Group Of Major Depressive Disorder Patients Research Articles

MICRO-RNA AS DIAGNOSTIC MODALITY OF MAJOR DEPRESSIVE DISORDER

Introduction – Major Depressive Disorder (MDD) is a chronic mental health disorder, with suicidal ideation, but until now an exact diagnostic approach has not been found. For the limitations of the current diagnosis, such as subjective reports of patients or their families with mental status examinations, there is still a lack of objective diagnostic results. In this case, it is still a challenge for researchers. Neutropic factors, hypothalamic-pituitary-adrenal hormones (HPA), indicators of inflammation, and metabolic factors, were found to be novel biomarkers for MDD. However, these biomarkers show limited sensitivity and specificity. The most recent diagnostic development effort is the use of microRNA as a diagnostic modality approach for MDD. Methods – This study uses a qualitative method by collecting valid journals with certain inclusion and exclusion criteria. The keywords used were MDD, microRNA, and Diagnostic. There are journals used as the source of this literature review which come from valid scientific sources such as NCBI, ScienceDirect, and PubMed which were published in the last 10 years. Results – The results of the miRNA-124-3p expression test showed a significant difference between the healthy control group and the MDD patient group. The specificity and sensitivity of miRNA-221-3p, miRNA-451a, miRNA-34a-5p, and let-7d-3p showed high accuracy in the diagnosis of MDD. Discuss – The unknown etiology of MDD makes some patients have no results or significant progress of their depression in clinical settings which is contributed by gene regulatory pathway that shows high significance associated with neural function brain in depressive disorders such as apoptotic pathway, P13K-Akt signaling, axon guidance, neurotrophin signaling pathway, mTOR signaling pathway. Conclusion- The diagnostic effectiveness of miRNA in major depressive disorder can be significantly enhanced by using miRNA expression coding and has been proven by various tests. Therefore, this research is expected to be an innovation in diagnosing MDD for further research. Keywords: MDD, depression, microRNA, diagnostic

Attenuated post-movement beta rebound reflects psychomotor alterations in major depressive disorder during a simple visuomotor task: a MEG study

BackgroundPsychomotor alterations are a common symptom in patients with major depressive disorder (MDD). The primary motor cortex (M1) plays a vital role in the mechanism of psychomotor alterations. Post-movement beta rebound (PMBR) in the sensorimotor cortex is abnormal in patients with motor abnormalities. However, the changes in M1 beta rebound in patients with MDD remain unclear. This study aimed to primarily explore the relationship between psychomotor alterations and PMBR in MDD.MethodsOne hundred thirty-two subjects were enrolled in the study, comprising 65 healthy controls (HCs) and 67 MDD patients. All participants performed a simple right-hand visuomotor task during MEG scanning. PMBR was measured in the left M1 at the source reconstruction level with the time–frequency analysis method. Retardation factor scores and neurocognitive test performance, including the Digit Symbol Substitution Test (DSST), the Making Test Part A (TMT-A), and the Verbal Fluency Test (VFT), were used to measure psychomotor functions. Pearson correlation analyses were used to assess relationships between PMBR and psychomotor alterations in MDD.ResultsThe MDD group showed worse neurocognitive performance than the HC group in all three neurocognitive tests. The PMBR was diminished in patients with MDD compared to HCs. In a group of MDD patients, the reduced PMBR was negatively correlated with retardation factor scores. Further, there was a positive correlation between the PMBR and DSST scores. PMBR is negatively associated with the TMT-A scores.ConclusionOur findings suggested that the attenuated PMBR in M1 could illustrate the psychomotor disturbance in MDD, possibly contributing to clinical psychomotor symptoms and deficits of cognitive functions.

