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ABSTRACT: Epidemiological studies have proposed that depression may increase the risk for Alzheimer's disease (AD), even in patients with early-onset depression. Although metabolism of amyloid β protein (Aβ) in elderly depression received attention in terms of their correlation, there is a serious heterogeneity in elderly depression in terms of age at onset of depression. Moreover, it is unknown whether early-onset major depressive disorder (MDD) has a long-term effect on the involvement of Aβ metabolism and later development of AD. Thus, we evaluated serum Aβ40 and Aβ42 levels, the Aβ40/Aβ42 ratio in 89 elderly (≥60 years of age) inpatients with MDD and 81 age-matched healthy controls, and compared them among patients with early-onset (<60 years) and late-onset (≥60 years) MDD and controls. The results showed that the serum Aβ40/Aβ42 ratio was significantly higher in patients with both early- and late-onset MDD than in controls (early-onset, p=0.010; late-onset, p=0.043), and it is of great interest that the serum Aβ40/Aβ42 ratio was negatively correlated with the age at MDD onset (R=-0.201, p=0.032). These results suggest that an earlier onset of MDD may have a more serious abnormality in Aβ metabolism, possibly explaining a biological mechanism underlying the link between depression and AD.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/2012; · 3.25 Impact Factor
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ABSTRACT: BACKGROUND: There is accumulating evidence regarding gender differences in clinical symptoms or response to antidepressants in patients with depression. However, less attention has been given to sex differences in the underlying biological mechanisms of depression. The adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S), play a critical role in controlling affect, mood, and anxiety. Changes in serum adrenal androgen levels have been reported in conditions pertaining to stress as well as in psychiatric disorders. The objective of the present study was to investigate differences in serum levels of adrenal androgens in male and female patients with major depressive disorder (MDD). METHODS: Participants included 90 inpatients with MDD at the psychiatric ward of Juntendo University Koshigaya Hospital who were receiving antidepressants. Serum levels of DHEA and DHEA-S were assessed at the time of admission. Matched controls (based on sex and age) included 128 healthy individuals. First, data from male and female MDD patients and controls were compared. Second, correlations between serum hormone levels and scores on the Hamilton Rating Scale for Depression (HAM-D) of patients with MDD were assessed by gender. In addition, effects of various factors on adrenal androgens were analyzed using multiple regression analysis. RESULTS: Serum DHEA levels were significantly increased in both male and female MDD patients compared with controls. Serum levels of DHEA-S in male patients were significantly decreased compared with male controls, whereas no significant differences were seen in female patients and controls. No significant correlations among adrenal androgens were observed in male patients with MDD, whereas significant positive correlations were found in both male and female controls. No significant correlations were seen between adrenal androgens and HAM-D scores in male or female patients. Multiple regression analysis showed that both hormones were affected by the age at onset of depression. LIMITATIONS: All subjects in the present study were on antidepressant medications. CONCLUSIONS: Elevated levels of serum DHEA may be associated with the biological pathophysiology of depression, as DHEA administration has been found to be effective for the treatment of depression. Findings of differential changes in DHEA-S levels in men compared with women may suggest distinct characteristics of these hormones between men and women with depression. However, DHEA/DHEA-S may be a poor indicator for evaluating severity of depression.
