Abstract:
BACKGROUND:Recent genome-wide association studies have identified genetic loci that jointly make a considerable contribution to risk of developing Alzheimer's disease (AD). Because neuropathological features of AD can be present several decades before disease onset, we investigated whether effects of polygenic risk are detectable by neuroimaging in young adults. We hypothesized that higher polygenic risk scores (PRSs) for AD would be associated with reduced volume of the hippocampus and other limbic and paralimbic areas. We further hypothesized that AD PRSs would affect the microstructure of fiber tracts connecting the hippocampus with other brain areas. METHODS:We analyzed the association between AD PRSs and brain imaging parameters using T1-weighted structural (n = 272) and diffusion-weighted scans (n = 197). RESULTS:We found a significant association between AD PRSs and left hippocampal volume, with higher risk associated with lower left hippocampal volume (p = .001). This effect remained when the APOE gene was excluded (p = .031), suggesting that the relationship between hippocampal volume and AD is the result of multiple genetic factors and not exclusively variability in the APOE gene. The diffusion tensor imaging analysis revealed that fractional anisotropy of the right cingulum was inversely correlated with AD PRSs (p = .009). We thus show that polygenic effects of AD risk variants on brain structure can already be detected in young adults. CONCLUSIONS:This finding paves the way for further investigation of the effects of AD risk variants and may become useful for efforts to combine genotypic and phenotypic data for risk prediction and to enrich future prevention trials of AD.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Foley SF,Tansey KE,Caseras X,Lancaster T,Bracht T,Parker G,Hall J,Williams J,Linden DEdoi
10.1016/j.biopsych.2016.02.033subject
Has Abstractpub_date
2017-01-15 00:00:00pages
154-161issue
2eissn
0006-3223issn
1873-2402pii
S0006-3223(16)31114-3journal_volume
81pub_type
杂志文章abstract::Cocaine can cause a variety of neuropsychiatric and neurobehavioral complications; however, it is uncertain whether cocaine causes persistent cerebral structural and neurochemical abnormalities in asymptomatic users. We studied 52 African-American men (26 human immunodeficiency virus-negative asymptomatic heavy cocain...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/s0006-3223(97)00135-2
更新日期:1997-12-15 00:00:00
abstract:BACKGROUND:Difficulty with impulse control is heightened in children with a family history of alcohol use disorders and is a risk factor for later substance problems. Cross-sectional functional magnetic resonance imaging studies have shown altered impulse control processing in adolescents with a positive family history...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2014.03.005
更新日期:2014-11-01 00:00:00
abstract::Extensive work in the field has indicated a state-dependent hyperactivity of the hypothalamic-pituitary-adrenocortical (HYPAC) functions and unresponsiveness to dexamethasone suppression in at least 50% of patients suffering from endogenous depression. In this study, elderly outpatients, 60-85 years of age, suffering ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract:BACKGROUND:There is increasing evidence for an association between alterations of brain glutamatergic neurotransmission and the pathophysiology of affective disorders. METHODS:We studied the association between cerebrospinal fluid (CSF) metabolites, including glutamine, in unipolar and bipolar depressed patients versu...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(99)00284-x
更新日期:2000-04-01 00:00:00
abstract::We have investigated the dexamethasone suppression of cortisol release in a group of 28 patients with senile dementia of the Alzheimer type (SDAT) after stimulation by physostigmine and clonidine, as compared with basal conditions. All patients but one had previously been evaluated with a depression symptom checklist ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(88)90102-3
更新日期:1988-01-01 00:00:00
abstract::This study shows that chronic, long-hospitalized schizophrenics perform (tested by the Famous Events Questionnaire) at a higher level on remote memory than they do on word list recall. A post hoc, matched-tasks check suggested that this finding was not due to differences in the discriminating power of the tasks. Relat...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(87)90133-8
更新日期:1987-01-01 00:00:00
