Paying attention to ADHD and other research

Although scientists and clinicians continue to make new discoveries as well as refine existing practices over how to diagnose and treat ADHD— the FDA’s recent approval of the use of EEG or brainwave recording technology to aid in the diagnosis of ADHD in children (Food and Drug Administration, 2013) is one such example—there is no debate among well-informed healthcare professionals that ADHD is a real condition and causes significant impairments. The American Academy of Child and Adolescent Psychiatry acknowledges as such in its most recent Practice Parameters for the Assessment and Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder, naming it “a valid neurobiological condition” (2007). This refers to our current understanding of ADHD as caused by the combination of many inherited genes, some childhood experiences, and early medical history and these in turn cause a change in how the brain distributes certain chemical receptors and molecular pumps to its cells, changing how it uses signaling chemicals, in particular, one called dopamine. The genes involved are diverse, and environmental factors can include such things as birth weight, head trauma, and alcohol/nicotine exposure.

ADHD is not an American invention. Over the years, the ADHD is reported at fairly consistent rates across diverse geographic, racial, and socioeconomic conditions (Wood, Elia, Ambrosini, & Rapoport, 1991). Although different countries and cultures have tended to reported different rates, this difference has been shown as result of different definitions used (Faraone, Sergeant, Gillberg, & Biederman, 2003)—criteria more narrowly  focused on hyperactive behaviors had evolved over the years to include ‘subtypes’ which also capture impulsiveness and inattention, leading to more diagnosis. Neither is ADHD medication over-prescribed. A US national survey conducted to obtain reports from parents of 79,264 children between the ages of 4 and 17 found that although 7.8% were diagnosed with ADHD, only a little over half were currently taking medication for the disorder (Visser, Lesesne, & Perou, 2007). Certainly one good reason not to avoid treating ADHD is the finding that the brains of children show closer-to-normal growth in the number of brain cells and nerve fibers after long-term treatment, when compared to those whom had just been diagnosed and had not yet received treatment (Castellanos, et al., 2002).

Given our understanding of how ADHD is caused by genetic and developmental factors which influence the neurology of children around the world and across many cultures, we should therefore not expect many of these children to just “grow out of it”. A review on the diagnosis of adult ADHD (Primich & Iennaco, 2012) notes that although 4.4% of the adult population is estimated to have ADHD, only 10.9% of those are in treatment. Because the inattentive and distractible symptoms of ADHD can easily coexist or even cause the symptoms seen in other disorders such as anxiety and depression, clinicians must take special care to uncover the nuances of the impairments of an adult seeking help—they may be experiencing a variety of difficulties across many different settings of daily life stretching far back into earlier stages of life.

We can see that even though our understanding of ADHD has gone through definitional changes over the years, the core symptoms of this neurobiological syndrome has always been defined on the basis of behavioral characteristics. For example the authors of a 1976 preliminary report titled “Diagnosis and Treatment of Minimal Brain Dysfunction in Adults” (Wood, Reimherr, Wender, & Johnson) had identified a group of adult patients with the diagnostic labels (in use at that time) of sociopathy, explosive personality, hysterical character and labile personality that were difficult to treat but responded to low doses of stimulants and an antidepressant. They concluded with a set hypothesis that is striking in how similar it is to our current understanding of ADHD and how it can persist into adulthood with accompanying or related psychiatric disorders, including: MDB (minimal brain dysfunction) is a “genetically transmitted abnormality…in arousal that produces increased activity and an inability to focus attention, concentrate, or inhibit irrelevant responses”; untreated adults can produce a “heterogeneous and perhaps incomprehensible group of symptoms”; adults with MDB develop “abortive compensatory mechanisms” due to many impairments in all spheres of life leading to further diagnoses etc.

With so much clinical data gathered over the years on the effectiveness of medications and other strategies in improving the symptoms of ADHD, it seems hard to imagine how recent discoveries in neurophysiology can bring new insights into its diagnosis and treatment. Indeed the AACAP quotes the American Medical Association’s Council on Scientific Affairs review of the literature (Goldman, Genel, Bezman, & Slanetz, 1998) in its Practice Parameter, saying “Overall, ADHD is one of the best-researched disorders in medicine, and the overall data on its validity are far more compelling than for many medical conditions”. A lack of clarity in our understanding of what we mean when we say “attention” may be behind our odd feelings as clinicians that both know too much and too little about ADHD at the same time. That is, continuing basic research into how certain parts or circuits of the brain contribute to our cognition and behavior may be causing the commonly used mentalist or psychological labels that we refer to (in the negative) when we describe the impairments of ADHD, such as “executive control”, “impulse inhibition”, “working memory”, etc. to fall apart. It is interesting to note that the public is already being made aware of how drawing conclusions from the parallel presentation of measures in the brain (neurophysiological data) and subjective reporting (behavioral observation) without adequate interpretation can be confusing if not disturbing. For example, this article from the magazine Science gives a good explanation by contrasting the difference between good fMRI imaging research on the recognition of faces using powerful pattern recognition techniques, and results published by the New York Times claiming that one or two differences in scanned brains could indicate which candidate a person would vote for in the 2008 presidential elections (Miller, 2008).

