Walther Andreas, Penz Marlene, Ijacic Daniela, Rice Timothy R
Department of Biological Psychology, Technische Universität Dresden, Dresden, Germany.
Department of Clinical Psychology and Psychotherapy, University of Zurich, Zurich, Switzerland.
Front Psychiatry. 2017 Oct 18;8:207. doi: 10.3389/fpsyt.2017.00207. eCollection 2017.
The morbidity and societal burden of youth bipolar spectrum disorders (BSD) are high. These disorders are multisystemic in that adult populations there are clear interactions with inflammatory processes and steroidal physiological systems. There are much less data concerning these areas of study in youth populations with BSD. This is surprising given the association of youth-onset BSD with puberty and its associated physiological changes. In this mini-review, we overview the theoretical role of inflammatory processes and steroidal physiological systems in youth BSD, describe the greater literature in adult populations, detail the literature in youth populations when available, and overview current proposed molecular mechanistic pathways and interaction effects based on the available data. We also attend to the interplay of this complex system with body composition and weight gain, an especially important consideration in relation to the role of second generation antipsychotics as the first line treatment for youth with BSD in major clinical guidelines. A developmental model of early onset BSD for boys is hypothesized with pubertal hormonal changes increasing risk for first (hypo-)manic/depressive episode. The dramatic androgen rise during puberty might be relevant for first onset of BSD in boys. A shift from general hypercortisolism driven by glucocorticoid resistance to hypocortisolism with further disease progression is assumed, while increased levels of inflammation are functionally associated with endocrine dysregulation. The interacting role of overweight body habitus and obesity in youth with BSD further indicates leptin resistance to be a central moderator of the dynamic neurobiology of BSD in youth. The intent of this mini-review is to advance our knowledge of youth BSD as multisystemic disorders with important contributions from endocrinology and immunology based on a developmental perspective. This knowledge can influence current clinical care and more importantly inform future research.
青少年双相谱系障碍（BSD）的发病率和社会负担很高。这些疾病具有多系统性，因为在成年人群中，它们与炎症过程和甾体生理系统存在明显的相互作用。而关于青少年BSD患者这些研究领域的数据要少得多。考虑到青少年期BSD与青春期及其相关生理变化之间的关联，这一点令人惊讶。在本综述中，我们概述了炎症过程和甾体生理系统在青少年BSD中的理论作用，描述了成年人群中更多的文献，详细介绍了现有青少年人群中的文献，并根据现有数据概述了当前提出的分子机制途径和相互作用效应。我们还关注这个复杂系统与身体组成和体重增加之间的相互作用，这在第二代抗精神病药物作为青少年BSD主要临床指南一线治疗药物的作用方面是一个特别重要的考虑因素。我们假设了一个针对男孩的早发性BSD发育模型，青春期激素变化会增加首次（轻）躁狂/抑郁发作的风险。青春期雄激素的急剧上升可能与男孩BSD的首次发病有关。假定随着疾病进展，从由糖皮质激素抵抗驱动的全身性高皮质醇血症转变为低皮质醇血症, 而炎症水平的升高在功能上与内分泌失调相关。超重体型和肥胖在青少年BSD中的相互作用进一步表明，瘦素抵抗是青少年BSD动态神经生物学的核心调节因子。本综述的目的是基于发育视角，增进我们对青少年BSD作为具有内分泌学和免疫学重要贡献的多系统疾病的认识。这些知识可以影响当前的临床护理，更重要的是为未来的研究提供信息。
