March 15, 2022

Meta-analysis finds no significant increase in natural mortality, but almost tripled risk of unnatural death, in persons with ADHD

A meta-analysis of eight studies with a combined total of over 396,000 persons with ADHD reported a twofold greater risk of premature death in persons with ADHD as compared with the general population. There was no significant difference in mortality between males and females with ADHD.

But when natural causes of death, primarily disease, were distinguished from unnatural causes, such as injuries and poisoning, virtually all the increased risk was attributable to the latter.

A meta-analysis of four studies with a combined total of over 394,000 participants with ADHD found no significant increase in natural mortality among persons with ADHD. This held for both males and females.

But a meta-analysis of ten studies with over 430,000 persons with ADHD found a nearly threefold increase in unnatural mortality (injuries, poisoning, etc.) in persons with ADHD. Among females (five studies, over 110,000 participants) the increase was threefold. Males with ADHD (five studies, over 310,000 participants) were 2.5 times more susceptible to premature death.

An important caution: in all of these meta-analyses, between-study heterogeneity was extreme, meaning there was little consistency from one study to the next. Moreover, no effort was made to evaluate the likelihood of publication bias.

The largest study, with over 275,000 participants with ADHD, found a negligible and only marginally significant 7% increased all-cause risk of death. It found no increase in natural causes of mortality, but a 50% increase in unnatural causes of premature mortality.

The authors described these results as "suggestive," but emphasized that "the evidence was judged as only low confidence," in line with "inconsistent" evidence from previous nationwide population studies: in Denmark, a twofold increase in all-cause mortality; in Sweden, a fourfold increase; but in Taiwan, a tiny 7% increase that was at the limit of statistical significance, once the data was fully adjusted for confounding factors.

That led the authors to suggest "that all relevant potential confounders should be accounted for" in "future studies."

FerránCatalá-López,Brian Hutton, Matthew J. Page, Jane A. Driver, Manuel Ridao, AdolfoAlonso-Arroyo, Alfonso Valencia, Diego Macías Saint-Gerons, RafaelTabarés-Seisdedos, “Mortality in Persons With Autism Spectrum Disorder or Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis,”JAMAPediatrics(2022), https://doi.org/110.1001/jamapediatrics.2021.6401.

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Oppositional Defiant Disorder, Autism, and ADHD: New Research Examines the Connection

Oppositional Defiant Disorder (ODD)—a pattern of chronic irritability, anger, arguing, or defiance—is one of the most challenging behavioral conditions families and clinicians face. 

A new study involving 2,400 children ages 3–17 offers one of the clearest pictures yet. Using parent-reported data from the Pediatric Behavior Scale, researchers compared how often ODD appears in Autism spectrum disorder (ASD), ADHD-Combined presentation (ADHD-C), ADHD-Inattentive presentation (ADHD-I), and those with both ASD and ADHD.

Results

ADHD-Combined + ODD: The Highest-Risk Group

Children with ADHD-Combined presentation show both hyperactivity/impulsivity and inattention.  They had the highest ODD rates of any single diagnosis: 53% of kids with ADHD-Combined met criteria for ODD.

But when autism was added to ADHD-Combined, the prevalence jumped to 62%. This group also had the highest overall ODD scores, suggesting more severe or more impairing symptoms. 

This synergy matters: while autism alone increases ODD risk, the presence of ADHD-Combined is what pushes prevalence into the majority range. Other groups showed lower, but still significant, rates of ODD:

  • Autism + ADHD-Inattentive: 28%
  • Autism Only: 24%
  • ADHD-Inattentive Only: 14%

These findings echo what clinicians often see: children with inattentive ADHD, while struggling significantly with attention and learning, tend to show fewer behavioral conflict patterns than those with hyperactive/impulsive symptoms.

It is important to note that ODD is considered to have two main components. Across all diagnostic groups, ODD consistently broke down into these two components: either Irritable/Angry (emotion-based) or Oppositional/Defiant (behavior-based). But the balance between these components differed depending on diagnosis. Notably, Autism + ADHD-Combined showed higher levels of the irritable/angry component than ADHD-Combined alone. The oppositional/defiant component did not differ much between groups. This suggests that autism elevates the emotional side of ODD more than the behavioral side, which is important for clinicians to note before tailoring interventions.

Understanding ADHD , ASD, & Comorbidity:

The study notes that autism, ADHD, and ODD often cluster together, with 55–90% comorbidity in some combinations.

As the authors explain, The high co-occurrence of ADHD-Combined in autism (80% in our study) largely explains the high prevalence of ODD in autism.” 

Clinical Implications: Why This Study Matters

The researchers point to a straightforward recommendation: clinicians shouldn’t evaluate these conditions in isolation. A child referred for autism concerns might also be struggling with ADHD. A child referred for ADHD might have undiagnosed ODD. And ignoring one disorder can undermine treatment for the others.

Evidence-based interventions (behavioral therapy, parent training, school supports, and/or medication) can reduce symptoms across all three diagnoses while improving long-term outcomes, including overall quality of life.

November 21, 2025

What Sleep Patterns Reveal About Mental Health: A Look at New Research

Background:

Sleep is more than simple rest. When discussing sleep, we tend to focus on the quantity rather than the quality,  how many hours of sleep we get versus the quality or depth of sleep. Duration is an important part of the picture, but understanding the stages of sleep and how certain mental health disorders affect those stages is a crucial part of the discussion. 

Sleep is an active mental process where the brain goes through distinct phases of complex electrical rhythms. These phases can be broken down into non-rapid eye movement (NREM) and rapid eye movement (REM). The non-rapid eye movement phase consists of three stages of the four stages of sleep, referred to as N1, N2(light sleep), and N3(deep sleep). N4 is the REM phase, during which time vivid dreaming typically occurs. 