Association of childhood trauma with cognitive impairment and structural brain alterations in remitted patients with bipolar disorder

BackgroundCognitive impairment affects many patients with bipolar disorder (BD). No pro-cognitive treatment with robust efficacy exists partly due to limited insight into underlying neurobiological abnormalities. MethodsThis magnetic resonance imaging (MRI) study investigates structural neuronal correlates of cognitive impairment in BD by comparing brain measures in a large sample of cognitively impaired versus cognitively intact patients with BD or cognitively impaired patients with major depressive disorder (MDD) and healthy controls (HC). Participants underwent neuropsychological assessments and MRI scans. The cognitively impaired and – intact BD and MDD patient groups were compared with each other and HC regarding prefrontal cortex measures, hippocampus shape/volume, and total cerebral white (WM) and grey matter (GM). ResultsCognitively impaired BD patients showed lower total cerebral WM volume than HC, which scaled with poorer global cognitive performance and more childhood trauma. Cognitively impaired BD patients also showed lower adjusted GM volume and thickness in the frontopolar cortex than HC but greater adjusted GM volume in the temporal cortex than cognitively normal BD patients. Cognitively impaired BD patients showed decreased cingulate volume than cognitively impaired MDD patients. Hippocampal measures were similar across all groups. LimitationsThe cross-sectional study design prevented insights into causal relationships. ConclusionsLower total cerebral WM and regional frontopolar and temporal GM abnormalities may constitute structural neuronal correlates of cognitive impairment in BD, of which the WM deficits scale with the degree of childhood trauma. The results deepen the understanding of cognitive impairment in BD and provide a neuronal target for pro-cognitive treatment development.

The timing of transcranial magnetic stimulation relative to the phase of prefrontal alpha EEG modulates downstream target engagement

BackgroundThe communication through coherence model posits that brain rhythms are synchronized across different frequency bands and that effective connectivity strength between interacting regions depends on their phase relation. Evidence to support the model comes mostly from electrophysiological recordings in animals while evidence from human data is limited. MethodsHere, an fMRI-EEG-TMS (fET) instrument capable of acquiring simultaneous fMRI and EEG during noninvasive single pulse TMS applied to dorsolateral prefrontal cortex (DLPFC) was used to test whether prefrontal EEG alpha phase moderates TMS-evoked top-down influences on subgenual, rostral and dorsal anterior cingulate cortex (ACC). Six runs (276 total trials) were acquired in each participant. Phase at each TMS pulse was determined post-hoc using single-trial sorting. Results were examined in two independent datasets: healthy volunteers (HV) (n = 11) and patients with major depressive disorder (MDD) (n = 17) collected as part of an ongoing clinical trial. ResultsIn both groups, TMS-evoked functional connectivity between DLPFC and subgenual ACC (sgACC) depended on the EEG alpha phase. TMS-evoked DLPFC to sgACC fMRI-derived effective connectivity (EC) was modulated by EEG alpha phase in healthy volunteers, but not in the MDD patients. Top-down EC was inhibitory for TMS pulses during the upward slope of the alpha wave relative to TMS timed to the downward slope of the alpha wave. Prefrontal EEG alpha phase dependent effects on TMS-evoked fMRI BOLD activation of the rostral anterior cingulate cortex were detected in the MDD patient group, but not in the healthy volunteer group. DiscussionResults demonstrate that TMS-evoked top-down influences vary as a function of the prefrontal alpha rhythm, and suggest potential clinical applications whereby TMS is synchronized to the brain's internal rhythms in order to more efficiently engage deep therapeutic targets.

Discovery and validation of acetyl-L-carnitine in serum for diagnosis of major depressive disorder and remission status through metabolomic approach.

Major depressive disorder (MDD) is one of the most common psychiatric disorders that accompany psychophysiological and mood changes. However, the pathophysiology-based disease mechanism of MDD is not yet fully understood, and diagnosis is also conducted through interviews with clinicians and patients. Diagnosis and treatment of MDD are limited due to the absence of biomarkers underlying the pathophysiological mechanisms of MDD. Although various attempts have been made to discover metabolite biomarkers for the diagnosis and treatment response of MDD, problems with sample size and consistency of results have limited clinical application. In addition, it was reported that future biomarker studies must consider exposure to antidepressants, which is the main cause of heterogeneity in depression subgroups. Therefore, the purpose of this study is to discover and validate biomarkers for the diagnosis of depression in consideration of exposure to drug treatment including antidepressants that contribute to the heterogeneity of the MDD subgroup. In the biomarker discovery and validation set, the disease group consisted of a mixture of patients exposed and unexposed to drug treatment including antidepressants for the treatment of MDD. The serum metabolites that differed between the MDD patients and the control group were profiled using mass spectrometry. The validation set including the remission group was used to verify the effectiveness as a biomarker for the diagnosis of depression and determination of remission status. The presence of different metabolites between the two groups was confirmed through serum metabolite profiling between the MDD patient group and the control group. Finally, Acetylcarnitine was selected as a biomarker. In validation, acetylcarnitine was significantly decreased in MDD and was distinguished from remission status. This study confirmed that the discovered acetylcarnitine has potential as a biomarker for diagnosing depression and determining remission status, regardless of exposure to drug treatment including antidepressants.

