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The use of 'agonist therapy' for cocaine and methamphetamine addiction involves administration of stimulant-like medications (e.g. monoamine releasers) to reduce withdrawal symptoms and prevent relapse. A significant problem with this strategy is that many candidate medications possess abuse liability due to activation of mesolimbic dopamine (DA) neurons in the brain. One way to reduce DA-mediated abuse liability of candidate drugs might be to add in serotonin (5-HT)-releasing properties, since substantial evidence shows that 5-HT neurons provide an inhibitory influence over mesolimbic DA neurons. This chapter addresses several key issues related to the development of dual DA/5-HT releasers for the treatment of substance use disorders. First, we briefly summarize the evidence supporting a dual deficit in DA and 5-HT function during withdrawal from chronic cocaine or alcohol abuse. Second, we discuss data demonstrating that 5-HT release can dampen DA-mediated stimulant effects, and the 'anti-stimulant' role of 5-HT(2C) receptors is considered. Next, the mechanisms underlying potential adverse effects of 5-HT releasers are described. Finally, we discuss recently published data with PAL-287, a novel non-amphetamine DA/5-HT-releasing agent that suppresses cocaine self-administration but lacks positive reinforcing properties. It is concluded that DA/5-HT releasers could be useful therapeutic adjuncts for the treatment of cocaine and alcohol addictions as well as for obesity, attention deficit disorder and depression.
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PMID:Dopamine/serotonin releasers as medications for stimulant addictions. 1877 43

"Agonist therapy" for cocaine and methamphetamine addiction involves administration of stimulant-like medications (e.g., monoamine releasers) to reduce withdrawal symptoms and prevent relapse. A significant problem with this strategy is that many candidate medications possess abuse liability because of activation of mesolimbic dopamine (DA) neurons in the brain. One way to reduce DA-mediated abuse liability of candidate drugs is to add in serotonin (5-HT) releasing properties, since substantial evidence shows that 5-HT neurons provide an inhibitory influence over mesolimbic DA neurons. This article addresses several key issues related to the development of dual DA/5-HT releasers for the treatment of substance use disorders. First, the authors briefly summarize the evidence supporting a dual deficit in DA and 5-HT function during withdrawal from chronic cocaine or alcohol abuse. Second, the authors discuss data demonstrating that 5HT release can dampen DA-mediated stimulant effects, and the "antistimulant" role of 5-HT-sub(2C) receptors is considered. Next, the mechanisms underlying potential adverse effects of 5-HT releasers are described. Finally, the authors discuss recently published data with PAL-287, a novel nonamphetamine DA/5-HT releasing agent that suppresses cocaine self-administration but lacks positive reinforcing properties. It is concluded that DA/5-HT releasers could be useful therapeutic adjuncts for the treatment of cocaine and alcohol addictions, as well as for obesity, attention-deficit disorder, and depression.
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PMID:Dual dopamine/serotonin releasers: potential treatment agents for stimulant addiction. 1908 67

Overeating in industrial societies is a significant problem, linked to an increasing incidence of overweight and obesity, and the resultant adverse health consequences. We advance the hypothesis that a possible explanation for overeating is that processed foods with high concentrations of sugar and other refined sweeteners, refined carbohydrates, fat, salt, and caffeine are addictive substances. Therefore, many people lose control over their ability to regulate their consumption of such foods. The loss of control over these foods could account for the global epidemic of obesity and other metabolic disorders. We assert that overeating can be described as an addiction to refined foods that conforms to the DSM-IV criteria for substance use disorders. To examine the hypothesis, we relied on experience with self-identified refined foods addicts, as well as critical reading of the literature on obesity, eating behavior, and drug addiction. Reports by self-identified food addicts illustrate behaviors that conform to the 7 DSM-IV criteria for substance use disorders. The literature also supports use of the DSM-IV criteria to describe overeating as a substance use disorder. The observational and empirical data strengthen the hypothesis that certain refined food consumption behaviors meet the criteria for substance use disorders, not unlike tobacco and alcohol. This hypothesis could lead to a new diagnostic category, as well as therapeutic approaches to changing overeating behaviors.
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PMID:Refined food addiction: a classic substance use disorder. 1922 27

