The ability to generate tissue-specific ablation of gene expression has been extremely useful in connective tissue biology, as it can potentially overcome the early embryonic lethal phenotype often associated with universal gene knockout. The value of tissue-specific knockouts can be enhanced by also allowing gene ablation to occur at specific times during development, growth or aging. In the present work a transgenic mouse has been generated in which expression of Cre recombinase is under control of both the type II collagen promoter to allow cartilage-specific expression and a doxycycline response element to permit temporal control of expression. This mouse has been crossed with the Rosa26R reporter mouse, which possesses a floxed repressor element associated with a lacZ transgene, in order to validate the functional efficacy of the conditionally expressed Cre. The results demonstrate that excision of the floxed element can be achieved specifically in cartilage at different times during embryonic and juvenile development. The conditional Cre transgenic mouse should be a valuable tool to all interested in skeletal development.

BACKGROUND:Suicide rates among young people have been increasing in recent years, yet no validated methods are available for identifying those who are at greatest risk for suicide. Abnormalities in the medial prefrontal cortex have been previously observed in suicidal individuals, but confounding factors such as treatment and chronic illness may have contributed to these findings. Thus, in this study we tested whether the size of the medial prefrontal cortex is altered in suicidal young adults who have received no treatment with psychotropic medications.METHODS:Suicidality was evaluated using the Suicide Behaviors Questionnaire-Revised (SBQ-R) and surface areas of four regions-of-interest (ROIs) within the medial prefrontal cortex were measured using magnetic resonance imaging (MRI) in a cohort of college students (n = 102). In addition, a secondary seed-based functional connectivity analysis was conducted using resting-state functional MRI data. Areas and functional connectivity of the medial prefrontal cortex of young adults with high suicidality (HS; SBQ-R score > 7; n = 20) were compared to those with low suicidality (LS; SBQ-R score = 3, n = 37).RESULTS:Compared to the LS group, the HS group had a significantly lower surface area of the right frontal pole (p < 0.05, Bonferroni-corrected) and significantly lower functional connectivity of the right frontal pole with the bilateral inferior frontal cortex (p < 0.001, Monte-Carlo corrected).LIMITATION:These findings require replication in a larger sample and extension in younger (adolescent) populations.CONCLUSION:Diminished frontal pole surface area and functional connectivity may be linked to elevated levels of suicidality in young people.

BACKGROUND:Emerging data suggest cannabis use is a component cause of psychotic disorders; however, the sequence of processes accounting for this association is poorly understood. Some clues have come from studies in laboratory settings showing that acute cannabis intoxication is associated with subclinical hallucinations and delusional thinking, i.e., "psychotic experiences". Although psychotic experiences are relatively common, those that are severe and distressing are linked to an increased risk of developing a psychotic disorder. This study aimed to investigate the association between the frequency of cannabis use and psychotic experiences in young adults. METHODS:1034 U.S. college students completed questionnaires to assess: cannabis use in the past week, delusional ideation (Peters Delusions Inventory), hallucinations (Launay-Slade Hallucinations Scale-Extended), and depression (Beck Depression Inventory). RESULTS:Participants reporting higher rates of weekly cannabis use were more likely to report hallucinatory experiences and delusional ideation. The relationship between cannabis use and hallucinatory experiences, but not the relationship between cannabis use and delusional ideation, remained significant after controlling for levels of depression. Moreover, those who reported greater amounts of cannabis use had more distressing delusional ideas, that were held with more conviction. CONCLUSIONS:Cannabis use is linked to the presence of subclinical hallucinations and delusional ideation in U.S. college students.

