Novel multi-modal methodology to investigate placebo response in major depressive disorder.

The neurobiological mechanisms underlying the placebo phenomenon in patients with major depressive disorder (MDD) remain largely unknown. The progressive rise in rates of placebo responses within clinical trials over the past two decades may impede the detection of a true signal and thus present a major obstacle in new treatment development. Understanding the mechanisms would have several important implications, including (1) identifying biomarkers of placebo responders (thereby identifying those individuals who could benefit therapeutically from such interventions), (2) opening new avenues for manipulating such mechanisms to maximize symptom reduction, and (3) refining treatments with approaches that decrease (in clinical trials) or increase (in clinical practice) the placebo response. Here we investigated the research question: is the dopaminergic system one of the neurobiological underpinnings of the placebo response within MDD? Inspired by preclinical and clinical findings that have implicated dopamine in the occurrence, prediction, and expectation of reward, we hypothesized that dopaminergic activity in the mesolimbic system is a critical mediator of placebo response in MDD. To test this hypothesis, we designed a double-blind, placebo-controlled, sequential parallel comparison design clinical trial aimed at maximizing placebo antidepressant response. We integrated behavioral, imaging, and hemodynamic probes of mesocorticolimbic dopaminergic pathways within the context of manipulations of psychological constructs previously linked to placebo responses (e.g., expectation of improvement). The aim of this manuscript is to present the rationale of the study design and to demonstrate how a cross-modal methodology may be utilized to investigate the role of reward circuitry in placebo response in MDD.

A Deviance Regulation Theory Intervention Affects the Association Between Narcissistic Traits and Alcohol Harm Reduction Strategies in College Students.

Background: College students continue to report problematic alcohol use. To mitigate adverse outcomes, recent studies have employed harm reduction strategies known as Protective Behavioral Strategies (PBS). Deviance Regulation Theory (DRT), an impression management intervention, has been used to promote the use of PBS. DRT relies on impression management to modify behavior. This may be especially important for individuals with higher levels of trait narcissism. Method: College student drinkers (n = 132) were randomly assigned to receive a positive message about PBS users, a negative message about non-PBS users, or control. Participants reported on current PBS use norms, daily alcohol use, PBS use, and any alcohol-related problems experienced during the previous week for the next 10 weeks. Results: Data were analyzed using multilevel regression to examine PBS use across time by condition. When PBS norms were low, narcissism was strongly associated with lower rates of PBS use in the control group. If individuals received a positive or negative message, the association between narcissism and PBS use was diminished, among individuals with low PBS norms. There were no significant differences at mean or high levels of norms, indicating the messaging was only important for the highest risk group (i.e., those with low PBS norms). Discussion: The results of this study suggest that message framing may be effective at reducing the robust negative association between narcissism and PBS use for individuals with low PBS norms. Positive messages about individuals that use PBS may be one approach to mitigating problematic alcohol consumption in this at-risk group.

Effects of medical cannabis use on physical and psychiatric symptoms across the day among older adults.

INTRODUCTION: Older adults are increasingly using medical cannabis (MC). It is unclear if therapeutic effects increase problematic use patterns. The current study addresses this issue by examining symptom trajectories across the day and using trajectories to predict problematic use. METHODS: One-hundred six older adults (age range 55-74) who endorsed medical conditions approved for treatment using MC were recruited online. Participants received six text messages/day to assess momentary symptoms for 15 days. RESULTS: Participants provided 5,156 momentary assessments across 1,106 use days. Symptom trajectories were examined across the day. There was a decline in all symptoms following use. Negative affect, pain, and nausea evinced momentary negative reinforcement associations with cannabis intoxication. Momentary negative reinforcement was associated with adverse cannabis outcomes. Declines in post-use trauma symptoms and momentary negative reinforcement effects for negative affect were both associated with cannabis use disorder symptoms. DISCUSSION: These data suggest that MC may be effective in reducing common symptom clusters. However, the negative reinforcing effect (i.e., the link between use and symptom relief at the event level) may complicate the therapeutic nature (i.e., symptom reduction). Identifying interventions to maximize benefits while minimizing costs may increase the efficacy and safety of MC in older adults.

