The sustained stress that triggers depression releases a cascade of hormones linked to shrinkage of the hippocampus, a part of the brain essential for learning and storing and retrieving memories. Prominent changes to other brain areas, including the amygdala, create a sustained tendency to generate negatively coded emotions. Emotions are fleeting responses to stimuli; mood is a more sustained state of emotion.

Conditions and Disorders

In a life-threatening situation, a drug called naloxone can reverse the toxic effects of an opioid overdose. If a drug overdose is the cause of CNS depression, there are medications that can reverse these effects. In small doses, these drugs slow brain function, producing a calm or sleepy feeling.

The emerging role of polyamines in MDD etiology and treatment is another example of how interrelated the different pathways are 225. Polyamines are also important players in the stress response 226 and autophagy, which involves a unique post-translational modification of the eukaryotic translation initiation factor 5A requiring spermidine as an essential substrate 227. Thus, the autophagy inducer spermidine is proposed as a therapeutic strategy in aging and neurological disorders 228, 229, and dietary polyamines are considered to promote health in general 230.

Effects of depression on the digestive system

The most studied form of psychotherapy—cognitive behavioral therapy (CBT)—has been shown to produces long-lasting changes in emotion, cognition, behavior, and somatic symptoms of patients with depression and other mental health conditions. Using functional magnetic resonance imaging (fMRI), researchers find that CBT alters patterns of connections between brain regions, notably in circuits related to the processing of emotions. Two major areas of the brain—the hippocampus (seat of memory) and the cortex (the thinking part of the brain)— undergo shrinkage. Both the size of nerve cells and the number of their connections with other neurons are reduced.

Function

Proinflammatory cytokines have become pathological indicators of MDD, and using the right antioxidants to combat ROS may be a useful method for treating MDD. A recent meta-analysis has shown that the baseline default mode network connectivity in patients with depression can predict the clinical responses to treatments including cognitive behavioral therapy, pharmacotherapy, ECT, rTMS, and transcutaneous vagus nerve stimulation 164. However, so far, the biomarkers that predict treatment response at the individual level have not been well applied in the clinic, and there is still a lot of work to be conducted in the future. ECT is one of most effective treatments for depression, with the implementation of safer equipment and advancement of techniques such as modified ECT 153. Mounting evidence from randomized controlled trial (RCT) and meta-analysis studies has shown that rTMS can treat depressive patients with safety 154.

A study found that whereas cysteine and 1-methylinosine levels were much higher in males with MDD, they were significantly lower in females with MDD.456 These metabolites are related to OS. Genetic, molecular, and neuroimaging studies continue to increase our understanding of the neurobiological basis of depression. However, it is still not clear to what extent the results of neurobiological studies can help improve the clinical and functional prognosis of patients. Therefore, over the past 10 years, the neurobiological study of depression has become an important measure to understand the pathophysiological mechanism and guide the treatment of depression. The pathogenesis of depression is complex and all the hypotheses should be integrated to consider the many interactions between various systems and pathways. Depression is a mood disorder that causes a persistent feeling of sadness and loss of interest.

Support for the relevance of this “gut-brain axis” includes gut microbiome changes in MDD 178. Conversely, nutrient supplementation with probiotics or the Mediterranean diet elicits antidepressant effects in patients 179,180,181. Causality between microbiome alterations and depressive-like behavior can also be inferred from experiments transferring fecal microbiota or specific bacteria 182,183,184,185,186. The nutritional/microbiotic effects on the brain are described through links to established molecular pathways controlling synaptic function 187. Thus, we focus on an eminent example, the pathway of kynurenine, which is a metabolite of the essential amino acid tryptophan (Fig. 5). Together with carbohydrate metabolism, tryptophan is one of the earliest nutritional links to depression first reported more than 60–80 years ago 188.

It’s long been known that prolonged or excessive outpouring of stress hormones curbs the growth of nerve cells, particularly in the hippocampus, seat of memory and learning.Such changes are reflected in a smaller size hippocampus and impaired memory in depressed patients. Some types of brain imaging, such as CT scans and magnetic resonance imaging (MRI), take static pictures of the brain to determine whether any specific structures are larger or smaller than normal in depressed patients. Positron emission tomography (PET) scans and functional magnetic resonance imaging (fMRI) look at the brain in action, to see whether and where there are problems in the way the brain processes specific types of information. Such stress dysregulates the normal stress response through the overproduction of cortisol.

1. Depressants are widely used throughout the world as prescription medicines and illicit substances.
2. Cortisol is especially toxic to cells in the brain’s hippocampus, and one consequence of uncontrolled stress is shrinkage of the hippocampus, manifest in the impaired memory and learning that are characteristic of depression.
3. Recently, increasing evidence has shown that pathological changes in a single cell type or brain region limited are insufficient explain the pathogenesis of MDD.
4. People ages living with mild-to-major depression have a higher risk of developing atherosclerotic cardiovascular disease (CVD) for a period of 10 years.

The severity of CNS depression is influenced by the dose, the patient’s age and his clinical status prior to central nervous system depression ingestion as well as co-ingestion of other CNS depressants, as recently reviewed 11. Central nervous system depression may progress to its fourth and most dangerous stage. Stupor typically develops and may progress to seizures, coma, cardiopulmonary arrest, or death (20,46). It is estimated that more than 20% of individuals who die from SSDS have no prior history of solvent abuse (18).