Can Hippocampus damage cause depression? If it can, is this relationship interactive?

Can Hippocampus damage cause depression? If it can, is this relationship interactive?

Book Synopsis

The book, Patient H.M: A Story of Memory, Madness, and Family Secrets explores the scientific inquiry into the frontal lobe, with a particular focus on the components that make up individual memory.  The author, Luke Dittrich, uses the main patient, Patient H.M as well as other groups of patients to retell the various encounters these study participants as subjects of scientific experiments. Based on Dittrich’s description of his grand father, William Scoville’s characteristics, it is clear that scientific discoveries and progress within the field of medicine came as result of individual exploration and free-spiritedness.  Even though he experienced a few pitfalls, Dittrich’s grandfather helped come up with new procedures to facilitate brain surgeries. In fact, his failed experiment on patient H.M led to the many scientific inquiries in various fields including the field of psychology.

The letters he wrote from his childhood informs us that Dr. Scoville was both adventurous and ambitious. In these letters, Dr. Scoville asserts that he was selfish, mean and carefree. Ditrich (2017) however sees these assertions as a form of insecurity. Growing up, William Scoville felt like haws a constant failure.  This sense of insecurity however seems to disappear as he goes though medical school and discovers his new abilities. Dittrich (2017) narrates that he could drive through mountains at dangerously high speed.

His newly found confidence couple with his spirit of adventure made him to engage in scientific probes that had both positive and negative outcomes. On the one hand, Dr. Scoville made constant attempts to improve his practice and participated in the developments experienced in the entire field of medicine.  For example, his lobotomy procure became quite poplar even though some doctors were reluctant to use it. Dr. Scoville believed that old habits had no place in the filed of medicine. He therefore constantly engaged in scientific inquiry and experiments, which would him to even change some of his oldest procedures. His methods facilitated the changing of procedures that were decades old, to more efficient methods for the benefit of the patients and the entire filed of healthcare.

It is however worth noting that Dittrich’s grandfather care-free nature has also had many detrimental outcomes on his patients. Neurosurgery is a field that was founded on script procedures  that surgeons have followed for generations. In this filed, it is important that the doctor follows these procedures and adheres to every single guideline because a single wrong twitch could have fatal outcomes.  For example, Dittrich recounts the case of Gunner   who died after his grandfather performed a procedure on him. Gunner was a patient with a ruptured disk. He was supposed to undergo a usually simple and easy procedure. However, Dittrich’s grand father made the procedure rather unusual by performing the procedure with the patient seated as opposed to the customary position whereby the patient lies on a stretcher. This simple change caused the patient his life as the air embolism escaped through his blood stream up to his basilar artery resulting in a stroke in his brain. These types of experimentations were a common habit of Ditrich’s grandfather. As Dittrich recalls, neurosurgery was an adventure for his grandfather. In fact this neurosurgeon got the name ‘Wild Bill’ owing to his tendency of taking risks, and going against the laid out plans, rules, or procedures

Failing to go by-the book led him to remove the brain structures responsible for memory from Patient H.M’s brain. Henry Gustave Molaison, otherwise known as patient H.M was among the many victims of surgeries gone wrong which was a common occurrence during Wild Billy’s time. Born in 1926, February 26, in Manchester, Connecticut, Henry lived a rather normal life until he was hit by a riding bicyclist when he was about eight years old. Even though he seemed to have recovered from the accident, Henry’s life changed tremendously. After the accident, Henry developed epilepsy and could experience seizures frequently. He was unable to hold a job or even hold meaningful conversations because he experienced because he experienced hypnopompia. Hypnopompia here refers to absentmindedness. Henry could therefore experience momentary lapses, whereby his brain could freeze with eyes wide open. Each time ha had a seizure it would be he had just woken up even though he was not asleep. Dittrich (2017) argues that such seizures or epileptic experiences are common among patients who have suffered traumatic brain injuries. They are regarded as scars that are left behind upon healing. The author of this book also thinks that they could be products of the short-circuiting that the victims of accidents undergo. The short circuiting in tis case creates a new circuit that can cause dangerous convulsions in the patients.

Dr. Scoville thought that he could fix Henry’s problem, and he tried to. However, he created a whole new set of problems by removing parts of his brains that play a key role in retaining activities. After the surgery, Henry had memory deficits and could not remember important things in his life, especially those that occurred after the accident. He could not recall any events lasting for hours including special events such as his birthday, Christmas, or Easter. This patient could not even recall if he ever had a lover. Henry could not even notice that he had participated in certain experiments repeatedly since he could not remember being in any one of them. Notably, Henry developed the habit of telling and retelling stories over and over again. This repetition of stories partly demonstrates his inability to recall that he had told them before. Consequently, he could repeat the stories with the same level of enthusiasm.

Dittrich supposes that it was difficult for Henry to hold any meaningful relationship after the brain surgery performed by Dr. Scoville. This is because he was unable to remember anyone in his life. Henry could not even tell whether his father was still alive or not. In essence, he had lost connection to events and the people in his life. By willfully participating in a surgery, patient H.M possibly lost both of his Hippocampi. Dittrich (2017) purports that the damage caused on his frontal lobe caused him to lose his humanness.

