Pathways to Substance Use and Abuse

Neuroscience medicine clinicians encounter patients every day who have both a mental and substance use disorder.

This co-occurrence, or comorbidity, complicates diagnosis, treatment and outcome.

The exact mechanism for this comorbidity issue is unclear.

A recent study out of Washington University in St. Louis and King's College London provides some insight into this comorbidity issue.

They examined participants in the Study of Addiction: Genetics and Environment (SAGE). These subjects provided genetic samples and psychiatric interviews to the research team.

Five psychiatric disorders were studied including attention deficit hyperactivity, autism spectrum disorder, major depression, bipolar disorder and schizophrenia. A initial finding ruled out any link between genetic risk for autism spectrum disorder and any substance use/abuse risk.

The remaining four psychiatric disorders did increase risk for substance use and abuse in a general manner. This means genetic risk for ADHD, bipolar disorder, major depression and schizophrenia all contribute to a general risk for substance use/abuse across all drug categories.

Additionally, the team reported some specific drug use/abuse with individual genetic risk for ADHD, bipolar disorder, major depression and schizophrenia. These specific pathways included:

• Major depression polygenetic risk score and non-problem cannabis use
• Major depression polygenetic risk score and severe cocaine dependence
• Schizophrenia polygenetic risk score and  non-problem cannabis use and severe cannabis dependence
• Schizophrenia polygenetic risk score and severe cocaine dependence

The take-home message from this study is that genetic risk for many psychiatric disorders also contributes to a increased risk for general substance use/abuse. Additionally, some psychiatric disorders appear to increase risk for specific substance use/abuse issues.

Prevention, assessment and treatment services need to address this relationship and the needs for each component of illness in those with comorbidity.

Individuals with more interest in this topic can access the free full-text manuscript by clicking on the link in the citation below.

Follow me on Twitter WRY999

Image is an original graphic produced by me based on content in the manuscript.

Carey CE, Agrawal A, Bucholz KK, Hartz SM, Lynskey MT, Nelson EC, Bierut LJ, & Bogdan R (2016). Associations between Polygenic Risk for Psychiatric Disorders and Substance Involvement. Frontiers in genetics, 7 PMID: 27574527

Top @WRY999 Neuroscience Twitter Posts: August 2016

Here are selected top Twitter posts from my @WRY999 feed for the month of August.

Follow me on Twitter by clicking HERE.

I used the Twitter analytics page to sort out the Twitter posts with the most impressions and engagements for August of 2016.

Photos from the trip to Santa Fe, New Mexico were popular and I have included the top photo of a Santa Fe sunset. This photo was taken from the Cross of the Martyrs park .

"Jump starting the brain: Experimental device suggests new path to rousing coma patients" https://t.co/Uon030XRkj #science #feedly

— W.R.Yates, M.D.✍ (@WRY999) August 25, 2016

Common brain signature marks autism, attention deficit (disruption in corpus callosum)
https://t.co/2bm4EzEvwX

— W.R.Yates, M.D.✍ (@WRY999) August 8, 201

"Virtual reality and treadmill training could help prevent falls in older adults" #neuroscience #feedly https://t.co/xcEfjm5vdR

— W.R.Yates, M.D.✍ (@WRY999) August 12, 2016

"Face shape is in the genes" https://t.co/jzzng9vZN5 #neuroscience #feedly

— W.R.Yates, M.D.✍ (@WRY999) August 26, 2016

MT Some psychotic disorders may be induced by epilepsy drugs(women and temporal lobe seizures) https://t.co/r2zLHSnec8 #feedly

— W.R.Yates, M.D.✍ (@WRY999) August 9, 2016

Follow me on Twitter by clicking HERE.

Older Fathers: Epigenetic Factors

 A recent review article published in American Journal of Stem Cells summarized current knowledge of epigenetic factors in fathers.

Epigenetic factors are defined as environmental factors that change the expression of genetics.

We know that as men age, changes in genetic structures have effects on their offspring.

Men who have children after age 40 have higher rates of offspring with:

• schizophrenia
• autism and autism spectrum disorder
• birth defects including heart defects, Down syndrome and other chromosomal anomalies

These effects are not completely understood but do appear to be related to age-dependent methylation of DNA.

Older age is not the only epigenetic influence in fathers. Cigarette smoking, heavy alcohol intake, paternal diet and paternal stress all have some evidence of adversely affecting paternal epigenetic effects.

The effect of advanced paternal age on increased risk in offspring is important as the age at first child is increasing for both men and women. Part of older father effect appears related to the association of older parenthood with increased level of education in the population. (see original chart produced above from U.S. Census Bureau data)

You can read more about this review at MedicalXpress HERE.

Follow the author on Twitter @WRY999 HERE.

New Year Reading Links: Performance Enhancement

Happy New Year Brain Posts readers!

Thank you for following these posts. To begin 2016 I would like to highlight research related to performance enhancement. These posts will look at legal as well as illicit methods.

