Faculty Bibliography

The impact of childhood abuse on the presentation of bipolar disorder could be further elucidated by comparing the networks of affective symptoms among individuals with and with no history of childhood abuse. Data from 476 participants in the Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study were used to fit several regularised Gaussian Graphical Models. Differences in the presentation of depressive and manic symptoms were uncovered: only among participants with a history of childhood abuse, inadequacy and pessimism were central symptoms in the network of depressive symptoms, while racing thoughts was an important symptom in the network of manic symptoms. Following network theory, focusing treatments at the symptom-level and on central symptoms "“ like inadequacy, pessimism, and racing thoughts "“ could be an effective approach for managing affective symptoms among the sizeable proportion of people with bipolar disorder who have experienced childhood abuse. This study contributes a thorough investigation of the networks of affective symptoms among participants with and with no history of childhood abuse, albeit limited by the use of a binary, self-report measure of childhood abuse, thereby emphasising the importance of assessing for childhood abuse and taking needed steps towards identifying novel targets for treating bipolar disorder.

The impact of childhood abuse on the presentation of bipolar disorder could be further elucidated by comparing the networks of affective symptoms among individuals with and with no history of childhood abuse. Data from 476 participants in the Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study were used to fit several regularised Gaussian Graphical Models. Differences in the presentation of depressive and manic symptoms were uncovered: only among participants with a history of childhood abuse, inadequacy and pessimism were central symptoms in the network of depressive symptoms, while racing thoughts was an important symptom in the network of manic symptoms. Following network theory, focusing treatments at the symptom-level and on central symptoms - like inadequacy, pessimism, and racing thoughts - could be an effective approach for managing affective symptoms among the sizeable proportion of people with bipolar disorder who have experienced childhood abuse. This study contributes a thorough investigation of the networks of affective symptoms among participants with and with no history of childhood abuse, albeit limited by the use of a binary, self-report measure of childhood abuse, thereby emphasising the importance of assessing for childhood abuse and taking needed steps towards identifying novel targets for treating bipolar disorder.

This study aimed to evaluate the dose-dependent brain temperature effects of transcranial photobiomodulation (t-PBM). Thirty adult subjects with major depressive disorder were randomized to three t-PBM sessions with different doses (low: 50 mW/cm², medium: 300 mW/cm², high: 850 mW/cm²) and a sham treatment. The low and medium doses were administered in continuous wave mode, while the high dose was administered in pulsed wave mode. A 3T MRI scanner was used to perform proton magnetic resonance spectroscopy (¹H-MRS). A voxel with a volume of 30 × 30 × 15 mm³ was placed on the left prefrontal region. Brain temperature (°C) was derived by analyzing ¹H-MRS spectrum chemical shift differences between the water (~ 4.7 ppm) and N-acetyl aspartate (NAA) (~ 2.01 ppm) peaks. After quality control of the data, the following group numbers were available for both pre- and post-temperature estimations: sham (n = 10), low (n = 11), medium (n = 10), and high (n = 8). We did not detect significant temperature differences for any t-PBM-active or sham groups post-irradiation (p-value range = 0.105 and 0.781). We also tested for potential differences in the pre-post variability of brain temperature in each group. As for t-PBM active groups, the lowest fluctuation (variance) was observed for the medium dose (σ² = 0.29), followed by the low dose (σ² = 0.47), and the highest fluctuation was for the high dose (σ² = 0.67). t-PBM sham condition showed the overall lowest fluctuation (σ² = 0.11). Our ¹H-MRS thermometry results showed no significant brain temperature elevations during t-PBM administration.

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = -17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = -14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = -13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = -37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = -42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = -34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.Trial registration: ClinicalTrials.gov, NCT02977299.

INTRODUCTION/BACKGROUND:The use of antidepressants in major depressive disorder (MDD) has been reported to influence long-term risk of Alzheimer's disease (AD) and AD-related dementias (AD/ADRD), but studies are conflicting. METHODS:We used inverse probability weighted (IPW) Cox models with time-varying covariates in a retrospective cohort study among midlife veterans with MDD within the US Veterans Affairs healthcare system from January 1, 2000 to June 1, 2022. RESULTS:A total of 35,200 patients with MDD were identified. No associations were seen regarding the effect of being exposed to any antidepressant versus no exposure on AD/ADRD risk (events = 1,056, hazard ratio = 0.94, 95% confidence interval: 0.81 to 1.09) or the exposure to specific antidepressant classes versus no exposure. A risk reduction was observed for female patients in a stratified analysis; however, the number of cases was small. DISCUSSION/CONCLUSIONS:Our study suggests that antidepressant exposure has no effect on AD/ADRD risk. The association in female patients should be interpreted with caution and requires further attention. HIGHLIGHTS/CONCLUSIONS:We studied whether antidepressant use was associated with future dementia risk. We specifically focused on patients after their first-ever diagnosis of depression. We used IPW Cox models with time-varying covariates and a large observation window. Our study did not identify an effect of antidepressant use on dementia risk. A risk reduction was observed in female patients, but the number of cases was small.

OBJECTIVE/UNASSIGNED:Few studies have focused on medical students and residents' mental health impact on medical residency selection (MRS) performance. The authors evaluated the association of performance in MRS with depressive and anxiety symptoms and with a reported psychiatric diagnosis (rPD). METHODS/UNASSIGNED:The authors enrolled candidates after the second round of MRS examinations at a Brazilian Medical School. Performance was assessed by final grade. Depressive and anxiety symptoms were assessed by the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) and the State-Trait Anxiety Inventory (STAI). The authors performed mediation analysis and multiple linear regression analysis to investigate the impact of rPD, state and trait anxiety, and depressive symptom severity on performance. RESULTS/UNASSIGNED:515 of the 643 MRS candidates (80.1%) participated in the study. Higher age, attending a preparatory course for MRS, rPD, and the number of MRS applications that year were associated with poorer performance. In mediation analysis, trait anxiety was associated with a direct effect on performance and an indirect effect mediated by rPD. CONCLUSION/UNASSIGNED:The data suggest that psychiatric diagnosis is associated with poorer performance on MRS, regardless of current symptoms of anxiety and depression. Additionally, increased levels of trait anxiety may negatively impact performance, directly and indirectly.

INTRODUCTION/UNASSIGNED:Suicidal ideation and behavior (SIB) are serious problems in people with schizophrenia spectrum disorders (SSD). Nevertheless, relatively little is known about the circuitry underlying SIB in SSD. Recently, we showed that elevated emotional impulsivity (urgency) was associated with SIB in SSD. Here we examined brain activity in people with SSD and elevated SIB. METHODS/UNASSIGNED:We tested 16 people with SSD who had low SIB and 14 people with high SIB on a task in which emotion regulation in response to affective pictures was implicitly manipulated using spoken sentences. Thus, there were neutral pictures preceded by neutral statements (NeutNeut condition), as well as negative pictures preceded by either negative (NegNeg) or neutral (NeutNeg) statements. After each picture, participants rated how unpleasant each picture was for them. The latter two conditions were compared to the NeutNeut condition. We compared the emotion-regulated condition (NeutNeg) to the unregulated condition (NeutNeut). Statistics were threshold using threshold free cluster enhancement (TFCE). RESULTS/UNASSIGNED:People in the low SIB group showed higher activation in this contrast in medial frontal gyrus, right rostral anterior cingulate, bilateral superior frontal gyrus/DLPFC, and right middle cingulate gyrus, as well as right superior temporal gyrus. DISCUSSION/UNASSIGNED:This study provides clues to the neural basis of SIB in SSD as well as underlying mechanisms.

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.