abstract::The ability of beta-adrenergic receptors to adapt to reductions in stimulation might be impaired in depressed or schizophrenic patients. To test this hypothesis 12 normal controls, 12 depressed patients resistant to tricyclic antidepressants, and 8 chronic schizophrenic patients were treated with propranolol 160 mg/da...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
abstract::"Dale's Principle" states that each neuron releases one and only one synaptic transmitter. Mental disorders and behavioral drug effects are attributed to activation or blockade of one or more of these specific transmitters. A series of biochemical, electrophysiological, and behavioral studies suggests the alternative ...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:
更新日期:1976-08-01 00:00:00
abstract:BACKGROUND:Considering that platelets have been established to be good peripheral markers for the study of catecholaminergic neurons, we have applied an assay to measure the uptake of (3H)-dopamine (DA) into platelet storage granules (PSG). Recently, we reported that Tourette's syndrome (TS) patients (pts) show decreas...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(97)00476-9
更新日期:1998-12-01 00:00:00
abstract:BACKGROUND:Hyperactivity of the anterior cingulate cortex (ACC) in patients with obsessive-compulsive disorder (OCD) has been shown to increase with symptom provocation and to normalize with treatment-induced symptom reduction. Although the functional significance of anterior cingulate involvement in OCD remains unknow...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2004.10.038
更新日期:2005-02-01 00:00:00
abstract:BACKGROUND:Thalamic abnormalities resulting in impaired attention and information processing may form a foundation for cognitive and perceptual disturbances in schizophrenia. Measurements of the thalamus in patients with schizophrenia have shown reductions relative to normal comparison subjects. METHODS:In the current...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(97)00459-9
更新日期:1999-05-15 00:00:00
abstract:BACKGROUND:Inositol has been reported to be an effective treatment in depression, and we hypothesized that inositol addition might enhance or speed up response to serotonin selective reuptake inhibitors (SSRI). METHODS:Twenty-seven depressed patients completed a double-blind controlled 4-week trial of SSRI plus placeb...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0006-3223(98)00145-0
更新日期:1999-02-01 00:00:00
abstract::In a sample of 13 endogenous depressive inpatients, REM (rapid eye movement) latency (recorded over 4 consecutive nights after 2 habituation nights) and contingent negative variation amplitude showed significant relationship, suggesting that both parameters may depend on the same mechanisms, possibly cholinergic. ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(85)90115-5
更新日期:1985-12-01 00:00:00
abstract::Determinations of albumin and immunoglobulin G (IgG) were performed in paired cerebrospinal fluid (CSF) and serum samples from 24 subjects with schizophrenia. These determinations allowed calculation of two indices, one that is an indicator of integrity of the blood-brain barrier and the other a measure of selective I...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(85)90002-2
更新日期:1985-10-01 00:00:00
abstract:BACKGROUND:Comparing prefrontal cortical activity during particular phases of working memory in healthy subjects and individuals diagnosed with schizophrenia might help to define the phase-specific deficits in cortical function that contribute to cognitive impairments associated with schizophrenia. This study featured ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2008.07.029
更新日期:2008-12-15 00:00:00
abstract::Associations between cannabis use and psychotic outcomes are consistently reported, but establishing causality from observational designs can be problematic. We review the evidence from longitudinal studies that have examined this relationship and discuss the epidemiologic evidence for and against interpreting the fin...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.biopsych.2015.08.001
更新日期:2016-04-01 00:00:00
abstract::A group of 759 patients with final DSM-I and -II diagnoses of schizophrenia was identified among a cohort of 1494 adults who were hospitalized between 1965 and 1972. Admission EEG recordings were done in each patient during waking, activation procedures, drowsiness, and sleep. All cases were reclassified according to ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1984-04-01 00:00:00
abstract:BACKGROUND:Despite cognitive function impairment in depression, its relationship to treatment outcome is not well understood. Here, we examined whether pretreatment activation of cortical circuitry during test of cognitive functions predicts outcomes for three commonly used antidepressants. METHODS:Eighty medication-f...
