Serum levels of brain-derived neurotrophic factor in remission, but not the acute phase, may predict the development from depression to dementia.

OBJECTIVES: Depression may be a risk factor or a prodromal symptom of dementia, and decreased serum levels of brain-derived neurotrophic factor (BDNF) have been observed in both depression and dementia. The aim of the present study was to determine whether serum levels of BDNF in the remitted or acute phase of depression predicted the transition from depression to dementia. METHODS: Serum levels of BDNF were measured in the acute phase of depression (n = 204) and after remission (n = 117), and we followed (mean: 24.3 months) the participants to assess the subsequent onset of dementia or mild cognitive impairment (MCI). RESULTS: Serum levels of BDNF after remission, but not those in the acute depressive phase, predicted the future development of dementia or MCI. CONCLUSIONS: Patients with low serum BDNF levels, even after depression remission, might have an increased risk of developing dementia. These findings suggest a potential association between residual low serum BDNF levels after remission and the prodromal state of dementia, or the involvement of BDNF in the transition from depression to dementia. However, given that this study is low-powered and preliminary, interpretation of the results should be approached with caution.

Clinical course and serum amyloid ß levels in elderly patients with major depressive disorder.

BACKGROUND: Depression is known to be a risk factor for Alzheimer's disease (AD). Changes in amyloid ß protein (Aß) metabolism have been speculated as a factor contributing to the transition from depression to AD. The aim of this study is to reveal the time course and state-dependency of Aß metabolism. METHODS: Serum Aß levels in 277 elderly (≥60 years) patients with depression (both early- and late-onset) were measured at admission, immediately after remission, and 1 year after remission, and compared them with 178 healthy subjects. RESULTS: The analysis revealed decreased Aß42 levels and increased Aß42/40 ratios in elderly patients with depression at admission compared with healthy subjects. These changes in the acute phase of depression were not normalized immediately after remission; however, they recovered to healthy levels 1 year after remission. LIMITATIONS: There is a possibility that the results may be influenced by antidepressants. CONCLUSIONS: These results suggest that altered Aß metabolism caused by depression may ameliorate, although after a lengthy period of time after remission. Our findings also suggest that the AD-related pathological changes caused or increased by depression can be reduced by maintaining remission for an extended period of time.

Apolipoprotein E4 increases the risk of depression recurrence.

BACKGROUND: Possession of the ε4 allele of apolipoprotein E (APOE4) is related to the incidence of depression in old age. We investigated whether the presence of APOE4 is also associated with subsequent depression recurrence in a wide range of age groups. METHODS: Altogether, 163 patients with major depressive disorder (MDD) after remission were recruited between August 2004 and March 2016 and followed up prospectively. The patients were divided into two groups: APOE4 carriers and non-carriers. We compared the time to recurrence of depression between the two groups. Kaplan-Meier survival curves, log-rank test for trend for survivor functions, and Cox proportional hazard ratio estimates for a multivariate model were conducted to examine the effect of the APOE4 allele on risk of a depression recurrence. RESULTS: Cumulative probability of developing a depression recurrence was higher in APOE4 carriers than non-carriers. Presence of an APOE4 allele remained significantly associated with the incidence of depression recurrence. LIMITATIONS: All patients were treated with one or two different antidepressants, which may have had different effects on patients with MDD. Second, participants in the present study comprised patients with both first and multiple episodes of MDD. Third, we did not have the statistical power to perform a stratified analysis in consideration of heterozygous or homozygous genotypes of APOE4. CONCLUSION: Possession of an APOE4 allele may increase the risk of depression recurrence.

Serum levels and mutual correlations of amyloid ß in patients with depression.

