Guiyun Xu

Neuropsychological performance in bipolar I, bipolar II and unipolar depression patients: a longitudinal, naturalistic study.

BACKGROUND It has been suggested that cognitive deficits existed in mood disorders. Nevertheless, whether neuropsychological profiles differ three main subtypes of mood disorder (Bipolar I, Bipolar II and UP) remain understudied because most current studies include either mixed samples of bipolar I and bipolar II patients or mixed samples of different states of the illness. The main aim of the present study is to determine whether, or to some extent, specific cognitive domains could differentiate the main subtypes of mood disorders in the depressed and clinically remitted status. METHOD Three groups of bipolar I (n=92), bipolar II (n=131) and unipolar depression (UP) patients (n=293) were tested with a battery of neuropsychological tests both at baseline (during a depressive episode) and after 6 weeks of treatment, contrasting with 202 healthy controls on cognitive performance. The cognitive domains include processing speed, attention, memory, verbal fluency and executive function. RESULTS At the acute depressive state, the three patient groups (bipolar I, bipolar II and UP) showed cognitive dysfunction in processing speed, memory, verbal fluency and executive function but not in attention compared with controls. Post comparisons revealed that bipolar I depressed patients performed significantly worse in verbal fluency and executive function than bipolar II and UP depressed patients. No difference was found between bipolar II and UP depressed patients except for the visual memory. After 6 weeks of treatment, clinically remitted bipolar I and bipolar II patients only displayed cognitive impairment in processing speed and visual memory. Remitted UP patients showed cognitive impairment in executive function in addition to processing speed and visual memory. The three remitted patient groups scored similarly in processing speed and visual memory. LIMITATION Clinically remitted patients were just recovered from a major depressive episode after 6 weeks of treatment and in relatively unstable state. CONCLUSION Bipolar I, bipolar II and UP patients have a similar pattern of cognitive impairment during the state of acute depressive episode, but bipolar I patients experience greater impairment than bipolar II and UP patients. In clinical remission, both bipolar and UP patients show cognitive deficits in processing speed and visual memory, and executive dysfunction might be a status-maker for bipolar disorder, but a trait-marker for UP.

Neuropsychological performance in melancholic, atypical and undifferentiated major depression during depressed and remitted states: a prospective longitudinal study

BACKGROUND Considerable evidence has demonstrated that melancholic and atypical major depression have distinct biological correlates relative to undifferentiated major depression, but few studies have specifically delineated neuropsychological performance for them. METHOD In a six-week prospective longitudinal study, we simultaneously compared neuropsychological performance among melancholic depression (n=142), atypical depression (n=76), undifferentiated major depression (n=91), and healthy controls (n=200) during a major depressive episode and a clinically remitted state, respectively. We administered neuropsychological tests assessing processing speed, attention, shifting, planning, verbal fluency, visual spatial memory, and verbal working memory to all participants. RESULTS During the depressive state, the three subtypes displayed extensive cognitive impairment, except for attention, when compared with the healthy controls. Melancholic depression significantly differed from atypical depression in processing speed and verbal fluency. In the remitted state, the three subtypes recovered their visual spatial memory and verbal working memory functions to the healthy control level. The recovery of the other domains (processing speed, set shifting, planning, and verbal fluency), however, was different across the subtypes. No predictive relationship existed between neuropsychological performance and the treatment outcome. LIMITATIONS The drop-out rate in the six-week longitudinal study was relatively high. CONCLUSION Our data provide preliminary evidence that during depressed states the three major depressive subtypes display similar cognitive deficits in some domains but differ in such domains as processing speed and verbal fluency. The recovery of the cognitive deficits following clinical remission from depression may be associated with subtypes of major depressive disorder.

