On Mourning and Recovery: Integrating Stages of Grief and Change Toward a Neuroscience-Based Model of Attachment Adaptation in Addiction Treatment

Interpersonal attachment and drug addiction share many attributes across their behavioral and neurobiological domains. Understanding the overlapping brain circuitry of attachment formation and addiction illuminates a deeper understanding of the pathogenesis of trauma-related mental illnesses and comorbid substance use disorders, and the extent to which ending an addiction is complicated by being a sort of mourning process. Attention to the process of addiction recovery—as a form of grieving—in which Kubler-Ross's stages of grief and Prochaska's stages of change are ultimately describing complementary viewpoints on a general process of neural network and attachment remodeling, could lead to more effective and integrative psychotherapy and medication strategies

The Penrose Effect and its acceleration by the war on drugs: a crisis of untranslated neuroscience and untreated addiction and mental illness

In 1939, British psychiatrist Lionel Penrose described an inverse relationship between mental health treatment infrastructure and criminal incarcerations. This relationship, later termed the ‘Penrose Effect’, has proven remarkably predictive of modern trends which have manifested as reciprocal components, referred to as ‘deinstitutionalization’ and ‘mass incarceration’. In this review, we consider how a third dynamic—the criminalization of addiction via the ‘War on Drugs’, although unanticipated by Penrose, has likely amplified the Penrose Effect over the last 30 years, with devastating social, economic, and healthcare consequences. We discuss how synergy been the Penrose Effect and the War on Drugs has been mediated by, and reflects, a fundamental neurobiological connection between the brain diseases of mental illness and addiction. This neuroscience of dual diagnosis, also not anticipated by Penrose, is still not being adequately translated into improving clinical training, practice, or research, to treat patients across the mental illness-addictions comorbidity spectrum. This failure in translation, and the ongoing fragmentation and collapse of behavioral healthcare, has worsened the epidemic of untreated mental illness and addictions, while driving unsustainable government investment into mass incarceration and high-cost medical care that profits too exclusively on injuries and multi-organ diseases resulting from untreated addictions. Reversing the fragmentation and decline of behavioral healthcare with decisive action to co-integrate mental health and addiction training, care, and research—may be key to ending criminalization of mental illness and addiction, and refocusing the healthcare system on keeping the population healthy at the lowest possible cost.

The adverse childhood experiences questionnaire: Two decades of research on childhood trauma as a primary cause of adult mental illness, addiction, and medical diseases

Objective. In 1998, Felitti and colleagues published the first study of the Adverse Childhood Experiences-Questionnaire (ACE-Q), a 10-item scale used to correlate childhood maltreatment and adverse rearing contexts with adult health outcomes. This paper qualitatively reviews nearly two decades of research utilizing the ACE-Q, highlighting its contribution to our understanding of the causal roots of common, interlinked comorbidities of the brain and body.Methods. An OVID/PubMed search was conducted for English language articles published before 2016, containing the phrase “Adverse Childhood Experiences” in which the ACE-Q was utilized. Source review included a manual search of bibliographies, resulting in 134 articles, including 44 based on the original ACE-Q study population.Results. ACE-Q research has demonstrated that exposures to adverse childhood experiences converge dose-dependently to potently increase the risk for a wide array of causally interlinked mental illnesses, addictions, and multi-organ medical diseases. The intergenerational transmission of this disease burden via disrupted parenting and insecure rearing contexts is apparent throughout this literature. However, the ACE-Q does not tease out genetic or fetal drug exposure components of this transmission.Conclusions. Adverse childhood experiences and rearing may generate a public health burden that could rival or exceed all other root causes. Translating this information to health-care reform will require strengthening brain-behavioral health as core public and preventative health-care missions. Greater integration of mental health and addiction services for parents should be accompanied by more research into brain mechanisms impacted by different forms and interactions between adverse childhood experiences

Pathway Possibilities: The Lilly Endowment's Pathways for Tomorrow Initiative

Looking to the future for what supervision and mentoring will look like and be utilized

Polysubstance addiction vulnerability in mental illness: Concurrent alcohol and nicotine self‐administration in the neurodevelopmental hippocampal lesion rat model of schizophrenia

