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)

Women with Down's syndrome experience early onset of both menopause and Alzheimer's disease. This timing provides an opportunity to examine the influence of endogenous estrogen deficiency, indicated by age at menopause, on risk of Alzheimer's disease. A community-based sample of 163 postmenopausal women with Down's syndrome, 40 to 60 years of age, was ascertained through the New York State Developmental Disability service system. Information from cognitive assessments, medical record review, neurological evaluation, and caregiver interviews was used to establish ages for onset of menopause and dementia. We used survival and multivariate regression analyses to determine the relation of age at menopause to age at onset of Alzheimer's disease, adjusting for age, level of mental retardation, body mass index, and history of hypothyroidism or depression. Women with early onset of menopause (46 years or younger) had earlier onset and increased risk of Alzheimer's disease (AD) compared with women with onset of menopause after 46 years (rate ratio, 2.7; 95% confidence interval [CI], 1.2-5.9). Demented women had higher mean serum sex hormone binding globulin levels than nondemented women (86.4 vs 56.6 nmol/L, p = 0.02), but similar levels of total estradiol, suggesting that bioavailable estradiol, rather than total estradiol, is associated with dementia. Our findings support the hypothesis that reductions in estrogens after menopause contribute to the cascade of pathological processes leading to AD.
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PMID:Onset of dementia is associated with age at menopause in women with Down's syndrome. 1452 Jun 53

A review of the literature revealed that there was no adequate assessment instrument available that screens comprehensively for anxiety and depression in persons with mental retardation. The purpose of this research was to develop the Anxiety, Depression, and Mood Scale (ADAMS), an instrument intended to fill this gap. We developed a preliminary rating scale that included 55 symptom items. We examined the factor structure of these items by an exploratory factor analysis of behavior ratings on 265 individuals. A five-factor solution emerged that was both statistically sound and clinically meaningful. These factors were labeled "Manic/Hyperactive Behavior," "Depressed Mood," "Social Avoidance," "General Anxiety" and "Compulsive Behavior." We validated this solution by conducting a confirmatory factor analysis on ratings of 268 additional individuals. Model fit was acceptable. Internal consistency of the subscales and retest reliability for both the total scale and the subscales was high. Interrater reliability was satisfactory. The validity of the ADAMS was assessed with a clinical sample of 129 individuals with mental retardation who were seen in a psychiatric clinic; this provided additional support for the subscales. The ADAMS appears to be a psychometrically sound instrument for screening anxiety, depression and mood disorders among individuals with mental retardation.
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PMID:Reliability and validity of an assessment instrument for anxiety, depression, and mood among individuals with mental retardation. 1471 31

Differences in depression between Puerto Rican and non-Latina White mothers providing care to their adult child with mental retardation were examined. The focus of this study is on how family problems may mediate the effect of the adult's behavior problems on the mother's level of depressive symptoms and how this process differs across the two groups of mothers. As hypothesized, family problems was a stronger predictor of depressive symptoms for Puerto Rican mothers than for non-Latina White mothers. In addition, Puerto Rican mothers were in poorer physical health, which further accounted for differences in depression between the two groups.
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PMID:Cultural context of caregiving: differences in depression between Puerto Rican and non-Latina White mothers of adults with mental retardation. 1472 97

This paper will argue that suicidal ideation and suicidal gestures are evident in adults with mental retardation, including individuals not receiving mental health services currently, and that psychosocial correlates of suicidality are similar to those noted in the general population. Findings are based on structured interviews with 98 adults with mental retardation, with corroborative information from caregivers and clinical charts. One in three individuals reported that they think "life is not worth living" sometimes or a lot. Eleven percent of individuals reported previous suicide attempt(s). Twenty-three percent of informants were unaware of the current suicidal ideation that their family member/client was reporting. Individuals reporting suicidal ideation endorsed more loneliness, stress, anxiety and depression, along with less social support than other individuals, consistent with reports of suicidal individuals in the general population. Adults with mental retardation who report thinking that life is not worth living should be a target group for future suicide prevention efforts. More research is needed to better understand the risk factors and protective factors for suicidality in this population.
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PMID:Suicidality in a clinical and community sample of adults with mental retardation. 1513 90

