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)

Genetic manipulation of the alpha(2A)-adrenergic receptor (alpha(2A)-AR) in mice has revealed the role of this subtype in numerous responses, including agonist-induced hypotension and sedation. Unexpectedly, alpha(2)-agonist treatment of mice heterozygous for the alpha(2A)-AR (alpha(2A)-AR(+/-)) lowers blood pressure without sedation, indicating that more than 50% of alpha(2A)-AR must be activated to evoke sedation. We postulated that partial activation of alpha(2A)-AR in wild-type alpha(2A)-AR(+/+) animals could be achieved with partial agonists, agents with variable ability to couple receptor occupancy to effector activation, and might elicit one versus another pharmacological response. In vitro assays reveal that moxonidine is a partial agonist at alpha(2A)-AR. Although moxonidine was developed to preferentially interact with imidazoline binding sites, it requires the alpha(2A)-AR to lower blood pressure because we observe no hypotensive response to moxonidine in alpha(2A)-AR-null (alpha(2A)-AR(-/-)) mice. Moreover, we observe that moxonidine lowers blood pressure without sedation in wild-type mice, consistent with the above hypothesis regarding partial agonists. Our findings suggest that weak partial agonists can evoke response-selective pathways and might be exploited successfully to achieve alpha(2A)-AR pharmacotherapy where concomitant sedation is undesirable, i.e., in treatment of depression or attention deficit hyperactivity disorder, in suppression of epileptogenesis, or enhancement of cognition. Furthermore, rigorous physiological and behavioral assessment of mice heterozygous for particular receptors provides a general strategy for elucidation of pathways that might be selectively activated by partial agonists, thus achieving response-specific therapy.
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PMID:Heterozygous alpha 2A-adrenergic receptor mice unveil unique therapeutic benefits of partial agonists. 1220 90

In clinical practice many adult patients with attention deficit hyperactivity disorder (ADHD) ask for an additional psychotherapeutic intervention besides the medical therapy. In this paper we present a structured skill training program particularly tailored for adult patients with ADHD. The program is based on the principles of cognitive-behavioral treatment for borderline personality disorder developed by M. Linehan. It was modified to suit the special needs of adult patients with ADHD. In this exploratory pilot study we tested this program in a group setting. The following elements were presented: neurobiology of ADHD, mindfulness, chaos and control, behavior analysis, emotion regulation, depression, medication in ADHD, impulse control, stress management, dependency, ADHD in relationship and self respect. In an open study design patients were assessed clinically using psychometric scales (Attention Deficit Hyperactivity Disorder Checklist according to DSM-IV, 16 items of the SCL-90-R, Beck-Depression Inventory, visual analogue scale) prior to and following group therapy. This treatment resulted in positive outcomes in that patients improved on all psychometric scales.
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PMID:Psychotherapy of attention deficit hyperactivity disorder in adults--a pilot study using a structured skills training program. 1224 79

Receptor tyrosine kinases (RTKs) are membrane spanning proteins with intrinsic kinase activity. Although these receptors are known to be involved in proliferation and differentiation of cells, their roles in regulating central synaptic transmission are largely unknown. In CA1 pyramidal neurons, activation of D2 class dopamine receptors depressed excitatory transmission mediated by the NMDA subtype of glutamate receptor. This depression resulted from the quinpirole-induced release of intracellular Ca(2+) and enhanced Ca(2+)-dependent inactivation of NMDA receptors. The dopamine receptor-mediated depression was dependent on the "transactivation" of PDGFRbeta. Therefore, RTK transactivation provides a novel mechanism of communication between dopaminergic and glutamatergic systems and might help to explain how reciprocal changes in these systems could be linked to the deficits in cognition, memory, and attention observed in schizophrenia and attention deficit hyperactivity disorder.
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PMID:A D2 class dopamine receptor transactivates a receptor tyrosine kinase to inhibit NMDA receptor transmission. 1235

