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Transcranial photobiomodulation increases intrinsic brain activity within irradiated areas in early Alzheimer's disease: Potential link with cerebral metabolism [Letter]

Gaggi, Naomi L; Collins, Katherine A; Gonzalez-Castillo, Javier; Hurtado, Aura M; Castellanos, Francisco Xavier; Osorio, Ricardo; Cassano, Paolo; Iosifescu, Dan V
PMID: 38387555
ISSN: 1876-4754
CID: 5634492

Trajectories of Depressive Individual Symptoms over Time during Transcranial Photobiomodulation

Urata, Minoru; Cassano, Paolo; Norton, Richard; Sylvester, Katelyn M.; Watanabe, Koichiro; Iosifescu, Dan V.; Sakurai, Hitoshi
Transcranial photobiomodulation (t-PBM) is an innovative, non-invasive treatment for depression. This study aimed to investigate the changes in individual depressive symptoms during t-PBM treatment and identify the symptoms that improved in those who responded to treatment. The research analyzed data from two trials, the Evaluation of Light-emitting diodes Therapeutic Effect in Depression-2 and -3, focusing on patients with major depressive disorder. The patients received t-PBM treatment on the F3 and F4 regions of the scalp over eight weeks, with symptoms assessed weekly using the Quick Inventory for Depression Symptomatology (QIDS). A response was defined as a 50% or greater reduction in the QIDS score at eight weeks from baseline. Out of the 21 patients analyzed, 4 responded at eight weeks. Neurovegetative symptoms, including sleep disturbances and change in appetite, improved in ≥50% of the patients who had these symptoms at baseline. However, core depressive symptoms, including a depressed mood and lack of energy, persisted in about 80"“90% of the patients. The responders showed a more than 75% improvement in these core depressive symptoms. These findings suggest that t-PBM treatment may uniquely alleviate certain neurovegetative symptoms in depression, and the improvement in core depressive symptoms might be linked to a clinical response to this treatment.
ISSN: 2304-6732
CID: 5630542

Personality characteristics, not clinical symptoms, are associated with anhedonia in a community sample: A preliminary investigation

Tobe, Russell H; Tu, Lucia; Keefe, John R; Breland, Melissa M; Ely, Benjamin A; Sital, Melissa; Richard, Jasmin T; Tural, Umit; Iosifescu, Dan V; Gabbay, Vilma
Anhedonia is a salient transdiagnostic psychiatric symptom associated with increased illness severity and chronicity. Anhedonia is also present to varying degrees in non-clinical cohorts. Here, we sought to examine factors influencing expression of anhedonia. Participants (N = 335) were recruited through the Nathan Kline Institute-Rockland Sample, an initiative to deeply phenotype a large community sample across the lifespan. Utilizing a data-driven approach, we evaluated associations between anhedonia severity, indexed by Snaith-Hamilton Pleasure Scale (SHAPS), and 20 physical, developmental, and clinical measures, including Structured Clinical Interview for DSM-IV, Beck Depression Inventory, State-Trait Anxiety Inventory, NEO Five-Factor Inventory-3 (NEO-FFI-3), BMI, Hemoglobin A1C, and demography. Using a bootstrapped AIC-based backward selection algorithm, seven variables were retained in the final model: NEO-FFI-3 agreeableness, extraversion, and openness to experience; BMI; sex; ethnicity; and race. Though median SHAPS scores were greater in participants with psychiatric diagnoses (18.5) than those without (17.0) (U = 12238.5, z = 2.473, p = 0.013), diagnosis and symptom measures were not retained as significant predictors in the final robust linear model. Participants scoring higher on agreeableness, extraversion, and openness to experience reported significantly lower anhedonia. These results demonstrate personality as a mild-to-moderate but significant driver of differences in experiencing pleasure in a community sample.
PMID: 37922596
ISSN: 1879-1379
CID: 5611652

Augmentation of learning in schizophrenia by d-serine and auditory remediation is related to auditory and frontally-generated biomarkers: A randomized, double-blind, placebo-controlled study [Letter]

