Stress-Immune Response & Trichotillomania (TTM)

I have been reading a lot of interesting literature on the immune system and psychological disorders. For example, studies have described onset of tics and OCD following infection from strep, or fever in childhood. Another study suggests that early early-onset forms of TS and OCD may be causally related to streptococcal infections and immune abnormalities.

I actually got strep bad when I was 8 or so. I remember my aunt Windy saying I lost weight and I felt surprised by her concern because I always assumed my parents were “on top of it”. (I think I was just a skinny kid though it had nothing to do with the viral infection itself honestly). I have some weird memories of a horrible fever I got at summer camp too 7-10. The camp called my mom but she couldn’t or wouldn’t get me ( I’m sure campy ain’t cheap and I wasn’t going to die from strep/fever). So they left me alone in a cottage in the woods away from the other kids for 5 days. Someone brought me food and would check-in of course. I remember going to this pool filled with cold murky pond water and swimming in it and then getting afraid there were monsters in it. Not sure they should have left me alone thinking about the bacteria in that pool when I was fighting an infection but that’s how the 90’s childhood was and it was great.

Anyway, I did end up getting TTM shortly there after. Of course I started when a kid told me if an eye lash fell out, you could make a wish and it would come true. So I went to the bathroom to strategically make wishes and “fix” the whole world. That could have been the end of it but it wasn’t. I stopped wishing but kept pulling. I do remember having OCD thoughts/impulses. If I moved my toe in a shoe, I would have to move the other. I also developed a stutter. I could not say “lemonade” well. Words starting with “L” were hard for me. It didn’t last long though. I haven’t had a stutter since age 9 or so.

So for me reading about the viral infections leading to higher incidence of OCD/TS (Tourettes) and the relationship of those disorders with TTM, I can’t help but wonder how the pathways (muscle memory, brain circuitry, skin immune response) could have been heavily influenced to be more ingrained by a virus that dysregulated my immune response to stress to allow TTM to take the shape it has.

Some interesting aspects to this.

1.) “Broadly, the immune system comprises cells, proteins, organs, and tissues that work together to provide protection against bodily disease and damage (see Box for explanations of relevant immunological parameters). Several facets of the human immune system have been empirically associated with stress. During acute stress lasting a matter of minutes, certain kinds of cells are mobilized into the bloodstream, potentially preparing the body for injury or infection during “fight or flight” [1]. Acute stress also increases blood levels of pro-inflammatory cytokines [2]. Chronic stress lasting from days to years, like acute stress, is associated with higher levels of pro-inflammatory cytokines, but with potentially different health consequences [3]. Inflammation is a necessary short-term response for eliminating pathogens and initiating healing, but chronic, systemic inflammation represents dysregulation of the immune system and increases risk for chronic diseases, including atherosclerosis and frailty [4]. Another consequence of chronic stress is activation of latent viruses. Latent virus activation can reflect the loss of immunological control over the virus, and frequent activation can cause wear-and-tear on the immune system [5].

Interestingly, these responses may not be the same for everyone. Those who have experienced early adversity, for example, may be more likely to exhibit exaggerated immune reactions to stress [67]. Currently, the field is moving toward a greater understanding of who might be most at risk for chronic inflammation and other forms of immunological dysregulation, and why. This question is important not only for health, but also for longevity, as evidence suggests that the immunological effects of chronic stress can advance cellular aging and shorten telomere length [8]. “


Thoughts: Does this mean that stress in childhood could dysregulated my immune response making me more susceptible to TTM? Maybe.

“Stress that occurs early in development (e.g., maltreatment, poverty, and other adverse experiences) has immunological consequences that can be observed both in the near and long term after the stressor occurs. Early life stress (ELS) in children associates with immunological dysregulation, including low basal levels of cytokines that control immune responses [10]. When immune cells were stimulated in vitro (e.g., with tetanus toxoid), those cells from children who experienced ELS produced more pro-inflammatory cytokines [10].”

Ok, why aren’t we looking at this TTM populations? FINALLY, someone did do an interesting study on TTM “Salivary Inflammatory Markers in Trichotillomania: A Pilot Study


Background: Immune dysregulation has been hypothesized to be important in the development and pathophysiology of compulsive disorders such as obsessive compulsive disorder (OCD), which has a high comorbid overlap with trichotillomania (both are OC-related disorders). The role of inflammation in the pathophysiology of trichotillomania has garnered little research to date.”

BTW, This was published August 2018 so its NEW new stuff. Exciting!