Here are a few recent research abstracts that caught my attention and will be on my reading list over the next few days.

Memory Neuroenhancement in Autism

This study examined the effects of a Chinese mind-body training technique named Nei Gong training in children with autism.

Perceptual Training in Beach Volleyball

Beach volleyball players were studied in a trial of methods for gaze-path training.

Supplement Use by UK Army Soldiers

This study surveyed UK Army soldiers in training for use of supplements. Protein supplements, carbohydrate-electrolyte sport drinks and creatine were the most commonly endorsed supplements in use in the cohort. 

Monthly Testosterone Use in Older Men

Twenty four elderly men participated in a trial of supplemental testosterone in two formats versus placebo on body composition and muscle strength. 

Time of Day and Performance in a Cycling Trial

Nine male subjects participated in a trial examining cycling performance at various times of the day. Cycling performance and hormonal/metabolic effects were the key outcome variables in this study.

Follow the author on Twitter WRY999

Photo of red-shouldered hawk is from the author's files. 

Genetics Leading to Better Bipolar Disorder Diagnosis

I wanted to alert Brain Posts readers to an important new review of genetics and diagnosis in brain disorders including bipolar disorder.

One hope for the emerging genetics research in mental disorders is a better diagnostic classification system.

The current psychiatric diagnostic system is hampered by use of a primary symptoms and signs approach leading to messy heterogeneous groups of clinical conditions.

Elliot Gerson has been a giant in neuroscience genetics for quite some time and recently published an important manuscript titled: "Genetic and genomic analyses as a basis for new diagnostic nosologies" in the journal Dialogues in Clinical Neuroscience.

Gershon notes current clinical diagnostic categories in psychiatry fail three of five tests for diagnostic validity described by Feigher in 1972:

• family study clustering
• course of illness 
• laboratory tests

There is promise for using genetic and genomic findings to improve diagnostic validity in psychiatric disorders. Gershon goes on to outline what is currently known in psychiatric genetics and how future genetic research can lead to "biologically coherent diagnostic entities".

Here is my summary on what I see as the key points in the review:

• The number of common gene single-neucleotide polymorphisms (SNPs) linked to brain disorders is growing (from 10 to over 100 for schizophrenia an example)
• Summing risk across known schizophrenia SNPs using risk profile scores accounts for 7% of genetic variance in schizophrenia (this increases to up to 23% of variance when broader phenotypic systems are used)
• A similar SNP risk profile approach separates bipolar disorder groups from controls
• Larger sample sizes may increase this SNP genetic variance understanding in schizophrenia and bipolar disorder
• Some SNPs contribute to risk for more than one disorder i.e. schizophrenia, bipolar disorder and major depression showing weakness of current classification system
• Common genome-wide SNP data may be a promising path to defining better diagnostic categories
• Rare variants such as copy number variations (CNVs) may also be promising for improved psychiatric diagnosis
• Chromosome 22q11 deletion (DiGeorge syndrome or velocardiofacial syndrome) occurs in 1/4000 births and has high penetrance for psychiatric diagnosis although nonspecific (23% autism sprectrum, 68% schizophrenia, 26% bipolar disorder)
• Brain molecular network modeling also holds promise as a basis for diagnosis
• Many known risk genes for psychiatric illness have been linked to key brain network nodes
• Genetic variants could be mapped to human molecular networks and this map may lead to predictable "therapeutic targets"
• Brain connectivity networks (fMRI) may be a promising alternate approach to psychiatric diagnosis

The validity criteria for psychiatric diagnosis described by Feighner in 1972 continue to be a gold standard. Emerging genetic, genomic and brain connectivity research may be part of the tool set that has been missing. Applying these tools to better diagnosis holds promise for new and better treatment and the reduction in pain and suffering for many brain disorders.

Interested readers can access the free full-text manuscript of the Gerson and Grennan review by clicking on the PMID link in the citation below.

Photo of brown pelican and ruddy turnstone is from the author's files.

Follow the author on Twitter WRY999

Gershon ES, & Grennan KS (2015). Genetic and genomic analyses as a basis for new diagnostic nosologies. Dialogues in clinical neuroscience, 17 (1), 69-78 PMID: 25987865

ADHD and Autism Overlap: Adult Twin Study

Clinical studies show high rates of ADHD in adults with autism or autism spectrum disorder (ASD). 

These studies have estimated the prevalence of ADHD in adults with ASD at between 28 and 44% of individuals. The prevalence of ADHD in the adult general population without ASD is estimated at 2.5%.

Given the overlap between these two developmental disorders, it makes sense to examine genetic factors that might contribute to co-occurrence.

TJC Polderman along with colleagues from the Netherlands, the UK and Sweden looked at this issue using a sample of adult twins. Twin studies provide a powerful tool for teasing out genetic from environmental influence by comparing identical (monozygotic) to fraternal (dizygotic) twin pairs.

