Changes In Major Depressive Disorder Research Articles

Structural MRI at 7T reveals amygdala nuclei and hippocampal subfield volumetric association with Major Depressive Disorder symptom severity

Subcortical volumetric changes in major depressive disorder (MDD) have been purported to underlie depressive symptomology, however, the evidence to date remains inconsistent. Here, we investigated limbic volumes in MDD, utilizing high-resolution structural images to allow segmentation of the hippocampus and amygdala into their constituent substructures. Twenty-four MDD patients and twenty matched controls underwent structural MRI at 7T field strength. All participants completed the Montgomery-Asberg Depression Rating Scale (MADRS) to quantify depressive symptomology. For the MDD group, volumes of the amygdala right lateral nucleus (p = 0.05, r2 = 0.24), left cortical nucleus (p = 0.032, r2 = 0.35), left accessory basal nucleus (p = 0.04, r2 = 0.28) and bilateral corticoamygdaloid transition area (right hemisphere p = 0.032, r2 = 0.38, left hemisphere p = 0.032, r2 = 0.35) each displayed significant negative associations with MDD severity. The bilateral centrocortical (right hemisphere p = 0.032, r2 = 0.31, left hemisphere p = 0.032, r2 = 0.32) and right basolateral complexes (p = 0.05, r2 = 0.24) also displayed significant negative relationships with depressive symptoms. Using high-field strength MRI, we report the novel finding that MDD severity is consistently negatively associated with amygdala nuclei, linking volumetric reductions with worsening depressive symptoms.

The prognosis and changes of regional brain gray matter volume in MDD with gastrointestinal symptoms.

Objective: It is common that major depressive disorder (MDD) is accompanied by gastrointestinal (GI) symptoms. However, few studies have focused on the clinical characteristics and its possible mechanism, while brain gray matter (GM) structure is important in the pathogenesis of GI symptoms. In this study, we aimed to investigate the basic clinical characteristics and regional GM volume changes in MDD accompanied by GI symptoms.Method: Patients with MDD (n=49) and age, gender, and educational level-matched healthy controls (n=30) were recruited. Patients with MDD were divided into two groups based on the GI status: MDD with (n=27) and without (n=22) GI symptoms. The 24-item Hamilton Depression Rating Scale (HAMD) was administered. T1-weighted anatomical images were obtained and analyzed. Correlation analysis was used to identify the possible associations between changed regional GM volume and GI symptoms and depressive symptoms.Results: The HAMD reductive ratio for 2 weeks of treatment in the GI symptoms group was significantly higher than the non-GI symptoms group (P<0.05). The regional GM volume showed significant differences among the three groups (Gaussian Random Field [GRF] correction, voxel-P<0.01, cluster-P <0.05). Compared with non-GI symptoms group, GI symptoms group exhibited significantly increased GM volume in the left hippocampus, left parahippocampal gyrus, right parahippocampal gyrus; and decreased GM volume in the right middle frontal gyrus, right precentral gyrus, right cuneus, right precuneus, right superior occipital gyrus (GRF correction, voxel-P <0.01, cluster-P <0.05). These altered brain areas were correlated with the GI symptoms, not depressive symptoms.Conclusion: The changed regional brain GM volume in GI-MDD group may be the pathogenesis for the GI symptoms. In addition, the GI symptoms may predict the prognosis of MDD.

Abnormal coupling among spontaneous brain activity metrics and cognitive deficits in major depressive disorder

BackgroundA variety of functional metrics derived from resting-state functional magnetic resonance imaging (rs-fMRI) have been employed to explore spontaneous brain activity changes in major depressive disorder (MDD) and have enjoyed significant success in unraveling the neurobiological mechanisms underlying this disorder. However, it is unclear whether spatial and temporal coupling relationships among these rs-fMRI metrics are altered in MDD. Methods50 patients with MDD and 36 well-matched healthy controls underwent rs-fMRI scans. A dynamic analysis was applied to compute multiple frequently used metrics including fractional amplitude of low frequency fluctuations, regional homogeneity, voxel-mirrored homotopic connectivity, degree centrality and global signal connectivity. Kendall's W was used to calculate volume-wise (across voxels) and voxel-wise (across time windows) concordance among these metrics. Inter-group differences in the concordance and their associations with clinical and cognitive variables were tested. ResultsCompared to healthy controls, patients with MDD showed decreased whole gray matter volume-wise concordance. Despite similar spatial distributions, quantitative comparison analysis revealed that MDD patients exhibited reduced voxel-wise concordance in multiple cortical and subcortical regions. Moreover, the lower concordance was associated with worse performances in prospective memory and sustained attention in the MDD group. LimitationsThe study design of fairly modest sample size did not allow us to perform a full analysis of the potential effects of medication and illness duration. ConclusionsOur findings suggest that spatial and temporal decoupling of multiple resting-state brain activity metrics may help elucidate the neural mechanisms of cognitive deficits in depression.