Prevalence of major depressive disorder in 51,658 otherwise healthy adult Danes: Sex differences in symptomatology and prediction of future anti-depressive medication

Major Depressive Disorder (MDD) is a heterogeneous disease, which displays sex differences in symptomatology. This study aimed to assess point prevalence of MDD in undiagnosed, healthy adults as well as sex differences in symptomatology and clarify if specific symptoms increased the later need for anti-depressive medication. The study included 51,658 blood donors. Depressive symptoms were assessed according to ICD-10 using the Major Depression Inventory. Demographics, previous MDD, anti-depressive medication were collected from questionnaires and population registers. Descriptive, Logistic and Cox regression analyses were conducted.In total, 1.15% participants met the criteria for MDD. Women were significantly more likely to experience "increased appetite" and less likely to experience “a feeling of life not worth living”, compared to men. MDD significantly associated with an increased hazard of later receiving a prescription for anti-depressive medication. The risk increased proportionally with increasing MDD severity. The two symptoms, “feeling that life is not worth living” and "trouble sleeping" were the strongest individual predictive symptoms of future anti-depressive medication in women and men, respectively.The results confirm findings in MDD patient groups. The diagnostic and prognostic value should be investigated further to address their potential as part of the clinical assessment.

Differences in mGluR5 Availability Depending on the Level of Social Avoidance in Drug-Naïve Young Patients with Major Depressive Disorder.

BackgroundPrevious research has shown that metabotropic glutamate receptor-5 (mGluR5) signaling is significantly involved in social avoidance. We investigated the relationship between levels of social avoidance and mGluR5 availability in drug-naïve young patients with major depressive disorder (MDD).MethodsTwenty non-smoking patients and eighteen matched non-smoking healthy controls underwent [11C]ABP688 positron emission tomography (PET) and magnetic resonance imaging scans. The binding potential (BPND) of [11C]ABP688 was obtained using the simplified reference tissue model. Patients’ level of social avoidance was assessed using the Social Avoidance and Distress Scale (SADS). For [11C]ABP688 BPND, the region-of-interest (ROI)-based between-group comparisons and correlations with SADS scores were investigated. The frontal cortices were chosen as a priori ROIs based on previous PET investigations in MDD, and on literature underscoring the importance of the frontal cortex in social avoidance.ResultsIndependent samples t-tests revealed no significant differences in [11C]ABP688 BPND in the frontal cortices between the MDD patient group as a whole and healthy controls. One-way analysis of variance with post-hoc tests revealed significantly lower BPND in the bilateral superior frontal cortex (SFC) and left middle frontal cortex (MFC) in MDD patients with low levels of social avoidance (L-SADS) than in healthy controls. The L-SADS patients also had significantly lower BPND in the medial part of the right SFC than both MDD patients with high levels of social avoidance (H-SADS) and healthy controls. The L-SADS patients also showed significantly lower BPND in the orbital parts of the SFC, MFC, and inferior frontal cortex than H-SADS patients. No significant group differences were found between H-SADS patients and healthy controls. The ROI-based correlation analysis revealed significant positive correlations between social avoidance levels and frontal [11C]ABP688 BPND in the entire patients.ConclusionOur exploratory study shows significant differences in frontal mGluR5 availability depending on the level of social avoidance in drug-naïve non-smoking MDD patients, suggesting that social avoidance should be considered as one of the clinical factors involved in mGluR5 signaling changes in depression.

Relationship of explicit/implicit self-esteem discrepancies, suicide ideation, and suicide risk in patients with major depressive disorder.