Psychometric properties of the Chinese (Mandarin) TEMPS-A: A population study of 985 non-clinical subjects in China

BACKGROUND The TEMPS-A (Temperament Evaluation of Memphis, Pisa, Paris and San Diego) is a 110-item auto-questionnaire (self-rated) which consists of five temperament scales: depressive, cyclothymic, hyperthymic, irritable and anxious temperaments. It has been translated into over 25 languages and validated in at least 12, with broad cross-cultural cogency. This is a first attempt to validate the TEMPS-A in a very large Chinese population speaking Mandarin. METHODS The Chinese TEMPS-A was adapted from the original English version following a rigorous process of forward translation and backward translation (after the approval of the English back translation by H.S.A. and K.K.A.), it was administered to 985 non-clinical Chinese subjects aged between 18-60 years (53.8% female) in four communities in Guangzhou City, China. A subset of 105 subjects was retested approximately six weeks later. Standard psychometric tests of reliability and validation were performed. RESULTS The test-retest reliability for depressive (0.74), cyclothymic (0.71), hyperthymic (0.67), irritable (0.66) and anxious (0.83) were respectively as shown in the parentheses. For internal consistency, Chronbach alphas coefficients were 0.68, 0.85, 0.82, 0.83 and 0.87, respectively. Exploratory factor analysis revealed 2 super factors, Factor I loading on anxious, cyclothymic, irritable, and depressive temperaments; and Factor II loading on hyperthymic. Depressive, cyclothymic, irritable and anxious temperaments were correlated with each other. Males had significantly higher scores than females for the hyperthymic and irritable temperaments. The prevalence of the dominant depressive (2.9%), cyclothymic (5.6%), hyperthymic (1.3%), irritable (7.0%) and anxious (5.3%) temperaments were respectively as shown in the parentheses. LIMITATIONS Although it is likely that generalizability of our scale is good for the entire Mandarin-speaking ethnic composition of China today, future research is needed to establish this conclusively. CONCLUSION The Chinese TEMPS-A standardized on one of the largest non-clinical samples in any of the other national studies to date, has good internal consistency, coheres well with validated versions in other languages. The findings suggest that it is a psychometrically sound instrument to assess affective temperaments in clinical and biological studies in China.

Brain-derived neurotrophic factor gene polymorphism (Val66Met) and the early response to antidepressant in Chinese Han population.

Major depressive disorder (MDD) is a genetically complex and heterogeneous disorder. Accumulating evidence suggests that brain derived neurotrophic factor (BDNF) is involved in the pathophysiology of MDD. A functional nonsynonymous single nucleotide polymorphism that causes an amino-acid substitution of valine to methionine is located in the coding exon of BDNF gene at amino acid position 66 (Val66Met, rs6265) (Sen et al., 2003). The BDNF Val/Met polymorphism has become a main target for pharmacogenetic studies because of its role in the pathophysiology of MDD. In this study, we investigated the association between treatment outcome with different antidepressants [selective serotonin reuptake inhibitors (SSRIs) and venlafaxine] and BDNF Val/Met polymorphism in a prospective naturalistic setting in Chinese Han population.

A Multi-Dimensional and Integrative Approach to Examining the High-Risk and Ultra-High-Risk Stages of Bipolar Disorder.

Background Validating the high-risk (HR) and ultra-high-risk (UHR) stages of bipolar disorder (BP) may help enable early intervention strategies. Methods We followed up with 44 offspring of parents with BP, subdividing into the HR and UHR categories. The offspring were aged 8–28 years and were free of any current DSM-IV diagnoses. Our multilevel, integrative approach encompassed gray matter (GM) volumes, brain network connectivity, neuropsychological performance, and clinical outcomes. Findings Compared with the healthy controls (HCs) (n = 33), the HR offspring (n = 26) showed GM volume reductions in the right orbitofrontal cortex. Compared with the HR offspring, the UHR offspring (n = 18) exhibited increased GM volumes in four regions. Both the HR and UHR offspring displayed abnormalities in the inferior occipital cortex regarding the measures of degree and centrality, reflecting the connections and roles of the region, respectively. In the UHR versus the HR offspring, the UHR offspring exhibited upwards-shifted small world topologies that reflect high clustering and efficiency in the brain networks. Compared with the HCs, the UHR offspring had significantly lower assortativity, which was suggestive of vulnerability. Finally, processing speed, visual–spatial, and general function were impaired in the UHR offspring but not in the HR offspring. Interpretation The abnormalities observed in the HR offspring appear to be inherited, whereas those associated with the UHR offspring represent stage-specific changes predisposing them to developing the disorder.

Adverse effects of obesity on cognitive functions in individuals at ultra high risk for bipolar disorder: Results from the global mood and brain science initiative

The burden of illness associated with bipolar disorder (BD) warrants early pre‐emption/prevention. Prediction models limited to psychiatric phenomenology have insufficient predictive power. Herein, we aimed to evaluate whether the presence of overweight/obesity is associated with greater cognitive decline in individuals at high risk (HR) or ultra high risk (UHR) for BD.

