence of hyperthyroidism and the patient was treated with antithyroid and anxiolytics. CONCLUSION: A thorough examination and investigation are required in late-onset cases of bipolar disorder to rule out secondary causes. Definitive antimanic agents or mood stabilizers may not be required in such cases.     

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.     

S100B-immunopositive astrocytes and oligodendrocytes in the hippocampus are differentially afflicted in unipolar and bipolar depression: A postmortem study

Background

Previous studies have suggested that affective disorders are characterized by glial pathology. In this context, it has been hypothesized that elevated S100B serum and cerebrospinal fluid levels may represent a suitable surrogate marker. However, brain studies on the cellular distribution pattern of S100B in depressed patients are lacking so far. Such analyses are crucial, since S100B has been detected in various other cell types, even outside the central nervous system.

Methods

Therefore, we performed a first postmortem analysis on this topic in the hippocampus – which is of major importance for emotional and cognitive aspects of affective disorders. S100B-immunopositive astrocytes and oligodendrocytes were evaluated in the alveus and the CA1 pyramidal layer of patients with major depressive disorder (MDD) or bipolar I disorder (BD) compared to controls.

Results

As revealed by the optical disector cell-counting method, the numerical density of S100B-immunopositive astrocytes was bilaterally decreased in the CA1 pyramidal layer of MDD and BD patients compared to controls, whereas only the bipolar group showed a decreased density of S100B-immunopositive oligodendrocytes in the left alveus. These results were not confounded by gender, age, duration of disease, medication dosage, or autolysis time.

Conclusions

Confirming the idea of previous S100B serum and cerebrospinal fluid studies, our data suggest that S100B-immunopositive glia is dysregulated in the brains of depressed patients. These findings are in accordance with animal experiments in rodents showing a reduced astrocytic S100B-immunoreactivity in the hippocampus after pharmacological serotonin depletion (modeling depression).     

Irritability is associated with anxiety and greater severity,but not bipolar spectrum features,in major depressive disorder

Objective: Irritability is common during major depressive episodes, but its clinical significance and overlap with symptoms of anxiety or bipolar disorder remains unclear. We examined clinical correlates of irritability in a confirmatory cohort of Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study participants with major depressive disorder (MDD). Method: Logistic regression was used to identify features associated with presence of irritability on the clinician‐rated Inventory of Depressive Symptomatology. Results: Of 2307 study participants, 1067(46%) reported irritability at least half the time during the preceding week; they were more likely to be female, to be younger, to experience greater depression severity and anxiety, and to report poorer quality of life, prior suicide attempts and suicidal ideation. Bipolar spectrum features were not more common among those with irritability. Conclusion: Irritable depression is not a distinct subtype of MDD, but irritability is associated with greater overall severity, anxiety comorbidity and suicidality.