Papers by Edward Justin Modestino, Ph.D., M.S., L.M.H.C., N.C.C., ADHD-PT, C.Ht.
Acta Scientific Neurology, 2024
The authors of this publication describe herein a cluster of symptoms and behaviors in patients w... more The authors of this publication describe herein a cluster of symptoms and behaviors in patients with ADHD. The authors have called this Rejection Sensitivity Dysphoria (RSD), as episodes begin with the experience of perceived rejection, demonstrating rejection sensitivity, that progresses into a nearly instantaneous dysphoric mood, which causes significant distress and impairment. We present a case series of four case studies from the first author's private practice in great detail. At present, the authors have seen hundreds of patients and clients with this same clinical profile (ADHD with RSD), which the authors have not been able to attribute to any other known comorbid psychopathology with ADHD (i.e., mood disorders, anxiety disorders, personality disorders, or other developmental disorders). Notably, clinicians worldwide have contacted the first author, confirming that they have seen ADHD patients and clients who have presented with this in their professional experience. Individuals with RSD have tended to respond favorably to alpha-2 agonists. We provide the details of RSD based on the larger group of individuals from our clinical experience. Research needs to be conducted to elucidate the underlying nature of RSD in ADHD. We are currently doing such research.
Journal of Addiction Psychiatry (ISSN: 2474-0713), 2024
Reward Deficiency Syndrome (RDS) is an umbrella term encompassing a wide array of addictive behav... more Reward Deficiency Syndrome (RDS) is an umbrella term encompassing a wide array of addictive behaviors that affect individuals across diverse spectra of society. Our research group has conducted a plethora of studies investigating the utilization of KB220 and its various iterations for addressing Reward Deficiency Syndrome (RDS), including: dopamine homeostasis, brain areas associated with dopamine, functional connectivity, qEEG, reductions of cravings, relapse prevention and detoxification, opioid-seeking and attenuation of intake, binge-drinking and withdrawal, DUIs, shopping and hoarding behaviors, memory decline, nightmares, paraphilias, ADHD, eating disorders and weight loss, anger and stress reduction, and genetically customized compounds. In this review, we compare studies using KB220 (and variants) for these things with GLP-1 analogs. We suggest that KB220 (and its variants) demonstrate superiority over GLP-1 analogs for addressing all these issues, as evidenced by various reasons outlined herein, particularly their impact on the brain’s reward cascade and dopamine homeostasis, all while avoiding antagonism of the reward system.
Current Psychopharmacology, 2024
The above article has been published, as is, ahead-of-print, to provide early visibility but is n... more The above article has been published, as is, ahead-of-print, to provide early visibility but is not the final version. Major publication processes like copyediting, proofing, typesetting and further review are still to be done and may lead to changes in the final published version, if it is eventually published. All legal disclaimers that apply to the final published article also apply to this ahead-of-print version.
The widespread adoption of Glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of... more The widespread adoption of Glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of obesity and diabetes has raised concerns about their potential adverse effects, including the induction of depression and suicide ideation. We report on a male patient in his early 50s with a complex medical history, including adult Attention-Deficit/Hyperactive Disorder, narcolepsy with cataplexy, and major depressive disorder in remission, who experienced exacerbated hemiplegic migraines after initiating treatment with an injectable GLP-1 agonist (Saxenda) for weight loss. Despite a previous history of experiencing hemiplegic migraines once or twice a year, the patient reported daily occurrences of migraines, many of which were hemiplegic, during the 60 days of GLP-1 agonist treatment. The migraines abated only upon discontinuation of the medication. This case underscores the need to carefully consider patient history and potential genetic predispositions when prescribing GLP-1 agonists, highlighting the complex interactions between these medications, existing comorbidities, and the dopaminergic and calcitonin gene-related peptide pathways. Our findings suggest that GLP-1 agonists, while beneficial for some, may pose significant risks for patients with specific genetic backgrounds or neurological conditions, calling for personalized approaches to treatment and increased awareness of potential adverse effects.