Association of affective temperaments measured by TEMPS-A with cognitive deficits in patients with bipolar disorder

BACKGROUND Affective temperaments such as cyclothymia, which may be the fundamental substrates for bipolar disorder and bipolar II in particular, have been reported to be associated with abnormalities in the regions that are related to cognitive deficits in bipolar disorder. However, few studies have examined the effects of affective temperaments on neuropsychological performance in individuals with bipolar disorder. METHOD In a six-week prospective study, we administered Chinese version of TEMPS-A (Temperament Evaluation of Memphis, Pisa, San Diego-Autoquestionnair) to 93 patients with bipolar I depression, 135 patients with bipolar II depression, and 101 healthy controls. Cognitive function was assessed with a battery of neuropsychological tasks, including attention, processing speed, set shifting, planning, verbal working memory, verbal fluency, and visual spatial memory. Mixed-effects statistical models were used to assess the effects of affective temperaments on cognitive function. RESULTS Bipolar patients with hyperthymic temperament showed greater cognitive deficits in set shifting (p=0.05) and verbal working memory (p=0.026) than did bipolar patients with non-predominant temperaments (predominant temperament was defined as one standard deviation above the mean). The differences in estimated marginal means were -0.624 (95% CI, -1.25 to 0) and -0.429 (95% CI, -0.81 to -0.05), respectively. Significant temperament X bipolar subtype interaction effects were observed for set shifting (Wald X(2)=18.161, p<0.001), planning (Wald X(2)=7.906, p=0.048), and visual spatial memory (Wald X(2)=16.418, p=0.001). LIMITATION The anxious temperament was not evaluated. CONCLUSION Our data suggest that hyperthymic temperament may be associated with cognitive deficits in some specific domains in bipolar disorder; and that the effect of temperaments may be different across subtypes of bipolar disorder.

The use of 15-point hypomanic checklist in differentiating bipolar I and bipolar II disorder from major depressive disorder.

OBJECTIVES Individuals with bipolar disorder (BP) are often misdiagnosed with major depressive disorder (MDD). In this study, we developed a Chinese version of 15-point hypomania scale (HCL-15) in order to determine its sensitivity and specificity in the diagnosis of BP and BP-II in particular. METHODS A total of 623 individuals suffering a major depressive episode (MDE) were systematically interviewed with both Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Patient Edition, and HCL-15. A cutoff score of 8 or more in HCL-15 was suggested for BP. RESULTS Of the 623 depressed patients, 115 (18.5%) actually required a diagnosis of BP-I, and another 159 (25.5%) could be more appropriately diagnosed with BP-II, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The sensitivity of 15-HCL in detection of BP-II was 0.78 and 0.46 for BP-I; the specificity was 0.9 and 0.69, respectively. The specificity of HCL-15 for BP versus MDD was as high as 0.93. Approximately 60%-80% of all questions in the HCL-15 questionnaire revealed positive responses from patients, while items 11 and 12, measuring the consumption of alcohol, coffee and cigarettes, demonstrated a low positive response rate. CONCLUSIONS The HCL-15 assessment scale was fairly sensitive and highly specific for a BP-II diagnosis but not for a BP-I diagnosis. Some items in the HCL-15 symptom list need to be further modified to better fit Chinese culture and customs. The HCL-15 scale could be a useful tool in clinical practice for screening individuals with BP-II in order to avoid a misdiagnosis of MDD.

Neuropsychological performance of patients with soft bipolar spectrum disorders

There is much evidence that shows that a substantial number of individuals with DSM‐IV‐defined unipolar depression (UP) manifest hypomanic sub‐syndrome and bipolar diathesis. Other definitions have conceptualized the term soft bipolar spectrum (SBP) for these individuals. Little is known about the cognitive profiles of individuals with SBP. We hypothesized that they are representative of individuals with bipolar II disorder and are different from that of ‘strict’ UP.

Obesity and frontal-striatal brain structures in offspring of individuals with bipolar disorder: Results from the global mood and brain science initiative

To compare frontal‐striatal brain volumes between offspring of individuals with bipolar disorder (BD) and healthy controls; to investigate the associations of body mass index (BMI) and age with brain volumes; and to assess the moderating effects of BMI and age on the relationship between risk status and structural brain differences.