Impact of dysfunctional parenting, affective temperaments, and stressful life events on the development of melancholic and non-melancholic depression: A path analysis study.

BACKGROUND: The influence of psychosocial factors on differentiating between melancholic depression (MEL) and non-melancholic depression (NMEL) remains unclear. In this study, we aimed to investigate the interrelationship between dysfunctional parenting, personality traits, stressful life events, and the diagnosis of MEL and NMEL among patients with major depressive disorder (MDD). METHODS: Ninety-eight patients with MDD completed the following self-administered questionnaires: the Parental Bonding Instrument (PBI) for dysfunctional parenting, the short version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A) for affective temperaments, and the Life Experiences Survey (LES) for stressful life events. The data were analyzed using single and multiple regression analyses and path analysis. RESULTS: Dysfunctional parenting did not have a significant direct effect on MEL. However, paternal care had a significant indirect effect on MEL through depressive temperament. The total indirect effect of paternal care on MEL was significant (indirect path coefficient = 0.161, p <0.05). In other words, low levels of paternal care were associated with the development of NMEL via increased depressive temperament. None of the paths from paternal care to MEL via negative change scores of the LES were significant. LIMITATIONS: This study used cross-sectional data, so the possibility that current depressive status may affect the assessment of LES and TEMPS-A cannot be ruled out. CONCLUSIONS: We found that low levels of paternal care did not directly affect the development of NMEL, but affected the development of NMEL through the mediation of depressive temperament rather than stressful life events.

Affective Temperaments in Differentiation Between Melancholic and Nonmelancholic Depression: A Case-Control Study.

ABSTRACT: The association between major depressive disorder (MDD) and personality traits has been extensively studied. However, differences in personality traits between patients with melancholic MDD (MEL) and nonmelancholic MDD (NMEL) remain unclear. In this study, we aimed to determine whether neuroticism, which has been associated with MDD, and the five affective temperament subtypes assessed by the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A) can be used to distinguish MEL and NMEL. A total of 106 patients with MDD (MEL, n = 52; NMEL, n = 54) and 212 age- and sex-matched healthy controls answered the Eysenck Personality Questionnaire-revised and the short version of TEMPS-A. In hierarchical logistic regression analysis, only depressive temperament scores were identified as a statistically significant feature distinguishing NMEL from MEL. Depressive temperament scores assessed by the short version of TEMPS-A were found to be significantly higher in NMEL patients than in MEL patients.

Identifying Subjective Symptoms Associated with Psychomotor Disturbance in Melancholia: A Multiple Regression Analysis Study.

PURPOSE: Melancholia has recently been re-evaluated, because patients with major depressive disorder (MDD) were found to be heterogeneous. However, the DSM-5 criteria for melancholia (DSM-MEL) have been criticized, because of the difficulty in clearly distinguishing between melancholic and non-melancholic depression using DSM-MEL. Psychomotor disturbance (PMD) is one of the most important, as well as one of the only measurable symptoms of melancholia. Parker et al developed the CORE measure, which assesses PMD as a behavioral characteristic. The aim of our study was to objectively identify the subjective symptoms of melancholia by analyzing the symptoms associated with PMD. PATIENTS AND METHODS: A total of 106 participants with MDD were examined by psychiatrists. Multiple regression analysis was performed in which the total CORE score was the dependent variable, and items of the DSM-MEL and historically suggested melancholic features were independent variables. RESULTS: The following five independent variables were able to predict the total CORE score: 1) feelings of having lost feeling, 2) depressive delusions, 3) perplexity, 4) indecisiveness, and 5) no aggression against others. These five variables were more strongly associated with the total CORE score than the DSM-MEL. LIMITATION: The major limitation of this study was that when choosing non-DSM melancholic signs and symptoms, we did not comprehensively evaluate and select the symptoms but chose items that are clinically important. CONCLUSION: We identified five subjective symptoms that were associated with PMD. These five symptoms may be clinically useful as diagnostic criteria for melancholia.

Influence of painful physical symptoms in the treatment of Japanese patients with melancholic major depressive disorder: A prospective cohort study.