Journal of Personalized Medicine
Scientific studies have provided evidence that there is a relationship between violent and aggres... more Scientific studies have provided evidence that there is a relationship between violent and aggressive behaviors and addictions. Genes involved with the reward system, specifically the brain reward cascade (BRC), appear to be associated with various addictions and impulsive, aggressive, and violent behaviors. In our previous research, we examined the Taq A1 allele (variant D2 dopamine receptor gene) and the DAT-40 base repeat (a variant of the dopamine transporter gene) in 11 Caucasian boys at the Brown School in San Marcus, Texas, diagnosed with intermittent explosive disorder. Thirty supernormal controls were screened to exclude several reward–deficit behaviors, including pathological violence, and genotyped for the DRD2 gene. Additionally, 91 controls were screened to exclude ADHD, pathological violence, alcoholism, drug dependence, and tobacco abuse, and their results were compared with DAT1 genotype results. In the schoolboys vs. supercontrols, there was a significant associatio...
EXPLORE: The Journal of Science and Healing, 2016
A research participant came to our lab with self-proclaimed, ecstatic, Kundalini meditative exper... more A research participant came to our lab with self-proclaimed, ecstatic, Kundalini meditative experiences. Using neurophenomenology and fMRI, we were able to identify brain activation in the left prefrontal cortex (primarily in left Brodmann's areas (BA's) 46 and 10, but also extending into BA's 11, 47 and 45) associated with this experience. The Phenomenology of Consciousness Inventory provided evidence that this was a perceived altered state of consciousness. Additionally, the Physio-Kundalini Syndrome Index strongly suggested that what he was experiencing was indeed Kundalini. The feelings of joy, happiness and the left prefrontal brain region found in this study are consistent with many published neuroimaging and electrophysiological studies of meditation. This case study suggests that using first person subjective experience within a phenomenological reduction process can be combined with neuroimaging to divulge objective brain regions associated such experiences. Furthermore, this provides evidence that at least in this participant, the Kundalini experience is associated with brain activation in the left prefrontal cortex. Future research is needed to confirm these results in a large group study, perhaps contrasting brain activation of those who experience spontaneously emerging Kundalini with trained Kundalini practitioners.
Journal of Attention Disorders, 2013
Objective: This study examined the retrospective history of childhood ADHD symptomatology in an a... more Objective: This study examined the retrospective history of childhood ADHD symptomatology in an adult narcoleptic population (Narcolepsy Group [NG]: n = 161) compared with a control group (CG: n = 117). Method: Both groups completed the Wender Utah Rating Scale (WURS), a retrospective self-report questionnaire indicating the presence of childhood ADHD symptomatology in adults. Results: Childhood ADHD symptoms were significantly greater in NG than CG ( p < .001). Joint prevalence calculations of childhood ADHD symptomatology in NG were more than 8 to 15 times greater than expected. Among NG, those individuals with a greater score on the WURS, indicative of childhood ADHD symptomatology, also had shorter sleep onsets on the Multiple Sleep Latency Test, a common objective measure of sleepiness, t(97) = −7.11, p < .05. Conclusion: It appears that self-reported childhood ADHD symptomatology history among adult narcoleptics is common. Future research is warranted with adult narcolep...
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.... more This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY)
Brain and Behavior, 2016
Background: Parkinson's disease (PD) usually emerges with a unilateral side-of-onset (left-onset:... more Background: Parkinson's disease (PD) usually emerges with a unilateral side-of-onset (left-onset: LOPD; right-onset: ROPD; Marinus & van Hilten, 2015) due to an asymmetrical degeneration of striatal dopaminergic neurons (Donnemiller et al., Brain, 135, 2012, 3348). This has led to a body of research exploring the cognitive, neuropsychological, and clinical differences between LOPD and ROPD (e.g., Verreyt et al.,
Frontiers in Human Neuroscience, 2016
Recent studies suggest changes in religious cognition in a subgroup of patients with Parkinson's ... more Recent studies suggest changes in religious cognition in a subgroup of patients with Parkinson's disease (PD e.g., Butler et al., 2011). It is unclear whether this deficit extends to both doctrinal and experiential categorization forms of religious cognition. Kapogiannis et al. (2009b) dissociated experiential and doctrinal religious knowledge to different neural networks using fMRI. We examined Kapogiannis' dissociation against the background of PD side of onset (LOPD, ROPD), assessing performance both On-and Off-medication. In the behavioral portion of the study, we used a statement classification task in combination with scholar derived test sets for experiential and doctrinal religious knowledge categorization in conjunction with neuropsychological measures. In the neuroimaging portion of the study, we expanded on Kapogiannis' study by examining the same networks in PD. The behavioral data revealed that all groups rated (categorized) the scholar derived tests of experiential and doctrinal significantly differently than the scholars. All groups, including the scholars, classified more phrases as doctrinal than experiential. Religious cognition differed in the PD groups: those with PD Off-medication and LOPD Off-medication comprehended scholar defined experiential phrases with more difficulty, making them more likely to be classified as mixed or doctrinal. This was in contrast to the subjective frequency of classification of phrases as experiential paired with a cognitive decline in PD Off-medication; whereas PD On-medication showed a positive correlation with cognitive state and subjective doctrinal classification. For ROPD, cognitive state was associated with subjective experiential and doctrinal frequency of classification. With more intact intellect, there was a greater likelihood of classifying phrases subjectively as mixed, and the converse for experiential. Furthermore, religiosity negatively predicted subjective doctrinal frequency in LOPD, with the converse in ROPD. In fcMRI in PD, we found resting state functional intrinsic connectivity of reward networks associated with classification of statements using seeds in bilateral nucleus accumbens in PD. For experiential regressors, there was a negative correlation in bilateral frontal lobes paired with a positive correlation in left occipital visual areas (BAs 17, 18). For doctrinal regressors, there was a positive correlation in right BA 20.