The present study was conducted to explore the associations between explicit self-esteem (ESE), implicit self-esteem (ISE), ESE/ISE discrepancies, depression severity, suicidal ideation (SI), and suicide risk among patients with major depressive disorder (MDD). To this end, 36 MDD patients with SI, 35 MDD patients without SI, and 32 healthy controls were recruited. All participants were interviewed using the Mini International Neuropsychiatric Interview (MINI), and they also completed the Beck Depression Inventory (BDI). The Beck Scale for Suicide Ideation-Chinese Version (BSI-CV) and the Rosenberg Self-Esteem Scale (SES) were used for the analysis. Further, the Implicit Association Test (IAT) was conducted to assess participants' ISE. The study revealed significant differences in ESE among the three groups, F(2, 90)=44.88, p < .001. In particular, the group of MDD patients with SI had the lowest score. The interaction between the size and direction of ESE/ISE discrepancy was associated with depression severity, β=-.50, p=.004, and SI, β=-.39, p=.045. Among the four types of self-esteem, individuals with diminished self-esteem had the highest SI score whereas individuals with low congruent self-esteem had the highest suicide risk score. Based on these findings, the study suggested that diminished self-esteem could help in the early detection of depression and SI. Low-congruent self-esteem may also be considered a screening factor for suicide risk.

Interaction of recent stressful life events and childhood abuse on orbitofrontal grey matter volume in adults with depression

BackgroundThe diathesis-stress model of major depressive disorder (MDD) predicts interactions of recent stressful life events (SLEs) in adulthood and early developmental risk factors. We tested, for the first time, the diathesis stress model on brain structure in a large group of MDD patients. MethodsStructural magnetic resonance imaging data of 1465 participants (656 with lifetime diagnosis MDD; 809 healthy controls) were analyzed using voxel-based morphometry to identify clusters associated with recent SLEs (Life Events Questionnaire). Those clusters were then examined for group (healthy/MDD) × early developmental risk (operationalized as childhood abuse [Childhood Trauma Questionnaire] and a major psychiatric disorder [i.e., MDD, bipolar disorder, schizophrenia, and schizoaffective disorder] in a first-degree relative) × recent SLEs three-way interactions on grey matter volume. ResultsThere was a group × childhood abuse × recent SLEs interaction on left medial orbitofrontal cortex grey matter volume. This three-way interaction arose because childhood abuse and recent SLEs interacted in MDD subjects but not in healthy subjects. LimitationsWe are not able to draw conclusions about the cause and effect relationship due to our cross-sectional study design. ConclusionsOur data provides evidence for an interplay between orbitofrontal cortex structure, childhood abuse and recent SLEs. These factors have previously been linked to MDD and their complex interaction contributes to the pathogenesis of MDD.

Lack of association of FKBP5 SNPs and haplotypes with susceptibility and treatment response phenotypes in Han Chinese with major depressive disorder: A pilot case-control study (STROBE).

The identification of single-nucleotide polymorphisms (SNPs) in genes putatively related to pathophysiological processes in major depressive disorder (MDD) might improve both diagnosis and personalized treatment strategies eventually leading to more effective interventions. Considering the important role of the glucocorticoid receptor and the related FK506 binding protein 51 (FKBP51) in the pathophysiology of MDD, we aimed to investigate putative associations between variants of FKBP5, the coding gene of FKBP51, with antidepressant treatment resistance and MDD susceptibility.Nine common SNPs of the FKBP5 gene prioritized based on location and, putative or known functions were genotyped in Han Chinese population, including MDD patients with or without antidepressant-treatment resistance and healthy controls. Associations of FKBP5 SNPs with MDD susceptibility and treatment response were examined in the whole group of MDD patients, as well as in subgroups stratified by antidepressant treatment resistance, compared with healthy controls.In total, 181 Han Chinese patients with MDD and 80 healthy controls were recruited. No significant SNP or haplotype associations were observed in the whole patient group. There were nominal significant differences both for the haplotype block with SNPs in strong LD (r2 > 0.8, P = .040) and haplotype block with SNPs in moderate LD (r2 > 0.1, P = .017) between the haplotype distributions of patients with antidepressant treatment resistance (n = 81) and healthy controls, but both significances did not survive multiple testing correction. Furthermore, no specific haplotype could be observed causing a significant difference in any combination between all comparisons.No associations were observed of FKBP5 variants with MDD or antidepressant treatment response. The lack of associations might be due to the relatively small sample size of this study (power ranged from 0.100 to 0.752). A follow-up study will need larger, better phenotyped, and more homogeneous samples to draw a definitive conclusion regarding the involvement of this gene in MDD.

