Rostral Anterior Cingulate Glutamine/Glutamate Disbalance in Major Depressive Disorder Depends on Symptom Severity

2019 ◽  
Vol 4 (12) ◽  
pp. 1049-1058 ◽  
Author(s):  
Lejla Colic ◽  
Felicia von Düring ◽  
Dominik Denzel ◽  
Liliana Ramona Demenescu ◽  
Anton R. Lord ◽  
...  
2019 ◽  
Vol 29 ◽  
pp. S699-S700
Author(s):  
L. Colic ◽  
F. Von Duering ◽  
D. Denzel ◽  
L.R. Demenescu ◽  
A. Lord ◽  
...  

2020 ◽  
pp. 070674372097482
Author(s):  
Shane J. McInerney ◽  
Trisha Chakrabarty ◽  
Malgorzata Maciukiewicz ◽  
Benicio N. Frey ◽  
Glenda M. MacQueen ◽  
...  

Objectives: Major depressive disorder (MDD) is associated with impairments in both cognition and functioning. However, whether cognitive deficits significantly contribute to impaired psychosocial and occupational functioning, independent of other depressive symptoms, is not well established. We examined the relationship between cognitive performance and functioning in depressed patients before and after antidepressant treatment using secondary data from the first Canadian Biomarker Integration Network in Depression-1 study. Methods: Cognition was assessed at baseline in unmedicated, depressed participants with MDD ( n = 207) using the Central Nervous System Vital Signs computerized battery, psychosocial functioning with the Sheehan Disability Scale (SDS), and occupational functioning with the Lam Employment Absence and Productivity Scale (LEAPS). Cognition ( n = 181), SDS ( n = 175), and LEAPS ( n = 118) were reassessed after participants received 8 weeks of open-label escitalopram monotherapy. A series of linear regressions were conducted to determine (1) whether cognitive functioning was associated with psychosocial and occupational functioning prior to treatment, after adjusting for overall depressive symptom severity and (2) whether changes in cognitive functioning after an 8-week treatment phase were associated with changes in psychosocial and occupational functioning, after adjusting for changes in overall symptom severity. Results: Baseline global cognitive functioning, after adjusting for depression symptom severity and demographic variables, was associated with the SDS work/study subscale (β = −0.17; P = 0.03) and LEAPS productivity subscale (β = −0.17; P = 0.05), but not SDS total (β = 0.19; P = 0.12) or LEAPS total (β = 0.41; P = 0.17) scores. Although LEAPS and SDS scores showed significant improvements after 8 weeks of treatment ( P < 0.001), there were no significant associations between changes in cognitive domain scores and functional improvements. Conclusion: Cognition was associated with occupational functioning at baseline, but changes in cognition were not associated with psychosocial or occupational functional improvements following escitalopram treatment. We recommend the use of more comprehensive functional assessments to determine the impact of cognitive change on functional outcomes in future research.


2016 ◽  
Vol 22 (1) ◽  
pp. 113-119 ◽  
Author(s):  
J Ernst ◽  
A Hock ◽  
A Henning ◽  
E Seifritz ◽  
H Boeker ◽  
...  

2012 ◽  
Vol 43 (6) ◽  
pp. 1219-1230 ◽  
Author(s):  
N. L. Nixon ◽  
P. F. Liddle ◽  
G. Worwood ◽  
M. Liotti ◽  
E. Nixon

BackgroundRecent models of major depressive disorder (MDD) have proposed the rostral anterior cingulate (rACC) and dorsomedial prefrontal cortex (dmPFC) as nexus sites in the dysfunctional regulation of cognitive-affective state. Limited evidence from remitted-state MDD supports these theories by suggesting that aberrant neural activity proximal to the rACC and the dmPFC may play a role in vulnerability to recurrence/relapse within this disorder. Here we present a targeted analysis assessing functional activity within these two regions of interest (ROIs) for groups with identified vulnerability to MDD: first, remitted, high predicted recurrence-risk patients; and second, patients suffering observed 1-year recurrence.MethodBaseline T2* images sensitive to blood oxygen level-dependent (BOLD) contrast were acquired from patients and controls during a Go/No-Go (GNG) task incorporating negative feedback, with 1-year patient follow-up to identify recurrence. BOLD contrast data for error commission (EC) and visual negative feedback (VNF) were used in an ROI analysis based on rACC and dmPFC coordinates from the literature, comparing patientsversuscontrols and recurrenceversusnon-recurrenceversuscontrol groups.ResultsAnalysis of patients (n = 20)versuscontrols (n = 20) showed significant right dmPFC [Brodmann area (BA) 9] hypoactivity within the patient group, co-localized during EC and VNF, with additional significant rACC (BA 32) hypoactivity during EC. The results from the follow-up analysis were undermined by small groups and potential confounders but suggested persistent right dmPFC (BA 9) hypoactivity associated with 1-year recurrence.ConclusionsConvergent hypoactive right dmPFC (BA 9) processing of VNF and EC, possibly impairing adaptive reappraisal of negative experience, was associated most clearly with clinically predicted vulnerability to MDD.


2018 ◽  
Author(s):  
Francesca Cormack ◽  
Maggie McCue ◽  
Nick Taptiklis ◽  
Caroline Skirrow ◽  
Emilie Glazer ◽  
...  

