Presentation Slides – The Enduring Neurobiological Effects of Abuse and Neglect
Australia Conference June 7, 2016 slides
Slides from all day workshop presentation 6/6/16
Currently recruiting pairs of subjects consisting of an adult (18 – 40 years of age) with ADHD plus an adult same-sex blood relative without ADHD or other psychiatric disorders for a very interesting study. Participants with ADHD can be on or off medications. The study involves comprehensive assessment and testing plus collection of a small skin sample. The skin sample will be cultured, converted into induced pluripotent stem cells (a very complex process), and the stem cells transformed into dopamine neurons. We will then compare dopamine neurons of participants with ADHD to dopamine neurons from family members without ADHD. Subjects will be paid $75 for their participation. If you are interested and would like some more information, please call Cindy at (617) 855-2973 or email firstname.lastname@example.org
For more about induced Pluripotent Stem Cells – see:
Robinton, D.A. and G.Q. Daley, The promise of induced pluripotent stem cells in research and therapy. Nature, 2012. 481(7381): p. 295-305
Bellin, M., et al., Induced pluripotent stem cells: the new patient? Nat Rev Mol Cell Biol, 2012. 13(11): p. 713-26.
An article, by Scott Eddie, highlighting our work on this topic has been published in NIDA Notes. I’ve attached the link. NIDA Notes Article
•Research Project 1. Comparison of Treatment with Hemi-Sync™ Sounds Versus Multimodal Sensory Enrichment for 8-12-Year-Old Children with ADHD.
•Research Project 2. Open Evaluation of Brain Balance Exercises and Interactive Metronome for Treatment of 8-14-Year-Old Children with ADHD.
The problem with current treatments for attention-deficit hyperactivity disorder (ADHD) is that medications typically play an important role in controlling symptoms, but symptoms resurface when the medication wears off1. Unfortunately, there are few if any enduring benefits from medications used to treat ADHD. This is seen most clearly in the follow-up analyses of the NIH-sponsored Multimodal Treatment Study of Children with ADHD (MTA)2. Initially they found that careful medication management, or medication management combined with behavioral treatment of children with ADHD, produced better outcomes at 14-months than did behavioral treatments alone or community care. However, when participants were reassessed 2 years after the studies end2, or 6-8 years post enrollment3, it was clear that there was no significant beneficial effects on ADHD symptoms or academic performance, of having received 14-months of medication management or medication management combined with behavioral treatments2, 3. Consequently, we are interested in non-pharmacological treatments that may have enduring beneficial effects on children with ADHD.
Treatments with enduring beneficial effects may require many weeks or months to work. Hence, an ideal long-term treatment might function in conjunction with pharmacological treatments so that ADHD children can receive some rapid short-term beneficial effects of medication, but they then may be able to stop using medications, or benefit from lower doses of medications, as the long-term treatment takes hold.
We are currently studying three potential non-pharmacological treatments for ADHD in the Developmental Biopsychiatry Research Program at McLean Hospital, a major Harvard Teaching Hospital.
Research Project 1. In this study we are comparing two non-pharmacological treatments in boys and girls with ADHD who are 8 – 12 years of age. This is a 6-month long free treatment program that we provide in addition to whatever treatments the child is currently receiving. Hence, they can be taking medication, receiving counseling, family therapy, school accomodations, etc. An important requirement though is that if they are taking medications that the medications be short acting (like Ritalin, Adderall or Atomoxetine) that can be stopped for 2 days so we can assess how symptomatic the child is off medication at the beginning, middle and end of the study. Non-invasive MRI scans will also be performed at the beginning and end of the study to determine if the non-pharmacological treatment led to any alterations in blood flow and connectivity in brain regions implicated in ADHD. Children will receive a comprehensive evaluation as part of the study. They can also enter the trial if they are not receiving any other treatments. All components of this study are free. Monies are provided to help cover local traveling expenses to McLean Hospital and to compensate children for their time going through the different evaluations. Participants are randomly assigned to either Treatment 1 or 2. If two children from the same family enroll they are randomly assigned to the same treatment. This is an ongoing study but still has several openings for new participants as of 11/20/15.
Treatment 1. Hemi-Sync™ sounds and classical music. Hemi sync™ is an “audio-guidance” technology, developed many years ago by Robert Monroe, that uses sound to influence brain wave activity to produce a focused, whole-brain state known as hemispheric synchronization, where the left and right hemispheres work together in a state of coherence. The specific Hemi Sync™ programs are designed to enhance concentration and attention by predominantly increasing alpha and beta EEG activity. Beneficial effects on sustained attention, resistance to distraction, alertness and irritability have been reported in a study of individuals with developmental disabilities4. Beta frequency binaural beats were also found to have a more beneficial effect on attention and mood than theta frequency beats5. Van der Schaar6 reported in a small study that Hemi-Synch ADD tapes hastened and augmented therapeutic benefits of a nutritional supplement for children with ADHD. These findings are also consistent with an expanding literature on the potential benefits of EEG-based neurofeedback approaches that augment beta activity in children with ADHD7, 8. While these Hemi-Sync™ findings are encouraging it must be pointed out that very few Hemi-Sync™ studies have been published in main-stream journals or even journals not directly linked to The Monroe Institute. Hence, a rigorous independent trial is needed.
