The study involved 481 individuals experiencing their first episode of psychosis (the first time a person has symptoms such as delusions, hallucinations, or losing touch with reality). Among them, 14.5% showed signs of skin issues (24% of females and 9.8% of males), including rashes, itching, or sensitivity to light. All participants received four weeks of antipsychotic treatment, after which researchers assessed various mental health indicators.

Lead researcher Dr. Joaquín Galvañ (Instituto de Investigación Sanitaria Gregorio Marañón, Madrid) explained:

"After 4 weeks of follow-up, patients with a first episode of psychosis presenting with skin conditions experienced higher levels of depression and risk of suicide. We found that just 7% of the patients without the initial skin conditions had suicidal thoughts or attempts, in contrast, around 25% of the patients with initial skin conditions had suicidal thoughts or attempts. Initial skin conditions are also linked to greater depression and poorer well-being at follow-up.

"This discovery suggests that the presence of skin conditions indicates that these patients are more at risk for worse outcomes than patients who do not have skin conditions after a first episode of psychosis."

The team noted that, if further research supports these results, skin symptoms could serve as an early warning sign for elevated mental health risks, much like how blood tests can signal the likelihood of cancer or heart disease.

Because both the brain and skin develop from the same embryonic layer called the ectoderm, the scientists set out to explore how these two systems might be connected.

Dr. Galvañ added:

"It was already known that between 30% and 60% of people with skin conditions show psychiatric symptoms. What we have done is look at things from the opposite direction; do people with mental health problems have skin conditions, and if so, can this tell us anything useful?

Our findings suggest that dermatological symptoms may represent a marker of illness severity and poor short-term outcomes in the early stages of psychosis, potentially identifying a subgroup of patients with a poorer clinical prognosis who may benefit from early tailored interventions. The reason for the connection is still unclear, but our working hypothesis is that this may be due to the skin and neurological systems having common developmental origins and inflammatory pathways; but this needs to be confirmed. As far as we know this is the first study to show this link in patients with psychosis, so we need follow-up studies to confirm the finding. We also need to understand if this link applies also to a range of other psychiatric conditions, such as bipolar disorder, ADHD, anxiety or depression."

Offering an independent perspective, Professor Eric Ruhe (Professor of Difficult-to-Treat Depression at Radboud University, the Netherlands) commented:

"This is an interesting association between skin problems and a first episode of psychosis. These results need replication in different cohorts but might indeed show a new link between skin and psychopathology.

As the skin and the brain derive from the same embryonic origin, this would worth pursuing further, both diagnostically and mechanistically (which may be more interesting). For example, this association might be used to culture skin cells to begin to understand which treatment is appropriate."

This is an independent comment, Professor Ruhe was not involved in this work.

This research is one of the first to use Centers for Disease Control and Prevention (CDC) data to reveal that older adults -- often left out of overdose analyses -- are increasingly part of the national surge in fentanyl-stimulant deaths. People in this age group face higher risks of overdose because many manage chronic illnesses, take multiple medications, and metabolize drugs more slowly as they age.

Experts describe the opioid epidemic as unfolding in four distinct "waves," each tied to a different drug driving fatal overdoses: prescription opioids in the 1990s, heroin beginning around 2010, fentanyl taking hold in 2013, and a combination of fentanyl and stimulants emerging in 2015.

"A common misconception is that opioid overdoses primarily affect younger people," said Gab Pasia, M.A., lead author of the study and a medical student at the University of Nevada, Reno School of Medicine. "Our analysis shows that older adults are also impacted by fentanyl-related deaths and that stimulant involvement has become much more common in this group. This suggests older adults are affected by the current fourth wave of the opioid crisis, following similar patterns seen in younger populations."

To conduct the study, researchers examined 404,964 death certificates listing fentanyl as a cause of death from 1999 to 2023, using data from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) system. Of those deaths, 17,040 involved adults 65 and older, while 387,924 were among adults aged 25 to 64.

Between 2015 and 2023, fentanyl-related deaths rose from 264 to 4,144 among older adults (a 1,470% increase) and from 8,513 to 64,694 among younger adults (a 660% increase). Within the older population, deaths involving both fentanyl and stimulants grew from 8.7% (23 of 264 fentanyl deaths) in 2015 to 49.9% (2,070 of 4,144) in 2023 -- a staggering 9,000% rise. In comparison, among younger adults, fentanyl-stimulant deaths rose from 21.3% (1,812 of 8,513) to 59.3% (38,333 of 64,694) over the same period, a 2,115% increase.

Researchers chose to highlight 2015 and 2023 in their analysis because 2015 marked the beginning of the epidemic's fourth wave, when fentanyl-stimulant deaths among older adults were at their lowest, and 2023 represented the most recent year of CDC data available.

The researchers noted that the rise in fentanyl deaths involving stimulants in older adults began to sharply rise in 2020, while deaths linked to other substances stayed the same or declined. Cocaine and methamphetamines were the most common stimulants paired with fentanyl among the older adults studied, surpassing alcohol, heroin, and benzodiazepines such as Xanax and Valium.

"National data have shown rising fentanyl-stimulant use among all adults," said Mr. Pasia. "Because our analysis was a national, cross-sectional study, we were only able to describe patterns over time -- not determine the underlying reasons why they are occurring. However, the findings underscore that fentanyl overdoses in older adults are often multi-substance deaths -- not due to fentanyl alone -- and the importance of sharing drug misuse prevention strategies to older patients."

The authors noted anesthesiologists and other pain medicine specialists should:

• Recognize that polysubstance use can occur in all age groups, not only in young adults.
• Be cautious when prescribing opioids to adults 65 or older by carefully assessing medication history, closely monitoring patients prescribed opioids who may have a history of stimulant use for potential side effects, and considering non-opioid options when possible.
• Use harm-reduction approaches such as involving caregivers in naloxone education, simplifying medication routines, using clear labeling and safe storage instructions and making sure instructions are easy to understand for those with memory or vision challenges.
• Screen older patients for a broad range of substance exposures, beyond prescribed opioids, to better anticipate complications and adjust perioperative planning.

"Older adults who are prescribed opioids, or their caregivers, should ask their clinicians about overdose prevention strategies, such as having naloxone available and knowing the signs of an overdose," said Richard Wang, M.D., an anesthesiology resident at Rush University Medical Center, Chicago and co-author of the study. "With these trends in mind, it is more important than ever to minimize opioid use in this vulnerable group and use other pain control methods when appropriate. Proper patient education and regularly reviewing medication lists could help to flatten this terrible trend."