Therefore the EEG (brainwave) scanning device developed by Neba Health© to aid in the diagnosis of ADHD in children previously mentioned to be approved by the FDA for marketing deserves scrutiny. The Neba device compares the amount of beta and theta waves measured and uses that to determine if a child is likely to have ADHD, and whether the child will need further testing for another condition that is not ADHD. According to the study data released by the company (Neba Health, 2013), a triple-blinded study was conducted at 13 clinical sites on 275 children and adolescents who were seeking help for attentional and behavioral concerns and the device was found to reduce the rate at which a clinician working alone misdiagnosed ADHD—that is, when another factor could better account for the problematic behavior of the child —from 34% of the time down to 3%. The strength of this study may be supported by the multidisciplinary team used to eventually evaluate all these children, and whose diagnoses were used as the “benchmark”—this team included a child and adolescent psychiatrist, a clinical psychologist, and a neurodevelopmental pediatrician, and they tested for a variety of conditions which could indicate that a child’s problematic behaviors were not due to ADHD, such as hearing and vision problems, having tried medications with no improvement, and acting out mostly due to anger.

Although the study data provided is not extensive perhaps due to propriety concerns, the potential for this device to be used to improve practice especially in settings where an extensive multidisciplinary screening for a child may not be readily available is clear. More importantly, the materializing idea that “biomarkers” derived directly from neurophysiology such as the “standardized theta/beta ratio” that this device measures can lead to direct applications in clinical practice and decision-making, points to the possibility of an increasingly less “dualist” approach to ADHD and other neurodevelopmental disorders to come.

 

References:

American Academy of Child and Adolescent Psychiatry. (2007). Practice Parameter for the Assessment and Treatment. Journal of the American Academy of Child and Adolescent Psychiatry, 894-920.

Castellanos, F., Lee, P., Sharp, W., Jeffries, N., Greenstein, D., Clasen, L., . . . Rapoport, J. (2002). Developmental Trajectories of Brain Volume Abnormalities in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder. The Journal of the American Medical Association, 288(14), 1740-1748.

Faraone, S., Sergeant, J., Gillberg, C., & Biederman, J. (2003). The worldwide prevalence of ADHD: is it an American condition? World Psychiatry, 2(2), 104-113.

Food and Drug Administration. (2013, July 15). Press Announcements > FDA permits marketing of first brain wave test to help assess children and teens for ADHD. Retrieved from US Food and Drug Administration Home Page: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm360811.htm

Goldman, L., Genel, M., Bezman, R., & Slanetz, P. (1998). Diagnosis and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. The Journal of the American Medical Association, 279(14), 1100-1107.

Miller, G. (2008). Growing Pains for fMRI. Science, 320, 1412-1414.

Neba Health. (2013, July 22). Summary of Neba Clinical Investigation – Key Results. Retrieved October 20, 2013, from http://www.nebahealth.com/PR0779_neba_press_release-20130722_Cr.pdf

Primich, C., & Iennaco, J. (2012). Diagnosing adult attention-deficit hyperactivity disorder:. Journal of Psychiatric and Mental Health Nursing, 19, 362-373.

Visser, S., Lesesne, C., & Perou, R. (2007). National Estimates and Factors Associated With Medication Treatment for Childhood Attention-Deficit/Hyperactivity Disorder. Pediatrics, 119(1), 99-106.

Wood, A., Elia, J., Ambrosini, P., & Rapoport, J. (1991). Treatment of Attention-Deficit-Hyperactivity Disorder. The New England Journal of Medicine, 340(10), 780-788.

Wood, D., Reimherr, F., Wender, P., & Johnson, G. (1976). Diagnosis and Treatment of Minimal Brain Dysfunction in Adults. Archives of General Psychiatry, 33, 1453-1460.

The Controversial and Societal Weight of Measuring Intelligence

No discussion of intelligence would be entirely complete without a nod to measures of intelligence, in other words, the polemical standardized tests of IQ.  The idea of IQ, or an intelligence quotient, has remained an issue of controversy since its inception.  The IQ has been applied to such an extensive array of uses and meanings in human society that it has continued to accumulate a weightiness that few other quantifiable concepts have attained.  Modernity uses it to indicate impairment, predict academic achievement, and success in the workplace (Deary, 2001).  It likely inspired the development of other tests such as the Scholastic Assessment Test (SAT), formerly the Scholastic Aptitude Test, which is still used to predict collegiate success, or essentially, admission to the halls of scholarship.  In its most audacious application, IQ is inadvertently used to define one’s status in society.  As such, many have remained wary of a single number defining one’s intellect and all the inferences that accompany such an assertion.

To illustrate the aforementioned point, I recall a situation during my training in which we were assigned to practice administering and scoring IQ tests on subjects who were willing to participate.  This volunteerism came with the caveat that the results could not be shared as they would likely be invalid given our amateur status as trainees.  As I went about recruiting my “victims,” I recall approaching an acquaintance who was generally known for her high intellectual abilities.  She pleasantly agreed and arrived promptly several days later for testing.  However, I soon witnessed the confidence of a successful and highly respected individual suddenly quiver under the weight of a mere practice test.  She was visibly nervous and began to express concerns that perhaps the test would uncover an impairment of some sort or reveal that perhaps she was not as intelligent as she had perceived herself to be.  She tended to give each answer tentatively occasionally adding, “I am probably getting all of these questions wrong.” 

