Geographic Distribution of Poisoning Deaths in U.S.

President Obama is visiting West Virginia today to address the opiate and other drug overdose death epidemic.

There is significant geographic variability in the prescription of narcotic opiate analgesics in the U.S.

Opiate overdose deaths tend to be increased in states with higher opiate prescription rates.

The chart above is reproduced from a figure in the NCHS Fact Sheet titled NCHS Data on Drug Poisoning Deaths. States in blue color have higher than expected numbers of poisoning death in 2012 U.S. data.

Unintentional drug poisoning represent 80% of all poisoning deaths with suicide representing about 13% and undetermined intent about 7%.

Opiate analgesics are present in about 40% of unintentional drug poisoning deaths. Opiate analgesic poisoning deaths have tripled in the U.S. over the last decade.

Readers with more interest in this topic are directed to the CDC website on Prescription Drug Overdose

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Leading Causes of Early Death in U.S. 1990-2010

The manuscript in this post is two years old but I thought it was worthy of comment.

The Global Burden of Disease study seeks to provide an estimate of the relative contribution of a variety of medical disorders on disability and death.

I have summarized data with an original chart with data abstracted on the leading causes of early death in the U.S. This is provided by the chart in numbers (x1000). The most recent estimate rates heart disease as the continuing cause of years of life lost (2010 estimate 7164 x 1000=7,164,000 years of life lost for the U.S. population).

The changes over the two decades are worthy of note. Two brain disorder categories, death due to self-harm (suicide) and Alzheimer's have increased over this 20 year period with the relative increase most remarkable for Alzheimer's. Heart disease and road deaths have been dramatically reduced.

Readers with more interest in this topic can access the free full text manuscript by clicking on the PMID link below.

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Murray CJ, Atkinson C, Bhalla K, Birbeck G, Burstein R, Chou D, Dellavalle R, Danaei G, Ezzati M, Fahimi A, Flaxman D, Foreman, Gabriel S, Gakidou E, Kassebaum N, Khatibzadeh S, Lim S, Lipshultz SE, London S, Lopez, MacIntyre MF, Mokdad AH, Moran A, Moran AE, Mozaffarian D, Murphy T, Naghavi M, Pope C, Roberts T, Salomon J, Schwebel DC, Shahraz S, Sleet DA, Murray, Abraham J, Ali MK, Atkinson C, Bartels DH, Bhalla K, Birbeck G, Burstein R, Chen H, Criqui MH, Dahodwala, Jarlais, Ding EL, Dorsey ER, Ebel BE, Ezzati M, Fahami, Flaxman S, Flaxman AD, Gonzalez-Medina D, Grant B, Hagan H, Hoffman H, Kassebaum N, Khatibzadeh S, Leasher JL, Lin J, Lipshultz SE, Lozano R, Lu Y, Mallinger L, McDermott MM, Micha R, Miller TR, Mokdad AA, Mokdad AH, Mozaffarian D, Naghavi M, Narayan KM, Omer SB, Pelizzari PM, Phillips D, Ranganathan D, Rivara FP, Roberts T, Sampson U, Sanman E, Sapkota A, Schwebel DC, Sharaz S, Shivakoti R, Singh GM, Singh D, Tavakkoli M, Towbin JA, Wilkinson JD, Zabetian A, Murray, Abraham J, Ali MK, Alvardo M, Atkinson C, Baddour LM, Benjamin EJ, Bhalla K, Birbeck G, Bolliger I, Burstein R, Carnahan E, Chou D, Chugh SS, Cohen A, Colson KE, Cooper LT, Couser W, Criqui MH, Dabhadkar KC, Dellavalle RP, Jarlais, Dicker D, Dorsey ER, Duber H, Ebel BE, Engell RE, Ezzati M, Felson DT, Finucane MM, Flaxman S, Flaxman AD, Fleming T, Foreman, Forouzanfar MH, Freedman G, Freeman MK, Gakidou E, Gillum RF, Gonzalez-Medina D, Gosselin R, Gutierrez HR, Hagan H, Havmoeller R, Hoffman H, Jacobsen KH, James SL, Jasrasaria R, Jayarman S, Johns N, Kassebaum N, Khatibzadeh S, Lan Q, Leasher JL, Lim S, Lipshultz SE, London S, Lopez, Lozano R, Lu Y, Mallinger L, Meltzer M, Mensah GA, Michaud C, Miller TR, Mock C, Moffitt TE, Mokdad AA, Mokdad AH, Moran A, Naghavi M, Narayan KM, Nelson RG, Olives C, Omer SB, Ortblad K, Ostro B, Pelizzari PM, Phillips D, Raju M, Razavi H, Ritz B, Roberts T, Sacco RL, Salomon J, Sampson U, Schwebel DC, Shahraz S, Shibuya K, Silberberg D, Singh JA, Steenland K, Taylor JA, Thurston GD, Vavilala MS, Vos T, Wagner GR, Weinstock MA, Weisskopf MG, Wulf S, Murray, & U.S. Burden of Disease Collaborators (2013). The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA, 310 (6), 591-608 PMID: 23842577