Characteristics of Intrinsic Brain Functional Connectivity Alterations in Major Depressive Disorder Patients With Suicide Behavior.

The intrinsic brain functional connectivity of suicide attempts in major depressive disorder (MDD) remains incompletely understood. To investigate graph-theoretical based functional connectivity strength (FCS) alterations in MDD patients with suicidal behavior. Prospective. Fifty medication-free MDD patients, with (suicide attempters, SA, N=15) and without (non-attempters, nSA, N=35) a history of a suicide attempt, and 37 healthy controls (HC). Resting-state functional magnetic resonance imaging (fMRI) using a gradient-echo imaging sequence was acquired at 3.0 T. For each individual, voxel-wise whole-brain functional network was constructed and graph-theoretical based FCS map was calculated. For each individual in two patient groups, the seed-based functional connectivity map was constructed. Non-parameter permutation tests, analysis of covariance, two-sample t-test, Chi-square test, and Pearson correlation analysis. A P value <0.05 was considered statistically significant. Relative to the HC group, two MDD patient groups showed significantly lower FCS in the left hippocampus, while nSA patients showed additionally lower FCS in more widespread regions (P < 0.05). Importantly, comparing to nSA patients, SA patients had significantly higher FCS in the right orbitofrontal cortex (OFC) and bilateral dorsomedial prefrontal cortex (dmPFC) (P < 0.05). Further seed-based functional connectivity analysis revealed that the right OFC exhibited significantly higher connectivity to right middle frontal gyrus and lower connectivity to the left anterior cingulate cortex and left calcarine sulcus, and the bilateral dmPFC had significantly higher connectivity to the left middle frontal gyrus and right inferior temporal gyrus in the SA patients than in the nSA patients (P < 0.05). This study identified disconnections of the OFC and dmPFC which were putatively related to a higher risk of suicidal behavior in MDD patients, thus extended the understanding of suicidal behavior at a brain circuit level. 3 TECHNICAL EFFICACY STAGE: 3.

Altered interhemispheric signal propagation in schizophrenia and depression

ObjectiveAltered interhemispheric connectivity is implicated in the pathophysiology of schizophrenia (SCZ) and major depressive disorder (MDD) and may account for deficits in lateralized cognitive processes. We measured transcranial magnetic stimulation evoked interhemispheric signal propagation (ISP), a non-invasive measure of transcallosal connectivity, and hypothesized that the SCZ and MDD groups will have increased ISP compared to healthy controls. MethodsWe evaluated ISP over the dorsolateral prefrontal cortex in 34 patients with SCZ and 34 patients with MDD compared to 32 age and sex-matched healthy controls. ResultsISP was significantly increased in patients with SCZ and patients with MDD compared to healthy controls but did not differ between patient groups. There were no effects of antidepressant, antipsychotic, and benzodiazepine medications on ISP and our results remained unchanged after re-analysis with a region of interest method. ConclusionAltered ISP was found in both SCZ and MDD patient groups. This indicates that disruptions of interhemispheric signaling processes can be indexed with ISP across psychiatric populations. SignificanceThese findings enhance our knowledge of the physiological mechanisms of interhemispheric imbalances in SCZ and MDD, which may serve as potential treatment targets in future patients.

