Sports-Related Concussion Effect on Pituitary Function Causes Depression in Athletes

This paper was written by Allison Frattaroli, who has a B.S Degree in Psychology from Lafayette University.

Despite more attention being paid to concussions in recent years, this form of Traumatic Brain Injury (TBI) is still startlingly common among athletes.  According to the Center for Disease Control, 329,290 children under the age of 19 were treated for sport-related concussions in 2012. Further, the rate of emergency department visits for sports-related concussions has more than doubled among children between 2001 and 2012.  This rise likely is not due to an increasing number of injuries, but an increasing number of reported injuries that are now being brought to medical attention rather than being brushed aside (Edwards & Bodle, 2014). Even so, these numbers are still likely an underestimation of concussions as many go undetected by neurological testing and can create long-lasting effects without proper treatment (Talavage et al., 2014).  With the rise in concussions reported over the last decade, more attention has been given to their consequences. One consequence in particular that has perplexed the neuroscience community is an increase in depression. This paper will examine the relationship between concussions and depression in current literature, particularly focusing on damage to the pituitary gland as a potential cause.

To better understand concussions, it’s important to understand what effect they have on the brain, what damage they can cause, the parts of the brain associated with that damage, and the short and long-term consequences of concussions.  While concussions are typically thought of as resulting from a direct impact to the head, they can also be sustained as a result of an impact to the body causing the force of the impact to be transmitted to and absorbed by the brain (Edwards & Bodle, 2014).  Upon impact, the brain struggles to keep up with the movement of the skull, and then rebounds in the direction of impact and hitting the interior of the skull (Edwards & Bodle, 2014). Early symptoms of concussions can occur within minutes of impact. These can include delayed verbal and motor responses, confusion, inability to focus, slurred speech, incoordination, memory deficits, and nausea.  Depending on the severity, these symptoms can last anywhere from minutes to days. Later symptoms generally occur in the days and weeks following impact, but in some cases, can be life-long. These include persistent headaches, insomnia, hypersomnia, poor attention and concentration, memory deficits, irritability, personality changes, and depression (Edwards & Bodle, 2014).

While one concussion is bad enough, multiple concussions can be life-threatening.  One potential long-term consequence of multiple concussions is Chronic Traumatic Encephalopathy (CTE), which has far more severe consequences.  This disease is often associated with severe depression and suicidal behavior. CTE is known for being associated with depression, but little research has been done on the correlation between mild TBI (mTBI), or concussions, and depression (Edwards & Bodle, 2014).  Some studies (Yang et al., 2015) suggest that concussions do not cause depression; rather, concussions can exacerbate pre-existing depression. Other studies (Yrondi et al., 2017), however, suggest that repeat concussions increase the risk of long-term depressive disorder compared to athletes with no history of concussions, implying that the concussion itself may cause depression.

Yang et al. (2015) studied the effect of baseline psychological symptoms on post-concussion depression among a sample of 71 male and female D1 collegiate athletes who had recently endured concussions.  Out of the 71 student athletes, 21.4% reported depression as a post-concussion symptom. However, they found that athletes who experienced depression in their lives prior to their injury were 4.59 times more likely to experience depression post-injury.  Therefore, depression at baseline served as a significant predictor for post-concussion anxiety and depression. This means that athletes with pre-existing depression could be a particularly vulnerable group (Yang et al., 2015).

Similarly, Mainwaring et al. (2004) examined mood states in a sample of concussed collegiate athletes in comparison to uninjured collegiate athletes and non-athlete college students.  At baseline, mood scores did not significantly differ between the three groups, but they found that concussed athletes scored higher on depression, confusion and overall mood disturbance compared to the two control groups 14 days post-concussion.  They did find, however, that the depressive symptoms were not long lasting. Most of the athletes’ mood disturbances resolved to baseline after three weeks (Mainwaring et al., 2004). Although this study found that depression tended to resolve in concussed athletes, others suggest that this might not be the case.  Ellis et al. (2015) found that 10% of their sample of 14-year-old athletes with concussions experienced suicide ideation—one participant even committed suicide during the timeline of the experiment. These results contrast Mainwaring et al. (2004) to suggest that depressive symptoms might not be easy to solve with typical concussion treatment.