Contemporary models of psychosis suggest that a continuum of severity of psychotic symptoms exists, with subthreshold psychotic experiences (PEs) potentially reflecting some genetic and environmental risk factors shared with clinical psychosis. Thus, identifying abnormalities in brain activity that manifest across this continuum can shed new light on the pathophysiology of psychosis. Here, we investigated the moment-to-moment engagement of brain networks (“states”) in individuals with schizophrenia (SCZ) and PEs and identified features of these states that are associated with psychosis-spectrum symptoms. Transient brain states were defined by clustering “single snapshots” of blood oxygen level-dependent images, based on spatial similarity of the images. We found that individuals with SCZ ( n = 35) demonstrated reduced recruitment of three brain states compared to demographically matched healthy controls ( n = 35). Of these three illness-related states, one specific state, involving primarily the visual and salience networks, also occurred at a lower rate in individuals with persistent PEs ( n = 22), compared to demographically matched healthy youth ( n = 22). Moreover, the occurrence rate of this marker brain state was negatively correlated with the severity of PEs ( r = −0.26, p = 0.003, n = 130). In contrast, the spatial map of this state appeared to be unaffected in the SCZ or PE groups. Thus, reduced engagement of a brain state involving the visual and salience networks was demonstrated across the psychosis continuum, suggesting that early disruptions of perceptual and affective function may underlie some of the core symptoms of the illness.

Background: Attachment, or affiliative bonding among conspecifics, is thought to involve neural mechanisms underlying behavioral responses to threat and reward-related social signals. However, attachment-oriented responses may also rely on basic sensorimotor processes. One sensorimotor system that may play a role in attachment is the parietofrontal cortical network that responds to stimuli that are near or approaching the body, the peripersonal space (PPS) monitoring system. We hypothesized that this network may vary in responsivity to such potentially harmful stimuli, particularly those with social salience, based on individual differences in attachment styles. Methods: Young adults viewed images of human faces or cars that appeared to move towards or away from them, while functional magnetic resonance imaging data were collected. Correlations between each of four adult attachment styles, measured using the Relationship Questionnaire, and responses of the PPS network to approaching (versus withdrawing) stimuli were measured. Results: A region-of-interest (ROI) analysis, focused on six cortical regions of the PPS network that showed significant responses to approaching versus withdrawing face stimuli in an independent sample (n = 80), revealed that anxious attachment style (but not the other 3 attachment styles) was significantly positively correlated with responses to faces (but not to cars) in all six ROIs (r = 0.33-0.49, p = 0.01-0.0001, n = 50). Conclusions: These findings suggest that anxious attachment is associated with over-responsivity of a sensorimotor network involved in attending to social stimuli near the body.

Abstract Objective: Nonresponse to selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor treatment is common in patients with major depressive disorder (MDD), particularly in women, occurring in about 70% of patients despite adequate dosing. Well-tolerated augmentation strategies are needed, particularly ones that do not cause or exacerbate symptoms such as fatigue and sexual dysfunction. Low-dose testosterone has been shown to improve depression symptom severity, fatigue and sexual function in small studies of women not formally diagnosed with MDD. We sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with treatment-resistant MDD. A functional MRI (fMRI) substudy examined effects of testosterone on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation. Methods: Randomized, double-blind, placebo-controlled, 8-week trial of adjunctive testosterone cream (AndroFeme® 1, Lawley Pharmaceuticals, Australia) in 101 women, ages 21–70, with treatment-resistant MDD. Testosterone was titrated to achieve blood levels near the upper normal reference limit. Primary outcome measure was depression severity by Montgomery-Asberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. fMRI substudy (n=20) primary outcome was change in ACC activity. Results: Mean age was 47±14 (SD) years and mean baseline MADRS score was 26.6±5.9. Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS depression scores decreased in both arms [testosterone: 26.8±6.3 to 15.3±9.6; placebo: 26.3±5.4 to 14.4±9.3 (baseline to 8 weeks, respectively)], with no difference between groups (p=0.91). Fatigue and sexual function improved without differences between groups. There were no group differences in side effects. fMRI results demonstrated a relationship between ACC activation and androgen levels pretreatment but no difference in ACC activation with treatment. Conclusions: This rigorously designed, double-blinded clinical trial did not find significant group differences between adjunctive low dose transdermal testosterone and placebo for antidepressant augmentation in women with treatment-resistant MDD and had a high placebo response rate. Low-dose testosterone was well tolerated but failed to differentially impact overall depressive symptom severity, fatigue, or sexual dysfunction. Testosterone did not result in greater activity in a brain region (ACC) implicated in MDD etiopathology compared to placebo. Thus, the addition of low-dose testosterone to ineffective antidepressant treatment should not be recommended for women with MDD. Further studies using strategies designed to reduce placebo effects may be warranted.

