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July 14, 2025
Serotonin is a key chemical in the body that helps regulate mood, behavior, and also many physical functions such as sleep and digestion. It has also been linked to how ADHD (attention-deficit/hyperactivity disorder) develops in the brain. This study looks at how serotonin may be involved in both the mental health and physical health conditions that often occur alongside ADHD.
It is well-established that ADHD is more than just trouble focusing or staying still. For many, it brings along a host of other physical and mental health challenges. It is very common for those with ADHD to also have other diagnosed disorders. For example, those with ADHD are often also diagnosed with depression, anxiety, or sleep disorders. When these issues overlap, they are called comorbidities.
A new comprehensive review, led by Dr. Stephen V. Faraone and colleagues, delves into how serotonin (5-HT), a major brain chemical, may be at the heart of many of these common comorbidities.
Serotonin is a neurotransmitter most often linked to mood, but its role in regulating the body has much broader implications. It regulates sleep, digestion, metabolism, hormonal balance, and even immune responses. Although ADHD has long been associated with dopamine and norepinephrine dysregulation, this review suggests that serotonin also plays a central role, especially when it comes to comorbid conditions.
This research suggests that serotonin dysregulation could explain the diverse and sometimes puzzling range of symptoms seen in ADHD patients. It supports a more integrative model of ADHD—one that goes beyond the brain’s attention, reward and executive control circuits and considers broader physiological and psychological health.
future research into the role of serotonin could help develop more tailored interventions, especially for patients who don't respond well to stimulant medications. Future studies may focus on serotonin’s role in early ADHD development and how it interacts with environmental and genetic factors.
This study is a strong reminder that ADHD is a complex, multifaceted condition. Differential diagnosis is crucial to properly diagnosing and treating ADHD. Clinicians' understanding of the underlying link between ADHD and its common comorbidities may help future ADHD patients receive the individualized care they need. By shedding light on serotonin’s wide-reaching influence, this study may provide a valuable roadmap for improving how we diagnose and treat those with complex comorbidities in the future.
Faraone SV, Ward CL, Boucher M, Elbekai R, Brunner E. Role of serotonin in psychiatric and somatic comorbidities of attention-deficit/hyperactivity disorder: A systematic literature review. Neurosci Biobehav Rev. 2025 Jul 5:106275. doi: 10.1016/j.neubiorev.2025.106275. Epub ahead of print. PMID: 40623558.
In the general population, most mothers experience mood disturbances right after childbirth, commonly known as postpartum blues, baby blues, or maternity blues. Yet only about one in six develop symptoms with a duration and magnitude that require treatment for depressive disorder, and one in ten for anxiety disorder.
To what extent does ADHD contribute to the risk of such disorders following childbirth? A Swedish study team used the country’s single-payer health insurance database and other national registers to conduct the first nationwide population study to explore this question.
They used the medical birth register to identify all 420,513 women above 15 years of age who gave birth to their first child, and all 352,534 who gave birth to their second child, between 2005 and 2013. They excluded miscarriages. They then looked for diagnoses of depression and/or anxiety disorders up to a year following childbirth.
In the study population, 3,515 mothers had been diagnosed with ADHD, and the other 769,532 had no such diagnosis.
Following childbirth, depression disorders were five times more prevalent among mothers with ADHD than among their non-ADHD peers. Excluding individuals with a prior history of depression made little difference, lowering the prevalence ratio to just under 5. Among women under 25, the prevalence ratio was still above 3, while for those 25 and older it was above 6.
Similarly, anxiety disorders were over five times more prevalent among mothers with ADHD than among their non-ADHD peers. Once again, excluding individuals with a prior history of depression made little difference, lowering the prevalence ratio to just under 5. Among women under 25, the prevalence ratio was still above 3, while for those 25 and older it was above 6.
The team cautioned, “There is a potential risk of surveillance bias as women diagnosed with ADHD are more likely to have repeated visits to psychiatric care and might have an enhanced likelihood of also being diagnosed with depression and anxiety disorders postpartum, compared to women without ADHD.”