Altered whole brain functional connectivity pattern homogeneity in medication-free major depressive disorder

BackgroundMany previous studies have revealed abnormal functional connectivity patterns between brain areas underlying the onset of major depressive disorder (MDD) using resting-state functional magnetic resonance imaging (rs-fMRI). However, how to exactly characterize the voxel-wise whole brain functional connectivity pattern changes in MDD remains unclear, which will provide more convincing evidence for localizing the exactly functional connectivity abnormality in MDD. MethodsIn this study, we employed our newly developed whole brain functional connectivity homogeneity (FcHo) method to identify the voxel-wise changes of functional connectivity patterns in 27 medication-free MDD patients and 34 gender-, age-, and education level-matched healthy controls (HC). Furthermore, seed-based functional connectivity analysis was then used to identify the alteration of corresponding functional connectivity. ResultsSignificantly decreased FcHo values in right ventral anterior insula (INS) and medial prefrontal cortex (MPFC) were identified in MDD patients. The ensuing functional connectivity analyses identified decreased functional connectivity between MPFC and left angular gyrus (AG) in MDD patients. Moreover, both decreased FcHo values in INS, MPFC and functional connectivity between MPFC and left AG showed significant negative correlations with Hamilton depression rating scale (HDRS) scores. The FcHo values in INS were also negatively correlated with disease duration. Finally, meta-analysis based functional characterization found that these brain areas are mainly involved in emotion, theory of mind and reward processing. ConclusionsOur findings revealed abnormal whole brain FcHo in INS and MPFC and functional interactions between MPFC and AG in MDD and suggested that dysfunctions of INS and MPFC play an important role in the neuropathology of MDD.

Heart rate variability changes in major depressive disorder during sleep: Fractal index correlates with BDI score during REM sleep

We investigated the relationship between autonomic nervous system activity during each sleep stage and the severity of depressive symptoms in patients with major depressive disorder (MDD) and healthy control subjects. Thirty patients with MDD and thirty healthy control subjects matched for sex, age, and body mass index completed standard overnight polysomnography. Depression severity was assessed using the Beck Depression Inventory (BDI). Time- and frequency-domain, and fractal HRV parameters were derived from 5-min electrocardiogram segments during light sleep, deep sleep, rapid eye movement (REM) sleep, and the pre- and post-sleep wake periods. Detrended fluctuation analysis (DFA) alpha-1 values during REM sleep were significantly higher in patients with MDD than in control subjects, and a significant correlation existed between DFA alpha-1 and BDI score in all subjects. DFA alpha-1 was the strongest predictor for the BDI score, along with REM density as a covariate. This study found that compared with controls, patients with MDD show reduced complexity in heart rate during REM sleep, which may represent lower cardiovascular adaptability in these patients, and could lead to cardiac disease. Moreover, DFA alpha-1 values measured during REM sleep may be useful as an indicator for the diagnosis and monitoring of depression.

Reduction in serum IL-1β, IL-6, and IL-18 levels and Beck Depression Inventory-II score by combined sertraline and ketoprofen administration in major depressive disorder: A clinical trial