This scenario has remained with me as a lesson to the incredible complexity and precarious nature of attempting to quantify a concept that can become such a part of our identity.  Still, in order for a concept to be effectively measured it must be defined.  The g factor, an abbreviated term for general factor, is the psychometric construct currently used to measure cognitive ability.  In essence, g factor is synonymous with IQ and is what most tests of intelligence are presumed to be measuring. 

Some of the earliest investigations looking at g factor emerged from psychologist Alfred Binet.  Binet was commissioned by the French government to identify children within the school system who may need special assistance (Kaufman, 2009).  Through the process of meeting this request, Binet began to develop a theory of intelligence, which eventually culminated in the well-known Stanford-Binet Intelligence Scale used today (2009).  Several years later American psychologist David Wechsler emerged with his own measurement of intelligence.  The Wechsler Adult Intelligence Scale (WAIS) was published in 1955 and has since undergone several revisions and branched into other tests such as the Wechsler Intelligence Scale for Chldren (WISC), among others (Groth-Marnat, 2003).  Wechsler’s theory of intelligence was similar to Binet’s in that he believed multiple facets and functions made up overall intelligence.  More specifically, Wechsler’s definition of intelligence referred to, “…the global capacity of a person to act purposefully, to think rationally, and to deal effectively with his environment” (Wechsler, 1939, p. 229).  Wechsler designed the test to offer a single number that the general public understands to be the participant’s IQ score, referred to by the WAIS as the Full Scale IQ (FSIQ).  However, in situations where the clinician may statistically determine that the participant’s intellectual functioning is not best explained by the FSIQ, there is additional analysis at the level of the other scales, Verbal IQ (VIQ) and Performance IQ (PIQ) (Groth-Marnat, 2003).

In an attempt to challenge the traditional sense of IQ, additional theories of intelligence have been derived over time.  An article in the Monitor on Psychology succinctly identified several of the most prominent theories including Daniel Goleman’s, PhD, theory of emotional intelligence, Harvard University psychologist Howard Gardner’s multiple intelligences theory, and the triarchic theory of successful intelligence by Robert J. Sternberg, PhD, of Yale University (Benson, 2003).  While the length of this assignment is not conducive to explaining the premise of each, the author of the article effectively summarized their place within the measures of intelligence arena as theories that pick up where traditional thought fell short of capturing “…essential aspects of intelligence” (Benson, 2003, p.48). 

Certainly the most controversial issue surrounding the notion of IQ is group differences in mean IQ.  For example, Asians consistently obtain higher IQ scores than Whites and Blacks score lower than Asians and Whites (Rushton & Jensen, 2005).  In particular, the Black-White difference has been studied at such an extensive rate that it has been asserted, “…the 1.1 standard deviation difference in average IQ between Blacks and Whites in the United States is not in itself a matter of empirical dispute,” (Rushton & Jensen, 2005, p 236).  In essence, we know this phenomenon occurs and is not a function of deficient psychometrics, but fully understanding its cause remains elusive. 

The most common argument for IQ test bias is that test items are culturally bias in favor of a European American middle-class society.  Critics of IQ tests offer that they are not measuring innate abilities, but rather how familiar one is with the White American culture (Young, 2010; Whiting & Ford, 2009).  On the other hand, some researchers have found that when culturally biased items are removed, scores have not been shown to improve and also suggest IQ is merely a sample of one’s intellectual functioning (Groth-Marnat, 2003).  In effect, the debate continues while investigations into a multitude of explanations such as heritability, brain size, environmental variables, life-history traits and genetic components are heavily evaluated (Deary, 2012; Rushton & Jensen 2005; Groth-Marnat 2003).

The discussion of intelligence has almost innumerable facets and without question this student has neglected many areas of important discussion.  For instance, the phenomenon of the Flynn effect, which shows that worldwide IQ has increased over the course of decades, is highly applicable. Historical litigations such as Larry P. v. Wilson Riles (1979) provide essential insights into IQ’s function in current society.  Also the discoveries of fluid intelligence (Gf) and crystallized intelligence (Gc) were seminal to the function of testing.  Instead, it is hoped the brief overview provided thus far has afforded some foundational information while encouraging readers to engage in critical assessment of the implications of intelligence. 

 References

Benson, E. (2003). Intelligent intelligence testing. Monitor on Psychology, 34(2), 48.

          Retrieved from www.apa.org.

Deary, I.J. (2001) Intelligence: A very short introduction. New York, NY: Oxford University

          Press Inc.

Deary, I.J. (2012). Intelligence. Annual Review of Psychology, 63, 453-482.

Groth-Marnat, G. (2003). Handbook of psychological assessment fourth edition. Hoboken,

          NJ: John Wiley & Sons, Inc.

Kaufman, A.S. (2009). IQ testing 101. New York, NY: Springer Publishing Company.

Rushton, J.P. & Jensen, A.R. (2005). Thirty years of research on race differences in

          cognitive ability. Psychology, Public Policy, and Law, 11(2), 235-294.

Wechsler, D. (1939). The measurement of adult intelligence. Baltimore, MD: Williams &

          Witkins.

Whiting, G. & Ford, D. (2009). Cultural bias in testing. Retrieved from

          www.education.com.

Young, E.M. (2010). Dealing with the culture bias in intelligence testing culture free and

         culture fair IQ tests. Retrieved from www.sciences360.com.