Background A large body of evidence has demonstrated that childhood trauma increases the risk for developing a psychotic disorder. However, the path by which psychotic symptoms develop following trauma is still debated. Emotional reactivity, a tendency to experience more intense and enduring emotional responses, and hallucinations are sequelae of childhood trauma that may predict the emergence of delusional ideation. This study aimed to examine evidence for this hypothesis in a college student sample. Methods Self-report measures were used to cross-sectionally assess childhood trauma (Childhood Trauma Questionnaire), delusional ideation (Peters et al Delusions Inventory), hallucinations (Launay-Slade Hallucinations Scale), and emotional reactivity (Emotion Reactivity Scale) in 1703 US college students. Results Hallucinations and emotional reactivity fully mediated the relationship between childhood trauma and delusional ideation, after controlling for covariates (gender, age, levels of current stress, stressful life events, and resilience). Discussion These results suggest that hallucinations and emotional reactivity associated with childhood trauma may represent quantifiable targets for early intervention.

Background Subclinical delusional ideas, including persecutory beliefs, in otherwise healthy individuals are heritable symptoms associated with increased risk for psychotic illness, possibly representing an expression of one end of a continuum of psychosis severity. The identification of variation in brain function associated with these symptoms may provide insights about the neurobiology of delusions in clinical psychosis. Methods A resting-state functional magnetic resonance imaging scan was collected from 131 young adults with a wide range of severity of subclinical delusional beliefs, including persecutory ideas. Because of evidence for a key role of the amygdala in fear and paranoia, resting-state functional connectivity of the amygdala was measured. Results Connectivity between the amygdala and early visual cortical areas, including striate cortex (V1), was found to be significantly greater in participants with high (n = 43) v. low (n = 44) numbers of delusional beliefs, particularly in those who showed persistence of those beliefs. Similarly, across the full sample, the number of and distress associated with delusional beliefs were positively correlated with the strength of amygdala-visual cortex connectivity. Moreover, further analyses revealed that these effects were driven by those who endorsed persecutory beliefs. Conclusions These findings are consistent with the hypothesis that aberrant assignments of threat to sensory stimuli may lead to the downstream development of delusional ideas. Taken together with prior findings of disrupted sensory-limbic coupling in psychosis, these results suggest that altered amygdala-visual cortex connectivity could represent a marker of psychosis-related pathophysiology across a continuum of symptom severity.

Objective: Low-dose testosterone has been shown to improve depression symptom severity, fatigue, and sexual function in small studies in women not formally diagnosed with major depressive disorder. The authors sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with antidepressant-resistant major depression. A functional MRI (fMRI) substudy examined effects on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation. Methods: The authors conducted an 8-week randomized double-blind placebo-controlled trial of adjunctive testosterone cream in 101 women, ages 21-70, with antidepressant-resistant major depression. The primary outcome measure was depression symptom severity as assessed by the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. The primary outcome of the fMRI sub study (N= 20) was change in ACC activity. Results: The participants' meanage was 47 years (SD=14) and their mean baseline MADRS score was 26.6 (SD=5.9). Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS scores decreased in both study arms from baseline to week 8 (testosterone arm: from 26.8 [SD=6.3] to 15.3 [SD=9.6]; placebo arm: from 26.3 [SD=5.4] to 14.4 [SD=9.3]), with no significant difference between groups. Improvement in fatigue and sexual function did not differ between groups, nor did side effects. fMRI results showed a relationship between ACC activation and androgen levels before treatment but no difference in ACC activation with testosterone compared with placebo. Conclusions: Adjunctive transdermal testosterone, although well tolerated, was not more effective than placebo in improving symptoms of depression, fatigue, or sexual dysfunction. Imaging in a subset of participants demonstrated that testosterone did not result in greater activation of the ACC.

