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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuronal nicotinic acetylcholine receptors (nAChRs) are a class of ion channels with significant potential as molecular targets for the design of drugs to treat a variety of CNS disorders. The discovery that neuronal nAChRs are further subdivided into multiple subtypes suggests that drugs which act selectively at specific nAChR subtypes might effectively treat Parkinson's disease (PD), Alzheimer's disease (AD), schizophrenia, ADHD, depression, anxiety or pain without the accompanying adverse side effects associated with non-selective agents such as nicotine (1) and epibatidine. Altinicline (SIB-1508Y) is a novel, small molecule designed to selectively activate neuronal nAChRs and is undergoing clinical evaluation for the treatment of PD. It was selected from a series of compounds primarily on the basis of results from functional assays, including (a) measurement of Ca2+ flux in stable cell lines expressing specific recombinant human neuronal nAChR subtypes; (b) determination of in vitro and in vivo neurotransmitter release; (c) in vivo models of PD. Biological data on both altinicline and the series of compounds from which it was selected are reported.
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PMID:Recombinant human receptors and functional assays in the discovery of altinicline (SIB-1508Y), a novel acetylcholine-gated ion channel (nAChR) agonist. 1081 48

The most frequently encountered developmental problems of learning disabilities/ADHD often co-exist with severe behavioral disorders. As a direct consequence, this condition opens the way to delinquency, school drop-out, depression, suicide, substance abuse, work absenteeism, and other psycho-social complications. In this paper, we are presenting a selective overview of our previous research and its clinical applications in this field as it relates to our present research data pertaining to the effects of our original Memory Workload Paradigm on the event-related brain potentials in differentiating normal and pathological pre-adolescents (learning disabled/ADHD with concomitant severe behavioral disorders such as oppositional and conduct). In addition, it provides data on the bilateral electrodermal activity during cognitive workload and Mangina-Test performance of pathological and normal pre-adolescents conducted in separate sessions. The results of our present research indicate that a significant memory load effect for the P450 latency (F(3,27)=4.98, P<0.01) and the P450 amplitude (F(3,27)=3.57, P<0.05) was present for normal pre-adolescents which was absent in pathological pre-adolescents. Moreover, enhanced N450 ERP amplitudes to our Memory Workload Paradigm in pre-frontal and frontal regions clearly differentiated normal from pathological pre-adolescents (F(1, 18)=12.21, P<0.004). Furthermore, significant differences between normal and pathological groups were found in bilateral electrodermal activity (F(1,18)=23.86, P<0.001) and on the Mangina-Test performance (F(1,18)=75.35, P<0.001). Our present research findings provide an original and valuable demonstration of an integrative and effective clinical psychophysiological application of central (ERPs), autonomic (bilateral electrodermal activity) and neuro-psychometric aspects (Mangina-Test) which characterize normal and pathological pre-adolescents and underpin the neurophysiological basis of learning disabled/ADHD with severe behavioral disorders as opposed to normal subjects.
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PMID:Event-related brain potentials, bilateral electrodermal activity and Mangina-Test performance in learning disabled/ADHD pre-adolescents with severe behavioral disorders as compared to age-matched normal controls. 1082 76

The frontostriatal system (dorsolateral prefrontal cortex, lateral orbitofrontal cortex, anterior cingulate, supplementary motor area, and associated basal-ganglia structures) is subject to a range of neurodevelopmental disorders: Tourette's syndrome (TS), obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), autism, and probably depression. The system is responsible for our adaptive responses (initiation, execution, or withholding) to environmental situations, and the above disorders, involving effectively excessive release or withholding of various types of response, are all a consequence of changes in specific frontostriatal regions. The disorders all have a genetic component, and their persistence in the genome indicates that their clinical manifestations may also be associated, perhaps in low levels in close relatives, with certain adaptive advantages in given situations. Thus autism is associated with computational careers, depression with literary creativity, SCZ with lateral thinking and the Odyssean personality, ADHD with an Ice-Age readiness to respond, OCD with a focused range of interests, and TS with competitive sports and jazz improvisation. The disorders are all highly comorbid, and which one predominantly manifests may depend on how the frontostriatal system happens to be compromised as a result of inherited genetic predispositions and environmental contingency. We review the adaptive nature of the various subclinical manifestations and the evidence for concomitant phenomena (possibly epiphenomena): alterations in structural, functional, and behavioral lateralization in each syndrome. Indeed it is not clear that altered lateralization in frontostriatal disorders of a neurodevelopmental origin generally has any adaptive significance; it may often simply serve as a marker for altered regulatory function of the frontostriatal system, alterations which in low genetic dosage or penetrance continue to play an adaptive role in clinically unaffected close relatives of probands, but which, in high dosage or penetrance in the probands themselves, are generally deleterious.
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PMID:The neurodevelopmental frontostriatal disorders: evolutionary adaptiveness and anomalous lateralization. 1085 79