Two of the most important measurable brain rhythms occur during non-rapid eye movement (NREM) sleep. These electrical rhythms are referred to as slow waves and sleep spindles. Slow waves reflect deep, restorative sleep, while spindles are brief bursts of brain activity that support memory and learning.

The Study: 

A new research review has compiled data on how these sleep oscillations differ across psychiatric conditions. The findings suggest that subtle changes in nightly brain rhythms may hold important clues about a range of disorders, from ADHD to schizophrenia.

The Results:

ADHD: Higher Spindle Activity, Mixed Slow-Wave Findings

People with ADHD showed increased slow-spindle activity, meaning those brief bursts of NREM activity were more frequent or stronger than in people without ADHD. Why this happens isn’t fully understood, but it may reflect differences in how the ADHD brain organizes information during sleep. Evidence for slow-wave abnormalities was mixed, suggesting that deep sleep disruption is not a consistent hallmark of ADHD.

Autism: Inconsistent Patterns, but Some Signs of Lower Sleep Amplitude

Among individuals with autism spectrum disorder (ASD), results were less consistent. However, some studies pointed to lower “spindle chirp” (the subtle shift in spindle frequency over time) and reduced slow-wave amplitude. Lower amplitude suggests that the brain’s deep-sleep signals may be weaker or less synchronized. Researchers are still working to understand how these patterns relate to sensory processing, learning differences, or daytime behavior.

Depression: Lower Slow-Wave and Spindle Measures—Especially With Medication

People with depression tended to show reduced slow-wave activity and fewer or weaker sleep spindles, but this pattern appeared most strongly in patients taking antidepressant medications. Since antidepressants can influence sleep architecture, researchers are careful not to overinterpret the changes.  Nevertheless, these changes raise interesting questions about how both depression and its treatments shape the sleeping brain.

PTSD: Higher Spindle Frequency Tied to Symptoms

In post-traumatic stress disorder (PTSD), the trend moved in the opposite direction. Patients showed higher spindle frequency and activity, and these changes were linked to symptom severity which suggests that the brain may be “overactive” during sleep in ways that relate to hyperarousal or intrusive memories. This strengthens the idea that sleep physiology plays a role in how traumatic memories are processed.

Psychotic Disorders: The Most Consistent Sleep Signature

The clearest and most reliable findings emerged in psychotic disorders, including schizophrenia. Across multiple studies, individuals showed: Lower spindle density (fewer spindles overall), reduced spindle amplitude and duration, correlations with symptom severity, and cognitive deficits.

Lower slow-wave activity also appeared, especially in the early phases of illness. These results echo earlier research suggesting that sleep spindles, which are generated by thalamocortical circuits, might offer a window into the neural disruptions that underlie psychosis.

The Take-Away:

The review concludes with a key message: While sleep disturbances are clearly present across psychiatric conditions, the field needs larger, better-standardized, and more longitudinal studies. With more consistent methods and longer follow-ups, researchers may be able to determine whether these oscillations can serve as reliable biomarkers or future treatment targets.

For now, the take-home message is that the effects of these mental health disorders on sleep are real and measurable.

Population Study Links ADHD Medication with Reduced Criminality, Suicides, Automotive Crashes, Substance Abuse

Many studies have shown that ADHD is associated with increased risks of suicidal behavior, substance misuse, injuries, and criminality. As we often discuss in our blogs, treatments for ADHD include medication and non-medication options, such as CBT (Cognitive Behavioral Therapy). While non-drug approaches are often used for young children or mild cases of ADHD, medications – both stimulants and non-stimulants – are common for adolescents and adults. 

Global prescriptions for ADHD drugs have risen significantly in recent years, raising questions about their safety and effectiveness. Randomized controlled trials have demonstrated that medication can help reduce the core symptoms of ADHD. However, research from these trials still offers limited or inconclusive insights into wider and more significant clinical outcomes, such as suicidal behavior and substance use disorder.

An international study team conducted a nationwide population study using the Swedish national registers. Sweden has a single-payer national health insurance system, which covers nearly every resident, enabling such studies. The researchers examined all Swedish residents aged 6 to 64 who received their first ADHD diagnosis between 2007 and 2018. Analyses of criminal behavior and transport accidents focused on a subgroup aged 15 to 64, since individuals in Sweden must be at least 15 years old to be legally accountable for crimes or to drive.

The team controlled for confounding factors, including demographics (age at ADHD diagnosis, calendar year, sex, country of birth, highest education (using parental education for those under 25), psychiatric and physical diagnoses, dispensations of psychotropic drugs, and health care use (outpatient visits and hospital admissions for both psychiatric and non-psychiatric reasons).

Time-varying covariates from the previous month covered diagnoses, medication dispensations, and healthcare use. During the study, ADHD treatments licensed in Sweden included amphetamine, atomoxetine, dexamphetamine, guanfacine, lisdexamphetamine, and methylphenidate.

After accounting for covariates, individuals diagnosed with ADHD who received medication treatment showed better outcomes than those who did not. Specifically:

-Suicidal behaviors dropped by roughly 15% in both first-time and recurrent cases.

-Initial criminal activity decreased by 13%, with repeated offences falling by 25%.

-Substance abuse initiation declined by 15%, while recurring substance abuse was reduced

by 25%.

-First automotive crashes were down 12%, and subsequent crashes fell by 16%.

There was no notable reduction in first-time accidental injuries, and only a marginally significant 4% decrease in repeated injuries.

The team concluded, “Drug treatment for ADHD was associated with beneficial effects in reducing the risks of suicidal behaviours, substance misuse, transport accidents, and criminality, but not accidental injuries when considering first event rate. The risk reductions were more pronounced for recurrent events, with reduced rates for all five outcomes.”