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.

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.

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.

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.

Duration of last depressive episode may influence serum BDNF levels in remitted patients with major depression.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Metabolism of amyloid-ß protein may be affected in depression.

OBJECTIVE: 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-ß protein (Aß)40 to Aß42 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 Aß metabolism. METHOD: 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 Aß40 and Aß42 levels, Aß40/Aß42 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. RESULTS: The serum Aß40/Aß42 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. CONCLUSIONS: Our findings suggest that Aß 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.

Correlations between brain-derived neurotrophic factor and clinical symptoms in medicated patients with major depression.

BACKGROUND: 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. METHODS: 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". RESULTS: 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. LIMITATIONS: All patients in the present study were on antidepressant medications. CONCLUSIONS: These results suggest that serum BDNF level may offer a biological marker for anxiety symptoms in medicated patients with MDD.