Structural brain correlates of serum and epigenetic markers of inflammation in major depressive disorder

Inflammatory processes are implicated in the aetiology of Major Depressive Disorder (MDD); however, the relationship between peripheral inflammation, brain structure and depression remains unclear, partly due to complexities around the use of acute/phasic inflammatory biomarkers.Here, we report the first large-scale study of both serological and methylomic signatures of CRP (considered to represent acute and chronic measures of inflammation respectively) and their associations with depression status/symptoms, and structural neuroimaging phenotypes (T1 and diffusion MRI) in a large community-based sample (Generation Scotland; N_{MDD cases} = 271, N_controls = 609).Serum CRP was associated with overall MDD severity, and specifically with current somatic symptoms- general interest (β = 0.145, P_FDR = 6 × 10⁻⁴) and energy levels (β = 0.101, P_FDR = 0.027), along with reduced entorhinal cortex thickness (β = −0.095, P_FDR = 0.037). DNAm CRP was significantly associated with reduced global grey matter/cortical volume and widespread reductions in integrity of 16/24 white matter tracts (with greatest regional effects in the external and internal capsules, β_FA= −0.12 to −0.14). In general, the methylation-based measures showed stronger associations with imaging metrics than serum-based CRP measures (βaverage = −0.15 versus βaverage = 0.01 respectively).These findings provide evidence for central effects of peripheral inflammation from both serological and epigenetic markers of inflammation, including in brain regions previously implicated in depression. This suggests that these imaging measures may be involved in the relationship between peripheral inflammation and somatic/depressive symptoms. Notably, greater effects on brain morphology were seen for methylation-based rather than serum-based measures of inflammation, indicating the importance of such measures for future studies.     

Neuroanatomic correlates of psychopathologic components of major depressive disorder

BACKGROUND: The Hamilton Depression Rating Scale (HDRS) is widely used to measure the severity of depression in mood disorders. Total HDRS score correlates with brain metabolism as measured by fludeoxyglucose F 18 ([(18)F]-FDG) positron emission tomography. The HDRS comprises distinct symptom clusters that may be associated with different patterns of regional brain glucose metabolism. OBJECTIVE: To examine associations between HDRS component psychopathologic clusters and resting glucose cerebral metabolism assessed by [(18)F]-FDG positron emission tomography.Patients We evaluated 298 drug-free patients who met the DSM-III-R criteria for major depressive disorder. MAIN OUTCOME MEASURES: Five principal components were extracted from the 24-item HDRS for all subjects and ProMax rotated: psychic depression, loss of motivated behavior, psychosis, anxiety, and sleep disturbance. The [(18)F]-FDG scans were acquired in a subgroup of 43 drug-free patients in twelve 5-minute frames. Voxel-level correlation maps were generated with HDRS total and factor scores. RESULTS: Total HDRS score correlated positively with activity in a large bilateral ventral cortical and subcortical region that included limbic, thalamic, and basal ganglia structures. Distinct correlation patterns were found with the 3 individual HDRS factors. Psychic depression correlated positively with metabolism in the cingulate gyrus, thalamus, and basal ganglia. Sleep disturbance correlated positively with metabolism in limbic structures and basal ganglia. Loss of motivated behavior was negatively associated with parietal and superior frontal cortical areas. CONCLUSIONS: Different brain regions correlate with discrete symptom components that compose the overall syndrome of major depression. Future studies should extend knowledge about specific regional networks by identifying responsible neurotransmitters related to specific psychopathologic components of mood disorders.     

The neural correlates of anhedonia in major depressive disorder.

