01/10/2018
First draft of a few thoughts about links between the brain and depression:
There have been quite a lot of studies into how the brain is affected by depression. These studies show that quite a number of different regions seem to show abnormalities in people who have MDD. Of particular interest to me is an article entitled Where in the brain is depression (Pandya, Altinay, Malone, & Anand, 2012) which helps to identify what is going on. I use Pandya et al but also cite many other studies in attempting to provide a lay readers guide (and a lay writer’s guide for that matter) on how depression affects the brain.
I’m going to talk about the brain using three divisions. The cortical brain, that is the crinkly outer surface of the brain. The subcortical brain, that is the inner part of the brain and the brain stem, the bit right at the bottom. I like Margot Sunderland’s terms. She calls the cerebral cortex the upstairs brain and the sub-cortex the downstairs brain. The brain stem can then be thought of as the basement.
Cerebral cortex
In the upstairs brain the following areas area affected:
• The dorsal and medial prefrontal cortex,
• The orbital frontal cortex
• The dorsal and ventral anterior cingulate cortex,
• The insula.
The prefrontal cortex
The dorsolateral prefrontal cortex [DLPFC] is at the front of the brain and is an area associated with executive decision making, working memory and inhibiting responses. The medial prefrontal cortex is implicated in activities such as decision making, memory processing and learning (Euston, Gruber, & McNaughton, 2012). It’s important to remember through that none of these regions acts alone. Most higher level processing involves multiple regions: the mPFC, for example, has many connections to other regions including the hippocampus which we know is important in memory storage and recall.
There is a lower metabolism [less happening chemically](Kimbrell et al., 2002; Rigucci, Serafini, Pompili, Kotzalidis, & Tatarelli, 2010) and less oxygenated blood flowing [perfusion] through the dorsal and medial prefrontal cortex. This leads to a decreased ability to think together with an increased response to negative thoughts which has been linked to an increased suicidal risk (Desmyter, Van Heeringen, & Audenaert, 2011).
The orbital frontal cortex
One 2002 study of 15 patients with depression found they had a 32% reduced volume of their smaller medial orbitofrontal. This is an area associated with cognitive processing and decision making.
The anterior cingulate cortex
The ACC is involved in a whole host of activities including decision making, focussing attention and impulse control and emotion. The dorsal [upper] and the lateral [side] bits of it seem to have different functions. The dorsal ACC has also been linked with conflict resolution particularly for experiences which are experienced as unpleasant. The ventral AAC has links with some of the downstairs areas of the brain that produce emotional responses such as the amygdala and dorsomedial thalamus, of which more in a moment.
There have also been many studies of this region which link it specifically with depression. A 1997 study (Drevets et al., 1997) showed a decrease metabolism in this area in families who had a history of depression. Another study (Mayberg et al., 1999) found that links between this area and the right prefrontal cortex are linked with mood changes.
The Insula
This is a part of the brain that is located in the lateral sulcus. That’s the bit of the brain in the deep fold that separates the temporal and parietal region from the frontal bit. Given that we have two hemispheres to the brain, we have two insulas as well.
The sub cortex
In the downstairs brain the following areas are affected by depression:
• Amygdala
• Hippocampus
• Hypothalamus
• Dorsomedial thalamus
The area in the brain that sits around the thalamus is usually referred to as the limbic system. John Pinel calls this the part of the brain that is responsible for the four Fs of motivation: feeding, fleeing, fighting and sexual behaviour (Pinel, 2011, p. 69). I am going t focus n two areas the hippocampus and the amygdala.
The Amygdala
We have two of these almond shaped clusters of neurons, each situated deep in the temporal lobes of our brains. They are seen as involved in a number of emotional responses, particularly fear.
A meta-analysis of studies that looked depression and the amygdala (Hamilton, Siemer, & Gotlib, 2008) showed a significant difference in depressed patient between those that were o medication and those that were not. Those who were not on antidepressants showed a reduced amygdala size while those on these drugs showed an increased amygdala size. It is by no means clear as to why this might be. One study(Wennström, Hellsten, & Tingström, 2004) of rats, for example, showed that the increase in size in medicated people might be due to the production of oligodendrocytes. These are cells that create the myelin sheath that provides insulation to the axon of the neuron.
Hippocampus
There have been more studies into the hippocampus and depression. Again, we have two hippocampi, one in each hemisphere of the brain. This is a part of the brain that is linked to the formation and retrieval of memory.
In 1953 a patient known usually just as HM who was suffering from repeated epileptic seizures underwent surgery which removed areas of the brain associated with the left and right hippocampus (Scoville & Milner, 1957). The operation cured his epilepsy but hugely disrupted his ability to store memories for more than a few minutes at a time. In another study of London taxi drivers it was shown that undertaking a task requiring lots of remembering increases the size of the hippocampi. Cabbies who had passed ‘the knowledge’ test requiring them to be able to know their way around all 25,000 streets within a six mile radius of Charing Cross had significantly larger posterior hippocampi relative to those of control subjects (Maguire et al., 2000).
There have been quite a few studies of the brain in depressed patients. Taken together these show that people who are experiencing depression are likely to have smaller hippocampi than those who are not (Videbech & Ravnkilde, 2004). What seems unclear at the moment is whether a reduced hippocampi volume is the result of depressed or whether it can be seen as a biomarker for vulnerability to depression. There is even the suggestion that large hippocampi could be a measure of resilience against depression (Chan et al., 2016).
Hypothalamus
There is a 2018 study (Schindler et al., 2018)which shows that people with an affective disorder such as depression or bipolar have a left hypothalamus which is 5% larger than in the normal population. This is a study with 84 participants at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig and the Department of Psychiatry and Psychotherapy of the University Clinic also in Leipzig. They even found that in one group of participants there was a correlation between the size of the hypothalamus and the severity of the depression.
Brain stem
In the basement:
• Striatum
• Nuclei of several neurotransmitters including those for serotonin, norepinephrine and dopamine.
There has been a growing discussion around whether the attempt to find an area of the brain associated with depression is, in fact, missing the point. Maybe, depression affects many areas of the brain and particularly affects the connectivity between different areas. In this respect Pandya et al conclude that, “Depression seems to lie in many brain regions as well as nowhere in particular (2012, p. 7). Frustrating as this is for those who want to find a direct causal link between brains and depression, it does indicate just how complicated this is and why it has proved so difficult to find a bio-chemical brain-based explanation for depression.