We have identified truncating mutations in the human DLG3 (neuroendocrine dlg) gene in 4 of 329 families with moderate to severe X-linked mental retardation. DLG3 encodes synapse-associated protein 102 (SAP102), a member of the membrane-associated guanylate kinase protein family. Neuronal SAP102 is expressed during early brain development and is localized to the postsynaptic density of excitatory synapses. It is composed of three amino-terminal PDZ domains, an src homology domain, and a carboxyl-terminal guanylate kinase domain. The PDZ domains interact directly with the NR2 subunits of the NMDA glutamate receptor and with other proteins responsible for NMDA receptor localization, immobilization, and signaling. The mutations identified in this study all introduce premature stop codons within or before the third PDZ domain, and it is likely that this impairs the ability of SAP102 to interact with the NMDA receptor and/or other proteins involved in downstream NMDA receptor signaling pathways. NMDA receptors have been implicated in the induction of certain forms of synaptic plasticity, such as long-term potentiation and long-term depression, and these changes in synaptic efficacy have been proposed as neural mechanisms underlying memory and learning. The disruption of NMDA receptor targeting or signaling, as a result of the loss of SAP102, may lead to altered synaptic plasticity and may explain the intellectual impairment observed in individuals with DLG3 mutations.
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PMID:Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation. 1518 69

Many of the diverse functional consequences of activating group 1 metabotropic glutamate receptors require translation of pre-existing mRNA near synapses. One of these consequences is long-term depression (LTD) of transmission at hippocampal synapses. Loss of fragile X mental retardation protein (FMRP), the defect responsible for fragile X syndrome in humans, increases LTD in mouse hippocampus. This finding is consistent with the growing evidence that FMRP normally functions as a repressor of translation of specific mRNAs. Here we present a theory that can account for diverse neurological and psychiatric aspects of fragile X syndrome, based on the assumption that many of the protein-synthesis-dependent functions of metabotropic receptors are exaggerated in fragile X syndrome. The theory suggests new directions for basic research as well as novel therapeutic approaches for the treatment of humans with fragile X, the most frequent inherited cause of mental retardation and an identified cause of autism.
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PMID:The mGluR theory of fragile X mental retardation. 1521 35

Fragile X syndrome is the leading inherited form of mental retardation, and second only to Down's syndrome as a cause of mental retardation attributable to an identifiable genetic abnormality. Fragile X syndrome is caused by a defect in the fragile X mental retardation 1 gene (FMR1), located near the end of the long arm of the X chromosome. FMR1 normally synthesises the fragile X protein (FMRP), but mutations in FMR1 lead to a lack of FMRP synthesis, resulting in fragile X syndrome. While the specific function of FMRP is not yet fully understood, the protein is known to be important for normal brain development. The physical, cognitive and behavioural features of individuals with fragile X syndrome depend on gender (females have two X chromosomes, one active and one inactive) and the molecular status of the mutation (premutation, full mutation or mosaic). Features of the behavioural profile of individuals with fragile X syndrome include hypersensitivity to stimuli, overarousability, inattention, hyperactivity and (mostly in men) explosive and aggressive behaviour to others or self. Social anxiety, other anxiety disorders, depression, impulse control disorder and mood disorders are the most common psychiatric disorders diagnosed in individuals with fragile X syndrome, although no formal studies have been undertaken. There have been very few psychopharmacological studies of the treatment of behaviours associated with fragile X syndrome. These limited studies and surveys of psychotropic drugs used in individuals with fragile X syndrome suggest that stimulants are helpful for hyperactivity, that alpha(2)-adrenoceptor agonists and beta-adrenoceptor antagonists help to control overarousability, impulsivity and aggressiveness, and that SSRIs can control anxiety, impulsivity and irritability, alleviate depressive symptoms and decrease aggressive and self-injurious behaviour. Typical and atypical antipsychotics in combination with other psychotropics have been used for control of psychotic disorders and severe aggressive behaviours. Mood stabilisers have been found to be useful when mood dysregulation or mood disorders are present with or without aggressive behaviour. Folic acid and L-acetylcarnitine (levacecarnine) have not been found to improve deficits or behaviours. As there is no specific psychotropic drug for any of the deficits or behaviours associated with fragile X syndrome, clinicians are advised to diagnose any psychiatric syndromes or disorders present and treat them with the appropriate psychotropic drug. If no psychiatric disorder can be diagnosed and the patient's challenging behaviours cannot be controlled with environmental manipulation or behaviour modification techniques, the most benign psychotropic drug should be used. Antipsychotics should be reserved for psychotic disorders, for impulse control disorders (used in combination with other psychotropics), or when challenging behaviours constitute an emergency. In the future, new medications targeting molecules implicated in the modulation of anxiety, fear and fear responding will be useful for treating the social anxiety and overarousability exhibited by individuals with fragile X syndrome.
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PMID:Neuropsychiatric symptoms of fragile X syndrome: pathophysiology and pharmacotherapy. 1533 Jun 85