journal_title:Biological psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.biopsych.2015.02.037
更新日期:2016-02-15 00:00:00
abstract::Smooth pursuit eye movements (SPEM) for two stimulus velocities (sinusoidal and triangular) were studied by visual inspection in 12 unmedicated RDC-diagnosed schizophrenic patients and in 13 matched controls. SPEM was worse in the patient group and their performance deteriorated with repeated presentations of the task...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract:BACKGROUND:Regional brain perfusion in patients during alcohol-withdrawal has been relatively less studied with brain SPECT technique. In this study, the hypothesis that possible regional cerebral blood flow (rCBF) alterations due to alcohol withdrawal might be transitory in a homogenous group of alcoholic patients in ...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/s0006-3223(97)00322-3
更新日期:1998-06-15 00:00:00
abstract::Evidence is presented for the occurrence of a locus for schizotaxia on the short arm of chromosome 6. This derives from study of 63 informative members of seven pedigrees in which the proband and a parent (or a sib of parent) suffered with schizophrenia and other kin were either normal or fell within a spectrum of con...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1979-02-01 00:00:00
abstract::Over the past 20 years, converging lines of evidence have both linked glutamatergic dysfunction to the pathophysiology of depression and demonstrated that the glutamatergic synapse presents multiple targets for developing novel antidepressants. The robust antidepressant effects of the N-methyl-D-aspartate receptor ant...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.biopsych.2013.01.021
更新日期:2013-06-15 00:00:00
abstract:BACKGROUND:Fear learning in stressful situations is highly adaptive for survival by steering behavior in subsequent situations, but fear learning can become disproportionate in vulnerable individuals. Despite the potential clinical significance, the mechanism by which stress modulates fear learning is poorly understood...
journal_title:Biological psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.biopsych.2015.02.014
更新日期:2015-12-15 00:00:00
abstract:BACKGROUND:Recent reports suggest that gamma-glutamyl transferase (GGT) decreases with coffee intake. The aim of this study was to examine the joint influence of alcohol, tobacco, cotinine, coffee, and caffeine on biological markers of heavy drinking in an alcoholic population. METHODS:Subjects were 160 alcohol-depend...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/s0006-3223(97)00438-1
更新日期:1998-10-01 00:00:00
abstract::Depersonalization and other behavioral and physiological indices were monitored before and after the administration of high- and low-potency marijuana cigarettes and a placebo cigarette in 35 physically and mentally healthy normal volunteers. The cigarettes were administered under double-blind conditions during three ...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0006-3223(93)90171-9
更新日期:1993-03-15 00:00:00
abstract::Methysergide a clinically used blocker of serotonin receptors, was given for 48 hr to 11 normal adults, at a dose of 8 mg per 24 hr. Total REM sleep time was decreased, although total sleep time was unchanged. Stage 4 decreased and stage 3 increased, while total slow wave sleep remained constant. There was a tendency ...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:
更新日期:1975-08-01 00:00:00
abstract::Probenecid is used to block the transport of acid monoamine metabolites from cerebrospinal fluid (CSF), on the assumption that the resultant rise in CSF concentrations of the metabolites will reflect presynaptic "turnover" of the parent monoamine. However, CSF levels of probenecid correlate with CSF levels of the meta...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:
更新日期:1983-11-01 00:00:00
abstract::IgA antibody levels in serum were examined in two groups of schizophrenic patients. All were diagnosed according to DSM-III-R criteria. One group of 36 males and 12 females were compared to historical controls. The other group consisted of 13 males off drugs for at least 3 months; these were compared with age- and sex...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(94)00176-4
更新日期:1995-03-15 00:00:00
abstract::Twenty-three inpatients who met DSM-III criteria for schizophrenia were selected for cerebrospinal fluid (CSF) neurochemical study of tardive dyskinesia (TD). Ten inpatients had tardive dyskinesia, and the remaining 13 patients without TD served as controls. There were no intergroup differences in sex, age, duration o...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(89)90243-6
更新日期:1989-03-15 00:00:00
abstract:BACKGROUND:Accurate recognition of facial expressions is crucial for social functioning. In depressed individuals, implicit and explicit attentional biases away from happy and toward sad stimuli have been demonstrated. These may be associated with the negative cognitions in these individuals. METHODS:Using event-relat...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2004.10.028
更新日期:2005-02-01 00:00:00