All twins in the studies rated their ASD and ADHD symptoms from those used as criteria in the Fifth Revision of the Diagnostic and Statistical Manual (DSM-5). This produced scores in four key symptom domain scores:

• ASD social/communication deficits
• ASD repetitive and restrictive behavior interest
• ADHD inattention
• ADHD hyperactivity/impulsivity

Using the twin study design the authors were able to identify:

• A strong genetic contribution to the overlap of ASD repetitive scores with ASDH inattention in both men and women
• A strong genetic contribution to the overlap of ASD repetitive scores with ADHD hyperactivity/impulse control in both men and women
• ASD social/communication deficit showed only modest

The authors conclude their study is one of the first suggesting ASD repetitive/restriction symptoms contribute specifically to high ADHD symptom levels. One potential explanation would be a common genetic factor or factors that produce both repetitive/restrictive ASD symptoms along with inattention and hyperactivity.

The authors note their findings support giving attention to specific symptom domains in designing research in ADHD and ASD. Specific symptom domains may have specific genetic and environmental risk factors.

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

Photo of wood stork near Fort Myers, FL is from the author's files.

Follow the author on Twitter @WRY999

Polderman TJ, Hoekstra RA, Posthuma D, & Larsson H (2014). The co-occurrence of autistic and ADHD dimensions in adults: an etiological study in 17,770 twins. Translational psychiatry, 4 PMID: 25180574

Twin Studies in ADHD: Research Links

Twin studies provide a strong research study design in understanding the genetics of a variety of brain conditions.

This is true for understanding the genetics of ADHD.

Here are a few selected recent twin studies in ADHD that I think are important and noteworthy.

Readers can access the abstract and in some cases the free full-text manuscript by clicking on the title.

Shared Features of ADHD and Autism

This study featured results of an analysis of over 17000 adult twins from Sweden. The authors examined scores on two features of autism (social/communication and repetitive/restricted behavior) and scores on two features of ADHD (inattention and hyperactivity/impulsivity). The authors found support for a genetic overlap between the repetitive/restrictive autism dimension with both the attention and hyperactivity dimensions of ADHD.

Cognitive Impairments, Reading Difficulty and ADHD

Using a sample of twins between ages 7 and 10 the authors found a link between ADHD inattention scores and three measures of cognition (reaction time variability, verbal short-term memory and working memory. These associations accounted for a significant portion of the reading difficulties in children with ADHD.

ADHD, Autism Traits and Substance Use and Misuse

3080 adult Australian twins participated in a study of the overlap between ADHD, autism traits and substance use. Both ADHD symptoms and autism traits were linked to smoking and cannabis use. Autism traits were linked to lower frequency of drinking to intoxication but higher rates of alcohol dependence once drinking was initiated.

EEG Theta Activity, Reaction Time and ADHD

EEG abnormalities have been noted in ADHD. In this twin study, twins between 12 and 15 years of age completed EEG frontal theta phase assessments, reaction time variability and ADHD symptomatology. The authors found evidence to support a genetic link between frontal EEG theta, reaction time variability and ADHD status.

ADHD, Homework Behavior and Reading Comprehension

This study analyzed data from the Florida Twin Project on Behavior and Environment. Overlapping genetic contributions for found for ADHD symptoms, homework behavior and reading comprehension. Additionally, some shared environmental influences contributed to the association between homework behavior and reading comprehension. This study supports both genetic and environmental influences on the link between ADHD and reading performance.

The findings from these recent twin studies show the importance of genetic influences in ADHD and highlight the key overlap with autism, cognitive function and academic achievement.

Photo of black-bellied whistling duck and teal is from the author's files.

Follow the author on Twitter WRY999

Autism and MRI Physical Biomarkers

Minor physical anomalies (MPAs) commonly occur in those with autism.  I have previously published a post on a study outlining the type and prevalence of these anomalies in a series of case of autism and austim spectrum disorder.

One of the MPAs noted in the 1970s in autism spectrum disorder is an increased intraorbital distance (distance between the eyes).   This abnormality also noted as hypertelorism has been noted in a variety of brain developmental abnormalities as well as in some normal individuals.

The brain developmental correlates of hypertelorism have not been studied extensively.  It is possible that developmental hypertelorism may reflect brain developmental variations linked to clinical disorders.

Cheung et al and colleagues from the University of Hong Kong and Harvard School of Dental Medicine recently published a brain MRI study of intraorbital distance in autism spectrum disorder in PloS One.  This study examined the correlation of intraorbital distance with a variety of brain structural measurements.

Thirty six children between the ages of 7 and 16 years with autism spectrum disorder were compared to a group of 55 developmentally normal children matched by age and gender.  The two groups were in the normal intelligence range with the verbal IQ of the autism spectrum group 112 compared to a verbal IQ of 117 in the control group.

Magnetic resonance imaging scans were used to accurately measure the intraorbital distance.  This measurement was then compared with brain structure volumes.