We investigated whether substance abuse/dependence, conduct disorder, and other psychiatric disorders improved in adolescent females who were referred to outpatient treatment and which variables were related to 1-year outcome. Forty-six out of 60 conduct-disordered (CD) adolescent females with substance abuse or dependence were re-evaluated approximately 1 year after discharge. Treatment length averaged 16 weeks. Significant improvements were seen in three areas: (1) criminality and CD; (2) attention deficit hyperactivity disorder (ADHD); and (3) educational and vocational status. However, neither substance involvement nor depression improved, regardless of length of stay in treatment, and these females demonstrated significant risky sexual behaviors. In contrast to our previous work with adolescent males (Crowley, T.J., Mikulich, S.K., Macdonald, M., Young, S.E., Zerbe, G.O., 1998. Substance-dependent, conduct-disordered adolescent males: severity of diagnosis predicts 2-year outcome. Drug Alcohol Depend. 49, 225-237), we were not able to identify pre-intake variables, other than performance IQ, that were related to substance use and conduct outcomes. Only two post-treatment factors (peer problems and number of ADHD symptoms at follow-up) were found to be related to CD and substance use disorders outcomes. The overall lack of pre- and post-treatment predictors presents interesting challenges for future research on adolescent females with these disorders.
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PMID:One-year outcome of adolescent females referred for conduct disorder and substance abuse/dependence. 1089 26

A variety of behavioral and emotional problems have been associated with attention deficit disorder with hyperactivity (ADHD) in children of average intellect. In contrast, little is known about concomitant behavioral and emotional problems in children with ADHD and mental retardation. In this study, we used the Personality Inventory for Children-Revised to assess the behavioral adjustment of 48 children with mental retardation and ADHD compared to that of 47 children with mental retardation without ADHD. The ADHD group had significantly more symptoms of depression, family conflict, noncompliance, anxiety, hyperactivity, inadequate social skills, and academic problems. Results are strongly suggestive of significant behavioral and emotional problems in children with ADHD and mental retardation, thus mirroring the pattern associated with ADHD in the general school-age population.
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PMID:Patterns of behavioral adjustment and maladjustment in mental retardation: comparison of children with and without ADHD. 1093 66

Phospholipids make up about 60% of the brain's dry weight and play key roles in many brain signal tranduction mechanisms. A recent review(1)identified the increasing evidence that abnormal phospholipid and related fatty acid metabolism may contribute to illnesses such as schizophrenia, bipolar disorder, depression and attention deficit hyperactivity disorder. This current paper reviews the main pathways of phospholipid metabolism, emphasizing the role of phospholipases of the A2 in signal tranduction processes. It also updates the chromosomal locations of regions likely to be involved in these disorders, and relates these to the known locations of genes directly or indirectly involved in phospholipid and fatty acid metabolism.
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PMID:Gene targets related to phospholipid and fatty acid metabolism in schizophrenia and other psychiatric disorders: an update. 1097 Jul 13