Journal of affective disorders 10/2012; · 3.76 Impact Factor
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ABSTRACT: BACKGROUND: Depression may increase the risk of developing Alzheimer's disease. Large cohort studies have shown that recurrent depression is associated with a risk of developing dementia. Other studies have documented smaller hippocampal volume in patients with recurrent depression. It is speculative that a greater risk of developing dementia may result from a higher number of previous depressive episodes. This study compared patients with recurrent and single-episode depression in the remitted stage, and healthy controls to elucidate the impact of the number of depressive episodes on memory. METHODS: Logical memory and visual reproduction subtests of the Wechsler Memory Scale-Revised were given to 68 patients with major depressive disorder (MDD) (30 patients with a single episode and residual 38 patients with recurrent multiple episodes) and 57 healthy controls. The patients with MDD received memory assessment at the time of initial remission and at the follow-up period 3 years after remission. RESULTS: At the time of initial remission, scores of both logical memory and visual reproduction subtests were significantly lower in both patient groups compared with healthy controls. At follow-up, memory dysfunction of the single-episode group disappeared, whereas scores in the recurrent group remained significantly lower than those of the single-episode group and controls. LIMITATIONS: All patients in the present study were on antidepressant medications. CONCLUSIONS: Patients with recurrent MDD with multiple depressive episodes showed residual memory dysfunction even after 3 years of remission. Persistence of memory deficits in the recurrent depression may be a risk factor for developing dementia.
Journal of affective disorders 07/2012; · 3.76 Impact Factor
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Maiko Kitazawa,
Tohru Ohnuma,
Yuto Takebayashi,
Nobuto Shibata, Hajime Baba,
Kazutaka Ohi,
Yuka Yasuda,
Yukako Nakamura,
Branko Aleksic,
Akira Yoshimi,
Tomo Okochi,
Masashi Ikeda,
Hiroshi Naitoh,
Ryota Hashimoto,
Nakao Iwata,
Norio Ozaki,
Masatoshi Takeda,
Heii Arai
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ABSTRACT: Recent GWAS demonstrated an association between candidate genes located at region 6p22.1 and schizophrenia. This region has been reported to house certain candidate SNPs, which may be associated with schizophrenia at HIST1H2BJ, PRSS16, and PGBD1. These genes may presumably be associated with pathophysiology in schizophrenia, namely epigenetics and psychoneuroimmunology. A three-step study was undertaken to focus on these genes with the following aims: (1) whether these genes may be associated in Japanese patients with schizophrenia by performing a 1st stage case-control study (514 cases and 706 controls) using Japanese tagging SNPs; (2) if the genetic regions of interest for the disease from the 1st stage of analyses were found, re-sequencing was performed to search for new mutations; (3) finally, a replication study was undertaken to confirm positive findings from the 1st stage were reconfirmed using a larger number of subjects (2,583 cases and 2,903 controls) during a 2nd stage multicenter replication study in Japan. Genotyping was performed using TaqMan PCR method for the selected nine tagging SNPs. Although three SNPs situated at the 3' side of PGBD1; rs3800324, rs3800327, and rs2142730, and two-window haplotypes between rs3800327 and rs2142730 showed positive associations with schizophrenia, these associations did not have enough power to sustain significance during the 2nd stage replication study. In addition, re-sequencing for exons 5 and 6 situated at this region did not express any new mutations for schizophrenia. Taken together these results indicate that the genes HIST1H2BJ, PRSS16, and PGBD1 were not associated with Japanese patients with schizophrenia.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 04/2012; 159B(4):456-64. · 3.70 Impact Factor
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ABSTRACT: Brain-derived neurotrophic factor (BDNF) may have an important role in the pathophysiology of depression. Previous studies indicate that serum BDNF levels were lower in patients with depression and increased after treatment with antidepressants. However, results of studies on serum BDNF levels in remitted patients with depression have been inconsistent. The purpose of the present study was to determine which factors influence the alteration of serum BDNF levels in depression in the remitted state.
Serum BDNF levels were evaluated in 75 remitted inpatients with major depressive disorder (MDD) and 108 controls. Multiple regression analyses were conducted using serum BDNF levels as the dependent variable; and the number of episodes, Hamilton Rating Scale for Depression score at admission, or duration of last depressive episode as independent variables.
Serum BDNF levels were lower in remitted patients with MDD than in controls (P < .001). Multiple regression analysis showed a significant effect between the duration of the last depressive episode and serum BDNF levels (P < .022).
