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ABSTRACT: BACKGROUND: Evidence shows that depression is associated with hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, although such findings are not entirely unequivocal. In contrast, various psychiatric conditions, including atypical depression, are associated with hypocortisolism. Another line of research has demonstrated that personality is associated with HPA axis alteration. It is thus hypothesized that different personality pathology in depression would be associated with distinct cortisol reactivity. METHODS: Eighty-seven outpatients with DSM-IV major depressive disorder were recruited. Personality was assessed by the temperament and character inventory (TCI). HPA axis reactivity was measured by the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test. According to our previous studies, two subgroups were considered based on their cortisol responses to the DEX/CRH test: incomplete-suppressors whose cortisol response was exaggerated and enhanced-suppressors whose cortisol response was blunted. RESULTS: The analysis of covariance, controlling for age, gender and symptom severity, revealed that incomplete-suppressors scored significantly higher on cooperativeness than enhanced-suppressors (p=0.002). A multivariate stepwise logistic regression analysis predicting the cortisol suppression pattern from the seven TCI dimensions, controlling for age, gender and symptom severity, revealed that lower cooperativeness (p=0.001) and higher reward dependence (p=0.018) were significant predictors toward enhanced suppression. LIMITATIONS: The neuroendocrine challenge test was administered only once, based on a simple test protocol. CONCLUSIONS: Our findings suggest that (personality-related) subtypes of depression might be differentiated based on the different pattern of cortisol reactivity. Future studies are warranted to further characterize the HPA axis alteration in relation to various subtypes of depression.
Journal of affective disorders 11/2012; · 3.76 Impact Factor
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ABSTRACT: BACKGROUND: Growing evidence suggests that schizotypy and genetic loading for schizophrenia both represent risk for the development of schizophrenia. Although these conditions are known to be associated with neurocognitive impairments, such an association has not been studied in patients with bipolar II disorder (BPII) or unipolar major depressive disorder (UP). METHODS: Forty-one depressed patients with BPII, 131 patients with UP and demographically matched 225 healthy controls were recruited. Schizotypy was assessed by the Schizotypal Personality Questionnaire. Neuropsychological functioning was measured by the Wechsler Memory Scale-Revised, the Wechsler Adult Intelligence Scale-Revised and the Wisconsin Card Sorting Test. RESULTS: Mood disorder patients performed significantly worse than controls in verbal and visual memory, working memory and processing speed. BPII patients performed significantly more poorly than UP patients in verbal memory and executive functioning. Both BPII and UP patients demonstrated significantly greater schizotypal traits than controls. Schizotypy was significantly negatively correlated with verbal comprehension both in BPII and UP patients and with working memory and processing speed in healthy controls. Patients who had one or more first-degree relatives with schizophrenia performed significantly more poorly than the remaining patients in all cognitive domains. LIMITATIONS: Most of our patients were on psychotropic medication, and the sample of BPII patients was not very large. CONCLUSIONS: Liability for schizophrenia could play a pivotal role in neurocognitive functioning in mood disorders, suggesting that such liability might lie on a continuum ranging from normality through mood disorders to full-blown schizophrenia.
Journal of affective disorders 06/2012; · 3.76 Impact Factor
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Takashi Fujii,
Miho Ota,
Hiroaki Hori,
Daimei Sasayama,
Kotaro Hattori,
Toshiya Teraishi,
Noriko Yamamoto, Miyako Hashikura,
Masahiko Tatsumi,
Teruhiko Higuchi,
Hiroshi Kunugi
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ABSTRACT: Human P-glycoprotein (P-gp), which is encoded by ABCB1 (ATP-binding cassette, sub-family B member 1), is expressed in the blood brain barrier and protects the brain from many kinds of drugs and toxins including glucocorticoids by acting as an efflux pump. We examined whether functional polymorphisms of ABCB1 give susceptibility to major depressive disorder (MDD). The five functional single nucleotide polymorphisms (SNPs), A-41G (rs2188524), T-129C (rs3213619), C1236T (Gly412Gly: rs1128503), G2677A/T (Ala893Ser/Thr: rs2032582), and C3435T (Ile1145Ile: rs1045642) were genotyped in 631 MDD patients and 1100 controls in the Japanese population. A tri-allelic SNP, G2677A/T, was genotyped by pyrosequencing and the remaining SNPs were genotyped by the TaqMan 5'-exonuclease allelic discrimination assay. The minor T3435 allele was significantly increased in MDD patients than in the controls (χ(2) = 4.5, df = 1, p = 0.034, odds ratio [OR] 1.16, 95% confidential interval [CI] 1.01-1.34). Homozygotes for the T3435 allele was significantly more common in patients than in the controls (χ(2) = 7.5, df = 1, p = 0.0062, OR 1.43, 95%CI 1.11-1.85). With respect to the other 4 SNPs, there was no significant difference in genotype or allele distribution. In the haplotype-based analysis, the proportion of individuals with the TT1236-TT3435 haploid genotype was significantly increased in patients than in controls (χ(2) = 8.5, df = 1, p = 0.0037, OR 1.50, 95%CI 1.14-1.98). Our results suggest that the T3435 allele or carrying two copies of this allele confers susceptibility to MDD in the Japanese population.