Nevertheless, they concluded, “ADHD is an important risk factor for both depression and anxiety disorders in the postpartum period and should be considered in the post- pregnancy maternal care, regardless of sociodemographic factors and the presence of other psychiatric disorders. Parental education prior to conception, psychological surveillance during, and social support after childbirth should be provided to women diagnosed with ADHD.”
Israel has a military draft that applies to males and females alike, except orthodox women and orthodox male seminary(yeshiva) students, who are exempt. Upon turning 17 every Israeli undergoes a medical review, including both a physical and psychiatric assessment, in preparation for the draft. The Draft Board Registry maintains comprehensive health information on all unselected Israelis until they turn 21. The registry also tracks all family members of draft registrants, including full siblings.
An Israeli study team used registry records from 1998 through2014 to obtain data for a total of over a million individuals (1,085,388). Because of the exemption for orthodox women, 59% were male.
The team identified 903,690 full siblings in the study population (58% males), including 166,359 male-male sibling pairs, 104,494 female-female sibling pairs, and 197,571 opposite-sex sibling pairs.
Next, the team identified all cases in the study population with a diagnosis of a psychiatric disorder, low IQ (≥2 standard deviations below the population mean), Type-1 diabetes, hernia, or hematological malignancies. It matched each case with ten age- and sex-matched controls selected at random from the study population. Then, for each case and case-matched controls, it identified all siblings.
There were 3,272 cases receiving treatment for ADHD, 2,128 with autistic spectrum disorder, 9,572 with severe/profound intellectual disability, 7,902 with psychotic disorders, 9,704 with mood disorders, 10,606with anxiety disorders, 24,815 with personality disorders, 791 with substance abuse disorders, 31,186 with low IQ, 2,770 with Type-1 diabetes, 30,199 with a hernia, and 931 with hematological malignancies.
Draftees with ADHD were five and a half times more likely to have a sibling with ADHD than controls.
There were no significant associations between ADHD and any of the somatic disorders - Type-1 diabetes, hernia, or hematological malignancies - nor between ADHD and low IQ.
There were also no significant associations between ADHD and autism spectrum disorder, severe/profound intellectual disability, mood disorders, and substance use disorders.
On the other hand, draftees with ADHD were more than 40% more likely to have siblings with anxiety or personality disorders than controls.
Surprisingly, draftees with ADHD were less than half as likely to have siblings with psychotic disorders than controls.
There were some limitations. The psychiatric classification system used by the Israeli military did not permit assessing the risk of bipolar disorder and depression separately. That meant having to use a broader category of mood disorders, including both disorders. In addition, the military diagnostic system does not allow diagnosis of comorbid psychiatric disorders in the same individual, instead of assigning only the most severe diagnosis.
Although there has been much research documenting that ADHD adults are at risk for other psychiatric and substance use disorders, relatively little is known about whether ADHD puts adults at risk specifically for somatic medical disorders.
Given that people with ADHD tend toward being disorganized and inattentive, and that they tend to favor short-term over long-term rewards, it seems logical that they should be at higher risk for adverse medical outcomes. But what does the data say?
In a systematic review of the literature, Instances and colleagues have provided a thorough overview of this issue. Although they found 126 studies, most were small and were of "modest quality". Thus, their results must be considered to be suggestive, not definitive for most of the somatic conditions they studied.
Also, they excluded articles about traumatic injuries because the association between ADHD and such injuries is well established. Using qualitative review methods, they classified associations as being a) well-established; b) tentative, or c) lacking sufficient data.
Only three conditions met their criteria for being a well-established association: asthma, sleep disorders, and obesity.
They found tentative evidence implicating ADHD as a risk factor for three conditions: migraine headaches, celiac disease, and diseases of the circulatory system.
These data are intriguing, but cannot tell us why ADHD people are at increased risk for somatic conditions. One possibility is that suffering from ADHD symptoms can lead to an unhealthy lifestyle, which leads to increased medical risk. Another possibility is that the biological systems that are dysregulated in ADHD are also dysregulated in some medical disorders. For example, we know that there is some overlap between the genes that increase the risk for ADHD and those that increase the risk for obesity. We also know that the dopamine system has been implicated in both disorders.
