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Cited by 119Nicotinic Acetylcholine Receptors StudyTreatment of Major DepressionSmoking Behavior and Cessation

Persistent β 2 *-Nicotinic Acetylcholinergic Receptor Dysfunction in Major Depressive Disorder

Open access
Saricicek, Aybala, Esterlis, Irina, Maloney, Kathleen H., Mineur, Yann S., Ruf, Barbara M., Muralidharan, Anjana, Chen, Jason I., Cosgrove, Kelly P. +10 more·2012·American Journal of Psychiatry
DOI 10.1176/appi.ajp.2012.11101546PMC PMC3494404
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Abstract

BACKGROUND: Modulation of nicotinic acetylcholine receptors (nAChRs), specifically those containing the β2 subunit, may be effective in treating patients with major depressive disorder. Using [123I]5-I-A-85380 single photon emission computed tomography (SPECT), the authors studied the availability of β2-subunit-containing nAChRs (β2*-nAChRs) in depressed patients. To understand its molecular basis, the authors also studied β2*-nAChR binding in postmortem brain samples from depressed subjects. METHOD: The participants were 23 medication-free, nonsmoking subjects with familial, early-onset depression (eight acutely ill and 15 recovered) and 23 age- and gender-matched nonsmoking comparison subjects. Each received one [123I]5-I-A-85380 SPECT scan and an MRI scan. The availability of β2*-nAChRs was quantified as VT/fP. Postmortem analysis of β2*-nAChR binding was conducted with [123I]5-I-A-85380 on prefrontal cortex samples from 14 depressed subjects and 14 age-matched comparison subjects. RESULTS: The β2*-nAChR availability in both the acutely ill and recovered depressed subjects was significantly lower across all brain regions than in the respective comparison subjects, and it was lower in the acutely ill subjects than in those who were recovered. In the depressed patients, β2*-nAChR availability was significantly correlated with lifetime number of depressive episodes, trauma score, and anxiety score. There were no differences in β2*-nAChR number between groups in the postmortem study. CONCLUSIONS: Depressed patients have lower β2*-nAChR availability than do healthy subjects. The difference between β2*-nAChR availability in vivo and in post-mortem samples may be analogous to data with dopaminergic PET ligands and dopamine receptor availability; lower receptor availability for the SPECT ligand could be caused by greater endogenous acetylcholine.

AI snapshot

Written from the paper’s full text.

TL;DR

In medication-free, non-smoking patients with familial major depressive disorder (MDD), β2*-nicotinic acetylcholine receptor (β2*-nAChR) availability measured by [123I]5-I-A-85380 SPECT was lower in acutely depressed and recovered subjects than in controls, and lower in acutely depressed than recovered subjects. Postmortem prefrontal cortex showed no difference in β2*-nAChR number, suggesting lower in vivo availability may reflect increased endogenous acetylcholine rather than receptor loss.

Key findings

  • Acutely depressed MDD subjects had decreased β2*-nAChR availability versus controls in 9 of 11 regions examined, except hippocampus and amygdala (all adjusted p<0.007); the omnibus model showed a significant group effect (F(3,42)=8.65, p<.0001) and group-by-region interaction (F(30,420)=1.82, p=.006).
  • Recovered MDD subjects had lower β2*-nAChR availability than controls in frontal cortex (adjusted p=0.03), anterior cingulate (adjusted p=0.04), and thalamus (adjusted p=0.008); overall group effect F(1,28)=7.9, p=0.009.
  • Acutely depressed subjects had lower overall β2*-nAChR availability than recovered subjects (F(1,21)=10.0, p=0.005), with no significant group-by-region interaction (F(10,210)=1.34, p=0.21).
  • Postmortem prefrontal cortex showed no differences in β2*-nAChR number between 14 MDD subjects and age-matched controls; in vivo availability correlated positively with lifetime number of depressive episodes in combined MDD subjects for temporal cortex (r=0.46, p=0.049), occipital cortex (r=0.48, p=0.037), and striatum (r=0.49, p=0.034).

Methods

  • Cross-sectional SPECT/MRI study: 23 medication-free, non-smoking subjects with recurrent familial MDD (8 acutely depressed, 15 recovered) and 23 age- and gender-matched non-smoking controls had one [123I]5-I-A-85380 SPECT scan and one MRI; β2*-nAChR availability was quantified as VT/fp.
  • Postmortem study: [125I]5-I-A-85380 binding was analyzed in prefrontal cortex samples from 14 subjects with MDD and age-matched controls.
  • Main analysis used linear mixed models with region as a within-subjects factor, diagnostic group as a between-subjects factor, and group-by-region interaction; post-hoc tests were Bonferroni-corrected for 11 regional comparisons (2-sided alpha=.0045). Clinical correlations, postmortem ANOVA, and voxel-based morphometry (SPM5, p<.05 uncorrected) were also performed.