The aim of this study was to clarify how painful physical symptoms affect treatment outcomes in patients with melancholic major depressive disorder. The subjects comprised 100 consecutive Japanese outpatients with melancholic major depressive disorder who visited our clinic from October 2011 to October 2014. All subjects were interviewed for Diagnostic and Statistical Manual of Mental Disorders Axis 2, 3, and 4 and family history of major depressive disorder, and then grouped according to the presence of painful physical symptoms. We evaluated painful physical symptoms at baseline and after 12, 24, and 36 weeks of treatment and scores on the 17-item Hamilton Rating Scale for Depression, compared major depressive disorder remission between groups, and assessed responsiveness to antidepressants. The group with painful physical symptoms had a significantly more positive family history of major depressive disorder. The major depressive disorder remission rate was high in both groups, and no significant differences were observed. However, a significant relationship between major depressive disorder and painful physical symptoms remission was observed in the group with painful physical symptoms. A significantly higher number of remitted patients with painful physical symptoms (N=61) were administered serotonin-noradrenaline reuptake inhibitors, with significantly more receiving duloxetine than milnacipran.

Effect of augmentation with olanzapine in outpatients with depression in partial remission with melancholic features: consecutive case series.

The aim of the present 12-week, open-label study was to investigate the effect of olanzapine augmentation in outpatients with depression with melancholic features who demonstrated partial response to standard antidepressants but who were reluctant to change antidepressants. The subjects consisted of 22 outpatients meeting the DSM-IV-TR criteria for major depression. Olanzapine was initially added at 2.5 mg/day and the dose was adjusted according to the clinical condition. Data were analyzed using an intention-to-treat methodology. A paired t-test was used to compare total Montgomery Asberg Depression Rating Scale (MADRS) scores before treatment, at baseline (prior to olanzapine), and 4, 8, and 12 weeks after starting olanzapine. Of 22 enrolled patients, 20 completed the trial. The mean (±SD) MADRS score was 17.1 ± 1.0 at baseline and decreased significantly to 8.1 ± 3.2 at 4 weeks after the administration of olanzapine. This significant reduction continued until 12 weeks, when the mean MADRS score was 4.9 ± 2.9, indicating full remission. These results suggest that olanzapine augmentation may be useful for patients with depression in partial remission. A controlled, double-blind trial, however, is needed to confirm these preliminary findings.

Progression of P300 in a patient with bilateral hippocampal lesions.

OBJECTIVE: To evaluate the effects of hippocampal damages on P300 of event-related potentials (ERPs). METHODS: ERPs were recorded over about 8 months using the auditory oddball paradigm in a patient with bilateral hippocampal lesions confirmed on brain magnetic resonance imaging. Findings were compared with those from clinical electroencephalography (periodic lateralized epileptiform discharges (PLEDs) or bilateral independent PLEDs (BIPLEDs)). The patient displayed no marked clinical symptoms aside from mild memory impairment during this time, and was able to fully perform the oddball task. RESULTS: Clearly identifiable P300 were present in all recordings. Furthermore, increases in the number of right PLEDs were significantly correlated with increases in P300 latency. CONCLUSIONS: Two key results were apparent. First, the appearance of P300 in all ERP recordings supports the suggestion that the hippocampus is not indispensable for P300 generation. Second, the correlation between the number of PLEDs and P300 latency supports the suggestion that the hippocampus affect the components of P300 latency. SIGNIFICANCE: This case thus offers very suggestive evidence regarding the generation of P300.

Enhanced heat loss and age-related hypersensitivity to diazepam.

Whether elderly people suffer from age-related changes in pharmacokinetics and/or pharmacodynamics with administration of benzodiazepines is still a matter of controversy. We investigated the course of brain function and thermoregulation after oral administration of a standard benzodiazepine, diazepam (DZP), in 8 healthy young men (mean age, 19.8 years; range, 18 to 23 years) and 8 healthy middle-aged and older men (mean age, 60.9 years; range, 53 to 71 years). Placebo or DZP was administered in a single-blind crossover manner to the young men (placebo, 5-mg, 10-mg DZP) and to the older men (placebo, 5-mg DZP), and plasma DZP concentration, choice reaction time, proximal body temperature, and distal body temperature were monitored with high time resolution under a modified constant routine condition to exclude masking effects. Whereas there was no evidence of age-related alterations in pharmacokinetics between the 2 groups, the older subjects, in comparison to the young subjects, showed a more delayed choice reaction time in response to the same plasma DZP level, suggesting that hypersensitivity is related to increased age. DZP at 5 mg in the older subjects induced acute and transient hypothermia to the same degree as that induced by DZP at 10 mg in the young subjects. The distal-proximal body temperature gradient (difference between distal body temperature and proximal body temperature), an indicator of blood flow in distal skin regions, showed strong positive correlation with the delay in choice reaction time in both groups. These findings suggest that hypersensitivity to benzodiazepine in older persons may be due, at least in part, to age-related changes in thermoregulation, especially in the heat loss process.