 

 

 

A closer look at mirror neurons and their role in autism spectrum disorder

One of the noteworthy changes introduced by the new DSM 5 is its revision of the categorical diagnoses of autism-related disorders. Previously, patients were diagnosed with one of four discrete disorders: Autistic Disorder, Asperger’s disorder, Childhood Disintegrative Disorder, or a kind of catch-all category: Pervasive Developmental Disorder NOS (DSM 4). Not only were these diagnoses inconsistently applied, they no longer reflected our most current understanding of the disorders (http://www.dsm5.org/Documents/Autism%20Spectrum%20Disorder%20Fact%20Sheet.pdf). By reframing diagnoses along a spectrum, the hope was that clinicians would be better equipped to capture more specific variations in symptoms and behaviors –variations that could paint a more precise picture of the individual. Implicit in the shift to a conceptualization of autistic disorders along a spectrum was the recognition that these disorders share certain, aberrant developmental processes. Though much of the pathology remains a mystery, research into the neurobiology of Autism Spectrum Disorder (ASD) has deepened our understanding of its nature and generated a number of promising findings.

Some of the most promising ASD research has centered on a specialized set of neurons found in the Superior Temporal Sulcus (STS). These neurons –sometimes called “action-coding neurons” – are involved in the recognition of hand and body movements and the interpretation of their intentions (Williams et al, 2001, p 290). One study demonstrated the activation of the same subset of action-coding neurons in the STS of monkeys during the execution of grasping and in observation of the same action performed by another monkey (Grafton et al, 1996). This was one of the first studies to observe and conceptualize what are now known as mirror neurons (MN).

All MNs operate in the same way: by taking incoming sensory information that depicts some motor action done by another and translating it into the kind of “motor format similar to that the observers themselves generate when they perform those acts,” (Rizzolatti & Fabbri-Destro, 2010, p 227). Nevertheless, MNs serve different purposes and realize different effects in the brain. fMRI studies support the idea that the effect MNs realize within the observer is dependent on the location of the ‘mirror system’ (network of MNs) that is firing in the brain. So, a mirror system active in the emotional centers such as the insula plays an active role in empathy (Gallese et al, 2004). Other studies similarly attest, MNs facilitate social functioning by enabling typically developing individuals to place themselves in others’ shoes (Williams et al, 2001). At what level does the mirror system break down or dysfunction for the individual with ASD?

One of the leading accounts of MNs’ implication in ASD-related social deficits posits that the MNs are disorganized. It’s not that there are too many or too few in individuals with ASD; the basic MN mechanism works. Instead, the dysfunction is related to the integrity of their organization in ‘chains’. In a recent study, a group of typically developing children (TD) and ASD children were presented with numerous pictures each showing individuals executing goal-directed actions (Boria et al, 2009). Each group was asked to explain not simply what was being done, but why. The TD group was able to explain each –e.g. what: turning a doorknob; why: to escape a dangerous situation. The ASD group recognized what was being done but were unable to explain why. Interestingly, the individuals with ASD nearly all offered the same incorrect explanation of intention, one that based its interpretation on the common use of the object rather than basing it on the motor behavior of the actors (Rizzolatti & Fabbri-Destro, 2010). Here, the ASD individual lacks a ready and immediate association between the correctly identified motor action and some social meaning. In its disorganization, the MN chain links MNs mirroring motor action with object associations, missing the social significance.

Is there any way to correct these dissociations, to reorganize MNs so that they link motor actions with their intended social meaning? A study of imitation in autism suggests the possibility that therapeutic training in imitative skill could be used not only to develop those skills of imitation (the how of smiling) but also the socio-cognitive aspects of the act (reason/motivation) (Hadjikhani, 2007). In a second study, children with ASD participated in repeated sessions of adult imitation; the repetitious work increased not only their imitative skill but, for some, attendant, socially appropriate behaviors as well (Wallen & Bulkeley, 2006). Although the mechanism behind the development of the socially appropriate behaviors in this particular example is not well understood, it is hopeful that evidence exists in support of the plasticity of mirror mechanisms. Other studies have shown that “the mirror responses triggered by a corresponding movement could be modified by repetitively coupling the performed movement with the observation of different movements” (Rizolatti, 2008, p 184). In other words, the child who must learn to imitate the handshake, might also learn through repetition the associated actions of smiling and making eye contact. Though such a process might not offer the child with ASD direct access to the intention behind these three coordinated actions, it might begin the work of laying down a network of understood actions-intentions upon which the child could later base rudimentary interpretations of social cues. A smile and an outstretched hand usually invite social engagement.

___________________________________________________________________________

Boria S., Fabbri-Destro M., Cattaneo L., Sparaci L., Sinigaglia C., Santelli E., Cossu G., Rizzolatti G. (2009). Intention understanding in autism. PLoS ONE 4(5), e5596.

Gallese V., Keysers C., Rizzolatti G. (2004). A unifying view of the basis
of social cognition. Trends in Cognitive Science 8, 396–403.

Grafton, S. T., Arbib, M. A., Fadiga, L., & Rizzolatti, G. (1996). Localization of grasp representations in humans by positron emission tomography. 2. observation compared with imagination. Experimental Brain Research, 112(1), 103-111.

Hadjikhani, N., (2007). Mirror neuron system and autism. Progress in Autism Research, 6, 151-166.