BACKGROUND: Anhedonia is a relative lack of pleasure in response to formerly rewarding stimuli. It is an important diagnostic feature of major depressive disorder (MDD), and predicts antidepressant efficacy. Understanding its neurobiological basis may help to target new treatments and predict treatment outcomes. Using a novel paradigm, we aimed to explore the correlations between anhedonia severity and magnitude of neural responses to happy and sad stimuli in regions previously implicated in studies of human reward processing and depressive anhedonia. METHODS: Neural responses to happy and sad emotional stimuli (autobiographical prompts and mood congruent facial expressions) were measured using blood oxygen level dependent (BOLD) functional magnetic resonance imaging in twelve MDD individuals with varying degrees of anhedonia. RESULTS: In response to happy stimuli, anhedonia, but not depression severity per se, was positively and negatively correlated with ventromedial prefrontal cortex (VMPFC) and amygdala/ventral striatal activity, respectively. State anxiety independently contributed to a VMPFC-subcortical dissociation of response to happy (but not sad) stimuli, which was similar, but different, to anhedonia. CONCLUSIONS: These findings suggest that anhedonia and state anxiety are associated with dysfunction within neural systems underlying the response to, and assessment of, the rewarding potential of emotive stimuli in MDD, and highlight the importance of employing a symptom-dimension-based approach in the examination of the neurobiology of depression.     

Anatomical MRI study of basal ganglia in major depressive disorder

The basal ganglia form a part of the brain neuroanatomic circuits that may be involved in mood regulation. Decreases in basal ganglia volumes have been previously reported in major depressive disorder patients in comparison to healthy controls. In this study, we measured caudate, putamen, and globus pallidus volumes in 25 patients with major depressive disorder (4 M; age+/-S.D.=41+/-11 years) and 48 healthy controls (29 M; age+/-S.D.=35+/-10 years), using high-resolution magnetic resonance imaging (MRI), in an attempt to replicate prior findings. Unlike most previous studies, we did not find significant differences between patient and control groups in basal ganglia volumetric measures. Nonetheless, there was a significant interaction between diagnosis and cerebral hemisphere, with MDD patients showing decreased asymmetry in globus pallidus volumes in comparison with healthy controls. Furthermore, in the patient group, left putamen volumes correlated inversely with length of illness, and left globus pallidus volume correlated directly with number of prior depressive episodes. These findings suggest that abnormalities in lateralization and possibly neurodegenerative changes in basal ganglia structures participate in the pathophysiology of major depressive disorder.     

重症抑郁障碍的结构性磁共振影像学研究进展

重症抑郁障碍(MDD)是一种以持续情感低落、思维迟缓、意志减退为主要临床特征的精神障碍,通常伴有认知功能障碍和躯体症状。1980年,美国精神障碍诊断与统计手册第3版(DSM-Ⅲ)开始采用"major depressive disorder"作为临床抑郁症的正规命名,以描述该症候群作为一种情感障碍的主要特征;而通用名词"depression"也兼指其他心理性抑郁障碍。重症抑郁障碍在所有精神障碍中的患病率最高,通常在青壮年发病,多为慢性迁延病程,易     

部分多模态MRI在重度抑郁症中的研究进展

重度抑郁症是最常见的高致残性的精神疾病之一,其发病机制尚不清楚。MRI技术作为非侵入性的神经影像技术,可揭示重度抑郁症患者大脑功能状态。与健康对照者相比,重度抑郁症患者额叶、颞叶、海马、扣带回、基底节、小脑等脑区功能改变,可能提示重度抑郁症的病理生理异常。现就多模态MRI,包括弥散张量成像(DTI)、弥散峰度成像(DKI)、磁共振波谱成像(MRS)、功能MRI(fMRI)、神经突方向分散度和密度成像(NODDI)在重度抑郁症中的最新研究成果进行综述,以期对其神经生物学机制有更充分的理解。     

Cognitive hypnotherapy for major depressive disorder

Since the publication of the special issue on cognitive hypnotherapy in the Journal of Cognitive Psychotherapy: An International Quarterly (1994), there have been major developments in the application of hypnosis to the treatment of depression. However, there is no "one-size-fits-all" treatment for depressive disorders as the conditions represent a complex set of heterogeneous symptoms, involving multiple etiologies. It is thus important for therapists to promote a multimodal approach to treating depressive disorders. This article describes cognitive hypnotherapy (CH), an evidence-based multimodal psychological treatment that can be applied to a wide range of depressed patients. CH combines hypnosis with cognitive behavior therapy as the latter provides the best integrative lodestone for assimilating empirically supported treatment techniques derived from various psychotherapies.     