Serum BDNF levels in remitted patients with MDD did not recover to the level of healthy controls, and lower serum BDNF levels were influenced by a longer duration of last depressive episode. It is possible that persistent hippocampal reduction in remitted depression may be caused by lower BDNF levels associated with a longer duration of the last depressive episode.
Depression and Anxiety 03/2012; 29(9):775-9. · 4.18 Impact Factor
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ABSTRACT: Epidemiologic studies have demonstrated that a history of depression increases the risk of developing Alzheimer's disease, particularly among individuals with early-onset depression. On the other hand, recent studies have suggested that a higher amyloid-β protein (Aβ)40 to Aβ42 ratio may be associated with the future onset of Alzheimer's disease. Our objective was to assess whether the pathophysiology of early-onset depression may involve or affect Aβ metabolism.
In this extension of a case-control pilot study, 193 inpatients with DSM-IV major depressive disorder (MDD) (mean age = 55.9 years) from the Juntendo Koshigaya Hospital, Saitama, Japan, and 413 healthy controls from the community (mean age = 56.6 years) were recruited between May 2004 and April 2009. Serum Aβ40 and Aβ42 levels, Aβ40/Aβ42 ratio, and other clinical and biological factors were compared between controls and patients in 3 age groups: young (< 40 years), middle-aged (≥ 40 to < 65 years), and elderly (≥ 65 years). Depressive symptoms were assessed with the Hamilton Depression Rating Scale. All patients were receiving antidepressant medication at the time of the study, and doses of current antidepressants were converted to an equivalent imipramine dose.
The serum Aβ40/Aβ42 ratio was significantly higher in MDD patients than controls in all age groups (young: P = .003; middle-aged: P < .001; elderly: P = .006). These differences were also observed in noncarriers of the apolipoprotein E ε4 allele.
Our findings suggest that Aβ metabolism may be affected in depression; these findings also possibly answer the question of why even early-onset depression is a risk factor for developing Alzheimer's disease.
The Journal of Clinical Psychiatry 11/2011; 73(1):115-20. · 5.80 Impact Factor
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Yuto Takebayashi,
Tohru Ohnuma,
Ryo Hanzawa,
Nobuto Shibata,
Hitoshi Maeshima, Hajime Baba,
Tokiko Hatano,
Yuri Hotta,
Maiko Kitazawa,
Motoyuki Higa,
Heii Arai
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ABSTRACT: Disrupted glutamatergic neurotransmission may be a pathophysiological feature in the brains from patients with schizophrenia, and glutamatergic amino acids including d-serine have been found to be involved in pathophysiology. Endogenous and exogenous d-serine have shown potential as biological markers for the pathophysiology of schizophrenia and especially as a therapeutic strategy in treatment-resistant schizophrenia (TRS). This is the first study investigating whether SLC7A10, a d-serine transporter gene, is associated with schizophrenia in Japanese patients.We investigated the association between schizophrenia in Japanese patients with SLC7A10 using six tag single nucleotide polymorphisms (SNPs). Results failed to show any association between Japanese schizophrenia and each individual SNP or with two-, three-, or four-window haplotype analyses. We also investigated whether SLC7A10 contributes to TRS in Japanese participants. Results showed no association.In conclusion, SLC7A10 had no apparent degree of association with schizophrenia as a candidate susceptibility gene in the disease per se.Highlights► SCL7A10, a D-serine transporter might be a susceptibility gene for schizophrenia. ► We examined whether SLC7A10 were related to Japanese schizophrenia. ► SLC7A10 had no association with Japanese patients with schizophrenia.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 08/2011; 35(8):1965-1968. · 3.25 Impact Factor
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ABSTRACT: Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family and plays a critical role in growth, differentiation, maintenance and synaptic plasticity of neuronal systems. Previous studies have demonstrated lower serum BDNF concentrations in major depressive disorder (MDD), with concentrations negatively correlating with the severity of the disease. However, few investigations have examined the relationship between serum BDNF and detailed clinical symptoms. The aim of present study was to clarify the magnitudes of the relationships between various depressive symptom and serum BDNF.