Prior studies have found evidence for abnormalities of medial temporal lobe structures in patients with psychotic disorders. It has been hypothesized that these abnormalities, which have been linked to dysregulation of dopaminergic neurotransmission in animal models of psychosis, may be associated with a cognitive bias to mislabel neutral events or objects in the environment as salient, which may, in turn, give rise to delusional beliefs and other psychotic symptoms. One persistent challenge for this line of research arises from the confounds associated with testing such models in psychotic disorder patients who have been treated with antipsychotic medication. In light of recent evidence for a neurobiological continuum between clinical and subclinical psychosis, in the current study, medial temporal lobe connectivity was measured in non-help-seeking young people (college students) with a range of severity of subclinical delusional beliefs (n = 131). We sought to determine whether changes in medial temporal lobe connectivity are associated with such beliefs, in particular persecutory ideas, as well as with a bias to mislabel neutral information as negatively-valenced. We also sought to better understand the phenomenology and antecedents of delusional beliefs in this young adult population, by examining relationships to other subthreshold psychotic experiences and childhood adversity in a larger cohort of subjects (n = 399). Participants with a range of severity of delusional beliefs were identified and recruited from college campuses in the Boston area. Associations among symptoms and childhood trauma were examined using hierarchical regression modeling. Resting-state functional magnetic resonance imaging data were collected in a subset of these subjects, and seed-based functional connectivity analyses were conducted using atlas-based amygdala and hippocampus seeds. Also, biases to mislabel neutral information were measured using a validated word classification task. Lastly, a portion of the cohort was followed longitudinally, via on-line assessments. A history of childhood trauma was highly associated with both delusional beliefs and hallucinatory experiences, which were highly correlated with each other. The severity of delusional beliefs in this cohort strongly correlated with the strength of the connectivity of the amygdala to early visual cortical areas. This effect remained significant after accounting for symptoms of depression, anxiety and hallucinatory experiences. Moreover, the effect was stronger when the analyses were limited to those participants with delusional beliefs that had persisted over a period of one year. Further analyses revealed that these effects were mainly accounted for by the presence of persecutory beliefs, rather than other delusion types. The hippocampal seed showed a similar, but less robust, pattern of effects. Lastly, a significant association between the tendency to mislabel neutral information as negatively-valenced and delusional belief severity was mediated by the strength of amygdala-visual cortex connectivity. Subclinical delusional beliefs, particularly persecutory ideas, are associated with a history of childhood trauma and increased connectivity between the amygdala and visual cortex, which was linked to a tendency to mislabel neutral information as negatively-valenced. These findings suggest a mechanistic path by which early stress-induced abnormalities in medial temporal lobe function could give rise to misperceptions and misinterpretations of incoming sensory stimuli.

Objectives: There are no known studies of concurrent exposure to high temperature and yoga for the treatment of depression. This study explored acceptability and feasibility of heated (Bikram) yoga as a treatment for individuals with depressive symptoms. Design: An 8-week, open-label pilot study of heated yoga for depressive symptoms. Subjects: 28 medically healthy adults (71.4% female, mean age 36 [standard deviation 13.57]) with at least mild depressive symptoms (Hamilton Rating Scale for Depression [HRSD-17] score >= 10) who attended at least one yoga class and subsequent assessment visit. Intervention: Participants were asked to attend at least twice weekly community held Bikram Yoga classes. Assessments were performed at screening and weeks 1, 3, 5, and 8. Hypotheses were tested using a modified-intent-to-treat approach, including participants who attended at least one yoga class and subsequent assessment visit (N = 28). Results: Almost half of our subjects completed the 8-week intervention, and close to a third attended three quarters or more of the prescribed 16 classes over 8 weeks. Multilevel modeling revealed significant improvements over time in both clinician-rated HRSD-17 (p = 0.003; d(GLMM) = 1.43) and self-reported Beck Depression Inventory (BDI; p < 0.001, d(GLMM) = 1.31) depressive symptoms, as well as the four secondary outcomes: hopelessness (p = 0.024, d(GLMM) = 0.57), anxiety (p < 0.001, d(GLMM) = 0.78), cognitive/physical functioning (p < 0.001, d(GLMM) = 1.34), and quality of life (p = 0.007, d(GLMM) = 1.29). Of 23 participants with data through week 3 or later, 12 (52.2%) were treatment responders (>= 50% reduction in HRSD-17 score), and 13 (56.5%) attained remission (HRSD score <= 7). More frequent attendance was significantly associated with improvement in self-rated depression symptoms, hopelessness, and quality of life. Conclusions: The acceptability and feasibility of heated yoga in this particular sample with this protocol warrants further attention. The heated yoga was associated with reduced depressive symptoms, and other improved related mental health symptoms, including anxiety, hopelessness, and quality of life.