A case of mild Alzheimer's disease accompanied by periodic synchronous discharges.

Periodic synchronous discharges (PSD) on the electroencephalogram can be observed in diseases such as Creutzfeldt-Jakob disease, hypoxic encephalopathy and Alzheimer's disease (AD). However, in previously reported cases of AD with PSD, PSD have only been found many years after the diagnosis of AD. We recently encountered a patient with mild AD accompanied by transient PSD. To our knowledge, this is the first case report to suggest that PSD can occur in mild AD.

Structural and enzymatic analysis of soybean beta-amylase mutants with increased pH optimum.

Comparison of the architecture around the active site of soybean beta-amylase and Bacillus cereus beta-amylase showed that the hydrogen bond networks (Glu380-(Lys295-Met51) and Glu380-Asn340-Glu178) in soybean beta-amylase around the base catalytic residue, Glu380, seem to contribute to the lower pH optimum of soybean beta-amylase. To convert the pH optimum of soybean beta-amylase (pH 5.4) to that of the bacterial type enzyme (pH 6.7), three mutants of soybean beta-amylase, M51T, E178Y, and N340T, were constructed such that the hydrogen bond networks were removed by site-directed mutagenesis. The kinetic analysis showed that the pH optimum of all mutants shifted dramatically to a neutral pH (range, from 5.4 to 6.0-6.6). The Km values of the mutants were almost the same as that of soybean beta-amylase except in the case of M51T, while the Vmax values of all mutants were low compared with that of soybean beta-amylase. The crystal structure analysis of the wild type-maltose and mutant-maltose complexes showed that the direct hydrogen bond between Glu380 and Asn340 was completely disrupted in the mutants M51T, E178Y, and N340T. In the case of M51T, the hydrogen bond between Glu380 and Lys295 was also disrupted. These results indicated that the reduced pKa value of Glu380 is stabilized by the hydrogen bond network and is responsible for the lower pH optimum of soybean beta-amylase compared with that of the bacterial beta-amylase.

Heat loss, sleepiness, and impaired performance after diazepam administration in humans.

In spite of the accumulation of knowledge regarding the neuropharmacological action of benzodiazepines (Bz), the physiological process by which their sedative/hypnotic effects are induced remains poorly understood. We conducted a single-blind, crossover trial to evaluate the role of the thermoregulatory process in sleepiness and impaired psychomotor performance induced by a standard Bz, diazepam (DZP). Each of the eight healthy young male volunteers (mean age, 19.75 years; range, 18-23 years) was given a single oral dose of either 5 or 10 mg of DZP or placebo 12 h after his average sleep onset time. Changes in plasma DZP concentration, proximal body temperature (p-BT), distal body temperature (d-BT), subjective sleepiness measured by the Visual Analog Scale and Stanford Sleepiness Scale, and psychomotor performance measured by Choice Reaction Time were monitored under a modified constant routine condition in which various factors affecting thermoregulation, alertness, and psychomotor performances were strictly controlled. Orally administered DZP induced a significant transient decrease in p-BT and psychomotor performance as well as an increase in d-BT and subjective sleepiness. Distal-p-BT gradient (DPG; difference between d-BT and p-BT), which is an indicator of blood flow in distal skin regions, showed a strong positive correlation with the plasma DZP concentration, indicating that DZP in clinical doses promotes heat loss in a dose-dependent manner. The DPG also correlated positively with the magnitude of subjective sleepiness and impaired psychomotor performance. These findings indicate that the sedative/hypnotic effects of Bz could be due, at least in part, to changes in thermoregulation, especially in the process of heat loss, in humans.

Changes in P300 latency during the early withdrawal period in chronic alcohol-dependent patients: two case reports.

AIMS: The present study focused on changes in P300 of the event-related potential (ERP) in two patients with alcohol dependence recorded throughout their alcohol withdrawal period. RESULTS: As a result of this investigation, the peak latency of P300 in each patient was significantly shorter 2 or 3 days after abstinence from alcohol, when marked neurological manifestations appeared, compared to that of the control obtained from 8 to 10 days after cessation of drinking. CONCLUSIONS: It seems reasonable to conclude that the shortening of P300 latency reflects the enhancement of brain activity during the early withdrawal period and that an investigation of changes in P300 would be helpful to clarify the nature of neural activity in the brain associated with alcohol withdrawal.