Neurobiology of Child Neglect/Abuse: Nemeroff Lecture Notes

I had the opportunity to attend the Warren Neuroscience Lecture presented by Dr. Charles Nemeroff in Tulsa, OK on June 2, 2015.

Dr. Nemeroff has been an international leader in research in mood and anxiety disorders. His recent focus has been on the effects of adverse childhood environments on risk for adult mood and anxiety disorders. 

Here are my notes that summarize some of the key points from his lecture.

Introduction:

• Stress is an important factor in understanding depression
• Early life stress is a risk factor for later adult depression
• Genes account for a significant portion of the variation in risk following stress exposure
• Brain systems that regulate emotions are disrupted during episodes of major depression

Psychiatry research slowed by complexity of brain, multiple cell types, complex heterogeneous disorders. But we are beginning to understand the key role genes play in a variety of key disorders. Genetic factors account for 65% of bipolar disorder variance, 50% of schizophrenia variance and around 35% of variance in major depression.

Early childhood abuse and neglect is common. Recent surveys estimate prevalence rates for each of the following:

• Physical abuse 15-28% of general population in U.S.
• Sexual abuse in 11-21% 
• Emotional abuse in 11-36%
• Parental divorce or separation in 25%

Early childhood abuse and neglect has multiple effects in neurobiology and later adult mood and anxiety disorder risk:

• Increased adult cerebral spinal marker of stress known as corticotrophin releasing factor (CRF)
• Increase serum ACTH and cortisol
• Increase inflammatory markers  such as interleukin-6
• Decreased cerebral spinal fluid oxytocin that may impair social function and bonding with children
• Reduced brain cortex thickness and hyperactivy amygdala response
• Increased adult PTSD and depression
• Increased adult rates of substance abuse
• Increased risk of suicidal behavior and completed suicide

There is a growing body of evidence that ten or more genes influence vulnerability to childhood abuse and neglect including genes regulating the HPA axis, serotonin function and a gene known as FKBP5. These genetic effects may interact with environmental stresses to reduce or amplify stress vulnerability. Stress may be viewed as a teratogen that influences genetic features through epigenetic and gene regulation effects.

For clinicians there are important treatment implications:

• Major depression in the context of moderate to severe childhood abuse is less responsive to medication or to psychotherapy intervention
• Childhood abuse and neglect in bipolar disorder is linked to early onset, greater severity and poor treatment response.

During the discussion following the lecture Dr. Nemeroff noted the importance of population-based efforts to reduce societal levels of exposure to child abuse and neglect including:

• Early education with teacher training to look for evidence of abuse/neglect
• Increased training for primary care physicians treating infants/children
• Increased training and funding for social services that evaluate and treat children referred for child abuse/neglect
• Increased detection and surveillance for sexual predators
• More research in the treatment of sexual disorders including pedophilia. There is almost no NIH funding in this area and little research interest and activity.

Below I have added citations featured in the presentation to allow readers with more interest to delve into some of the primary research studies.