Clonidine is a central acting a2-agonist used primarily as an antihypertensive agent. Recently, it has been used for the treatment of attention deficit hyperactivity disorder in children and adolescents. When taken in excess, it can produce profound CNS depression, apnea, bradycardia and hypotension. A transient period of hypertension can sometimes occur. Treatment is primarily supportive, including respiratory support, atropine for bradycardia, and fluids and dopamine for hypotension. The CNS depression sometimes responds to naloxone. Young children are very sensitive to the toxic effects of clonidine. A case of an 11 year old adolescent who took an overdose of his clonidine is described to illustrate the toxicity of this agent.
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PMID:Clonidine toxicity in an adolescent patient. 1103 97

Over the past 10 years, innovations in physics and computer science have promoted magnetic resonance imaging (MRI) as an essential tool for investigating the biological substrates of psychiatric disorders. Requiring no radiation exposure, MRI is now the preferred imaging technique for pediatric populations. However, the rapid technical advances in MRI pulse sequences, data processing, and analysis have made it increasingly complex for clinicians to compare and critically evaluate MRI research studies. This paper selectively reviews MRI research on five psychiatric conditions occurring in childhood or adolescence: ADHD, autism, childhood-onset schizophrenia, Tourette syndrome, and early-onset depression. The selection of papers reviewed was based on four criteria: the originality of the idea underlying the paper, the quality of the sample and methodologies used, the presence of controversial findings in the paper, and whether the paper was a clear illustration of specific methodological strengths or weaknesses. The two goals of this review paper are to update clinicians on morphometric brain imaging in child psychiatry and the methodological issues pertaining to image acquisition and analysis, and to promote critical reading of future MRI studies.
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PMID:MRI neuroimaging of childhood psychiatric disorders: a selective review. 1103 81

This study used data from a completed longitudinal study to examine the effects of methylphenidate on 6-12-year-old boys presumably at risk for bipolar disorder. Of 75 boys referred, diagnosed with hyperkinetic reaction of childhood (minimal brain dysfunction), treated clinically with methylphenidate, and followed as young adults, 23% (the maximorbid or MAX group) had childhood symptoms of irritability and emulated DSM-IV diagnoses of attention deficit hyperactivity disorder (ADHD), plus oppositional defiant or conduct disorder (ODD/CD) and anxiety or depression or both. The remaining boys (the minimorbid or MIN group) had fewer symptoms and disorders. MAX and MIN groups did not differ in rated response to methylphenidate, duration of treatment, clinically determined maintenance doses, concurrent or subsequent treatment with other medications, or other aspects of medication experience. At ages 21-23, individuals with bipolar-related lifetime diagnoses (adult mania, hypomania, or cyclothymia) did not differ from those without bipolar-related diagnoses in any aspect of early methylphenidate treatment history. These findings indicate that ADHD boys with symptoms suggesting childhood mania do not respond differently to methylphenidate than boys without such symptoms, and there is no evidence here that methylphenidate precipitates young adult bipolar disorders in susceptible individuals.
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PMID:Stimulant treatment in young boys with symptoms suggesting childhood mania: a report from a longitudinal study. 1105 7

This study investigated the association between reading disability (RD) and internalizing and externalizing psychopathology in a large community sample of twins with (N = 209) and without RD (N = 192). The primary goals were to clarify the relation between RD and comorbid psychopathology, to test for gender differences in the behavioral correlates of RD, and to test if common familial influences contributed to the association between RD and other disorders. Results indicated that individuals with RD exhibited significantly higher rates of all internalizing and externalizing disorders than individuals without RD. However, logistic regression analyses indicated that RD was not significantly associated with symptoms of aggression, delinquency, oppositional defiant disorder, or conduct disorder after controlling for the significant relation between RD and ADHD. In contrast, relations between RD and symptoms of anxiety and depression remained significant even after controlling for comorbid ADHD, suggesting that internalizing difficulties may be specifically associated with RD. Analyses of gender differences indicated that the significant relation between RD and internalizing symptoms was largely restricted to girls, whereas the association between RD and externalizing psychopathology was stronger for boys. Finally, preliminary etiological analyses suggested that common familial factors predispose both probands with RD and their non-RD siblings to exhibit externalizing behaviors, whereas elevations of internalizing symptomatology are restricted to individuals with RD.
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PMID:Psychiatric comorbidity in children and adolescents with reading disability. 1109 20


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