Rizzolatti, G., & Fabbri-Destro, M. (2008). The mirror system and its role in social cognition. Current Opinion in Neurobiology, 18(2), 179-184.

Rizzolatti, G., & Fabbri-Destro, M. (2010). Mirror neurons: From discovery to autism. Experimental Brain Research, 200(3-4), 223-237.

Wallen, M., and Bulkeley, K. (2006). Three sessions of adult imitation increased some appropriate social behaviors of young children with autism. Australian Occupational Therapy, 53(2), 139-140.

Williams, J. H., Whiten, A., Suddendorf, T., & Perrett, D. I. (2001). Imitation, mirror neurons and autism. Neuroscience & Biobehavioral Reviews, 25(4), 287-295.

The role of oxytocin in social attachment and mental illness

Oxytocin is a neuropeptide hormone that has well characterized functions on both the peripheral reproductive system and the central nervous system. The hormone is produced within the supraoptic and paraventricular nuclei the hypothalamus and transported to the posterior pituitary gland. From here it is released can be released into general circulation where it plays a critical role in delivery by stimulating uterine contractions and promoting milk letdown during lactation (Ross & Young, 2009).

In the central nervous system, oxytocin has been long known to facilitate mother and infant and adult pair bonding (Ross & Young, 2009), however, a rapidly growing body of research suggests that oxytocin also plays an important role in broader aspects of social cognition and affiliation in both sexes (Ross & Young, 2009). A study of mice found that those without oxytocin receptors were unable to recognize mice they had previously met (Ross & Young, 2009). Similarly, studies have found that humans had an improved memory for faces they had recently met after oxytocin administration (Rimmele, Hediger, Heinrichs, & Klaver, 2009). Oxytocin administration has been associated with increased eye contact (Bartz, Zaki, Bolger, & Ochsner, 2011) and increased ability for humans to identify emotional states based on pictures of the eye region (Bartz et al., 2010). Several studies have shown that humans are better able to infer emotions from others’ facial expressions after given an intranasal oxytocin administration (Bartz, et al., 2010).

Studies exploring oxytocin’s role in attachment and affiliation have found that participants receiving intranasal oxytocin demonstrated increased cooperation with and trust of strangers in a game, even after being betrayed by the stranger (Miller, 2013). Similarly, a group of adults receiving oxytocin were more likely to rate strangers as more attractive and trustworthy than controls. (Theodoridou, Rowe, Penton-Voak, & Rogers, 2009). In contrast to these studies, some recent research has demonstrated that the effects of oxytocin may not be uniformly positive and may be dependent on person and context. In studies using the same game as mentioned above, subjects only demonstrated increased cooperation with those within their same ethnic group, or those who they considered to be socially similar (Miller, 2013). Oxytocin has also been implicated in decreased trust perceptions in those with insecure or avoidant attachment styles (Bartz et al., 2010).

These early results have generated excitement over the potential therapeutic applications of oxytocin and clinical trials have extended to populations with disorders characterized by social deficits, including autism spectrum disorder (ASD), schizophrenia, and borderline personality disorder (Kuehn, 2011; Modi & Young, 2012). Studies involving exogenous administration of oxytocin to adults and adolescents with ASD have demonstrated improvements on social cognitions tests including emotion recognition and increased eye contact (Modi &Young, 2012; Yamasue, 2013). Plasma studies have revealed lower endogenous levels of oxytocin in those with ASD, although these findings are not consistent (Green & Hollander, 2010). Studies in the schizophrenic population have found that higher levels of endogenous oxytocin in schizophrenic patients were associated with less severe positive symptoms and reduced psychopathology (Kuehn, 2011). Interestingly, after intranasal oxytocin was administered to a group of adults with borderline personality disorder (BPD), a disorder characterized by emotional instability and increased sensitivity to rejection, the subjects were less trusting and less likely to cooperate with a partner in a social dilemma game than controls with BPD (Modi & Young, 2012).

Unfortunately, the neural mechanisms behind this promising research are not yet well understood. Animal and human studies have demonstrated that oxytocin receptors are distributed densely in areas of the brain involved in fear and emotional processing, including the amygdala, nucleus accumbens, and ventromedial hypothalamus (Green & Hollander, 2010). Functional magnetic resonance imaging (fMRI) studies have found that oxytocin modulates amygdala responses to fearful, stressful, and anxiety provoking stimuli (Yamasue et al., 2012), suggesting that oxytocin promotes pro-social behavior by decreasing anxiety in unfamiliar social situations. An interaction between oxytocin and dopamine in the ventral striatum in animal studies suggests that oxytocin may be involved in the reward circuit in social contexts (Yamasue et al., 2012). Other studies point to increased functional connectivity between the amygdala and visual processing areas to suggest that oxytocin may also work by increasing the salience of social cues (Yamasue et al., 2012).

Genetic studies have recently identified variations in the gene that encodes for oxytocin receptors in the brain, the oxytocin receptor gene (OXTR). Variations in the OXTR have been linked to variations in pro-social traits in normally developed adults (Yamasue, 2013). They have furthermore linked variations in the oxytocin receptor gene to susceptibilities for mental disorders including ASD, schizophrenia, and severe aggressive behaviors in children (Yamasue, 2012).