Journal of the Neurological Sciences
Current Opinion in Ophthalmology, Dec 1, 2001
Functional magnetic resonance imaging (fMRI), which is a technique useful for non-invasive mappin... more Functional magnetic resonance imaging (fMRI), which is a technique useful for non-invasive mapping of brain function, is well suited for studying the visual system. This review highlights current clinical applications and research studies involving patients with visual deficits. Relevant reports regarding the investigation of the brain's role in visual processing and some newer fMRI techniques are also reviewed. Functional magnetic resonance imaging has been used for presurgical mapping of visual cortex in patients with brain lesions and for studying patients with amblyopia, optic neuritis, and residual vision in homonymous hemianopia. Retinotopic borders, motion processing, and visual attention have been the topics of several fMRI studies. These reports suggest that fMRI can be useful in clinical and research studies in patients with visual deficits.
PubMed, Apr 22, 2023
An estimated 3% to 10% of school children meet the DSM-V criteria for ADHD (Attention-Deficit/Hyp... more An estimated 3% to 10% of school children meet the DSM-V criteria for ADHD (Attention-Deficit/Hyperactivity Disorder), however, to be over-diagnosed, the rate of children inappropriately diagnosed with ADHD (false positives) would have to be larger than the number of children with ADHD who are under-identified and not diagnosed (false negatives). Accordingly, a number of investigators take the position that under-treatment with psychostimulants, especially in children and adolescence, will result in continued ADHD symptomatology including future Substance Use Disorder (SUD). However, other researchers and clinicians believe otherwise and espouse laudable arguments for caution and prolonged methamphetamine treatment. While there is ongoing controversy of the role of genetics and epigenetics linked to ADHD, it seems clear that a number of dopaminergic genes and their risk polymorphisms act as DNA antecedents impacted by epigenetic induced methylation. Our hypothesis and literature review suggest that one possible solution is to embrace non addictive interventions to induce global dopamine homeostasis.
Current Psychopharmacology
Background: The risk for all addictive drug and non-drug behaviors, especially, in the unmyelinat... more Background: The risk for all addictive drug and non-drug behaviors, especially, in the unmyelinated Prefrontal Cortex (PFC) of adolescents, is important and complex. Many animal and human studies show the epigenetic impact on the developing brain in adolescents, compared to adults. Some reveal an underlying hyperdopaminergia that seems to set our youth up for risky behaviors by inducing high quanta pre-synaptic dopamine release at reward site neurons. In addition, altered reward gene expression in adolescents caused epigenetically by social defeat, like bullying, can continue into adulthood. In contrast, there is also evidence that epigenetic events can elicit adolescent hypodopaminergia. This complexity suggests that neuroscience cannot make a definitive claim that all adolescents carry a hyperdopaminergia trait. Objective: The primary issue involves the question of whether there exists a mixed hypo or hyper - dopaminergia in this population. Methods: Genetic Addiction Risk Score (...