AIM: Epidemiological studies have shown that depression is a risk factor for Alzheimer's disease (AD). Although the biological mechanism underlying the link between depression and AD is unclear, altered amyloid ß (Aß) metabolism in patients with depression has been suggested as a potential mechanism. Results from previous studies of Aß metabolism in patients with depression have been inconsistent, and Aß polymerization, which is a crucial process in AD pathology, has not previously been assessed. METHODS: Serum levels of Aß40, Aß42 and Aß oligomers were evaluated in 104 inpatients with major depressive disorder (MDD) and 132 healthy control individuals. RESULTS: Lower serum Aß42 levels were observed in patients with MDD, but there was no difference in serum Aß oligomer levels between the MDD group and the healthy control group, even in older adults. Interestingly, serum Aß oligomer levels in patients with MDD were dependent on serum Aß42 levels, regardless of age, and this relationship was not observed in the control group. CONCLUSIONS: These results suggest that Aß42 is more prone to aggregation and polymerization in patients with depression than in healthy individuals, suggesting a possible mechanism underlying the transition from depression to AD. Geriatr Gerontol Int 2020; 20: 125-129.

Serum levels of TDP-43 in late-life patients with depressive episode.

BACKGROUND: Recent reports have suggested a relationship between affective disorder including depression and bipolar disorder (BP) and frontotemporal dementia (FTD). TAR DNA binding protein (TDP) -43 is a protein found in the brain and peripheral fluid of patients with FTD. To examine a possible association between affective disorders and FTD, serum levels of TDP-43 were evaluated in late-life patients with major depressive episode (MDE). METHODS: The subjects were 74 late-life (≥50 years old) inpatients with DSM-IV or -5 MDE (58 had major depressive disorders and 16 had BP) and 58 healthy subjects. Patients were recruited from Juntendo Koshigaya Hospital, Saitama, Japan, between January 2005 and May 2017. Serum TDP-43 levels were measured using an ELISA kit. RESULTS: Serum levels of TDP-43 were significantly higher in the MDE group than the control group independent of age and sex. LIMITATIONS: All patients were on antidepressant medication. CONCLUSIONS: Our finding suggests that some depressive patients may be in a prodromal stage of FTD or very-early stage of FTD comorbid with depression.

Increased Serum Levels of α-Synuclein in Patients With Major Depressive Disorder.

OBJECTIVE: Epidemiologic studies have demonstrated that depression is a risk factor for dementia. In particular, dementia with Lewy bodies (DLB) has been noted to be highly relevant to depression. It has been suggested that α-synuclein (α-syn), a major component of Lewy bodies, is related to the onset and progression of DLB. To investigate the relationship between depression and DLB, we compared serum α-syn levels of patients with depression to those of healthy subjects. METHODS: The subjects were 103 inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), or DSM-5 major depressive disorder (MDD) and 132 healthy comparisons. Patients were recruited from Juntendo Koshigaya Hospital, Saitama, Japan, between June 2010 and November 2016. Serum α-syn levels were measured using an enzyme-linked immunosorbent assay kit. Serum α-syn levels were compared using a 2 (age group [<60 years versus ≥60 years]) × 2 (diagnosis [MDD versus comparison]) analysis of variance. RESULTS: There was no significant main effect of age (F = 1.167, df = 1, 231, p = 0.281). There was a significant main effect of diagnosis (F = 44.657, df = 1, 231, p <0.001), with higher α-syn levels in the MDD group versus the healthy comparison group, regardless of age. CONCLUSION: The present results suggest that depression may affect the metabolism of α-syn; there is a possibility that depression is not only a prodromal symptom of DLB but also a causal risk factor for DLB.

Glucocorticoid may influence amyloid ß metabolism in patients with depression.