Govani, Viraj; Shastry, Adithya M; Iosifescu, Dan V; Govil, Preetika; Mayer, Megan R; Sobeih, Tarek; Choo, Tse-Hwei; Wall, Melanie M; Sehatpour, Pejman; Kantrowitz, Joshua T
PMID: 37690312
ISSN: 1573-2509
CID: 5594212

Efficacy of Transcranial Photobiomodulation on Depressive Symptoms: A Meta-Analysis

Cho, Yoonju; Tural, Umit; Iosifescu, Dan V
PMID: 37651208
ISSN: 2578-5478
CID: 5618172

Dose-Dependent Augmentation of Neuroplasticity-Based Auditory Learning in Schizophrenia: A Double-Blind, Placebo-Controlled, Randomized, Target Engagement Clinical Trial of the NMDA Glutamate Receptor Agonist d-serine

Sehatpour, Pejman; Iosifescu, Dan V; De Baun, Heloise M; Shope, Constance; Mayer, Megan R; Gangwisch, James; Dias, Elisa; Sobeih, Tarek; Choo, Tse-Hwei; Wall, Melanie M; Medalia, Alice; Saperstein, Alice M; Kegeles, Lawrence S; Girgis, Ragy R; Carlson, Marlene; Kantrowitz, Joshua T
BACKGROUND:Patients with schizophrenia show reduced NMDA glutamate receptor-dependent auditory plasticity, which is rate limiting for auditory cognitive remediation (AudRem). We evaluate the utility of behavioral and neurophysiological pharmacodynamic target engagement biomarkers, using a d-serine+AudRem combination. METHODS:Forty-five participants with schizophrenia or schizoaffective disorder were randomized to 3 once-weekly AudRem visits + double-blind d-serine (80, 100, or 120 mg/kg) or placebo in 3 dose cohorts of 12 d-serine and 3 placebo-treated participants each. In AudRem, participants indicated which paired tone was higher in pitch. The primary outcome was plasticity improvement, operationalized as change in pitch threshold between AudRem tones [(test tone Hz - reference tone Hz)/reference tone Hz] between the initial plateau pitch threshold (mean of trials 20-30 of treatment visit 1) to pitch threshold at the end of visit(s). Target engagement was assessed by electroencephalography outcomes, including mismatch negativity (pitch primary). RESULTS:There was a significant overall treatment effect for plasticity improvement (p = .014). Plasticity improvement was largest within the 80 and 100 mg/kg groups (p < .001, d > 0.67), while 120 mg/kg and placebo-treated participants showed nonsignificant within-group changes. Plasticity improvement was seen after a single treatment and was sustained on subsequent treatments. Target engagement was demonstrated by significantly larger mismatch negativity (p = .049, d = 1.0) for the 100 mg/kg dose versus placebo. CONCLUSIONS:Our results demonstrate sufficient proof of principle for continued development of both the d-serine+AudRem combination and our target engagement methodology. The ultimate utility is dependent on the results of an ongoing larger, longer study of the combination for clinically relevant outcomes.
PMID: 36958998
ISSN: 1873-2402
CID: 5538092

Protocol Report on the Transcranial Photobiomodulation for Alzheimer"™s Disease (TRAP-AD) Study

Iosifescu, Dan V.; Song, Xiaotong; Gersten, Maia B.; Adib, Arwa; Cho, Yoonju; Collins, Katherine M.; Yates, Kathy F.; Hurtado-Puerto, Aura M.; McEachern, Kayla M.; Osorio, Ricardo S.; Cassano, Paolo
Background: Alzheimer"™s disease"™s (AD) prevalence is projected to increase as the population ages and current treatments are minimally effective. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates into the cerebral cortex, stimulates the mitochondrial respiratory chain, and increases cerebral blood flow. Preliminary data suggests t-PBM may be efficacious in improving cognition in people with early AD and amnestic mild cognitive impairment (aMCI). Methods: In this randomized, double-blind, placebo-controlled study with aMCI and early AD participants, we will test the efficacy, safety, and impact on cognition of 24 sessions of t-PBM delivered over 8 weeks. Brain mechanisms of t-PBM in this population will be explored by testing whether the baseline tau burden (measured with 18F-MK6240), or changes in mitochondrial function over 8 weeks (assessed with 31P-MRSI), moderates the changes observed in cognitive functions after t-PBM therapy. We will also use changes in the fMRI Blood-Oxygenation-Level-Dependent (BOLD) signal after a single treatment to demonstrate t-PBM-dependent increases in prefrontal cortex blood flow. Conclusion: This study will test whether t-PBM, a low-cost, accessible, and user-friendly intervention, has the potential to improve cognition and function in an aMCI and early AD population.
ISSN: 2227-9032
CID: 5568022