Serum BDNF concentrations were evaluated from 109 inpatients with MDD and 163 healthy controls. Depressive symptoms were assessed using the Hamilton rating scale for depression (HAM-D), and symptoms were categorized into four groups: "anxiety somatization"; "cognitive disturbance"; "retardation"; and "sleep disturbance".
Serum BDNF concentration was significantly lower in patients with MDD compared to controls (p<0.001). We identified significant negative correlations between serum BDNF concentration and both total score (R=-0.19, p=0.044) and "anxiety somatization" sub-score (R=-0.32, p=0.001) from the HAM-D in patients with MDD.
All patients in the present study were on antidepressant medications.
These results suggest that serum BDNF level may offer a biological marker for anxiety symptoms in medicated patients with MDD.
Journal of affective disorders 07/2011; 135(1-3):332-5. · 3.76 Impact Factor
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ABSTRACT: Previous papers have reported that clusterin (CLU, also called apolipoprotein J) maintains amyloid β-peptide (Aβ) solubility and protects against Aβ neurotoxicity. Recently, two large genome-wide association studies (GWAS) identified that a specific single nucleotide polymorphism (SNP) on the gene has been reported to modify the risk for Alzheimer's disease (AD). The present study aimed to investigate whether common single nucleotide polymorphisms (SNP) of the CLU gene are associated with AD.
Six SNP, genotyped using TaqMan technology, were analyzed using a case-control study design. Furthermore, an analysis of the cases divided according to apolipoprotein E (APO E) status was also carried out. Our case-control dataset consisted of 180 AD patients and 130 age-matched controls.
The present study failed to detect any association between the SNP of the CLU gene and AD. Although rs7982 and rs1532277 showed marginal association in the APO E4 negative group, the linkage disequilibrium analysis results suggest this to be a false positive.
The negative associations were mainly the result of our small sample size. Larger genetic studies in different ethnics and future meta-analysis are needed to clarify the relationship between the CLU gene and AD.
Psychogeriatrics 03/2011; 11(1):14-8. · 1.21 Impact Factor
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Ryo Hanzawa,
Tohru Ohnuma,
Yasuhito Nagai,
Nobuto Shibata,
Hitoshi Maeshima, Hajime Baba,
Tokiko Hatano,
Yuto Takebayashi,
Yuri Hotta,
Maiko Kitazawa,
Heii Arai
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ABSTRACT: Schizophrenia is a major psychiatric disorder with complex genetic, environmental, and psychological causes, and oxidative stress may be involved in the pathogenesis of the disease. Glutathione (GSH), one of the main cellular non-protein antioxidants and redox regulators, and altered GSH levels have been reported in various regions in patients with schizophrenia. Three enzymes are responsible for GSH synthesis: glutamate cysteine ligase modifier (GCLM), glutamate cysteine ligase catalytic subunit (GCLC), and glutathione synthetase (GSS). Previously, positive associations between GCLM and schizophrenia were reported in Europeans, but not in the Japanese population. Thus, in this study, we investigated the association between the GSH synthesis genes (GCLM, GCLC, and GSS) and schizophrenia in Japanese individuals.
Seventeen single-nucleotide polymorphisms (SNP) in GCLM, GCLC, and GSS were genotyped in 358 patients with schizophrenia and in 359 controls.
No SNP showed a significant association between their allelic or genotypic frequencies and schizophrenia. Case-control haplotype association analysis using windows of two or three SNP showed no significant associations with schizophrenia. The case-control haplotype analyses based on the ascertained linkage disequilibrium blocks also showed no significant associations in any genes with schizophrenia.
The three primary GSH synthesis genes do not have an apparent degree of association with schizophrenia in the Japanese population.