Intraorbital distance correlated with several brain regions volumes in the autism spectrum group but not in the control group.  The areas with increased volume correlating with intraorbital distance in the autism spectrum group included:

• Bilateral amygdala
• Bilateral medial temporal lobe regions
• Left inferior frontal cortex lobes

Amygdala developmental abnormalities have previously been noted in studies of autism.  The medial lobe appears to be important in social and language skills developments.

The authors note the possible relationship between intraorbital distance and brain development in this statement from the manuscript discussion section: 

     "The inference is that in this group, the growth of midline bony and brain regions are tightly linked; that is, regions involved in the regulation of socialization, emotion and memory appear to enlarge with the visual system".

These finding suggest that MRI intraorbital distance may be a potential biomarker for autism spectrum disorders.   Additional longitudinal studies of intraorbital distance and brain development in children may provide additional support for the findings in this cross-sectional studies.

Image of intraorbital distance measurement in autism from Cheung et al distributed under the terms of Creative Commons Attributions License which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 

Cheung C, McAlonan GM, Fung YY, Fung G, Yu KK, Tai KS, Sham PC, & Chua SE (2011). MRI study of minor physical anomaly in childhood autism implicates aberrant neurodevelopment in infancy. PloS one, 6 (6) PMID: 21687660

Autism Spectrum: Why Boys Are At Higher Risk

It is no secret gender plays a key role in the risk for a variety of childhood developmental disorders. Discussion of this issue is often difficult as biases in how boys and girls are raised and evaluated can contribute to confusion. Nevertheless, research progresses in explaining why boys are more likely to develop autism spectrum condition (ASC) and other neurodevelopmental abnormalities.

Baron-Cohen and colleagues from the UK and US recently summarized some of the potential mechanisms for male predominance in autism spectrum. They note a significant male predominance in a group of childhood neurodevelopmental disorders in addition to ASC:

• ADHD
• Conduct disorder
• Developmental reading disorders (dyslexia)
• Specific language impairment
• Tourette Syndrome

They note rates for ASC in boys is 4:1 compared to girls and for full autism is estimated as high as 11:1.

The authors note that predominance of ASC and other neurodevelopmental disorders in boys may be an “extreme expression of the male brain”. This concept states that boys and girls brains begin to differ early in the uterus. These differences result in different strengths and weaknesses. ASC may be an example of the male brain development gone too far.

Females appear to have a stronger drive to empathize (identify and respond to the feelings of others) while the male brain appears to have a stronger drive to systemize (analyze and construct rule based systems). The ASC as extreme male brain theory would propose the ASC brain is just the prototypical male brain gone to far in masculinization.

Males typically have three surges of the male hormone or androgen testosterone. The first surge occurs between 2 and 6 months in the uterus. This surge if felt to be responsible for brain masculization. The second surge occurs in the first six months of life and the third and final surge occurs in adolescence around puberty. If ASC is an example of the extreme male brain, then the fetal testosterone surge might be expected to be higher in those with ASC.

Progress in this front has evolved by comparing fetal testosterone levels with a variety of cognitive, behavioral and and emotional traits. Among normal children the following relationships have be discovered:

Positive associations with fetal testosterone levels (high levels with higher evidence of trait)

• Autistic traits
• Restricted or reduced interests
• Tendency to systemize
• Rightward asymmetry of brain corpus callosum (isthmus)

Negative associations with fetal testosterone (high levels with lower evidence of trait)

• Amount of eye contact
• Quality of social relationships
• Vocabulary size
• Empathy

Studies in those with ASC also appear to support the extreme brain hypothesis. Ten genes related to sex steroid synthesis, transport or metabolism have been linked to ASC or empathy traits. Testosterone levels tend to be higher in males with ASC than those without. Research in progress is likely to provide additional information on the merit of the extreme male brain hypothesis

The authors note there are other theories that might be supported in future research on the gender ratio in ASC. Two of these theories stem from differences in the X and Y chromosome.

A better understanding of why boys are at higher risk of ASC and autism is important. Such understanding might provide insight into avenues for early diagnosis and treatment.

Molecular model of the chemical structure of testosterone from Wikipedia Creative Commons file by Ben Mills. 


Baron-Cohen S, Lombardo MV, Auyeung B, Ashwin E, Chakrabarti B, & Knickmeyer R (2011). Why are autism spectrum conditions more prevalent in males? PLoS biology, 9 (6) PMID: 21695109

Preterm Births Increase Risk of ADHD and Autism

Understanding the factors contributing to the prevalence of ADHD and autism requires examining the type and magnitude of risk factors for the disorders.  One risk factors common to both disorders is early or pre-term birth.  Advances in neonatal care dramatically increase survival in infants born as early as the fifth or sixth month of pregnancy.

A recent study published in the journal Pediatrics provides some important new data about the risk of ADHD in pre-term birth infants.  Scientists in Sweden examined the prevalence rates for ADHD in a group of children born preterm and compared it to the rates in infants born at term or slightly later.  Using several statistical models, they estimated the magnitude of effect of preterm birth on ADHD.  They found a significant statistical effect--the earlier the birth in gestation the greater the likelihood of childhood ADHD.

