Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology)

Publisher: Nature Publishing Group, Nature Publishing Group

Journal description

Neuropsychopharmacology is an international scientific journal and the official publication of the American College of Neuropsychopharmacology. The journal focuses on clinical and basic science contributions that advance our understanding of the brain and behavior.

Current impact factor: 7.05

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 7.048
2013 Impact Factor 7.833
2012 Impact Factor 8.678
2011 Impact Factor 7.991
2010 Impact Factor 6.685
2009 Impact Factor 6.993
2008 Impact Factor 6.835
2007 Impact Factor 6.157
2006 Impact Factor 5.889
2005 Impact Factor 5.369
2004 Impact Factor 4.941
2003 Impact Factor 5.201
2002 Impact Factor 4.497
2001 Impact Factor 4.715
2000 Impact Factor 4.579
1999 Impact Factor 4.858
1998 Impact Factor 4.318
1997 Impact Factor 4.105
1996 Impact Factor 3.936
1995 Impact Factor 3.567
1994 Impact Factor 2.78
1993 Impact Factor 2.521
1992 Impact Factor 3.661

Impact factor over time

Impact factor

Additional details

5-year impact 8.17
Cited half-life 6.40
Immediacy index 1.58
Eigenfactor 0.05
Article influence 2.64
Website Neuropsychopharmacology website
Other titles Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
ISSN 1740-634X
OCLC 855449
Material type Periodical, Internet resource
Document type Journal / Magazine / Newspaper, Internet Resource