Multiple addictions frequently occur in patients with mental illness. However, basic research on the brain‐based linkages between these comorbidities is extremely limited. Toward characterizing the first animal modeling of polysubstance use and addiction vulnerability in schizophrenia, adolescent rats with neonatal ventral hippocampal lesions (NVHLs) and controls had 19 weekdays of 1 hour/day free access to alcohol/sucrose solutions (fading from 10% sucrose to 10% alcohol/2% sucrose on day 10) during postnatal days (PD 35‐60). Starting in adulthood (PD 63), rats acquired lever pressing for concurrent oral alcohol (10% with 2% sucrose) and iv nicotine (0.015 mg/kg/injection) across 15 sessions. Subsequently, 10 operant extinction sessions and 3 reinstatement sessions examined drug seeking upon withholding of nicotine, then both nicotine and alcohol, then reintroduction. Adolescent alcohol consumption did not differ between NVHLs and controls. However, in adulthood, NVHLs showed increased lever pressing at alcohol and nicotine levers that progressed more strongly at the nicotine lever, even as most pressing by both groups was at the alcohol lever. In extinction, both groups showed expected declines in effort as drugs were withheld, but NVHLs persisted with greater pressing at both alcohol and nicotine levers. In reinstatement, alcohol reaccess increased pressing, with NVHLs showing greater nicotine lever activity overall. Developmental temporal‐limbic abnormalities that produce mental illness can thus generate adult polydrug addiction vulnerability as a mechanism independent from putative cross‐sensitization effects between addictive drugs. Further preclinical modeling of third‐order (and higher) addiction‐mental illness comorbidities may advance our understanding and treatment of these complex, yet common brain illnesses

Deep Network Pharmacology: Targeting Glutamate Systems as Integrative Treatments for Jump-Starting Neural Networks and Recovery Trajectories

Significant advances in pharmacological treatments for mental illness and addiction will require abandoning old monoaminergic theories of psychiatric disorders and traditionally narrow approaches to how we conduct treatment research. Reframing our efforts with a view on integrative treatments that target core neural network function and plasticity may provide new approaches for lifting patients out of chronic psychiatric symptom sets and addiction. For example, we discuss new treatments that target brain glutamate systems at key transition points within longitudinal courses of care that integrate several treatment modalities. A reconsideration of what our novel and already available medications are intended to achieve and how and when we deliver them for patients with complex illness trajectories could be the key to unlocking new advances in general and addiction psychiatry

Nicotine is more addictive, not more cognitively therapeutic in a neurodevelopmental model of schizophrenia produced by neonatal ventral hippocampal lesions

Nicotine dependence is the leading cause of death in the United States. However, research on high rates of nicotine use in mental illness has primarily explained this co-morbidity as reflecting nicotine's therapeutic benefits, especially for cognitive symptoms, equating smoking with 'self-medication'. We used a leading neurodevelopmental model of mental illness in rats to prospectively test the alternative possibility that nicotine dependence pervades mental illness because nicotine is simply more addictive in mentally ill brains that involve developmental hippocampal dysfunction. Neonatal ventral hippocampal lesions (NVHL) have previously been demonstrated to produce post-adolescent-onset, pharmacological, neurobiological and cognitive-deficit features of schizophrenia. Here, we show that NVHLs increase adult nicotine self-administration, potentiating acquisition-intake, total nicotine consumed and drug seeking. Behavioral sensitization to nicotine in adolescence prior to self-administration is not accentuated by NVHLs in contrast to increased nicotine self-administration and behavioral sensitization documented in adult NVHL rats, suggesting periadolescent neurodevelopmental onset of nicotine addiction vulnerability in the NVHL model. Delivering a nicotine regimen approximating the exposure used in the sensitization and self-administration experiments (i.e. as a treatment) to adult rats did not specifically reverse NVHL-induced cortical-hippocampal-dependent cognitive deficits and actually worsened cognitive efficiency after nicotine treatment stopped, generating deficits that resemble those due to NVHLs. These findings represent the first prospective evidence demonstrating a causal link between disease processes in schizophrenia and nicotine addiction. Developmental cortical-temporal limbic dysfunction in mental illness may thus amplify nicotine's reinforcing effects and addiction risk and severity, even while producing cognitive deficits that are not specifically or substantially reversible with nicotine

Prescription drug monitoring program inquiry in psychiatric assessment: detection of high rates of opioid prescribing to a dual diagnosis population

OBJECTIVE: An epidemic of prescription drug abuse is disproportionately impacting the mentally ill. We examined the utility of a state prescription drug monitoring database for assessing recent controlled substance prescribing to patients presenting for dual diagnosis treatment. METHOD: In a community mental health center that provides integrated dual diagnosis care, we queried the Indiana Scheduled Prescription Electronic Collection and Tracking (INSPECT) system for all cases that were open as of August 2, 2011, and had been practitioner-diagnosed (per DSM-IV criteria) by January 2, 2012. INSPECT provided a record of controlled substance dispensations to each patient; diagnostic evaluation was conducted blind from prescription data compilation covering the prior 12 months. Demographic data, insurance status, and DSM-IV diagnoses were compiled from the clinic's electronic medical record. RESULTS: The sample (N = 201) was 51% female, 56% white, and two-thirds uninsured. Over 80% were dually diagnosed with substance use disorders and psychotic, mood, or anxiety disorders. Nicotine and alcohol disorders were identified in most, with about a third diagnosed with cannabis, cocaine, or opioid disorders. A majority of patients (n = 115) had been prescribed opioids in the prior year, with nearly 1 in 5 prescribed an opioid and benzodiazepine simultaneously. Patients were dispensed a mean of 4 opioid prescriptions and 213 opioid pills. More opioid prescriptions correlated with opioid dependence (OR = 1.08; 95% CI, 1.016-1.145), and more prescribers correlated with personality disorder diagnoses (OR = 1.112; 95% CI, 1.001-1.235). Higher rates and riskier patterns of controlled substance prescribing were identified in patients with Medicaid/Medicare insurance compared to uninsured patients. CONCLUSIONS: Prescription drug monitoring is a powerful tool for assessing addictions and high frequencies of patient exposures to prescribed opioids in a dual diagnosis clinic. Improved prevention and treatment strategies for addictions as facilitated by more research and clinical use of prescription drug monitoring in psychiatric care are warranted