Limitations

  • The paper states the sample size is relatively small and composed nearly entirely of subjects without a past history of cigarette smoking; only 11 of 46 subjects had a past smoking history, so the relationship between past smoking and β2*-nAChR availability could not be adequately analyzed.
  • The paper states SPECT limitations include absence of a quantifiable reference region and input function, absence of a measurement of non-displaceable binding in MDD patients, poor resolution for small regions such as the amygdala, and the need for a PET study to confirm results; use of current non-smokers limits generalizability.
  • Evident from the text: the postmortem results are described as provided in the supplement, limiting detail in the main paper, and the cross-sectional design cannot establish whether cholinergic changes are a cause or effect of MDD.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1176/appi.ajp.2012.11101546

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

7 tests recomputed · 0 with the reported and recomputed p on opposite sides of .05

Claims the paper makes

0 of 30 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Acutely depressed MDD subjects had lower overall β2*-nAChR availability than recovered MDD subjects.

    “There was a significant overall group effect (F(1,21)=10.0, p=0.005) with lower overall β2*-nAChR availability observed among acute MDD patients compared to recovered patients.”
    Quote in the paperSubstantial claim
  • Findingown data

    In vivo, acutely depressed MDD subjects had significantly lower β2*-nAChR availability than healthy controls in nine of the eleven ROIs examined (all except hippocampus and amygdala).

    “Post hoc comparison revealed decreased β2*-nAChR availability in aMDD subjects compared to healthy controls in nine of the eleven ROIs examined (except hippocampus and amygdala, all adjusted p<0.007).”
    Quote in the paperSubstantial claim
  • Findingown data

    In recovered MDD subjects alone, lifetime number of depressive episodes was positively correlated with β2*-nAChR availability in temporal cortex, occipital cortex, thalamus, and striatum.

    “This was also observed in the rMDD group alone (temporal cortex r=0.54, p=0.036, occipital cortex r=0.56, p=0.03, thalamus r=0.54, p=0.038 and striatum r=0.58, p=0.022).”
    Quote in the paperSubstantial claim
  • Findingown data

    In acutely depressed MDD subjects but not recovered MDD subjects, CTQ total score and emotional abuse subscale were negatively correlated with β2*-nAChR availability in all ROIs studied except amygdala.

    “The CTQ total score and emotional abuse subscale were negatively correlated with receptor availability in all ROIs studied except amygdala in the aMDD but not the rMDD group.”
    Quote in the paperSubstantial claim
  • Findingown data

    In vivo, recovered MDD subjects had lower β2*-nAChR availability than controls in the frontal cortex, anterior cingulate, and thalamus.

    “Post hoc comparisons showed lower β2*-nAChR availability among patients compared to controls in the frontal cortex (adjusted p=0.03), anterior cingulate (adjusted p=0.04), and thalamus (adjusted p=0.008).”
    Quote in the paperSubstantial claim
  • May combine two claims. 15
  • Classified as probably not a substantial claim. 15

  • May combine two claims.

    Findingown data

    In recovered MDD subjects but not acutely depressed MDD subjects, STAI Trait subscale score was negatively correlated with β2*-nAChR availability in anterior cingulate, temporal, and occipital regions and showed a trend for significance in striatum.

    “The STAI Trait subscale score was negatively correlated with receptor availability in anterior cingulate (r=−0.65, p=0.027), temporal (r=−0.64, p=0.026) and, occipital (r=−0.65, p=0.021) regions and showed a trend for significance in striatum (r=−0.51, p=0.09) in the rMDD group but not in the aMDD group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There were no significant changes in brain volume between all MDD subjects and all controls, between aMDD subjects and their controls, between rMDD subjects and their controls, or between aMDD and rMDD subjects.

    “An SPM analysis of brain volumes of all MDD subjects compared to all controls showed no significant changes in volume in this population even at the relatively generous threshold used in the analysis. Similarly, there were no significant changes in volume between the aMDD subjects and their respective controls, the rMDD subjects and their respective controls, or between the aMDD and rMDD subjects.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The observed β2*-nAChR dysfunction may reflect a cause or effect of dysfunction in serotonin, noradrenaline, glutamate and GABA systems.