BackgroundThe immunological changes in major depressive disorder (MDD) and the use of some anti-inflammatory drugs as adjuvant treatment to some antidepressants have been mentioned in many studies. The effect of nonsteroidal anti-inflammatory drug ketoprofen on depression was studied previously in animals only. Aim of the studyThe adjuvant effect of ketoprofen on the antidepressant effect of sertraline in patients with MDD was examined by a follow-up study. The effect of the drug combination on the serum level of interleukin (IL)-1ß, IL-6, and IL-18 in patients with MDD was also investigated. MethodsOut of 140 patients with MDD included in the study, 34 were followed up for 2 months of treatment combining sertraline and ketoprofen. The cytokine levels and Beck Depression Inventory-II scores of the patients with MDD were compared with those of 40 healthy controls. All cytokine levels were measured with ELISA. ResultsThe serum IL-1ß, IL-6, and IL-18 levels in patients with MDD increased and became significantly higher than those of the controls (p < 0.05). The follow-up study indicated that the MDD group treated with the drug combination exhibited lower cytokine levels and Beck score compared the group that treated with sertraline alone. ConclusionKetoprofen enhances the treatment outcome of patients with MDD and reduces the level of immunological markers by its anti-inflammatory properties. This study also further confirms the inflammatory changes in MDD and may attract attention on the use of anti-inflammatory drugs as adjuvant therapy in MDD.

A comprehensive regional neurochemical theory in depression: a protocol for the systematic review and meta-analysis of 1H-MRS studies in major depressive disorder

BackgroundMagnetic resonance spectroscopy (MRS) is a non-invasive analytical technique that investigates the presence and concentrations of brain metabolites. In the context of major depressive disorder (MDD), MRS has revealed regional biochemical changes in GABA, glutamate, and choline across different brain compartments. Technical and methodological advances in MRS data acquisition, in particular proton-based 1H-MRS, have resulted in a significant increase in the incidence of reports utilizing the technique for psychiatric disorder research and diagnosis. The most recent comprehensive meta-analysis reviewing MRS in MDD stems from 2006. Using contemporary systemic reviews and meta-analysis, the aim is to first test a neurochemical circuit-based theory of depression and then to determine if clinical scores relate to metabolite concentrations before and during treatment.MethodsRegion-specific metabolite changes in MDD will be assessed by systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Inclusion criteria will include participant age (18 to 65), English language studies, known regions of interest, and detailed documentation of 1H-MRS procedures. Reported brain regions will be standardized according neuroanatomical expertise allowing increased power of the meta-analysis. Regions of interest will initially include the hippocampus, thalamus, prefrontal cortex, anterior and posterior cingulate gyri, parietal lobe, and basal ganglia. Exclusion criteria will include comorbid psychiatric illness and drug use. Two independent reviewers will undertake all data extraction, while a third reviewer will check for reviewer discrepancies. Statistical analysis will be performed using STATA supplemented by Metan software and SPSS.DiscussionThis data will shed new light on the biochemical basis of depression in different brain regions, thereby highlighting the potential of MRS in identifying biomarkers and generating models of MDD and treatment response.Systematic review registrationPROSPERO CRD42018091494

Effects of tumor necrosis factor-\u03b1 polymorphism on the brain structural changes of the patients with major depressive disorder

Single Nucleotide Polymorphic (SNP) variations of proinflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α) have been reported to be closely associated with the major depressive disorder (MDD). However, it is unclear if proinflammatory genetic burden adversely affects the regional gray matter volume in patients with MDD. The aim of this study was to test whether rs1799724, an SNP of TNF-α, contributes to the neuroanatomical changes in MDD. In this cross-sectional study, a total of 144 MDD patients and 111 healthy controls (HC) well matched for age, sex and education were recruited from Shanghai Mental Health Center. Voxel-based morphometry (VBM) followed by graph theory based structural covariance analysis was applied to locate diagnosis x genotype interactions. Irrespective of diagnosis, individuals with the high-risk genotype (T-carriers) had reduced volume in left angular gyrus (main effect of genotype). Diagnosis x genotype interaction was exclusively localized to the visual cortex (right superior occipital gyrus). The same region also showed reduced volume in patients with MDD than HC (main effect of diagnosis), with this effect being most pronounced in patients carrying the high-risk genotype. However, neither global nor regional network of structural covariance was found to have group difference. In conclusion, a genetic variation which can increase TNF-α expression selectively affects the anatomy of the visual cortex among the depressed subjects, with no effect on the topographical organization of multiple cortical regions. This supports the notion that anatomical changes in depression are in part influenced by the genetic determinants of inflammatory activity.

Longitudinal brain volume changes in major depressive disorder.

