共查询到10条相似文献，搜索用时 187 毫秒
1.
Michael S. Gaffrey Deanna M. Barch Ryan Bogdan Katrina Farris Steven E. Petersen Joan L. Luby 《Neuropsychopharmacology》2018,83(2):128-136
Background
Research in adolescents and adults has suggested that altered neural processing of reward following early life adversity is a highly promising depressive intermediate phenotype. However, very little is known about how stress response, neural processing of reward, and depression are related in very young children. The present study examined the concurrent associations between cortisol response following a stressor, functional brain activity to reward, and depression severity in children 4 to 6 years old.Methods
Medication-naïve children 4 to 6 years old (N = 52) participated in a study using functional magnetic resonance imaging to assess neural reactivity to reward, including gain, loss, and neutral outcomes. Parent-reported child depression severity and child cortisol response following stress were also measured.Results
Greater caudate and medial prefrontal cortex reactivity to gain outcomes and increased amygdala reactivity to salient (i.e., both gain and loss) outcomes were observed. Higher total cortisol output following a stressor was associated with increased depression severity and reduced amygdala reactivity to salient outcomes. Amygdala reactivity was also inversely associated with depression severity and was found to mediate the relationship between cortisol output and depression severity.Conclusions
Results suggest that altered neural processing of reward is already related to increased cortisol output and depression severity in preschoolers. These results also demonstrate an important role for amygdala function as a mediator of this relationship at a very early age. Our results further underscore early childhood as an important developmental period for understanding the neurobiological correlates of early stress and increased risk for depression. 相似文献2.
Alice M. Graham Jerod M. Rasmussen Marc D. Rudolph Christine M. Heim John H. Gilmore Martin Styner Steven G. Potkin Sonja Entringer Pathik D. Wadhwa Damien A. Fair Claudia Buss 《Neuropsychopharmacology》2018,83(2):109-119
Background
Maternal inflammation during pregnancy increases the risk for offspring psychiatric disorders and other adverse long-term health outcomes. The influence of inflammation on the developing fetal brain is hypothesized as one potential mechanism but has not been examined in humans.Methods
Participants were adult women (N = 86) who were recruited during early pregnancy and whose offspring were born after 34 weeks’ gestation. A biological indicator of maternal inflammation (interleukin-6) that has been shown to influence fetal brain development in animal models was quantified serially in early, mid-, and late pregnancy. Structural and functional brain magnetic resonance imaging scans were acquired in neonates shortly after birth. Infants’ amygdalae were individually segmented for measures of volume and as seeds for resting state functional connectivity. At 24 months of age, children completed a snack delay task to assess impulse control.Results
Higher average maternal interleukin-6 concentration during pregnancy was prospectively associated with larger right amygdala volume and stronger bilateral amygdala connectivity to brain regions involved in sensory processing and integration (fusiform, somatosensory cortex, and thalamus), salience detection (anterior insula), and learning and memory (caudate and parahippocampal gyrus). Larger newborn right amygdala volume and stronger left amygdala connectivity were in turn associated with lower impulse control at 24 months of age, and mediated the association between higher maternal interleukin-6 concentrations and lower impulse control.Conclusions
These findings provide new evidence in humans linking maternal inflammation during pregnancy with newborn brain and emerging behavioral phenotypes relevant for psychiatric disorders. A better understanding of intrauterine conditions that influence offspring disease susceptibility is warranted to inform targeted early intervention and prevention efforts. 相似文献3.
Olivier Bodart Enrico Amico Francisco Gómez Adenauer G. Casali Sarah Wannez Lizette Heine Aurore Thibaut Jitka Annen Melanie Boly Silvia Casarotto Mario Rosanova Marcello Massimini Steven Laureys Olivia Gosseries 《Brain stimulation》2018,11(2):358-365
Background
Previous studies have separately reported impaired functional, structural, and effective connectivity in patients with disorders of consciousness (DOC). The perturbational complexity index (PCI) is a transcranial magnetic stimulation (TMS) derived marker of effective connectivity. The global fractional anisotropy (FA) is a marker of structural integrity. Little is known about how these parameters are related to each other.Objective
We aimed at testing the relationship between structural integrity and effective connectivity.Methods
We assessed 23 patients with severe brain injury more than 4 weeks post-onset, leading to DOC or locked-in syndrome, and 14 healthy subjects. We calculated PCI using repeated single pulse TMS coupled with high-density electroencephalography, and used it as a surrogate of effective connectivity. Structural integrity was measured using the global FA, derived from diffusion weighted imaging. We used linear regression modelling to test our hypothesis, and computed the correlation between PCI and FA in different groups.Results
Global FA could predict 74% of PCI variance in the whole sample and 56% in the patients' group. No other predictors (age, gender, time since onset, behavioural score) improved the models. FA and PCI were correlated in the whole population (r = 0.86, p < 0.0001), the patients, and the healthy subjects subgroups.Conclusion
We here demonstrated that effective connectivity correlates with structural integrity in brain-injured patients. Increased structural damage level decreases effective connectivity, which could prevent the emergence of consciousness. 相似文献4.