Nicotine effects in adolescence and adulthood on cognition and α₄β₂-nicotinic receptors in the neonatal ventral hippocampal lesion rat model of schizophrenia

Rational Nicotine use in schizophrenia has traditionally been explained as ‘self-medication’ of cognitive and/or nicotinic acetylcholinergic receptor (nAChR) abnormalities. Objectives We test this hypothesis in a neurodevelopmental rat model of schizophrenia that shows increased addiction behaviors including enhanced nicotine reinforcement and drug-seeking. Methods Nicotine transdermal patch (5 mg/kg/day vs. placebo × 10 days in adolescence or adulthood) effects on subsequent radial-arm maze learning (15 sessions) and frontal-cortical-striatal nAChR densities (α4β2; [3H]-epibatidine binding) were examined in neonatal ventral hippocampal lesion (NVHL) and SHAM-operated rats. Results NVHL cognitive deficits were not differentially affected by nicotine history compared to SHAMs. Nicotine history produced minimal cognitive effects while increasing food–reward consumption on the maze, compounding with NVHL-induced overconsumption. Acute nicotine (0.5 mg/kg) delivered before the final maze sessions produced modest improvements in maze performance in rats with nicotine patch histories only, but not differentially so in NVHLs. Consistent with in vivo neuroimaging of β2 nAChR binding in schizophrenia smokers vs. non-smokers and healthy controls, adult NVHLs showed 12% reductions in nAChR binding in MPFC (p.40), whereas nicotine history elevated nAChRs across both regions (>30%, p<0.001) without interacting with NVHLs. Adolescent vs. adult nicotine exposure did not alter nAChRs differentially. Conclusions Although replicating nicotine-induced up-regulation of nAChRs in human smokers and demonstrating NVHL validity in terms of schizophrenia-associated nAChR density patterns, these findings do not support hypotheses explaining increased nicotine use in schizophrenia as reflecting illness-specific effects of nicotine to therapeutically alter cognition or nAChR densities

Prescription drug monitoring program data tracking of opioid addiction treatment outcomes in integrated dual diagnosis care involving injectable naltrexone

BACKGROUND AND OBJECTIVES: Fourfold increases in opioid prescribing and dispensations over 2 decades in the U.S. has paralleled increases in opioid addictions and overdoses, requiring new preventative, diagnostic, and treatment strategies. This study examines Prescription Drug Monitoring Program (PDMP) tracking as a novel measure of opioid addiction treatment outcomes in a university-affiliated integrated mental health-addiction treatment clinic. METHODS: Repeated measure parametrics examined PDMP and urine drug screening (UDS) data before and after first injection for all patients (N = 68) who received at least one long-acting naltrexone injection (380 mg/IM) according to diagnostic groupings of having either (i) alcohol (control); (ii) opioid; or (iii) combined alcohol and opioid use disorders. RESULTS: There were no group differences post-injection in treatment days, injections delivered, or treatment service encounters. UDS and PDMP measures of opioid exposures were greater in opioid compared to alcohol-only patients. Post-first injection, UDS's positive for opioids declined (p < .05) along with PDMP measures of opioid prescriptions (p < .001), doses (p < .01), types (p < .001), numbers of dispensing prescribers (p < .001) and pharmacies (p < .001). Opioid patients without alcohol disorders showed the best outcomes with 50% to 80% reductions in PDMP-measures of opioids, down to levels of alcohol-only patients. CONCLUSIONS: This study shows PDMP utility for measuring opioid addiction treatment outcomes, supporting the routine use of PDMPs in clinical and research settings. SCIENTIFIC SIGNIFICANCE: These findings demonstrate that opioid addiction in patients with complex addictions and mental illnesses comorbidities can show effective treatment responses as measured by PDMP tracking of decreases in opioid prescriptions to those patients. (Am J Addict 2016;25:557-564)