Unfortunately, it’s hard to differentiate between concussion symptoms and general depression symptoms, because many of them overlap, including feelings of sadness and fatigue, which can be associated with both (Iverson, 2006).  Similarly, it’s believed that the athlete’s removal from their preferred sport may also result in depressive behavior or the indefinite recovery time (Bloom et al., 2004). While it is difficult to determine the exact cause of depression symptoms in concussion patients, many researchers suggest that it might be caused by injury to the brain’s endocrine system, which produces and transmits hormones throughout the body.  In the brain, the pituitary gland plays a crucial role in emotion regulation and the onset of depression. Therefore, it is believed that damage to these areas during a concussion could cause depression symptoms post-injury.

A study by Bondanelli et al. (2004) found that pituitary dysfunction had been documented in 37% of their patients with a history of mTBI in the last five years.  The most significant impairment they found in the pituitary gland was impaired growth hormone secretion (Bondanelli et al., 2004). Growth hormone deficiency (GHD) is associated with both changes in body composition and cognitive dysfunctions like mood disorders and depression (Maric et al., 2010).  Richmond & Rogol (2014) suggest that GHD, whether or not caused by TBI, may lead to mental health-related problems. It is believed that upon impact, not enough oxygen reaches the tissue in the pituitary gland, resulting in hypopituitarism, in which the pituitary gland does not secrete hormones properly (Bondanelli et al., 2004).

Researchers Tanriverdi et al. (2008) studied pituitary volume and function in 61 competitive and retired male boxers.  They found that 15% of the 61 boxers showed GHD and 18% had general pituitary dysfunction. Out of the retired boxers, who experienced the most concussions or injuries, 57% had hypopituitarism, which was significantly higher than the prevalence in non-athletes of similar age.  Additionally, mean pituitary volume was significantly lower in retired boxers when compared to younger boxers. This lower pituitary volume in addition to the high prevalence of GHD in contact-sport athletes suggest that boxing might affect both the function and anatomy of the pituitary gland (Tanriverdi et al., 2008).

Contact sports like football and boxing seem to be highly correlated with concussions and resulting depression or pituitary damage.  In a study by Didehbani et al. (2013), retired NFL players received significantly higher scores on depression ratings than did matched healthy controls, which might indicate similar pituitary damage as a cause as seen in Tanriverdi et al.’s (2008) study on retired boxers.  It’s possible that the forceful contact in sports like football and boxing that put these athletes at greater risk for concussions. A study on soldiers by Baxter et al. (2013) reported that 32% of soldiers with TBI also exhibited anterior pituitary dysfunction and hormone deficiency.  They found that pituitary dysfunction was a particular problem after TBIs resulting from blast exposure, compared to non-blast related TBI injuries (Baxter et al. 2013). While not entirely the same, the force in which soldiers could be thrown and hit the ground after an explosion could be replicated in a football collision or an intense boxing match.  Therefore, it is possible that athletes who partake in sports with more intense contact or that replicate blast exposure could be at higher risk for concussions that effect pituitary gland function, further putting them at risk for GHD and depression.

Despite the risk that these athletes might have, growth hormone therapy has shown to be successful to aid the recovery of the pituitary gland and in turn, reduce depression in concussed athletes.  A study by Maric et al. (2010) tested the psychiatric and cognitive functions in TBI patients with GHD both before and after the implementation of growth hormone therapy. They found that after six months of growth hormone therapy, TBI patients significantly improved in cognitive abilities, like verbal and non-verbal memory, and improved psychiatric functioning.  Specifically, they found that the severity of depression decreased, as well as hostility, paranoia, anxiety and psychoticism. They also found that GHD patients who ceased therapy for 12 months significantly regressed in both cognitive abilities and certain psychiatric functions like anxiety and paranoia. Further, TBI patients with GHD who did not undergo growth hormone therapy scored more highly on depression compared to those who did pursue the therapy.

This study alone gives hope to concussed athletes who might be experiencing depression as a result of growth hormone deficiency.  Damage to the pituitary gland due to concussion or more severe TBI could have long lasting consequences and could put athletes at risk not only for cellular brain damage but depression and suicidal behavior without proper treatment.  All together, these studies point to the correlation between concussion and depression, but few address the topic outwardly. With further research, we might be able to further identify if depression and pituitary gland damage can be directly caused by a concussion or if a concussion only exacerbates existing depression in student athletes.

Annotated Bibliography

Baxter, D., Sharp, D. J., Feeney, C., Papadopoulou, D., Ham, T. E., Jilka, S., & McGilloway, E.

(2013). Pituitary Dysfunction After Blast Traumatic Brain Injury. Annals of

Neurology, 74(4), 527-536.

