Stability of self-esteem in bipolar disorder: comparisons among remitted bipolar patients, remitted unipolar patients and healthy controls

OBJECTIVES: Changes in beliefs about the self are a central feature of bipolar disorder, with grandiose self-belief common in mania and low self-esteem evident in periods of depression. We investigated whether unstable self-esteem is a characteristic of bipolar disorder in remission. METHODS: We compared 18 patients with DSM-IV bipolar disorder in remission, 16 patients with unipolar disorder in remission, and 19 healthy controls. The primary measure was a diary kept for one week and completed twice each day, measuring self-esteem and positive and negative affect. We also administered Winters and Neale's (J Abnorm Psychol 1985; 94: 282-290) implicit measure of attributional style. RESULTS: Whereas mean levels of self-esteem and affect were not abnormal in the remitted bipolar patients, the bipolar patients showed strong fluctuations in these processes. In common with the unipolar patients, they also showed a pessimistic attributional style on the Pragmatic Inference Task (PIT). CONCLUSIONS: Instability of self-esteem and affect is present in bipolar patients, even when their symptoms are in remission, and has previously been found in people at genetic risk of the disorder. It may be a marker of vulnerability to the disorder.     

Comorbidity of anxiety disorders in patients with remitted bipolar disorder

Comorbidity between bipolar disorder and anxiety disorders has attracted considerable attention in recent years. However, a majority of the earlier studies examined anxiety disorders in acutely ill patients resulting in a possible confounding effect of the affective episodes. This study examines the prevalence of anxiety disorders in remitted bipolar subjects recruited from a psychiatric hospital in India and their effect on the severity of bipolar illness. A total of eighty remitted DSM-IV adult bipolar subjects and 50 non-psychiatric controls were recruited over a 10-month period. They were evaluated using a structured interview and various scales. The effect of anxiety disorders on bipolar severity was analyzed using multiple regression analyses. Anxiety disorders were highly prevalent in bipolar subjects compared to controls (49 [61%] vs. 7 [14%], χ² = 28.01, P < 0.001). Commonest lifetime anxiety disorder was obsessive-compulsive disorder (35%). Lifetime anxiety disorder had significant effect on all four indices of severity of illness, that included (1) percentage of time spent in episodes (Beta = 18.67, SE = 5.11, P < 0.001), (2) maximum period of continuous euthymia in the preceding 2 years (Beta = −5.26, SE = 1.71, P = 0.003), (3) presence of psychosis (Beta = 3.22, SE = 1.02, P = 0.002), and 4) response to mood stabilizers (Beta = −2.11, SE = 0.76, P = 0.006). The findings of this study confirm previous observations of the high prevalence and negative impact of comorbid anxiety disorders in bipolar disorder and also demonstrate that the findings are similar in culturally diverse settings. Future studies should systematically examine the various treatment options for anxiety disorders in bipolar patients. It is also necessary to examine the neurobiological and family/genetic correlates of anxious bipolar subjects to validate if they are a subgroup of bipolar disorders.     

缓解期双相障碍患者认知功能损害影响因素分析

目的:探讨缓解期双相障碍(BPD)患者认知功能损害的影响因素。方法:采用8个神经心理测验(共17项)对缓解期BPD50例和正常对照组50例进行注意力、言语学习和记忆、视觉记忆和执行功能的评定,并对上述神经心理测验结果和临床变量的关系进行相关分析。结果:即刻逻辑记忆、延迟逻辑记忆、威斯康星卡片分类测验(WCST)完成分类数、WCST持续性错误数、WCST非持续性错误数、完成第一分类应答数、连线测验-A、连线测验-B均与病程、住院次数、躁狂发作次数、抑郁发作次数呈显著性相关(P<0.05或P<0.01),数字广度测验-倒背和住院次数呈负相关(P<0.05)。结论:病程越长、住院次数和发作次数越多,缓解期BPD患者认知功能测验成绩越差。     

Salivary cortisol secretion in remitted bipolar patients and offspring of bipolar parents

