Neurobiological approach to brain functional asymmetry in depression

The modern literature data were observed, which dedicated to the study of neurobiological mechanisms of depressive states of different origin. The results of the investigations of structurally functional features of depression in healthy volunteers in experiments and in patients with the neurological diseases were viewed. The data cited confirm the modern concepts of R. Davidson concerning to the role of brain functional asymmetry in depression: i.e., the associations between depression and a decrease of the functional activation of the left prefrontal lobe, and also the involving of amygdale in the processes of the forming of negative emotions and depression. The literature data observed and findings of our investigations allow us to conclude that depressive states are characterized not only by the decrease of the functional activity of the left hemisphere, especially, its prefrontal area, but also reciprocal increase of the physiological activity of the prefrontal area of the right hemisphere combined with right-hemispheric functional insufficiency, especially, of its posterior (parieto-temporal) areas.     

Reliable change in depression during behavioral weight loss treatment among women with major depression

Objective: Although behavioral weight loss interventions generally have been shown to improve depressive symptoms, little is known as to whether some people with major depressive disorder experience worsening of depression during a weight loss intervention. Design and Methods: Rates and predictors of change in depression symptoms among 148 obese women with major depressive disorder who participated in a trial comparing depression treatment plus behavioral weight loss treatment (Behavioral Activation; BA) to behavioral weight loss treatment alone (Lifestyle Intervention; LI) were examined. A statistically reliable change in depression was calculated as ≥9 points on the Beck Depression Inventory in this sample. Results: At 6 months, 73% of participants in BA and 54% of participants in LI showed reliable improvement in depression symptoms and 1.5% of participants in BA and 1.3% of participants in LI showed reliable worsening in depression symptoms. Rates of reliable change were similar at 12 months. Participants who experienced reliable improvement in depression lost significantly more weight than those who did not in both conditions. In the LI condition, baseline psychiatric variables and change in physical activity during treatment were also related to reliable improvement in depression. Conclusion: No evidence for an iatrogenic effect of behavioral weight loss treatment on depressive symptoms among obese women with major depressive disorder was detected; rather, behavioral weight loss treatment appears to be associated with significant concurrent improvement in depression. Even greater rates of reliable improvement were observed when depression treatment was added to weight loss treatment.     

Advanced melatonin onset relative to sleep in women with unmedicated major depressive disorder

ABSTRACT

Studies on circadian timing in depression have produced variable results, with some investigations suggesting phase advances and others phase delays. This variability may be attributable to differences in participant diagnosis, medication use, and methodology between studies. This study examined circadian timing in a sample of unmedicated women with and without unipolar major depressive disorder. Participants were aged 18–28 years, had no comorbid medical conditions, and were not taking medications. Eight women were experiencing a major depressive episode, nine had previously experienced an episode, and 31 were control participants with no history of mental illness. Following at least one week of actigraphic sleep monitoring, timing of salivary dim light melatonin onset (DLMO) was assessed in light of <1 lux. In currently depressed participants, melatonin onset occurred significantly earlier relative to sleep than in controls, with a large effect size. Earlier melatonin onset relative to sleep was also correlated with poorer mood for all participants. Our results indicate that during a unipolar major depressive episode, endogenous circadian phase is advanced relative to sleep time. This is consistent with the early-morning awakenings often seen in depression. Circadian misalignment may represent a precipitating or perpetuating factor that could be targeted for personalized treatment of major depression.     

Recent progress in neurobiological mechanisms of depression

Revealing the neurobiological mechanism of depression has always been a big challenge in the field of neuroscience. Not only are depressive syndromes heterogeneous and their aetiologies diverse, but also some symptoms are impossible to reproduce in animal models. Nevertheless, great progress has been made on the understanding and treatment of depression in recent years. In this review, we focus on key leading hypotheses in the neurobiological mechanism of depression, examine their strengths and weaknesses critically, and also highlight new insights that promise to extend the understanding of depression and its treatment.     

