This short piece is intended to be a primer on the neurobiological underpinnings of depression and to give a neuropsychotherapeutic perspective on the disorder. Later on in this series we will go into more depth and detail on each of these brain regions, but for now here is a brief overview.There are four main brain areas that have been studies in relationship to depressive disorders and we will look at each of these and what part they play in depression.
1. PFC – The prefrontal cortex
2. ACC – The anterior cingulate cortex
3. The hippocampus
4. The amygdala
The Role of the Prefrontal Cortex in Depression
The prefrontal cortex (PFC) plays a vital role in the planning and pursuit of long-term goals and can maintain a focus and volition toward goals despite transient and/or short-term stimuli that may compete with such long-term goals. If we have a damaged PFC we may not have the ability to orient our behavior toward valued goals and can be left a victim of automatically responding to whatever is the current stimuli. Damasio (2000) describes Phineas Gage, who suffered major traumatic damage to his PFC at the age of 25, as one who not only had a major personality change, but as one who was unable to pursue goals or behave according to his own wishes.
The two halves of the PFC play different roles in guiding our behaviour based on our goals and values. The left PFC (lPFC) tends to operate along the lines of positive goals and emotions, whereas the right PFC (rPFC) has a bias toward negative emotions and avoidance goals (for a detailed study of the lateralization of the hemispheres, see McGilchrist, 2012). Some people have a tendency to be more lPFC activated and others more rPFC activated, thus manifesting a personality difference in pursuit of positive goals and generating positive emotions. Generally people will respond to stimuli and their circumstances with a bias to the right or left hemisphere depending on the context of the situation. A stable personality will be horizontally well integrated between the two hemispheres when dealing with life and pursuing goals.
In the case of a depressed individual the lPFC is underactive in an overall sense and in comparison to the rPFC. This lateral asymmetry is well documented (see Grawe, 2007, p.130) and accounts for the negative feelings and low volition for positive goal attainment in the depressed individual. Responsiveness to rewards, as opposed to punishment, is a function of the left medial region of the PFC, and with the lPFC underactive, there is less motivation for rewards. There have been studies showing depressed individuals responding to punishment but not to rewards (Henriques & Davidson, 2000), thus demonstrating the ineffectiveness of trying to establish positive goal attainment with the depressed client.
It has also been found that rPFC hyperactivity is linked to avoidance behaviors and negative emotions, and that this hyperactivity can be a global right-sided activation often associated with increased anxiety.
The depressed individual with an under activated PFC can have a reduced volume of PFC gray matter, likely due to underuse of the area. Both neurons and glia have been found to be less dense in the depressed PFC and suggest a lack of PFC structural requirements to perform the rational, motivating, positive goal pursuing tasks attributed to a healthy PFC (see Grawe, 2007. P.131 for statistics of PFC volume reduction). It would be unfair to expect a client to feel joy, and motivate themselves, if the neural underpinnings for such activity is severely degraded. There is something more fundamental that needs to be addressed, and restored in the capacity of the lPFC, before the depressed client can be expected to embrace positive motivations.
The Role of the Anterior Cingulate Cortex in Depression
The Anterior Cingulate Cortex (ACC) is consistently implicated in depressive disorders. The ACC can broadly be divided into two functional regions: 1) the rostral and ventral division involved with affect and autonomic function and connected with the hippocampus, amygdala, orbital prefrontal cortex, anterior insula, and nucleus accumbens; 2) a caudal division involved with cognitive processing and connected with the dorsal regions of the PFC, secondary motor cortex, and posterior cingulate cortex (Kandel, et al., 2012, p.1406).
The ACC is vital in monitoring inconsistency and conflict and mobilizes resources to attend to the conflict (like the executive functions of working memory and volitional effort). When a situation is encountered that is contrary to one’s wishes (including pain) then the ACC will recruit brain areas such as the PFC to resolve the situation and maintain desired goals.
In the case of depression the ACC is under-activated and the mobilization of volitional effort, for example, to change a situation from an undesirable direction is dampened. There is a typical resignation to circumstances and a passiveness and inability to cope with the demands of life.
Davidson et al. (2002b) proposes two subtypes of depression based on what we have discussed so far about the PFC and ACC:
1) ACC Subtype of Depression: Individuals with an underactive ACC and have resigned and lost the will to change.
2) PFC Subtype of Depression: Individuals who do experience a discrepancy between their state and the demands of the environment, but are unable to activate positive goal-oriented behaviour to effect change.
The Role of the Hippocampus in Depression
The hippocampus is part of the limbic system and is critical in consolidating short-term memory to long-term memory, contextualization, special memory and navigation. It contains a large number of glucocorticoid receptors, making it more vulnerable to long-term stress (chronically increased level of cortisol) than other brain regions.
The majorly depressed individual can have a volume reduction (between 8%-19%, see Campbell, et al., 2004; Davidson, et al., 2002a; Bidebech & Ravnkilde, 2004) of neurons and glia in the hippocampus. This hippocampal atrophy hinders the individual to place current events in context based on prior experience and thus impairs the cognitive ability to cope effectively with current challenges. The tendency to remember negative events and to interpret neutral or positive information as negative may be linked to hippocampal atrophy (see Gradin & Pomi, 2008, for an interesting neural network model).
The Role of the Amygdala in Depression
We know the amygdala as a primary center for anxiety as it performs it’s role of monitoring all incoming stimuli and evaluating that stimuli in terms of importance for the individuals motivational goals. If the stimuli are of high emotional/motivational value, then the amygdala ensures a higher level of cortical arousal and environmental monitoring.
With depressed individuals there is often increased activation of the amygdala as well as an increase in amygdala volume. It has been found that the degree of amygdala activation correlates with the severity of depression and that the amygdala may play an important role in the onset of depression. The heightened anxiety-readiness of the amygdala, particularly attuned to negative events, plays an important role in a bias toward storing negative memories and the tendency to ruminate and be preoccupied with negative thoughts.
As you can appreciate from the very brief outline above, mental disorders like depression have some serious neurobiological underpinnings that need to be addressed before the individual has the capacity to engage positive neural networks and resulting behaviour and emotions