Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ADHD is a polygenic disorder due to the additive effect of genes affecting dopamine, norepinephrine, serotonin, GABA, and other neurotransmitters. Some of the specific loci involved are dopamine genes--DRD2, DRD4, DRD5, and the dopamine transporter; norepinephrine (NE) and epinephrine (EPI) genes--dopamine beta-hydroxylase, ADRA2A, ADRA2C, PNMT, norepinephrine transporter, MAOA, COMT; serotonin genes--TDO2, HTR1A, HTR1DA, serotonin transporter; GABA genes--GABRB3; androgen receptor and other genes. This model is consistent with all of the present knowledge about ADHD including (a) the increased frequency of ADHD in the relatives of ADHD probands, (b) the presence of a wide spectrum of comorbid behaviors (depression, anxiety, learning, conduct, oppositional-defiant, conduct and substance abuse disorders) in ADHD probands and their relatives on both parental sides, (c) the close relationship to Tourette syndrome (TS), (d) the failure to find the genes for TS using linkage analysis, (e) the brain imaging studies showing hypometabolism of the frontal lobes, (f) the relationship between dopamine D2 receptor density and regional blood flow, (g) the correlation between tics and dopamine D2 receptor density in TS, (h) the motor hyperactivity of dopamine transporter and dopamine D3 receptor gene knockout mice, (i) the LeMoal and Shaywitz dopamine deficiency animal models of ADHD, (j) the NE models of ADHD, (k) the failure to explain ADHD on the basis of any single neurotransmitter defect, (l) the response of ADHD to dopamine and alpha 2-adrenergic agonists, (m) the small percentage of the variance of specific behaviors accounted for by each gene, and numerous other aspects of ADHD. The implications of the polygenic model for the understanding, diagnosis and treatment of ADHD and TS, as well as other psychiatric disorders, are reviewed.
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PMID:Clinical and molecular genetics of ADHD and Tourette syndrome. Two related polygenic disorders. 1146 57

Adults with attention deficit hyperactivity disorder (ADHD; n = 104) were compared with a control group (n = 64) on time estimation and reproduction tasks. Results were unaffected by ADHD subtype or gender. The ADHD group provided larger time estimations than the control group, particularly at long intervals. This became nonsignificant after controlling for IQ. The ADHD group made shorter reproductions than did the control group (15- and 60-s intervals) and greater reproduction errors (12-, 45-, 60-s durations). These differences remained after controlling for IQ and comorbid oppositional defiant disorder, depression, and anxiety. Only the level of anxiety contributed to errors (at 12-s duration) beyond the level of ADHD. Results extended findings on time perception in ADHD children to adults and ruled out comorbidity as the basis of the errors.
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PMID:Time perception and reproduction in young adults with attention deficit hyperactivity disorder. 1149 90

The need for empirical, objective, clear, and practical outcome measures for therapy has long been recognized by clinicians and researchers. Pragmatic tools for objective determination of the efficacy of therapy have been scarce in clinical practice settings. Heart rate variability (HRV) is increasing in popularity for use in clinical settings as a measure of treatment success. Since HRV is stable and placebo-free, it has the potential to meet this need. Thirty-nine cases are presented from the clinical practices of the authors and three other clinicians where HRV was used as an outcome measure for Thought Field Therapy (TFT). The cases included TFT treatments which addressed a wide variety of problems including phobias, anxiety, trauma, depression, fatigue, attention deficit hyperactivity disorder, learning difficulties, compulsions, obsessions, eating disorders, anger, and physical pain. A lowering of subjective units of distress was in most cases related to an improvement in HRV.
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PMID:Heart rate variability as an outcome measure for Thought Field Therapy in clinical practice. 1152 7

We report about a five year-old patient suffering from tics and ADHD (attention deficit hyperkinetic disorder), aggressions, depression and emotional disorder. Furthermore, an epileptic focus and perinatal encephalopathy were diagnosed. Lofexidine (Britlofex) medication did not reduce Tic symptomatology, but showed remarkable sedative effects. Family therapy and Clonidine (Catapressan) medication reduced symptomatology significantly.
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PMID:[Therapy of tic disorders apparently of organic origin in a multi-morbid 5-year-old patient with lofexidine (Britlofex) and clonidine (Catapressan)]. 1158 98