The magnitude of this effect is an approximate doubling of the risk for the earliest births.  The data from the study (model 3) estimated the risk (odds ratio) of childhood ADHD at several stages of development at birth:

• 23-28 weeks  Odds ratio=2.1
• 29-32 weeks  Odds ratio=1.6
• 33-34 weeks  Odds ratio=1.4
• 35-36 weeks  Odds ratio=1.3
• 37-38 weeks  Odds ratio=1.1
• > 38 weeks    Odds ratio=1.0

Similar studies in autism and autism spectrum disorder estimated a similar magnitude of risk for autism and autism spectrum disorder in preterm birth.  Infants born before 30 weeks appear to have approximately a doubled risk for autism and ASD.

From a prevention viewpoint, these studies support efforts to reduce the risk of preterm birth.  Although it is impossible to eliminate preterm births, the following measures can significantly reduce the risk:

• Smoking cessation during pregnancy
• Early and regular prenatal care
• Reducing the number of multiple birth pregnancies in infertility couples
• Progesterone use in women with a previous history of preterm birth
• Reducing the number of pregnancy inductions and C-sections in preterm pregnancies

Increased number of viable preterm births may be contributing to a portion of the number of children with ADHD and autism/autism spectrum disorders.  Improved neonatal care of preterm infants carries the potential for more children with special needs.  Improving neonatal care for infants in the neonatal intensive care as well as public health efforts to reduce the number of preterm births are critical initiatives for prevention of ADHD and autism.

The March of Dimes has an online resource site that provides professional education of the issue of reducing preterm births.

Photo of St. Louis Cardinal Tony LaRussa hitting balls to outfielders in 2011 Spring Training

Lindstrom, K., Lindblad, F., & Hjern, A. (2011). Preterm Birth and Attention-Deficit/Hyperactivity Disorder in Schoolchildren PEDIATRICS DOI: 10.1542/peds.2010-1279

Schendel D, & Bhasin TK (2008). Birth weight and gestational age characteristics of children with autism, including a comparison with other developmental disabilities. Pediatrics, 121 (6), 1155-64 PMID: 18519485

Recent Neuroscience Videos: TBI, Bipolar Disorder, Autism

This will be a little different Brain Post from the traditional research summaries I have posted in the past.  Instead this post will highlight some of the best videos I have recently run across related to neuroscience topics.  Most of these videos have a brief commercial prior to a video lasting 3 to 15 minutes.

Wall Street Journal: Nutrition Important to Healing Brain Injury-A brief discussion of issues related to providing the best nutrition in soldiers suffering a war-related brain injury.



Wall Street Journal: Shedding Light on Bipolar Disorder.  A six minute overview of bipolar disorder of recent intersest with the report that Catherine Zeta-Jones suffers from the disorder.



PBS NewsHour: The first in a series on autism from former anchor Robert McNeil.  This touching video shows McNeil's grandson who has autism.  It highlights the effects of autism on siblings and other family members.



Let me know if you find this format useful.  It will not be replacing the previous format but will become an occasional post to provide readers with some of the excellent video to better understand the disorders of clinical neuroscience.

Autism Twin Studies Point to Key Next Steps

Angelica Ronald and Rosa Hoekstra have written a nice review of recent twin studies in autism spectrum and autism traits.  The review is online prior to print in the American Journal of Medical Genetics Neuropsychiatric Genetics.

They note in the review that twin studies have evolved from a perspective of looking at narrowly defined autism, to the broader category of autism spectrum to an even broader phenotype, the dimensional character of autistic traits in the general population.

I don't know much about autism traits in the general population but this twin studies review highlighted some current understanding.

• Relatives of individuals with autism spectrum disorder show elevated autistic traits
• Autistic traits in the general population show a smooth distribution through the normal range to the clinical extreme--this suggests a biological continuum rather than a normal or disease clinical status
• Understanding the cause of variation of autistic traits in the general population is likely to aid in the understanding of autism
• The heritability of autistic traits in the population is very heritable (genetic) ranging from 40 to 60% in young twins but increasing to 60 to 90% in adolescence.

Another insightful section of the manuscript dealt with the degree of genetic and environmental overlap between different autistic symptoms.  Autism spectrum is made up of a triad of symptoms: social impairment, communication impairment and restrictive behaviors and interests.  Twin studies suggest these different symptom clusters may be "fractionable", meaning they may have some independence from each of the other clusters.  The authors note more genetic and twin studies should focus on one symptom cluster of the triad, rather than only studying those who have all three components.

The authors note that twin studies have helped explain the relationship between autism and intellectual disability and low IQ.  There appears to be some common genetic contribution to autism and intellectual disability.  However, since some individuals with autism and ASD have relatively normal intelligence, the picture is complex.  Studying ASD in those with normal intelligence may provide further insight into specific autism genetic influences. 

