Prefrontal cortex function in remitted major depressive disorder

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.

Author(s):  
Brianne Disabato ◽  
Isabelle E. Bauer ◽  
Jair C. Soares ◽  
Yvette Sheline

Unipolar major depressive disorder (MDD) and bipolar disorder (BD) are among the world’s leading causes of disability. This chapter highlights the importance of neuroimaging in understanding their neural mechanisms. Depression affects limbic-corticostriatopallidothalamic regions. Structurally, depressed subjects showed increased volume of lesions in white matter (WMH) and decreased gray matter in prefrontal-striatum, orbitofrontal, anterior cingulate cortices, and hippocampus. Functionally, depressed subjects showed abnormal activation in amygdala and medial prefrontal cortex and dsyconnectivity in executive and emotional networks. BD was associated with frontocingulate, limbic-striatal, and hippocampus abnormalities. Specifically, BD subjects showed increased WMH in frontocortical and subcortical areas and altered microstructure in limbic-striatal, cingulate, thalamus, corpus callosum, and prefrontal regions. Functionally, abnormal activations in dorsolateral prefrontal and ventrolimbic regions, hypoconnectivity in the cinguloinsularopercular, mesoparalimbic, and cerebellar networks, and hyperconnectivity in affective and executive networks were also observed. These studies show congruence. Full integration of them would allow better understanding of mood disorders.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joshua T. Kantrowitz ◽  
Zhengchao Dong ◽  
Matthew S. Milak ◽  
Rain Rashid ◽  
Lawrence S. Kegeles ◽  
...  

AbstractGlutamate (Glu) and gamma-aminobutyric acid (GABA) are implicated in the pathophysiology of major depressive disorder (MDD). GABA levels or GABAergic interneuron numbers are generally low in MDD, potentially disinhibiting Glu release. It is unclear whether Glu release or turnover is increased in depression. Conversely, a meta-analysis of prefrontal proton magnetic resonance spectroscopy (1H MRS) studies in MDD finds low Glx (combination of glutamate and glutamine) in medicated MDD. We hypothesize that elevated Glx or Glu may be a marker of more severe, untreated MDD. We examined ventromedial prefrontal cortex/anterior cingulate cortex (vmPFC/ACC) Glx and glutamate levels using 1H MRS in 34 medication-free, symptomatic, chronically ill MDD patients and 32 healthy volunteers, and GABA levels in a subsample. Elevated Glx and Glu were observed in MDD compared with healthy volunteers, with the highest levels seen in males with MDD. vmPFC/ACC GABA was low in MDD. Higher Glx levels correlated with more severe depression and lower GABA. MDD severity and diagnosis were both linked to higher Glx in vmPFC/ACC. Low GABA in a subset of these patients is consistent with our hypothesized model of low GABA leading to glutamate disinhibition in MDD. This finding and model are consistent with our previously reported findings that the NMDAR-antagonist antidepressant effect is proportional to the reduction of vmPFC/ACC Glx or Glu levels.


2020 ◽  
Vol 29 ◽  
Author(s):  
C. E. Lloyd ◽  
N. Sartorius ◽  
H. U. Ahmed ◽  
A. Alvarez ◽  
S. Bahendeka ◽  
...  

Abstract Aims To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries. Methods People with type 2 diabetes treated in out-patient settings aged 18–65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of ‘upset’) between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables. Results In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS. Conclusion This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.


2021 ◽  
pp. 102883
Author(s):  
Neslihan ALTUNSOY ◽  
Didem SÜCÜLLÜOĞLU DİKİCİ ◽  
Fikret Poyraz ÇÖKMÜŞ ◽  
Hüseyin Murat ÖZKAN ◽  
Kadir AŞÇIBAŞI ◽  
...  

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

RSC Advances ◽  
2016 ◽  
Vol 6 (31) ◽  
pp. 25751-25765 ◽  
Author(s):  
Xinyu Yu ◽  
Shanlei Qiao ◽  
Di Wang ◽  
Jiayong Dai ◽  
Jun Wang ◽  
...  

An untargeted metabolomics study to investigate the metabolome change in plasma, hippocampus and prefrontal cortex (PFC) in an animal model with a major depressive disorder (MDD) had been conducted.


2004 ◽  
Vol 65 (4) ◽  
pp. 492-499 ◽  
Author(s):  
Thomas Frodl ◽  
Eva M. Meisenzahl ◽  
Thomas Zetzsche ◽  
Tom Höhne ◽  
Sandra Banac ◽  
...  

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