Baseline mood-state measures as predictors of antidepressant response to scopolamine

Furey, Maura L.; Nugent, Allison C.; Speer, Andrew B.; Luckenbaugh, David A.; Hoffman, Elana M.; Frankel, Erica; Drevets, Wayne C.; Zarate, Carlos A.

doi:10.1016/j.psychres.2012.01.003

Cited by 30 publications

(23 citation statements)

References 31 publications

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“…Several preclinical and clinical studies have provided extensive evidence supporting the role of ACh in depressive-like behavior and demonstrating that administration of AChR antagonists produces antidepressant-like effects [29–31, 35–38, 52, 53]. Our findings strongly point to VTA AChR mechanisms as important modulators of behavioral phenotypes in the FST.…”

Section: Discussionsupporting

confidence: 67%

Ventral tegmental area cholinergic mechanisms mediate behavioral responses in the forced swim test

Addy

Nunes

Wickham

2015

Behavioural Brain Research

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Recent studies revealed a causal link between ventral tegmental area (VTA) phasic dopamine (DA) activity and pro-depressive and antidepressant-like behavioral responses in rodent models of depression. Cholinergic activity in the VTA has been demonstrated to regulate phasic DA activity, but the role of VTA cholinergic mechanisms in depression-related behavior is unclear. The goal of this study was to determine whether pharmacological manipulation of VTA cholinergic activity altered behavioral responding in the forced swim test (FST) in rats. Here, male Sprague-Dawley rats received systemic or VTA-specific administration of the acetylcholinesterase inhibitor, physostigmine (systemic; 0.06 or 0.125 mg/kg, intra-cranial; 1 or 2 μg/side), the muscarinic acetylcholine receptor (AChR) antagonist scopolamine (2.4 or 24 μg/side), or the nicotinic AChR antagonist mecamylamine (3 or 30 μg/side), prior to the FST test session. In control experiments, locomotor activity was also examined following systemic and intra-cranial administration of cholinergic drugs. Physostigmine administration, either systemically or directly into the VTA, significantly increased immobility time in FST, whereas physostigmine infusion into a dorsal control site did not alter immobility time. In contrast, VTA infusion of either scopolamine or mecamylamine decreased immobility time, consistent with an antidepressant-like effect. Finally, the VTA physostigmine-induced increase in immobility was blocked by co-administration with scopolamine, but unaltered by co-administration with mecamylamine. These data show that enhancing VTA cholinergic tone and blocking VTA AChRs has opposing effects in FST. Together, the findings provide evidence for a role of VTA cholinergic mechanisms in behavioral responses in FST.

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Section: Discussionsupporting

confidence: 67%

Ventral tegmental area cholinergic mechanisms mediate behavioral responses in the forced swim test

Addy

Nunes

Wickham

2015

Behavioural Brain Research

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“…The VAS is typically used in measuring pain or somatic symptoms in pain related disorders as well as in association with depression (Hung et al 2014). In a recent clinical trial of patients with MDD and bipolar disorder, baseline VAS restlessness, sad, and irritated was associated with an antidepressant response to scopolamine, a potentially effective and novel agent for depression (Furey et al 2012). In future work, we will explore other scales that enable correlation to symptom dimensions (eg., anhedonia, irritability, and fatigue).…”

Section: Resultsmentioning

confidence: 99%

Cortical abnormalities and association with symptom dimensions across the depressive spectrum

Lener¹,

Kundu

Wong

et al. 2016

Journal of Affective Disorders

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Background Few studies have investigated the relationship between structural brain abnormalities and dimensions of depressive symptomatology. Methods In the current study, we examined the relationship between cortical structural abnormalities and specific behavioral dimensions relevant to depression in a sample of unmedicated patients with major depressive disorder (MDD, n=57) and demographically similar healthy control volunteers (HC, n=29). All subjects underwent diagnostic assessment with the SCID, MRI at 3T, and behavioral dimensional assessments using the visual analog scales (VAS). Cortical regions were extracted for each subject, and group comparisons of cortical volume (CV), surface area (SA), and cortical thickness (CT) were performed controlling for multiple comparisons using a bootstrapping technique. Regions demonstrating group differences were analyzed for correlation with specific behavioral dimensions. Results As compared with HC, MDD subjects exhibited reduced CV within the left supramarginal gyrus, right ventrolateral prefrontal cortex (VLPFC), entorhinal cortex, parahippocampal gyrus, fusiform gyrus and pericalcarine, reduced SA in the right VLPFC, cuneus, and left temporal pole, and reduced CT in the right rostral anterior cingulate cortex (rACC) (all p’s < 0.05, corrected). The largest effect occurred within the right VLPFC CV and SA (MDD

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“…For example, both the muscarinic cholinergic receptor antagonist scopolamine, and the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine have rapid-acting antidepressant effects 4, 5 , and clinical indicators and biomarkers of rapid treatment response to both medications have been investigated 6 . Baseline scores on the Profile of Mood States (POMS) depression subscale, as well as the restlessness, sad, and irritated items on the Visual Analog Scales (VAS), discriminated scopolamine responders from nonresponders in both major depressive disorder (MDD) and bipolar depression 7 . Increased functional magnetic resonance imaging (MRI) baseline blood-oxygen level dependent (BOLD) signal in the middle occipital cortex during the stimulus-processing component of an emotional memory task also predicted increased antidepressant response to scopolamine 8 .…”

Section: Introductionmentioning

confidence: 99%

Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression

Niciu¹,

Luckenbaugh²,

Ionescu³

et al. 2014

J. Clin. Psychiatry

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133

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Objective The N-methyl-D-aspartate receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD) and bipolar depression. Clinical predictors may identify those more likely to benefit from ketamine within clinically-heterogeneous populations. Method Treatment-resistant inpatients with DSM-IV-TR-diagnosed MDD or bipolar I/II depression currently experiencing a moderate-to-severe major depressive episode were enrolled between November 2004 and March 2013. All subjects received a single subanesthetic (0.5mg/kg) ketamine infusion over 40 minutes. Patients were analyzed at the 230-minute post-infusion time point (N=108), at Day 1 (N=82), and at Day 7 (N=71). Univariate Pearson correlations were performed for each variable with change-from-baseline in the 17-item Hamilton Depression Rating Scale (HDRS). Multivariate linear regression was then conducted for statistically significant predictors (p<0.05, two-tailed). Results Higher body mass index (BMI) correlated with greater HDRS improvement at 230 minutes and at Day 1 (standardized β=−0.30, p=0.004), but not at Day 7 (standardized β=−0.18, p=0.10). Family history of an alcohol use disorder in a first-degree relative was associated with greater HDRS improvement at Day 1 (standardized β=−0.37, p=0.001) and Day 7 (standardized β=−0.41, p<0.001). No prior history of suicide attempt(s) was associated with greater improvement only at Day 7 (standardized β=0.28, p=0.01). The overall statistical model explained 13, 23, and 36 percent of HDRS percent change variance at 230 minutes, Day 1, and Day 7, respectively. Conclusion Despite its post-hoc nature, the study identified several clinical correlates of ketamine's rapid and durable antidepressant effects. Further investigation of these relationships is critical for individualized treatment of depression.

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Baseline mood-state measures as predictors of antidepressant response to scopolamine

Cited by 30 publications

References 31 publications

Ventral tegmental area cholinergic mechanisms mediate behavioral responses in the forced swim test

Ventral tegmental area cholinergic mechanisms mediate behavioral responses in the forced swim test

Cortical abnormalities and association with symptom dimensions across the depressive spectrum

Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression

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