The human hypothalamus in mood disorders: The HPA axis in the center

Abstract

There are no specific structural neuropathological hallmarks found in the brain of mood disorders. Instead, there are molecular, functional and structural alterations reported in many brain areas. The neurodevelopmental underpinning indicated the presence of various genetic and developmental risk factors. The effect of genetic polymorphisms and developmental sequalae, some of which may start in the womb, result in functional changes in a network mediated by neurotransmitters and neuropeptides, which make the emotion- and stress-related brain systems more vulnerable to stressful events. This network of stress-related neurocircuits consists of, for instance, brainstem nuclei, the amygdala, habenula, prefrontal cortex and hypothalamus. Various nuclei of the hypothalamus form indeed one of the crucial hubs in this network. This structure concerns not only the hypothalamo-pituitary-adrenal (HPA) axis that integrate the neuro-endocrine-immune responses to stress, but also other hypothalamic nuclei and systems that play a key role in the symptoms of depression, such as disordered day-night rhythm, lack of reward feelings, disturbed eating, sex, and disturbed cognitive functions. The present review will focus on the changes in the human hypothalamus in depression, with the HPA axis in the center. We will discuss the inordinate network of neurotransmitters and neuropeptides involved, with the hope to find the most vulnerable neurobiological systems and the possible development of tailor-made treatments for mood disorders in the future.

WITHDRAWN: The secret behind peripheral inflammation and depression: The hypothalamus

“…The role of the HPA axis in regulating stress responses and their effects on mood and emotions has been well described 4,5 . In recent years, the importance of the HPA axis for the pathophysiology of various mood disorders such as depression [6][7][8] has been emphasized. Models that support the in uence of the HPA axis on depression postulate chronically dysregulated activation of the HPA axis, which is also associated with dysregulation of immune function [8][9][10][11] .…”

An in‐depth neurobehavioral characterization shows anxiety‐like traits, impaired habituation behavior, and restlessness in male Cryptochrome‐deficient mice

“…For instance, Cryptochromes counteract the activation of glucocorticoid receptors, as it was shown that the reaction to glucocorticoids is significantly enhanced when Cryptochromes are not present. Moreover, the loss of Cry1 and 2 results in constitutively high levels of corticosterone in rodents, suggesting a decreased suppression of the HPA axis, 63 which in turn is highly associated with anxiety and mood disorders 64,65 . Moreover, lack of Cry2 leads to lowered dopamine levels in the striatum of mice 66 .…”

Short photoperiod restores ventral subicular lesion‐induced deficits in affective and socio‐cognitive behavior in male Wistar rats

“…The existing literature suggests that the hippocampus is a prominent inhibitory modulator of the HPA axis (Jacobson & Sapolsky, ) and its ablation or lesion results in hypersecretion of adrenocorticotrophic hormone (ACTH) and corticosterone (Herman et al, ). Further, glucocorticoid imbalance has been implicated in several neuropsychiatric disorders such as anxiety, depression, and BD (Bao & Swaab, ), wherein subicular pathology is implicated. Together, these findings highlight the importance of vSub as an integrative site for stress regulation through the HPA axis, thereby modulating affective behavior and cognition.…”