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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

The correlation between exposure to forms of violence and development of mental disorders in victims is well established. The purpose of this paper was to identify mental health problems in an adolescent medicine clinic population in Lexington, KY and to investigate potential correlation of mental disorders with psychosocial factors. Data were gathered from the charts of 169 adolescent clinic patients (age 10-22) seen in the clinic for mental health care and analyzed using Excel. Of the patient population, 68% were urban, whereas 32% were rural. In terms of gender, 40% of the patients were male and 60% were female, 80% were white, 13% black, and 7% had other racial background(s). The most prevalent mental disorders in this group were depression 32.12%, 13% with generalized anxiety disorder, 8.2% with an attention deficit disorder (including ADHD), and 5.76% with an adjustment disorder. The abovementioned demographic trends showed that depression continues to be the most common mental health problem in this population regardless of gender, ethnic origin, or economic status. This finding highlights the need for availability of mental health support to this patient population. Further work is needed to spotlight the most significant psychosocial factors and root causes of mental health conditions in this age group.
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PMID:Trends in mental health of an adolescent medicine clinic patient population. 1952 91

ABSTRACT In a large, heterogeneous sample (N = 182) of children with attention deficit disorder (ADD), the prevalences of additional DSM-III diagnoses were determined using the Diagnostic Interview for Children and Adolescents (DICA). More than half the children had additional DSM-III psychiatric diagnoses. Oppositional disorder and anxiety/mood disorders were the most frequent diagnoses. White male children with ADD were selected into four contrast groups based on comorbidity: ADD children with no additional diagnosis (neither), with anxiety or depression (ANX/DEP), with oppositional or conduct disorder (OPP/CON), and with both ANX/DEP and OPP/CON diagnoses (both). ADD children who had both ANX/DEP and OPP/CON were significantly more improved on a high dose (0.6 mg/kg bid) than a low dose (0.3 mg/kg bid), but ADD boys in the other diagnostic groups responded as well to both doses. There was no evidence that ADD children with comorbid emotional or disruptive behavior disorders respond any less well to psychostimulants than other ADD children. However, there is a concern for those children who have the comorbid combination of (1) ADD, (2) an additional externalizing disorder (disruptive behavior disorder), and (3) an internalizing disorder (a mood or anxiety disorder). These children may not respond to low clinical doses of psychostimulants, but may respond well at higher doses. Children's self-ratings on the DICA may provide important clinical data concerning stimulant dosing which are not provided by teacher or parent ratings. We found no evidence that ADD children with comorbid emotional disorders respond any less well to a psychostimulant than ADD children without emotional comorbidity.
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PMID:Psychiatric comorbidity and response to two doses of methylphenidate in children with attention deficit disorder. 1963 Jun 49

In order to better understand factors that account for the emergence and persistence of negative attitudes towards mental health problems, attributions about and stigma towards children's mental and physical illnesses were examined using National Stigma Study-Children data. Parent blame attributions were most strongly associated with attention deficit disorder, environmental causes with depression, and biology with asthma. Parent blame was more frequent for mental than physical health conditions. Child blame was associated with higher preferred social distance from the child, but no clear links were observed between social distance and attributions about genetic/biology, environment, or parent blame. Rurality was not significantly associated with attributions or social distance preference. Higher educational achievement was associated with increased endorsement of environmental stress factors and reduced odds of child blaming. The general public holds complex explanatory models of and nuanced responses to children's mental disorders that need further investigation, including effects on parents' and children's help-seeking.
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PMID:Factors associated with attributions about child health conditions and social distance preference. 2057 9

Extract: Complaints of impaired memory are amongst the most common symptoms voiced by patients to physicians in the fields of neurology, psychiatry, medicine, and surgery. Impairment of memory is one of the most disabling aspects of many neurological disorders, including neurodegenerative diseases, strokes, tumors, head trauma, hypoxia (reduced exposure of tissue to oxygen), cardiac surgery, malnutrition, attention deficit disorder, depression, anxiety, medication side-effects, and normal aging. This memory loss often impairs the patient's normal daily activities, profoundly affecting both the patients and their families. Research in memory began with neuropsychological studies of patients with focal brain lesions and now includes new methods such as PET (positron emission tomography, where the decay of an injected radioactive element or drug creates an image) and functional MRI (magnetic resonance imaging, where hydrogen atoms are polarized by a magnet and the summation of their spinning energy creates an image). Event-related methodologies have provided us with more refined and improved classification systems. Rather than conceptualizing memory as "short-term" and "long-term," we now think of memory as a collection of mental abilities that use different systems within the brain. In the present article we will summarize the four memory systems that are of clinical relevance: episodic memory, semantic memory, procedural memory, and working memory.
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PMID:Memory dysfunction in clinical practice. 2070 99

Exposure of individuals to natural environments, such as forests and coastlines, can promote stress reduction and assist in mental recovery following intensive cognitive activities. Settings as simple as hospital window views onto garden-like scenes can also be influential in reducing patients' postoperative recovery periods and analgesic requirements. This paper reviews the evidence supporting the exploitation of these restorative natural environments in future healthcare strategies. The paper also describes early research addressing the development of multisensory, computer-generated restorative environments for the benefit of patients with a variety of psychologically related conditions (including depression, attention deficit disorder, pain, and sleep deficit), who may be unable to access and experience real natural environments, such as those in hospices, military rehabilitation centers, and long-term care facilities. The Table of Contents art is a virtual reconstruction of Wembury Bay, in the southwest of the UK, based on imported Digital Terrain Elevation Data (DTED) to provide the topography and a high-resolution aerial image to provide a template for the location of 3D building and vegetation models, rock features, and pathways. The 3D environment is rendered using the Unity 3 Game Development Tool and includes spatial sound effects (waves, wind, birdsong, etc.), physics-based features (such as early morning sea mist), time-of-day cycles, and real-time weather changes. The Village Church of St. Werburgh can also be seen in this image.
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PMID:Can natural and virtual environments be used to promote improved human health and wellbeing? 2150 54