Publisher details

Nature Publishing Group

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 6 months embargo
  • Conditions
    • Authors retain copyright
    • Published source must be acknowledged and DOI cited
    • Must link to publisher version
    • Publisher's version/PDF cannot be used
    • On author's personal website and institutional repository
    • If funding agency rules apply, authors may post authors version to their relevant funding body's archive, 6 months after publication
    • This policy is an exception to the default policies of 'Nature Publishing Group'
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Addiction is a behavioral disease, of which core components can be modeled in rodents. Much evidence implicates drug-evoked synaptic plasticity in cocaine-evoked locomotor sensitization, cue-induced cocaine seeking and incubation of cocaine craving. However the type of plasticity evoked by different modalities of cocaine administration (eg contingent versus non-contingent) and its role in reshaping circuit function remains largely elusive. Here we exposed mice to various regimens of cocaine and recorded excitatory transmission onto identified medium-sized spiny neurons (MSN, expressing fluorescent proteins under the control of either D1R or D2R dopamine receptor promotor) in the nucleus accumbens (NAc) at time points when behavioural adaptations are observed. In D1-MSN, we found the presence of GluA2-lacking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) after single or chronic non-contingent exposure to cocaine, as well as after cocaine self-administration. We also report an increase in the AMPA/NMDA ratio (A/N) in D1-MSN, which was observed only after repeated passive injections associated with locomotor sensitization as well as in a condition of self-administration (SA) leading to seeking behaviour. Remarkably, insertion of GluA2-lacking AMPARs was also detected in D2-MSN after self-administration of a high dose of cocaine but not regular dose (1.5 vs 0.75 mg/kg), which was the only condition where incubation of cocaine craving was observed in this study. Moreover, synapses containing GluA2-lacking AMPARs belonged to amygdala inputs in D2-MSN and to medial prefrontal cortex (mPFC) inputs in D1-MSN. Taken together this study allows for a refinement of a circuit model of addiction based on specific synaptic changes induced by cocaine.Neuropsychopharmacology accepted article preview online, 20 November 2015. doi:10.1038/npp.2015.345.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2015; DOI:10.1038/npp.2015.345
  • [Show abstract] [Hide abstract]
    ABSTRACT: Brain-derived neurotrophic factor (BDNF) regulates diverse biological functions ranging from neuronal survival and differentiation during development to synaptic plasticity and cognitive behavior in the adult. BDNF disruption in both rodents and humans is associated with neurobehavioral alterations and psychiatric disorders. A unique feature of Bdnf transcription is regulation by nine individual promoters, which drive expression of variants that encode an identical protein. It is hypothesized that this unique genomic structure may provide flexibility that allows different factors to regulate BDNF signaling in distinct cell types and circuits. This has led to the suggestion that isoforms may regulate specific BDNF-dependent functions; however, little scientific support for this idea exists. We generated four novel mutant mouse lines in which BDNF production from one of the four major promoters (I, II, IV, or VI) is selectively disrupted (Bdnf-e1, -e2, -e4, -e6 mice), and used a comprehensive comparator approach to determine whether different Bdnf transcripts are associated with specific BDNF-dependent molecular, cellular and behavioral phenotypes. Bdnf-e1 and -e2 mutant males displayed heightened aggression accompanied by convergent expression changes in specific genes associated with serotonin signaling. In contrast, BDNF-e4 and -e6 mutants were not aggressive, but displayed impairments associated with GABAergic gene expression. Moreover, quantifications of BDNF protein in hypothalamus, prefrontal cortex, and hippocampus revealed that individual Bdnf transcripts make differential, region-specific contributions to total BDNF levels. The results highlight the biological significance of alternative Bdnf transcripts and provide evidence that individual isoforms serve distinct molecular and behavioral functions.Neuropsychopharmacology accepted article preview online, 20 November 2015. doi:10.1038/npp.2015.349.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2015; DOI:10.1038/npp.2015.349
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    ABSTRACT: Nociceptin/Orphanin FQ (N/OFQ) is an endogenous ligand of the N/OFQ peptide receptor (NOP), which is a G protein-coupled receptor in brain regions associated with mood disorders. We used a novel, potent, and selective orally-bioavailable antagonist, LY2940094, to test the hypothesis that blockade of NOP receptors would induce antidepressant effects. In this paper, we demonstrate that targeting NOP receptors with LY2940094 translates to antidepressant-like effects in rodent models, and importantly to antidepressant efficacy in patients with major depressive disorder (MDD). The proof-of-concept study (POC) was an 8-week, double-blind, placebo-controlled trial that evaluated LY2940094 as a novel oral medication for the treatment of patients with MDD. Once daily oral dosing of LY2940094 at 40 mg for 8 weeks versus placebo provided some evidence for an antidepressant effect based on the change from baseline to week 8 in the GRID-Hamilton Depression Rating Scale-17 item total score although the pre-defined POC efficacy criterion (probability of LY2940094 being better than placebo ≥88%) was not met (82.9%). LY2940094 also had an early effect on the processing of emotional stimuli at Week 1 as shown by an increased recognition of positive relative to negative facial expressions in an emotional test battery. LY2940094 was safe and well tolerated. Overall, these are the first human data providing evidence that the blockade of NOP receptor signaling represents a promising strategy for the treatment of MDD.Neuropsychopharmacology accepted article preview online, 20 November 2015. doi:10.1038/npp.2015.348.