Journal of psychiatric research 02/2012; 46(4):555-9. · 3.72 Impact Factor
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Daimei Sasayama,
Hiroaki Hori,
Toshiya Teraishi,
Kotaro Hattori,
Miho Ota,
Junko Matsuo,
Yumiko Kawamoto,
Yukiko Kinoshita, Miyako Hashikura,
Naoji Amano,
Teruhiko Higuchi,
Hiroshi Kunugi
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ABSTRACT: Mood disorders are associated with various neurocognitive deficits. However, few studies have reported the impairment of motor dexterity in unipolar depression and bipolar disorder. In the present study, manual dexterity was compared between unipolar major depression, bipolar disorder, and healthy controls.
Manual dexterity was assessed by the Purdue pegboard test in 98 patients with unipolar major depression, 48 euthymic or depressed patients with bipolar disorder, and 158 healthy controls, matched for age and gender.
Compared to healthy controls, sum of the scores of right, left, and both hands subtests (R+L+B) was significantly lower in both patients with unipolar depression and bipolar disorder (P=0.0034 and P<0.0001, respectively). Furthermore, R+L+B was significantly lower in bipolar disorder compared to unipolar depression (P=0.0016). Lithium dose and chlorpromazine equivalent dose of antipsychotics were significantly negatively correlated with some of the subtest scores. On the other hand, depression severity did not significantly correlate with any of the subtest scores. Difference in R+L+B between unipolar depression and bipolar disorder remained statistically significant even after controlling for gender, age, lithium dose, and chlorpromazine equivalent dose (P=0.0028). Limitations Bipolar patients during manic episode were not included in the study.
Gross movement dexterity was impaired in both patients with unipolar depression and bipolar disorder. The severity of impairment was significantly greater in patients with bipolar disorder. The functional difference between unipolar and bipolar patients may suggest different pathological conditions between the two depressive disorders.
Journal of affective disorders 12/2011; 136(3):1047-52. · 3.76 Impact Factor
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Takashi Fujii,
Noriko Yamamoto,
Hiroaki Hori,
Kotaro Hattori,
Daimei Sasayama,
Toshiya Teraishi, Miyako Hashikura,
Masahiko Tatsumi,
Nagahisa Okamoto,
Teruhiko Higuchi,
Hiroshi Kunugi
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ABSTRACT: Altered neurotrophin functions have been implicated in major depressive disorder (MDD). Previously, we reported an association between MDD and a missense polymorphism (Ser205Leu: rs2072446) of the gene encoding the p75 neurotrophin receptor (p75(NTR)). However, contradictive negative results have also been reported. This study tried to replicate the association in an independent sample. Subjects were 668 patients with MDD and 1130 healthy controls. The proportion of individuals carrying the Leu205 allele was significantly decreased in the patients than in the controls (χ(2)=5.3, d.f.=1, P=0.021, odds ratio (OR) 0.74, 95% confidential interval (CI) 0.58-0.96). When allele frequencies were compared, the Leu205 allele was significantly reduced in the patients than in the controls (χ(2)=4.4, d.f.=1, P=0.037, OR 0.78, 95% CI 0.61-0.99). When men and women were examined separately, there was a significant difference in genotype and allele distributions in women (genotype: χ(2)=8.3, d.f.=1, P=0.0039, OR 0.60, 95% CI 0.43-0.85; allele: χ(2)=7.3, d.f.=1, P=0.0069, OR 0.64, 95% CI 0.47-0.89), but not in men. The present study provided support for the previously reported association between the Ser205Leu polymorphism of the p75(NTR) gene and MDD, indicating that the Leu205 allele has a protective effect against the development of MDD, particularly in women.
Journal of Human Genetics 09/2011; 56(11):806-9. · 2.57 Impact Factor
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Daimei Sasayama,
Hiroaki Hori,
Toshiya Teraishi,
Kotaro Hattori,
Miho Ota,
Junko Matsuo,
Yumiko Kawamoto,
Yukiko Kinoshita, Miyako Hashikura,
Norie Koga,
Nagahisa Okamoto,
Kota Sakamoto,
Teruhiko Higuchi,
Naoji Amano,
Hiroshi Kunugi
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ABSTRACT: Although some core personality variables are known to be characteristic of unipolar or bipolar depression, few studies have compared the personality profile between these two disorders.
Temperament and Character Inventory (TCI) was employed to assess the personality of 36 depressed patients with bipolar II disorder (BPII), 90 patients with unipolar major depressive disorder (UP), and 306 healthy controls. The TCI was administered during the depressive episode in BPII and UP patients so that the results can be applied in a clinical setting.
Significantly higher scores in harm avoidance (p<0.0001) and lower scores in self-directedness (p<0.0001) and cooperativeness (p<0.05) were observed in both BPII and UP patients compared to controls. Lower novelty seeking in UP patients compared to BPII patients and controls was observed in females (p<0.0001, p<0.01, respectively). A significant difference in self-transcendence score was observed between BPII and UP patients in females (p<0.0005), with higher scores in BPII (p=0.009) and lower scores in UP (p=0.046) patients compared to controls. A logistic regression model predicted BPII in depressed females based on novelty seeking and self-transcendence scores with a sensitivity of 89% and a specificity of 73%, but did not accurately predict BPII in males.
Patients in our study were limited to those receiving outpatient treatments, and bipolar patients were limited to those with BPII.
Novelty seeking and self-transcendence scores of TCI might be useful in the differentiation of UP and BPII in female patients.
Journal of affective disorders 03/2011; 132(3):319-24. · 3.76 Impact Factor
