Author name cluster

Philip van Eijndhoven

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4 papers

1 author row

YNICL Journal 2022 Journal Article

Decreased reward circuit connectivity during reward anticipation in major depression

Hanneke Geugies
Nynke A. Groenewold
Maaike Meurs
Bennard Doornbos
Jessica M. de Klerk-Sluis
Philip van Eijndhoven
Annelieke M. Roest
Henricus G. Ruhé

An important symptom of major depressive disorder (MDD) is the inability to experience pleasure, possibly due to a dysfunction of the reward system. Despite promising insights regarding impaired reward-related processing in MDD, circuit-level abnormalities remain largely unexplored. Furthermore, whereas studies contrasting experimental conditions from incentive tasks have revealed important information about reward processing, temporal difference modeling of reward-related prediction error (PE) signals might give a more accurate representation of the reward system. We used a monetary incentive delay task during functional MRI scanning to explore PE-related striatal and ventral tegmental area (VTA) activation in response to anticipation and delivery of monetary rewards in 24 individuals with MDD versus 24 healthy controls (HCs). Furthermore, we investigated group differences in temporal difference related connectivity with a generalized psychophysiological interaction (gPPI) analysis with the VTA, ventral striatum (VS) and dorsal striatum (DS) as seeds during reward versus neutral, both in anticipation and delivery. Relative to HCs, MDD patients displayed a trend-level (p = 0.052) decrease in temporal difference-related activation in the VS during reward anticipation and delivery combined. Moreover, gPPI analyses revealed that during reward anticipation, MDD patients exhibited decreased functional connectivity between the VS and anterior cingulate cortex / medial prefrontal cortex, anterior cingulate gyrus, angular/middle orbital gyrus, left insula, superior/middle frontal gyrus (SFG/MFG) and precuneus/superior occipital gyrus/cerebellum compared to HC. Moreover, MDD patients showed decreased functional connectivity between the VTA and left insula compared to HC during reward anticipation. Exploratory analysis separating medication free patients from patients using antidepressant revealed that these decreased functional connectivity patterns were mainly apparent in the MDD group that used antidepressants. These results suggest that MDD is characterized by alterations in reward circuit connectivity rather than isolated activation impairments. These findings represent an important extension of the existing literature since improved understanding of neural pathways underlying depression-related reward dysfunctions, may help currently unmet diagnostic and therapeutic efforts.

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YNICL Journal 2017 Journal Article

The Global ECT-MRI Research Collaboration (GEMRIC): Establishing a multi-site investigation of the neural mechanisms underlying response to electroconvulsive therapy

Leif Oltedal
Hauke Bartsch
Ole Johan Evjenth Sørhaug
Ute Kessler
Christopher Abbott
Annemieke Dols
Max L Stek
Lars Ersland

Major depression, currently the world's primary cause of disability, leads to profound personal suffering and increased risk of suicide. Unfortunately, the success of antidepressant treatment varies amongst individuals and can take weeks to months in those who respond. Electroconvulsive therapy (ECT), generally prescribed for the most severely depressed and when standard treatments fail, produces a more rapid response and remains the most effective intervention for severe depression. Exploring the neurobiological effects of ECT is thus an ideal approach to better understand the mechanisms of successful therapeutic response. Though several recent neuroimaging studies show structural and functional changes associated with ECT, not all brain changes associate with clinical outcome. Larger studies that can address individual differences in clinical and treatment parameters may better target biological factors relating to or predictive of ECT-related therapeutic response. We have thus formed the Global ECT-MRI Research Collaboration (GEMRIC) that aims to combine longitudinal neuroimaging as well as clinical, behavioral and other physiological data across multiple independent sites. Here, we summarize the ECT sample characteristics from currently participating sites, and the common data-repository and standardized image analysis pipeline developed for this initiative. This includes data harmonization across sites and MRI platforms, and a method for obtaining unbiased estimates of structural change based on longitudinal measurements with serial MRI scans. The optimized analysis pipeline, together with the large and heterogeneous combined GEMRIC dataset, will provide new opportunities to elucidate the mechanisms of ECT response and the factors mediating and predictive of clinical outcomes, which may ultimately lead to more effective personalized treatment approaches.

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YNIMG Journal 2011 Journal Article

Amygdala responsivity related to memory of emotionally neutral stimuli constitutes a trait factor for depression

Philip van Eijndhoven
Guido van Wingen
Guillén Fernández
Mark Rijpkema
Robbert Jan Verkes
Jan Buitelaar
Indira Tendolkar

Episodic memory impairment is considered to be a core cognitive deficit of Major Depressive Disorder (MDD) and has motivated a line of research investigating the role of the amygdala and the hippocampus in depression. While functional neuroimaging studies have focused on memory for emotional but not for neutral stimuli, in order to probe amygdala function, structural imaging studies have tied episodic memory to hippocampal function. We therefore investigated the neural correlates of episodic memory formation for neutral stimuli in 20 patients with a first depressive episode, 20 patients recovered from a first episode and 20 healthy controls. Because there is evidence that the amygdala exhibits hyperactive responses even to neutral stimuli in depressed subjects, we specifically explored the potential role of the amygdala in forming episodic memories with neutral content. Both patient groups showed stronger subsequent memory effects in the amygdala when compared to controls, in the absence of any differences in hippocampal activity between groups. Patients with a first episode of MDD showed increased activity related to episodic memory formation in a fronto-limbic network. These state-related activations may be related to a compensatory mechanism, which is supported by the absence of any differences in memory performance between groups. These findings represent initial evidence for a neurocognitive trait or vulnerability marker of depression—amygdala involvement in episodic memory formation of neutral stimuli.

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YNIMG Journal 2010 Journal Article

The brain-derived neurotrophic factor Val66Met polymorphism affects memory formation and retrieval of biologically salient stimuli

Guido van Wingen
Mark Rijpkema
Barbara Franke
Philip van Eijndhoven
Indira Tendolkar
Robbert Jan Verkes
Jan Buitelaar
Guillén Fernández

Brain-derived neurotrophic factor (BDNF) is involved in memory and the pathophysiology of various neuropsychiatric disorders. A single nucleotide polymorphism in the human BDNF gene (Val66Met) affects memory, and influences Alzheimer's disease and depression vulnerability in a sex-specific manner. Recent animal studies suggest that BDNF mediates memory for emotional experiences in the amygdala, but it is currently unknown whether BDNF Val66Met influences memory processing in the amygdala. Here, we investigated its effect on the successful encoding and recognition of biologically salient stimuli. Forty-seven healthy volunteers memorized and recognized faces while their brain activity was measured with event-related functional MRI. No significant differences in memory performance were observed between Val homozygotes and Met allele carriers. The imaging results demonstrated BDNF genotype×sex interactions in the amygdala during memory formation, and in the prefrontal cortex and posterior cingulate cortex during memory retrieval. Subsequent tests showed a larger contribution of these brain regions to successful encoding and retrieval in male Met allele carriers than male Val homozygotes, whereas no significant differences were observed in females. These results provide preliminary evidence that the BDNF Val66Met polymorphism influences specific mnemonic operations underlying encoding and retrieval of salient stimuli, and suggest less efficient memory processing in male Met allele carriers. Furthermore, the sex-specific genotype effects may contribute to sex-specific effects of BDNF Val66Met on depression vulnerability.

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