Social neuroscience in psychiatry: pathways to discovering neurobiological risk and resilience
Social neuroscience in psychiatry: pathways to discovering neurobiological risk and resilience
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精神病学中的社会神经科学：发现神经生物学风险和恢复力的途径
DOI：
10.1002/wps.20123
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发表时间：
2014
期刊：
影响因子：
73.3
通讯作者：
C. Bartholomeusz
中科院分区：
文献类型：
--
作者：
C. Pantelis;C. Bartholomeusz
卡奇奥波等人对社会神经科学可以显著促进我们对精神障碍的理解和治疗的方式进行了深思熟虑的概述。
它们涉及到基因调控、表观遗传学和环境可以改变神经发育轨迹，进而影响社会行为和社会功能的方式。在这里，我们想强调未来研究的重要性，探索发生在青春期2，3的动态社会性大脑变化，作为理解精神障碍在这一关键成熟阶段出现的可能关键，当这种疾病的风险达到顶峰时。
我们实验室最近的工作表明，在12至16岁期间，海马体生长减弱和壳核体积减弱与抑郁症的发病有关4。性别也是一个重要因素，因为女性杏仁核生长过度和男性生长减弱似乎增加了抑郁的风险。考虑到男孩和女孩的神经发育背景与包括社会认知在内的认知的所有方面有关，是了解精神障碍及其神经生物学的必要前提。
社会主题在自闭症谱系障碍(ASD)表征中的突出地位也值得简要讨论。我们最近在ASD 5上的工作与涉及生物学和工程学的跨学科研究相关，并将统计学方法与生物学联系起来。重要的是，虽然大多数研究的重点都是发现此类疾病的神经生物学风险标记，但在我们的研究中，我们也发现了几个对ASD具有保护作用的单核苷酸多态(SNPs)，即可能与疾病的发展弹性有关。
例如，我们发现SNP rs12317962对ASD 5具有保护作用。该SNP位于编码与神经元兴奋性有关的钾通道的基因KCNMB4中，该钾通道在梭形回和关键的社会脑区，即颞叶上皮层、扣带回和眶前叶皮质中高度表达。其他SNP，如CD38中rs3796863的变异，也与杏仁核，特别是梭状回的激活有关。CD38是一种与自闭症相关的基因，已知与催产素分泌有关。我们正在通过神经成像检测等位基因变异对大脑区域的影响，从而在自闭症中进一步开展这项研究。
精神分裂症是另一种涉及社会认知缺陷的障碍。最近的理论认为，多巴胺能和谷氨酸能皮质下-杏仁核-前额叶回路的异常导致显著信号的失调，导致情绪相关的感知、学习和记忆障碍，类似于Ccioppo等人1在抑郁症背景下描述的Phillips等人的模型。
Walter等人的跨学科研究表明，在一项心理任务理论中，SNP rs1344706(基因ZNF804A)的精神病风险变体的携带者在内侧前额叶和左侧临时顶叶皮质以及镜像神经元系统的区域有异常的神经激活。这种来自功能成像的潜在中间表型可能对精神分裂症的社会认知障碍的生物治疗有意义。
从卡乔波等人的论文1中可以明确的一点是，在各种障碍中，常见的社交脑区是功能失调的：杏仁核、眶前皮质、内侧前额叶皮质、颞上沟、前脑岛和前扣带回。然而，它们偏离正常功能的方式(低激活和高激活/两者的混合)取决于正在研究的疾病和所讨论的社会过程。因此，我们不仅应该跨学科，而且应该跨精神障碍进行研究，并在仔细控制的治疗干预的背景下，为与特定疾病的发展相关的风险和复原力因素提供见解。
催产素已被建议作为一种潜在的辅助治疗方法，用于治疗社交焦虑症、自闭症、精神分裂症和边缘人格障碍中常见的社交认知和行为缺陷10。虽然有几个与催产素相关的风险等位基因与社交大脑功能有关，但对催产素在大脑中的作用机制知之甚少。这是未来精神病学研究的一个很有前途的途径。
总而言之，卡乔波等人关于社会神经科学和精神障碍的论文为我们提供了许多思考的食粮。有必要在生物学和其他科学之间进行动态的跨学科(而不仅仅是多学科)交流；评估大脑结构和功能轨迹的变化；将这些动态变化与可能赋予疾病发展风险或韧性的基因联系起来；以及审查调节社会认知的干预措施的影响。所有这些方法及其组合为理解一些影响人类的最具挑战性和最复杂的疾病提供了令人兴奋的前进道路。
Cacioppo et al 1 provide a thoughtful overview of the ways in which social neuroscience can significantly advance our understanding and treatment of mental disorders.