OBJECTIVES: It is generally believed that cortisol secretion normalizes during clinical remission in mood disorders. However, this assumption has been challenged by preliminary reports of enhanced cortisol secretion in remitted bipolar patients and in the offspring of bipolar parents. The purpose of this study is to replicate findings of increased cortisol secretion during clinical remission in bipolar patients and in the offspring of bipolar parents, rigorously controlling for known confounders. METHODS: We conducted intensive cortisol sampling (six samples per day for three test days, on three consecutive weekends) on 15 bipolar type I and type II patients and 28 unrelated offspring of bipolar parents. Offspring had a history of unipolar depression. Participation was restricted to cases in complete sustained remission. Controls were matched as closely as possible for age, sex, and education. Mood and sleep measures were recorded on each sampling day. RESULTS: In total, 743 samples were collected from the patient group and 576 from controls. Correcting for repeat measures, there was no statistically significant difference in cortisol secretion at any sampling time between remitted bipolar patients, remitted offspring of bipolar parents, and normal controls. The cortisol waking response did not differ between patients and controls. Covariates, including sex, age, Beck depression score and hours of sleep, were not statistically significant. CONCLUSIONS: Our observations are consistent with the view that complete sustained clinical remission is associated with normal salivary cortisol levels throughout the day. A personal or family history of bipolar disorder per se does not appear to confer added risk for increased salivary cortisol secretion during sustained clinical remission.     

缓解期双相情感性精神障碍患者认知功能

目的:了解缓解期双相情感性精神障碍患者认知功能损害的特点。方法:采用逻辑记忆、视觉再生记忆、连线测验A和B、数字广度测验、威斯康星卡片分类测验(WCST)及字色混淆测验(stroop)对62例缓解期双相情感性精神障碍患者(患者组)和62名健康者(对照组)进行有关言语学习和记忆、非言语学习和记忆、注意以及执行功能的神经心理学评定,比较两组间认知功能的差异。结果:患者组在即刻逻辑记忆、延迟逻辑记忆、连线测验A和B、WCST正确应答数、完成分类数、持续性错误数以及Stroop C-W操作分上均显著低于对照组(P<0.05~0.01)。结论:双相情感性精神障碍患者的认知缺陷有其特点。     

Self‐esteem in remitted bipolar disorder patients: a meta‐analysis

Nilsson KK, Jørgensen CR, Craig TKJ, Straarup KN, Licht RW. Self‐esteem in remitted bipolar disorder patients: a meta‐analysis.
Bipolar Disord 2010: 12: 585–592. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Low self‐esteem has been found to be a risk factor for depression in major depressive disorder (MDD). In contrast, the role of self‐esteem in bipolar disorder (BD) is still uncertain. In order to examine the characteristics of self‐esteem in BD, we synthesized studies comparing self‐esteem in BD patients with self‐esteem in MDD patients and in normal controls. Methods: Database searches and identification of studies were conducted by two of the authors independently. Remission of BD and MDD was a major selection criterion. The results were generated through meta‐analyses. Results: Random‐effects models of 19 between‐group comparisons (N = 1,838) suggested that the self‐esteem of remitted BD patients was significantly lower than that of normal controls (Cohen’s d = ?0.83), while significantly higher than that of remitted MDD patients (Cohen’s d = 0.54). Fail‐safe numbers and tests for funnel plot asymmetry indicated that the results were robust and unlikely to reflect publication biases. Additional studies indicated that self‐esteem may take a fluctuating course during remission of BD. Conclusions: By revealing that BD patients do experience low self‐esteem, the findings implicate a need for further understanding the causes and therapeutic impact of such abnormality in BD.     