Ketamine, a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is capable of triggering excessive glutamate release and subsequent cortical excitation which may induce psychosis-like behavior and cognitive anomalies. Growing evidence suggests that acute ketamine administration can provoke dose-dependent positive and negative schizophrenia-like symptoms. While the acute effects of ketamine are primarily linked to aberrant activation of the prefrontal cortex and limbic structures with elevated glutamate and dopamine levels, the long-term effects of ketamine on brain functions and neurochemical homeostasis remain incompletely understood. In recent years, reports of ketamine abuse, especially among young individuals, have surged rapidly, with profound socioeconomic and health impacts. We herein investigated the chronic effects of ketamine on brain function integrity in an animal model of adolescent cynomolgus monkeys (Macaca fascicularis) by functional magnetic resonance imaging (fMRI). Immunohistochemical study was also conducted to examine neurochemical changes in the dopaminergic and cholinergic systems in the prefrontal cortex following chronic ketamine administration. Our results suggest that repeated exposure to ketamine markedly reduced neural activities in the ventral tegmental area, substantia nigra in midbrain, posterior cingulate cortex, and visual cortex in ketamine-challenged monkeys. In contrast, hyperfunction was observed in the striatum and entorhinal cortex. In terms of neurochemical and locomotive changes, chronically ketamine-challenged animals were found to have reduced tyrosine hydroxylase (TH) but not choline acetyltransferase (ChAT) levels in the prefrontal cortex, which was accompanied by diminished total movement compared with the controls. Importantly, the mesolimbic, mesocortical and entorhinal-striatal systems were found to be functionally vulnerable to ketamine's chronic effects. Dysfunctions of these neural circuits have been implicated in several neuropsychiatric disorders including depression, schizophrenia and attention deficit disorder (ADD). Collectively, our results support the proposition that repeated ketamine exposure can be exploited as a pharmacological paradigm for studying the central effects of ketamine relevant to neuropsychiatric disorders.
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PMID:Mapping the central effects of chronic ketamine administration in an adolescent primate model by functional magnetic resonance imaging (fMRI). 2217 34

Buspirone is an anxiolytic drug and is a partial agonist for the serotonin 5-HT(1A) receptors as well as possessing low affinity and is an antagonist for the dopamine D(2) autoreceptors, with some evidence of a weak affinity to 5-HT(2) receptors. The underlying mechanism of action of buspirone is not clear; however it is thought that its main pharmacology is mediated via the 5-HT(1A) receptors. Initially developed for use in the treatment of generalised anxiety disorder, it appears that buspirone may be useful in various other neurological and psychiatric disorders, such as attenuating side effects of Parkinson's disease therapy, ataxia, depression, social phobia, and behaviour disturbances following brain injury, and those accompanying Alzheimer's disease, dementia and attention deficit disorder. Considering the potential of this drug to be included in the management of many conditions, thorough and controlled studies are required to elucidate the exact mechanism of action. This review will consider the evidence so far for both the potential underlying mechanisms and its use in various conditions.
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PMID:Buspirone: what is it all about? 2260 68

We used a national online registry to examine variation in cumulative prevalence of community diagnosis of psychiatric comorbidity in 4343 children with autism spectrum disorders (ASD). Adjusted multivariate logistic regression models compared influence of individual, family, and geographic factors on cumulative prevalence of parent-reported anxiety disorder, depression, bipolar disorder, and attention deficit/hyperactivity disorder or attention deficit disorder. Adjusted odds of community-assigned lifetime psychiatric comorbidity were significantly higher with each additional year of life, with increasing autism severity, and with Asperger syndrome and pervasive developmental disorder-not otherwise specified compared with autistic disorder. Overall, in this largest study of parent-reported community diagnoses of psychiatric comorbidity, gender, autistic regression, autism severity, and type of ASD all emerged as significant factors correlating with cumulative prevalence. These findings could suggest both underlying trends in actual comorbidity as well as variation in community interpretation and application of comorbid diagnoses in ASD.
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PMID:Parent report of community psychiatric comorbid diagnoses in autism spectrum disorders. 2293 48

Neurophysiological studies may explain how breathing techniques normalize stress response, emotion regulation, and autonomic and neuroendocrine system function. Breath practices have been shown to reduce symptoms of stress, anxiety, insomnia, post-traumatic stress disorder, mass disasters, depression, and attention deficit disorder. Technology-assisted breathing interventions facilitate therapeutic breathing by using either static cues such as a breath pacer or real-time feedback based on physiological parameters such as heart rate variability. The empirical literature indicates that technology-assisted breathing can be beneficial in mental health treatment, though it may not be appropriate for all individuals. Initial in-person training and evaluation can improve results.
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PMID:Breathing practices for treatment of psychiatric and stress-related medical conditions. 2353 82


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