Obesity and substance abuse during adolescence have reached epidemic proportions, and both are among the leading major public health problems in the United States. There is a significant amount of weight and Body Mass Index (BMI) gain in adolescent ex-addicts during supervised and confirmed abstinence from drugs and alcohol. The primary purpose of this secondary data analysis was to examine the effectiveness of two interventions implemented to address weight management in residential facilities treating adolescent substance use disorders. The secondary purpose was to establish if the outcome was a function of mandated smoking cessation and prescribed psychotropic medications. The results of the study suggest adolescents experienced weight gain in all groups, however there was no interaction effect for smokers and those adolescents on psychotropic medication for either outcome variable.
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PMID:Weight gain during substance abuse treatment: the dual problem of addiction and overeating in an adolescent population. 1928 73

The objectives of this study were to assess the prevalence of prognostic factors previously known to be associated with poor antibody response to hepatitis B vaccination in a sample of veterans presenting for substance use disorders treatment at a Veterans Health Administration (VA) Medical Center, assess vaccination response, and identify markers for poor response in this population. Results indicated that most participants had multiple prognostic factors previously known to be associated with poor antibody response including male gender, age over 40, smoking, and obesity. The rate of seroconversion in this sample was 51.9%. This is substantially lower than seen in healthy adults. Alcohol dependence was the only significant independent negative predictor of seroconversion in this sample. Substance use disorders treatment providers who are considering adding hepatitis B vaccination services to their clinics should be aware that the antibody response to the hepatitis B vaccination is inconsistent and that patients with particular demographic characteristics may be at heightened risk of poor antibody response.
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PMID:Antibody response to hepatitis B vaccine in substance use disorder patients. 1978 29

It is now generally accepted that complex mental disorders are the results of interplay between genetic and environmental factors. This holds out the prospect that by studying G x E interplay we can explain individual variation in vulnerability and resilience to environmental hazards in the development of mental disorders. Furthermore studying G x E findings may give insights in neurobiological mechanisms of psychiatric disorder and so improve individualized treatment and potentially prevention. In this paper, we provide an overview of the state of field with regard to G x E in mental disorders. Strategies for G x E research are introduced. G x E findings from selected mental disorders with onset in childhood or adolescence are reviewed [such as depressive disorders, attention-deficit/hyperactivity disorder (ADHD), obesity, schizophrenia and substance use disorders]. Early seminal studies provided evidence for G x E in the pathogenesis of depression implicating 5-HTTLPR, and conduct problems implicating MAOA. Since then G x E effects have been seen across a wide range of mental disorders (e.g., ADHD, anxiety, schizophrenia, substance abuse disorder) implicating a wide range of measured genes and measured environments (e.g., pre-, peri- and postnatal influences of both a physical and a social nature). To date few of these G x E effects have been sufficiently replicated. Indeed meta-analyses have raised doubts about the robustness of even the most well studied findings. In future we need larger, sufficiently powered studies that include a detailed and sophisticated characterization of both phenotype and the environmental risk.
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PMID:From nature versus nurture, via nature and nurture, to gene x environment interaction in mental disorders. 2002 96

Practical strategies are available for primary care physicians to monitor psychiatric and medical outcomes as well as treatment adherence in patients with bipolar disorder. Current depressive symptoms can be assessed with tools like the 9-item Patient Health Questionnaire or Beck Depression Inventory. Lifetime presence or absence of manic or hypomanic symptoms can be assessed using the Mood Disorder Questionnaire (MDQ). These measures can be completed quickly by patients prior to appointments. Sensitivity of such ratings, particularly the MDQ, can be increased by having a significant other also rate the patient. Clinicians should also screen mood disorder patients for psychiatric comorbidities that are common in this population such as anxiety and substance use disorders. While patients with bipolar disorder may commonly be nonadherent with prescribed medication regimens, strategies that can help include having frank discussions with the patient, selecting medication collaboratively, adding psychotherapy with a psychoeducation element, monitoring appointment-keeping, using patient self-reports of medication-taking, enlisting the aid of significant others, and measuring plasma drug levels. Medical monitoring is needed to assess the safety and tolerability of psychotropic medications. All of the approved medications for bipolar disorder have at least 1 boxed warning for serious side effects, but are also associated with other common management-limiting side effects such as sedation, tremor, unsteadiness, restlessness, nausea, vomiting, diarrhea, constipation, weight gain, and metabolic problems. Routine monitoring is particularly needed for obesity, metabolic syndrome, and cardiovascular disorders, which lead to high rates of medical morbidity and mortality in patients with bipolar disorder. Monitoring protocols such as the one recommended by the American Diabetes Association for patients taking second-generation antipsychotics can be used for regular assessment.
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PMID:Strategies for monitoring outcomes in patients with bipolar disorder. 2062 1