Epidemiological studies have demonstrated that depression may be a risk factor for Alzheimer's disease (AD); however, the biological mechanisms of the transition from depression to AD are still not clear. Changes of amyloid ß protein (Aß) metabolism and increased glucocorticoid (GC) levels have been found in both depression and AD. Moreover, several studies in animal models have demonstrated that GC administration changes Aß metabolism. To reveal whether GC affects amyloid metabolism in patients with depression, we evaluated serum levels of Aß40, Aß42 and cortisol at admission in 187 inpatients with major depressive disorder (MDD) and 224 healthy comparisons. Additionally, we re-evaluated the serum levels of Aßs in 27 patients with MDD 1 year later. The results of multiple regression analyses revealed that serum cortisol and Aß levels are not correlated at the time of admission. However, serum cortisol levels at admission correlated with serum Aß42 levels and Aß40/Aß42 ratio 1 year later. These findings suggest that increased cortisol in patients with MDD may influence the metabolism of Aß over prolonged periods of time.

Renal concerns relative to the use of lithium in geriatric bipolar disorder patients.

BACKGROUND: Lithium is a first-line treatment for bipolar disorder in geriatric patients; however, it has long been associated with potentially significant renal consequences, including chronic kidney disease (CKD). METHODS: We reviewed the available evidence to characterize the effects of lithium on renal function, provide a consensus on periodic monitoring, and propose criteria for transitioning an older patient with bipolar disorder and renal issues to an alternate medication. RESULTS: Although the evidence on lithium use, duration, and dosage on progression of CKD and end-stage renal disease in geriatric patients is mixed, there is solid evidence that patients receiving lithium generally have a reduced glomerular filtration rate compared with controls. The current guidelines for monitoring lithium use in geriatric patients are nearly sufficient, but adherence in clinical practice frequently falls short. Alternative medications for bipolar disorder in geriatric patients are generally considered safe and effective, but do not have the strength of evidence that exists in the general adult population. CONCLUSIONS: Currently, there is no compelling evidence that lithium should be avoided in geriatric patients; however, prudent monitoring strategies are recommended, with a strong consideration of transitioning geriatric patients with poor tolerance to an alternative medication.

Residual memory impairment in remitted depression may be a predictive factor for recurrence.

OBJECTIVE: Memory impairment in remitted depression is reported to be related to the number of previous depressive episodes. A recent report hypothesized that each depressive episode increases the risk of memory impairment during remission, which further increases the risk of recurrence. We investigated whether the risk for recurrence increased as a function of memory impairment at remission. METHOD: One hundred ten participants with DSM-IV-TR major depressive disorder (MDD) after remission (defined as a score ≤ 7 on the Hamilton Depression Rating Scale) were recruited between April 2004 and March 2012 and were followed up prospectively. All patients were divided into 2 groups: those who had memory impairment and those who had no memory impairment after remission. (Memory impairment was determined with the Wechsler Memory Scale-Revised.) The time to recurrence of depression (a score ≥ 4 on the Clinical Global Impressions-Severity of Illness scale) was compared between the groups prospectively. Kaplan-Meier survival curves, log-rank test for trend for survivor functions, and Cox proportional hazard ratio (HR) estimates for a multivariate model were conducted to examine the risk of recurrence by presence of memory impairment after remission. RESULTS: One hundred nine participants completed this study. In the follow-up period, recurrence occurred in 25 (55.6%) of the 45 patients with memory impairment and 21 (32.8%) of the 64 patients with no memory impairment. In the Kaplan-Meier survival estimates for time to incidence of recurrence in patients with and without memory impairment, the cumulative probability of developing a recurrence for patients with memory impairment was higher than for patients with no memory impairment (log-rank test: χ(2)1 = 4.63, P = .03). Survival analysis was also performed using Cox proportional hazards regression in a multivariate model. The presence of memory impairment remained significantly associated with incidence of recurrence (HR = 2.55; 95% CI, 1.30-4.99; P = .006). CONCLUSIONS: The presence of residual memory impairment in patients with remitted MDD may increase the risk of recurrence.

