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Introduction

Severe and persistent mental illnesses (SPMI) encompass psychiatric conditions including psychotic disorders (eg, schizophrenia), affective and mood disorders (eg, bipolar disorder, major depression), anxiety disorders including posttraumatic stress disorder (PTSD) and trauma-related conditions, and developmental disorders such as autism spectrum disorder (ASD).

Emerging research supports a multifactorial causation model in which polygenic genetic vulnerability interacts dynamically with diverse modifiable environmental factors, notably including postinfectious inflammation and substance use (petty drug abuse), as key pathways affecting illness onset and persistence^1,2,3

Genetic Vulnerability Across Disorders

• Psychotic disorders such as schizophrenia demonstrate heritability estimates up to 80%, mediated by genetic variants affecting neural networks and cognitive endophenotypes.⁴
• Mood and affective disorders show high polygenic risk (40% to 70%) overlapping with psychosis and anxiety disorders.⁵
• Anxiety, obsessive compulsive disorder (OCD), PTSD, and trauma-related disorders share moderate to high heritability (40% to 65%) along with genetic overlap with mood disorders.^6,7
• Autism spectrum disorder is highly heritable (70% to 90%) with broad genetic heterogeneity impacting related developmental and psychiatric vulnerabilities.⁸ The majority of spectrum-disorder patients suffer with neuropsychiatric comorbidities such as depression, epilepsy, anxiety, and psychosis such as schizophrenia.^9,10

Environmental Risk Factors

Key environmental contributors to SPMI include:

1. Parental Communication Deviance: Fragmented, ambiguous family communication patterns elevate risk for schizophrenia spectrum and impact social and emotional development relevant to mood, anxiety, and autistic spectrum conditions.^3,11,12
2. Inadequacy or Deprivation, Maltreatment: Whether intentional or not, caretakers can directly affect physical and psychiatric well-being.^13-17
3. Childhood Lead Exposure: Lead neurotoxicity disrupts brain development and neurotransmission, increasing multifactorial risk for psychiatric and neurodevelopmental disorders.^2,18
4. Head Injury/Traumatic Brain Injury (TBI): Neural damage and neuroinflammation after traumatic injury amplify genetic vulnerability to psychosis, mood, anxiety, and developmental impairments.^5,19
5. Postinfectious Inflammation: Systemic infections trigger cytokine storms and brain neuroinflammation disrupting neurotransmitter systems, neuroendocrine regulation, and sometimes induc autoimmune injury, contributing to diverse psychiatric syndromes.^1,20
6. Petty Drug Abuse: Use of caffeine, tobacco or nicotine, cannabis, alcohol, and energy drinks constitutes a modifiable environmental risk factor interacting with genetic vulnerability, elevating risk and persistence of psychiatric disorders.⁵

Post-Infectious Inflammation as a Distinct Environmental Factor

Infections provoke systemic immune activation with elevated cytokines (IL-6, TNF-α, IL-1β) that signal across the blood-brain barrier activating microglia, causing neuroinflammation, impaired synaptic plasticity, neurotransmitter balance disruption, and sometimes autoimmune neuronal injury.^1,20 These contribute to onset or worsening of depression, psychosis, PTSD, OCD, and neurodevelopmental disorders.

Concluding Thoughts

Severe and persistent mental illnesses arise from the intersection of inherited genetic liability, aberrant communication in the family, and multiple environmental risks including concussion/TBI, environmental toxin exposure, postinfectious inflammation, and petty drug abuse.¹⁷

Together, neuroinflammation, exposures to environmental toxins, brain trauma, family environment, and substance use or abuse synergistically disrupt brain function governing cognition, mood, and behavior. Prevention and treatment must integrate approaches addressing infectious, toxic, psychosocial, and substance-related risks to reduce illness burden and improve outcomes.