BACKGROUND Cognitive symptoms are common in major depressive disorder, and may help to identify patients that need treatment or who are not experiencing adequate treatment response. Digital tools to provide real time data assessing cognitive function could help to support patients treatment and remediation of cognitive and mood symptoms. OBJECTIVE This study examined adherence, feasibility, and validity of a wearable high-frequency cognitive and mood assessment app over 6 weeks, corresponding to when antidepressant pharmacotherapy begins to show efficacy. METHODS Thirty patients (aged 19−63; 19 women) with mild-moderate depression participated. The new Cognition Kit application was delivered via the Apple Watch, providing a high-resolution touch screen display for task presentation and logging responses. Cognition was assessed by the n-back task up to 3 times daily and depressed mood by 3 short questions once daily. Selected tests sensitive to depression from the Cambridge Neuropsychological Test Automated Battery and validated questionnaires of depression symptom severity were administered on 4 occasions (baseline, weeks 1, 3, and 6). Adherence was defined as participants completing at least one assessment daily. RESULTS Adherence was excellent for mood and cognitive assessments (95% and 96%, respectively), did not deteriorate over time, and was not influenced by depression symptom severity or cognitive function at study onset. Daily mood assessments showed good correspondence with validated depression questionnaires (correlations range from .45 to .69 for total daily mood score) and daily cognitive assessments showed good correspondence with cognitive tests sensitive to depression (correlations ranged from .37 to .50 for mean n-back). CONCLUSIONS The study supports the feasibility and validity of high-frequency assessment of cognitive function and mood function using wearable devices over an extended period in patients with major depressive disorder. CLINICALTRIAL clinicaltrials.gov NCT03067506


1992 ◽  
Vol 20 (3) ◽  
pp. 199-212 ◽  
Author(s):  
Lyne Prud'homme ◽  
Pierre Barron

In light of Rational-Emotive Theory, this study was undertaken to determine the pattern of irrational beliefs underlying Major Depressive Disorder (MDD). A total of 126 subjects (50 males, 76 females) volunteered to participate. Patients clinically diagnosed with MDD (unipolar type) and a control group of non-depressed patients were solicited from the inpatient and outpatient facilities of several Ottawa and Montreal hospitals; the normal control group comprised students and civil servants. The subjects completed questionnaires to measure irrational belief endorsement (IBT, RBI) and symptom severity (STAI, BDI) and to verify the depression diganosis (IDD). Multivariate statistics were used to determine the pattern of beliefs which best discriminates between the MDD group, the psychiatric control group, and the normal controls. Discriminant analysis of the IBT revealed a pattern of four irrational beliefs generally known as demand for approval, frustration reactivity, anxious overconcern, and helplessness over past. The implications of such findings for RET theory are discussed.


2012 ◽  
Vol 42 (10) ◽  
pp. 2071-2081 ◽  
Author(s):  
C. G. Davey ◽  
B. J. Harrison ◽  
M. Yücel ◽  
N. B. Allen

BackgroundDepression has been associated with functional alterations in several areas of the cingulate cortex. In this study we have taken a systematic approach to examining how alterations in functional connectivity vary across the functionally diverse subregions of the rostral cingulate cortex.MethodEighteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging (fcMRI), we systematically investigated the functional connectivity of four subregions of the rostral cingulate cortex. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the patient and control groups.ResultsThe depressed participants showed altered patterns of connectivity with ventral cingulate subregions. They showed increased connectivity between subgenual anterior cingulate cortex (ACC) and dorsomedial frontal cortex, with connectivity strength showing positive correlation with illness severity. Depressed participants also showed increased connectivity between pregenual ACC and left dorsolateral frontal cortex, and decreased connectivity between pregenual ACC and the caudate nucleus bilaterally.ConclusionsThe results reinforce the importance of subgenual ACC for depression, and show a close link between brain regions that support self-related processes and affective visceromotor function. The pregenual ACC also has an important role, with its increased connectivity with dorsolateral frontal cortex suggesting heightened cognitive regulation of affect; and reduced connectivity with the caudate nucleus potentially underlying symptoms such as anhedonia, reduced motivation and psychomotor dysfunction.


2019 ◽  
Vol 50 (10) ◽  
pp. 1653-1662 ◽  
Author(s):  
Mathew A. Harris ◽  
Xueyi Shen ◽  
Simon R. Cox ◽  
Jude Gibson ◽  
Mark J. Adams ◽  
...  

AbstractBackgroundSubstantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.MethodsThe present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.ResultsThere was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.ConclusionsOur significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.


2019 ◽  
Vol 45 (4) ◽  
pp. 703-712 ◽  
Author(s):  
Qian Li ◽  
Youjin Zhao ◽  
Ziqi Chen ◽  
Jingyi Long ◽  
Jing Dai ◽  
...  

Abstract Alterations in cortical thickness have been identified in major depressive disorder (MDD), but findings have been variable and inconsistent. To date, no reliable tools have been available for the meta-analysis of surface-based morphometric (SBM) studies to effectively characterize what has been learned in previous studies, and drug treatments may have differentially impacted findings. We conducted a comprehensive meta-analysis of magnetic resonance imaging (MRI) studies that explored cortical thickness in medication-free patients with MDD, using a newly developed meta-analytic mask compatible with seed-based d mapping (SDM) meta-analytic software. We performed the meta-regression to explore the effects of demographics and clinical characteristics on variation in cortical thickness in MDD. Fifteen studies describing 529 patients and 586 healthy controls (HCs) were included. Medication-free patients with MDD, relative to HCs, showed a complex pattern of increased cortical thickness in some areas (posterior cingulate cortex, ventromedial prefrontal cortex, and anterior cingulate cortex) and decreased cortical thickness in others (gyrus rectus, orbital segment of the superior frontal gyrus, and middle temporal gyrus). Most findings in the whole sample analysis were confirmed in a meta-analysis of studies recruiting medication-naive patients. Using the new mask specifically developed for SBM studies, this SDM meta-analysis provides evidence for regional cortical thickness alterations in MDD, mainly involving increased cortical thickness in the default mode network and decreased cortical thickness in the orbitofrontal and temporal cortex.


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