Situational major depressive disorder

Fifty-seven patients with situational major depression diagnosed by the Research Diagnostic Criteria were compared with 72 subjects with nonsituational major depression on demographic, clinical, and psychosocial variables. The situational patients tended to be younger and had fewer prior episodes of depression and fewer hospitalizations. No differences were found in categories of life events, in overall clinical picture, in social supports, or in family history.     

单相抑郁症的遗传方式探讨

目的　探讨单相抑郁症的遗传方式。方法 对108例（男32例,女76例）单相抑郁症家系采用分离分析和多基因阈值理论进行遗传方式的探讨。结果　单相抑郁症加权平均遗传率为（96.5±4.5）％,预期发病率为4.35％,与实际发病率4.14％相比较无显著性差异;未发现父-子同病的情况。结论　单相抑郁症的遗传方式为多基因遗传方式,并提示单相抑郁症可能与X连锁显性遗传方式有关。     

Risks for suicidality in major depressive disorder

This investigation developed a hierarchical multiple regression model to assess the potential risk factors for suicidality in youths 7 to 17 years old. Variables were assessed in three domains: self-perceptions, demography and diagnosis, and home/environment. The model controlled for major depressive disorder (MDD), which has confounded previous investigations, by evaluating potential risks in a diagnostically heterogenous sample, and then evaluating these risks in a subsample with MDD. Conduct problems and depressive thinking emerged as the most powerful predictors in both samples. Hopelessness, life stress, and maternal psychopathology predicted suicidality only in the total sample. Separation anxiety protected MDD youths. These results suggest that suicidal MDD youths may comprise a distinct subgroup of depressed youths.     

Anatomical and functional correlates in major depressive disorder: The contribution of neuroimaging studies

Several studies suggested the neural networks modulating aspects of emotional behaviour to be implicated in the pathophysiology of mood disorders. These networks involve the medial prefrontal cortex (MPFC) and closely related areas in the medial and caudolateral orbital cortex (medial prefrontal network), amygdala, hippocampus, and ventromedial parts of the basal ganglia, where alterations in grey matter volume and neurophysiological activity are found in cases with recurrent depressive episodes. Such findings hold major implications for models of the neurocircuits that underlie depression. In particular, evidence from lesion analysis studies suggests that MPFC and related limbic and striato-pallido-thalamic structures organize emotional expression. The aim of this paper is to review the contribution of the most relevant studies with single photon emission tomography (SPECT), positron emission tomography (PET) and magnetic resonance imaging (MRI) to the understanding of pathophysiology of major depressive disorder (MDD), with particular focus on the reversibility of functional correlates with treatment.     

Clinical and socio-demographic correlates of anxious distress in Asian outpatients with major depressive disorder

Background: Anxious distress in major depressive disorder (MDD) is common and associated with poor outcomes and management difficulties.

Aims: This post hoc analysis aimed to examine the socio-demographic and clinical correlates of anxiety distress in Asian outpatients with MDD.

Methods: Instead of two out of five specifiers defined by the Diagnostic and Statistical Manual Version-5, anxious distress defined in this study was operationalized as the presence of at least two out of four proxy items drawn from the 90-item Symptom Checklist, Revised (SCL-90-R). Other measures included the Montgomery–Asberg Depression Rating Scale (MADRS), the Fatigue Severity Scale, the Sheehan Disability Scale and the Multidimensional Scale of Perceived Social Support.