Symptoms of Depression in Elderly Korean Immigrants: Narration and the Healing Process

This paper explores ways in which depressive symptoms are expressed by elderly Korean immigrants in the USA. Depressed elderly Korean immigrants in the Washington DC area were interviewed in depth to explore their conceptualizations of depression in terms of explanatory models and semantic networks. The expressions of depressive symptoms were influenced by linguistic and psycho-socio-cultural factors, therapeutic behaviors, and efficacy of treatment. The data were interpreted in terms of traditional Korean medical principles, cosmological, socio-cultural, and religious influences, and an individual's family structural changes and acculturation. Findings indicate the construction of somatization among Korean elders is more complex than is generally reported: in most cases, a dynamic, holistic blend of processes appears to operate simultaneously, instead of as somatization in isolation. Informants placed different degrees of emphasis on psychologization or somatization, or the two combined. The roles of personality, value orientation, intellect, emotion, economic status, degree of acculturation, degree of dependence on children, living situation (with or not with children), and self-will or self-confidence are important influences on the depression symptoms in the psychologization-somatization continuum. The more self-directed the informants are, the more they psychologize; the more other-directed, the more they seem to somatize. Names and symptoms of depression (a Western concept) and popular illnesses (traditional Korean concepts) were used interchangeably by the informants. When informants were asked to explain the signs and symptoms of depression and sadness, some described symptoms similar to the criteria of major depression in DSM-III (American Psychiatric Association), while others gave different symptoms and ways of expressing them. Some informants believed that symptoms and signs of depression can be concealed from others if one chooses to do so. Many felt that manifestations of depression can be controlled by willpower, personality, and self-care.     

Nutritional Interventions in Depression and Perinatal Depression

Depression is the leading cause of mental disability worldwide. Women who are depressed during pregnancy are at a higher risk for preterm delivery, preeclampsia, birth difficulties, and postpartum depression. The treatment of depression in conventional medicine has focused on physiological factors that lead to impaired neurotransmitter function and treatments to improve neurotransmitter function. Pharmaceutical substances pose risks for pregnant and lactating women, and lower risk options are preferred. Micronutrients, including certain B vitamins, folate, and docosahexaenoic acid (DHA), play a role in the synthesis and absorption of neurotransmitters. Experimental studies suggest that supplementation with specific micronutrients may alleviate depressive symptoms and improve birth outcomes in patients with perinatal depression. Alternative treatments for depression, including nutritional supplements, are an important treatment option for depressive symptoms while limiting potential side effects and treatment costs. This article explores the biological basis of perinatal depression and reviews the potential benefits of non-pharmacological interventions.     

Direct and Indirect Effects of Five Factor Personality and Gender on Depressive Symptoms Mediated by Perceived Stress

This study was designed to investigate associations among five factor personality traits, perceived stress, and depressive symptoms and to examine the roles of personality and perceived stress in the relationship between gender and depressive symptoms. The participants (N = 3,950) were part of a cohort study for health screening and examination at the Kangbuk Samsung Hospital. Personality was measured with the Revised NEO Personality Inventory (NEO-PI-R). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Perceived stress level was evaluated with a self-reported stress questionnaire developed for the Korea National Health and Nutrition Examination Survey. A higher degree of neuroticism and lower degrees of extraversion, agreeableness, and conscientiousness were significantly associated with greater perceived stress and depressive symptoms. Neuroticism and extraversion had significant direct and indirect effects (via stress as a mediator) on depressive symptoms in both genders. Agreeableness and conscientiousness had indirect effects on depression symptoms in both genders. Multiple mediation models were used to examine the mediational roles of each personality factor and perceived stress in the link between gender and depressive symptoms. Four of the personality factors (except openness) were significant mediators, along with stress, on the relationship between gender and depressive symptoms. Our findings suggest that the links between personality factors and depressive symptoms are mediated by perceived stress. As such, personality is an important factor to consider when examining the link between gender and depression.     