Distribution and acute stressor-induced activation of corticotrophin-releasing hormone neurones in the central nervous system of Xenopus laevis

In mammals, corticotrophin-releasing hormone (CRH) and related peptides are known to play essential roles in the regulation of neuroendocrine, autonomic and behavioural responses to physical and emotional stress. In nonmammalian species, CRH-like peptides are hypothesized to play similar neuroendocrine and neurocrine roles. However, there is relatively little detailed information on the distribution of CRH neurones in the central nervous system (CNS) of nonmammalian vertebrates, and there are currently no comparative data on stress-induced changes in CRH neuronal physiology. We used a specific, affinity-purified antibody raised against synthetic Xenopus laevis CRH to map the distribution of CRH in the CNS of juvenile South African clawed frogs. We then analysed stress-induced changes in CRH immunoreactivity (CRH-ir) throughout the CNS. We found that CRH-positive cell bodies and fibres are widely distributed throughout the brain and rostral spinal cord of juvenile X. laevis. Strong CRH-immunoreactivity (ir) was found in cell bodies and fibres in the anterior preoptic area (POA, an area homologous to the mammalian paraventricular nucleus) and the external zone of the median eminence. Specific CRH-ir cell bodies and fibres were also identified in the septum, pallium and striatum in the telencephalon; the amygdala, bed nucleus of the stria terminalis and various hypothalamic and thalamic nuclei in the diencephalon; the tectum, torus semicircularis and tegmental nuclei of the mesencephalon; the cerebellum and locus coeruleus in the rhombencephalon; and the ventral horn of the rostral spinal cord. To determine if exposure to an acute physical stressor alters CRH neuronal physiology, we exposed juvenile frogs to shaking/handling and conducted morphometric analysis. Plasma corticosterone was significantly elevated by 30 min after exposure to the stressor and continued to increase up to 6 h. Morphometric analysis of CRH-ir after 4 h of stress showed a significant increase in CRH-ir in parvocellular neurones of the anterior preoptic area, the medial amygdala and the bed nucleus of the stria terminalis, but not in other brain regions. The stress-induced increase in CRH-ir in the POA was associated with increased Fos-like immunoreactivity (Fos-LI), and confocal microscopy showed that CRH-ir colocalized with Fos-LI in a subset of Fos-LI-positive neurones. Our results support the view that the basic pattern of CNS CRH expression arose early in vertebrate evolution and lend further support to earlier studies suggesting that amphibians may be a transitional species for descending CRH-ergic pathways. Furthermore, CRH neurones in the frog brain exhibit changes in response to a physical stressor that parallel those seen in mammals, and thus are likely to play an active role in mediating neuroendocrine, behavioural and autonomic stress responses.     

双相障碍缓解期残留症状自评与他评的一致性研究

目的:探讨双相障碍(BD)缓解期残留症状自评与他评的一致性。方法:收集240例经过急性期治疗有效的BD患者人口学资料、疾病临床特征;分别于急性期治疗后(基线)及此后的3个月和6个月时采用抑郁症状快速评估量表(QIDS-SR16)、心境障碍问卷(MDQ)自评方式与汉密尔顿抑郁量表17项(HAMD-17)、杨氏躁狂量表(YMRS)他评方式对入组者进行残留症状评估;采用组内相关系数(ICC)对连续变量做一致性检验。结果:HAMD-17与QIDS-SR16基线、3个月和6个月的总分、核心条目呈较强一致性(ICC=0.62～0.85;P均<0.01);睡眠条目在基线呈中等一致性(ICC=0.49,P<0.01),3及6个月呈较强一致性(ICC=0.65;P均<0.01);自杀条目随着缓解时间延长,一致性逐渐增强;躯体症状一致性一般(ICC=0.49～0.52;P均<0.01),且随着缓解期延长,一致性减弱。YMRS与MDQ在总分、精力充沛和/或心境高涨、冒险和/或易激惹条目上随着缓解时间延长,从基线呈一般或中等一致性(ICC=0.37～0.50;P均<0.01)到6...     