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2015; DOI:10.1038/npp.2015.348
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuropsychiatric disorders are of complex etiology, often including a large genetic component. In order to help identify and study the molecular and physiological mechanisms that such genes participate in, numerous animal models have been established in a variety of species. Over the past decade, this has increasingly included the vinegar fly, Drosophila melanogaster. Here, we outline why we study an invertebrate organism in the context of neuropsychiatric disorders, and we discuss how we can gain insight from studies in Drosophila. We focus on a few disorders and findings to make the larger point that modeling these diseases in flies can have both mechanistic and predictive validity. Highlighting some translational examples, we underline the fact that their brains works more like ours than one would have anticipated.Neuropsychopharmacology advance online publication, 18 November 2015; doi:10.1038/npp.2015.322.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2015; DOI:10.1038/npp.2015.322
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    ABSTRACT: Childhood adversity (CA) has been associated with long-term structural brain alterations and an increased risk for psychiatric disorders. Evidence is emerging that subtypes of CA, varying in the dimensions of threat and deprivation, lead to distinct neural and behavioral outcomes. However, these specific associations have yet to be established without potential confounders such as psychopathology. Moreover, differences in neural development and psychopathology necessitate the exploration of sexual dimorphism. Young healthy adult subjects were selected based on history of childhood adversity from a large database to assess gray matter (GM) differences associated with specific subtypes of adversity. We compared voxel-based morphometry data of subjects reporting specific childhood exposure to abuse (n=127) or deprivation (n=126) and a similar sized group of controls (n=129) without reported childhood adversity. Subjects were matched on age, gender and educational level. Differences between CA-subtypes were found in the fusiform gyrus and middle occipital gyrus, where subjects with a history of deprivation showed reduced GM compared to subjects with a history of abuse. An interaction between sex and CA-subtype was found. Women showed less GM in the visual posterior precuneal region after both subtypes of CA than controls. Men had less GM in the postcentral gyrus after childhood deprivation compared to abuse. Our results suggest that even in a healthy population CA subtypes are related to specific alterations in brain structure, which are modulated by sex. These findings may help understand neurodevelopmental consequences related to childhood adversity.Neuropsychopharmacology accepted article preview online, 18 November 2015. doi:10.1038/npp.2015.344.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2015; DOI:10.1038/npp.2015.344
  • [Show abstract] [Hide abstract]
    ABSTRACT: Current treatment strategies for anxiety disorders are predominantly symptom-based. However, a third of anxiety patients remain unresponsive to anxiolytics highlighting the need for more effective, mechanism-based therapeutic approaches. We have previously compared high vs. low anxiety mice and identified changes in mitochondrial pathways, including oxidative phosphorylation and oxidative stress. In this work, we show that selective pharmacological targeting of these mitochondrial pathways exerts anxiolytic effects in vivo. We treated high anxiety-related behavior (HAB) mice with MitoQ, an antioxidant that selectively targets mitochondria. MitoQ administration resulted in decreased anxiety-related behavior in HAB mice. This anxiolytic effect was specific for high anxiety as MitoQ treatment did not affect the anxiety phenotype of C57BL/6N and DBA/2J mouse strains. We furthermore investigated the molecular underpinnings of the MitoQ-driven anxiolytic effect and found that MitoQ treatment alters the brain metabolome and that the response to MitoQ treatment is characterized by distinct molecular signatures. These results indicate that a mechanism-driven approach based on selective mitochondrial targeting has the potential to attenuate the high anxiety phenotype in vivo, thus paving the way for translational implementation as long-term MitoQ administration is well-tolerated with no side-effects in mice and humans.Neuropsychopharmacology accepted article preview online, 16 November 2015. doi:10.1038/npp.2015.341.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2015; DOI:10.1038/npp.2015.341

  • Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2015; DOI:10.1038/npp.2015.321
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuropsychopharmacology, the official publication of the American College of Neuropsychopharmacology, publishing the highest quality original research and advancing our understanding of the brain and behavior.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2015; DOI:10.1038/npp.2015.320
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    ABSTRACT: Depression is a common mental illness and a leading cause of disability. The most widely prescribed antidepressant medications are serotonin (5-HT) selective reuptake inhibitors (SSRIs). Although there is much support for 5-HT transporter (SERT) antagonism as a basis of antidepressant efficacy, this evidence is indirect and other targets and mechanisms have been proposed. In order to distinguish SERT-dependent and -independent effects of SSRIs, we developed a knock-in mouse model whereby high-affinity interactions of many antidepressants at SERT have been ablated via knock-in substitution (SERT Met172) without disrupting 5-HT recognition or uptake (Thompson et al, 2011). Here, we utilize the C57BL/6J SERT Met172 model to evaluate SERT dependence for the actions of two widely prescribed SSRIs, fluoxetine and citalopram, in tests sensitive to acute and chronic actions of antidepressants. In the tail suspension (TST) and forced swim tests (FST), fluoxetine and citalopram fail to reduce immobility in SERT Met172 mice. Additionally, SERT Met172 mice are insensitive to chronic fluoxetine and citalopram administration in the novelty induced hypophagia test (NIH) and fail to exhibit enhanced proliferation or survival of hippocampal stem cells. In both acute and chronic studies, SERT Met172 mice maintained sensitivity to paroxetine, an antidepressant that is unaffected by the Met172 mutation. Together, these studies provide definitive support for an essential role of SERT antagonism in the acute and chronic actions of two commonly used SSRIs in these tests, and reinforce the utility of the SERT Met172 model for isolating SERT/5-HT contributions of drug actions in vivo.Neuropsychopharmacology accepted article preview online, 30 October 2015. doi:10.1038/npp.2015.335.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2015; DOI:10.1038/npp.2015.335
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    ABSTRACT: Excessive alcohol use in young adults is associated with greater impulsivity and neurobiological alterations in executive control systems. The maximum number of drinks consumed during drinking occasions ('MaxDrinks') represents a phenotype linked to vulnerability of alcohol use disorders, and an increase, or 'escalation', in MaxDrinks may be indicative of greater risk for problematic drinking. Thirty-six young adult drinkers performed a Go/No-Go task during fMRI, completed impulsivity-related assessments, and provided monthly reports of alcohol use during a 12-month follow-up period. Participants were characterized by MaxDrinks at baseline and after follow-up, identifying 18 escalating-drinkers and 18 constant-drinkers. Independent component analysis was used to investigate functional brain networks associated with response inhibition, and relationships with principal component analysis derived impulsivity-related domains were examined. Greater baseline MaxDrinks was associated with an average reduction in the engagement of a right-lateralized fronto-parietal functional network, while an escalation in MaxDrinks was associated with a greater difference in fronto-parietal engagement between successful inhibitions and error trials. Escalating-drinkers displayed greater impulsivity/compulsivity-related domain scores that were positively associated with fronto-parietal network engagement and change in MaxDrinks during follow-up. In young adults, an escalating MaxDrinks trajectory was prospectively associated with altered fronto-parietal control mechanisms and greater impulsivity/compulsivity scores. Continued longitudinal studies of MaxDrinks trajectories, functional network activity and impulsivity/compulsivity-related features may lend further insight into an intermediate phenotype vulnerable for alcohol use and addictive disorders.Neuropsychopharmacology accepted article preview online, 30 October 2015. doi:10.1038/npp.2015.332.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2015; DOI:10.1038/npp.2015.332
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    ABSTRACT: Stimulation of the cortical muscarinic M1 receptor (CHRM1) is proposed as a treatment for schizophrenia, a hypothesis testable using CHRM1 allosteric modulators. Allosteric modulators have been shown to change the activity of CHRMs using cloned human CHRMs and CHRM knockout mice but not human CNS, a prerequisite for them working in humans. Here we show in vitro that BQCA, a positive allosteric CHRM1 modulator, brings about the expected change in affinity of the CHRM1 orthosteric site for acetylcholine in human cortex. Moreover, this effect of BQCA is reduced in the cortex of a subset of subjects with schizophrenia, separated into a separate population because of a profound loss of cortical [(3)H]pirenzepine binding. Surprisingly, there was no change in [(3)H]NMS binding to the cortex from this subset or those with schizophrenia but without a marked loss of cortical CHRM1. Hence, we explored the