Serum brain-derived neurotrophic factor levels and personality traits in patients with major depression.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. Previous studies have demonstrated lower serum BDNF levels in patients with major depressive disorder (MDD) and reported an association between BDNF levels and depression-related personality traits in healthy subjects. The aim of the present study was to explore for a possible association between peripheral BDNF levels and personality traits in patients with MDD. METHODS: In this cross-sectional study, a total of 123 inpatients with MDD (Diagnostic and Statistical Manual for Mental Disorders, 4th edition) at the Juntendo University Koshigaya Hospital were recruited. Serum levels of BDNF were measured. Personality traits were assessed using the 125-item short version of the Temperament and Character Inventory (TCI). RESULTS: Multiple regression analysis adjusted for age, sex, body mass index, dose of antidepressant, and depression severity showed that TCI Self-Directedness (SD) scores were negatively associated with serum BDNF levels (ß = -0.23, p = 0.026). CONCLUSIONS: MDD patients who have low SD did not show the reduction in serum BDNF levels that is normally associated with depressive state. Our findings suggest that depression-related biological changes may not occur in these individuals.

Altered serum glyceraldehyde-derived advanced glycation end product (AGE) and soluble AGE receptor levels indicate carbonyl stress in patients with schizophrenia.

Recent cross-sectional and longitudinal studies indicate that measurements of peripheral blood carbonyl stress markers such as the advanced glycation end product (AGE) pentosidine and the reactive carbonyl-detoxifying B6 vitamin pyridoxal could be used as therapeutic biological markers in subpopulations of schizophrenia patients. Glyceraldehyde-derived AGEs (Glycer-AGE) have strong neurotoxicity, and soluble receptors for AGEs (sRAGE) may ameliorate the effects of AGEs. In the present study, we measured Glycer-AGEs and sRAGE levels to determine their potential as diagnostic, therapeutic, or clinical biological markers in patients with schizophrenia. After enrollment of 61 admitted Japanese patients with acute schizophrenia and 39 healthy volunteers, 54 patients were followed up from the acute stage to remission. Serum biomarkers were measured in blood samples taken before breakfast using competitive enzyme-linked immunosorbent assays, and Glycer-AGEs were significantly higher and sRAGE levels were significantly lower in patients with acute schizophrenia than in healthy controls. Glycer-AGEs/sRAGE ratios were also higher in schizophrenia patients and were stable during the clinical course. Furthermore, discriminant analyses confirmed that Glycer-AGEs and Glycer-AGEs/sRAGE ratios are significant diagnostic markers for schizophrenia, and distinguished between patients and healthy controls in 70.0% of cases. However, these markers of carbonyl stress were not correlated with clinical features, including disease severity, or with daily chlorpromazine doses. These data indicate the potential of Glycer-AGEs, RAGEs, and their relative ratios as diagnostic markers for patients with schizophrenia.

Temperament and character as predictors of recurrence in remitted patients with major depression: a 4-year prospective follow-up study.

The aim of the present study was to examine whether the specific personality traits, Harm-Avoidance (HA) and Self-Directedness (SD) as measured by the Temperament and Character Inventory (TCI), were predictive for subsequent depressive episodes in remitted patients with major depressive disorders (MDDs) over a 4-year follow-up. A total of 109 inpatients with MDD participated in this study. The subjects completed the TCI when they were assessed to be in remission. They were divided into high or low HA groups and high or low SD groups, as discriminated by the quartile value. A total of 69 patients were followed-up over a 4-year period or until recurrence. Both Kaplan-Meier analysis and Cox׳s proportional hazards regression analysis indicated that patients with a low SD score had a significantly shorter time to recurrence from remission than patients with a high SD score even when some prognostic predictors were controlled for. In contrast, HA was not found to be a predictor of recurrence for future depressive episodes. A part of MDD patients with low scores in Self-Directedness are likely to develop depression over a subsequent period of time. Interventions that improve SD may help to delay recurrence of depression in MDD patients.

Psychomotor agitation in major depressive disorder is a predictive factor of mood-switching.

