Dysregulated Processing of Negative and Positive Responses in Depression
Depression is widely known as a mood disorder which involves symptoms of frequent negative affect, decreased pleasure in activities that one used to enjoy and an increased sense of self-guilt (American Psychiatric Association, 2013). However, as research has progressed in identifying variable treatment outcomes in patients, the assumption that depression affects solely an individual’s mood paints a rather incomplete picture of the syndrome, which also encompasses neurophysiological, cognitive and behavioural functioning. To achieve a comprehensive account of the etiology of this disorder, it therefore requires a consideration of multiple factors which contribute to rendering this disorder as one of the most disabling and counterproductive to the society.
There is currently a growing research focus on reward dysfunction in depression, which suggests that aspects of early life negative experiences could play a role in impacting one’s lasting perception of reward. Inconsistent drug treatment outcomes and their undesirable side effects for clinically depressed individuals have encouraged further research of the disorder in various directions, such as cognitive-behavioural strategies and transcranial magnetic brain stimulation of neural regions, with the goal of expanding the range of better and promising alternative therapies in alleviating persistent symptoms (Butler, Chapman, Forman, & Beck, 2006; George et al., 2000). Therefore, the widely-held understanding which associates neurotransmitter imbalance with depressive disorder bears limitations compared with a broader scope of dysfunctional reward processing perspective, which emphasises possible etiology of a cognitive and behavioural nature. In a study which restricted healthy subjects’ intake of tryptophan, a precursor of serotonin, depression was not exhibited as a result of decreased serotonin in these individuals, which suggests that factor(s) influencing the greater predisposition of already depressed individuals may be a more significant contributor (Delgado, Charney, Price, Landis, & Heninger, 1989). Such causality of depression as proposed by the serotonin hypothesis is therefore questionable and can be challenged due to the lack of consistent observation in studies (Blier, & El Mansari, 2013).
The mesolimbic dopaminergic reward pathway of the brain, with neuronal projections which run from the midbrain region to the nucleus accumbens, has long fascinated researchers who studies the significance of its role in reward-seeking behaviour, addiction and impulsivity. Nowadays, research is beginning to extend the concept of reward processing to include its influence on the psychopathology of depression. A reward is anything with an attractive value which creates a tendency for an individual to approach and consume it (Schultz, 2015). Such approach and consuming behaviour are called appetitive and consummatory respectively. A reward is associated with the positive reinforcing effect of operant conditioning, which is a learning process which associates the outcome of a behaviour with either a reward or punishment. A person who is given a positive reward after a correct intended behavioural response would be encouraged to engage in that particular behaviour again. On the contrary, when the consequence of our behaviour leads to receiving a negative punishment, the behaviour would be discouraged and its frequency reduced. Studies with depressive patients have demonstrated their reduced sensitivity to reinforcement of positive stimuli, possibly due to dysregulation in reward learning invoked by repeated negative punishments, which leads to an atypical response that shows decreased aversion of negative stimuli (McFarland & Klein, 2009; Murphy, Michael, Robbins, & Sahakian, 2003).
It is wondered whether the above process of dysregulation lead to a disruption in an individual’s healthy balance of brain activation responses to positive and negative valenced reward stimuli in such ways that neurotransmission is more reactive to their negative aspects. Increasingly, research is exploring the association of early life stress with pathology of depression, focusing on areas such as increased inflammatory responses, childhood sensitive periods, changes in corticotropin-releasing factor pathways and compromised cognitive and affective functions (Heim & Binder, 2012; Heim, Owens, Plotsky, & Nemeroff, 1997; Pace et al., 2006; Pechtel & Pizzagalli, 2011). Such examples of outcome of early life stress all point toward the common denominator of negativity that produces adverse results on what used to be normal and healthy psychophysiological processes in an individual. There is a probable considerable reduction in threshold for response to aspects of negativity in stimuli coupled with a corresponding increase in threshold for response to positive aspects. Epstein and colleagues (2006) reported a decreased response in the brain’s ventral striatal region of unmedicated depressed subjects to positive stimuli compared with healthy controls. The mechanism of pathology could therefore lie in the tipping of the balance of cumulative activation towards negative and positive components of a stimulus entity that is mediated by opposing threshold levels in such a pattern that an increase in one would produce a decrease in the other.
Future research in reward dysregulation should therefore test the above hypothesis of the link between neural activation and threshold levels in order to expand our understanding of how the dysregulation between negative and positive perception responses came to work and how this progresses through various stages to culminate in long-term depressive symptoms. It is likely that increased exposure to negative events and stimuli increases the frequency and intensity of neural activation which leads to the development of a cascade of psychophysiological pathological processes that could also affect structural and volumetric changes in the brain (Drevets, Price, & Furey, 2008). Further investigation of the relationship between response activation patterns and consequential structural alterations is of much use to draw an intimate and seamless connection between the two and can help guide treatment alternatives for the depressed.