nature of [(3)H]pirenzepine and [(3)H]NMS binding to human cortex and showed total [(3)H]pirenzepine and [(3)H]NMS binding was reduced by Zn(2+), acetylcholine displacement of [(3)H]NMS binding was enhanced by Mg(2+) and Zn(2+), acetylcholine displacement of [(3)H]pirenzepine was reduced by Mg(2+) and enhanced by Zn(2+) whilst BQCA effects on [(3)H]NMS, but not [(3)H]pirenzepine, binding was enhanced by Mg(2+) and Zn(2+). These data suggest the orthosteric and allosteric sites on CHRMs respond differently to divalent cations and the effects of allosteric modulation of the cortical CHRM1 is reduced in a sub-set people with schizophrenia, a finding that may have ramification for the use of CHRM1 allosteric modulators in the treatment of schizophrenia.Neuropsychopharmacology accepted article preview online, 29 October 2015. doi:10.1038/npp.2015.330.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2015; DOI:10.1038/npp.2015.330
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    ABSTRACT: DNA methylation variation at HP1BP3 and TTC9B is modified by estrogen exposure in the rodent hippocampus and was previously shown to be prospectively predictive of postpartum depression (PPD) when modeled in antenatal blood. The objective of this study was to replicate the predictive efficacy of the previously established model in women with and without a previous psychiatric diagnosis and to understand the effects of changing hormone levels on PPD biomarker loci. Using a statistical model trained on DNA methylation data from N=51 high risk women, we prospectively predicted PPD status in an independent N=51 women using first trimester antenatal gene expression levels of HP1BP3 and TTC9B with an AUC of 0.81 (95% CI: 0.69-0.92, P<5 × 10(-4)). Modeling DNA methylation of these genes in N=240 women without a previous psychiatric diagnosis resulted in a cross sectional prediction of PPD status with an AUC of 0.81 (95% CI: 0.68-0.93, p=0.01). TTC9B and HP1BP3 DNA methylation at early antenatal time points showed moderate evidence for association to the change in estradiol and allopregnanolone over the course of pregnancy, suggesting that epigenetic variation at these loci may be important for mediating hormonal sensitivity. Additionally both loci showed PPD specific trajectories with age, possibly mediated by age associated hormonal changes. The data add to the growing body of evidence suggesting that PPD is mediated by differential gene expression and epigenetic sensitivity to pregnancy hormones and that modeling proxies of this sensitivity enable accurate prediction of PPD.Neuropsychopharmacology accepted article preview online, 27 October 2015. doi:10.1038/npp.2015.333.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2015; DOI:10.1038/npp.2015.333
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    ABSTRACT: Methamphetamine Use Disorder is associated with striatal dopaminergic deficits, which have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as non-displaceable binding potential, BPND) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise-training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1-hr supervised exercise training (n=10) or one that received equal-time health-education training (n=9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using (18)F-fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BPND. At baseline, striatal D2/D3 BPND did not differ between groups. However, after 8-weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BPND, while those in the education group did not. There were no changes in D2/D3 BPND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.Neuropsychopharmacology accepted article preview online, 27 October 2015. doi:10.1038/npp.2015.331.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2015; DOI:10.1038/npp.2015.331
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    ABSTRACT: Cortical network hyper-excitability is a common phenotype in mouse models lacking in the transcriptional regulator MeCP2. Here, we implicate enhanced GABAB receptor activity stemming from diminished cortical expression of the GABA transporter GAT-1 in the genesis of this network hyper-excitability. We found that the administering the activity-dependent GABAB receptor allosteric modulator GS-39783 to female Mecp2(+/-) mice at doses producing no effect in wild-type mice strongly potentiated their basal rates of spontaneous cortical discharge activity. Consistently, administering the GABAB receptor antagonist CGP-35348 significantly decreased basal discharge activity in these mice. Expression analysis revealed that while GABAB or extra-synaptic GABAA receptor prevalence is preserved in the MeCP2-deficient cortex, the expression of GAT-1 is significantly reduced from wild-type levels. This decrease in GAT-1 expression is consequential, as low doses of the GAT-1 inhibitor NO-711 that had no effects in wild-type mice strongly exacerbated cortical discharge activity in female Mecp2(+/-) mice. Taken together, these data indicate that the absence of MeCP2 leads to decreased cortical levels of the GAT-1 GABA transporter, which facilitates cortical network hyper-excitability in MeCP2-deficient mice by increasing the activity of cortical GABAB receptors.Neuropsychopharmacology accepted article preview online, 26 October 2015. doi:10.1038/npp.2015.323.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2015; DOI:10.1038/npp.2015.323