Revised Alcohol Protective Behavioral Strategies Scale-20 (PBSS-20) Sub-Types: An Analysis of Direct/Controlled Consumption and Indirect/Harm Reduction PBS.

Alcohol protective behavioral strategies (PBS) are commonly conceptualized with a three-factor model, as used in the Protective Behavioral Strategies Scale-20 (PBSS-20). However, inconsistencies exist between factors and drinking outcomes. The current study used factor analysis to test a two-factor structure directly via controlled consumption (Direct/CC) and indirectly via harm reduction (Indirect/HR) using the PBSS-20 among a combined sample of n = 4,883 drinkers. Both the two- and three-factor structures evince similar model fit. A two-factor model yielded more concise PBS measurement. Negative associations were observed with consumption (Direct/CC PBS) and problems (Indirect/HR). A condensed, eight-item, two-factor model accounted for less variance in alcohol consumption, however more variance in alcohol-related problems. A more consistent framework for understanding the impact of PBS on alcohol-related outcomes is provided.

Examination of the Sexual and Negative Dating Inventory (SANDI) Among Sexual and Gender Minorities: An Analysis of Psychometrics and Outcomes.

ObjectiveAdverse sexual experiences (ASE), including sexual violence, sexual risk behaviors, and regretted sex, are highly prevalent among sexual and gender minorities (SGM) compared to cisgender and heterosexual individuals. Research indicates ASEs are associated with increased mental health symptomatology and decreased subsequent protective behavior use. The Sexual and Negative Dating Inventory (SANDI) measures dating and sexual protective strategies and includes five factors: Location Sharing, Assertiveness, Self-Protection, Risk Reduction and Privacy. SANDI total scores are linked to lower ASEs in heteronormative samples. Method: SANDI was previously validated in a sample of n = 1,289 college students. Data were examined from n = 313 (24.28%) SGM individuals at baseline, and n = 95 at one-month follow-up. Individuals were 19.70 (2.98 SD) years old, and 25% were non-white. Model fit was adequate for SGM: χ2(484) = 1729.621, p < .001, CFI = .947, RMSEA = .063 (90% CI = .060, .066), SRMR = .048. Results: Non-cisgender men and non-heterosexual individuals endorse using more of the SANDI at the factor level. Using logistic regression, SANDI was not associated with history of sexual violence or sexual violence over the next month. SANDI is inversely associated with history of sexual risk and prospectively associated with less sexual risk over the next month. Negative binomial regression analyses showed SANDI was not associated with a history of regretted sex; however, SANDI was moderately associated with decreased regretted sex over the next month. Conclusion: Findings highlight the importance of dating and sexual protective behaviors across dimensions of gender and sexual orientation.

Support for incentive-sensitization theory in adolescent ad libitum smokers using ecological momentary assessment.

The incentive-sensitization theory (IST) has emerged as a potentially useful theory in explaining substance addiction. IST postulates that the prolonged use of a substance can alter neural systems that are often involved in incentive motivation and reward processes, leading to an increased "sensitization" to the substance and associated stimuli. However, this increased sensitization is thought to mediate only the individual's craving of the substance (e.g., their "wanting"), not their enjoyment of the substance (e.g., their "liking"), a process that may involve unconscious implicit changes in cognitive networks linked to specific substances. Consequently, IST may better explain the real-world dissonance reported for individuals who want to accomplish long-term substance cessation but fail to do so, a phenomenon that is common in adolescent smokers. Thus, the present study aimed to examine the principles of IST in a sample of 154 adolescent ad libitum smokers (Mage = 16.57, SDage = 1.12, 61.14% male) utilizing ecological momentary assessment. Data were analyzed utilizing a multilevel structural equation model examining changes in positive affect (PA), negative affect (NA), and stress from Time 1 (T1) and Time 2 (T2) as a function of smoking and tested the influence of implicit cognition (specifically, implicit attitudes about smoking [Implicit Association Test (IAT)]) on these associations. Consistent with the principles of IST, results found a modest significant negative association between smoking status at T1 and PA at T2 (B = -0.11, p = .047). This association was further moderated by IAT (B = -0.19, p = .029) and was particularly potentiated at high levels of IAT (B = -0.44, p < .001), compared to low (B = -0.05, p = .663) or mean levels of IAT (B = -0.25, p = .004). Findings from this study provide additional support to the principles underlying IST and indicate that, in adolescents, smoking may result in thwarted PA indicative of a transition from "liking" toward "wanting," and this is especially pronounced among those with stronger implicit smoking cognitions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A mixed method, phase 2 clinical evaluation of a novel device to treat postpartum haemorrhage.