This growing body of research elucidates the incredible potential that oxytocin may have in addressing social behavior deficits in mental disorders like ASD and schizophrenia. These studies also highlight the many gaps in knowledge there are regarding the genetic and neural mechanisms behind both endogenous and exogenous oxytocin. Similarly, little is known about the long term developmental effects of exogenous oxytocin as many studies have examined participants after a single dosage of intranasal oxytocin. This will be especially salient for its potential use in disorder like ASD, where early treatment initiation may lead to improved functionality. Disconcertingly, one study found that male voles treated for several weeks with daily oxytocin administration around the time of adolescence later exhibited impaired social bonding with females (Kuehn, 2011). Finally, it is important to define the individual and contextual differences that moderate the effectiveness of exogenous oxytocin administration. What kind of psychotherapy should be administered simultaneously to pharmacological treatment and to whom? Though there is work to be done, examining the role that this hormone plays in social attachment and the potential effectiveness it has in treating related disorders is deserving of the considerable attention it has received in recent years.

References

Bartz, J. A., Zaki, J., Bolger, N., Hollander, E., Ludwig, N. N., Kolevzon, A., & Ochsner, K. N. (2010). Oxytocin selectively improves empathic accuracy. Psychological Science, 21, 1426-1428. Retrieved from OVID database.

Bartz, J.A., Zaki, J., Bolger, N., & Ochsner, K. N. (2011). Social effects of oxytocin in humans: Context and person matter. Trends in Cognitive Science, 15, 301-309. Retrieved from OVID database.

Farmer, C., Thurm, A., & Grant, P. (2013). Pharmacotherapy for the core symptoms in autistic disorder: Current status of the research. Drugs, 73, 303-314. Retrieved from OVID database.

Green, J. J., & Hollander, E. (2010). Autism and oxytocin: New developments in translational approaches to therapeutics. Neurotherapeutics, 7, 250-257. Retrieved from OVID database.

Guastella, A. J., Einfeld, S. L., Gray, K. M., Rinehart, N. J., Tonge, B. J., Lambert, T. J., & Hickie, I. B. (2010). Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biological Psychiatry, 67, 692-694. Retrieved from OVID database.

Kuehn, B. M. (2011). Scientists probe oxytocin therapy for social deficits in autism, schizophrenia. Jama, 305, 659-661. Retrieved from OVID database.

Miller, G. (2013). Neuroscience. the promise and perils of oxytocin. Science, 339, 267-269. Retrieved from OVID database.

Modi, M. E., & Young, L. J. (2012). The oxytocin system in drug discovery for autism: Animal models and novel therapeutic strategies. Hormones & Behavior, 61, 340-350. Retrieved from OVID database.

Rimmele, U., Hediger, K., Heinrichs, M., & Klaver, P. (2009). Oxytocin makes a face in memory familiar. Journal of Neuroscience, 29, 38-42. Retrieved from OVID database.

Ross, H. E., & Young, L. J. (2009). Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Frontiers in Neuroendocrinology, 30, 534-547. Retrieved from OVID database.

Aggression and Violence

This week in class we are discussing aggression and violence. In this blog post I would like to bring your attention to a frequently discussed hot topic in the media: bullying. Bullying is a form of aggression and violence that can happen in any social setting. As we have already been learning, the young brain is continually developing into the early 20s. As such, I would like to share with you some research on the social and neurological impacts aggression and violence, such as bullying, can have on school aged children, and then ask you all your opinions on how to prevent this tragedy.

Bullying is a widespread phenomenon across the United States. Peterson and Ray (2006) investigated the prevalence of being bullied in school children. In a sample of 432 eighth graders across 16 school districts and 11 states, 67% had been bullied between kindergarten and eighth grade (73% of males and 63% of females). Repeated bullying was reported to be greatest in the sixth grade. The study indicated that name calling was the most common form of bullying, followed by teasing about appearance, teasing about intelligence, pushing or shoving, knocking books, and hitting or punching. Data also demonstrate that bullying occurred fairly universally across location, population density, and race and ethnicity. These high rates of bullying in school children is not only concerning for their social development, but also for their mental health.

In a nationwide cohort study in Finland, Sourander et al (2009) examined reports from 5,038 children, their parents, and their teachers.  The study began when the children were eight years old, and followed them until they were twenty-four. Results demonstrate that female children who were frequent victims of bullying had higher rates of psychiatric hospital treatment and higher rates of antipsychotic, antidepressant, and anxiolytic drug use irrespective of their psychiatric problems at baseline. This suggests that repeated exposure to bullying has a direct correlation with poor mental health outcomes in the future.

But in what way is this bullying impacting our mental health? Many researchers have set out to determine just how bullying is affecting the brain. Vaillancourt et al (2008) studied cortisol levels in relation to reports of bullying victimization in a sample of 154 12 year-old children at six points throughout one day. Results indicate that rates of depression and anxiety were positively correlated with peer victimization. They also demonstrate that occasional and frequent verbal peer victimization was associated with a hyposecretion of cortisol in females, and a hypersecretion of cortisol in males. This ties nicely to Jaime’s discussion of the hypothalamic-pituitary- adrenal axis [HPA] and suggests that exposure to verbal bullying can intricately affect children’s cortisol regulator.