This community study assigned 129 4-year-olds to groups at risk for attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), both ADHD and ODD, or no problems. Mothers of children at risk for ODD reported more family dysfunction, felt less competent as parents, suggested fewer solutions to child behavior problems, demonstrated a less assertive approach to child management, and reported more child internalizing problems than did mothers of children not elevated on ODD symptoms. Mothers of children at risk for ADHD reported higher personal depression scores than did those of the non-ADHD subgroup. Children at risk for ADHD evidenced the most difficulties in school where teachers reported more social behavior, classroom management, and internalizing problems relative to other children not at risk for ADHD. When solving child management problems, mothers of children in all groups suggested twice as many controlling/negative management strategies as positive/preventive strategies. In addition, faced with oppositional and conduct problems, mothers of children in all groups increased controlling/negative suggestions and decreased positive/preventive suggestions. Mothers of girls at risk for ADHD, ODD, and ADHD/ODD gave more rewards per positive behavior than did mothers of boys.
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PMID:Preschoolers at risk for attention-deficit hyperactivity disorder and oppositional defiant disorder: family, parenting, and behavioral correlates. 1248 71

Tourette syndrome (TS) is characterised by multiple motor and one or more vocal tics. There have been no controlled studies using standardised instruments of depressive symptoms and obsessive compulsive symptomatology (OCS) in young people with TS. We completed a study of phenomenology and psychopathology in children with TS, including a controlled evaluation of the association between depressive symptoms, OCS, and TS. 57 people aged 15 or under with TS were recruited. Phenomenology and psychopathology were assessed using standardised instruments. The association between TS, depressive symptoms and obsessionality was investigated using 75 age- and gender-matched controls. There were high levels of depressive symptomatology and OCS in the TS group. Twenty-three (40 %) had carried out self-injurious behaviours and 34 (60 %) met criteria for Attention Deficit Hyperactivity Disorder (ADHD). Depressive symptoms and obsessionality were higher in the TS cohort compared with the control group; this excess persisted after adjustment for the effects of age, gender and comorbidity between depression and obsessionality. This study demonstrates high levels of psychopathology in children with TS, including ADHD, OCS and depressive symptoms. The findings illustrate the potentially complex, challenging combination of difficulties encountered by children with TS and those who care for them.
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PMID:Obsessive compulsive behaviour and depressive symptoms in young people with Tourette syndrome. A controlled study. 1254 Oct 4

The Beck Depression Inventory-II (BDI-II; Beck, Steer, & Brown, 1996) and the Conners' Adult ADHD Rating Scale-Self-Report: Screening Version (CAARS-S:SV; Conners, Erhardt, & Sparrow, 1999) were administered to 371 (64%) female and 204 (36%) male adult (> 18 years old) outpatients who were diagnosed with various psychiatric disorders to determine whether any of the 21 items or subsets of items in the BDI-II were related to symptoms of attention deficits and hyperactivity as measured by the CAARS-S:SV DSM-IV Total ADHD Symptoms scale (attention-deficit/hyperactivity disorder [ADHD] Symptoms). Stepwise multiple-regression analyses found that the BDI-II Concentration Difficulty explained 30% of the variance in these total scores. Ratings > 1 for the BDI-II Concentration Difficulty item were discussed as being useful for ruling out possible symptoms of ADHD.
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PMID:Beck Depression Inventory-II items associated with self-reported symptoms of ADHD in adult psychiatric outpatients. 1258 68

The present study investigated the ability of the General Behavior Inventory (GBI) to discriminate between diagnostic groups using youth self-report. One hundred and ninety-seven youths ages 10-17 years presenting at a midwestern urban outpatient clinic specializing in mood disorders completed the GBI as part of the intake process. Diagnoses were determined by a structured clinical interview (K-SADS) administered by either a child and adolescent psychiatrist or a research assistant trained to a high level of interrater reliability (kappa > .85). Games-Howell post hoc tests showed that the diagnostic groups significantly differed on the GBI's 2 subscales, Depression and Hypomanic-Biphasic. Logistic regression demonstrated that the scales discriminated between bipolar and disruptive behavior disorders, unipolar and bipolar depression, and mood and disruptive behavior disorders or no diagnosis. Receiver Operating Characteristic (ROC) curves further indicated the good diagnostic efficiency of the scales. Results indicate that the GBI's subscales might aid in making traditionally difficult differential diagnoses, such as between bipolar disorder and Attention Deficit Hyperactivity Disorder (ADHD) and between unipolar and bipolar depression.
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PMID:Discriminative validity of the general behavior inventory using youth report. 1259 97