Depression is highly prevalent in college students with a lack of access to care on college campuses. This study utilized a novel recruitment strategy and examined the efficacy of CBT provided by specialists in a depression clinical research center. We conducted depression screenings at four universities in the Boston area. 30 college students (ages 18–24 between 2009 and 2013) who were experiencing symptoms of depression and/or suicidal ideation were offered 12-weeks of a flexible manualized form of CBT. CBT resulted in a significant reduction in depression, anxiety, suicidality, and some forms of negative cognition. CBT was effective for reducing depression and related symptoms, including suicidality. Larger-scale, controlled trials, utilizing novel recruitment strategies joining academic medical centers with college campuses in desperate need of services, are needed to confirm whether this treatment and methodology would be feasible and effective for this vulnerable population.

BACKGROUND: Amygdala overactivity has been frequently observed in patients with depression, as well as in nondepressed relatives of patients with depression. A remaining unanswered question is whether elevated amygdala activity in those with familial risk for depression is related to the presence of subthreshold symptoms or to a trait-level vulnerability for illness. METHODS: To examine this question, functional magnetic resonance imaging data were collected in nondepressed young adults with (family history [FH+]) (n = 27) or without (FH-) (n = 45) a first-degree relative with a history of depression while they viewed images of "looming" or withdrawing stimuli (faces and cars) that varied in salience by virtue of their apparent proximity to the subject. Activation of the amygdala and 2 other regions known to exhibit responses to looming stimuli, the dorsal intraparietal sulcus (DIPS) and ventral premotor cortex (PMv), were measured, as well as levels of resilience, anxiety, and psychotic and depressive symptoms. RESULTS: Compared with the FH- group, the FH+ group exhibited significantly greater responses of the amygdala, but not the dorsal intraparietal sulcus or ventral premotor cortex, to looming face stimuli. Moreover, amygdala responses in the FH+ group were negatively correlated with levels of resilience and unrelated to levels of subthreshold symptoms of psychopathology. CONCLUSIONS: These findings indicate that elevated amygdala activity in nondepressed young adults with a familial history of depression is more closely linked to poor resilience than to current symptom state.

[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).

BackgroundThe Anxiety Symptoms Questionnaire (ASQ) is a brief self-report questionnaire which measures frequency and intensity of symptoms and was developed to improve assessment of anxiety symptoms in a clinical setting. We examined the reliability and validity of the ASQ in patients with anxiety disorders and/or depression, non-clinical control subjects and college students.Methods240 outpatients with generalised anxiety disorder, social anxiety disorder, panic disorder or major depressive disorder were administered the ASQ and additional questionnaires measuring depression and anxiety, as were 111 non-clinical control subjects and 487 college students. Factor analysis, Pearson’s correlation coefficients and logistic regression were used to assess reliability and validity. Test–retest reliability of the ASQ was measured using a subset who were re-administered the ASQ after 4 weeks.ResultsFactor analysis revealed measurement of a single dimension by the ASQ. Internal consistency and test–retest reliability were strong. The ASQ total score also significantly distinguished patients with an anxiety disorder from the clinical controls above and beyond the clinician-rated Hamilton Anxiety Scale.ConclusionsThe ASQ is a valid, reliable and effective self-rated measure of anxiety and may be a useful tool for screening and assessing anxiety symptoms in psychiatric as well as college settings.

Functional magnetic resonance imaging (fMRI) studies indicate that the emotional and cognitive symptoms of depression may be linked to aberrant resting-state functional connectivity (rsFC). However, much remains unknown about how abnormalities in higher frequency connectivity contribute to these disturbances. Furthermore, while concurrent evidence suggests glutamatergic abnormalities in the rostral anterior cingulate (rACC) may be implicated in depression and may contribute to disrupted rsFC, no study has examined whether these disturbances are linked in depressed populations.