Patients with major depressive disorder (MDD) exhibit gray matter volume (GMV) reductions in limbic regions. Clinical variables-such as the number of depressive episodes-seem to affect volume alterations. It is unclear whether the observed cross-sectional GMV abnormalities in MDD change over time, and whether there is a longitudinal relationship between GMV changes and the course of disorder. We investigated T1 structural MRI images of 54 healthy control (HC) and 37 MDD patients in a 3-Tesla-MRI with a follow-up interval of 3years. The Cat12 toolbox was used to analyze longitudinal data (p < 0.05, FWE-corrected, whole-brain analysis; flexible factorial design). Interaction effects indicated increasing GMV in MDD in the bilateral amygdala, and decreasing GMV in the right thalamus between T1 and T2. Further analyses comparing patients with a mild course of disorder (MCD; 0-1 depressive episode during the follow-up) to patients with a severe course of disorder (SCD; > 1 depressive episode during the follow-up) revealed increasing amygdalar volume in MCD. Our study confirms structural alterations in limbic regions in MDD patients and an association between these impairments and the course of disorder. Thus, we assume that the reported volumetric alterations in the left amygdala (i.e. volumetric normalization) are reversible and apparently driven by the clinical phenotype. Hence, these results support the assumption that the severity and progression of disease influences amygdalar GMV changes in MDD or vice versa.

Problematic eating behaviours, changes in appetite, and weight gain in Major Depressive Disorder: The role of leptin

BackgroundAppetite and weight changes are core symptoms of Major Depressive Disorder (MDD), and those with MDD are at increased risk of obesity, cardiovascular disease and metabolic disorders. Leptin promotes satiety, with leptin dysregulation and resistance noted in obesity. However, the role of leptin in weight changes in MDD is not established. This study investigates leptin levels in relation to appetite and weight changes and problematic eating behaviours in MDD. MethodsPlasma leptin levels, psychopathology and biometrics were compared between participants meeting DSM-5 diagnostic criteria for MDD (n = 63) and healthy controls (n = 60). Depressed participants were also sub-categorised according to increased, decreased or unchanged appetite and weight. The Dutch Eating Behaviour Questionnaire and Yale Food Addiction Scale were examined in a subset of participants with MDD. ResultsFemales with increased appetite/weight had higher leptin levels than those with stable or reduced appetite/weight, however males showed the opposite effect. Leptin levels were positively correlated with problematic eating behaviours. One quarter of the depressed subset, all females, met the Yale criteria for food addiction, approximately double the rates reported in general community samples. LimitationsThe study is limited by a cross sectional design and a small sample size in the subset analysis of eating behaviours. ConclusionsThe results provide new information about associations between leptin, sex-specific weight and appetite changes and problematic eating behaviours, which may be risk factors for cardiovascular and metabolic diseases in MDD, particularly in females. Future longitudinal research investigating leptin as a risk factor for weight gain in MDD is warranted, and may lead to early interventions aimed at preventing weight gain in at-risk individuals.

Elevated hippocampal choline level is associated with altered functional connectivity in females with major depressive disorder: A pilot study

Metabolic and functional alterations in hippocampus have been associated with the pathophysiology of major depressive disorder (MDD). However, how the hippocampal biochemical disruptions lead to dysfunction of limbic-cortical circuit remains unclear. The present pilot study combined magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (rs-fMRI) to investigate the hippocampal metabolic alteration and its relationship with the intrinsic functional connectivity (FC) changes in MDD. Both MRS and fMRI data were obtained from twelve women with MDD and twelve age-matched, healthy women. Bilateral hippocampi were chosen as regions of interest, in which metabolite concentrations of total choline (tCho), N-acetylaspartate and creatine were quantified. Bilateral hippocampal FC to the whole brain and its correlations with hippocampal metabolite concentrations were conducted. Females with MDD showed significantly elevated left hippocampal tCho level, and decreased anti-correlations between the left hippocampus and bilateral superior frontal gyrus (SFG), left inferior frontal gyrus, and right superior temporal gyrus. More importantly, the left hippocampal tCho level was associated with FC to the right SFG and right fusiform gyrus in healthy women, whereas it was significantly associated with FC to the right lingual gyrus in women with MDD. Our findings suggested that regional metabolic alterations in the left hippocampus might be related to the network-level dysfunction.

Elevated peripheral blood glutamate levels in major depressive disorder.