    “nAChRs have a ubiquitous role in the modulation of multiple neurotransmitter systems considered crucial in the pathophysiology of MDD such as serotonin, noradrenaline, glutamate and GABA (43) and the observed dysfunction may reflect a cause or effect of dysfunction in these other systems.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The continued significant decrease in β2*-nAChR availability in fully recovered, euthymic, medication-free rMDD subjects suggests that the changes in MDD are not an epiphenomenon of treatment or illness but may be associated with trait vulnerability to depression.

    “The continued, significant decrease in β2*-nAChR availability in fully recovered, euthymic, medication free rMDD subjects suggests that the changes in MDD are not an epiphenomenon of treatment or illness but may be associated with trait vulnerability to depression as demonstrated by us previously for other targets (26, 41, 42).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [26] source

      Not checked in the free run.

    • cites [41] source

      Not checked in the free run.

    • cites [42] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Tobacco smokers have higher β2*-nAChR availability compared with non-smokers in non-psychiatric populations, which normalizes by 6-12 weeks of abstinence.

    “Studies suggest that tobacco smokers have higher β2*-nAChR availability compared with non-smokers in non-psychiatric populations (34) which normalizes by 6–12 weeks of abstinence (44).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [34] source

      Not checked in the free run.

    • cites [44] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Lower binding of [123I]5-IA to β2*-nAChR could reflect either an actual absolute change in the amount of receptor or a change in synaptic ACh levels.

    “Therefore, lower binding of [123I]5-IA to the β2*-nAChR could reflect one of two processes: an actual, absolute change in the amount of receptor or a change in synaptic ACh levels, such that an increased amount of ACh would prevent the radioligand from binding to the receptor, resulting in low binding of the radioligand.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The sample size of the SPECT study is relatively small and composed nearly entirely of subjects without a past history of cigarette smoking; only 11 of the 46 subjects studied had a past history of cigarette smoking.

    “Notwithstanding the robust statistical significance of the SPECT binding results, the sample size of the population studied is relatively small and composed nearly entirely of subjects without a past history of cigarette smoking; only 11 of the 46 subjects studied had a past history of cigarette smoking.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Cholinergic hyperactivity plays a role in the pathophysiology of depression and can exacerbate depression-like symptoms in patients and controls.

    “First, cholinergic hyperactivity plays a role in the pathophysiology of depression (2–4) and can exacerbate depression-like symptoms in patients and controls (4–6).”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [2] Owens MJ, 1991, Neuropsychopharmacology

      Not checked in the free run.

    • cites [3] source

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    • cites [4] source

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    • cites [5] source

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    • cites [6] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Population-based studies show that smokers are twice as likely as nonsmokers to have a lifetime history of major depression.

    “Population-based studies show that smokers are twice as likely as nonsmokers to have a lifetime history of major depression (11–13).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [11] source

      Not checked in the free run.

    • cites [12] source

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    • cites [13] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The groups were well matched on most parameters studied, though there were significant differences in ethnicity and lifetime smoking history between the groups.

    “Clinical and demographic characteristics of participants in each group are shown in Table 2; the groups were well matched on most parameters studied though there were significant differences in ethnicity and lifetime smoking history between the groups.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    All data were approximately normal.

    “All data were approximately normal.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Inclusion of age and gender as covariates did not alter results and they were therefore dropped from the analysis.

    “Inclusion of age and gender as co-variates did not alter results and were therefore dropped from the analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The use of a population exclusively composed of current non-smokers limits generalizability.

    “The use of a population exclusively composed of current non-smokers while essential to interpretation of the results limits generalizability and should be examined in future studies.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The study was approved by the Yale University School of Medicine Human Investigation Committee and the Radiation Safety Committee; written informed consent was obtained; and the use of the radiotracer [123I]5-IA was approved by the US Food and Drug Administration.

    “This study was approved by the Yale University School of Medicine Human Investigation Committee and the Radiation Safety Committee. After complete description of the study to the subjects, written informed consent was obtained. The use of the radiotracer [123I]5-IA was approved by the US Food and Drug Administration.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    SPECT has poor resolution for small brain regions, so findings for the amygdala should be interpreted with caution.

    “While the amygdala is a crucial structure in the pathophysiology of depression, SPECT has poor resolution for small brain regions and the findings for the amygdala should be interpreted with caution a.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Tobacco dependence is highly prevalent in MDD populations and MDD patients have a higher prevalence of smokers.

