Major depression is a heterogeneous disorder regarding clinical and biological characteristics. Whereas low mood is the defining parameter of depression, autonomic/metabolic characteristics differentiate subtypes in terms of increases/decreases in weight/appetite and changes in sleep (e.g., insomnia or hypersomnia). Cardiovascular parameters, including heart rate, heart rate variability, and blood pressure, are regulated by the autonomic nervous system in areas that overlap with areas involved in affect regulation. The NTS is a key regulator for either system. Via NTS-related networks, brain perfusion as well as the perfusion of the choroid plexi (important for immune function) is regulated. This means that autonomic activity feeds back to brain function, therefore, placing autonomic regulation, particularly as it relates to NTS activity, into the center of a model of brain activity regulation may provide a more complete model of brain function in depression.