Psychiatry and Clinical Neurosciences 02/2011; 65(1):39-46. · 2.13 Impact Factor
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Yuri Hotta,
Tohru Ohnuma,
Ryo Hanzawa,
Nobuto Shibata,
Hitoshi Maeshima, Hajime Baba,
Tokiko Hatano,
Yuto Takebayashi,
Maiko Kitazawa,
Motoyuki Higa,
Toshihito Suzuki,
Heii Arai
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ABSTRACT: Treating the 20-30% of patients with schizophrenia whose symptoms are resistant to antipsychotic treatment, a condition known as treatment-resistant schizophrenia (TRS), can be problematic. Recently, an association between Disrupted-in-Schizophrenia-1 (DISC1), a candidate susceptibility gene for schizophrenia, and TRS was reported. Associations between three missense SNPs, rs3738401 (Q264R), rs6675281 (L607F), and rs821616 (S704C) in DISC1, especially rs3738401, showed strong significance. Thus, the main aim of our current study was to examine if the reported possible functional polymorphisms in DISC1 were related to Japanese TRS. First, DISC1 was re-investigated in 485 Japanese patients with schizophrenia and 660 healthy controls with a case-control study using four candidate SNPs, rs751229, rs3738401, rs821597, and rs821616. DISC1 was not associated with schizophrenia in the Japanese population. Second, we investigated whether these SNPs contributed to TRS in 127 inpatients with schizophrenia (35 patients; TRS and 92 patients; non-TRS). The genotypic distributions of these four SNPs were not significantly different between TRS and non-TRS in either genotypic or recessive models of minor alleles. In addition, clinical variables, such as improvement in clinical symptoms, duration of hospitalization, and total antipsychotics dose amounts, were not different among the genotypes of these SNPs. Taken together, results showed that DISC1 had no apparent degree of association with Japanese patients with schizophrenia as a candidate susceptibility gene for disease per se or TRS.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2011; 35(2):636-9. · 3.25 Impact Factor
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ABSTRACT: A recent paper reported that Aβ oligomer causes neuronal cell death through the phosphatidylinositol-3-OH kinase (PI3K)-Akt-mTOR signaling pathway. Intraneuronal Aβ, a main pathological finding of Alzheimer's disease (AD), is also known as inhibiting activation of Akt. This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the Akt1 gene are associated with AD. SNPs genotyped using TaqMan technology was analyzed using a case-control study design. Our case-control dataset consisted of 180 AD patients and 130 age-matched controls. Although two SNPs showed superficial positive, Hardy-Weinberg equilibrium (HWE) tests, and linkage disequilibrium (LD) analyses suggested that genetic regions of the gene are highly polymorphic. We failed to detect any synergetic association among Akt1 polymorphisms, Apolipoprotein E (APO E), and AD. Further genetic studies are needed to clarify the relationship between the Akt1 and AD.
International journal of Alzheimer's disease. 01/2011; 2011:762471.
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Ryo Hanzawa,
PhD Tohru Ohnuma MD,
Yasuhito Nagai,
Nobuto Shibata,
Hitoshi Maeshima, Hajime Baba,
Tokiko Hatano,
Yuto Takebayashi,
Yuri Hotta,
Maiko Kitazawa,
Heii Arai
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ABSTRACT: Aims: Schizophrenia is a major psychiatric disorder with complex genetic, environmental, and psychological causes, and oxidative stress may be involved in the pathogenesis of the disease. Glutathione (GSH), one of the main cellular non-protein antioxidants and redox regulators, and altered GSH levels have been reported in various regions in patients with schizophrenia. Three enzymes are responsible for GSH synthesis: glutamate cysteine ligase modifier (GCLM), glutamate cysteine ligase catalytic subunit (GCLC), and glutathione synthetase (GSS). Previously, positive associations between GCLM and schizophrenia were reported in Europeans, but not in the Japanese population. Thus, in this study, we investigated the association between the GSH synthesis genes (GCLM, GCLC, and GSS) and schizophrenia in Japanese individuals.Methods: Seventeen single-nucleotide polymorphisms (SNP) in GCLM, GCLC, and GSS were genotyped in 358 patients with schizophrenia and in 359 controls.Results: No SNP showed a significant association between their allelic or genotypic frequencies and schizophrenia. Case–control haplotype association analysis using windows of two or three SNP showed no significant associations with schizophrenia. The case–control haplotype analyses based on the ascertained linkage disequilibrium blocks also showed no significant associations in any genes with schizophrenia.Conclusions: The three primary GSH synthesis genes do not have an apparent degree of association with schizophrenia in the Japanese population.
