抑郁伴创伤人群的任务态核磁结果

人类不可避免地会经历各种应激事件，这些事件会引发一连串的神经内分泌反应，可能会影响大脑功能，并导致精神病理症状。先前研究表明，个体在重复应激下前额叶到边缘系统区域表现出持续的失活。然而，这一结论尚未在脑网络层面得到验证。该研究采用ScanSTRESS范式诱发应激，使用ROI-to-ROI的功能连接分析方法探讨重复应激下大脑网络间交互模式的动态变化。结果表明，突显网络充当信息中枢，突显网络内部，突显网络同视觉网络以及感觉运动网络的功能连接皆发生显著的上升。这种动态上升的幅度和应激反应的关系受到个体行为激活系统的调节。

随着心理健康问题在青少年群体中日益严重，尤其是与童年创伤相关的抑郁障碍，研究者们对有效的治疗方法愈发关注。近年来，EMDR作为一种有效的创伤治疗方法，逐渐被应用于复杂创伤后应激障碍(cPTSD)及相关抑郁症状的干预中。通过整合现有研究，本文重点探讨了EMDR在缓解抑郁症状、改善情绪调节和促进认知重构方面的有效性；同时，分析了EMDR的神经生物学机制，并与其他创伤疗法进行比较，分析了各自的优势与局限。此外，文章还讨论了治疗策略的阶段性设计及未来研究方向，以期为临床实践提供理论依据，促进针对童年创伤青少年抑郁障碍的精准治疗。

替代性社会排斥是一种消极的社会互动现象，会对个体的情绪及基本需求造成威胁。童年期的创伤经历可能会使个体对替代性社会排斥更敏感，进而影响后续的行为反应。本研究使用改编的线上替代性社会排斥范式，考察童年期创伤组与健康控制组观察他人遭受排斥后情绪及基本需求评分的变化，同时记录参与者后续选择被排斥者合作的次数。结果发现，与健康控制组相比，童年期创伤组在经历替代性社会排斥后对自我以及受排斥者的情绪评价更消极，并在选人合作环节更多地选择受排斥者。结果提示童年期创伤个体在替代性社会排斥中产生了更强烈的情绪反应，并愿意做出更多的亲社会补偿行为，以缓解社会排斥中带来的痛苦体验。

反刍思维是一种消极认知方式，与精神疾病密切相关，严重影响个体的心理健康水平。研究表明，反刍思维使个体对消极信息具有注意偏向，无法脱离消极信息和控制注意过程，并削弱了抑制无关信息的加工能力。反刍思维具有独特的认知神经机制，它与前额叶皮层密切相关，还涉及杏仁核和皮质醇等生理因素，对奖赏更加敏感。未来的研究可以进一步探索反刍思维的发展机制和个体差异。

抑郁障碍是最常见的精神疾病之一，快感缺乏是其核心症状，是指愉快体验能力的降低，在抑郁障碍患者中普遍存在，被证实是抗抑郁治疗预后差的预测因子，随着功能磁共振技术的发展，越来越多通过该方法的研究发现，具有快感缺乏的抑郁障碍患者与正常人相比，大脑奖赏网络各个脑区的功能变化存在差异，本文对具有快感缺乏的抑郁患者的奖赏网络内不同脑区功能变化的研究开展叙述。

... 抑郁、创伤后应激障碍、自伤自杀、物质滥用等心理行为问题相关(何影，2010)。 1.4 ... 奖赏或者避免受到惩罚；内部动机则是指源于个体内心真正的需求，是指向个体 ...