PurposeThere is growing evidence that glutamatergic signaling may be involved in major depressive disorder (MDD). In regard to peripheral blood glutamate changes in MDD, inconsistent findings have been reported. The purpose of the present study was to evaluate whether blood glutamate levels differed between MDD patients and control participants.Materials and methodsWe conducted a systematic review and meta-analysis of 12 association studies between blood glutamate levels and MDD in a total of 529 MDD patients and 590 controls. Subsequently, we conducted subgroup analyses and a meta-regression analysis to examine the sources of potential heterogeneity.ResultsA random effects model showed that blood glutamate levels were significantly higher in MDD patients than in controls (standardized mean difference=0.54, 95% CI=0.27–0.82, p=8.5×10−5) with high heterogeneity (I2=75.0%, p<0.05). Subgroup analyses showed elevated glutamate levels in MDD patients compared with controls in plasma, but not serum studies, and in studies using high-performance liquid chromatography but not with mass spectrometry for glutamate assay. A meta-regression analysis showed no effects of age, gender, medication use, sample size, and published year on blood glutamate levels.ConclusionOur findings suggest that altered glutamate levels may be implicated in MDD, which provides further evidence of glutamatergic dysfunction in MDD.

The effects of 5-HTTLPR and BDNF Val66Met polymorphisms on neurostructural changes in major depressive disorder

The serotonin-transporter-linked polymorphic region (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphism have been implicated in the pathophysiology of major depressive disorder (MDD). We aimed to investigate the effects of genetic variants of the 5-HTTLPR and BDNF Val66Met polymorphisms and their interactions with MDD on cortical volume and white matter integrity. Ninety-five patients with MDD and 65 healthy participants aged 20–65 years were recruited. The subjects were genotyped for the 5-HTTLPR and BDNF Val66Met polymorphisms and scanned with T1-weighted and diffusion tensor imaging. The gray matter volumes of 24 gyri in the prefrontal and anterior cingulate cortices and the fractional anisotropy values of nine white matter tracts in both hemispheres were determined. In the pooled sample of subjects from both groups, 5-HTTLPR L-allele carriers had significantly decreased cortical volume in the right anterior midcingulate gyrus compared to S-allele homozygotes. A significant effect of the interaction of the BDNF Val66Met polymorphism and MDD on the fractional anisotropy values of the right uncinate fasciculus was observed. Our results suggested that these genetic polymorphisms play important roles in the neurostructural changes of emotion-processing regions in subjects with MDD.

Altered cortical functional network in major depressive disorder: A resting-state electroencephalogram study.

BackgroundElectroencephalogram (EEG)-based brain network analysis is a useful biological correlate reflecting brain function. Sensor-level network analysis might be contaminated by volume conduction and does not explain regional brain characteristics. Source-level network analysis could be a useful alternative. We analyzed EEG-based source-level network in major depressive disorder (MDD).MethodResting-state EEG was recorded in 87 MDD and 58 healthy controls, and cortical source signals were estimated. Network measures were calculated: global indices (strength, clustering coefficient (CC), path length (PL), and efficiency) and nodal indices (eigenvector centrality and nodal CC) in six frequency. Correlation analyses were performed between network indices and symptom scales.ResultsAt the global level, MDD showed decreased strength, CC in theta and alpha bands, and efficiency in alpha band, while enhanced PL in alpha band. At nodal level, eigenvector centrality of alpha band showed region dependent changes in MDD. Nodal CCs of alpha band were reduced in MDD and were negatively correlated with depression and anxiety scales.ConclusionDisturbances in EEG-based brain network indices might reflect altered emotional processing in MDD. These source-level network indices might provide useful biomarkers to understand regional brain pathology in MDD.

Distance-dependent alterations in local functional connectivity in drug-naive major depressive disorder

Previous studies using resting-state functional magnetic resonance imaging (fMRI) have found abnormal functional connectivity in patients with major depressive disorder (MDD). Yet, effect of distance thresholds on local functional connectivity changes in MDD is largely unknown. Here, we used resting-state fMRI data and functional connectivity strength (FCS) method to test local functional connectivity differences at different distance thresholds between 47 drug-naive patients with MDD and 47 healthy controls. For the distribution of functional brain hubs with high local FCS, the overall changing trend from distance thresholds of 10mm to 100mm was from lateral to medial. Compared to controls, MDD patients exhibited decreased local FCS independent of distance threshold in the sensorimotor system (postcentral gyrus, paracentral lobule, and supplementary motor area). MDD Patients exhibited increased local FCS in the inferior temporal gyrus at two lower distance thresholds (20mm and 30mm) and a higher distance threshold (100mm). In addition, MDD patients showed increased local FCS in the putamen at higher distance thresholds (80–100mm). These findings suggest that local functional connectivity abnormalities in MDD are dependent on distance thresholds and that future studies should take the distance thresholds into account when measuring local functional connectivity in MDD.