 

• Article studied pituitary dysfunction after TBI from improvised explosive devices in soldiers
• Found that 32% of soldiers with TBI had anterior pituitary dysfunction hormone deficiency when compared to participants who had TBI from non-blast related injuries, blast TBI injuries were correlated with more pituitary dysfunction
• Injuries found affected the hypothalamus, pituitary gland or pituitary stalk, resulting in damage to cell bodies or white matter connections
• Pituitary dysfunction is a particular problem after blast exposure – the blast itself may have been the specific cause of the damage / the manner in which the TBI is achieved could be the reason pituitary gland damage is prevalent in TBI patients
• Blast injuries could also be seen in football
  • Suggests correlation between type of contact/TBI and pituitary dysfunction
  • Large blows to the body with head being thrown back, hitting the ground
• Overall: Pituitary dysfunction following blast TBI was associated with worse cognitive function and greater severity of head injury, including white matter damage
• Recommends that soldiers should go through frequent PG screenings to ensure endocrine system is working properly at all times

 

Bloom, G. A., Horton, A. S., McCrory, P., & Johnston, K. M. (2004). Sport Psychology and

Concussion: New Impacts to Explore. British Journal of Sports Medicine, 38, 519 –521.

 

• There is a rising interest in examining the psychological effects of athletic injuries, especially concussions as they are so common to many sports
• Concussed athletes may be prone to experience isolation, pain, anxiety and disruption of daily life
• Pose different psychological effects than a physical injury like a broken bone
• Lack of routine and consistent support from teammates can further this isolation and even cause depression symptoms in some patients

 

Bondanelli, M., De Marinis, L., Ambrosio, M. R., Monesi, M., Valle, D., Zatelli, M. C., & Degli,

1. C. (2004). Occurrence of Pituitary Dysfunction Following Traumatic Brain

Injury. Journal of Neurotrauma, 21(6), 685-696.

 

• Purpose was to evaluate the occurrence of long-term pituitary dysfunction in patients after a closed or penetrating head injury over 5 years (1997-2001).
• Found that pituitary dysfunction has been documented in a substantial portion (54%) of the patients with a history of TBI in the last 5 years.
• Impaired GH secretion was the most common abnormality, present in 28% of patience.
• PD was 37.5% in mild TBI but 59% in severe TBI (according to GCS), suggesting that clinical severity of trauma may be a risk factor for developing post-traumatic hypopituitarism
• Post-traumatic hypopituitarism could be due to a hypoxia (not enough oxygen in tissue) that leads to functional damage of the hypothalamus or pituitary.
• The most frequent alteration in endocrine function detected was partial or severe growth hormone deficiency, documented in 28% of patients and in 52% of those affected by pituitary abnormalities
• Overall, pituitary dysfunction was more frequent in patients with severe TBI, BUT the occurrence of growth hormone deficiency was not significantly influenced by severity of trauma — meaning it could occur even in mild TBI/concussion patients

Edwards, J. C., & Bodle, J. (2014). Causes and Consequences of Sports Concussion. Journal Of

Law, Medicine And Ethics: A Journal Of The American Society Of Law, Medicine And

Ethics, 42(2), 128-132.

Explains the damage caused to the brain by a forceful blow to the head.

• Discusses early and late symptoms of concussions and how long they last. Parts of the brain most usually associated in concussion damage.
• Long-term consequences of multiple concussions.
• Definition and explanation of Chronic Traumatic Encephalopathy (CTE) — often associated with depression and suicidal behavior (often reported in veterans who experienced TBI in combat).

 

Ellis, M. J., Ritchie, L. J., Koltek, M., Hosain, S., Cordingley, D., Chu, S., & Russell, K. (2015).

Psychiatric Outcomes After Pediatric Sports-Related Concussion. Journal of

Neurosurgery Pediatrics, 16, 709–718.

• Goal was to examine prevalence of emotional symptoms among children and adolescents with sports-related concussions and to examine the prevalence, clinical features, risk factors, and management of post-injury psychiatric outcomes of those patients
• Looked at suicide ideation in young athletes (14 years old) with concussions
• Found that 11.5% of child patients met criteria for post-injury psychiatric disorders and 10% of them had suicidal ideation, one even committed suicide
• Overall: adult and childhood survivors of TBI are at an elevated risk of suicidal behavior

 

Didehbani, N., Munro Cullum, C., Mansinghani, S., Conover, H., & Hart, J. (2013). Depressive

Symptoms and Concussions in Aging Retired NFL Players. Archives of Clinical

Neuropsychology, 28(5), 418-424.

