Abstract:
BACKGOUND:Alcohol use disorder (AUD) is devastating and poorly treated, and innovative targets are actively sought for prevention and treatment. The orphan G protein-coupled receptor GPR88 is enriched in mesocorticolimbic pathways, and Gpr88 knockout mice show hyperactivity and risk-taking behavior, but a potential role for this receptor in drug abuse has not been examined. METHODS:We tested Gpr88 knockout mice for alcohol-drinking and -seeking behaviors. To gain system-level understanding of their alcohol endophenotype, we also analyzed whole-brain functional connectivity in naïve mice using resting-state functional magnetic resonance imaging. RESULTS:Gpr88 knockout mice showed increased voluntary alcohol drinking at both moderate and excessive levels, with intact alcohol sedation and metabolism. Mutant mice also showed increased operant responding and motivation for alcohol, while food and chocolate operant self-administration were unchanged. Alcohol place conditioning and alcohol-induced dopamine release in the nucleus accumbens were decreased, suggesting reduced alcohol reward in mutant mice that may partly explain enhanced alcohol drinking. Seed-based voxelwise functional connectivity analysis revealed significant remodeling of mesocorticolimbic centers, whose hallmark was predominant weakening of prefrontal cortex, ventral tegmental area, and amygdala connectional patterns. Also, effective connectivity from the ventral tegmental area to the nucleus accumbens and amygdala was reduced. CONCLUSIONS:Gpr88 deletion disrupts executive, reward, and emotional networks in a configuration that reduces alcohol reward and promotes alcohol seeking and drinking. The functional connectivity signature is reminiscent of alterations observed in individuals at risk for AUD. The Gpr88 gene, therefore, may represent a vulnerability/resilience factor for AUD, and a potential drug target for AUD treatment.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Ben Hamida S,Mendonça-Netto S,Arefin TM,Nasseef MT,Boulos LJ,McNicholas M,Ehrlich AT,Clarke E,Moquin L,Gratton A,Darcq E,Harsan LA,Maldonado R,Kieffer BLdoi
10.1016/j.biopsych.2018.01.026subject
Has Abstractpub_date
2018-08-01 00:00:00pages
202-212issue
3eissn
0006-3223issn
1873-2402pii
S0006-3223(18)30081-7journal_volume
84pub_type
杂志文章abstract:BACKGROUND:A large number of studies suggest the presence of deficits in dorsolateral prefrontal cortex function during performance of working memory tasks in individuals with schizophrenia. However, working memory deficits may also present in other psychiatric disorders, such as major depression. It is not clear wheth...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(02)01674-8
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND:Evidence suggests that the noradrenergic and corticotrophin-releasing factor (CRF) systems play critical roles in relapse and stress-related behaviors. In particular, behavioral studies point to a serial signaling process initiated by β-adrenergic receptors that requires CRF receptor (CRFR)-dependent signali...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2010.12.030
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Genetic studies of schizophrenia have implicated numerous risk loci including several copy number variants (CNVs) of large effect and hundreds of loci of small effect. In only a few cases has a specific gene been clearly identified. Rare CNVs affecting a single gene offer a potential avenue to discovering sc...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2019.09.023
更新日期:2020-04-15 00:00:00
abstract:BACKGROUND:Sleep disturbance is associated with activation of systemic and cellular inflammation, as well as proinflammatory transcriptional profiles in circulating leukocytes. Whether treatments that target insomnia-related complaints might reverse these markers of inflammation in older adults with insomnia is not kno...