Hippocampal structure is particularly sensitive to trauma and other stressors. However, previous findings linking hippocampal function with trauma-related psychopathology have been mixed. Heterogeneity in psychological responses to trauma has not been considered with respect to hippocampal function and may contribute to mixed findings. To address these issues, we examined associations between data-driven symptom dimensions and episodic memory formation, a key function of the hippocampus, in a trauma-exposed sample. Symptom dimensions were defined using principal components analysis (PCA) in 3881 trauma-exposed African-American women recruited from primary care waiting rooms of a large urban hospital. Hippocampal and amygdala function were subsequently investigated in an fMRI study of episodic memory formation in a subset of 54 women. Participants viewed scenes with neutral, negative, and positive content during fMRI, and completed a delayed cued recall task. PCA analysis produced five symptom dimensions interpreted as reflecting negative affect, somatic symptoms, re-experiencing, hyper-arousal, and numbing. <i>Re</i>-experiencing was the only symptom type associated with hippocampal function, predicting increased memory encoding-related activation in the hippocampus as well as the amygdala. In contrast, the negative affect component predicted lower amygdala activation for subsequently recalled scenes, and lower functional coupling with other important memory-related regions including the precuneus, inferior frontal gyrus, and occipital cortex. Symptom dimensions were not related to hippocampal volume. The fMRI findings for re-experiencing versus negative affect parallel differences in behavioral memory phenomena in PTSD versus MDD, and highlight a need for more complex models of trauma-related pathology.

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In the context of chronic childhood emotional maltreatment (CEM; emotional abuse and/or neglect), adequately responding to facial expressions is an important skill. Over time, however, this adaptive response may lead to a persistent vigilance for emotional facial expressions. The amygdala and the medial prefrontal cortex (mPFC) are key regions in face processing. However, the neurobiological correlates of face processing in adults reporting CEM are yet unknown. We examined amygdala and mPFC reactivity to emotional faces (Angry, Fearful, Sad, Happy, Neutral) vs scrambled faces in healthy controls and unmedicated patients with depression and/or anxiety disorders reporting CEM before the age of 16 years (n = 60), and controls and patients who report no childhood abuse (n = 75). We found that CEM was associated with enhanced bilateral amygdala reactivity to emotional faces in general, and independent of psychiatric status. Furthermore, we found no support for differential mPFC functioning, suggesting that amygdala hyper-responsivity to emotional facial perception in adults reporting CEM may be independent from top-down influences of the mPFC. These findings may be key in understanding the increased emotional sensitivity and interpersonal difficulties, that have been reported in individuals with a history of CEM.

Childhood maltreatment is strongly associated with depression, which is characterized by reduced reactivity to reward. Identifying factors that mitigate risk for depression in maltreated children is important for understanding etiological links between maltreatment and depression as well as improving early intervention and prevention. We examine whether high reward reactivity at behavioral and neurobiological levels is a marker of resilience to depressive symptomology in adolescence following childhood maltreatment. A sample of 59 adolescents (21 with a history of maltreatment; Mean Age = 16.95 years, SD = 1.44) completed an fMRI task involving passive viewing of emotional stimuli. BOLD signal changes to positive relative to neutral images were extracted in basal ganglia regions of interest. Participants also completed a behavioral reward-processing task outside the scanner. Depression symptoms were assessed at the time of the MRI and again 2 years later. Greater reward reactivity across behavioral and neurobiological measures moderated the association of maltreatment with baseline depression. Specifically, faster reaction time (RT) to cues paired with monetary reward relative to those unpaired with reward and greater BOLD signal in the left pallidum was associated with lower depression symptoms in maltreated youth. Longitudinally, greater BOLD signal in the left putamen moderated change in depression scores over time, such that higher levels of reward response were associated with lower increases in depression over time among maltreated youths. Reactivity to monetary reward and positive social images, at both behavioral and neurobiological levels, is a potential marker of resilience to depression among adolescents exposed to maltreatment. These findings add to a growing body of work highlighting individual differences in reactivity to reward as a core neurodevelopmental mechanism in the etiology of depression. (PsycINFO Database Record