BACKGROUND: The relationship between psychomotor agitation in unipolar depression and mood-switching from depression to manic, hypomanic and mixed states has been controversial. We investigated the future risk of initial mood-switching as a function of psychomotor agitation in unipolar depression. METHODS: We identified 189 participants diagnosed with major depressive disorder (MDD). We divided all patients with MDD into two categories (1) agitated patients (n=74), and (2) non-agitated patients (n=115). These groups were prospectively followed and compared by time to mood-switching. Kaplan-Meier survival curves, log-rank test for trend for survivor functions, and Cox proportional hazard ratio estimates for a multivariate model were conducted to examine the risk of mood-switching by psychomotor agitation. RESULTS: During follow-up, mood-switching occurred in 20.3% of the agitated patients and 7.0% of the non-agitated patients. In the Kaplan-Meier survival estimates for time to incidence of mood-switching with agitated or non-agitated patients, the cumulative probability of developing mood-switching for agitated patients was higher than those for non-agitated patients (log-rank test: χ(2)=7.148, df=1, p=0.008). Survival analysis was also performed using Cox proportional hazards regression within a multivariate model. The agitation remained significantly associated with incidence of mood-switching (HR=2.98, 95% CI: 1.18-7.51). LIMITATIONS: We did not make a clear distinction between antidepressant-induced mood-switching and spontaneous switching. CONCLUSIONS: The main finding demonstrated that MDD patients with agitation were nearly threefold as likely to experience mood-switching, suggesting that psychomotor agitation in MDD may be related to an indicator of bipolarity.

Comparative study of cognitive impairment between medicated and medication-free patients with remitted major depression: class-specific influence by tricyclic antidepressants and newer antidepressants.

Patients with major depressive disorder (MDD) are known to present with cognitive deficits; however, the presence of these deficits in the remitted state have been inconsistent. One of the most important factors potentially contributing to inconsistencies between studies may be the influence of medications. To explore the influence of antidepressants on cognitive performance in remitted MDD, we evaluated memory and executive functions using Wechsler Memory Scale-Revised and Stroop Color and Word Test, and compared performance among 50 medicated (29 treated with tricyclic antidepressants [TCA], 21 treated with selective serotonin reuptake inhibitors or serotonin noradrenalin reuptake inhibitors) and 19 medication-free MDD patients and 31 controls. The results showed that all 3 MDD groups had significantly lower performance for verbal memory compared with controls. Both medicated groups showed significantly lower performance for visual memory compared with controls; however, the medication-free group did not differ from controls. For the executive function, only the TCA group showed a significantly lower performance compared with controls. These results suggest that cognitive impairment remained even in remitted patients with MDD, however, part of this impairment may be influenced by class-specific antidepressant side effects.

Significance of measurements of peripheral carbonyl stress markers in a cross-sectional and longitudinal study in patients with acute-stage schizophrenia.

Altered peripheral carbonyl stress markers, high levels of serum pentosidine, which accumulates following carbonyl stress, and low levels of pyridoxal (vitamin B6), which detoxifies reactive carbonyl compounds, have been reported in a cross-sectional study of chronic schizophrenia. However, changes in the levels of these compounds in patients with schizophrenia have not been investigated in a longitudinal study. To clarify whether these markers may be biological markers that reflect the clinical course of the disease, the serum levels of these compounds were investigated in a cross-sectional and a longitudinal study. One hundred and thirty-seven acute-stage Japanese patients were enrolled. Among these, 53 patients were followed from the acute stage to remission. A portion of patients in the acute stage (14 cases, 10.2%) showed extremely high pentosidine levels. These levels were not associated with the severity of symptoms but were associated with antipsychotic dose amounts. Pyridoxal levels were lower in schizophrenia and increased according to the clinical course of the illness. Furthermore, 18 patients with decreased pyridoxal levels according to the clinical course showed that the greater the decrease in pyridoxal levels, the lesser the improvement in symptoms. Thus, extremely high pentosidine levels in a portion of patients may be caused by higher daily antipsychotic doses, whereas pyridoxal levels were lower in schizophrenia and increased according to the clinical course. Patients with decreasing pyridoxal levels during the clinical course showed less improvement in symptoms. Carbonyl stress markers may also be therapeutic biological markers in some patients with schizophrenia.