Fatigue and brain arousal in patients with major depressive disorder

Fatigue is considered a key symptom of major depressive disorder (MDD), yet the term lacks specificity. It can denote a state of increased sleepiness and lack of drive (i.e., downregulated arousal) as well as a state of high inner tension and inhibition of drive with long sleep onset latencies (i.e., upregulated arousal), the latter typically found in depression. It has been proposed to differentiate fatigue along the dimension of brain arousal. We investigated whether such stratification within a group of MDD patients would reveal a subgroup with distinct clinical features. Using an automatic classification of EEG vigilance stages, an arousal stability score was calculated for 15-min resting EEGs of 102 MDD patients with fatigue. 23.5% of the patients showed signs of hypoarousal with EEG patterns indicating drowsiness or sleep; this hypoaroused subgroup was compared with remaining patients (non-hypoaroused subgroup) concerning self-rated measures of depressive symptoms, sleepiness, and sleep. The hypoaroused subgroup scored higher on the Beck Depression Inventory items “loss of energy” (Z = − 2.13, p = 0.033; ɳ2 = 0.044, 90% CI 0.003–0.128) and “concentration difficulty” (Z = − 2.40, p = 0.017; ɳ2 = 0.056, 90% CI 0.009–0.139), and reported higher trait and state sleepiness (p < 0.05) as compared to the non-hypoaroused group. The non-hypoaroused subgroup, in contrast, reported more frequently the presence of suicidal ideation (Chi2 = 3.81, p = 0.051; ɳ2 = 0.037, 90% CI 0.0008–0.126). In this study, we found some evidence that stratifying fatigued MDD patients by arousal may lead to subgroups that are pathophysiologically and clinically more homogeneous. Brain arousal may be a worth while target in clinical research for better understanding the mechanisms underlying suicidal tendencies and to improve treatment response.

Altered resting-state dynamic functional brain networks in major depressive disorder: Findings from the REST-meta-MDD consortium

BackgroundMajor depressive disorder (MDD) is known to be characterized by altered brain functional connectivity (FC) patterns. However, whether and how the features of dynamic FC would change in patients with MDD are unclear. In this study, we aimed to characterize dynamic FC in MDD using a large multi-site sample and a novel dynamic network-based approach.MethodsResting-state functional magnetic resonance imaging (fMRI) data were acquired from a total of 460 MDD patients and 473 healthy controls, as a part of the REST-meta-MDD consortium. Resting-state dynamic functional brain networks were constructed for each subject by a sliding-window approach. Multiple spatio-temporal features of dynamic brain networks, including temporal variability, temporal clustering and temporal efficiency, were then compared between patients and healthy subjects at both global and local levels.ResultsThe group of MDD patients showed significantly higher temporal variability, lower temporal correlation coefficient (indicating decreased temporal clustering) and shorter characteristic temporal path length (indicating increased temporal efficiency) compared with healthy controls (corrected p < 3.14×10−3). Corresponding local changes in MDD were mainly found in the default-mode, sensorimotor and subcortical areas. Measures of temporal variability and characteristic temporal path length were significantly correlated with depression severity in patients (corrected p < 0.05). Moreover, the observed between-group differences were robustly present in both first-episode, drug-naïve (FEDN) and non-FEDN patients.ConclusionsOur findings suggest that excessive temporal variations of brain FC, reflecting abnormal communications between large-scale bran networks over time, may underlie the neuropathology of MDD.

BDNF genetic variants and methylation: effects on cognition in major depressive disorder

Brain-derived neurotrophic factor (BDNF) gene regulation has been linked to the pathophysiology of major depressive disorder (MDD). MDD patients show cognitive deficits, and altered BDNF regulation has a relevant role in neurocognitive functions. Our goal was to explore the association between BDNF genetic and epigenetic variations with neurocognitive performance in a group of MDD patients and healthy controls considering possible modulating factors. The sample included 134 subjects, 64 MDD patients, and 70 healthy controls. Clinical data, childhood maltreatment, and neurocognitive performance were assessed in all participants. Eleven single nucleotide polymorphisms (SNPs) and two promoter regions in the BDNF gene were selected for genotype and methylation analysis. The role of interactions between BDNF genetic and epigenetic variations with MDD diagnosis, sex, and Childhood Trauma Questionnaire (CTQ) scores was also explored. We observed significant associations between neurocognitive performance and two BDNF SNPs (rs908867 and rs925946), an effect that was significantly mediated by methylation values at specific promoter I sites. We identified significant associations between neurocognitive results and methylation status as well as its interactions with MDD diagnosis, sex, and CTQ scores. Our results support the hypothesis that BDNF gene SNPs and methylation status, as well as their interactions with modulating factors, can influence cognition. Further studies are required to confirm the effect of BDNF variations and cognitive function in larger samples.