BackgroundHeavy episodic drinking (HED) is a common behavior among college students that is associated with severe negative consequences. Negative reinforcement processes have been applied to elucidate mechanisms underlying relationships between consumption of alcohol and the desire to alleviate negative feelings. Distress tolerance (DT) and emotional reactivity are two mechanisms that are consistent with the self-medication model that may contribute to HED. The current study investigated relationships between DT, emotional reactivity, defined as frustration reactivity and irritability reactivity, and HED in a non-depressed college population. Given differential patterns of consumption and motivation for drinking between males and females, sex differences were also examined.Short SummaryThe study examined two constructs consistent with negative reinforcement processes, behavioral distress tolerance (DT) and emotional reactivity (frustration reactivity and irritability reactivity), to explain heavy episodic drinking (HED) among non-depressed college students. Behavioral DT and frustration reactivity independently predicted HED. Higher HED was associated with higher frustration reactivity and lower behavioral DT in women, but nor in men.MethodsOne-hundred-ten college students without depressive symptoms completed alcohol use measures and the Paced Auditory Serial Attention Task (PASAT-C) to assess behavioral DT and emotional reactivity.ResultsDT and frustration reactivity independently predicted HED. The association between DT and HED was moderated by sex such that higher levels of DT predicted higher HED among females, but not among males. Higher frustration reactivity scores were associated with a greater number of HED.ConclusionsResults provide supporting evidence that DT and emotional reactivity are distinct factors, and that they predict HED independently. Results underscore the importance of examining sex differences when evaluating the association between HED and negative reinforcement processes in this population.

Background: Early adulthood is a period of increased risk for depression and suicide. Emotional reactivity (a tendency to react to stress with increases in negative affect and maladaptive interpretations of events) is an important risk factor for these outcomes that has been under-studied. We hypothesized that elevated emotional reactivity would be associated with higher levels of depressive symptoms and suicidal thoughts and behaviors. Further, we hypothesized that experiences of childhood maltreatment would amplify this relationship, whereas the presence of resilience would act as a buffer. Methods: 1703 young adults (Mean Age=19.56 years), 71% female) completed well-validated self-report questionnaires at a single time point. Results: Higher emotional reactivity was directly associated with higher levels of depressive symptoms and suicidal thoughts and behaviors. Further, resilience levels significantly moderated the relationships between emotional reactivity and depressive symptoms and suicidal thoughts and behaviors. Finally, childhood trauma significantly moderated the relationship between emotional reactivity and suicidal thoughts and behaviors only. Limitations: This study was cross-sectional in design and relied upon self-report measures only. Conclusions: The current study demonstrates an association between emotional reactivity, depressive symptoms, and suicidal thoughts and behaviors during emerging adulthood. Whereas a history of childhood maltreatment may amplify the relationship between emotional reactivity, depression, and suicidal thoughts and behaviors, certain qualities associated with resilience may buffer against the effects of emotional reactivity. Future studies can identify the resilience-promoting factors that are most protective and develop and test interventions that can potentially augment those factors.

OBJECTIVEOur objective was to test the antidepressant effect of transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light in subjects suffering from major depressive disorder (MDD).BACKGROUNDt-PBM with NIR light is a new treatment for MDD. NIR light is absorbed by mitochondria; it boosts cerebral metabolism, promotes neuroplasticity, and modulates endogenous opioids, while decreasing inflammation and oxidative stress.MATERIALS AND METHODSWe conducted a double-blind, sham-controlled study on the safety and efficacy (change in Hamilton Depression Rating Scale [HAM-D17] total score at end-point) of adjunct t-PBM NIR [823 nm; continuous wave (CW); 28.7 × 2 cm2; 36.2 mW/cm2; up to 65.2 J/cm2; 20-30 min/session], delivered to dorsolateral prefrontal cortex, bilaterally and simultaneously, twice a week, for 8 weeks, in subjects with MDD. Baseline observation carried forward (BOCF), last observation carried forward (LOCF), and completers analyses were performed.RESULTSThe effect size for the antidepressant effect of t-PBM, based on change in HAM-D17 total score at end-point, was 0.90, 0.75, and 1.5 (Cohen's d), respectively for BOCF (n = 21), LOCF (n = 19), and completers (n = 13). Further, t-PBM was fairly well tolerated, with no serious adverse events.CONCLUSIONSt-PBM with NIR light demonstrated antidepressant properties with a medium to large effect size in patients with MDD. Replication is warranted, especially in consideration of the small sample size.