BACKGROUND: We evaluated the safety, efficacy, and acceptability of a new device designed to facilitate uterine compression in women with postpartum haemorrhage (PPH). METHODS: A prospective, phase two clinical device trial with concurrent qualitative study, conducted in a UK consultant obstetric unit. The device was used in addition to standard care in women unresponsive to initial oxytocin therapy. The primary effectiveness outcome was additional blood loss of over 1000mls, whilst safety was assessed through adverse events. Interviews assessed device feasibility and acceptability, and were analysed using framework analysis. RESULTS: We recruited 57 women with clinical PPH after vaginal birth; 67% were primiparous and 47% had undergone operative birth. All but two (96%) had atony as a cause of the haemorrhage; in addition, 30% also had bleeding from lacerations and 11% had retained tissue. After device use, only one woman had additional blood loss over 1000mls, although 3 women (7%) needed a Bakri balloon and 14% received a blood transfusion. All but one clinician felt that the device was easy to use. Clinicians stated that the device assisted management in 85% of cases. All 56 women who responded stated that if they bled in a future birth they would want the device to be used again. There were no serious adverse events related to the device. However, 3 events were judged as 'possibly' being caused by the device - 2 minor vaginal grazes and one postnatal episiotomy infection and breakdown. Lax vaginal tissue complicated the use of the device in three women. In 47 interviews, participants, birth partners, clinician users and attending midwives viewed the device positively. Clinicians found it useful as a way of stopping blood loss and as an aid to diagnose the source of bleeding. CONCLUSIONS: The PPH Butterfly may provide a rapid, acceptable and effective treatment for postpartum haemorrhage. Clinical Trial Registration prospective with ISRCTN15452399 11/09/2017 (www.isrctn.com/ISRCTN15452399).

An Examination of Discrimination on Stress, Depression, and Oppression-Based Trauma During the COVID-19 Pandemic and the Racial Awakening of 2020.

Background: Discrimination is a pervasive societal issue that monumentally impacts people of color (POC). Many Black, Asian, and Hispanic/Latinx individuals report experiencing race-based discrimination in their lifetime. Discrimination has previously been linked to adverse health outcomes among POC, including stress, depressive, and posttraumatic stress disorder symptoms. These health disparities are posited to have become exacerbated by COVID-19 and the racial awakening of 2020. The current study examined the short- and long-term effects of discrimination on stress, depression, and oppression-based trauma among POC. Methods: Participants were (n = 398) who identified as Black, Indigenous, Hispanic/Latinx, and Asian completed an online self-report survey assessing discrimination, depression, stress, and oppression-based trauma collected at 3 time points: (T1) beginning of the COVID-19 pandemic (May 2020), (T2) 6 weeks later during the racial awakening of 2020 (June 2020), (T3) one year later (June 2021). Results: Significant positive paths were revealed from T1 discrimination to T2 depression, T2 stress, and T3 oppression-based trauma. The association between T1 discrimination and T3 oppression-based trauma was partially mediated by T2 depression, but not by stress; total and total indirect effects remained significant. The final model accounted for a significant proportion of the variance in T3 oppression-based trauma, T2 depression, and T2 stress. Conclusion: Findings are consistent with prior research linking discriminatory experiences with mental health symptomatology and provide evidence that race-based discrimination poses harmful short-and long-term mental health consequences. Further research is necessary to better understand oppression-based trauma to improve the accuracy of clinical diagnosis and treatment of POC.