In 2011, Vaillancourt et al returned to study cortisol levels in 168 12 year-old children at four separate occasions over a two year period. Researchers were interested in determining the relationship between peer victimization, depressive symptoms, and cortisol levels with memory. Data from this longitudinal collection found that peer victimization and elevated levels of depression were concurrently linked at every sample collection. They also indicate that at the third sample collection, peer victimization, depressive symptoms and higher morning and evening cortisol levels uniquely predicted memory deficits at the fourth sample collection. This is indicative of an HPA dysregulation in children exposed to bullying. As the HPA axis controls reactions to stress responses and regulates moods, emotions, energy storage, energy expenditure, and immune functioning, the proposition that bullying can directly impact the HPA is cause for concern.

In addition to bullying’s suggested impact on the HPA axis, Teicher et al (2010) found that bullying may also impact neural trajectories of the brain. In a study of 848 young adults aged 18-25 years old, researchers examined responses from a self-report packet of peer verbal abuse. Results from the survey demonstrate a dose dependent effect of peer verbal abuse on anxiety (3-4x increase), depression (2x increase), dissociation (10x increase), limbic irritability (3-4x increase), anger hostility, and drug use. Peer verbal abuse during middle school years had the most significant effect on symptom scores. Of the respondents, 63 participants were selected to have diffusion tensor images collected. Data demonstrate that degree of exposure to peer verbal abuse correlate with increased mean and radial diffusivity and decrease fractional anisotropy in the corpus callosum and corona radiata. But what does this mean? The corpus callosum is the structure in the brain that connects the right and left hemispheres, while the corona radiata is the structure in the brain that comprises the descending and ascending axons, allowing for neural messages to enter and leave the cerebral cortex. Essentially, what these results tell us is that the white matter tracts communicating between the hemispheres of the brain in bullying victims is demyelinated, thus impacting the brain’s ability to relay information. In the long term, this is likely to influence the cognition and personality of such kids.

With such a broad spectrum of children affected by bullying and such critical correlations with mental health and brain functioning, every community has a responsibility to stand up against bullying. One way to prevent bullying in children is by improving school-based prevention and intervention policies. Smith and Brain (2000), O’Moore (2000), and Limper (2000) express the impact teacher training, school protocols, media campaigns and cooperative efforts can have on bullying awareness and prevention in the school system. Below you will find the link to the bullying policy from Seymour Public Schools, my home school district. I would like to invite you all to look back at your home school district and see if there is standing policy on bullying prevention and intervention. If it exists, what do you think about their standard? Is there room for improvement? Space for interpretation? Do you have other ideas on what has worked in preventing aggression and violence? Preventing the neural impact of aggression and violence?

Policy:

http://www.policy.cabe.org/seymour/ click the link, click the small folder on the left with “Online Policy Manual” typed next to it. Click “Students – Series 5000”, then go down and click “5131.911”

References:

Limper, R. (2000). Cooperation between parents, teachers, and school boards to prevent bullying in education: An overview of work done in the Netherlands. Aggressive Behavior, 26, 125-134.

O’Moore, M. (2000). Critical issues for teacher training to counter bullying and victimization in Ireland. Aggressive Behavior, 26, 99-111.

Peterson, J. S. & Ray K. E. (2006). Bullying and the gifted: Victims, perpetrators, prevalence, and effects. Gifted Child Quarterly, 50, (2), 148-168.

Smith, P. K. & Brain, P. (2000). Bullying in schools: Lessons from two decades of research. Aggressive Behavior, 26, 1-9.

Sourander, A. et al. (2009). Childhood bullying behavior and later psychiatric hospital and psychopharmacologic treatment: Findings from the 1981 birth cohort study. Archives of General Psychiatry, 66 (9), 1005-1012.

Teicher, M. H., Samson, J. A., Sheu, Y. S., Polcari, A., & McGreenery, C. E. (2010). Hurtful words: Association of exposure to peer verbal abuse with elevated psychiatric symptom scores and corpus callosum abnormalities. American Journal of Psychiatry, 167, 1464-1471.

Vaillancourt, T., et al. (2008). Variation in hypothalamic-pituitary- adrenal axis activity among bullied and non-bullied children. Aggressive Behavior, 34, 294-305.

Vaillancourt, T. et al. (2011). Peer victimization, depressive symptoms, and high salivary cortisol predict poorer memory in children. Brain and Cognition, 77, 191-199.

Stress and the HPA Axis: fight, flight, and personality disorders?

Our bodies are designed for stress; in fact, we need it – at least some of it – to function at optimal levels.  It is what strengthens our bodies and motivates our minds.  Stress, or exerted challenge, is essential to our growth and development from the emotional level right down to the basic cellular level; it may even shed light on severe and puzzling psychopathology.

Consider first, an example of physical stress.  Lifting weights is a type of stress we may use to develop muscle mass.  Built from repeated exertion of physical stress on our muscle cells, increased mass and strength is the body’s response to micro-traumas of the muscle fibers.  The body repairs, or even replaces, the weak and damaged tissues by laying down stronger and longer fibers capable of meeting the new demands put upon them.

As for psychological stress, consider an academic course with challenging material.  The right amount of intellectual “stress” – that which stretches our cognitive abilities – provides not only for the laying down of new neural circuitry, but motivates us to stay engaged as well.  New connections and associations among the brains cells take shape as we push the boundaries of what is already cataloged in our brains.  It also helps stave off apathy and get us to school every day.  The graph below, developed by Mihaly Csikszentmihalyi, a psychologist known for his research in happiness and motivation, provides a model for thinking about this balance.