    “Second, tobacco dependence is highly prevalent in MDD populations (7) and MDD patients have a higher prevalence of smokers (8–10).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [7] source

      Not checked in the free run.

    • cites [8] source

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    • cites [9] source

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    • cites [10] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    There were no significant differences in total injected dose, bolus dose, infusion dose, and bolus to infusion ratio between depressed and control groups.

    “There were no significant differences in the total injected dose, bolus dose, infusion dose, and bolus to infusion ratio between depressed and control groups (Table 1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Inter-rater variability for VT/fp was <10% across all regions.

    “Inter-rater variability for VT/fp was <10% across all regions, which was computed as percent difference between two raters via following equation [(VT/fp 1/VT/fp 2)−1]*100=% difference.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The relationship between a history of past cigarette smoking and β2*-nAChR availability could not be studied because of the small and unbalanced number of subjects with a past history of cigarette smoking.

    “The relationship between a history of past cigarette smoking and β2*-nAChR availability could not be studied because of the small and unbalanced number of subjects with a past history of cigarette smoking.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Nicotine binds to neuronal nAChRs and partial agonists and antagonists of nAChRs including nicotine, mecamylamine, DHβE, cytisine and varenicline have antidepressant-like effects in preclinical studies.

    “Furthermore, nicotine binds to neuronal nicotinic acetylcholine receptors (nAChRs) and partial agonists and antagonists of nAChRs including nicotine (14), mecamylamine and dihydro-beta-erythroidine (DHβE) (15), cytisine (16) and varenicline (17), have antidepressant-like effects in preclinical studies.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [14] source

      Not checked in the free run.

    • cites [15] source

      Not checked in the free run.

    • cites [16] source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Changes in receptor availability in vivo could be due to a change in receptor number or a change in receptor occupancy.

    “Analogous to findings from radioligand based studies of dopamine in humans, it is critically important to note that changes in receptor availability in vivo could be due to a change in receptor number or a change in receptor occupancy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The difference between β2*-nAChR availability in vivo and in postmortem samples may be analogous to data with dopaminergic PET ligands and dopamine receptor availability.

    “The difference between β2*-nAChR availability in vivo and in postmortem samples may be analogous to data with dopaminergic PET ligands and dopamine receptor availability; lower receptor availability for the SPECT ligand could be caused by increased endogenous acetylcholine.”
    Quote in the paperNot a substantial claim
22 of 22

  • The paper relies on this without support.

    Postmortem brain samples are free of endogenous acetylcholine, so their β2*-nAChR binding reflects receptor number.

    “β2*-nAChR availability in the postmortem human samples, in the absence of endogenous acetylcholine, would help interpret the precise mechanism of potential changes in binding observed with [123I]5-IA in humans.”
    “under conditions that washed out any endogenous bound ACh”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Elevated ACh levels observed in human subjects who are actively depressed contribute to the disorder.

    “supports the idea that the elevated ACh levels observed in human subjects who are actively depressed contributes to the disorder (Saricicek et al. 2012;Hannestad et al. 2013).”

    From Mechanisms of Nicotine Addiction (2021) · cites this paper as Saricicek et al. 2012

    The Discussion reports lower β2*-nAChR availability in actively depressed patients and suggests that increased extracellular ACh, rather than fewer receptors, likely explains it. ACh levels were inferred rather than directly observed, and this study does not establish that the inferred increase causes or contributes to depression. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Anomalies in the availability or expression of specific nAChR subunits have been implicated in depression and schizophrenia patients.

    “Notably, anomalies in the availability or expression of specific nAChR subunits have been implicated in depression [104] and schizophrenia patients [105, 106].”

    From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [104]

  • Human imaging and post mortem studies suggested that there is increased occupancy of nAChRs by ACh that is highest in individuals who are actively depressed and intermediate in those who have a history of depression with no change in overall nAChR number.

    “More recently, human imaging and post mortem studies suggested that there is increased occupancy of nAChRs by ACh that is highest in individuals who are actively depressed and intermediate in those who have a history of depression with no change in overall nAChR number (Saricicek et al., 2012).”

    From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Saricicek et al., 2012

  • Availability of β2* nAChRs for tracer binding was greatly decreased in actively depressed patients but was intermediate in remitted subjects.

    “Recent imaging studies have shown that availability of β2* nAChRs for tracer binding was greatly decreased in actively depressed patients but was intermediate in remitted subjects (Saricicek et al., 2012).”