Interferon-alpha-induced depression: Comparisons between early- and late-onset subgroups and with patients with major depressive disorder

Interferon (IFN)-alpha, until recently the standard treatment of hepatitis C virus (HCV) infection, is associated with a significant risk of major depressive episode (MDE, or IFN-alpha-induced depression). However, it is little studied the comparisons of clinical manifestations between IFN-alpha-induced depression and major depressive disorder (MDD). In addition, IFN-alpha induces different neuroinflammation and neuroendocrine status throughput the HCV treatment course; however, the clinical presentations have never been compared between early-onset and later-onset IFN-alpha-induced depression. We assessed 200 HCV patients starting IFN-alpha therapy bi-weekly for 24 weeks, with the structured interview for confirmation of diagnosis of IFN-alpha-induced depression and with clinical rating scales for depressive symptoms and neuropsychiatric symptoms. Subjects developed IFN-alpha-induced depression (n = 59, 30%) during the first 6 weeks of IFN-alpha therapy were defined as the early-onset group (n = 32), while those developed depression after the 6th week were defined as the late-onset group (n = 27). A matched group of MDD patients (n = 60) was used to compare specific clusters of depressive symptoms with early- and late-onset IFN-alpha-induced depression. Compared to the matched group of MDD patients, IFN-alpha-induced depression was significantly associated with more somatic symptoms and fewer symptoms of mood, anxiety and negative cognition. More somatic symptoms were also found in those who became clinically depressed at early stage of IFN-alpha therapy. We suggest that the specific somatic features of interferon-alpha-induced depression, and especially of early-onset depression, characterise individuals who are more sensitive to cytokines-induced changes in mood.

Tryptophan hydroxylase-2 polymorphism is associated with white matter integrity in first-episode, medication-naïve major depressive disorder patients

Considerable evidence suggests that the tryptophan hydroxylase-2 (TPH2) gene is associated with the pathophysiology of major depressive disorder (MDD). In the present study, we investigated alterations of white matter (WM) integrity and the impact of TPH2 polymorphism on WM in a sample of 118 first-episode, medication-naïve, MDD patients and 118 well-matched healthy controls. Whole brain analyses of fractional anisotropy (FA) were performed using tract-based spatial statistics (TBSS). The results showed that the MDD group had significantly reduced FA values for the genu and body of the corpus callosum (CC) and the bilateral anterior corona radiate (ACR). In the MDD patient group, the GG homozygote subgroup exhibited a widespread reduction of FA (uncorrected) and significantly reduced FA in the left retrolenticular portion of the internal capsule and left superior longitudinal fasciculus (SLF) compared with those of the T carriers (GT/TT) (FWE corrected). No significant correlation was found between the FA values in any brain region and the patients' clinical variables. Our findings demonstrate the presence of abnormal white matter integrity in untreated patients with first-episode depression. TPH2-rs4570625 polymorphisms may be involved in the pathological mechanism of WM microarchitecture in patients.

Decreased functional connectivity of the insula within the salience network as an indicator for prospective insufficient response to antidepressants.

Insufficient response to treatment is the main cause of prolonged suffering from major depressive disorder (MDD). Early identification of insufficient response could result in faster and more targeted treatment strategies to reduce suffering. We therefore explored whether baseline alterations within and between resting state functional connectivity networks could serve as markers of insufficient response to antidepressant treatment in two years of follow-up. We selected MDD patients (N = 17) from the NEtherlands Study of Depression and Anxiety (NESDA), who received ≥ two antidepressants, indicative for insufficient response, during the two year follow-up, a group of MDD patients who received only one antidepressant (N = 32) and a healthy control group (N = 19) matched on clinical characteristics and demographics. An independent component analysis (ICA) of baseline resting-state scans was conducted after which functional connectivity within the components was compared between groups. We observed lower connectivity of the right insula within the salience network in the group with ≥ two antidepressants compared to the group with one antidepressant. No difference in connectivity was found between the patient groups and healthy control group. Given the suggested role of the right insula in switching between task-positive mode (activation during attention-demanding tasks) and task-negative mode (activation during the absence of any task), we explored whether right insula activation differed during switching between these two modes. We observed that in the ≥2 antidepressant group, the right insula was less active compared to the group with one antidepressant, when switching from task-positive to task-negative mode than the other way around. These findings imply that lower right insula connectivity within the salience network may serve as an indicator for prospective insufficient response to antidepressants. This result, supplemented by the diminished insula activation when switching between task and rest related networks, could indicate an underlying mechanism that, if not sufficiently targeted by current antidepressants, could lead to insufficient response. When replicated, these findings may contribute to the identification of biomarkers for early detection of insufficient response.