The aim of this research was to study the psychological effects of disorders such as schizophrenia and depression associated with mental retardation. The Rorschach Inkblot Test and the Wechsler Adult Intelligence Scale were administered to a group of 97 subjects (52 women and 45 men) ages 15:10 yr. to 36:6 yr. (M=21:5, SD=5:3). The subjects were divided into four subgroups according to the presence or absence of mental retardation and psychiatric diagnosis (schizophrenia versus depression). The quality of the perception in Rorschach responses and the ErlebnisTypus scores differentiated psychotic and depressed subjects well. These disorders, when associated with mental retardation, make impairment of perceptual performance worse. The interaction between Axis I mental disorders (according to DSM-IV diagnosis) and mental retardation, an Axis II disorder, is discussed.
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PMID:Psychopathology and mental retardation: a study using the Rorschach Inkblot Test. 1536 10

In an attempt to dissect classical and operant conditioning in Drosophila melanogaster, we have isolated the gene for ribosomal S6 kinase II (S6KII). This enzyme is part of a family of serine-threonine kinases that in mammals have been implicated in the MAPK (mitogen-activated protein kinase) signaling cascade controlling (among other processes) synaptic plasticity (long-term potentiation/long-term depression) and memory formation. The human homolog rsk2 has been linked to mental retardation (Coffin-Lowry syndrome). Mutant analysis in Drosophila shows that S6KII serves different functions in operant place learning and classical (pavlovian) olfactory conditioning. Whereas in the null mutant only pavlovian olfactory learning is affected, a P-element insertion mutant reducing the amount of S6KII only affects operant place learning. A mutant lacking part of the N-terminal kinase domain and performing poorly in both learning tasks is dominant in the operant paradigm and recessive in the pavlovian paradigm. The behavioral defects in the pavlovian task can be rescued by the genomic S6KII transgene. Overexpression of S6KII in wild type has a dominant-negative effect on the operant task that is rescued by the null mutant, whereas in the pavlovian task overexpression may even enhance learning performance.
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PMID:The S6KII (rsk) gene of Drosophila melanogaster differentially affects an operant and a classical learning task. 1552 59

The neurologic dysfunction underlying epilepsy can predispose patients to psychiatric disorders, and the incidence of both depression and psychosis is increased in people with epilepsy. Depressive disorders are the most frequently recognized psychiatric comorbidities in people with epilepsy, but depression in children can be particularly difficult to recognize. Clinicians need to inquire about not only classic symptoms of depression such as anhedonia but also less obvious symptoms such as unprovoked irritability, unsubstantiated complaints of lack of love from family members, somatic complaints, and problems with concentration and poor school performance. The diagnosis of depressive disorders in children with epilepsy and mental retardation is even more difficult. Physicians need to be alert for the presence of iatrogenic depression, which may result from antiepileptic drugs or epilepsy surgery. People with epilepsy are also at increased risk for psychosis, which can be interictal, postictal, or (rarely) an expression of ictal activity. This psychosis can be related to seizure remission (ie, alternative psychosis) or iatrogenic (eg, related to antiepileptic drugs or following temporal lobectomy). Although both antidepressants and antipsychotic drugs have the potential to lower the seizure threshold and increase seizures, careful drug selection, dosing, and slow titration can minimize this risk, allowing treatment to proceed.
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PMID:Diagnosis and management of depression and psychosis in children and adolescents with epilepsy. 1552 62


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