Instances and colleagues also point out that some medical conditions might lead to symptoms that mimic ADHD. They give sleep-disordered breathing as an example of a condition that can lead to the symptom of inattention.
But this seems to be the exception, not the rule. Other medical conditions co-occurring with ADHD seem to be true comorbidities, rather than the case of one disorder causing the other. Thus, primary care clinicians should be alert to the fact that many of their patients with obesity, asthma, or sleep disorders might also have ADHD.
By screening such patients for ADHD and treating that disorder, you may improve their medical outcomes indirectly via increased compliance with your treatment regime and an improvement in health behaviors. We don't yet have data to confirm these latter ideas, as the relevant studies have not yet been done.
Antidepressants are the primary drug treatment for depressive disorders, which affect 15–20% of pregnant women. They are among the most widely prescribed medications worldwide, and their use has increased in recent decades. Understanding their reproductive safety is critical to support informed, evidence-based prescribing during pregnancy.
A new meta-analysis sheds important light on one of the most debated concerns: whether children born to mothers who took antidepressants during pregnancy face a higher risk of ADHD.
The Study:
Pooling 14 studies covering more than 14 million participants, the analysis found that prenatal antidepressant exposure was associated with a 35% higher rate of ADHD in offspring compared to no exposure. A separate look at SSRIs (the most widely prescribed class of antidepressants, including Prozac and Zoloft) across 11 studies and over four million pregnancies found an even higher apparent risk (44%) after correcting for publication bias. On the surface, these are striking numbers.
Both associations came with an important caveat: enormous variation between individual studies, a statistical red flag suggesting the results may not reflect a true underlying effect. More tellingly, the apparent risk evaporated entirely when researchers applied a more rigorous method — comparing siblings within the same family, where one child was exposed to antidepressants in the womb, and another was not.
This sibling-comparison design is particularly powerful because it automatically controls for factors that run in families: shared genes, household environment, parenting, and socioeconomic conditions. When those influences are held constant, the link between antidepressant exposure and ADHD disappears. The same pattern held for SSRIs specifically.
Two other antidepressant classes, SNRIs (serotonin norepinephrine reuptake inhibitors) and tricyclics, showed no significant association in any analysis.
“Confounding by Indication”:
The probable driver of the initial association is what researchers call confounding by indication. The very condition being treated (depression) is itself a risk factor for ADHD in offspring, independently of any medication. Mothers with more severe depression are also more likely to be prescribed antidepressants, meaning the drug and the underlying illness are difficult to disentangle in standard analyses. Sibling studies cut through this problem cleanly.
The Take-Away:
The authors concluded that the association between antidepressants and ADHD risk was non-significant across all analyses designed to account for these confounding factors. This doesn’t mean antidepressants are without any reproductive considerations, but it does suggest that ADHD risk, at least, is driven by heritable and family-level factors rather than medication exposure itself.
For clinicians and patients weighing the risks of treating or not treating depression during pregnancy, this distinction matters considerably.
Executive functions are the mental processes that allow us to plan, adapt, and follow through. This encompasses working memory, inhibitory control, cognitive flexibility, goal-directed planning, and problem-solving. In people with ADHD, weaknesses in these areas compound the disorder's core symptoms, making it substantially harder to manage complex, real-world demands.
Background:
Medication remains the frontline clinical response. Stimulant medications can meaningfully reduce both executive function deficits and ADHD symptoms, and are often combined with behavioral or psychological therapies for better overall outcomes.
Medication, however, is not entirely without risk of side effects. These risks have spurred interest in new, non-pharmacological alternatives that target the same neural pathways. One of these new therapies is Computerized Cognitive Remediation Therapy (CCRT). This therapy uses digital programs delivered via computer, tablet, or smartphone that train attention, memory, and inhibitory control through structured cognitive exercises. A key feature of many CCRT platforms is adaptive difficulty: tasks adjust in real time to match the child’s current ability, keeping training both challenging and engaging.