journal_title:Biological psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.biopsych.2015.01.010
更新日期:2015-11-15 00:00:00
abstract:BACKGROUND:Studies in elderly patients demonstrate antipsychotic efficacy and favorable safety profiles for olanzapine. We report results from two placebo-controlled, double-blind studies of olanzapine for treatment of dopamimetic drug-induced psychosis in patients with Parkinson's disease (PD). METHODS:Patients were ...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0006-3223(02)01392-6
更新日期:2002-09-01 00:00:00
abstract::The present study was undertaken in order to further explore the relationship between monoamine levels and hypothalamic-pituitary-adrenocortical (HYPAC) functioning and suicidal behavior in depressed patients. One hundred and thirty-two depressed inpatients participated in the NIMH Collaborative Study on the Psychobio...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(86)90241-6
更新日期:1986-07-01 00:00:00
abstract:BACKGROUND:Cognitive control impairments in schizophrenia are thought to arise from dysfunction of interconnected networks of brain regions, but interrogating the functional dynamics of large-scale brain networks during cognitive task performance has proved difficult. We used functional magnetic resonance imaging to ge...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2011.02.019
更新日期:2011-07-01 00:00:00
abstract::The aim of the present study was to evaluate the pattern of basal cortisol release in PTSD and major depression using a chronobiological analysis. Plasma for cortisol determination was obtained from 15 combat veterans with PTSD, 14 subjects with major depression, and 15 normal men every 30 min during a 24-hour period ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(95)00451-3
更新日期:1996-07-15 00:00:00
abstract::Previous studies have suggested that tardive dyskinesia may occur more frequently in patients who smoke. Further evidence of an interaction between smoking and movement disorders includes the low lifetime exposure to cigarettes found in Parkinson's disease patients. In this study 126 patients with chronic psychiatric ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(91)90163-g
更新日期:1991-07-15 00:00:00
abstract:BACKGROUND:A polymorphism in the serotonin transporter (5-HTT) gene modulates the association between adverse early experiences and risk for major depression in adulthood. Although human imaging studies have begun to elucidate the neural circuits involved in the 5-HTT x environment risk factor, a molecular understandin...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2007.08.013
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:In a Swedish study, delinquent boys had high serum levels of triiodothyronine (T3). Furthermore, former delinquents, followed up after about 30 years, had T3 levels significantly related to repeated criminality. The aim of the present study was to shed further light on the relationship between the thyroid ho...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(97)00302-8
更新日期:1998-05-15 00:00:00
abstract::Specific electroencephalogram (EEG) changes during clozapine therapy were prospectively studied in a cohort of 50 chronic state hospital patients with schizophrenia who were randomly assigned to one of three nonoverlapping clozapine serum level ranges (50-150 ng/mL, 200-300 ng/mL, and 350-450 ng/mL). EEGs were obtaine...
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(96)00298-3
更新日期:1997-07-15 00:00:00
abstract:BACKGROUND:Animal and human studies implicate forebrain neural circuits in maternal behavior. Here, we hypothesized that human brain response to emotional stimuli relevant for social interactions between infants and adults are modulated by sex- and experience-dependent factors. METHODS:We used functional magnetic reso...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(03)00697-8
更新日期:2003-12-15 00:00:00
abstract::The benzodiazepines are generally safe and effective drugs with usually only minor side effects, dose-related sedation being the most common. A range of paradoxical effects can occur of which release of aggressive and hostile feelings has excited most attention. These responses are idiosyncratic however, as most patie...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1981-12-01 00:00:00
abstract:BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder characterized by deficits in attention, increased motor impulsivity, and hyperactivity. Preliminary work in mice and humans has suggested the X-linked gene STS (which encodes the enzyme steroid sulfatase) as a mediator o...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2009.01.001
更新日期:2009-08-15 00:00:00
abstract:BACKGROUND:Previous reports of ventricular and hippocampal volumes in patients with bipolar disorder (BP) have been inconsistent in their findings. One possibility is that volumetric abnormalities are determined by disease subtype. Prior evidence suggests that psychotic (PBP) and nonpsychotic (NPBP) forms of BP are two...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2004.12.009
更新日期:2005-03-15 00:00:00
abstract:BACKGROUND:Animal and human newborn studies suggest that exposure to cocaine in utero delays glial maturation and white matter myelination. Postmortem data show that in the frontal and temporal lobes, white matter myelination continues into middle age. Recent magnetic resonance imaging (MRI) data have confirmed continu...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(02)01315-x