Table 1. Integrated Risk Factors and Mechanisms In Severe and Persistent Mental Illness

Table 2. Post-Infectious Neuroinflammatory Pathway to Psychiatric Symptoms

Table 3. Clinical and Public Health Intervention Stratification for Post-Infectious Neuropsychiatric Risks

Dr Best is the director of The Neuroscience Center in Deerfield, Illinois.

References

1. Boldrini M, Canoll PD, Klein RS. How COVID-19 affects the brain. JAMA Psychiatry. 2021;78(6):682-683.

2. McFarland MJ, Reuben A, Hauer M. Contribution of childhood lead exposure to psychopathology in the us population over the past 75 years. J Child Psychol Psychiatry. 2024.

3. Roisko R, Wahlberg KE, Hakko H, et al. Communication deviance in parents of families with adoptees at a high or low risk of schizophrenia-spectrum disorders and its associations with attributes of the adoptee and the adoptive parents. Psych Res. 2011;185(1):66-71.

4. Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry. 2003;60(12):1187-1192.

5. Robinson N, Bergen SE. Environmental risk factors for schizophrenia and bipolar disorder and their relationship to genetic risk: current knowledge and future directions. Front Genet. 2021;12:686666.

6. Burton CL, Park LS, Corfield EC, et al. Heritability of obsessive–compulsive trait dimensions in youth from the general population. Transl Psychiatry. 2018;8:191.

7. Mataix-Cols D, Fernández de la Cruz L, Beucke JC, et al. Heritability of clinically diagnosed obsessive-compulsive disorder among twins. JAMA Psychiatry. 2024;81(6):631-632.

8. Sandin S, Lichtenstein P, Kuja-Halkola R, et al. The heritability of autism spectrum disorder. Am J Psychiatry. 2017;318(12):1182.

9. Hughes JR, Melyn M. EEG and seizures in autistic children and adolescents: further findings with therapeutic implications. Clin EEG Neurosci. 2005;36(1):15-20.

10. Underwood JFG, DelPozo-Banos M. Neurological and psychiatric disorders among autistic adults: a population healthcare record study.Psychological Medicine. 2022;53(12):5663-5673.

11. Levy DL, Coleman MJ, Sung H, et al. (2010). The genetic basis of thought disorder and language and communication disturbances in schizophrenia. J Neurolinguistics. 2010;23(3):176-192.

12. de Sousa P, Varese F, Sellwood W, et al. Parental communication and psychosis: a meta-analysis. Schizophr Bull. 2014;40(4):756-768.

13. Binder EB, Bradley RG, Liu W, et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA. 2008;299(11):1291-1305.

14. McGrath JJ, Eyles DW, Pedersen CB, et al. Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study. Arch Gen Psychiatry. 2010;67(9):889-894.

15. Schulz-Heik RJ, Rhee SH, Silvern LE. Testing genetic and environmental mediation. Behavior Genetics. 2009;40(3), 338-348.

16. South SC, Schafer MH, Ferraro KF. Genetic and environmental overlap between childhood maltreatment and adult physical health. twin research and human genetics. 2015;18(5):533-544.

17. Uher R. Gene–environment interactions in severe mental illness. Frontiers in Psychiatry. 2014;5:48.

18. Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry. 2003;60(12):1187-1192.

19. Orlovska S, Pedersen MS, Benros ME, et al.Head injury as risk factor for psychiatric disorders: a nationwide register-based follow-up study of 113,906 persons with head injury. Am J Psychiatry. 2014;171(4):463-469.

20. Okobi OE, Ayo-Farai O, Tran M, et al. The impact of infectious diseases on psychiatric disorders: a systematic review. Cureus. 2024.

Jocelyn Solis-Moreira is a freelance health and science journalist based in New York.

There’s nothing like shutting the bathroom door, maybe even locking it and hiding away from one’s family, even just for a few minutes.

The toilet has long been a sanctuary to catch up on some light reading and, for the harried parent, a spot for some rare “me time.” But the amount of toilet time has become a more pressing medical issue as people shift from reading physical books and magazines to endlessly scrolling on their smartphones.