Results: The data of 496 patients with MDD were included. Anxious distress was found in 371 participants (74.8%). The binary logistic regression analysis found that anxious distress was independently and significantly correlated with working status, higher MADRS scores, severe insomnia and functional impairment.

Conclusions: Three-fourths of Asian patients with MDD in tertiary care settings may have DSM-5 anxious distress of at least moderate distress. Its prevalence may vary among working groups. The specifier was associated with greater depressive symptom severity, severe insomnia and functional impairment.     

Electroconvulsive therapy for comorbid major depressive disorder and posttraumatic stress disorder

OBJECTIVE: Posttraumatic stress disorder (PTSD) and major depressive disorder frequently co-occur. Electroconvulsive therapy (ECT) is the most effective treatment for refractory major depressive disorder. We examined the effect of ECT in patients with co-occurring major depression and PTSD. METHOD: Using a retrospective chart review, we examined the outcome of the cases of 26 patients with major depression and co-occurring PTSD who received a course of ECT. The patients received either suprathreshold right unilateral, bilateral, or a combination of both. Using paired t test analysis, we compared the pretreatment and the posttreatment symptoms using the Montgomery-Asberg Depression Rating Scale and the PTSD Checklist. RESULTS: The patients receiving ECT had a significant reduction in the symptoms of major depression and some amelioration in PTSD symptoms. CONCLUSIONS: Electroconvulsive therapy may be an effective treatment for patients with refractory depression and co-occurring PTSD.     

A self-report scale to diagnose major depressive disorder

The Inventory to Diagnose Depression (IDD) is a self-report scale designed to diagnose DSM-III major depressive disorder (MDD). In our analysis, its test-retest reliability and internal consistency were high. The IDD was significantly associated with other self-report and interviewer rated depression scales and was sensitive to clinical change. Diagnostic agreement between the IDD and clinician's diagnosis of MDD was as high as that found in studies examining the interrater reliability of the diagnosis of MDD. Moreover, our results suggested that the IDD may aid clinicians in detecting secondary depression and distinguishing psychotic depression from nonaffective psychoses. The IDD may be particularly useful in light of the recent evidence that American psychiatrists continue to underdiagnose depression and overdiagnose schizophrenia.     

Prevalence and symptomatic correlates of interpersonal trauma in South Korean outpatients with major depressive disorder

BackgroundThere is growing evidence that exposure to severe interpersonal trauma (IPT) has a pivotal role in the development and manifestation of depression. However, it is not clearly understood whether patients with major depressive disorder (MDD) have specifically increased prevalence of IPT than other non-interpersonal traumatic events and whether those with IPT have unique symptom profile within depressed groups. In this study, we investigated the prevalence of past traumatic events and symptomatic features of treatment-seeking outpatients with MDD.MethodsA consecutive sample of 111 South Korean outpatients with MDD was recruited on their first visit to a psychiatric department of a university-affiliated hospital. Participants completed the Life Events Checklist (LEC), the Symptom Checklist-90-Revised (SCL-90-R), Beck Depression Inventory (BDI), State–Trait Anxiety Inventory (STAI), Dissociative Experience Scale (DES) and Impact of Event Scale-Revised (IES-R). The prevalence of past traumatic events on LEC was compared to medical outpatients.ResultsCompared to medical outpatients, MDD patients had significantly higher rates of IPT (physical and sexual) but not other traumatic events of non-interpersonal origin such as accidents or disaster. Compared to MDD patients without IPT (n = 44, 40%), those with IPT (n = 67, 60%) had higher subscale scores on hostility in SCL-90-R, as well as greater depressive and post-traumatic symptoms. However, multivariate analysis revealed that the best model to discriminate those with IPT was interaction of depressive and posttraumatic symptoms.LimitationsLimitations include sample characteristics (treatment-seeking outpatients) and possible effects of comorbid conditions, which were not investigated.ConclusionsClinicians managing individuals with depressive disorder need to include the assessment of lifetime IPT and its impact on presenting symptoms.