双相障碍抑郁发作及单相抑郁症患者血清T3、T4、TSH和BDNF水平的相关性分析

目的:分析双相障碍抑郁发作及单相抑郁症患者与血清三碘甲状腺原氨酸(T3)、甲状腺素(T4)、甲状腺激素(TSH)和脑源性神经营养因子(BDNF)水平的相关性。方法:选取2017年12月～2019年12月我院收治的120例抑郁症患者为研究对象,按照病情不同分为双相障碍抑郁发作组(n=50)、单相抑郁症组(n=70),同时选取同期于本院进行体检的30例健康者作为对照组,检测血清T3、T4、TSH和BDNF水平,并进行汉密尔顿抑郁(HAMD)量表评分,分析血清T3、T4、TSH和BDNF水平的相关性。结果:双相障碍抑郁发作组起病年龄低于单相抑郁症组(P0.05);治疗前双相障碍抑郁发作组和单相抑郁症组血清T3水平高于对照组,TSH、BDNF水平低于对照组(P0.05),双相障碍抑郁发作组血清T4水平高于对照组,单相抑郁症组和对照组血清T4水平比较差异无统计学意义(P0.05),双相障碍抑郁发作组血清T4水平高于单相抑郁症组,TSH、BDNF水平低于单相抑郁症组(P0.05);治疗后双相障碍抑郁发作组和单相抑郁症组血清T4水平低于对照组,双相障碍抑郁发作组血清T4水平低于单相抑郁症组(P0.05),且三组血清T3、TSH、BDNF水平比较差异无统计学意义(P0.05);治疗后双相障碍抑郁发作组认知障碍因子评分低于单相抑郁症组(P0.05);Spearman相关分析显示,血清T3、T4、TSH水平和HAMD评分与BDNF呈负相关,TSH水平与BDNF呈正相关(P0.05)。结论:抑郁症患者血清T3、T4、TSH和BDNF水平存在异常,可作为判断双相障碍抑郁发作及单相抑郁症的指标。     

Emotionally Biased Cognitive Processes: The Weakest Link Predicts Prospective Changes in Depressive Symptom Severity

Emotional biases in attention, interpretation, and memory are predictive of future depressive symptoms. It remains unknown, however, how these biased cognitive processes interact to predict depressive symptom levels in the long-term. In the present study, we tested the predictive value of two integrative approaches to model relations between multiple biased cognitive processes, namely the additive (i.e., cognitive processes have a cumulative effect) vs. the weakest link (i.e., the dominant pathogenic process is important) model. We also tested whether these integrative models interacted with perceived stress to predict prospective changes in depressive symptom severity. At Time 1, participants completed measures of depressive symptom severity and emotional biases in attention, interpretation, and memory. At Time 2, one year later, participants were reassessed to determine depressive symptom levels and perceived stress. Results revealed that the weakest link model had incremental validity over the additive model in predicting prospective changes in depressive symptoms, though both models explained a significant proportion of variance in the change in depressive symptoms from Time 1 to Time 2. None of the integrative models interacted with perceived stress to predict changes in depressive symptomatology. These findings suggest that the best cognitive marker of the evolution in depressive symptoms is the cognitive process that is dominantly biased toward negative material, which operates independent from experienced stress. This highlights the importance of considering idiographic cognitive profiles with multiple cognitive processes for understanding and modifying effects of cognitive biases in depression.     

灵孢多糖辅助治疗抑郁症的作用及机制

目的:建立大鼠抑郁模型,研究和探讨灵孢多糖注射液辅助治疗抑郁症的作用及机制。方法:将48只SD大鼠随机分为正常组、抑郁组、生理盐水组及灵孢多糖(低剂量、中剂量、高剂量)治疗组各8只。应用慢性应激刺激的方法诱导抑郁组、生理盐水组、灵孢多糖治疗组大鼠抑郁,通过行为学指标评估建模是否成功。建模成功后,在生理盐水组中注射生理盐水;在灵孢多糖治疗组中分别注射低、中、高剂量灵孢多糖注射液,比较各组间的疗效差异。采用免疫组化的方法测定大鼠脑内多巴胺、去甲肾上腺素、5-羟色胺、酪氨酸羟化酶等单胺类神经递质含量的表达情况。结果:成功的建立了大鼠抑郁模型,抑郁组中大鼠各项行为学指标与正常组相比均明显减少,差异有统计学意义(P0.05);灵孢多糖治疗组大鼠脑内的多巴胺、去甲肾上腺素、5-羟色胺、酪氨酸羟化酶与抑郁组、生理盐水组大鼠脑内的含量均明显升高,差异有统计学意义(P0.05)。结论:灵孢多糖注射液对改善抑郁症状有良好的疗效,具有辅助治疗抑郁症的作用。     