The Study:
Despite this promise, the evidence base in younger populations has been limited. This meta-analysis pooled results from randomized controlled trials enrolling participants under 18 who either carried an ADHD diagnosis or scored above the threshold on a validated rating scale. Comparators included no treatment (waitlist), placebo (pharmacological or psychological), or treatment as usual. The primary outcomes (overall executive function and clinical symptom severity) were assessed via questionnaires and neuropsychological testing. Studies including participants with comorbid autism, tic disorders, epilepsy, or other psychiatric conditions were excluded.
The findings were informative, but overall results were mixed. CCRT produced a small but statistically meaningful reduction in inattention symptoms across 13 studies (885 participants), with consistent results across individual trials and no evidence of publication bias. However, it had no detectable effect on hyperactivity and impulsivity (12 studies, 833 participants) or on total ADHD symptom burden (10 studies, 731 participants).
The picture was more encouraging for executive function. Nine studies (500 participants) showed small overall improvements, with specific gains in working memory (454 participants), inhibitory control (428 participants), and planning (6 studies, 335 participants). Emotional control showed no significant change (5 studies, 265 participants), nor did cognitive flexibility (4 studies, 189 participants).
The Take-Away:
Taken together, these results are modest rather than transformative, but context matters. CCRT is low-cost, digitally scalable, and carries negligible side effects. For a population where medication often comes with a significant burden of adverse reactions, even small, reliable improvements in executive function represent a meaningful clinical option.
The evidence positions CCRT not as a replacement for established treatments, but as a practical and well-tolerated addition to the therapeutic toolkit for children and adolescents with ADHD.
Methylphenidate is an effective treatment for ADHD in adults who also have bipolar disorder (BD), but it carries a potential risk of triggering manic episodes. Current guidelines therefore recommend using it only alongside mood-stabilizing medication. A new study using French nationwide claims data sought to test and extend those recommendations with greater statistical power than previous research.
The study built on findings by Viktorin et al. (2017), who observed that adults with BD not taking mood stabilizers had more than a sixfold higher risk of manic events (defined as hospitalization for mania or a new antimanic prescription) within six months of starting methylphenidate. Patients on mood-stabilizing treatment, by contrast, showed nearly half the baseline risk in the first three months. Those findings were limited, however, by small event counts (fewer than 61 manic episodes) and an effect that did not persist beyond the initial three-month window.
To build on this, researchers drew on the French National Health Data System (which is a claims database covering more than 60 million people) spanning 2008 to 2024. The final sample included 6,022 adults with BD (56% women) who had started methylphenidate. Using a self-controlled design, the study compared each patient's rate of manic events in the six months before their first methylphenidate prescription with the rate in the six months after, effectively eliminating stable individual differences as a confound.
Patients were classified as receiving continuous mood-stabilizing treatment if they had been dispensed at least two courses of specific antipsychotics (aripiprazole, olanzapine, or quetiapine) or mood stabilizers (lithium or valproate) in the nine months before starting methylphenidate, including at least one dispensation in the final six months of that window.
The results largely confirmed the earlier findings. Among the 2,745 patients not on mood stabilizers, the rate of inpatient mania diagnosis was 5.1 times higher in the first three months after starting methylphenidate, though this elevation fell to a non-significant level over the subsequent three months. Patients receiving continuous mood-stabilizing treatment showed no statistically significant change in mania risk across the full six-month post-initiation period. A formulation-specific pattern also emerged: patients without mood-stabilizing treatment had a 2.5-fold higher risk associated with extended-release methylphenidate, while no significant risk increase was seen with the immediate-release formulation or in treated patients regardless of formulation.
The authors conclude that methylphenidate at doses below 30 mg does not appear to elevate manic relapse risk when prescribed alongside mood stabilizers. The elevated risk seen in untreated patients, particularly with extended-release formulations, must be interpreted cautiously, given limited statistical power and the likelihood that it partly reflects the natural fluctuation of manic relapse over time. The authors flag this as an inherent limitation of self-controlled survival analyses when studying drug-induced mania, where temporal trends in the underlying condition can be difficult to disentangle from treatment effects.
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