The use of DSM-IV based questionnaires in child psychopathology is on the increase. The internal construct validity of a DSM-IV based model of ADHD, CD, ODD, Generalised Anxiety, and Depression was investigated in 11 samples by confirmatory factor analysis. The factorial structure of these syndrome dimensions was supported by the data. However, the model did not meet absolute standards of good model fit. Two sources of error are discussed in detail: multidimensionality of syndrome scales, and the presence of many symptoms that are diagnostically ambiguous with regard to the targeted syndrome dimension. It is argued that measurement precision may be increased by more careful operationalisation of the symptoms in the questionnaire. Additional approaches towards improved conceptualisation of DSM-IV are briefly discussed. A sharper DSM-IV model may improve the accuracy of inferences based on scale scores and provide more precise research findings with regard to relations with variables external to the taxonomy.
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PMID:DSM-IV internal construct validity: when a taxonomy meets data. 1158 54

A retrospective record review of one year of admissions to a residential adolescent substance abuse treatment program (N = 91) examined the prevalence of comorbid psychiatric disorders and factors associated with successful treatment participation. Psychiatric and substance use disorders (SUD) were diagnosed by DSM-IV criteria. Successful participation was based on multiple factors assessed by the treatment team. Consistent with prior studies, there was considerable comorbidity (63.7%) with both disruptive (Attention Deficit Hyperactivity Disorder [ADHD], 11%; Conduct Disorder [CD], 24%) and other disorders (depression, 24%; adjustment disorder, 7.7%; bipolar disorder, 3.3%). Male gender was negatively associated (OR = 0.23, P = 0.019) with successful participation in univariate analyses, as was ADHD (OR = 0.18, P = 0.007). CD (OR = 0.37, P = 0.053) approached significance. Multivariate analysis reveals ADHD was significant while having CD and being male approached significance. Psychotropic medication use and other diagnoses were not associated with successful participation. It is concluded that further research on the relationship between ADHD, CD, and substance abuse treatment is needed.
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PMID:Dual diagnosis and successful participation of adolescents in substance abuse treatment. 1172 90

Clinic-referred teens (ages 12-19) with ADHD and ODD (N = 101) were compared to community control (CC) teens, equated for age and sex, (N = 39) on a variety of psychological tasks assessing executive functioning (EF), temporal reward discounting, and time estimation and reproduction. A factor analysis reduced the EF measures to three dimensions, representing CPF Inattention, Working Memory, and CPT Inhibition. Results indicated that the ADHD group had significantly more CPT Inattention than the CC group. No differences were found for Working Memory or CPT Inhibition. The ADHD group displayed significantly greater temporal discounting of delayed hypothetical monetary rewards relative to immediate ones and manifested more impaired time reproduction, but not time estimation, than did the CC group. Main effects for level of IQ were found only on the Working Memory factor and largely did not interact with the group factor otherwise. The group differences in CPT Inattention, temporal discounting, and time reproduction were not a function of level of comorbid oppositional defiant disorder, delinquency, or anxiety-depression. Results are reasonably consistent with past research on EF and sense of time in children with ADHD and extend these findings to the adolescent age group. Problems with working memory and CPT inhibition found in prior studies of children with ADHD, however, were not evident here, perhaps owing to age-related improvements or insufficient task difficulty.
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PMID:Executive functioning, temporal discounting, and sense of time in adolescents with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). 1176 Dec 87