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Reports an error in "Neurobehavioral markers of resilience to depression amongst adolescents exposed to child abuse" by Meg J. Dennison, Margaret A. Sheridan, Daniel S. Busso, Jessica L. Jenness, Matthew Peverill, Maya L. Rosen and Katie A. McLaughlin (<i>Journal of Abnormal Psychology</i>, 2016[Nov], Vol 125[8], 1201-1212). In the article there was an error in the title. The word "Adolescents" was singular. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2016-52992-014.) Childhood maltreatment is strongly associated with depression, which is characterized by reduced reactivity to reward. Identifying factors that mitigate risk for depression in maltreated children is important for understanding etiological links between maltreatment and depression as well as improving early intervention and prevention. We examine whether high reward reactivity at behavioral and neurobiological levels is a marker of resilience to depressive symptomology in adolescence following childhood maltreatment. A sample of 59 adolescents (21 with a history of maltreatment; Mean Age = 16.95 years, SD = 1.44) completed an fMRI task involving passive viewing of emotional stimuli. BOLD signal changes to positive relative to neutral images were extracted in basal ganglia regions of interest. Participants also completed a behavioral reward-processing task outside the scanner. Depression symptoms were assessed at the time of the MRI and again 2 years later. Greater reward reactivity across behavioral and neurobiological measures moderated the association of maltreatment with baseline depression. Specifically, faster reaction time (RT) to cues paired with monetary reward relative to those unpaired with reward and greater BOLD signal in the left pallidum was associated with lower depression symptoms in maltreated youth. Longitudinally, greater BOLD signal in the left putamen moderated change in depression scores over time, such that higher levels of reward response were associated with lower increases in depression over time among maltreated youths. Reactivity to monetary reward and positive social images, at both behavioral and neurobiological levels, is a potential marker of resilience to depression among adolescents exposed to maltreatment. These findings add to a growing body of work highlighting individual differences in reactivity to reward as a core neurodevelopmental mechanism in the etiology of depression. (PsycINFO Database Record

Background Childhood maltreatment is a potent predictor of poor mental health across the life span. We argue that there is a need to improve the understanding of the mechanisms that confer psychiatric vulnerability following maltreatment, if we are to progress from simply treating those with a manifest disorder, to developing effective preventative approaches that can help offset the likelihood that such disorders will emerge in the first place. Methods We review extant functional neuroimaging studies of children and adolescents exposed to early neglect and/or maltreatment, including physical, sexual and emotional abuse across four neurocognitive domains: threat processing, reward processing, emotion regulation and executive control. Findings are discussed in the context of ‘latent vulnerability’, where alterations in neurocognitive function are considered to carry adaptive value in early adverse caregiving environments but confer long‐term risk. Results Studies on threat processing indicate heightened as well as depressed neural responsiveness in maltreated samples, particularly in the amygdala, thought to reflect threat hypervigilance and avoidance respectively. Studies on reward processing generally report blunted neural response to anticipation and receipt of rewards, particularly in the striatum, patterns associated with depressive symptomatology. Studies on emotion regulation report increased activation of the anterior cingulate cortex (ACC) during active emotion regulation, possibly reflecting greater effortful processing. Finally, studies of executive control report increased dorsal ACC activity during error monitoring and inhibition. Conclusions An emerging body of work indicates that altered neurocognitive functioning following maltreatment: (a) is evident even in the absence of overt psychopathology; (b) is consistent with perturbations seen in individuals presenting with psychiatric disorder; (c) can predict future psychiatric symptomatology. These findings suggest that maltreatment leads to neurocognitive alterations that embed latent vulnerability to psychiatric disorder, establishing a compelling case for identifying those children at most risk and developing mechanistically informed models of preventative intervention. Such interventions should aim to offset the likelihood of any future psychiatric disorder.

Maltreatment is associated with heightened neural response to positive and negative facial affect, even to stimuli outside awareness. This may represent a latent neural risk factor for future psychiatric disorder.

Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression.