Image is this post is "PBB Protein CRH image" from Wikipedia chapter on CRH. Image by ProteinBoxBot.  Licensed under Public Domain via Wikimedia Commons  

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Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall R, Miller AH, & Nemeroff CB (2000). Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA, 284 (5), 592-7 PMID: 10918705

Heim C, Mletzko T, Purselle D, Musselman DL, & Nemeroff CB (2008). The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma. Biological psychiatry, 63 (4), 398-405 PMID: 17825799

Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB, Tang Y, Gillespie CF, Heim CM, Nemeroff CB, Schwartz AC, Cubells JF, & Ressler KJ (2008). Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA, 299 (11), 1291-305 PMID: 18349090

Saveanu, R., & Nemeroff, C. (2012). Etiology of Depression: Genetic and Environmental Factors Psychiatric Clinics of North America, 35 (1), 51-71 DOI: 10.1016/j.psc.2011.12.001

Is Insomnia a Risk Factor for Suicide?

Sleep is known to be important for physical as well as emotional well-being.  Mood and anxiety disorders commonly present with a variety of sleep problems including initial, middle and early morning insomnia.  Although the association of mood disorders and anxiety disorders in suicide is established, the independent contribution of insomnia to suicide risk is less well studied.

Bjorngaard and colleagues recently published a results of a Norwegian study on this issue in the Journal Sleep.  Using data from the HUNT epidemiologic study, they conducted an analysis of suicide risk over a twenty year follow-up period.

Over 75,000 subjects completed baseline assessment of sleep problems as assessed by a single question: "During the last month have you had any problems falling asleep or sleep disorders?  This question had four levels of response listed below with the prevalence of endorsement in (parentheses):

• almost every night (3%)
• often (5%)
• sometimes (31%)
• never (62%)

Endorsing sleep problems almost every night or often was more common among women (10% vs 5% for men) and for those over 50 years of age (11% versus 5% for those 50 and under.

After controlling for sociodemographic variables, those respondents endorsing sleep problems almost every night had a four fold increase in risk for suicide over the follow up period.  Controlling for alcohol use and self-report of anxiety and depressive symptoms reduced the size of this effect by about 50% but did not eliminate the independent effect of sleep problems and suicide risk.

The authors noted the link between sleep problems and suicide risk appeared stronger in those younger and the index assessment.  Interestingly, the link also appeared primarily in those not taking sleeping pills or sedatives.  Individuals reporting regular use of sleeping aids did not have an association between self-reported sleep problems and suicide rates.

Physical illnesses and chronic pain increase risk for sleep problems as well as for suicide.  The study did control for presence of a long-standing medical illness, body mass index and decreased functional ability.  Of note, suicide risk was not increased for those respondents who endorsed regular use of "painkillers".

This study supports further research into the independent association of sleep problems in suicide risk.  In an accompanying editorial, Dr. W. Vaughn McCall notes the need for exploring  "physiologic/neurochemical and psychological mechanisms" for link between sleep problems and suicide risk.  Further understanding of the role of sleep apnea in this association is also needed.

New Mexico wildflowers and butterflies from author's private collection.

Bjørngaard JH, Bjerkeset O, Romundstad P, & Gunnell D (2011). Sleeping Problems and Suicide in 75,000 Norwegian Adults: A 20 Year Follow-up of the HUNT I Study. Sleep, 34 (9), 1155-9 PMID: 21886352

Economic Distress and Suicide: Japan and U.S.

My colleagues and I are presenting a new research poster presentation this week at the 2011 American Psychiatric Association meeting in Honolulu. I wanted to use this post to summarize some of the current research related to our presentation as well as highlight the findings from our poster.

Over the last few years, I have had the opportunity to meet yearly with a group of Japanese and American researchers and psychiatrists in a retreat setting in Itasca State Park in Minnesota. This group has recently been named the Itasca Brain and Behavior Association. The goal of the group is to promote international research collaboration in clinical neuroscience and areas of psychosomatic medicine.