Low cocaine- and amphetamine-regulated transcript (CART) peptide levels in human cerebrospinal fluid of major depressive disorder (MDD) patients

BackgroundCocaine- and amphetamine-regulated transcript (CART) peptide is a candidate neuropeptide as a biomarker for major depressive disorder (MDD) because of its effects on emotion and distribution covering brain areas involved in the pathophysiology of MDD symptoms. However, it is unknown whether CART peptide levels are altered in the cerebrospinal fluid (CSF) of patients with MDD patients and are correlated with MDD symptoms. MethodsSubjects were 24 patients with MDD and 25 healthy controls matched for age, gender and ethnicity (Japanese). We measured CSF CART levels by a commercially available immunoassay kit and analyzed the relationships of the levels with antidepressant dose and symptoms assessed with the 21 item Hamilton Depression Rating Scale (HAMD-21). ResultsCSF CART levels were significantly decreased in the patients than in the controls (p < 0.05). In MDD patient group, the CART levels had a negative correlation with antidepressant dose (imipramine-equivalent dose) (ρ = −0.55, p < 0.01) and significantly decreased in antidepressant-treated group (AD-treated group) compared to controls (p < 0.05). CSF CART levels showed significant negative correlations with psychomotor retardation, somatic anxiety, and general somatic symptoms (all p < 0.05) and a positive correlation with obsessive and compulsive symptoms (p < 0.05). LimitationsIn our analysis, all classes of antidepressants were combined together and the effects of medication use in a longitudinal manner did not confirm. ConclusionsWe report for the first time that CSF CART peptide levels are reduced in patients with MDD compared with healthy controls. The CART levels showed negative correlations with antidepressant dose and some symptoms, supporting the possibility that CART peptide is involved in the development of depressive symptoms.

Simultaneous rTMS and psychotherapy in major depressive disorder: Clinical outcomes and predictors from a large naturalistic study

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is considered an efficacious non-invasive neuromodulation treatment for major depressive disorder (MDD). However, little is known about the clinical outcome of combined rTMS and psychotherapy (rTMS + PT). Through common neurobiological brain mechanisms, rTMS + PT may exert enhanced antidepressant effects compared to the respective monotherapies. ObjectiveThe current naturalistic study aimed to evaluate feasibility and clinical outcome of rTMS + PT in a large group of MDD patients. The second aim was to identify clinical predictors of response and remission. MethodsA total of 196 patients with MDD were treated with at least 10 sessions of simultaneous rTMS and PT. rTMS was applied over the DLPFC, either 10 Hz left or 1 Hz right. Psychotherapy was based on principles of cognitive behavioral therapy (CBT). Symptoms were measured using the BDI each fifth session until end of treatment and at 6-month follow-up. Comparisons were made between responders and non-responders, as well as between the 10 Hz and 1 Hz protocol. Additionally, baseline variables and early BDI change were evaluated as predictors of response/remission. Major findings and conclusions1) Combining rTMS and PT resulted in a 66% response and a 56% remission rate at the end of treatment with 60% sustained remission at follow-up. Compared to previous findings in RCTs, these rates are relatively high; 2) No differences were found between the 10 Hz and 1 Hz TMS regarding clinical outcome; 3) Clinical baseline variables were not predictive of treatment outcomes; 4) Early symptom improvement (at session 10) was highly predictive of response, and may therefore be used to guide rTMS + PT continuation; 5) Based on the current findings in a large naturalistic study, future studies employing a more standardized method are warranted to draw solid conclusions on the unique effect of rTMS + PT.