灵孢多糖辅助治疗抑郁症的作用及机制

目的：建立大鼠抑郁模型,研究和探讨灵孢多糖注射液辅助治疗抑郁症的作用及机制。方法：将48只SD大鼠随机分为正常组、抑郁组、生理盐水组及灵孢多糖（低剂量、中剂量、高剂量）治疗组各8只。应用慢性应激刺激的方法诱导抑郁组、生理盐水组、灵孢多糖治疗组大鼠抑郁,通过行为学指标评估建模是否成功。建模成功后,在生理盐水组中注射生理盐水;在灵孢多糖治疗组中分别注射低、中、高剂量灵孢多糖注射液,比较各组间的疗效差异。采用免疫组化的方法测定大鼠脑内多巴胺、去甲肾上腺素、5-羟色胺、酪氨酸羟化酶等单胺类神经递质含量的表达情况。结果：成功的建立了大鼠抑郁模型,抑郁组中大鼠各项行为学指标与正常组相比均明显减少,差异有统计学意义（P〈0．05）;灵孢多糖治疗组大鼠脑内的多巴胺、去甲肾上腺素、5一羟色胺、酪氨酸羟化酶与抑郁组、生理盐水组大鼠脑内的含量均明显升高,差异有统计学意义（P〈0．05）。结论：灵孢多糖注射液对改善抑郁症状有良好的疗效,具有辅助治疗抑郁症的作用。     

Disentangling the link between depressive symptoms and plasma oxytocin in men: The role of brooding rumination

The links between plasma oxytocin and depression are controversial, ranging from negative to positive associations. The present study was conducted to reconcile those conflicting findings; amongst the features of depression, we considered rumination and hypothesised that rumination would function as moderator between depressive symptoms and oxytocin. Seventy five clinically normal adult male volunteers were assessed for depressive characteristics by means of the Ruminative Responses Scale and Beck’s Depression Inventory-II; plasma oxytocin was measured by means of competitive enzyme immunoassay. The results demonstrate that high depressive symptoms were negatively associated with oxytocin concentrations at high rumination levels while such an association did not exist at low levels of rumination. The present findings suggest there are complex associations between oxytocin and brooding rumination, the latter being an important feature among depressive symptoms observed in clinically normal individuals. This complexity can underlie the current lack of consensus on the role of oxytocin in depression.     

The Effects of a Problem Solving-Based Intervention on Depressive Symptoms and HIV Medication Adherence Are Independent

Depression and depressive symptoms predict poor adherence to medical therapy, but the association is complex, nonspecific, and difficult to interpret. Understanding this association may help to identify the mechanism explaining the results of interventions that improve both medical therapy adherence and depressive symptoms as well as determine the importance of targeting depression in adherence interventions. We previously demonstrated that Managed Problem Solving (MAPS) focused on HIV medication adherence improved adherence and viral load in patients initiating a new antiretroviral regimen. Here, we assessed whether MAPS improved depressive symptoms and in turn, whether changes in depressive symptoms mediated changes in adherence and treatment outcomes. We compared MAPS to usual care with respect to presence of depressive symptoms during the trial using logistic regression. We then assessed whether MAPS’ effect on depressive symptoms mediated the relationship between MAPS and adherence and virologic outcomes using linear and logistic regression, respectively. Mediation was defined by the disappearance of the mathematical association between MAPS and the outcomes when the proposed mediator was included in regression models. Although MAPS participants had a lower rate of depressive symptoms (OR = 0.45, 95% confidence interval 0.21–0.93), there was no evidence of mediation of the effects of MAPS on adherence and virological outcome by improvements in depression. Thus, interventions for medication adherence may not need to address depressive symptoms in order to impact both adherence and depression; this remains to be confirmed, however, in other data.     