I learned from my Japanese colleagues last year that suicide rates in Japan increased significantly around 1998--a increase that has continued now for the last 12 years. The figure below documents the trend in suicide rates in Japan as well as the U.S.   Suicide rates increased to a larger percent in males (47%) compared to females (23%) in this period. My Japanese colleagues reported that psychological autopsy information suggested unemployment and divorce as common factors felt to be contributing to this increased rate of suicide.

Epidemiological work has now supported a link between regional unemployment in Japan and increased rates of suicides.

Japan has experience a prolonged economic malaise since 1998. Several sources have suggested the U.S. and Japanese economic cycles may be similar with the U.S. trailing the pattern in Japan by 10 to 15 years. Unemployment began increasing in Japan in 1998 and jumped dramatically in the U.S. beginning in 2008. The housing bubble in Japan peaked in 1996 and in the U.S. peaked in 2008. The possibility that the U.S. is entering a prolonged economic downturn similar to Japan raises the question of the mental health and suicide rate response. Is the U.S. vulnerable to an increased rate of suicides similar to that found in Japan? If so, what would a similar response look like and could mental health clinicians and public health officials do anything to reduce of minimize this type of risk.

Our research focused on looking at the age and gender distribution of increased rates of suicide in Japan and applying those rates to the U.S. population based on the 2010 Census. The baseline number of suicides in the U.S. average around 33,000 per year. If suicide rates were to increase to the magnitude found in Japan, the number of increased suicides in the U.S. would be about 14,000 per year. Interestingly, our model found that approximately 90% of the increased number of suicides would occur in men as men have higher baseline rates and experienced a greater increase in Japan after 1998.

A recent manuscript published in the American Journal of Public Health looked at suicide rates in relation to economic cycles between 1929 and 2007. This analysis suggested that suicide rates in the U.S. do vary with economic cycles and need to be consider in public health planning.

The presence of a primary psychiatric disorder (major depression, bipolar disorder, schizophrenia, substance dependence) is the primary determinant of risk for suicide. Our research does not predict a dramatic increase in suicide rates but rather is a warning to U.S. clinicians and public health officials. The take home messages from our collaborative research would be:

The U.S. should be alert for the potential for economic crisis and unemployment to increase risk of suicide deaths

Elevated risk for suicide related to unemployment appears highest in middle to older aged men

Adults with pre-existing mental disorders losing there job may also lose prescription benefits as well as re-imbursement for mental health services. Efforts should be made to identify these individuals and provide alternate pathways to mental health care

Employers should examine the support services provided those involved in layoffs with an effort to provide psychiatric and psychological services to these vulnerable populations

Link to Copy of APA Poster is Here.


Chang SS, Gunnell D, Sterne JA, Lu TH, & Cheng AT (2009). Was the economic crisis 1997-1998 responsible for rising suicide rates in East/Southeast Asia? A time-trend analysis for Japan, Hong Kong, South Korea, Taiwan, Singapore and Thailand. Social science & medicine (1982), 68 (7), 1322-31 PMID: 19200631

Luo F, Florence C, Quispe-Agnoli M, Ouyang L, & Crosby A (2011). Impact of Business Cycles on US Suicide Rates, 1928-2007. American journal of public health PMID: 21493938

Paranoia: Prevalence and Correlates

Clinicians dealing with psychiatric disorders commonly encounter patients with paranoia in their clinical practices.  However, it is important for clinicians to understand the relatively frequency of paranoia endorsement by people in the general population.  Whether paranoia is a pathological phenomenon commonly depends on the degree of paranoia, associated signs and symptoms and presence (or absence) of a formal psychiatric diagnosis.  Freeman and colleagues from the Institute of Psychiatry other colleagues in London published an important paper to address this issue.