Nevertheless, the experiments performed by Dr. Scoville gave rise to numerous studies in neuroscience. Many scholars including Dr. Corkin tried to explore Henry’s transformations in order to understand fully the human anatomy.  Dittrich (2017) narrates that his grandfather’s lesion produced a breathing subject whose brain could be used to study the neurological underpinnings of memory in ways that had never been thought of before. In his perspective, Henry was a research participant of limitless value.

 

Can Hippocampus damage cause depression?

Traumatic brain injury (TBI) is one of the most common causes of permanent disability and death throughout the globe. TBI is important in this scenario because it has the potential to cause acute damage to the brain as well as neurological and neuropsychiatric defects. In fact Patient H.M’s seizures or epileptic episodes, as well as the memory loss were all a result of the sustained insults to the brain. Traumatic Brain Injuries can also cause of mood disorders, cognitive decline and impairment of fine motor skills among other symptoms (Mao et al., 2020)

Hippocampus is one of the most vulnerable regions of the brain.  Jorge et al. (2007) argues that the unique features of the hippocampal circuit and the hippocampal neurons make the hippocampus especially vulnerable to traumatic injuries and other insults that occur to the brain. One time or progressive insults to it can cause significant neuron-associated impairments. Jorge et al. (2007) notes that patients who have experienced moderate to severe brain injuries can experience neuronal and glial loss that would negatively impact their hippocampal volume. The study findings by Jorge et al. (2007) particularly suggest that those with moderate to severe head injurers experience hippocampus atrophy. Hippocampus atrophy here refers to the reduction in the hippocampus volume to abnormal levels after it has attained the normal maturity.  

Evidence suggests that there is a relationship between hippocampus and depression (Jorge et al., 2007; Macqueen et al., 2008; Sheline, 2011). On the one end, there is a supposition that low hippocampal volume can cause depressive symptoms. On the other end, some studies suggest that major depressive disorders can cause impairments in the hippocampus (Sheline, 2011). Jorge et al. (2007) for instance, argue for the causative relationship in which mood disorders seem to cause lower hippocampal volume in patients.  

According to Sheline (2011) this relationship between hippocampus and depression can be explained using the neurotoxicity hypothesis. Based on the neurotoxicity hypothesis, increased exposure to glucocorticoids can heighten the neural susceptibility to toxic materials thereby making it easier for such materials to damage the neural organs.  This hypothesis suggests that cumulative duration or recurrent episodes of depressive symptoms, chronic stress or post-traumatic stress disorder (PTSD) can result in low volumes of hippocampus (Mao et al., 2020; Sheline, 2011).  Small volumes of hippocampus can thus be an indication of major depressive disorder in a patient.  

Sheline (2011) also thinks that the relationship between hippocampus and depression can be explained using the vulnerability hypothesis. The latter supposes that the hippocampal volume can be considered as a pre-existing condition that can cause stress related disorders such as depression. In this case, low volumes of hippocampus would be a risk factor for the depressive condition. The experimental study conducted by Hickie et al. (2005) supports Sheline’s (2011) assertions that reduced hippocampal volumes are associated with depressive symptoms.  In particular, Macqueen et al. (2008) note that hippocampal volumes of patients with depressive disorder, on average, are approximately five percent smaller than that of the healthy population.

Hickie et al. (2005) further suggest that the condition is worse in patients with early and late onset depressive disorders. Older adults suffering from depression are thus likely to exhibit lower volumes of hippocampus.  Similarly, these scholars note that patients with melancholic subtype of the depressive condition could also experience worse clinical outcomes with regards to their hippocampal volume. Patients with depression also tend to show lower performance of visual and verbal memory. The findings by Hickie et al. (2005) show that people with depressive symptoms exhibit lower total hippocampal volumes as well as smaller whole-brain volumes.

Even though Hickie et al. (2005) do not explicitly explore the supposed reverse causal relationship, whereby reduced hippocampal volumes can lead to depressive disorders, their assessment seems to confirm this hypothesis.  In particular, these researchers argue that hippocampus plays a significant role in mood regulation as well as the regulation of cognition. Like Hickie et al. (2005), McQueen et al. (2008) acknowledges the interactive relationship between the hippocampal volume and the depressive disorder.  McQueen et al. (2008) agree that the Hippocampus facilitates mood regulation to a large extent.  It therefore seems logical to argue that impairments in the hippocampus would result in cognitive dysfunctions as well as mood disorders.

The potential risk factors identified include late and early onset of depressive disorder (Hickie et al., 2005; McQueen et al., 2008). On one hand, late onset occurs among older adults. This group is more susceptible because a majority tend to suffer from vascular diseases as well as neurodegeneration. On the other hand, patients who have experienced early onset depressive disorders also become susceptible to hippocampal changes because of their prolonged exposure to a lifetime of untreated depressive illness. It is worth noting that these groups of patients tend to show low levels of brain-derived neurotrophic factor (Mao et al., 2020). The neurotrophic factor helps the brain develop and maintain neurons, and ensures their survival.  The decline of the neurotrophic factor thus implies cognitive impairment such a memory loss. It could also be attributed to such abnormalities such as the reduced hippocampal volumes.

