Risk Factors for Accidental Overdose Death

The recent accidental overdose deaths of Whitney Houston and other celebrities highlights the growing problem of prescription drug abuse.  I have previous highlighted some recent important clinical research studies in prescription drug abuse including:

The Epidemiology of Prescription Opioid Abuse
Pathways to Prescription Opioid Overdose
Prescription Opioid Overdose Toxicology

Now there is a recent study that examines some of the risk factors for accidental overdose death.  This study by Bohnert and colleagues at the University of Michigan focused on a sample of U.S. veterans.  The key elements of the design of their study included:
Subject selection: All veterans accessing the VA health care system during a one year period from October 1, 1998 to September 30, 1999.
Case identification: Using the U.S. National Death Index, all subjects were queried for evidence of an accidental overdose death from their death certificates from fiscal year 2000 through fiscal year 2006.
Risk factor data: The risk factor information was collected from centralized VA health data bases and the charts.  Data included sociodemographic information and coded psychiatric and substance dependence diagnoses.
Data analysis: Cox proportional hazards statistical modeling adjusting for age, gender, VA priority status (service connected disabled individuals have higher priority status), and the medical illness severity using a measure known as the Charlson comorbidity score.

The study yielded some important results for understanding the risk factors for accidental overdose deaths.  There were 4, 485 accidental overdose deaths in this veterans population of over 3,000,000 individuals (.13%).  Men were approximately twice as likely as women to suffer an accidental overdose death.  The risk peaked in individuals in the 40-49 year age group and declined in those in older age cohorts.   The diagnoses associated with the highest non-adjusted risks (hazard ratios) were:

• Opioid use disorders (22.0)
• Stimulant use disorders (12.5)
• Cannabis use disorders (7.9)
• Alcohol use disorders (7.8)
• Bipolar disorder (5.1)
• Major depression (4.3)
• PTSD (3.9)
• Schizophrenia (3.6)

Alcohol and substance use disorders are more common in mental disorders so it is important to control for this is looking for risk with individual mental disorder diagnoses.  After controlling for this substance abuse comorbidity, the psychiatric disorders continued to contribute approximately a 20-80% increase in accidental overdose death. 

The authors review some of the potential mechanism for higher rates of accidental overdose deaths in those with a mental disorder.  These include more wreckless use of medication with lower fear of adverse consequences, misclassification of a suicide as an accidental overdose death, and simply that psychiatric disorders are treated with medications that can contribute to an accidental overdose death.

This study has important implications as it suggests those with mental disorders need assessment for risk accidental overdose death as well as assessment of risk for suicide.  In addition, the study supports the need for education about the risk of combining pain medication with antianxiety and antidepressant drugs as well as the increased risk of drinking and intoxication with psychotropic drugs.

Photo of Siamung from the Palm Beach Zoo from the author's files.

Bohnert, A., Ilgen, M., Ignacio, R., McCarthy, J., Valenstein, M., & Blow, F. (2011). Risk of Death From Accidental Overdose Associated With Psychiatric and Substance Use Disorders American Journal of Psychiatry DOI: 10.1176/appi.ajp.2011.10101476

Genetic Variants and Risk of ADHD

The search for specific genes contributing to the risk for attention deficit-hyperactivity has failed to demonstrate a consistent result.  Genetic factors do appear to be important given the results of family, adoption and twin studies.  The failure to find specific gene effects suggest the genetic contribution to ADHD risk is more complex and will require larger samples and more complex genetic research designs.

Stergiakouli and colleagues recently published a novel study examining the genetics of ADHD.  In this study, the combined an approach looking at copy number variations (CNVs) with more specific gene effects using the technique known as single-nucleotide polymorphisms (SNPs).  CNVs are genetic variations that represent not a specific genetic mutation, but rather a variation in the number of copies of specific genes.  CNVs appear to produce abnormalities in gene function and contribute to the risk of a variety of clinical disorders.