TESC gene-regulating genetic variant (rs7294919) affects hippocampal subfield volumes and parahippocampal cingulum white matter integrity in major depressive disorder

Two recent genome-wide association studies have suggested that rs7294919 is associated with changes in hippocampal volume. rs7294919 regulates the transcriptional products of the TESC gene, which is involved in neuronal proliferation and differentiation. We investigated the interactive effect of rs7294919 and major depressive disorder (MDD) on the volume of the hippocampal subfields and the integrity of the parahippocampal cingulum (PHC). We also investigated the correlation of these structural changes with the DNA methylation status of rs7294919. A total of 105 patients with MDD and 85 healthy control subjects underwent T1-weighted structural magnetic resonance imaging and diffusion tensor imaging. The rs7294919 was genotyped and its DNA methylation status was assessed in all the participants. We analyzed the hippocampal subfield volumes and PHC integrity using FreeSurfer and the Tracts Constrained by Underlying Anatomy (TRACULA) respectively. Significant interactive effects of rs7294919 and MDD were observed in the volumes of the dentate gyrus and CA4. The patients with MDD had increased methylation in two of the three CpG loci of rs7294919, and the methylation of CpG3 was significantly correlated with right PHC integrity in the MDD group. Our results provide neurobiological evidence for the association of rs7294919 with brain structural changes in MDD.

Genetic and environmental influences on the codevelopment among borderline personality disorder traits, major depression symptoms, and substance use disorder symptoms from adolescence to young adulthood.

Although borderline personality disorder (BPD) traits decline from adolescence to adulthood, comorbid psychopathology such as symptoms of major depressive disorder (MDD), alcohol use disorder (AUD), and drug use disorders (DUDs) likely disrupt this normative decline. Using a longitudinal sample of female twins (N = 1,763), we examined if levels of BPD traits were correlated with changes in MDD, AUD, and DUD symptoms from ages 14 to 24. A parallel process biometric latent growth model examined the contributions of genetic and environmental factors to the relationships between developmental components of these phenotypes. Higher BPD trait levels predicted a greater rate of increase in AUD and DUD symptoms, and higher AUD and DUD symptoms predicted a slower rate of decline of BPD traits from ages 14 to 24. Common genetic influences accounted for the associations between BPD traits and each disorder, as well as the interrelationships of AUD and DUD symptoms. Both genetic and nonshared environmental influences accounted for the correlated levels between BPD traits and MDD symptoms, but solely environmental influences accounted for the correlated changes between the two over time. Results indicate that higher levels of BPD traits may contribute to an earlier onset and faster escalation of AUD and DUD symptoms, and substance use problems slow the normative decline in BPD traits. Overall, our data suggests that primarily genetic influences contribute to the comorbidity between BPD features and substance use disorder symptoms. We discuss our data in the context of two major theories of developmental psychopathology and comorbidity.

Efficacy of an active implementation process of a computerized CPG of major depression disorder in primary care