The recently discovered default mode network (DMN) is a group of areas in the human brain characterized, collectively, by functions of a self-referential nature. In normal individuals, activity in the DMN is reduced during nonself-referential goal-directed tasks, in keeping with the folk-psychological notion of losing one's self in one's work. Imaging and anatomical studies in major depression have found alterations in both the structure and function in some regions that belong to the DMN, thus, suggesting a basis for the disordered self-referential thought of depression. Here, we sought to examine DMN functionality as a network in patients with major depression, asking whether the ability to regulate its activity and, hence, its role in self-referential processing, was impaired. To do so, we asked patients and controls to examine negative pictures passively and also to reappraise them actively. In widely distributed elements of the DMN [ventromedial prefrontal cortex prefrontal cortex (BA 10), anterior cingulate (BA 24/32), lateral parietal cortex (BA 39), and lateral temporal cortex (BA 21)], depressed, but not control subjects, exhibited a failure to reduce activity while both looking at negative pictures and reappraising them. Furthermore, looking at negative pictures elicited a significantly greater increase in activity in other DMN regions (amygdala, parahippocampus, and hippocampus) in depressed than in control subjects. These data suggest depression is characterized by both stimulus-induced heightened activity and a failure to normally down-regulate activity broadly within the DMN. These findings provide a brain network framework within which to consider the pathophysiology of depression.

In recent years, an explosion of neuroimaging studies has examined cognitive reappraisal, an emotion regulation strategy that involves changing the way one thinks about a stimulus in order to change its affective impact. Existing models broadly agree that reappraisal recruits frontal and parietal control regions to modulate emotional responding in the amygdala, but they offer competing visions of how this is accomplished. One view holds that control regions engage ventromedial prefrontal cortex (vmPFC), an area associated with fear extinction, that in turn modulates amygdala responses. An alternative view is that control regions modulate semantic representations in lateral temporal cortex that indirectly influence emotionrelated responses in the amygdala. Furthermore, while previous work has emphasized the amygdala, whether reappraisal influences other regions implicated in emotional responding remains unknown. To resolve these questions, we performed a meta-analysis of 48 neuroimaging studies of reappraisal, most involving downregulation of negative affect. Reappraisal consistently 1) activated cognitive control regions and lateral temporal cortex, but not vmPFC, and 2) modulated the bilateral amygdala, but no other brain regions. This suggests that reappraisal involves the use of cognitive control to modulate semantic representations of an emotional stimulus, and these altered representations in turn attenuate activity in the amygdala.

While characterization of pathogenetic mechanisms underlying major depression is a fundamental aim of neuroscience research, an equally critical clinical goal is to identify biomarkers that might improve diagnostic accuracy and guide treatment selection for individual patients. To this end, a synthesis of functional neuroimaging studies examining regional metabolic and blood flow changes in depression is presented in the context of a testable limbic-cortical network model. 'Network' dysfunction combined with active intrinsic compensatory processes is seen to explain the heterogeneity of depressive symptoms observed clinically, as well as variations in pretreatment scan patterns described experimentally. Furthermore, the synchronized modulation of these dysfunctional limbic-cortical pathways is considered critical for illness remission, regardless of treatment modality. Testing of response-specific functional relationships among regional 'nodes' within this network using multivariate approaches is discussed, with a perspective aimed at identifying biomarkers of treatment non-response, relapse risk and disease vulnerability. Characterization of adaptive and maladaptive functional interactions among these pathways is seen as a critical step towards future development of evidenced-based algorithms that will optimize the diagnosis and treatment of individual depressed patients.

Four SNPs of the FKBP5 gene interacted with severity of child abuse as a predictor of adult PTSD symptoms. There were no main effects of the SNPs on PTSD symptoms and no significant genetic interactions with level of non-child abuse trauma as predictor of adult PTSD symptoms, suggesting a potential gene-childhood environment interaction for adult PTSD.