There are consequences to sitting longer than we used to on the toilet: People are reporting a higher rate of hemorrhoids when they bring their smartphones to the bathroom, according to a new study in PLOS One.

Hemorrhoids are groups of veins in the rectum and outside the anus that can swell and enlarge due to increased pressure, which can create itchiness, discomfort, pain and bleeding.

This new research provides concrete evidence of what many have long suspected: People lose track of time in the bathroom when they have their phones, said Dr. Trisha Pasricha, the study’s senior author, a gastroenterologist at Massachusetts General Hospital and an instructor at Harvard Medical School.

All this scrolling is messing with people’s health.

“The entire business model of these social media apps is to distract us, make us lose track of time and addict us to the algorithm,” Pasricha said. “We’re just now understanding how much smartphones impact lots of other factors in our lives.”

The study invited 125 adults undergoing a screening colonoscopy to complete a survey on their toilet habits, including whether they scroll online in the bathroom. The survey also asked questions about straining, fiber intake and exercise routines — additional factors involved in hemorrhoid risk. Confirmation of hemorrhoids was detected by endoscopy.

Sixty-six percent of survey respondents reported regularly using their smartphones on the toilet. Those who did spent significantly more time on the loo than people who left their smartphones outside the bathroom. About 54% of respondents reported using their phones to read news, while about 44% spent their time on social media.

How much did mindless scrolling on the toilet affect hemorrhoid risk? Researchers found regular smartphone use on the toilet was associated with a 46% greater risk of having hemorrhoids. About 37% of smartphone users spend over five minutes on the toilet compared with 7% of non-smartphone users.

Hemorrhoids are often associated with prolonged sitting; however, the risk is higher when sitting for too long on a toilet. The open toilet seat compresses the rectal area, keeping your bottom in a lower position than if you were sitting on a chair. Over time, the increased pressure from the toilet seat can cause blood to pool in the rectum.

“When you’re sitting on an open toilet bowl, you have no pelvic floor support,” Pasricha said.

Along with spending more time sitting, using a smartphone on the toilet may increase the risk of hemorrhoids due to poor posture.

Dr. Hima Ghanta, a colorectal surgeon at Holy Name Medical Center in New Jersey who was not involved in the study, said people tend to hunch when looking down at their phones, which isn’t ideal for excretion because the rectum and anus curve from the colon. The squatted position is a better option for a smooth bowel movement.

“People way back who had to squat did not tend to have as many issues, but because we changed the angle we’re evacuating and sitting longer, these are exacerbating factors for hemorrhoids,” Ghanta said.

What about constipation? The study results suggest the issue is most likely the time spent sitting on the toilet rather than straining, Pasricha said.

People who used their smartphones weren’t more constipated than those who didn’t, she said. “They didn’t actually strain harder to have a bowel movement than the ones who didn’t. My hypothesis is that it’s passive smartphone use that causes these hemorrhoidal cushions to become engorged and bulge, and that’s what leads to hemorrhoids.”

While the study involved only adults 45 years and older, Pasricha said the results can also apply to younger people, as they are the most likely to always carry their phones with them.

“It was helpful to have this (45 and older) group because there were people who didn’t use their smartphones on the toilet. So we had a comparison group,” Pasricha explained. “Having a third of people not bringing their smartphones to the bathroom helped us understand what a baseline could look like, especially as I imagine the situation is more profound for younger individuals.”

Dr. Sandhya Shukla, a gastroenterologist at Atlantic Coast Gastroenterology Associates in New Jersey who was not involved in the study, said she is seeing younger patients diagnosed with hemorrhoid issues. Though other factors, such as low fiber intake and obesity, can explain why this is happening, she said that scrolling mindlessly on the toilet is one of the major contributors.