Treatment 2. Multimodal Sensory Enrichment. This treatment derived from translational neuroscience studies showing that simultaneous exposure to multimodal sensory stimuli enhanced dendritic branching of brain cells, the density of synaptic connections within the brain, and the birth of new brain cells (neurogenesis)9, 10. Professor Michael Leon at the University of California, Irvine, developed a procedure to provide multimodal sensory enrichment to children and found in a randomized control trial that it was effective in ameliorating some of the symptoms of autism11; with 69% of parents of children in the enriched group versus 31% of parents of children in the control group reporting improvement in their child over the 6-month study11. In the course of treating children with autism the investigators also noted improvements in attention and impulsivity, and found in an open trial that multimodal sensory enrichment attenuated these symptoms in children with ADHD. Parents will be supplied with a kit that contains materials needed for the sensorimotor exercises and a URL to an internet-based program that teaches the parent and child how to do the exercises. The UC Irvine study with autism suggests that gains made from the enrichment exercises endure. This is an innovative potential treatment in need of rigorous evaluation.
Research Project 2 – Brain Balance Exercises and Interactive Metronome. In this study we are conducting an open evaluation of ‘brain balance’ and timing exercises for 8-14-year-old boys and girls with ADHD. Brain Balance treatments were developed by Robert Mellilo12, 13, a neurologically sophisticated chiropractor, and consists of exercises to foster right hemisphere development and right-left hemispheric integration. The focus on right-hemisphere development and right-left hemispheric integration fits with what we, and others, have observed to be key neurobiological deficits in children with ADHD14-20. Children with ADHD also have deficits in timing21-24, which are addressed using a device called the Interactive Metronome25-27. Brain balance and Interactive Metronome remediation was found to produce, within 12-weeks, a greater than two-year gain in grade level in all academic domains except mathematical reasoning in children with ADHD28. Hence, we are interested in assessing whether this type of treatment is associated with improvement in objective indices of symptom severity and in changes in brain activity and functional connectivity in brain regions associated with ADHD.
Brain Balance exercises are typically offered at Brain Balance Achievement Centers throughout the US. We have had Dr. Melillo, and his staff, develop for this study a specific ADHD-focused internet-based training program for use by parent and child at home. This complements the internet-based interactive metronome training program. This is a 14-week study conducted at home. Children receive comprehensive evaluations and MRI scans before and after treatment. The entire program is free. Monies are provided to help cover costs of local transportation to McLean Hospital and for children’s time in going through testing and MRI. This study is underway and we are recruiting new participants as of 11/20/2015.
If you are interested in either of these studies please contact Cindy McGreenery email@example.com (617 855-2971). These studies are IRB-approved through Partner’s Health Care.
NOTE: Dr. Teicher and staff have no financial interest in any of these treatment modalities, and do not offer them as treatments outside of these IRB-approved research studies. We are interested in rigorously and objectively evaluating novel treatments that may be of benefit to children, adolescents and adults with ADHD, learning disabilities, depression and post-traumatic stress disorder. The research is conducted with the understanding that we will publish the results of these studies whether they are positive or negative. We have previously published negative results of novel technologies or treatments29-31. We do not presently recommend these treatments. Our decision to evaluate these treatments is an expression of interest but does not constitute an endorsement. We believe that there is a pressing need for new treatments that can produce enduring benefits and we are eager to rigorously evaluate potential treatments with plausible mechanisms or good preliminary data.
If you have developed a novel treatment and are interested in having it objectively evaluated by the Developmental Biopsychiatry Research Program at McLean Hospital please contact Dr. Teicher at firstname.lastname@example.org to discuss policies, logistics and costs.
- Pliszka S. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2007 Jul;46(7):894-921.
- Jensen PS, Arnold LE, Swanson JM, et al. 3-year follow-up of the NIMH MTA study. J Am Acad Child Adolesc Psychiatry 2007 Aug;46(8):989-1002.
- Molina BS, Hinshaw SP, Swanson JM, et al. The MTA at 8 years: prospective follow-up of children treated for combined-type ADHD in a multisite study. J Am Acad Child Adolesc Psychiatry 2009 May;48(5):484-500.
- Guilfoyle G, Carbone D. The facilitation of attention utilizing therapeutic sounds. Hemi-Sync Journal 1997;XV(2).
- Lane JD, Kasian SJ, Owens JE, Marsh GR. Binaural auditory beats affect vigilance performance and mood. Physiol Behav 1998 Jan;63(2):249-252.
