Neuronal correlates of depression

Abstract

Major depressive disorder (MDD) is a common psychiatric disorder effecting approximately 121 million people worldwide and recent reports from the World Health Organization (WHO) suggest that it will be the leading contributor to the global burden of diseases. At present the most commonly used treatment strategies are still based on the monoamine hypothesis that has been the predominant theory in the last 60 years. Clinical observations that only a subset of depressed patients exhibits full remission when treated with classical monoamine-based antidepressants together with the fact that patients exhibit multiple symptoms suggest that the pathophysiology leading to mood disorders may differ between patients. Accumulating evidence indicates that depression is a neural circuit disorder and that onset of depression may be located at different regions of the brain involving different transmitter systems and molecular mechanisms. This review synthesizes findings from rodent studies from which emerges a role for different, yet interconnected, molecular systems and associated neural circuits to the etiology of depression.

Cerebral microbleeds and neuropsychiatric symptoms in an elderly Asian cohort

“…Depression and disinhibition could be due to disorders in neural circuitry, involving different neurotransmitter systems and molecular mechanisms 23. The various parts of the brain involved in depression include the cortex (dorsal and medial prefrontal cortex, dorsal and ventral anterior cingulate cortex, orbital frontal cortex and the insula), subcortical limbic regions (amygdala, hippocampus, dorsomedial thalamus) and basal ganglia (striatum) 24.…”

The link between long noncoding RNAs and depression

“…Loss of hippocampal neurons is found in some depressed individuals and correlates with impaired memory and dysthymic mood (Sheline et al, 2003). Many other signaling pathways have also been reported to play important roles in the pathogenesis of MDD, such as hypothalamic-pituitary-adrenal (HPA)-axis, inflammatory pathways (Martin et al, 2015), the mammalian target of rapamycin (mTOR) signaling pathway (Jia and Le, 2015;Jernigan et al, 2011), and the extracellular signal-regulated kinase/ CREB/BDNF pathway (Wang et al, 2013), apoptosis (Miguel-Hidalgo et al, 2014), autophagy (Jia and Le, 2015;Gassen et al, 2015) and so on (for review, see (Chaudhury et al, 2015;Menard et al, 2015)). These evidences support the hypothesis that risk factors, which disrupt neuronal function and morphology resulting in dysfunction of the neural circuitry underlying the mood regulation and cognitive function through converging molecular and cellular mechanisms, may all contribute to the pathophysiology of MDD and are potential targets of antidepressants.…”

Proteomic investigation of the prefrontal cortex in the rat clomipramine model of depression

“…Still, most of the obtainable and effectively used medications are based on elevation of monoamine levels in line with the monoamine hypothesis of depression [4][5][6]. It is unknown, however, why mood improving effects of the medications appear only after several weeks of treatment, and depression cannot be initiated by reducing the levels of the monoamines in a healthy subject [7].…”

“…Neonatal rat pups, chronically treated with clomipramine or the selective serotonin reuptake inhibitor (SSRI) citalopram, demonstrated persistent changes in behavior in adulthood (which phenomenon A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 5 was named "neonatal antidepressant exposure syndrome" (NADES)) including characteristics of depression-like behaviors and changes in sleep pattern of adult rats [17][18][19][20]. In the clomipramine model, altered expression of 5-HT1A receptor was recently demonstrated, which is in accordance with the monoamine hypothesis of depression [21].…”