Molecular Neurobiology, 2021
Millions of Americans experience pain daily. In 2017, opioid overdose claimed 64,000 lives increa... more Millions of Americans experience pain daily. In 2017, opioid overdose claimed 64,000 lives increasing to 84,000 lives in 2020, resulting in a decrease in national life expectancy. Chronic opioid use results in dependency, drug tolerance, neuroadaptation, hyperalgesia, potential addictive behaviors, or Reward Deficiency Syndrome (RDS) caused by a hypodopaminergia. Evaluation of pain clinic patients with the Genetic Addiction Risk Score (GARS) test and the Addiction Severity Index (ASI- Media Version V) revealed that GARS scores equal to or greater than 4 and 7 alleles significantly predicted drug and alcohol severity, respectively. We utilized RT-PCR for SNP genotyping and multiplex PCR/capillary electrophoresis for fragment analysis of the role of eleven alleles in a ten-reward gene panel, reflecting the activity of brain reward circuitry in 121 chronic opioid users. The study consisted of 55 males and 66 females averaging ages 54 and 53 years of age, respectively. The patients incl...
Current Psychopharmacology, 2021
During Lucid Dreams, the dreamer is aware, experiences the dream as if fully awake, and may contr... more During Lucid Dreams, the dreamer is aware, experiences the dream as if fully awake, and may control the dream content. The dreamer can start, stop, and restart dreaming, depending on the nature and pleasantness of the dream. For patients with Reward Deficiency Syndrome (RDS) behaviors, like Attention Deficit Hyperactivity Disorder (ADHD), Tourette's-Syndrome, and Posttraumatic Stress Disorder (PTSD), the dream content may be pleasant, unpleasant, or terrifying. A sample of psychiatric center patients identified as having RDS reported the effectiveness of a neuronutrient, dopamine agonist, KB200Z, in combating terrifying, lucid dreaming. These reports motivated the study of eight clinical cases with known histories of substance abuse, childhood abuse, and PTSD. The administration of KB200Z, associated with eliminating unpleasant or terrifying lucid dreams in 87.5% of the cases. Subsequently, other published cases have further established the possibility of the long-term eliminati...
Psychology Research and Behavior Management, 2021
This is a review of research on "Precision Behavioral Management" of substance use disorder (SUD)... more This is a review of research on "Precision Behavioral Management" of substance use disorder (SUD). America is experiencing a high prevalence of substance use disorder, primarily involving legal and illegal opioid use. A 3000% increase in treatment for substance abuse has occurred between 2000 and 2016. Unfortunately, present day treatment of opioid abuse involves providing replacement therapy with powerful opioids to, at best, induce harm reduction, not prophylaxis. These interventions do not enhance gene expression and restore the balance of the brain reward system's neurotransmitters. We are proposing a generalized approach called "Precision Behavioral Management". This approach includes 1) using the Genetic Addiction Risk Severity (GARS, a 10 candidate polymorphic gene panel shown to predict ASI-alcohol and drug severity) to assess early predisposition to substance use disorder; 2) using a validated reward deficiency syndrome (RDS) questionnaire; 3) utilization of the Comprehensive Analysis of Reported Drugs (CARD™) to assess treatment compliance and abstinence from illicit drugs during treatment, and, importantly; 4) utilization of a "Pro-dopamine regulator (KB220)" (via IV or oral [KB220Z] delivery systems) to optimize gene expression, restore the balance of the Brain Reward Cascade's neurotransmitter systems and prevent relapse by induction of dopamine homeostasis, and; 5) utilization of targeted DNA polymorphic reward genes to direct mRNA genetic expression profiling during the treatment process. Incorporation of these events can be applied to not only the underconsidered African-American RDS community, but all victims of RDS, as a demonstration of a paradigm shift that uniquely provides a novel putative "standard of care" based on DNA guided precision nutrition therapy to induce "dopamine homeostasis" and rebalance neurotransmitters in the Brain Reward Cascade. We are also developing a Reward Deficiency Syndrome Diagnostic Criteria (RDSDC) to assist in potential tertiary treatment.
Open access journal of behavioural science & psychology, 2018
While the heroin and opioid epidemic has been front and center in the US, it appears that cocaine... more While the heroin and opioid epidemic has been front and center in the US, it appears that cocaine is making comeback. Since 1913 the expansion of Colombia's illegal coca crop has driven demand on US streets. The 2015 amphetamine users increased globally, reaching 37 million, and new cocaine use expanded to 2 percent of the US population last year. Unlike for opioids and alcohol, there is no FDA medication approval for psychostimulants. However, gene-guided therapy presented herein may be useful in treatment and relapse prevention for Abusable drugs [1].
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Papers by Edward Justin Modestino, Ph.D., M.S., L.M.H.C., N.C.C., ADHD-PT, C.Ht.