The Impact of Post-Stroke Depressive Symptoms on Cognitive Performance in Women and in Men: A 4 Month Prospective Study

Sobreiro, Matildes F.M.; Terroni, Luisa; Guajardo, Valeri Delgado; Mattos, Patricia Ferreira; Leite, Claudia da Costa; Amaro, Edson; Tinone, Gisela; Iosifescu, Dan V.; Fraguas, Renerio
Background: Depressive symptoms have been associated with cognitive impairment after stroke, and women may be specifically affected. Objective: The aim of this study was to investigate gender-specific characteristics in the relationship between changes in depression severity and changes in cognitive performance after stroke. Methods: We prospectively evaluated 73 patients without a previous history of depression in the first and fourth months after a first ischemic stroke. The severity of depressive symptoms was assessed using the 31-item version of the Hamilton Rating Scale for Depression, and executive function, attention, working memory, and verbal fluency were assessed using a neuropsychological battery. Results: We included 46 (63.0%) men and 27 (36.9%) women, with mean ages of 55.2 (SD ± 15.1) and 46.8 (SD ± 14.7) years, respectively. We found significant improvement in the digit span forward and Stroop dots from month 1 to month 4 post stroke for both men and women. Women, but not men, presented a correlation between changes in phonemic verbal fluency and changes in the 31-item version of the Hamilton Rating Scale for Depression scores. Improvement in depression was correlated with improvement in verbal fluency, and worsening in depression was correlated with worsening in verbal fluency. Conclusions: Our results suggest that women might be more vulnerable to the relationship between depressive symptoms and cognitive performance, and improvement of depression may be necessary for women"™s improvement in phonemic verbal fluency from the first to the fourth month after a stroke. We did not adjust the results for multiple comparisons. Thus, our findings might be considered preliminary, and confirmatory studies, also focusing on specific characteristics of women that could explain these differences, are warranted.
ISSN: 2075-1729
CID: 5568052

Photobiomodulation: An Emerging Treatment Modality for Depression

Vieira, Willians Fernando; Iosifescu, Dan V; McEachern, Kayla Marie; Gersten, Maia; Cassano, Paolo
Major depressive disorder (MDD) is considered a global crisis. Conventional treatments for MDD consist of pharmacotherapy and psychotherapy, although a significant number of patients with depression respond poorly to conventional treatments and are diagnosed with treatment-resistant depression (TRD). Transcranial photobiomodulation (t-PBM) therapy uses near-infrared light, delivered transcranially, to modulate the brain cortex. The aim of this review was to revisit the antidepressant effects of t-PBM, with a special emphasis on individuals with TRD. A search on PubMed and tracked clinical studies using t-PBM for the treatment of patients diagnosed with MDD and TRD.
PMID: 37149348
ISSN: 1558-3147
CID: 5509212

Sodium-Glucose Cotransporter-2 Inhibitors in Depression

Liebers, David T; Ebina, Wataru; Iosifescu, Dan V
Novel treatment strategies that refract existing treatment algorithms for depressive disorders are being sought. Abnormal brain bioenergetic metabolism may represent an alternative, therapeutically targetable neurobiological basis for depression. A growing body of research points to endogenous ketones as candidate neuroprotective metabolites with the potential to enhance brain bioenergetics and improve mood. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally approved for the treatment of diabetes, induce ketogenesis and are associated with mood improvement in population-based studies. In this column, we highlight the rationale for the hypothesis that ketogenesis induced by SGLT2 inhibitors may be an effective treatment for depressive disorders.
PMID: 37437254
ISSN: 1465-7309
CID: 5537082