Antipsychotic drugs are used to treat a wide variety of child psychiatric disorders characterized by psychotic symptoms, aggression, excitement, tics, stereotypies and hyperactivity nonresponsive to other therapies. Unfortunately, typical antipsychotics have many adverse effects limiting their long-term use. Novel antipsychotics with combined dopaminergic and serotonergic action, such as risperidone, appear to offer better safety and efficacy profiles in controlled studies of adult patients, and therefore appeared as promising pharmacotherapeutic agents in child psychiatry. The purpose of this retrospective chart review was to obtain data on the potential effectiveness and tolerability of risperidone in children and adolescents presenting with a variety of chronic and severe psychiatric disorders who had been unresponsive to previous pharmacological treatments. Charts for 106 children and adolescents (males n = 81 or 76.4%; females n = 25 or 23.6%), presenting with attention deficit and/or hyperactivity disorder (n = 49 or 46.2%), conduct disorder (n = 13 or 12.3%), oppositional-defiant disorder (n = 5 or 4.7%), behavioural problems not otherwise specified (n = 2 or 1.9%), autism (n = 8 or 7.5%), Asperger's syndrome (n = 8 or 7.5%), pervasive developmental disorder (PDD) not otherwise specified (n = 4 or 3.8%), anxiety (n = 6 or 5.7%), depression (n = 2 or 1.9%), dysthymia (n = 2 or 1.9%), schizophrenia (n = 4 or 3.8%), adjustment disorder (n = 1 or 0.9%) and obsessive-compulsive disorder (n = 2 or 1.9%) were reviewed retrospectively to determine the tolerability and potential efficacy of risperidone treatment for a variety of psychiatric disorders. Six subjects also presented with mental retardation. The average length of illness prior to risperidone treatment was 5 years and the average age of risperidone treatment onset was 11 years. The mean daily dose of risperidone was 1.2 mg (range = 0.25 to 8.0 mg). Very few adverse effects were reported. The average length of risperidone treatment was 11 months with the majority (n = 75 or 76%) of patients maintained on risperidone following study termination. Seven cases (6.6%) were missing follow-up data. The majority (n = 78 or 74%) of patients were taking concurrent psychiatric medications, most commonly stimulants for the treatment of ADHD. Clinical global improvements for children and adolescents at the final study visit were marked (n = .37 or 34.9%), moderate (n = .40 or 37.7%), mild (n = 13 or 12.4%), none (n = 12 or 11.3%), or worse (n = 1 or 1%). Three cases (2.9%) were missing clinical improvement data. Results suggest that risperidone may be useful for managing behavioural disturbances and psychotic symptoms associated with a wide variety of childhood psychiatric disorders. For most patients in the study, a combination of risperidone and adjunctive pharmacotherapy was beneficial. Controlled and discontinuation studies of risperidone treatment in children and adolescents with behavioural and psychotic disorders are recommended.
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PMID:A retrospective chart review of risperidone use in treatment-resistant children and adolescents with psychiatric disorders. 1181 3

Histamine H(3) receptor antagonists have been proposed as potentially useful therapeutic agents for the treatment of several disorders including attention deficit, schizophrenia, depression, and Alzheimer's disease. We have developed a repeated acquisition version of an inhibitory avoidance task using spontaneously hypertensive rat (SHR) pups that we believe provides a reproducible measure of the cognitive and attention deficits often characteristic of these disease states, and evaluated two H(3) receptor antagonists. Male SHR, Wistar (WI) and Wistar Kyoto (WKY) rat pups (20--24 days old) were trained to avoid a mild footshock (0.1 mA, 1 s duration), delivered when the pup had transferred from a brightly lit to a darkened compartment. After the first trial, the pup was removed and returned to its home cage. One minute later, the same pup was replaced in the brightly-lit compartment and the training process repeated. A total of five trials were recorded. SHR pups performed significantly more poorly than WI or WKY pups using this training schedule, and SHR pups were used for all subsequent studies. Methylphenidate and ABT-418, both clinically active in attention deficit hyperactivity disorder (ADHD), were tested to validate the model. Methylphenidate (1 and 3 mg/kg s.c.) and ABT-418 (0.03 mg/kg s.c.) significantly improved SHR pup performance. The H(3) receptor antagonists GT-2331 (1 mg/kg s.c.) and ciproxifan (3 mg/kg s.c.), also significantly, and in a dose-related manner, enhanced performance of the SHR pups. (R)-alpha-methylhistamine (3 mg/kg s.c.) blocked the pro-cognitive effects of ciproxifan, suggesting an H(3) receptor site of action for this compound. This model is useful for evaluating the cognition/attention-enhancing potential of H(3) receptor antagonists.
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PMID:Effects of histamine H(3) receptor ligands GT-2331 and ciproxifan in a repeated acquisition avoidance response in the spontaneously hypertensive rat pup. 1184 82

Compared 2 groups of children with attention deficit hyperactivity disorder, predominantly inattentive type (ADHD/IA)--those with high scores on a composite measure of sluggish cognitive tempo (SCT) and those without--using a large, school-based sample of children for which previous comparisons between ADHD subtypes have been reported. Although the 2 groups did not differ on level of attention or learning problems, high-SCT ADHD/IA children were rated by teachers as showing less externalizing behavior and higher levels of unhappiness, anxiety/depression, withdrawn behavior, and social dysfunction. Thus, SCT identifies a more homogeneous subgroup of ADHD/IA children who are, relative to the entire Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association [APA], 1994) diagnosed ADHD/IA group, more similar to those classified in previous research as "attention deficit disorder without hyperactivity." These results support a reconsideration of SCT symptoms as a component of diagnostic criteria for a category of nonhyperactive attention deficit disorder.
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PMID:Sluggish cognitive tempo predicts a different pattern of impairment in the attention deficit hyperactivity disorder, predominantly inattentive type. 1184 44


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