What needs to be done in the future?

Need for twin studies to tease out genetic and environmental factors that explain the common co-occurence of autism, ASD and autism traits with conduct disorder, sleep disorders, antisocial behavior and depression.

More attention needs to focus on genetic and environmental effects on developmental change in ASD and autistic traits in children (only two current studies published) and in adults (zero studies published).

More research on age-appropriate measures of autism traits--measures appropriate for one developmental age may not be appropriate for other ages.

More studies are necessary to look at cognitive phenotypes in autism and autism traits .

Photo of St. Louis Cardinal Daniel Descalso Courtesy of Yates Photography

Ronald, A., & Hoekstra, R. (2011). Autism spectrum disorders and autistic traits: A decade of new twin studies American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 156 (3), 255-274 DOI: 10.1002/ajmg.b.31159

Autism: Social Lives of Young Adults

One of the problems with understanding the natural history of autism is the lack of well-designed outcome studies in the disorder.  Outcome studies tend to be expensive and grant agencies commonly do not fund studies longer than a few years. However, given the increased interest and funding in autism, I suspect there will be more research in this area.

An example of how outcome studies help in understanding the natural history of autism is a study published ahead of print by the Journal of Developmental and Behavioral Pediatrics.  Dr. Gregory Liptak and colleagues from SUNY Upstate present a four year follow up of 725 adolescents with autism.  The average age at intake was 15.4 years with average age at follow up 19.2 years.

The study examined some key global items in function and social interaction.  I summarize some of the factors related to three key areas of function (% with this variable):

Being employed (48%) or in postsecondary education: This two-option level of achievement was positively correlated with higher family socioeconomic status (above the poverty level), not needing prescription drugs to control symptoms, good general physical health and having a parent who was involved in the school.  Negative correlations for this level of achievement was associated with conversational difficulty, a history of being teased and lower IQ.

Obtaining a driver's license (4.5%):  Few adolescents or young adults in this sample had a drivers's license.  Again this achievement was associated with higher socioeconomic status, caucasian race, a two-parent household and parental involvement in school activities.  A negative correlation with obtaining a driver's license was higher number of required school services.

Getting together with friends at least once in last 12 months (44.6%):   A positive correlation was noted with communication ability and good general health status.  A weak negative association was noted with non-white race status and male gender.

The authors note that this group of young adults with autism showed persistent differences in academic achievement and  social behavior compared to age-matched adults without autism.  In the young adults with autism 83% were living with their parents and 75% never used instant messaging, a chat room or e-mail.

The authors noted that their study did not examine whether young adults with autism (or their families) wanted more social interaction.  We often assume the more social participation the better, but this may not be the same for all. 

Even prospective studies have some limitations on interpreting causal contributions to outcome.  However, this study supports several components to planning services for children with autism.  These include reducing effects of poverty, reducing teasing/bullying in the environment, encouraging parents to be active in the school setting, early social and speech therapy and management of physical and mental co-occurring conditions.  

Photo of Female Cardinal Courtesy of Yates Photography

Liptak GS, Kennedy JA, & Dosa NP (2011). Social Participation in a Nationally Representative Sample of Older Youth and Young Adults With Autism. Journal of developmental and behavioral pediatrics : JDBP PMID: 21285894

How a Physician with Asperger Syndrome Made $100 Million

Life histories form one method of understanding some of the diversity of outcomes for clinical neuroscience disorders.  I had the opportunity over the holidays to read Michael Lewis’ The Big Short, a summary of some of the key players in the subprime mortgage debacle.  Expecting a financial education, it was a surprise to find an interesting story about a physician with high functioning Asperger syndrome.

Asperger syndrome is an autism spectrum disorder that includes difficulties in social interaction often paired with a restricted but intense focus on specific interests.  Cognitive development can be quite preserved in some individuals with Asperger syndrome, although most suffer from some cognitive impairment. 

The Big Short follows the history of the subprime mortgage problem as it developed in the mid 2000 time period.   A central question in the book is:  Why were so many experts surprised by the subprime crisis and unable to protect their financial assets from the manifestations of the subprime collapse?  A corollary to this question is:  Who were the people who saw the problem early and were able to financially benefit from their unique perspective and wisdom?

Enter Dr. Michael Burry.  Dr. Burry is a physician with an outstanding academic record.  Graduating from Vanderbilt University School of Medicine, Dr. Burry entered a prestigious residency in neurology at Stanford University.  Along with his busy medical career, Dr. Burry was fascinated by analysis of securities and other stocks.  He spent long hours at night during medical training pouring over financial statements and posting on financial message boards. 

During his residency training, he came to decide that he was more interested in financial analysis and money management.   To the dismay of family and colleagues he decided in 2000 to quit medicine and start his own hedge fund.  With $145,000 in student loan debt, such a decision seemed foolish to many.  But Dr. Burry knew he had good skills in finance and he also knew that some of the interpersonal aspects of medicine were not his strengths.

