Publications by authors named "Marc S Lener"

Background: This randomized, placebo-controlled, crossover trial examined the antidepressant efficacy of the muscarinic antagonist scopolamine in major depressive disorder subjects with more severe and refractory forms of major depressive disorder relative to previous reports.

Methods: Participants included 23 medication-free major depressive disorder subjects (12 F/11 M, 20-55 years) currently experiencing a major depressive episode. Subjects had scored ≥20 on the Montgomery-Asberg Depression Rating Scale.

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Background: Some glutamatergic modulators have demonstrated rapid and relatively sustained antidepressant properties in patients with major depressive disorder. Because the potassium channel activator diazoxide increases glutamate uptake via potassium channel activation, we hypothesized that it might exert antidepressant effects by increasing the removal of glutamate from the synaptic cleft, thereby reducing excessive glutamate transmission.

Methods: This randomized, double-blind, placebo-controlled, crossover, single-site inpatient clinical study was conducted at the National Institute of Mental Health to assess the efficacy and safety of a 3-week course of diazoxide (200-400 mg daily, twice a day) versus a 3-week course of placebo in 6 participants with treatment-refractory major depressive disorder.

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Article Synopsis
  • The study analyzed various depression rating scales to identify unique factors related to depressive symptoms, with a focus on patients undergoing treatment with the rapid-acting antidepressant ketamine.
  • Through exploratory factor analysis, eight key factors were identified: Depressed Mood, Tension, Negative Cognition, Impaired Sleep, Suicidal Thoughts, Reduced Appetite, Anhedonia, and Amotivation.
  • Limitations of the study include a small sample size, lack of an independent confirmation sample, and the specific treatment-resistant characteristics of the participants, which may affect the generalizability of the findings.
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Background: Glutamatergic system abnormalities are implicated in the pathophysiology and treatment of both major depressive disorder and bipolar depression (BDep). Subsequent to studies demonstrating the rapid and robust antidepressant effects of ketamine, an N-methyl-D-aspartate receptor antagonist, other glutamatergic modulators are now being studied in clinical trials of mood disorders. A previous open-label study found that riluzole, administered in combination with the mood stabilizer lithium, had antidepressant effects.

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Clinical and preclinical studies suggest that dysfunction of the glutamatergic system is implicated in mood disorders such as major depressive disorder and bipolar depression. In clinical studies of individuals with major depressive disorder and bipolar depression, rapid reductions in depressive symptoms have been observed in response to subanesthetic-dose ketamine, an agent whose mechanism of action involves the modulation of glutamatergic signaling. The findings from these studies have prompted the repurposing and/or development of other glutamatergic modulators for antidepressant efficacy, both as monotherapy or as an adjunct to conventional monoaminergic antidepressants.

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Article Synopsis
  • In patients with major depressive disorder or bipolar disorder, issues with neurotransmission and neural plasticity can disrupt brain network connectivity.
  • Research indicates that altered levels of glutamate and GABA (gamma-aminobutyric acid) are linked to depression in both animal and human studies.
  • Ketamine, in low doses, shows promise as an antidepressant by potentially correcting these neurochemical imbalances, leading to a need for future studies that use neuroimaging to better classify depression subtypes and identify treatment response markers.
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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 dimensional assessments using the visual analog scales (VAS).

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Over the last few decades, neuroimaging techniques have advanced the identification of structural, functional, and neurochemical brain abnormalities that are associated with the increased risk, clinical course, and treatment outcomes of major depressive disorder (MDD). This paper reviews specific neuroimaging abnormalities that, on the basis of early studies, may discriminate between MDD patients who do or do not respond to current therapeutic modalities, such as antidepressants, cognitive behavioral therapy, or novel therapies. Differences in gray matter volume, white matter coherence, brain activity via structural and functional magnetic resonance imaging techniques, and concentrations of specific brain metabolites (as measured with magnetic resonance spectroscopy), are potential biomarkers discussed in this review.

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Prior diffusion tensor imaging (DTI) studies examining schizotypal personality disorder (SPD) and schizophrenia, separately have shown that compared with healthy controls (HCs), patients show frontotemporal white matter (WM) abnormalities. This is the first DTI study to directly compare WM tract coherence with tractography and fractional anisotropy (FA) across the schizophrenia spectrum in a large sample of demographically matched HCs (n = 55), medication-naive SPD patients (n = 49), and unmedicated/never-medicated schizophrenia patients (n = 22) to determine whether (a) frontal-striatal-temporal WM tract abnormalities in schizophrenia are similar to, or distinct from those observed in SPD; and (b) WM tract abnormalities are associated with clinical symptom severity indicating a common underlying pathology across the spectrum. Compared with both the HC and SPD groups, schizophrenia patients showed WM abnormalities, as indexed by lower FA in the temporal lobe (inferior longitudinal fasciculus) and cingulum regions.

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Higher rates of non-right-handedness (i.e. left- and mixed-handedness) have been reported in schizophrenia and have been a centrepiece for theories of anomalous lateralization in this disorder.

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