• 30 retired NFL athletes with a history of concussion were examined and matched with IQ controls
• Found a significant correlation between the number of concussions and depressive symptom severity using the Beck Depression Inventory II
• The percentage of retired athletes with depression is 40% higher than the national average of 15% for healthy older adults
• Many of the participants did not self-identify as depressed despite their scores on BDI-II and therefore did not seek psychiatric help
• Overall: retired NFL players received significantly higher scores on depression ratings than did IQ-matched healthy controls

 

Iverson, G. L. (2006). Misdiagnosis of the Persistent Post-Concussion Syndrome in Patients with

Depression. Archives of Clinical Neuropsychology, 21, 303–310.

• Purpose was to examine the prevalence of post-concussion-like symptoms in patients with depression
• Recruited non-concussed depression patients took a post-concussion symptom inventory
• Approximately 9/10 patients with depression met the criteria for post-concussion symptoms
• Suggests that it’s necessary to consider depression as a factor in the diagnosis of concussions
• Overall: many of the symptoms for depression and for concussion overlap, including feelings of sadness and fatigue, which can be associated with both.  Therefore, depression should be used to more seriously diagnose concussions.

 

MacMaster, F. P., & Kusumakar, V. (2004). MRI Study of the Pituitary Gland in Adolescent

Depression. Journal of Psychiatric Research, 38(3), 231-236.

• Abnormalities in pituitary function have been described in major depressive disorder and may reflect neurodevelopment abilities.
• Measured volume of pituitary gland in 17 MDD patients and 17 healthy controls — MDD subjects demonstrated a 25% increase in pituitary gland volume, but no significant relationship between pituitary size and clinical severity of depression were found.
• Indicates the pituitary gland as playing an important role in regulating emotions and depression.

 

Mainwaring, L., Bisschop, S., Green, R., Antoniazzi, M., Comper, P., Kristman, V., & Richards,

1. (2004). Emotional Reaction of Varsity Athletes to Sport-Related Concussion. Journal

of Sport & Exercise Psychology, 26, 119–135.

• The Profile of Mood States (POMS) was administered to a sample of collegiate concussed athletes, uninjured collegiate athletes, and a non-athlete college student control group at baseline and within 72 hours, 7 days, and 14 days post-concussion
• Found that mood scores did not differ between the groups at baseline, but athletes with an concussion reported higher POMS scores for depression, confusion, and total mood disturbance compared with the two control groups at 14 days post-concussion
• Athletes’ mood disturbances resolved to baseline levels by 3 weeks post-injury

Maric, N. P., Doknic, M., Pavlovic, D., Pekic, S., Stojanovic, M., Jasovic-Gasic, M., & Popovic,

1. (2010). Psychiatric and Neuropsychological Changes in Growth Hormone-Deficient

Patients After Traumatic Brain Injury in Response to Growth Hormone Therapy. Journal

of Endocrinological Investigation, 33(11), 770-775.

• GHD is associated with changes in body composition and quality of life, cognitive dysfunctions and depression
• Psychiatric and cognitive functions were tested in six GHD patients at baseline (3 years after TBI) and reassessed after 6 months of GH therapy and then 12 months later
• Results: six months in GH therapy for TBI patients improved cognitive abilities (particularly verbal and non-verbal memory) and improved psychiatric functioning
  • Severity of depression decreased as well as intensity of interpersonal sensitivity, hostility, paranoid ideation, anxiety and psychoticism
  • Somatization, OCD symptoms and phobic anxieties also decreased (not just depression, other psychotic disorders wow amazing)
  • Three GHD patients who stopped therapy for 12 months regressed and got worse on verbal and non-verbal memory tasks as well as inter-personal sensitivity, anxiety and paranoid ideation
  • GHD patients with no GH therapy scored more highly on depression and showed more distress in mental dysfunction in follow up periods
• Conclusion: GH-deficient TBI patients are depressed and have cognitive impairment and GH therapy reduced depression, social dysfunction, and other cognitive domains

 

Richmond, E., & Rogol, A. D. (2014). Traumatic Brain Injury: Endocrine Consequences in

Children and Adults. Endocrine, 45(1), 3-8.