IntroductionThe application of scientific evidence in clinical practice management of Major Depressive Disorder (MDD) is complex. Generally, the usual dissemination process and implementation of Clinical Practice Guidelines (CPG) induce modest changes. A computerized version of a Clinical Practice Guideline for Major Depression (e-CPG-MD) has been integrated in Electronic Clinical Records of Primary Care in Catalonia (Spain). It offers an opportunity to improve clinical results. The design allows access to precise help in the visit itself, improving diagnosis, treatment and follow-up.ObjectivesTo evaluate the effects of a multifaceted implementation process of e-CPG-MD, analysing their use and changes in MDD diagnosis.MethodsA cluster randomized clinical trial was performed in 10 primary care centers (PCC) in Barcelona. In five of ten centers, a multifaceted implementation process of the e-CPG-MD was developed during 6 month. The active process includes: interactive training program, regular feedback audit, educational outreach visits and periodic reminders.ResultsThe multifaceted implementation of e-CPG-MD was associated with a significant increase in use during the first 6 months (4.1% + 3.1% vs. 52.7% + 7.3%, P &lt; 0.001). In the active centers, the MD diagnosis increased significantly (rate quotient = 1.56, P &lt; 0.001) and the proportion of moderate and severe MD increased (13.6% vs 41.1%, P = 0.002).ConclusionsA multifaceted implementation method of e-CPG-MD increased significantly its use in active centers at 6 months. Diagnosis of MDD and the proportion of moderate and severe cases also increased significantly.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Alterations in visual cortical activation and connectivity with prefrontal cortex during working memory updating in major depressive disorder.

The present study examined the impacts of major depressive disorder (MDD) on visual and prefrontal cortical activity as well as their connectivity during visual working memory updating and related them to the core clinical features of the disorder. Impairment in working memory updating is typically associated with the retention of irrelevant negative information which can lead to persistent depressive mood and abnormal affect. However, performance deficits have been observed in MDD on tasks involving little or no demand on emotion processing, suggesting dysfunctions may also occur at the more basic level of information processing. Yet, it is unclear how various regions in the visual working memory circuit contribute to behavioral changes in MDD. We acquired functional magnetic resonance imaging data from 18 unmedicated participants with MDD and 21 age-matched healthy controls (CTL) while they performed a visual delayed recognition task with neutral faces and scenes as task stimuli. Selective working memory updating was manipulated by inserting a cue in the delay period to indicate which one or both of the two memorized stimuli (a face and a scene) would remain relevant for the recognition test. Our results revealed several key findings. Relative to the CTL group, the MDD group showed weaker postcue activations in visual association areas during selective maintenance of face and scene working memory. Across the MDD subjects, greater rumination and depressive symptoms were associated with more persistent activation and connectivity related to no-longer-relevant task information. Classification of postcue spatial activation patterns of the scene-related areas was also less consistent in the MDD subjects compared to the healthy controls. Such abnormalities appeared to result from a lack of updating effects in postcue functional connectivity between prefrontal and scene-related areas in the MDD group. In sum, disrupted working memory updating in MDD was revealed by alterations in activity patterns of the visual association areas, their connectivity with the prefrontal cortex, and their relationship with core clinical characteristics. These results highlight the role of information updating deficits in the cognitive control and symptomatology of depression.

Frontostriatal Connectivity Changes in Major Depressive Disorder After Repetitive Transcranial Magnetic Stimulation: A Randomized Sham-Controlled Study.

The aim of this randomized, sham-controlled study was to investigate the therapeutic effects of underlying neurobiological changes after 2-week repetitive transcranial magnetic stimulation (rTMS) treatment using functional connectivity magnetic resonance imaging in patients with major depression. Twenty-four patients with major depressive disorder diagnosed with DSM-IV-TR criteria were randomly assigned to the active rTMS (n = 13) or sham (n = 11) groups from January 2009 to June 2011. rTMS was given for 2 weeks at 110% of the motor threshold for 10 minutes at 10 Hz over the left dorsolateral prefrontal cortex (DLPFC). Resting state functional connectivity was evaluated before and after rTMS. The 17-item Hamilton Depression Rating Scale (HDRS) was administered, and neurocognitive tasks were performed. We examined between-group differences in functional connectivity changes from the bilateral DLPFC. Participants in the active rTMS group showed significant clinical improvement in HDRS scores compared to those in the sham group (P < .001). After 2-week rTMS, there were significant differences in changes in DLPFC-left caudate connectivity (corrected P < .05): the active group showed a greater reduction of connectivity strength between the DLPFC and left caudate compared to the sham group. Reduced levels of DLPFC-left caudate connectivity predicted improvement in depressive symptoms (r = 0.58, P = .001). Additionally, a positive correlation between residual depressive symptoms and connectivity strength after 2-week rTMS was found (r = 0.46, P = .023). High-frequency rTMS over the left DLPFC showed therapeutic effects in patients with major depression. The therapeutic effect of rTMS is related to the modulation of functional connectivity in the frontostriatal network. ClinicalTrials.gov identifier: NCT01325831​.