They touch on the way gene regulation, epigenetics and the environment can alter neurodevelopmental trajectories and in turn influence social behavior and social functioning. We would like to emphasize here the importance of future research exploring dynamic social brain changes taking place during adolescence 2,3 as a possible key to understanding the emergence of mental disorders at this critical stage of maturation, when risk for such disorders peaks.
Recent work in our laboratory shows that attenuated growth of the hippocampus and attenuated reduction in putamen volume during age 12 to 16 years are associated with the onset of depression 4. Sex is also a significant factor, since exaggerated amygdala growth in females and attenuated growth in males seems to increase the risk of depression. Taking account of the neurodevelopmental background for boys and girls, relevant to all aspects of cognition, including social cognition, is a necessary prerequisite to understanding mental disorders and their neurobiology.
The prominence of social themes in the characterization of autism spectrum disorders (ASD) also warrants brief discussion. Our recent work on ASD 5 is relevant in being an interdisciplinary study involving biology and engineering, and in linking statistical approaches to biology. Importantly, while the emphasis of most studies has been on discovery of neurobiological risk markers for such disorders, in our study we also identified several single-nucleotide polymorphisms (SNPs) that protected against ASD, that is, might be associated with resilience to development of the disorder.
For example, we found that the SNP rs12317962 protected against ASD 5. This SNP lies in the gene KCNMB4, encoding a potassium channel involved in neuronal excitability, which is highly expressed in the fusiform gyrus and key social brain regions, namely the superior temporal, cingulate and orbitofrontal cortices. Other SNPs, such as variation in rs3796863 in CD38, a gene linked to ASD and known to be involved in oxytocin secretion, has also been linked with activation of the amygdala and in particular the fusiform gyrus, during visual processing of social stimuli in healthy young men 6. We are in the processes of furthering this research in ASD by examining the influence of allelic variation on brain regions using neuroimaging.
Schizophrenia is another disorder that involves deficits in social cognition. Recent theories propose that aberrations in dopaminergic and glutamatergic subcortical-amygdala-prefrontal circuits give rise to dysregulation of salience signaling, causing impairments in emotion-related perception, learning and memory 7, similar to the model of Phillips et al 8 described by Cacioppo et al 1 in the context of depression.
Interdisciplinary research of Walter et al 9 shows that carriers for the psychosis risk variant of the SNP rs1344706 (gene ZNF804A) have abnormal neural activation in the medial prefrontal and left temporo-parietal cortex, as well as in regions of the mirror neuron system, during a theory of mind task. This potential intermediate phenotype derived from functional imaging may have implications for biological treatment of social cognitive impairments in schizophrenia.
One thing that is clear from Cacioppo et al's paper 1 is that, across disorders, common social brain regions are dysfunctional: the amygdala, orbitofrontal cortex, medial prefrontal cortex, superior temporal sulcus, anterior insula and anterior cingulate. Yet, the way in which they deviate from normal functioning (hypo- vs. hyper-activation/mixture of both) depends on the illness being studied and the social processes in question. Therefore, we should study not only across disciplines but also across mental disorders, and in the context of carefully controlled treatment interventions, to provide insights into both risk and resilience factors associated with developing particular disorders.
Oxytocin has been proposed as a potential adjunctive treatment for the social cognitive and behavioural deficits common in social anxiety disorder, ASD, schizophrenia, and borderline personality disorder 10. While there are several oxytocin-related risk alleles that have been linked to social brain functioning, there is little insight into the mechanisms of the actions of oxytocin in the brain. This is a promising avenue for future research in psychiatry.
In conclusion, Cacioppo et al's paper on social neuroscience and mental disorders provides us much food for thought. There is a need for dynamic interdisciplinary (rather than just multidisciplinary) exchange between biological and other sciences; assessing changes in trajectories of brain structure and function; linking these dynamic changes to genes that may bestow risk or resilience to development of illness; and examining the impact of interventions that modulate social cognition. All of these approaches and their combination present exciting ways forward in understanding some of the most challenging and complex disorders affecting human beings.