Hickie et al. (2005) argue that the issue of reduced hippocampal volume can be redressed by addressing some of the risk factors identified. For example, the patients could be given anti-depressants, which seem to increase the neurotrophic factor, thereby preventing other neuron-related problems. Advising the patients to take the anti-depressants can help prevent further damage to the brain structures such as the hippocampus and its potential prognostic significance.

In a similar manner, McQueen et al. (2008) conducted a study to evaluate the patient’s potential response to treatment.  The study participants included a group of patients with Head/Tail Hippocampal volumes who also exhibited depressive symptoms. The findings of this study suggest that regional brain volumes tend to vary with the patient’s clinical response to antidepressant medication. Specifically, the patients who responded well through remission exhibited lower volumes of hippocampal volumes in comparison to those who did not show any remissions (Macqueen et al., 2008).

The implication of this latter study is that the low hippocampal volume in patients can be enhanced by the use of anti-depressants. In essence, the antidepressants do not only treat the major depressive disorders, but it also prevents further damage to the brain structures thereby preventing the continued decline of the hippocampal volume. Preventive strategies can thus focus on providing remedy for the identified clinical condition such as chronic stress, depression, or PTSD to prevent damages to the neurotrophic factor and the brain structures.

Based on the interactive causal relationship between hippocampus and depression, the treatment of one condition can result in better clinical outcomes of the other condition. As highlighted above, the positive response to the treatment of the depressive symptoms using anti-depressants could address the issue of low hippocampal volume. Macqueen et al. (2008) purports that pharmacotherapy models aimed at the fronto-temporal networks such as the hippocampus and the grey matter volume could also aid mood regulation thus helping deal with the depressive symptoms.  

It worth noting that patients suffering from mood disorders coupled with the reduced hippocampal volumes are unlikely to recover and return to productive life in a span of one year (Jorge et al., 2007). According to Jorge et al. (2007), the neural and glial elements of patients suffering from trauma or mood disorders can further be compromised by such functional and structural changes as reduced hippocampal volumes. The interactive relationship between the hippocampus and depression thus makes it rather difficult to treat either condition.  

Conclusion

As Dittrich (2017) presents in his book using patient H.M, insults to the brain can result in neurological changes that could negatively impact the life of the patient. In the case of Henry, the loss of both his hippocampi resulted in the partial loss of his memory and consequently degraded his social life. The studies analyzed in this case indicate that a simple damage or alterations of the brain structures such as the decline in the hippocampus volume could create such problems as mood disorders. In fact, the evidence suggests that any impairment in the hippocampus could result in major depressive disorders. Scholars such as Hickie et al. (2005); McQueen (2008) and Jorge et al. (2007) seem to agree that hippocampus and depressive disorder have an interactive relationship. On the one end, scientific studies indicate that patents with mood disorders exhibit a significantly smaller hippocampal volumes compared to those without any affective disturbances. This means that patient mood disorders affect the hippocampus, and that patients suffering from depression are likely to experience smaller hippocampal volumes. On the other end, some studies point to a causal relationship that point to the opposite direction. This means that smaller hippocampal volume can also trigger or perpetuate depressive disorders.

 

 

 

 

 

 

 

 

 

References

Dittrich, L. (2017). Patient HM: A Story of Memory, Madness, and Family Secrets. Random House Trade Paperbacks.

Hickie, I., Naismith, S., Ward, P. B., Turner, K., Scott, E., Mitchell, P., . . . Parker, G. (2005). Reduced hippocampal volumes and memory loss in patients with early- and late-onset depression. British Journal of Psychiatry, 186(3), 197-202. DOI:10.1192/bjp.186.3.197

Jorge, R. E., Acion, L., Starkstein, S. E., & Magnotta, V. (2007). Hippocampal volume and mood disorders after traumatic brain injury. Biological psychiatry, 62(4), 332-338.

Macqueen, G. M., Yucel, K., Taylor, V. H., Macdonald, K., & Joffe, R. (2008). Posterior Hippocampal Volumes Are Associated with Remission Rates in Patients with Major Depressive Disorder. Biological Psychiatry, 64(10), 880-883. DOI:10.1016/j.biopsych.2008.06.027

Mao, X., Terpolilli, N. A., Wehn, A., Cheng, S., Hellal, F., Liu, B., ... & Plesnila, N. (2020). Progressive histopathological damage occurring up to one year after experimental traumatic brain injury is associated with cognitive decline and depression-like behavior. Journal of Neurotrauma, 37, 1331–1341. DOI: 10.1089/neu.2019.6510

Sheline, Y. I. (2011). Depression and the Hippocampus: Cause or Effect? Biological Psychiatry, 70(4), 308. DOI: 10.1016/j.biopsych.2011.06.006