Dr. Burry was able to recruit investors to his hedge fund and received money by selling a portion of the fund.    Continuing his financial research, he identified the extreme risk associated with subprime mortgages, accurately assessing the risk for high default risks in these bonds.  Knowing the higher risk, he placed big bets the mortgage bonds would collapse.  Placing short investments in these bonds, he and his investors benefited with the collapse of the bonds.  Dr. Burry profited by taking $1 million to $100 million in only a few years. 

The neuroscience part of the story is unraveled late in the book.  After getting married, Dr. Burry has a son who displays problems with social interaction and restricted focus.   His son receives a comprehensive assessment and is given a diagnosis of Asperger syndrome.  As he receives this information, he and his wife begin to understand that Dr. Burry also has Asperger syndrome.  Despite his academic brilliance and medical training, it wasn’t until his son received an assessment that his own diagnosis became clear.

Since his diagnosis, Dr. Burry has received counseling specifically to help him understand his social limitations and how he can better relate to his family.  He understands that the intense interest in obscure subject matter is part of Asperger syndrome.  His intense interest in financial analysis led to his ability to be one of the first people to predict (and personally benefit) from the subprime mortgage collapse.

So here are the take away neuroscience messages for me on this story.  First, many adults with Asperger syndrome are undiagnosed with some only receiving a proper diagnosis later in life.  Second, although this disorder causes significant impairment in most, some individuals may turn their intense focus (a symptom of Asperger) into important discoveries in finance and well as other arenas, i.e. science or computer technology.   It’s a complex disorder with heterogeneous outcomes.  We need to better understand the neuroscience of this condition.

Vanity Fair article summarizing the Dr. Burry part of The Big Short

Amazon link to Michael Lewis’ The Big Short

Bloomberg video with Dr. Burry (September 2010) showing his current financial investments

Photo of Lions in Kenya Courtesy of Sarah Yates

Medications in Autism: Resources for Parents

Parents of children with autism face a myriad of decisions regarding treatment options.  Medications can be one component of a multidisciplinary treatment approach.  However, there is limited research to assist in making evidence-based decisions.  The only FDA approved medications approved for autism are risperidone and aripiprazole--atypical antipsychotic medications indicated for the irritability that can be associated with the disorder.

Williamson and Martin from Vanderbilt University and Yale University respectively, recently summarized some practical considerations on psychtropic medications targeted for parents. This review provides an up-to-date summary of research. The review identifies three clusters of symptoms common in autism: irritability, inattention and motor hyperactivity and repetitive behavior. Here is a synopsis of their recommendations:

Irritability

• Risperidone first FDA approved drug for irritability in autism
• New England Journal published study found 57% decrease in irritability in children with autism compared to only a 14% decrease in placebo group
• Aripiprazole is a newer atypical agent with some promise
• Primary side effects of these agents are metabolic-weight gain, increased cholesterol, increased prolactin hormone levels, increased risk is type 2 diabetes
• Adding psychoeducation and parental training augments effect of risperidone on irritability outcomes
• Older typical antipsychotics may be effective--these have less metabolic side effects but higher risk for inducing movement disorders (tardive dyskinesias)
• Mood stabilizers such as lithium and valproic acid have limited evidence of effectiveness for irritability
• One small study of 25 children with autism found 40% reduction in irritability with alpha-2 agonist guanfacine

Inattention and motor hyperactivity

• Symptoms similar to those found in children with ADHD common in autism
• Stimulants such as methylphenidate and dextroamphetamine very effective in ADHD without autism
• Stimulants have less effectiveness for inattention and hyperactivity in children with autism
• Response rates lower in this group--may require trials of several agents before effective response seen
• Children with autism appear more likely to experience side effects with stimulants
• Alpha-2 agonists (guanfacine) commonly used for ADHD but limited research in autism populations

Repetitive behaviors

• Medications studied have typically been drugs that have shown some effectiveness in treating repetitive behaviors in obsessive compulsive disorder, i.e. the selective serotoning re-uptake inhibitors
• However, randomized trial of the selective serotonin re-uptake inhibitor, citalopram found no benefit over placebo
• One small study of 13 patients found improvement in repetitive behaviors with the mood stabilizer valproic acid

The authors note one of the best studied drugs in autism is secretin. However, despite initial promise further large well-designed studies found no evidence of effectiveness in autism.

The authors note that parents should consider medication options only in the context of comprehensive treatment programs with a physician who has expertise in pediatric psychopharmacology.   Currently available medications are not a cure, but may substantially improve some target symptoms.   Side effects can be serious and require careful consideration of the risk-benefit profile and careful medical monitoring.

Our understanding of autism has evolved from a disorder once incorrectly considered a result of disordered parenting to a genetic disorder of neurodevelopment.   I agree with the authors closing statement: "Well-informed, engaged and proactive parents will continue to play a pivotal role in the treatment of their own children, and as the past two decades have shown, through their advocacy and involvement, help in the care of all children with autism spectrum disorders."