更新日期:2002-04-15 00:00:00
abstract::Eleven patients with senile dementia of the Alzheimer type and 11 age-matched control subjects were given the thyrotropin-releasing hormone (TRH) test. The two groups did not differ with respect to peak thyrotropin (TSH) response or TSH levels at baseline, 20, 30, and 45 min after TRH injection. There were significant...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(93)90293-m
更新日期:1993-02-15 00:00:00
abstract:BACKGROUND:The amplitude of the auditory P3 event-related potential is reduced in patients with axes I and II disorders. Data regarding P3 amplitude and normal personality traits in healthy individuals have been inconsistent, however, although more extreme variants of dimensional traits such as neuroticism and extraver...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(00)01067-2
更新日期:2001-06-01 00:00:00
abstract::The smooth pursuit responses to 5 degrees and 20 degrees/sec constant-velocity stimuli were recorded from 23 patients with schizophrenia, 16 affective disorder patients, and 21 normals using low-noise infrared oculography. Pursuit gain, catch-up saccade (CUS) rate and amplitude, and their interrelationships were exami...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(91)90248-k
更新日期:1991-06-01 00:00:00
abstract:BACKGROUND:To test the hypothesis that depression is associated with an increased ratio of cholinergic to serotonergic neurotransmission, we compared the effects of pilocarpine, a muscarinic agonist, and ipsapirone, a serotonin (5-HT)1A agonist, on electroencephalographic (EEG) sleep in depressed and healthy subjects. ...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/s0006-3223(97)00551-9
更新日期:1998-07-01 00:00:00
abstract::The current concept that blunted adrenocorticotropic hormone (ACTH) response to human corticotropin-releasing-hormone (h-CRH) in depression is primarily determined by elevated circulating plasma cortisol levels is still unproven. We tested this hypothesis by comparing ACTH release following intravenous administration ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(88)90254-5
更新日期:1988-11-01 00:00:00
abstract:BACKGROUND:Previous magnetic resonance imaging (MRI) studies indicate that compared with healthy volunteers, patients with bipolar disorder have structural and functional abnormalities in the prefrontal cortex. The aim of this study was to investigate differences in prefrontal subregions between bipolar patients and he...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(02)01350-1
更新日期:2002-07-15 00:00:00
abstract:BACKGROUND:Monoamine dysfunction, particularly of the serotonin system, has been the dominant hypothesis guiding research and treatment development in affective disorders. The majority of research has been performed in midlife depressed adults. The importance of understanding the neurobiology of depression in older adu...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/j.biopsych.2009.02.012
更新日期:2009-08-01 00:00:00
abstract:BACKGROUND:One of the most recognizable features of psychopathy is the reduced ability to successfully learn and adapt overt behavior. This might be due to deficient processing of error information indicating the need to adapt controlled behavior. METHODS:Event-related potentials (ERPs) and behavioral components of er...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2008.08.011
更新日期:2009-01-15 00:00:00
abstract::In order to evaluate the impact of aging on EEG sleep patterns we investigated the polysomnograms of 74 patients with major depression and 51 healthy volunteers aged 18-65 years. In most of the EEG sleep parameters, age-related changes were obvious in both the depressives and the normals. In the patients, some of thes...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(91)90355-p
更新日期:1991-05-15 00:00:00
abstract:BACKGROUND:Spectral analysis of heart rate variability has recently been shown to be a reliable noninvasive test for quantitative assessment of cardiovascular autonomic regulatory responses, providing a dynamic map of sympathetic and parasympathetic interaction. In a prior study exploring the state of hyperarousal char...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/s0006-3223(97)00475-7
更新日期:1998-11-15 00:00:00
abstract:BACKGROUND:Although cocaine is known to be a highly addictive drug, there appears to be a select subset of individuals who are able to use the substance recreationally without developing dependence. These individuals do not report experiencing feelings of craving for cocaine, an important distinction from dependent use...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2013.05.019
更新日期:2014-01-15 00:00:00
abstract:BACKGROUND:Cerebral myeloarchitecture shows substantial development across childhood and adolescence, and aberrations in these trajectories are relevant for a range of mental disorders. Differential myelination between intracortical and subjacent white matter can be approximated using signal intensities in T1-weighted ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2018.09.027
更新日期:2019-03-01 00:00:00
abstract::The efficacy of gamma-hydroxybutyrate (GHB) versus placebo for treating narcolepsy was evaluated in 20 patients with narcolepsy, 10 men and 10 women, using a double-blind counterbalanced crossover design. Each patient completed a daily sleep-wake log and questionnaire during a 14-day baseline, a 29-day placebo period,...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/0006-3223(89)90048-6
更新日期:1989-08-01 00:00:00