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。     

A combined dexamethasone/corticotropin-releasing hormone test in patients with chronic PTSD--first preliminary results

BACKGROUND: Reports about alterations of hypothalamic-pituitary-adrenocortical (HPA) function in patients with chronic posttraumatic stress disorder (PTSD) are inconsistent and controversial. More refined laboratory tests and subgrouping of PTSD patients might help to decrease variance of findings. METHODS: 14 subjects with chronic PTSD and 14 healthy controls were examined between 13:00 and 17:00 using a modified combined dexamethasone/CRH test (0.5 mg dexamethasone at 23:00, 100 microg CRH at 15:00). Plasma adenocorticotropic hormone (ACTH), cortisol and blood pressure were measured every 15 min from 14:45 until 17:00. RESULTS: No significant differences between patients and controls were found in the analyses of ACTH and cortisol levels, but a significantly elevated systolic and diastolic blood pressure in PTSD. Severity of depressive symptoms had no influence. However, explorative analyses showed that patients with a history of childhood traumatization had significantly higher post-dexamethasone-ACTH levels and a significantly lower diastolic blood pressure in comparison to patients without early trauma. CONCLUSIONS: In this first pilot study in a typical clinical sample of patients with chronic PTSD we found effects of severe adverse events in childhood on HPA axis regulation. Maybe, childhood traumatization could influence HPA axis findings in PTSD. Further research is needed, especially dose-response studies with different doses of dexamethasone in dexamethasone/CRH tests in PTSD.     

Augmented hypothalamic corticotrophin-releasing hormone mRNA and corticosterone responses to stress in adult rats exposed to perinatal hypoxia

Stressful events before or just after parturition alter the subsequent phenotypical response to stress in a general process termed programming. Hypoxia during the period before and during parturition, and in the postnatal period, is one of the most common causes of perinatal distress, morbidity, and mortality. We have found that perinatal hypoxia (prenatal day 19 to postnatal day 14) augmented the corticosterone response to stress and increased basal corticotrophin-releasing hormone (CRH) mRNA levels in the parvocellular portion of the paraventricular nucleus (PVN) in 6-month-old rats. There was no effect on the levels of hypothalamic parvocellular PVN vasopressin mRNA, anterior pituitary pro-opiomelanocortin or CRH receptor-1 mRNA, or hippocampus glucocorticoid receptor mRNA. We conclude that hypoxia spanning the period just before and for several weeks after parturition programmes the hypothalamic-pituitary-adrenal axis to hyper-respond to acute stress in adulthood, probably as a result of drive from the parvocellular CRH neurones.     

Persistent attentional dysfunction in remitted bipolar disorder

Objectives: Although previous research has shown that attentional dysfunction is common during acute mood episodes in individuals with bipolar disorder (BPD), few studies have examined whether attentional deficits are evident during periods of symptom stability. The goal of this study was to determine whether clinically stable individuals with BPD would have attentional disturbances relative to healthy subjects. Methods: Fourteen patients with BPD and 12 healthy comparison subjects participated in the study, and were administered the Degraded Stimulus Continuous Performance Test (DSCPT), Digit Span Distractibility Test (DSDT) and Grooved Pegboard Test (GPT). Psychiatric symptoms were assessed with the Young Mania Rating Scale and the Scale for the Assessment of Positive Symptoms. Medication side effects were measured with the Simpson Rating Scale. Results: The patient group responded significantly more slowly than the control group on the DSCPT (z=−2.52, p=0.01) and the GPT (z=−3.37, p=0.001). There was a trend towards the BPD patients demonstrating impaired perceptual sensitivity on the DSCPT (z=1.68, p=0.09). The two groups did not differ on the DSDT (z=−1.06, p=0.3). Poor performance on the GPT and DSCPT target reaction time were not associated with symptom ratings or medications. Conclusion: The findings suggest that impairments in fine motor skills and reaction time may be present in clinically stable patients with BPD, even after accounting for psychiatric symptoms and medication effects. Performance decrements on attentional tasks may be in part reflective of motor impairments in patients with BPD.     

