Towards individualized psychiatric practice: The legacy of neurotherapeutics

Abstract

In 1997, Freeman Dyson postulated two categories of scientific revolution in his book Imagined Worlds . One kind is a concept-driven revolution, allowing us to explain old things in ways; another kind is tool-driven revolution, allowing us to discover new things that have to be explained. Twenty years later, this perspective still sheds light on the emerging therapeutics in clinical practice. According to the annual report of the American Psychological Association (APA), prevalence of brain disorders is expected to rise tremendously over the coming decades. Taking dementia as an example, with rapid population aging in China, Alzheimers Disease (AD) is expected to have profound impacts on the individuals and society. At present, there are no effective pharmacological treatments to halt or slow the progression of AD. Recent evidence found that non-pharmacological interventions, such as transcranial brain stimulation, are able to improve the cognitive functions and alleviate the psychiatric symptoms. However, given the limited studies, less is known about the underlying mechanisms and the potential tailored treatment with individualized features considered. From the perspective of bioenergetics, brain disorders are due to the disturbance of metabolism or energy, such as entropy. One of the most profound links between metabolism and brain disorders is the dysfunction of mitochondria. Given the responsibility in producing ATP for energy, mitochondria use electrons and protons from molecular oxygen to reduce water and generate proton-motive force to produce ATP from ADP. Because the functioning of our brains only relies on the ATP mitochondria produced, thus when this process is impaired, a variety of brain disorders can occur. From the perspective of physics, four types of energy, including magnetic, electricity, ultrasound and light, can be transformed to the cutting-edge stimulation technologies for exploring brain functions and enhancing the non-pharma- ceutical therapeutics for brain disorders. In this review, we summarized the recent progress of the modality-driven brain stimulations and the state-of-art utility in psychiatric practice. The main interest will focus on the clinical applications of transcranial magnetic stimulation, transcranial electrical stimulation, transcranial focused ultrasound stimulation, transcranial infrared laser stimulation and deep brain stimulation. Except for the empirical evidence, we will also point out the major limitations in the current brain stimulation studies. The framework comprises three innovative points: (1) Heterogeneity: Due to the heterogeneity within clinical population, causal inference with observational data in medical science is nearly impossible without strong assumptions. (2) Lack of key parameters: Scalp-to-cortex distance (SCD), as one of the most important and fundamental parameters of brain imaging and stimulation, has been highlighted in the newly updated guidelines. (3) Monitoring and reporting of the side effects induced by brain stimulation: several reports have mentioned the skin burns, pain and headache during the treatment of brain stimulation. However, we still have no standardized protocol to monitor and record the potential side effects. Taken together, this review introduces an in-depth understanding of the mechanisms of brain stimulation and its applications and future directions in individualized psychiatric practice.