“There are several lines of evidence to suggest a role for immune-mediated pathophysiology in a variety of psychiatric conditions, including OCD, a disorder with phenomenological and possibly biological links to trichotillomania [4]. Studies measuring plasma cytokine levels have demonstrated a significant reduction in interleukin-1β (IL-1β) levels in OCD subjects compared with controls, but no significant differences in plasma levels of IL-6 and tumor necrosis factor-α (TNF-α) have been shown [5]. A recent case-control study of 20 adults with OCD who underwent PET imaging, however, found that translocator protein distribution volume (translocator protein density increases when microglia are activated during neuroinflammation and the distribution volume is an index of translocator protein density) was significantly elevated in the dorsal caudate, orbitofrontal cortex, thalamus, ventral striatum, and dorsal putamen [6] demonstrating inflammation within the neurocircuitry of OCD. The only study which included subjects with trichotillomania examined cerebrospinal fluid and found that the mean cerebrospinal fluid IL-6 levels did not differ between OCD patients (n = 26) and controls or between trichotillomania patients (n = 9) and their matched controls [7].

Cytokines are small, soluble proteins secreted by cells to influence the behavior of other cells via regulation of cellular immunity and inflammatory response. Pro-inflammatory cytokines include IL-1β, IL-6, and TNF-α, which are produced both peripherally and in the central nervous system. TNF-α stimulates vagal afferents and is produced by neurons and glial cells in an activity-dependent manner [89]. IL-6 and IL-1 are also produced in the brain, where they mediate neuroinflammation and response to injury [910]. Interestingly, IL-1β, IL-6, and TNF-α also mediate neuroprotection to excitotoxicity [11]. IL-8 is associated with inflammation and is increased by oxidant stress, which in a vicious cycle causes the recruitment of inflammatory cells and induces an increase in oxidant stress mediators. While poorly understood, it is increasingly recognized that there is important cross-talk between the peripheral immune system and central nervous system functioning, whereby inflammation may influence psychiatric symptoms and cognition [1213].

Although some studies shed some light on the topic of possible role inflammation in compulsive disorders, many questions remain unanswered. Understanding the role of cytokines in compulsive behaviors such as trichotillomania may allow for a greater understanding of the pathophysiology underlying this disorder and related disorders. Based on the extant literature, we hypothesized that salivary cytokine levels would be abnormal in trichotillomania. By examining the relationship between salivary cytokines and trichotillomania, we hope to determine a possible biological signal supportive of follow-up work using blood samples (which may more accurately capture central inflammatory pathways than saliva).”


“Inflammatory dysfunction has been implicated in other mental health disorders such as OCD and schizophrenia [412], but has received scant study in the context of trichotillomania. The current study examined a range of salivary inflammatory markers (IL-1β, IL-6, IL-8, and TNF-α) in a sample of patients with trichotillomania, and whether inflammation related to symptom severity and other clinical measures. The key finding was that patients overall had relatively low level of salivary inflammatory markers compared to externally published norms. Reduced autonomic response to painful stimulation, measured using the cold pressor task, has previously been reported in trichotillomania [23] and in skin picking disorder [24]. Many patients with trichotillomania report that hair pulling is not painful, especially after the habit has developed [25]. In the general population, cold pressor task pain perception was positively correlated with higher inflammation as indexed by C-reactive protein [26]. Acute inflammation in healthy volunteers, such as induced by an endotoxin model, increases pain response on the Cold Pressor test [27]. Therefore, 1 intriguing possibility raised by the present data is that inflammatory pathways are dampened in trichotillomania; and that this in turn may contribute to persistence of hair pulling due to reduced pain response. Thus, the current findings may indicate common reduction of IL-1β across OCD and trichotillomania, but that trichotillomania is linked with a broader range of inflammatory changes.”

HOLY MOLY. The treatment implications to this are totally untapped.

Other fun reading;

1. Camila d'Angelo LS, Eagle DM, Grant JE, Fineberg NA, Robbins TW, Chamberlain SR. Animal models of obsessive-compulsive spectrum disorders. CNS Spectr. 2014;19:28–49. [PubMed]

2. Mitchell RH, Goldstein BI. Inflammation in children and adolescents with neuropsychiatric disorders: a systematic review. J Am Acad Child Adolesc Psychiatry. 2014;53:274–296. [PubMed]

3. Gray SM, Bloch MH. Systematic review of proinflammatory cytokines in obsessive-compulsive disorder. Curr Psychiatry Rep. 2012;14:220–228.[PMC free article] [PubMed]

4. Attwells S, Setiawan E, Wilson AA, Rusjan PM, Mizrahi R, Miler L, Xu C, Richter MA, Kahn A, Kish SJ, Houle S, Ravindran L, Meyer JH. Inflammation in the ­neurocircuitry of obsessive-compulsive ­disorder. JAMA Psychiatry. 2017;74:833–840. [PMC free article] [PubMed]

5. Carpenter LL, Heninger GR, McDougle CG, Tyrka AR, Epperson CN, Price LH. Cerebrospinal fluid interleukin-6 in obsessive-compulsive disorder and trichotillomania. Psychiatry Res. 2002;112:257–262. [PubMed]

Emily Kight