• Many case reports series after TBI in children and adolescents have documented pituitary dysfunction, including a particularly high frequency of precocious puberty (occurs at an unusually early age).
• 34% of child patients in one study were found to have subnormal growth hormone levels and 43.5% had sub-optimal cortisol levels up to 12 months after TBI — has implications for lasting effects for concussions when received at a young age.
• Sports-related repetitive head trauma might induce pituitary dysfunction
• Further research — Tanriverdi, F., Unluhizarci, K., Kocyigit, I., Tuna, I. S., Karaca, Z., Durak, A. C., & Kelestimur, F. (2008). Brief communication: pituitary volume and function in competing and retired male boxers. Annals of internal medicine, 148(11), 827-831
• A study evaluated the pituitary function in 61 boxers and found that 15% had growth hormone deficiency and 8% had ACTH deficiency

 

Talavage, T. M., Nauman, E. A., Breedlove, E. L., Yoruk, U., Dye, A. E., Morigaki, K. E., &

Leverenz, L. J. (2014). Functionally-Detected Cognitive Impairment in High School

Football Players Without Clinically-Diagnosed Concussion. Journal of

Neurotrauma, 31(4), 327-338.

 

• Studied high school football players and assessed them with HIT helmet collision system, ImPACT testing (concussion test) and fMRI
• Found that many non-clinically diagnosed athletes still exhibited cognitive and neuropsychological deficits associated with concussions
• Underestimation of concussions as many go undetected by neurological testing and can create long-lasting effects without proper treatment
• Urgent need for improved detection of head trauma to reduce future injury risk
• Overall: more players are suffering from neuropsychological damage than is currently being detected with traditional concussion assessment toold

 

Tanriverdi, F., Unluhizarci, K., Kocyigit, I., Tuna, I. S., Karaca, Z., Durak, A. C., & Kelestimur,

831. (2008). Brief Communication: Pituitary Volume and Function in Competing and Retired Male Boxers. Annals of Internal Medicine, 148(11), 827-831.

 

• Investigated pituitary function in 61 retired or active amateur boxers
• 9 of the 61 boxers (15%) had GH deficiency on the GH-stimulation, 5 (8%) had peak cortisol levels lower than the cutoff value and 8 (13%) had isolated hormone deficiency and 3 (5%) had both GH and ACTH deficiency
• Overall, 11 (18%) had pituitary dysfunction
• 8/17 retired boxers (47%) had hypopituitarism, which is substantially higher than the prevalence in non-athletes
• Mean pituitary volume was significantly lower in adult and retired boxers (compared to young boxers) and even lower in GH-deficient boxers
• GH-deficient retired boxers had significantly lower pituitary volume than retired boxers with normal GH levels of the same age
• Overall: lower pituitary volume suggests that boxing/contact sports may affect both the function and anatomy of the pituitary gland

 

Yang, J., Peek-Asa, C., Covassin, T., & Torner, J. C. (2015). Post-concussion Symptoms of

Depression and Anxiety in Division I Collegiate Athletes. Developmental

Neuropsychology, 40(1), 18-23.

• This study examined the effect of baseline psychological symptoms on post-concussion depression and anxiety among a sample of 71 concussed D1 college athletes.
• One-fifth reported depression and one-third reported anxiety. 14.1% experienced both.
• Concussed athletes who had symptoms of depression pre-injury were 4.59 times more likely to experience depression post-injury  / Depression at baseline was the strongest predictor for post-concussion depression and anxiety.
• Athletes with pre-injury depressive symptoms could be considered a vulnerable group and a focus for interventions aimed to prevent or reduce post-concussion symptoms.
• Overall: concussion likely didn’t cause depression, but the concussion could have increased depression in participants who had pre-existing depression prior to injury.

 

Yrondi, A., Brauge, D., LeMen, J., Arbus, C., & Pariente, J. (2017). Depression and Sports-

Related Concussion: A Systematic Review. La Presse Médicale.

• This systematic review of 40 scientific research articles regarding post-concussive depression.
• Their review demonstrates that a depressive disorder can appear immediately after a concussion, within 48 hours.
• Depressive disorders can also appear sometime after a concussion and can be linked with the frequency and number of previous concussions.
• The existence of a mood disorder prior to a concussion was a contributing factor in the onset of a depressive disorder post-concussion (supporting Yang, Peek-Asa, Covassin & Torner, 2015)
• Collegiate athletes were at greater risk for depressive symptoms than high school athletes— different might be related to age (Kontos et al.)
• Repeat concussions increase the risk of a longer-term depressive disorder compared to athletes with no history of a concussion.