Darrick T. Balu Kendall Taylor Presti Cathy C.Y. Huang Kevin Muszynski Inna Radzishevsky Herman Wolosker Guia Guffanti Kerry J. Ressler Joseph T. Coyle 《Neuropsychopharmacology》2018,83(3):273-283
Background
The amygdala is a central component of the neural circuitry that underlies fear learning. N-methyl-D-aspartate receptor–dependent plasticity in the amygdala is required for pavlovian fear conditioning and extinction. N-methyl-D-aspartate receptor activation requires the binding of a coagonist, D-serine, which is synthesized from L-serine by the neuronal enzyme serine racemase (SR). However, little is known about SR and D-serine function in the amygdala.Methods
We used immunohistochemical methods to characterize the cellular localization of SR and D-serine in the mouse and human amygdala. Using biochemical and molecular techniques, we determined whether trace fear conditioning and extinction engages the SR/D-serine system in the brain. D-serine was administered systemically to mice to evaluate its effect on fear extinction. Finally, we investigated whether the functional single nucleotide polymorphism rs4523957, which is an expression quantitative trait locus of the human serine racemase (SRR) gene, was associated with fear-related phenotypes in a highly traumatized human cohort.Results
We demonstrate that approximately half of the neurons in the amygdala express SR, including both excitatory and inhibitory neurons. We find that the acquisition and extinction of fear memory engages the SR/D-serine system in the mouse amygdala and that D-serine administration facilitates fear extinction. We also demonstrate that the SRR single nucleotide polymorphism, rs4523957, is associated with posttraumatic stress disorder in humans, consistent with the facilitatory effect of D-serine on fear extinction.Conclusions
These new findings have important implications for understanding D-serine–mediated N-methyl-D-aspartate receptor plasticity in the amygdala and how this system could contribute to disorders with maladaptive fear circuitry. 相似文献5.
Anamaria Sudarov Xin-Jun Zhang Leighton Braunstein Eve LoCastro Shawn Singh Yu Taniguchi Ashish Raj Song-Hai Shi Holly Moore M. Elizabeth Ross 《Neuropsychopharmacology》2018,83(6):518-529
Background
Platelet-activating factor acetylhydrolase 1B1 (LIS1), a critical mediator of neuronal migration in developing brain, is expressed throughout life. However, relatively little is known about LIS1 function in the mature brain. We previously demonstrated that LIS1 involvement in the formation and turnover of synaptic protrusions and synapses of young brain after neuronal migration is complete. Here we examine the requirement for LIS1 to maintain hippocampal circuit function in adulthood.Methods
Effects of conditional Lis1 inactivation in excitatory pyramidal neurons, starting in juvenile mouse brain, were probed using high-resolution approaches combining mouse genetics, designer receptor exclusively activated by designer drug technology to specifically manipulate CA1 pyramidal neuron excitatory activity, electrophysiology, hippocampus-selective behavioral testing, and magnetic resonance imaging tractography to examine the connectivity of LIS1-deficient neurons.Results
We found progressive excitatory and inhibitory postsynaptic dysfunction as soon as 10 days after conditional inactivation of Lis1 targeting CA1 pyramidal neurons. Surprisingly, by postnatal day 60 it also caused CA1 histological disorganization, with a selective decline in parvalbumin-expressing interneurons and further reduction in inhibitory neurotransmission. Accompanying these changes were behavioral and cognitive deficits that could be rescued by either designer receptor exclusively activated by designer drug–directed specific increases in CA1 excitatory transmission or pharmacological enhancement of gamma-aminobutyric acid transmission. Lagging behind electrophysiological changes was a progressive, selective decline in neural connectivity, affecting hippocampal efferent pathways documented by magnetic resonance imaging tractography.Conclusions
LIS1 supports synaptic function and plasticity of mature CA1 neurons. Postjuvenile loss of LIS1 disrupts the structure and cellular composition of the hippocampus, its connectivity with other brain regions, and cognition dependent on hippocampal circuits. 相似文献6.