3 D Model of Risperidone Courtesy of Wikepedia Commons file authored by Ben Webber

Additional Recommended Resources for Parents with a Child with Autism

• American Academy of Pediatrics Autism Information
• American Academy of Child and Adolescent Psychiatry Autism Resource Center

Williamson ED, & Martin A (2010). Psychotropic Medications in Autism: Practical Considerations for Parents. Journal of autism and developmental disorders PMID: 21170674

Top Ten 2010 Brain Posts

Here's a recap of ten of the most viewed Brain Posts from 2010.  The list comes from the count totals from Clicky and Blogpost stats.

1. Perfectionism as a Risk Factor for Anorexia Perfectionism when combined with other psychological problems (low-self esteem, body dissatisfaction) increases risk for developing anorexia nervosa
2. Why People Believe Weird Things Michael Shermer, the publisher of Skeptic magazine recently presented at TED looking at why humans tend to be open to self-deception. 
3. Vitamin B and Brain Atrophy in Alzheimer's Disease A group of subjects taking a vitamin B complex supplement showed a reduced rate of brain atrophy.
4. REM Sleep Latency in Autism Children with autism show reduced level of REM sleep. 
5. Do Personalities Converge After Marriage? People who get married often share similar personality features, but personalities do not appear to become more similar with time.
6. Pitfalls in the Diagnosis of Adult ADHD ADHD is characterized by deficits in brain executive function.  These deficits are often not part of a diagnostic assessment. 
7. Neuroscience of Murder and Aggression, Part 1 Dr. Jim Fallon summarizes results of research into the minds of murders in a TED presentation. 
8. Deep Brain Stimulation for Depression Dr. Helen Mayberg summarizes research into the use of deep brain stimulation for depression at a NARSAD sponsored lecture. 
9. Chocolate Consumption and Depression A cross-sectional study found that people with higher depression scores tended to consume more chocolate.
10. Brain Neurocircuitry in Depression Dr. Wayne Drevets of the Laureate Institute for Brain Research summarizes research into the brain circuitry of depression.  


I want to thank the readers of Brain Posts.  It has been an exciting year in clinical neuroscience research.  I learned quite a bit through reading and posting on this blog.  Best wishes for a great 2011!


Photo of Santa Feeding Fish at the Oklahoma Aquarium Courtesy of Yates Photography.


Wade TD, Tiggemann M, Bulik CM, Fairburn CG, Wray NR, & Martin NG (2008). Shared temperament risk factors for anorexia nervosa: a twin study. Psychosomatic medicine, 70 (2), 239-44 PMID: 18158375


Krummenacher P, Mohr C, Haker H, & Brugger P (2010). Dopamine, paranormal belief, and the detection of meaningful stimuli. Journal of cognitive neuroscience, 22 (8), 1670-81 PMID: 19642883


Smith, A., Smith, S., de Jager, C., Whitbread, P., Johnston, C., Agacinski, G., Oulhaj, A., Bradley, K., Jacoby, R., & Refsum, H. (2010). Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial PLoS ONE, 5 (9) DOI:10.1371/journal.pone.0012244


Buckley AW, Rodriguez AJ, Jennison K, Buckley J, Thurm A, Sato S, & Swedo S (2010). Rapid eye movement sleep percentage in children with autism compared with children with developmental delay and typical development. Archives of pediatrics & adolescent medicine, 164 (11), 1032-7 PMID: 21041596


Humbad MN, Donnellan MB, Iacono WG, McGue M, & Burt SA (2010). Is Spousal Similarity for Personality A Matter of Convergence or Selection? Personality and individual differences, 49 (7), 827-830 PMID:21116446


Kessler RC, Green JG, Adler LA, Barkley RA, Chatterji S, Faraone SV, Finkelman M, Greenhill LL, Gruber MJ, Jewell M, Russo LJ, Sampson NA, & Van Brunt DL (2010). Structure and diagnosis of adult attention-deficit/hyperactivity disorder: analysis of expanded symptom criteria from the adult ADHD clinical diagnostic scale. Archives of general psychiatry, 67 (11), 1168-78 PMID: 21041618


Mayberg HS (2009). Targeted electrode-based modulation of neural circuits for depression. The Journal of clinical investigation, 119 (4), 717-25 PMID: 19339763


Cadoret RJ, Yates WR, Troughton E, Woodworth G, & Stewart MA (1995). Genetic-environmental interaction in the genesis of aggressivity and conduct disorders. Archives of general psychiatry, 52 (11), 916-24 PMID: 7487340


Rose N, Koperski S, & Golomb BA (2010). Mood food: chocolate and depressive symptoms in a cross-sectional analysis. Archives of internal medicine, 170 (8), 699-703 PMID: 20421555


Price JL, & Drevets WC (2010). Neurocircuitry of mood disorders. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 35 (1), 192-216 PMID: 19693001