Their data and research stems from a general population study of over 7,000 general population survey respondent in England.  To assess paranoia in the general population, subjects were asked three questions where positive responses reflected increasing severity of paranoia.  The three questions in the survery (and the general population rate of endorsement) were:

• Paranoia level 1. ‘Over the past year, have there been times when you felt that people were against you?  (18.6%)
• Paranoia level 2. ‘In the past year, have there been times when you felt that people were deliberately acting to harm you or your interests ? (8.2%)
• Paranoia level 3. ‘In the past year, have there been times you felt that a group of people was plotting to cause you serious harm or injury?  (1.8%)

I found it interesting the relatively high rate of endorsement of paranoia level 1 in the general population.  Nearly one in five endorsed feeling times in the last year when they felt that people were against them.  As the severity of paranoia increased, the prevalence rates decreased to less than 2% of the population fealing a good of people was plotting to cause them harm or injury.

The research also looked at some of the correlates of paranoia.  Those endorsing each level of paranoia were compared to those with no endorsement of paranoia.  The paper is packed with data but here are some of the things that stood out for me:

• Level 1 paranoia was more likely to be endorsed by women while level 3 paranoia was more likely to be endorsed by men
• Paranoia rates were higher in populations with a variety of medical conditions including: diabetes, hearing or visual problems, recent heart attack/angina.  There was a trend for increased level 3 paranoia in those with obesity (BMI greater than 30 kg/m2)
• Paranoia rates were higher in a variety variables indicating social isolation, i.e. separated, divorced or single marital status, fewer number of close family members or friends, fewer supportive relationships
• Paranoia rates were higher along with a variety of other psychiatric symptoms/disorders, i.e. insomnia, depression,worry, anxiety, panic and PTSD
• Paranoia rates were increased in those endorsing suicidal thoughts in past year, history of a suicide attempt, anxiolytic and antidepressant drug use and not surprisingly antipsychotic medication use
• Paranoia rates were strongly and progressively associated with cannabis use and less strongly associated with heavy drinking

In summary, this research manuscript provides a valuable overview of paranoia.  Elements of paranoia are relatively common in the general population.  Paranoia is a marker for many other psychiatric syndromes and cannabis abuse.  Clinicians should include screening questions for paranoia in routine clinical assessment.

Photo of Japanese Maple Courtesy of Yates Photography

Freeman, D., McManus, S., Brugha, T., Meltzer, H., Jenkins, R., & Bebbington, P. (2010). Concomitants of paranoia in the general population Psychological Medicine, 41 (05), 923-936 DOI: 10.1017/S0033291710001546

Suicide Tops Death List for Meth Heads

Methamphetamine Chemical Structure

Methamphetamine dependence can lead to an early death.  The magnitude and mechanism of this effect is not well understood.  One way to better understand effects of drug abuse/dependence on mortality is the prospective outcome study.  These types of studies tend to be costly and may require many years to yield research results.   That’s why there are not many published studies to answer the question of this post.

A recent study from Taiwan provides some valuable insight into this issue.  This study followed a cohort of 1254 individuals with a history of methamphetamine abuse and a psychiatric admission for treatment between 1990 and 2007.  National death records were queried and the methamphetamine abuse cases were compared to an age- and gender- matched control group.  One hundred thirty methamphetamine users died during follow up with the following leading categories of death:  

• Suicide n=42 (32.3%)
• Accidents n=26 (20.0%)
• Undetermined unnatural deaths n=14 (10.8%)
• Cardiovascular disease n=13 (10.0%)
• Undetermined natural deaths n=9 (6.9%)
• Liver disease n=6 (4.6%)

In this Taiwanese sample, methamphetamine abuse carried an overall six fold increase in mortality.  Unnatural deaths (suicides, accidents, homicides, undetermined natural deaths) were particularly elevated.  Male amphetamine abusers had about a 10-fold increase in unnatural deaths while female methamphetamine abusers had a remarkable 26-fold increase in unnatural death during follow up.

Being married appeared to reduce the risk of death from unnatural and natural causes in this cohort.  Use of other substances in addition to methamphetamine increased risk of death.

I would suspect that in the United States, homicide would be a greater contributor to mortality in those with a history of methamphetamine dependence.  Overall homicide rates in Taiwan are much lower than in the United States and may reduce risk for this type of unnatural death.

