Insights from Modern Psychiatry Research: A Reflection on Familial Depression, Brain Scans, and Treatment Approaches

Hey team,

Over Thanksgiving break I read a book discussing findings of more modern psychiatry research with the use of brain scans and genetic studies. Although it was not the most modern anymore since it was written a few years ago, I still learned quite a bit that I’d like to share. The main takeaways I got pertain to neuroplasticity and activity in specific brain regions.

Familial depression, as labeled in the book, is not a discreetly defined term but one that refers to more severe and heritable depression as the name implies. We all know that there is a genetic component to mental illness along with developmental/ environmental. We can never pin down what the exact cause is, and we probably never will, as many are required to intersect in order for symptoms to manifest and possibly persist in the case of chronic psychiatric disorders. Familial depression is depression that seems to have a dominant genetic component that is less determined by environment as shown by twin adoption/ separation studies. Let's say there is a woman who had depressive episodes at 17, 22, 25 and 30, each episode with moderate to high severity, and before her, her mom had a similar pattern of severe episodes for depression throughout her life,  if the woman (not the mom) goes on to have children the odds of them having depression as well is quite high, regardless of specific environment the children are raised in. Environments often play a protective role in people predisposed to developing certain disorders, but just as possible, the environment can go sour and allow psychiatric symptoms to manifest and stay severe. This is simplified and individuals are far more complex, but this gets the message across. Severe, episodic depression is more familial in nature . 

And expanding on familiar depression, there are interesting findings we see through brain scans. Increased activity in the anterior cingulate cortex. This is an area of the brain that when stimulated evokes a strong reactive fear response. At the same time, this area is atrophied (shrunken) which to me displays poor information processing. This is likely due to poor development in these regions from a “use it or lose it” case from growing up in which someone wasn’t able to learn to properly control an overactive (or even healthy) stress response and hence “lost” the needed utilization for healthy emotional regulation. 

Another important brain region is the hippocampus. This is huge in the limbic system (emotions). This is one of the sites of memory, and plays a major role in bringing short term experiences to long term memory. In individuals reported to have several “adverse childhood events” there is strong association with hippocampus atrophy. Again to me this displays an improperly utilized part of the brain that was unable to develop due to an overwhelming  and long term stress response. In chronic stress, high levels of cortisol, the hippocampus gets overwhelmed and isn’t able to properly function. Among many additional factors, glucocorticoids (i.e. cortisol) lead to oxidative products being produced that damage specific tissue and important organelles (like mitochondria). This is what produces synaptic changes and tissue shrinkage in the brain (along with glutamate excitotoxicity and probably a million other contributors as well).  When we go to treat major depression one of the treatments may be lithium. This is often reserved for patients with high suicidal ideation and mood fluctuations associated with bipolar disorder but it is not uncommon in treatment of depression at all. Lithium can be harsh on some organs like kidneys however it is quite incredible at its job. It shows strong neuroprotective effectiveness which is combating the excessive neuro destructive processes going on in patients with psychiatric conditions. It increases production of compounds that are anti-apoptotic which means anti cell suicide which is often decreased in unmedicated patients. I’m curious about how significant this autoimmune cell death response is in development and recurrence of depression amongst other disorders such as bipolar and schizophrenia which show similar abnormalities in a neuroimmune response.

When treating depression first line agents are serotonergic against which increase levels of serotonin throughout the brian. Though these drugs are not all that good they do show positive effects in comparison to placebo and have helped millions of people. These drugs do not work fast however, often taking 4-8 weeks to notice more significant and clinical effects, this is despite the fact that they increase serotonin quite rapidly after ingestion. We currently believe, though variable and more complicated, that the antidepressant response is due to genetic changes that occur due to changes in expression and sensitivity of serotonin 5HT1a receptors. The significance to note is the focus on this receptor and the brain areas where this receptor has its greatest density. 5HT1a is expressed a great deal in areas affected by depression such as the limbic system and prefrontal cortex. Activation of 5HT1a is important in the release of neurotrophic factors that help a developing brain healthily, and properly, grow and learn. As discussed above the brain regions involved in depression are under/ improperly developed by many estimates as caused by specific traumas/ stressors during childhood. By modulating serotonin with antidepressants in these regions, synaptic and neuronal changes arise that produce antidepressant effects. 

That is all I have for you today, hope you appreciate my takeaways from the book, I know I did. Thank you for reading