- Van Der Schaar PJ. Attention and learning deficit disorders: Impressions ofcombined treatment with amino acids and Hemi-Sync. TMI Journal, 2009( Winter).
- Gevensleben H, Holl B, Albrecht B, et al. Distinct EEG effects related to neurofeedback training in children with ADHD: a randomized controlled trial. Int J Psychophysiol 2009 Nov;74(2):149-157.
- Kropotov JD, Grin-Yatsenko VA, Ponomarev VA, Chutko LS, Yakovenko EA, Nikishena IS. ERPs correlates of EEG relative beta training in ADHD children. Int J Psychophysiol 2005 Jan;55(1):23-34.
- van Praag H, Kempermann G, Gage FH. Neural consequences of environmental enrichment. Nat Rev Neurosci 2000 Dec;1(3):191-198.
- Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci 2006 Sep;7(9):697-709.
- Woo CC, Leon M. Environmental enrichment as an effective treatment for autism: a randomized controlled trial. Behav Neurosci 2013 Aug;127(4):487-497.
- Melillo R. Disconnected Kids: The Groundbreaking Brain Balance Program for Children with Autism, ADHD, Dyslexia, and Other Neurological Disorders. New York: Penguin Group; 2009.
- Melillo R. Reconnected Kids: Help Your Child Achieve Physical, Mental, and Emotional Balance. New York: Penguin Group; 2011.
- Arnsten AF. Toward a new understanding of attention-deficit hyperactivity disorder pathophysiology: an important role for prefrontal cortex dysfunction. CNS Drugs 2009;23 Suppl 1:33-41.
- Casey BJ, Castellanos FX, Giedd JN, et al. Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1997;36(3):374-383.
- Clark L, Blackwell AD, Aron AR, et al. Association between response inhibition and working memory in adult ADHD: a link to right frontal cortex pathology? Biol Psychiatry 2007 Jun 15;61(12):1395-1401.
- Qiu MG, Ye Z, Li QY, Liu GJ, Xie B, Wang J. Changes of brain structure and function in ADHD children. Brain Topogr 2011 Oct;24(3-4):243-252.
- Valera EM, Faraone SV, Murray KE, Seidman LJ. Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biol Psychiatry 2007 Jun 15;61(12):1361-1369.
- Wolf RC, Plichta MM, Sambataro F, et al. Regional brain activation changes and abnormal functional connectivity of the ventrolateral prefrontal cortex during working memory processing in adults with attention-deficit/hyperactivity disorder. Hum Brain Mapp 2009 Jul;30(7):2252-2266.
- Zang YF, He Y, Zhu CZ, et al. Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain Dev 2007 Mar;29(2):83-91.
- Smith A, Taylor E, Rogers JW, Newman S, Rubia K. Evidence for a pure time perception deficit in children with ADHD. J Child Psychol Psychiatry 2002 May;43(4):529-542.
- Sonuga-Barke E, Bitsakou P, Thompson M. Beyond the dual pathway model: evidence for the dissociation of timing, inhibitory, and delay-related impairments in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2010 Apr;49(4):345-355.
- Toplak ME, Tannock R. Time perception: modality and duration effects in attention-deficit/hyperactivity disorder (ADHD). J Abnorm Child Psychol 2005 Oct;33(5):639-654.
- Yang B, Chan RC, Zou X, Jing J, Mai J, Li J. Time perception deficit in children with ADHD. Brain Res 2007 Sep 19;1170:90-96.
- Cosper SM, Lee GP, Peters SB, Bishop E. Interactive Metronome training in children with attention deficit and developmental coordination disorders. Int J Rehabil Res 2009 Dec;32(4):331-336.
- Bartscherer ML, Dole RL. Interactive metronome training for a 9-year-old boy with attention and motor coordination difficulties. Physiother Theory Pract 2005 Oct-Dec;21(4):257-269.
- Shaffer RJ, Jacokes LE, Cassily JF, Greenspan SI, Tuchman RF, Stemmer PJ, Jr. Effect of interactive metronome training on children with ADHD. Am J Occup Ther 2001 Mar-Apr;55(2):155-162.
- Leisman G, Melillo R, Thum S, et al. The effect of hemisphere specific remediation strategies on the academic performance outcome of children with ADD/ADHD. Int J Adolesc Med Health 2010 Apr-Jun;22(2):275-283.
- Joffe RT, Moul DE, Lam RW, et al. Light visor treatment for seasonal affective disorder: a multicenter study. Psychiatry Res 1993 Jan;46(1):29-39.
- Teicher MH, Glod CA, Oren DA, et al. The phototherapy light visor: more to it than meets the eye. Am J Psychiatry 1995 Aug;152(8):1197-1202.
- Oren DA, Teicher MH, Schwartz PJ, et al. A controlled trial of cyanocobalamin (vitamin B12) in the treatment of winter seasonal affective disorder. J Affect Disord 1994 Nov;32(3):197-200.
McLean_Hospital_Child_abuse_talk Talk presented at McLean Hospital 2012