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But what happens when the stress we face is too great or too frequent for our bodies and minds to handle?  While it is essential for our growth and development, there is no question that too much stress causes major, often prolonged, detriment to our bodies (for the muscle example, think tears, fatigue, or hypertrophy) and to our minds.

To understand the neurophysiological changes that occur with stress, one must first understand the HPA axis.

Deep within the brain lies the hypothalamus, an important communicator between the nervous system (of which it is a part) and the endocrine system.  Next to it, and largely under it’s influence, is the pituitary gland.

 2

In times of stress, the hypothalamus releases a hormone called corticotrophin-releasing hormone (CRH).  The increased level of CRH is detected by the neighboring pituitary gland, which in turn releases the hormone called adrenocorticotropic hormone (ACTH).  The ACTH then travels through the bloodstream, finding its way to the two adrenal glands that sit atop our kidneys.  The adrenal glands, in response, produce and release the hormone called cortisol – the main, and likely the most well known, component of HPA axis activation.  It is cortisol that alters our metabolic rate and revs us up for “fight or flight” in the face of danger, or at least that which we perceive as a threat.

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This HPA activation, of course, does not go on indefinitely.  Once out of harms way, or at least talked down from responding physically to the threat, a cortisol feedback system prompts our brain to cease the rapid storm of HPA hyperstimulation, and we return to baseline.  We calm and shift back into our normal routine.

The HPA axis has been well studied and scientists and clinicians can appreciate its role in various anxiety and mood disorders.  Perhaps not as obvious, however, is the role the HPA axis may play in the development and symptomology of a different domain of mental illnesses – the personality disorders.  In particular, several compelling studies have been published suggesting some sort of HPA involvement in Borderline Personality Disorder.

Borderline Personality Disorder (BPD) is this characterized by instability in interpersonal relationships osculating between unexpected extremes in idolizing and devaluing, unstable self-image, fear of abandonment, self-injurious behaviors, and recurrent suicidality and/or suicide attempts.  It prevalence is estimated to be between 1.6% and 5.9% of the general population, with 20% of all psychiatric inpatient holding the diagnosis.  About 75% of individuals diagnosed with BPD are female, with familial risk factors including substance abuse, antisocial personality disorders, and depressive or bipolar. The condition is chronic, with symptoms begining in early adulthood that are considered to be characterlogical in nature.  (American Psychiatric Association, 2013)

A 2010 literature review article regarding neurophysiological findings in BPD noted several studies supporting at least the potential of abnormal HPA axis sensitivity and function.  Preliminary studies found that individuals diagnosed with BPD tend to have:

1) an exaggerated response to HPA activation;

2) increased basal cortisol levels; and

3) reduced feedback system, which impairs the brains ability to know when to “shut off” the cascade of events leading to cortisol secretion,

when compared with psychiatric controls.   (Wingenfeld, Spitzer, Rullkotter,  & Lowe, 2010)

Additionally, individuals with BPD were more likely to have abnormalities in size (larger) and activity (increased activity when exposed to emotional stimuli) of their amygdala – the part of the brain, near the hypothalamus, that processes memories and emotions.  However, the authors are sure to acknowledge weaknesses in many of the studies they reference (small size, differences in the choice of serological test among studies, potentially confounding comorbidities).  (Wingenfeld, Spitzer, Rullkotter,  & Lowe, 2010)

While we do not know whether these psychological differences are causes, effects, or merely correlates of the disorder, the intrigue of the significance remains.  Many psychiatric disorders that were once thought to be rooted in negative attention-seeking, fueled by willful oppositionality, or possibly caused poor parenting, are now known to have strong biological components and genetic underpinnings.  Regardless if we can satisfactorily determine cause, effect, or otherwise, it would be scientifically absurd, for example, to deny that serotonin plays a significant role in mood disorders.  New research into cortisol and HPA axis – and stress in general – might greatly deepen our understanding of BPD and other challenging clinical presentations.

Or, at very least, may shed light on the physiology of the drive to keep looking.

 

References:

American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental  Disorders. (5th ed.). Washington, DC: American Psychiatric Publishing.

Higgins, E.S. & George, M.S. (2013). The Neuroscience of Clinical Psychiatry: The

Pathophysiology of Behavior and Mental Illness. (2nd ed.). Philadelphia, PA: Lippincott Williams & Wilkins.

Martin, A., Scahill, L., & Kratochvil, C.J. (2011). Pediatric Psychopharmacology: Principles and Practice (2nd ed.). New York, NY: Oxford University Press

Stahl, S. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications. (4th ed.). New York, NY: Cambridge University Press.  

Wingenfeld, K., Spitzer, C., Rulkotter, N., & Lowe, B.  (2010). Borderline personality disorder: Hypothalmus pituitary adrenal axis and findings from neuroimaging studies. Psychoneuroendocrinology, 35, 154-170. doi: 10.1016/j.psyneuen.2009.09.014.

Image credits:

1  http://upload.wikimedia.org/wikipedia/commons/thumb/f/f6/Challenge_vs_skill.svg/300px-Challenge_vs_skill.svg.png

2  http://www.typefreediabetes.com/v/vspfiles/templates/TF1112/images/images_files/hypothalamus%20&%20pituitary.jpg

3  http://total-body-psychology.com.au/wp-content/uploads/2012/07/hpa-axis.gif