LOS ANGELES — Mood episodes in patients with bipolar disorder (BD) that occur more frequently or severely during specific seasons — known as seasonality patterns — are associated with treatment response and different characteristics and subtypes of the disorder, new research suggested.

In a study of more than 1700 patients with BD, investigators found links between seasonality and age at BD onset, BD type, and lifetime use of antipsychotics and any psychotropics. The findings also showed associations between medication response and fall-winter depression and spring-summer hypomania.

“A take-home message is that people should start to think about seasonality with respect to distinct seasons; it shouldn’t just be that a patient has seasonal features or not,” co-investigator Mete Ercis, MD, research fellow in the Department of Psychiatry and Psychology at Mayo Clinic, Rochester, Minnesota, told Medscape Medical News.

Because this was a cross-sectional study, causality cannot be implied, he noted.

“We can say, for example, that people who had early onset of bipolar disorder tended to have higher seasonality, but we cannot say which came first,” Ercis said.

The findings were presented on May 17 at the American Psychiatric Association (APA) 2025 Annual Meeting.

No Standard Definition

Although about 25% of patients with BD experience seasonality, there is no standardized definition or classification of patterns, and the few studies on the topic have shown mixed findings, researchers noted.

The current study included 1702 patients (mean age, 41.4 years; 62% women) enrolled in the Mayo Clinic Bipolar Disorder Biobank who had data on seasonality.

Of these, 45% had at least one type of seasonality and were divided into one of four groups on the basis of when their prevailing mood episodes occurred: Fall-winter depression, spring-summer hypomania, the first two groups combined (biphasic seasonality), and indeterminate seasonality, used when a patient had seasonality patterns that did not fit the other categories.

Outcomes included having BD type 1, a history of psychosis or suicide attempts, early age of onset (≤ 19 years), rapid cycling, and number of lifetime antidepressants, antipsychotics, and any psychotropics used.

‘Striking’ Results

Results showed that any seasonality vs no seasonality was associated with early-onset BD (P = .03), BD type 1 (P = .02), and a higher count of lifetime antipsychotics and any psychotropics (P < .001 for both).

Compared with no seasonality, fall-winter depression was associated with a higher use of lifetime antidepressants (P = .02) and any psychotropic medication (P = .01), and lower Alda A scores for response to lithium (P = .03) and to all mood stabilizers (lithium, lamotrigine, valproate, and carbamazepine; P = .01).

“One thing that was striking was we noticed the treatment resistance to lithium or mood stabilizers were in individuals who had fall-winter depression but not in the other seasonality groups,” Ercis said.

“I was not expecting that, although it makes sense. I thought any seasonality would be associated with treatment resistance, but actually that was not statistically significant,” he added.

Spring-summer hypomania was linked to a lower likelihood of rapid cycling (odds ratio, 0.36; P < .001) and a lower number of lifetime antidepressants used (P = .01).

Higher counts of lifetime antipsychotics and any psychotropics were linked to biphasic seasonality (P = .03 for both) and with indeterminate seasonality (P < .001 for both). Indeterminate seasonality was also associated with having BD type 1 (P = .002), a history of psychosis (P = .03), and early onset (P = .04).

None of the seasonality patterns were significantly associated with a history of suicide attempts.

“These findings underscore the importance of studying how seasonal patterns influence the course and outcomes of BD,” the investigators wrote.

They added that future studies should also explore biologic mechanisms for the underlying seasonality found in the condition.

More Research Needed

Commenting for Medscape Medical News, Adrian Preda, MD, professor of clinical psychiatry at the University of California, Irvine, noted that because of the study’s design, “obviously you cannot comment on cause and effect.” Instead, the investigators presented correlations, he pointed out.

“They were looking at different types of seasonality, which was interesting because usually we don’t separate seasonal bipolar disorder into different subtypes,” said Preda, who was not involved with the research.

He noted that the link between seasonality and a higher count of antipsychotics made him wonder whether patients with seasonality are at risk of receiving more antipsychotic prescriptions, or if greater antipsychotic use is somehow increasing the risk for seasonal episodes. “We can’t know that, but it’s an interesting finding,” he said.

Preda also noted the compelling associations found between the specific seasonal subtypes and lithium response and cycling. “I think this study has very interesting correlations — but we need to know a little bit more in order to say, ‘This is the cause,’” he concluded.

Ercis and Preda reported having no relevant financial relationships.