Abandoning personalization to get to precision in the pharmacotherapy of depression

Effectiveness studies and analyses of naturalistic cohorts demonstrate that many patients with major depressive disorder do not experience symptomatic remission with antidepressant treatments. In an effort to better match patients with effective treatments, numerous investigations of predictors or moderators of treatment response have been reported over the past five decades, including clinical features as well as biological measures. However, none of these have entered routine clinical practice; instead, clinicians typically personalize treatment on the basis of patient preferences as well as their own. Here, we review the reasons why it has been challenging to identify and deploy treatment‐specific predictors of response, and suggest strategies that may be required to achieve true precision in the pharmacotherapy of depression. We emphasize the need for changes in how depression care is delivered, measured, and used to inform future practice.     

Near Infrared Spectroscopy Study of the Frontopolar Hemodynamic Response and Depressive Mood in Children with Major Depressive Disorder: A Pilot Study

AIM

The aim of this study was to evaluate the frontopolar hemodynamic response and depressive mood in children with mild or moderate major depressive disorder during six weeks treatment without medication.

METHODS

The subjects were 10 patients with mild or moderate depression. They were depressive drug-naive children and adolescents. The scores of Depression Self Rating Scale (DSRS), the results of the Verbal Fluency Test (VFT), and the concentrations of oxy-hemoglobin (Oxy-Hb) of frontal pole brain assessed by two-channel near infrared spectroscopy (NIRS) after six weeks of treatment was compared with those of initial treatment.

RESULTS

The score of DSRS was significantly reduced after six weeks of initial treatment (p<0.001, t-test). The word number of VFT was not significantly changed after six weeks of treatment. The oxy-Hb concentration significantly increased after six weeks of treatment (p<0.001, t-test).

CONCLUSIONS

This study demonstrated that the concentration of oxy-Hb of frontopolar cortex in children with mild and moderate depression improved along with their depressive mood. These results suggested that concentration of oxy-Hb using NIRS may be used as the state maker for change in depressive mood of children having depression, similar to that in adults.     

Clinical Patterns and Treatment Outcome in Patients with Melancholic,Atypical and Non-Melancholic Depressions

Objective

To assess sociodemographic, clinical and treatment factors as well as depression outcome in a large representative clinical sample of psychiatric depressive outpatients and to determine if melancholic and atypical depression can be differentiated from residual non-melancholic depressive conditions.

Subjects/Materials and Method

A prospective, naturalistic, multicentre, nationwide epidemiological study of 1455 depressive outpatients was undertaken. Severity of depressive symptoms was assessed by the Hamilton Depression Rating Scale (HDRS) and the Self Rated Inventory of Depressive Symptomatology (IDS-SR₃₀). IDS-SR₃₀ defines melancholic and atypical depression according to DSM-IV criteria. Assessments were carried out after 6–8 weeks of antidepressant treatment and after 14–20 weeks of continuation treatment.

Results

Melancholic patients (16.2%) were more severely depressed, had more depressive episodes and shorter episode duration than atypical (24.7%) and non-melancholic patients. Atypical depressive patients showed higher rates of co-morbid anxiety disorders and substance abuse. Melancholic patients showed lower rates of remission.

Conclusion

Our study supports a different clinical pattern and treatment outcome for melancholic and atypical depression subtypes.     

神经元再生:抑郁症治疗的新策略

成年哺乳动物一生中,海马等脑区神经元是可以再生的,而海马脑区神经元再生的减少和增多分别是抑郁症发生和恢复的重要因素。如果神经元再生过程被抑制,在抑郁症的动物模型上抗抑郁剂将会失去其行为学效应。长期给予不同种类的抗抑郁剂可以显著地促进动物海马神经元再生。随着对神经元再生调节机制研究的不断深入,为进一步探讨抑郁症的发生机制,以及发展新型抗抑郁治疗药物提供了新的思路与视角。     

Depressive Symptoms in Crohn's Disease: Relationship with Immune Activation and Tryptophan Availability