In this review, we have described the function of MR and GR in hippocampal neurons. The balance in actions mediated by the two corticosteroid receptor types in these neurons appears critical for neuronal excitability, stress responsiveness, and behavioral adaptation. Dysregulation of this MR/GR balance brings neurons in a vulnerable state with consequences for regulation of the stress response and enhanced vulnerability to disease in genetically predisposed individuals. The following specific inferences can be made on the basis of the currently available facts. 1. Corticosterone binds with high affinity to MRs predominantly localized in limbic brain (hippocampus) and with a 10-fold lower affinity to GRs that are widely distributed in brain. MRs are close to saturated with low basal concentrations of corticosterone, while high corticosterone concentrations during stress occupy both MRs and GRs. 2. The neuronal effects of corticosterone, mediated by MRs and GRs, are long-lasting, site-specific, and conditional. The action depends on cellular context, which is in part determined by other signals that can activate their own transcription factors interacting with MR and GR. These interactions provide an impressive diversity and complexity to corticosteroid modulation of gene expression. 3. Conditions of predominant MR activation, i.e., at the circadian trough at rest, are associated with the maintenance of excitability so that steady excitatory inputs to the hippocampal CA1 area result in considerable excitatory hippocampal output. By contrast, additional GR activation, e.g., after acute stress, generally depresses the CA1 hippocampal output. A similar effect is seen after adrenalectomy, indicating a U-shaped dose-response dependency of these cellular responses after the exposure to corticosterone. 4. Corticosterone through GR blocks the stress-induced HPA activation in hypothalamic CRH neurons and modulates the activity of the excitatory and inhibitory neural inputs to these neurons. Limbic (e.g., hippocampal) MRs mediate the effect of corticosterone on the maintenance of basal HPA activity and are of relevance for the sensitivity or threshold of the central stress response system. How this control occurs is not known, but it probably involves a steady excitatory hippocampal output, which regulates a GABA-ergic inhibitory tone on PVN neurons. Colocalized hippocampal GRs mediate a counteracting (i.e., disinhibitory) influence. Through GRs in ascending aminergic pathways, corticosterone potentiates the effect of stressors and arousal on HPA activation. The functional interaction between these corticosteroid-responsive inputs at the level of the PVN is probably the key to understanding HPA dysregulation associated with stress-related brain disorders. 5. Fine-tuning of HPA regulation occurs through MR- and GR-mediated effects on the processing of information in higher brain structures. Under healthy conditions, hippocampal MRs are involved in processes underlying integration of sensory information, interpretation of environmental information, and execution of appropriate behavioral reactions. Activation of hippocampal GRs facilitates storage of information and promotes elimination of inadequate behavioral responses. These behavioral effects mediated by MR and GR are linked, but how they influence endocrine regulation is not well understood. 6. Dexamethasone preferentially targets the pituitary in the blockade of stress-induced HPA activation. The brain penetration of this synthetic glucocorticoid is hampered by the mdr1a P-glycoprotein in the blood-brain barrier. Administration of moderate amounts of dexamethasone partially depletes the brain of corticosterone, and this has destabilizing consequences for excitability and information processing. 7. The set points of HPA regulation and MR/GR balance are genetically programmed, but can be reset by early life experiences involving mother-infant interaction. 8. (ABSTRACT TRUNCATED)

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In adulthood, stress exposure and genetic risk heighten psychological vulnerability by accelerating neurobiological senescence. To investigate whether molecular and brain network maturation processes play a similar role in adolescence, we analysed genetic, as well as longitudinal task neuroimaging (inhibitory control, incentive processing) and early life adversity (i.e., material deprivation, violence) data from the Adolescent Brain and Cognitive Development study (N = 980, age range: 9-13 years). Genetic risk was estimated separately for Major Depressive Disorder (MDD) and Alzheimer's Disease (AD), two pathologies linked to stress exposure and allegedly sharing a causal connection (MDD-to-AD). Adversity and genetic risk for MDD/AD jointly predicted functional network segregation patterns suggestive of accelerated (GABA-linked) visual/attentional, but delayed (dopamine [D2]/glutamate [GLU5R]-linked) somatomotor/association system development. A positive relationship between brain maturation and psychopathology emerged only among the less vulnerable adolescents, thereby implying that normatively maladaptive neurodevelopmental alterations could foster adjustment among the more exposed and genetically more stress susceptible youths. Transcriptomic analyses suggested that sensitivity to stress may underpin the joint neurodevelopmental effect of adversity and genetic risk for MDD/AD, in line with the proposed role of negative emotionality as a precursor to AD, likely to account for the alleged causal impact of MDD on dementia onset.