Psychiatry and Clinical Neurosciences 11/2010; 65(1):39 - 46. · 2.13 Impact Factor
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ABSTRACT: Background: Depression may increase the risk of developing Alzheimer's disease (AD). Recent large cohort studies have also shown that a low plasma amyloid β (Aβ)-42 level combined with a high Aβ40 level increases the risk of developing AD, suggesting plasma Aβ42/40 ratio as useful for identifying risk of developing mild cognitive impairment and AD. Although several studies have examined Aβ levels in the peripheral blood of elderly individuals with depression, results have been inconsistent. Furthermore, no results have been described for younger depression.Methods: Serum Aβ40, Aβ42 level and Aβ40/42 ratio were evaluated using enzyme-linked immunosorbent assay in 60 patients with major depressive disorder (MDD) and 60 healthy controls. The results were analyzed in two age groups (young, <60 years; elderly, ≥60 years).Results: Serum Aβ40 level was significantly higher in young MDD patients compared to young controls (P < 0.001), but it was not significantly deferent in the elderly group. Serum Aβ42 level did not differ significantly in both young and elderly groups. Aβ40/42 ratio was significantly higher in both young (P < 0.001) and elderly (P < 0.001) patients with MDD compared to controls.Conclusions: Serum Aβ40/42 ratio was significantly higher in MDD patients than in controls, and this difference was seen for both elderly and young subjects. This may suggest that even young subjects with MDD undergo pathological changes in the very early stage of amyloid deposition.
Psychogeriatrics 03/2010; 9(4):180 - 185. · 1.21 Impact Factor
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ABSTRACT: A recent paper reported that a variant (rs2986017) of the calcium homeostasis modulator 1 (CALHM1) gene affects risk for late-onset Alzheimer's disease (AD). This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the CALHM1 gene are associated with AD. SNPs in the genes of two other CALHM subtypes, CALHM2 and CALHM3, were also studied. Our study failed to detect any association between the SNPs of the three genes and AD. Although rs729211 showed marginal association in the APOE4 negative group, the linkage disequilibrium analysis results suggest this to be a false positive.
Journal of Alzheimer's disease: JAD 02/2010; 20(2):417-21. · 3.74 Impact Factor
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Tohru Ohnuma,
Nobuto Shibata, Hajime Baba,
Kazutaka Ohi,
Yuka Yasuda,
Yukako Nakamura,
Tomo Okochi,
Hiroshi Naitoh,
Ryota Hashimoto,
Nakao Iwata,
Norio Ozaki,
Masatoshi Takeda,
Heii Arai
Biological Psychiatry 02/2010; 118(1-3):300-2. · 8.28 Impact Factor
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ABSTRACT: The authors aimed to investigate whether remitted adult and elderly major depressive disorder patients show different patterns of executive dysfunction. Executive functions of 20 euthymic major depressive disorder patients and 29 healthy comparison subjects were evaluated using the Behavioral Assessment of the Dysexecutive Syndrome. Relative to adult patients and healthy comparison subjects, euthymic elderly patients were more impaired in the subtest of Modified Six Elements. Since the regions most implicated in this subtest are the medial prefrontal, the anterior cingulate, and the dorsolateral prefrontal areas, the authors conclude that dysfunctions of such frontal neural networks remain unresolved even in the remission phase of late-life depression.