Crohn''s disease (CD) is associated with immune activation and depressive symptoms. This study determines the impact of anti-tumor necrosis factor (TNF)-α treatment in CD patients on depressive symptoms and the degree to which tryptophan (TRP) availability and immune markers mediate this effect. Fifteen patients with CD, eligible for anti-TNF-α treatment were recruited. Disease activity (Harvey-Bradshaw Index (HBI), Crohn''s Disease Activity Index (CDAI)), fatigue (Multidimensional Fatigue Inventory (MFI)), quality of life (Inflammatory Bowel Disease Questionnaire (IBDQ)), symptoms of depression and anxiety (Symptom Checklist (SCL-90), Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS)), immune activation (acute phase proteins (APP)), zinc and TRP availability were assessed before treatment and after 2, 4 and 8 weeks. Anti-TNF-α increased IBDQ scores and reduced all depression scores; however only SCL-90 depression scores remained decreased after correction for HBI. Positive APPs decreased, while negative APPs increased after treatment. After correction for HBI, both level and percentage of γ fraction were associated with SCL-90 depression scores over time. After correction for HBI, patients with current/past depressive disorder displayed higher levels of positive APPs and lower levels of negative APPs and zinc. TRP availability remained invariant over time and there was no association between SCL-90 depression scores and TRP availability. Inflammatory reactions in CD are more evident in patients with comorbid depression, regardless of disease activity. Anti-TNF-α treatment in CD reduces depressive symptoms, in part independently of disease activity; there was no evidence that this effect was mediated by immune-induced changes in TRP availability.     

EEG correlates and possible predictors of the efficacy of the treatment of endogenous depression

Analysis of EEG spectral power values and quantitative clinical scores of depressive conditions has been carried out in the dynamics of the treatment of 40 patients with endogenous depression, with the main goal to study the neurophysiological correlates and to search for possible predictors of therapeutic outcome. The reduction of depressive symptoms by the end of the treatment course was associated with EEG signs of improvement of the brain’s functional state. Significant correlations have been revealed between the EEG narrow-band spectral power values and clinical scores. As well, significant correlations have been revealed between some initial (before the beginning of the treatment) EEG parameters and quantitative clinical scores at the initial stage of remission. The values of EEG β₁ and β₂ spectral power appeared to be predictors, while initially larger values of EEG spectral power were associated with the high manifestation of residual depressive symptoms after the treatment. The results support the basic views on the brain’s mechanisms of various aspects of depressive disorders and reveal the possible neurophysiological predictors of the efficacy of the treatment of endogenous depression.     

The Role of Family Environment in Depressive Symptoms among University Students: A Large Sample Survey in China

Objective

To explore the relationship between family environment and depressive symptoms and to evaluate the influence of hard and soft family environmental factors on depression levels in a large sample of university students in China.

Methods

A multi-stage stratified sampling procedure was used to select 6,000 participants. The response rate was 88.8%, with 5,329 students completing the Beck Depression Inventory (BDI) and the Family Environment Scale Chinese Version (FES-CV), which was adapted for the Chinese population. Differences between the groups were tested for significance by the Student’s t-test; ANOVA was used to test continuous variables. The relationship between soft family environmental factors and BDI were tested by Pearson correlation analysis. Hierarchical linear regression analysis was conducted to model the effects of hard environmental factors and soft environmental factors on depression in university students.

Results

A total of 11.8% of students scored above the threshold of moderate depression(BDI≧14). Hard family environmental factors such as parent relationship, family economic status, level of parental literacy and non-intact family structure were associated with depressive symptoms. The soft family environmental factors—conflict and control—were positively associated with depression, while cohesion was negatively related to depressive symptom after controlling for other important associates of depression. Hierarchical regression analysis indicated that the soft family environment correlates more strongly with depression than the hard family environment.

Conclusions

Soft family environmental factors—especially cohesion, conflict and control—appeared to play an important role in the occurrence of depressive symptoms. These findings underline the significance of the family environment as a source of risk factors for depression among university students in China and suggest that family-based interventions and improvement are very important to reduce depression among university students.