Interestingly, about two thirds of the cohort had exhibited methamphetamine psychosis-a psychiatric complication of methamphetamine use.  Those with a history of this type of psychosis were no more likely to die than those without a history of the psychosis.

One problem with this type of study is difficulty assessing the specific effect of methamphetamine from other potential confounding factors.  For example, methamphetamine use is higher in smokers than smokers and so some increased mortality risk could be related to effects of smoking.  Methamphetamine dependence is more prevalent in a variety of mental disorders linked to increased suicide.

Nevertheless, this study shows the magnitude and type of mortality risk linked to methamphetamine dependence.  Public health interventions that reduce the prevalence of methamphetamine dependence would like reduce the excess mortality associated with this drug.

Wikipedia Commons chemical structure of methamphetamine image authored by Harbin.

Kuo CJ, Liao YT, Chen WJ, Tsai SY, Lin SK, & Chen CC (2010). Causes of death of patients with methamphetamine dependence: A record-linkage study. Drug and alcohol review PMID: 21355920

Stressful Live Events and Suicide

The role of stressful life events in suicide attempts and completed suicides has been a key area of study in the epidemiology of mental disorders.  Although suicidal behavior often occurs in the context of acute and chronic stressor, this does not prove a causal link.  We all could probably report serious life stressors throughout out lives and these could be interpreted as a reason for suicidal behavior.  So these associations could simply be a coincidence and not have anything to do with suicidal behavior.

A recent analysis of the WHO (World Health Organization) World Mental Health Surveys attempts to shed some light on this issue.  This study focussed on traumatic life events, a subset of life stressors that are associated with the development of PTSD.  The traumatic events studied included:

1. natural and man-made disasters
2. combat, war and refugee experiences
3. sexual and interpersonal violence
4. witnessing or perpetrating violence
5. death or trauma to a loved one

These more serious stressful life events provide a opportunity focus on events everyone would agree as significant.  The authors then looked at five lifetime categories related to suicide:

1. suicide ideation
2. suicide attempt
3. suicide planning in those with ideation
4. suicide attempt in those with a suicide plan
5. suicide attempt in those without a plan

The most common traumatic events reported by respondents across the 20 country survey included: death of a loved one (30.5%), followed by witnessing violence (21.8%), interpersonal violence (18.8%), accidents (17.7%), exposure to war (16.2%) and trauma to a loved one (12.5%).

The authors of the study perform complex analysis of the individual and cumulative effects of traumatic events.  The key findings summarized by these analyses include:

• experiencing interpersonal or sexual violence appeared to have the strongest effect on suicidal ideation and suicide attempt
• suicidal ideation and attempts had a dose-response effect with traumatic experiences--the more number of experiences, the higher the risk although this effect plateaued after experiencing about 4 events
• traumatic effects had limited effect on the progression from suicidal ideation to a suicide attempt
• effects of traumatic events occurred across low-, middle- and high income countries
• it was estimated that elimination of traumatic life events could reduce population suicide ideation by 15% and suicide attempts by 22%

The study was not able to analyze the effect on the most important variable--completed suicide.  This would add significant weight to attributing a link between traumatic life events.  Nevertheless, this study provides additional insight into stressful life events and suicide ideation and plan.  Traumatic events appear to be important although playing a relatively minor role.  Presence of a serious mental disorder, i.e. major depression, bipolar disorder, substance abuse, schizophrenia, severe personality disorder continues to be the most important risk factor for suicide.

Photo of Baby Duck in Grass Courtesy of Yates Photography

Stein DJ, Chiu WT, Hwang I, Kessler RC, Sampson N, Alonso J, Borges G, Bromet E, Bruffaerts R, de Girolamo G, Florescu S, Gureje O, He Y, Kovess-Masfety V, Levinson D, Matschinger H, Mneimneh Z, Nakamura Y, Ormel J, Posada-Villa J, Sagar R, Scott KM, Tomov T, Viana MC, Williams DR, & Nock MK (2010). Cross-national analysis of the associations between traumatic events and suicidal behavior: findings from the WHO World Mental Health Surveys. PloS one, 5 (5) PMID: 20485530