In this combined CNV and SNP study, 727 children with ADHD were compared to 5081 comparison subjects.  Using a genome-wide association approach, the authors noted the following key findings:

• No SNP reached statistically significant levels in the sample
• Rare CNVs were more common in the ADHD sample than controls
• There were 13 biological pathways (linked with SNPs) that overlapped with the rare CNVs
• These pathways included pathways for cholesterol metabolism and central nervous system development
• At the specific gene level, the gene CHRNA7 (a nicotinic receptor subunit) was found in six CNV duplication subjects

The authors conclude their study demonstrates a "highly significant overlap of biological pathways hit by both   CNVs and SNPs".  They note this finding indicates a need to continue the search for both CNV and SNPs in further understanding the genetics of ADHD.  Additionally, they conclude that "CHRNA7 is a promising candidate" gene.

The authors the gene CHRNA7 is widely expressed in the hippocampus and other brain regions and has been implicated in rapid synaptic transmission, cognitive deficits, schizophrenia and nicotine dependence.  The findings support the potential importance of this gene in ADHD.

In summary, the search for a single gene in ADHD appears to be unlikely to yield a final answer in the genetics of ADHD.  However, more complex genetic effects are being found and further study of CNVs in conjunction with genome-wide association studies may produce important results in this common clinical neuroscience disorder.

Phote of green heron from the Busch Wildlife Refuge Center in Juno Beach, Florida for the authors files.

Stergiakouli, E. (2012). Investigating the Contribution of Common Genetic Variants to the Risk and Pathogenesis of ADHD American Journal of Psychiatry, 169 (2) DOI: 10.1176/appi.ajp.2011.11040551

Cell Phone Use and Risk of Brain Cancer

In my last post I examined the epidemiology of brain tumors using a summary of the latest data from the United States.  The summary noted the slight decline in the number of malignant brain cancers over the last twenty years.


One area of concern that is receiving increased attention is the potential for cell phone risk to raise the risk of brain cancers.


Obviously if cell phone use was a very large effect one might have expected an increase in the rates of brain tumors and cancer over the last twenty years.  This corresponding to the time when cell phone use has increased dramatically in the U.S. and around the world.


Multiple case control studies have been completed examining this possible association and the majority of studies have not demonstrated a significant effect.  One recent study from Frei in Denmark along with colleagues in France and Switzerland adds to the apparent safety of cell phones.


The key design elements of the Frei study included:
Study type: Cohort study using all individuals born in Denmark from April 1, 1968
Study groups: Cell phone subscribers status (subscribers versus non-subscribers) was identified via phone records and linked to centralized health records containing health registry information including presence or central nervous system tumors.
Confounding variables controlled: age, gender, education level, income
Outcome variable: incidence rates ratio with 95% confidence interal


This data set included over 300,000 individuals with a cell phone subscription and a larger group of control individuals.


The researchers grouped brain tumors into malignant gliomas, meningiomas (largely benign brain tumors) and a residual group of other brain tumor and cancer types.


The analysis showed the incidence rates for cell phones subscribers did not statistically differ from those who  did not differ from those without cell phone subscriptions in any brain tumor or cancer group.


This is an important study.  It represents a very large data set with comprehensive registry data that would be difficult to replicate in the United States health care system.   The authors noted no specific increase in temporal lobe gliomas in the cell phone user group.  This region of the brain would be the closest region to cell phone placement during calls and theoretically most likely to be affected if an association was present.


The authors concluded:  "a small to moderate increase in risk for subgroups of heavy users or after even longer induction periods than 10-15 years cannot be ruled out".  Nevertheless, this study should reduce worry that cell phones users are significantly increasing their risk for brain tumors or cancer.


Photo of male and female chachalaca pair from Bentsen Birding Center in Texas from the author's files.


Frei, P., Poulsen, A., Johansen, C., Olsen, J., Steding-Jessen, M., & Schuz, J. (2011). Use of mobile phones and risk of brain tumours: update of Danish cohort study BMJ, 343 (oct19 4) DOI: 10.1136/bmj.d6387