Cognitive functioning in euthymic bipolar I and bipolar II patients

Objective: There is growing evidence of cognitive impairment as a trait factor in bipolar disorder. The generalizability of this finding is limited because previous studies have either focussed exclusively on bipolar I disorder or have analysed mixed patient groups. Thus, it is still largely unknown whether bipolar II patients perform differently from bipolar I patients on measures of cognitive functioning. Methodology: A total of 65 patients with bipolar I disorder, 38 with bipolar II disorder, and 62 healthy controls participated in the study. Patients had to be euthymic for at least one month. Clinical and demographic variables were collected in a clinical interview and with the Structured Clinical Interview for DSM‐IV. Cognitive functioning was assessed using a neuropsychological battery. Univariate and multivariate analyses of variance were conducted for analyzing possible differences between the groups. Results: The multivariate analysis of covariance (MANCOVA) indicated overall differences in neuropsychological performance between the three groups (Pillai Spur: F 1.96, p = 0.003). Post hoc comparisons revealed that patients with bipolar I disorder showed significantly lower scores in psychomotor speed, working memory, verbal learning, delayed memory, and executive functions than healthy controls. Patients with bipolar II disorder showed significant deficits in psychomotor speed, working memory, visual/constructional abilities, and executive functions compared to controls, but not on verbal learning and delayed memory. The two patient groups did not differ significantly from each other on any domain tested. Conclusion: These results support a similar pattern of cognitive deficits in both subtypes of bipolar disorder.     

Oestrogenic regulation of pro-opiomelanocortin, neuropeptide Y and corticotrophin-releasing hormone mRNAs in mouse hypothalamus

It is well documented that oestrogen suppresses food intake by an action at the hypothalamic level. Using in situ hybridisation, we studied the effect of castration (CX) and short-term administration of oestradiol (E2) in CX female mice for three neuropeptides involved in feeding behaviour: two anorexigenic peptides, (i) the pro-opiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone and (ii) corticotrophin-releasing hormone (CRH), and the orexigenic peptide, (iii) neuropeptide Y (NPY). POMC-expressing neurones were mostly laterally located in the arcuate nucleus. POMC mRNA expression was decreased following CX and a single injection of E2 induced an increase in mRNA levels at 12- and 24-h time intervals. In the parvocellular area of the paraventricular nucleus, CRH mRNA levels were similarly decreased after CX and completely restored to normal levels at 12 and 24 h following E2 injection. On the other hand, the levels of NPY mRNA expressed in neurones located in the inner zone of the arcuate nucleus were increased by CX and decreased to the levels observed in intact animals by E2 injection (3-24 h). The present data suggest that oestrogen might exert an anorexigenic action by stimulating POMC and CRH mRNA expression and decreasing NPY mRNA expression in the hypothalamus.     

Difference in binocular rivalry rate between patients with bipolar I and bipolar II disorders

Objective:  When dissimilar figures are presented to each eye individually, perception alternates spontaneously between each monocular view. This phenomenon, known as binocular rivalry, has been used as a powerful tool to investigate conscious visual awareness. Of clinical relevance, Pettigrew and Miller ( Proc Biol Sci 1998; 265: 2141-2148 ) found slow perceptual alternation rates in patients with bipolar I disorder (BD-I). For a better understanding of differences between BD-I and bipolar II disorder (BD-II), we examined whether perceptual alternation rates of binocular rivalry differ between the two subtypes of bipolar disorder.
Methods:  The subjects comprised 25 healthy controls, 11 patients with BD-I, and 17 patients with BD-II. They underwent binocular rivalry examination. One-way analysis of variance was conducted to determine differences in the phase duration of binocular rivalry between the control, BD-I, and BD-II groups.
Results:  Significant differences were observed in the mean phase duration of binocular rivalry between the groups. Although the medication administered did not differ significantly between the BD-I and BD-II patients, the phase duration was significantly longer among the BD-I patients than the BD-II patients and controls, whereas no significant difference was observed in the phase duration between the BD-II patients and controls.
Conclusion:  The present results reveal a significant difference in the mean phase duration of binocular rivalry between subjects with BD-I and those with BD-II, suggesting the presence of some neurobiological difference between these two subtypes of bipolar disorder.