Time course for memory dysfunction in early-life and late-life major depression: a longitudinal study from the Juntendo University Mood Disorder Project.

BACKGROUND: Previous studies have demonstrated that patients with depression also have memory dysfunctions during depressive episodes. These dysfunctions partially remain immediately after remission from a depressive state; however, it is unclear whether these residual memory dysfunctions may disappear through long-term remission from depression. The present study compared patients during early-life (age<60) and late-life (age ≥ 60) depression while in their remitted stage with healthy controls to elucidate the impact of a long-term course on memory. METHODS: Logical memory from the Wechsler Memory Scale-Revised was administered to 67 patients with major depressive disorder (MDD) (47 patients with early-life depression and residual 20 patients with late-life depression) and 50 healthy controls. MDD patients received memory assessments at the time of their initial remission and at a follow-up three years after remission. RESULTS: At the time of initial remission, scores for logical memory were significantly lower in both patient groups compared to matched controls. At follow-up, memory dysfunction for early-life MDD patients disappeared, whereas scores in the late-life MDD group remained significantly lower than those of matched controls. LIMITATIONS: All patients in the present study were on antidepressant medications. CONCLUSIONS: Our findings suggested that the progress of memory performance in late-life MDD patients may be different from early-life MDD patients.

Heterogeneity of elderly depression: increased risk of Alzheimer's disease and Aß protein metabolism.

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 ß protein (Aß) 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 Aß metabolism and later development of AD. Thus, we evaluated serum Aß40 and Aß42 levels, the Aß40/Aß42 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 (≥60years) MDD and controls. The results showed that the serum Aß40/Aß42 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 Aß40/Aß42 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 Aß metabolism, possibly explaining a biological mechanism underlying the link between depression and AD.

Serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (S) levels in medicated patients with major depressive disorder compared with controls.

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.

Gender differences in serum testosterone and cortisol in patients with major depressive disorder compared with controls.

OBJECTIVE: Testosterone may have a role distinct from cortisol in the pathophysiology of depression. The hypothalamus-pituitary-adrenal (HPA) axis affects the functions of sex steroid hormones through interaction with corticotropin-releasing hormone (CRH) and gonadotropin-releasing hormone (GnRH). The objective of this study was to investigate differences in serum levels of testosterone and cortisol in male and female patients with major depressive disorder (MDD). METHODS: Participants included 87 inpatients with MDD at Juntendo University Koshigaya Hospital. Serum levels of testosterone and cortisol were assessed at admission. Matched controls included 128 healthy individuals. Data from MDD patients and controls were compared separately for men and women. Correlations between serum hormone levels and scores on the Hamilton Rating Scale for Depression (HAM-D) of patients were assessed by sex. Effects of various factors on testosterone and cortisol were analyzed using multiple regression analysis. RESULTS: In male patients with MDD, a significant negative correlation was seen between testosterone levels and the "retardation" score of HAM-D. However, serum testosterone levels were not significantly different in either male or female MDD patients compared with controls. Serum testosterone was negatively associated with the number of depressive episodes in male patients with MDD. Serum cortisol levels in female patients were significantly increased compared with female controls with no significant correlations between cortisol levels and HAM-D scores. CONCLUSIONS: The negative correlation between the sub-score of the HAM-D and testosterone may be associated with the biological pathophysiology of male depression. Findings of serum cortisol levels in women may suggest distinct characteristics of these hormones in men and women with MDD.

Residual memory dysfunction in recurrent major depressive disorder--a longitudinal study from Juntendo University Mood Disorder Project.

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.