The simplest answer is to avoid bringing your phone to the bathroom. If you do bring it, however, all the doctors recommend limiting your sitting time. Gastroenterologists previously advised people to spend no more than 10 minutes sitting on the toilet. Three to five minutes would be ideal.

“A lot of expert consensus is three minutes per bowel movement, but everyone is different,” Shukla said.

Setting a timer can be helpful if you’re prone to mindless scrolling. Pasricha also recommended checking in with yourself after two TikTok videos to see whether you’re having a productive toilet session. If the magic isn’t happening, it’s better to get up and try again later than to sit and wait on the toilet bowl.

Ghanta explained it best: There are many things in life we’re rushing to get through, and we often say to slow down and take time to smell the roses. But not on the toilet.

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Triple-negative breast cancer is particularly aggressive and difficult to treat; but recent research may offer a new way to target the often-deadly disease. 

A team of researchers from the University of Mississippi found that coating nanoparticles containing cancer therapies in a sugar-like substance makes them more effective in targeting this cancer. They published their research in Advanced Healthcare Materials. 

It’s called triple-negative because it does not have any of the three things that we have developed treatments to target in cancer. It particularly affects young women, and it particularly affects Black and African American women. 

What that means is we really urgently need to think creatively about new ways to try and treat this cancer.” 

Eden Tanner, assistant professor of chemistry and biochemistry

More than 1 in 10 breast cancer diagnoses are for triple-negative breast cancer. This cancer is particularly difficult to treat because it does not create high levels of estrogen, progesterone or the protein HER2, all of which are usually used to target cancer for drug delivery. 

Mississippi’s rates of triple-negative breast cancer are higher than average. A 2024 report from the University of Mississippi Medical Center showed that 37% of breast cancer cases treated at the center between 2016 and 2023 were triple-negative – more than double the national average. 

The aggressive nature of this cancer, combined with its resistance to many usual therapies, means its mortality rate is higher than that of other cancers. 

While this cancer may not elevate levels of usual drug targets, the research team found a novel way to deliver cancer therapies directly to the cancer cells. 

“One thing that’s consistent across all of the patients (with triple-negative breast cancer) is that they overexpress glucose transporters to bring more sugars to the cells,” Tanner said. “Essentially, it has a sweet tooth. So, how can we get it to take its medicine? We wrap it in sugar.” 

By coating the nanoparticle cancer therapy in sugar, the researchers effectively “trick” the cancer into absorbing the medication, Tanner said. 

“The drug itself is encapsulated in the nanoparticle, which is then coated in the glucose,” said Mira Patel, a junior chemistry major from Vicksburg, Mississippi. 

When injected into the bloodstream, these sugar-coated cancer therapies can “hitch a ride” on red and white blood cells, Tanner said. Riding the blood cells like a bus, the medication travels across the body and ultimately becomes trapped by the cancer’s glucose transporters. 

“Because triple-negative breast cancer cells overexpress GLUT-transporters, there’s more of an affinity between the nanoparticles and those cells,” said Patel, a co-author of the study who first joined the Tanner Lab through the ARISE Summer Program as a high school junior. 

“This method could provide something that will change the way we treat this cancer in the future, and in a way that won’t affect our regular, healthy cells.” 

Triple-negative breast cancer is not the only disease that overexpresses glucose transporters, meaning the drug delivery method could be used to treat other illnesses. 

“We haven’t tested the technology on those other diseases yet, but there’s a good reason to believe that a similar strategy might work,” Tanner said. “That’s exciting news for diseases like colon cancer, brain cancer and fatty liver disease, which also have high levels of glucose transporters.” 

Before it can be put into practice, however, the researchers must test the delivery method in disease conditions. Given the prevalence of triple-negative breast cancer in the state, the results of their work could save lives in Mississippi. 

“One of our strongest motivations as a research group is to think about scientific innovations that can really help Mississippians,” Tanner said. “Given the profile of our state, we feel particularly motivated to address these problems.” 

This material is based on work supported by the National Institutes of Health grant no. P20GM130460.