Studies obtaining implicit measures of associations in Diagnostic and Statistical Manual of Mental Disorders (4th ed., Text Revision; American Psychiatric Association, 2000) Axis I psychopathology are organized into three categories: (a) studies comparing groups having a disorder with controls, (b) experimental validity studies, and (c) incremental and predictive validity studies. In the first category, implicit measures of disorder-relevant associations were consistent with explicit beliefs for some disorders (e.g., specific phobia), but for other disorders evidence was either mixed (e.g., panic disorder) or inconsistent with explicit beliefs (e.g., pain disorder). For substance use disorders and overeating, expected positive and unexpected negative associations with craved substances were found consistently. Contrary to expectation, implicit measures of self-esteem were consistently positive for patients with depressive disorder, social phobia, and body dysmorphic disorder. In the second category, short-term manipulations of disorder-relevant states generally affected implicit measures as expected. Therapeutic interventions affected implicit measures for one type of specific phobia, social phobia, and panic disorder, but not for alcohol use disorders or obesity. In the third category, implicit measures had predictive value for certain psychopathological behaviors, sometimes moderated by the availability of cognitive resources (e.g., for alcohol and food, only when cognitive resources were limited). The strengths of implicit measures include (a) converging evidence for dysfunctional beliefs regarding certain disorders and consistent new insights for other disorders and (b) prediction of some psychopathological behaviors that explicit measures cannot explain. Weaknesses include (a) that findings were inconsistent for some disorders, raising doubts about the validity of the measures, and (b) that understanding of the concept "implicit" is incomplete.
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PMID:Implicit measures of association in psychopathology research. 2121 60

With the present review, we intend to highlight the importance of considering the age- and development-dependent occurrence of comorbidity in ADHD and to outline distinct trajectories of symptom progression with possible impact on course and outcome of ADHD. The review will focus on introducing the concepts of "developmental epidemiology" and "developmental comorbidity". Psychiatric and non-psychiatric age-dependent comorbidity can be seen in the majority of children, adolescents and adults with ADHD, resulting in a severe impairment of everyday life with considerable functional and psychosocial problems. Concerning the temporal order of occurrence, psychiatric conditions may be present before the appearance of first definite ADHD symptoms ("pre-comorbidity", such as temperament factors, sleep disturbance, autism spectrum disorders and atopic eczema). They may coincide with the time when ADHD symptoms reach a clinically significant level ("simultaneous comorbidity": enuresis, encopresis, developmental dyslexia). The majority of comorbidity, however, appears after the onset of ADHD in the course of disease ("post-comorbidity": tic disorder, depression and suicidality, anxiety disorders, obsessive compulsive disorder, bipolar disorder, conduct and substance use disorders, obesity and personality disorders). The aetio-pathophysiology of ADHD and its comorbid disorders and also the nature of comorbidity itself being highly heterogeneous, we additionally discuss possible models of comorbidity. In the future, longitudinal data on distinct patterns of symptom and comorbidity progression would help to refine disease classification systems, strengthen the power of future genetic studies and finally allow for more specific treatment strategies.
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PMID:Developmental comorbidity in attention-deficit/hyperactivity disorder. 2143 12

Overeating and associated obesity are major public health problems. In addition to its notable adverse health consequences, the behavior of overeating has significant neurobiological and psychological underpinnings. Current classification systems of mental disorders (DSM-IV and ICD-10) address this increasingly prevalent "disorder" in a limited and inconsistent manner. Several similarities between overeating and substance dependence have been documented with regards to phenomenology, shared neurobiology, and treatment. This has led to suggestions that a new category of "food addiction" be added to our psychiatric nosology and that this category be included with substance use disorders under a broad rubric of "addiction disorders". In this article, we consider the rationale for this recommendation and evaluate its pros and cons. We summarize how the problem of overeating is addressed in our current classification systems and discuss DSM-5 approaches to the issue.
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PMID:Should overeating and obesity be classified as an addictive disorder in DSM-5? 2149 85


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