The Journal of neuropsychiatry and clinical neurosciences 01/2010; 22(1):70-4. · 2.34 Impact Factor
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Hajime Baba
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ABSTRACT: Epidemiological studies have demonstrated that a history of depression increases the risk of developing dementia, in particular Alzheimer's disease (AD). It has been suggested that cerebral vascular changes in elderly depression may be a biological basis for developing dementia. However, the recent large cohort study showed that a history of early-onset depression also increases the risk of developing dementia. On the other hand, recent studies have suggested that an amyloid protein 40 (A40) to A42 ratio may be associated with the future onset of AD. Higher plasma A40/A42 ratio have been reported in elderly depression suggesting as a subtype of elderly depression representing a prodromal manifestation of AD. To reveal further relationship between depression and AD, we compared serum A between patients with major depressive disorder (MDD) and healthy controls by age. The result demonstrated that the serum A40/A42 ratio was significantly higher in MDD patients than in controls, and this difference was seen for both elderly and young subjects. This finding may suggests that even young subjects with MDD undergo pathological changes similar to the very early stage of AD, and possibly answer the question of why even early-onset depression is a risk factor for developing AD.
Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica 01/2010; 112(10):1003-8.
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ABSTRACT: Depression may increase the risk of developing Alzheimer's disease (AD). Recent large cohort studies have also shown that a low plasma amyloid beta (Abeta)-42 level combined with a high Abeta40 level increases the risk of developing AD, suggesting plasma Abeta42/40 ratio as useful for identifying risk of developing mild cognitive impairment and AD. Although several studies have examined Abeta levels in the peripheral blood of elderly individuals with depression, results have been inconsistent. Furthermore, no results have been described for younger depression.
Serum Abeta40, Abeta42 level and Abeta40/42 ratio were evaluated using enzyme-linked immunosorbent assay in 60 patients with major depressive disorder (MDD) and 60 healthy controls. The results were analyzed in two age groups (young, <60 years; elderly, >or=60 years).
Serum Abeta40 level was significantly higher in young MDD patients compared to young controls (P < 0.001), but it was not significantly deferent in the elderly group. Serum Abeta42 level did not differ significantly in both young and elderly groups. Abeta40/42 ratio was significantly higher in both young (P < 0.001) and elderly (P < 0.001) patients with MDD compared to controls.
Serum Abeta40/42 ratio was significantly higher in MDD patients than in controls, and this difference was seen for both elderly and young subjects. This may suggest that even young subjects with MDD undergo pathological changes in the very early stage of amyloid deposition.
Psychogeriatrics 12/2009; 9(4):180-5. · 1.21 Impact Factor
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ABSTRACT: A recent paper reported that the TAR-DNA binding protein (TDP-43) is the disease protein in amyotrophic lateral sclerosis and frontotemporal lobar dementia with ubiquitin-positive inclusions. In addition, it has been shown that TDP-43 may play a role in the pathogenesis of Alzheimer's disease (AD). This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the TDP-43 gene are associated with AD.
Eight SNPs, genotyped using TaqMan technology, were analyzed using a case-control study design including a haplotype analysis. Furthermore, an analysis of the cases divided according to apolipoprotein E (APO E) status was also carried out. Our case-control dataset consists of 181 AD patients and 130 age-matched controls.
Although none of the SNPs showed statistically significant association, we identified an association between a specific haplotype (G-A-A-G) of the TDP-43 gene and risk for AD. We could not confirm any synergetic association between the SNPs and APO E in our AD patients. Despite the relatively small sample size, our results indicate a possible genetic association between TDP- 43 and AD.
Further genetic studies are needed to clarify the relationship between the TDP-43 gene and AD.
Dementia and Geriatric Cognitive Disorders 10/2009; 28(4):325-9. · 2.14 Impact Factor