A multi-pronged investigation of option generation using depression, PET and modafinil.

Option generation is a critical process in decision making, but previous studies have largely focused on choices between options given by a researcher. Consequently, how we self-generate options for behaviour remain poorly understood. Here, we investigated option generation in major depressive disorder and how dopamine might modulate this process, as well as the effects of modafinil (a putative cognitive enhancer) on option generation in healthy individuals. We first compared differences in self-generated options between healthy non-depressed adults [n = 44, age = 26.3 years (SD 5.9)] and patients with major depressive disorder [n = 54, age = 24.8 years (SD 7.4)]. In the second study, a subset of depressed individuals [n = 22, age = 25.6 years (SD 7.8)] underwent PET scans with 11C-raclopride to examine the relationships between dopamine D2/D3 receptor availability and individual differences in option generation. Finally, a randomized, double-blind, placebo-controlled, three-way crossover study of modafinil (100 mg and 200 mg), was conducted in an independent sample of healthy people [n = 19, age = 23.2 years (SD 4.8)] to compare option generation under different doses of this drug. The first study revealed that patients with major depressive disorder produced significantly fewer options [t(96) = 2.68, P = 0.009, Cohen's d = 0.54], albeit with greater uniqueness [t(96) = -2.54, P = 0.01, Cohen's d = 0.52], on the option generation task compared to healthy controls. In the second study, we found that 11C-raclopride binding potential in the putamen was negatively correlated with fluency (r = -0.69, P = 0.001) but positively associated with uniqueness (r = 0.59, P = 0.007). Hence, depressed individuals with higher densities of unoccupied putamen D2/D3 receptors in the putamen generated fewer but more unique options, whereas patients with lower D2/D3 receptor availability were likely to produce a larger number of similar options. Finally, healthy participants were less unique [F(2,36) = 3.32, P = 0.048, partial η2 = 0.16] and diverse [F(2,36) = 4.31, P = 0.021, partial η2 = 0.19] after taking 200 mg versus 100 mg and 0 mg of modafinil, while fluency increased linearly with dosage at a trend level [F(1,18) = 4.11, P = 0.058, partial η2 = 0.19]. Our results show, for the first time, that option generation is affected in clinical depression and that dopaminergic activity in the putamen of patients with major depressive disorder may play a key role in the self-generation of options. Modafinil was also found to influence option generation in healthy people by reducing the creativity of options produced.

Evaluating the combination of a Brief Motivational Intervention plus Cognitive Behavioral Therapy for Depression and heavy episodic drinking in college students.

[Correction Notice: An Erratum for this article was reported in Vol 34(2) of Psychology of Addictive Behaviors (see record 2020-16883-001). In the original article the order of authorship was incorrect. The correct second and third authors should appear instead as Brian Borsari and Jennifer E. Merrill.] Heavy episodic drinking (HED) and depressive symptoms often co-occur among college students and are associated with significant impairment. However, evidence-based treatments for these common co-occurring conditions are not available for college students. The current study compared the effectiveness of a treatment combining Cognitive-Behavioral Therapy for Depression and Brief Motivational Interviewing (CBT-D + BMI) versus Cognitive-Behavioral Therapy for Depression (CBT-D) alone among 94 college students with HED and depressive symptoms. Both treatment programs were associated with significant reductions of similar magnitude in HED, alcohol-related problems (ARP), and depressive symptoms at the end of treatment and at the 1-month follow-up assessment. Moderation analyses indicated that, among college students with fewer depressive symptoms at baseline, CBT-D was associated with greater sustained reduction in heavy drinking relative to CBT-D + BMI at the 1-month follow-up. Although the study did not include a no-treatment condition, the magnitude of improvement during treatment in both groups was greater than what is expected with passage of time. Although clinicians in college counseling centers may lack specialty training for co-occurring conditions, CBT-D is widely implemented in college settings. Our findings suggest that CBT-D may reduce both depressive symptoms and HED in college students and may be used to address a significant public health problem. (PsycINFO Database Record (c) 2020 APA, all rights reserved).