Publications of Swedish child and adolescent psychiatric out-patients have been scarce. This study is aimed to give a picture of conditions in a child and adolescent psychiatric out-patient setting by reporting five-year data from a five-year cohort of first-time visits. All first-visits, 0-18 years of age, where screened retrospectively for background factors, symptoms, diagnoses and types of treatment. Six hundred and ten patients were registered during the period. The estimated accumulated prevalence for 19-year-olds were 19,7 %. Nearly half of them were seen 1-3 times. A small group, 2,5 %, accounted for about 20 % of all consultations. No or mild psychosocial stress was registered in 37 % of the cases. A neuropsychiatric main diagnosis was found for 27 % (2,1:1, boys:girls) and depression and anxiety for 20 % [0, 5:1] of the index-cases. These findings show that 5,6 % of children applied for child and adolescent psychiatric help during a five-year period. Almost one third had a neuropsychiatric disorder. The results indicate that ADHD is one of the most common causes both among boys and girls to seek help in a child and adolescent out-patient clinic.
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PMID:Swedish child and adolescent psychiatric out-patients--a five-year cohort. 1260 62

Although responses are sometimes easy to predict, at other times responding seems highly variable, unpredictable, or even random. The inability to predict is generally attributed to ignorance of controlling variables, but this article is a review of research showing that the highest levels of behavioral variability may result from identifiable reinforcers contingent on such variability. That is, variability is an operant. Discriminative stimuli and reinforcers control it, resulting in low or high variability, depending on the contingencies. Schedule-of-reinforcement effects are orderly, and choosing to vary or repeat is lawfully governed by relative reinforcement frequencies. The operant nature of variability has important implications. For example, learning, exploring, creating, and problem solving may partly depend on it. Abnormal levels of variability, including those found in psychopathologies such as autism, depression, and attention deficit hyperactivity disorder, may be modified through reinforcement. Operant variability may also help to explain some of the unique attributes of voluntary action.
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PMID:Operant variability: evidence, functions, and theory. 1261 72

Posttraumatic stress disorder is a common cause of morbidity in children and adolescents. The disorder in youth is similar to that in adults, with high rates of psychiatric comorbidity. Children seem to be more sensitive to the effects of trauma, and early life trauma exposure may induce a complex sequence of events that leads to the development of multiple psychiatric disorders in adulthood. The state of knowledge regarding medication treatments for children and adolescents is in the earliest stages of development. There are no well-conducted, randomized clinical trials to guide practitioners. Medication may play an important role in reducing debilitating symptoms of PTSD and providing a buffer for children while they confront difficult material in therapy and may help to improve their general functioning in day-to-day life. Given the various medications with potential usefulness in PTSD, it is helpful to use a stepwise approach to treatment. As a general principal, broad-spectrum agents, such as the SSRIs, are a good first choice. The SSRIs have efficacy in treating the core symptoms of PTSD and conditions such as the anxiety disorders and depression that commonly co-occur with PTSD. These agents also improve social and occupational functioning and an individual's perception of improved quality of life [41, 45, 46]. Although the SSRIs are generally effective for a broad spectrum of problems, clinicians should systematically monitor for the persistence of symptoms that do not respond to these agents. For example, despite significant improvements in core PTSD symptoms in one study that used sertraline, little improvement was seen in patients' comorbid anxiety and depressive symptoms [41]. This finding demonstrates the value of continuous symptom monitoring and shows that residual or comorbid symptoms may require a different medication to augment effective SSRI treatment for PTSD. A reasonable approach is to begin with a broad-spectrum agent, such as an SSRI, which should target anxiety, mood, and reexperiencing symptoms. Adrenergic agents, such as clonidine, used either alone or in combination with an SSRI may be useful when symptoms of hyperarousal and impulsivity are problematic. Supplementing with a mood stabilizer may be necessary in severe affective dyscontrol. Similarly, introduction of an atypical neuroleptic agent may be necessary in cases of severe self-injurious behavior, dissociation, psychosis, or aggression. Comorbid conditions such as ADHD should be targeted with pharmacotherapy known to be effective, such as psychostimulants or newer agents such as atomoxetine. Pharmacologic treatment of PTSD in childhood is one approach to alleviating the acute and chronic symptoms of the disorder. Despite the lack of well-designed, randomized, controlled trials that support efficacy, medication can be used in a rational and safe manner. Reduction in even one disabling symptom, such as insomnia or hyperarousal, may have a positive ripple effect on a child's overall functioning. Pharmacotherapy is typically used as one component of a more comprehensive multiple modality treatment package, including psychoeducation of the parent and child, focused exposure-based psychotherapy with adjunctive family therapy when indicated, and long-term booster interventions that use an admixture of psychodynamic, cognitive-behavioral, and pharmacologic interventions.
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PMID:Pharmacologic treatment approaches for children and adolescents with posttraumatic stress disorder. 1272 11


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