Raphaëlle Richieri Antoine Verger Laurent Boyer Mohamed Boucekine Anthony David Christophe Lançon Michel Cermolacce Eric Guedj 《Brain stimulation》2018,11(5):1093-1097
Background
Previous clinical trials have suggested that repetitive transcranial magnetic stimulation (rTMS) has a significant antidepressant effect in patients with treatment resistant depression (TRD). However, results remain heterogeneous with many patients without effective response.Objective
The aim of this SPECT study was to determine before treatment the predictive value of the connectivity of the stimulated area on further rTMS response in patients with TRD.Methods
Fifty-eight TRD patients performed a brain perfusion SPECT before high frequency rTMS of the left dorsolateral prefrontal cortex (DLPFC). A voxel based-analysis was achieved to compare connectivity of the left DLPFC in responders and non-responders using inter-regional correlations (p?<?0.005, corrected for cluster volume). A multiple logistic regression model was thereafter used with the goal of establishing a predictive score.Results
Before rTMS, responders exhibited increased SPECT connectivity between the left DLPFC and the right cerebellum in comparison to non-responders, independently of age, gender, severity of depression, and severity of treatment resistance. The area under the curve for the combination of these two SPECT clusters to predict rTMS response was 0.756 (p?<?0.005).Conclusions
SPECT connectivity of the left DLPFC predicts rTMS response before treatment. 相似文献7.
Noah S. Philip Jennifer Barredo Mascha van ’t Wout-Frank Audrey R. Tyrka Lawrence H. Price Linda L. Carpenter 《Neuropsychopharmacology》2018,83(3):263-272
Background
Repetitive transcranial magnetic stimulation (TMS) therapy can modulate pathological neural network functional connectivity in major depressive disorder (MDD). Posttraumatic stress disorder is often comorbid with MDD, and symptoms of both disorders can be alleviated with TMS therapy. This is the first study to evaluate TMS-associated changes in connectivity in patients with comorbid posttraumatic stress disorder and MDD.Methods
Resting-state functional connectivity magnetic resonance imaging was acquired before and after TMS therapy in 33 adult outpatients in a prospective open trial. TMS at 5 Hz was delivered, in up to 40 daily sessions, to the left dorsolateral prefrontal cortex. Analyses used a priori seeds relevant to TMS, posttraumatic stress disorder, or MDD (subgenual anterior cingulate cortex [sgACC], left dorsolateral prefrontal cortex, hippocampus, and basolateral amygdala) to identify imaging predictors of response and to evaluate clinically relevant changes in connectivity after TMS, followed by leave-one-out cross-validation. Imaging results were explored using data-driven multivoxel pattern activation.Results
More negative pretreatment connectivity between the sgACC and the default mode network predicted clinical improvement, as did more positive amygdala-to-ventromedial prefrontal cortex connectivity. After TMS, symptom reduction was associated with reduced connectivity between the sgACC and the default mode network, left dorsolateral prefrontal cortex, and insula, and reduced connectivity between the hippocampus and the salience network. Multivoxel pattern activation confirmed seed-based predictors and correlates of treatment outcomes.Conclusions
These results highlight the central role of the sgACC, default mode network, and salience network as predictors of TMS response and suggest their involvement in mechanisms of action. Furthermore, this work indicates that there may be network-based biomarkers of clinical response relevant to these commonly comorbid disorders. 相似文献8.
Mark W. Logue Sanne J.H. van Rooij Emily L. Dennis Sarah L. Davis Jasmeet P. Hayes Jennifer S. Stevens Maria Densmore Courtney C. Haswell Jonathan Ipser Saskia B.J. Koch Mayuresh Korgaonkar Lauren A.M. Lebois Matthew Peverill Justin T. Baker Premika S.W. Boedhoe Jessie L. Frijling Staci A. Gruber Ilan Harpaz-Rotem Rajendra A. Morey 《Neuropsychopharmacology》2018,83(3):244-253
Background
Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)–Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group.Methods
We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium.Results
In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen’s d = ?0.17, p = .00054), and smaller amygdalae (d = ?0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063).Conclusions
Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma. 相似文献9.
10.
Michel M.M. Verheij Candice Contet Peter Karel Judith Latour Rick H.A. van der Doelen Bram Geenen Josephus A. van Hulten Francisca Meyer Tamas Kozicz Olivier George George F. Koob Judith R. Homberg 《Neuropsychopharmacology》2018,83(12):1024-1035