    From Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states (2015) · cites this paper as Saricicek et al., 2012

Statistics that don’t add up

Each reported p-value recomputed from its test statistic and degrees of freedom.

  • Inconsistent p-value: F(3,42)=8.65, p < .0001

    Minor

    The paper reports p < .0001 here; recomputing from the test statistic and its degrees of freedom gives p < .001. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p < .0001 · recomputed p < .001

1 of 1

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Doesn’t add upF(3, 42) = 8.65reported p < .0001 · recomputed p < .001

    “F(3,42)=8.65, p < .0001”

  • ConsistentF(30, 420) = 1.82reported p = .006 · recomputed p = .006

    “F(30,420)=1.82, p = .006”

  • ConsistentF(1, 14) = 15.8reported p = .0014 · recomputed p = .001

    “F(1,14)=15.8, p = .0014”

  • ConsistentF(10, 140) = 2.52reported p = .008 · recomputed p = .008

    “F(10,140)=2.52, p = .008”

  • ConsistentF(1, 28) = 7.9reported p = .009 · recomputed p = .009

    “F(1, 28)=7.9, p = .009”

  • ConsistentF(1, 21) = 10reported p = .005 · recomputed p = .005

    “F(1,21)=10.0, p = .005”

  • ConsistentF(10, 210) = 1.34reported p = .21 · recomputed p = .211

    “F(10,210)=1.34, p = .21”

7 of 7

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Abstract overstates the regional reductions

    Major

    The abstract says availability was significantly lower across all brain regions in both MDD groups. The results report reductions in nine of eleven regions for acute MDD and list only three regions for recovered MDD.

  • Positive correlation is interpreted in the opposite direction

    Major

    The paper reports a positive correlation between episode count and receptor availability, while proposing that lower availability represents higher extracellular ACh. Under that interpretation, more episodes would imply less-not more-extracellular ACh.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. Fujita M, 2000, J Nucl Med, 41, 1552
  2. Staley JK, 2005, J Nucl Med, 46, 1466
  3. First MB, 1997, Structured Clinical Interview for DSM-IV Axis I Disorders—Clinician Version (SCID-CV)
  4. Beck AT, 1996, Beck Depression Inventory, 2nd ed, Manual
  5. Costa PT, 1992, NEO PI-R Professional Manual

Cited by

Sorted by citations

Related

Authors
Saricicek, A., Esterlis, I., Maloney, K. H., Mineur, Y. S., Ruf, B. M., Muralidharan, A., Chen, J. I., Cosgrove, K. P., Kerestes, R., Ghose, S., Tamminga, C. A., Pittman, B., Bois, F., Tamagnan, G., Seibyl, J., Picciotto, M. R., Staley, J. K., & Bhagwagar, Z.
Affiliations
  • From the Department of Psychiatry, Yale University, New Haven, Conn.; the Neuroscience Group, Bristol-Myers Squibb, Wallingford, Conn.; the Institute for Neurodegenerative Disorders, New Haven, Conn.; and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas.
  • Yale University (US)
ORCID
Venue
American Journal of Psychiatry
Publisher
American Psychiatric Association Publishing
Published
2012-08
Volume
169
Issue
8
Pages
851-859
ISSN
  • 0002-953X (ISSN-L)
  • 1535-7228
DOI
10.1176/appi.ajp.2012.11101546
PMC
PMC3494404
OpenAlex
W2012803743
Semantic Scholar
509ecb3712492199234e49435e4fb63c5347c8ae
Cited by
118
References
49
Citations by year
2026: 5 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 5 · 2020: 6 · 2019: 9 · 2018: 9 · 2017: 14 · 2016: 5 · 2015: 10 · 2014: 11 · 2013: 12 · 2012: 5
FWCI
4.89
Type
journal article
Language
en
Open access
Locations
  • American Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5k23mh077914-02)
  • National Institute of Mental Health (MH077681, K23-MH077914, P50MH096890, MH-077914, R01MH077681)
  • National Center for Research Resources (UL1RR024139)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
Keywords
major depressive disorder, nicotinic acetylcholine receptors, beta2 subunit, receptor availability, prefrontal cortex, postmortem brain, endogenous acetylcholine, trauma, anxiety, depressive episodes, recovered depression
MeSH terms
Adult, Brain, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Magnetic Resonance Imaging, Male, Psychiatric Status Rating Scales, Receptors, Nicotinic, Tomography, Emission-Computed, Single-Photon, Case-Control Studies, Neuroimaging

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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