Electrical stimulation of the trigeminal nerve improves olfaction in healthy individuals: A randomized, double-blind, sham-controlled trial.

BACKGROUND: Both activated by environmental odorants, there is a clear role for the intranasal trigeminal and olfactory nerves in smell function. Unfortunately, our ability to perceive odorants decreases with age or with injury, and limited interventions are available to treat smell loss. OBJECTIVE: We investigated whether electrical stimulation of the trigeminal nerve via trigeminal nerve stimulation (TNS) or transcranial direct current stimulation (tDCS) modulates odor sensitivity in healthy individuals. METHODS: We recruited 20 healthy adults (12 Female, mean age = 27) to participate in this three-visit, randomized, double-blind, sham-controlled trial. Participants were randomized to receive one of three stimulation modalities (TNS, tDCS, or sham) during each of their visits. Odor detection thresholds were obtained at baseline, immediately post-intervention, and 30-min post-intervention. Furthermore, participants were asked to complete a sustained attention task and mood assessments before odor detection testing. RESULTS: Findings reveal a timeXcondition interaction for guaiacol (GUA) odorant detection thresholds (F (3.188, 60.57) = 3.833, P = 0.0125), but not phenyl ethyl alcohol (PEA) odorant thresholds. At 30-min post-stimulation, both active TNS and active tDCS showed significantly increased sensitivity to GUA compared to sham TNS (Sham TNS = -8.30% vs. Active TNS = 9.11%, mean difference 17.43%, 95% CI 5.674 to 29.18, p = 0.0044; Sham TNS = -8.30% vs. Active tDCS = 13.58%, mean difference 21.89%, 95% CI 10.47 to 33.32, p = 0.0004). CONCLUSION: TNS is a safe, simple, noninvasive method for boosting olfaction. Future studies should investigate the use of TNS on smell function across different stimulation parameters, odorants, and patient populations.

Anxiety-related shifts in smell function in children and adolescents.

Anxious adults show changes in smell function that are consistent with a durable shift in sensitivity toward particular odorants and away from others. Little is known regarding the development of these changes, including whether they exist in youth, are stable during the transition from childhood to adolescence, and whether odorant properties (e.g. trigeminal features, hedonic valence) affect anxiety-related differences in detection. To address this, we measured smell detection thresholds to phenyl ethyl alanine (PEA), a rose-like odorant with little trigeminal properties, and guaiacol (GUA), a smoke-like odorant with high trigeminal properties. These thresholds were measured at baseline and after an acute stress challenge, the Trier Social Stress Tests, in 131 healthy youth (in 4th, 7th, and 10th grades, age 9-16 years) that reported normal to elevated levels of anxiety. At baseline, high anxious youth exhibited heightened sensitivity to GUA coupled with reduced sensitivity to PEA, as well as a further exaggeration of this bias with acute stress. Importantly, sex, age, and hedonic valence moderated the relationship between trait anxiety and sensitivity to both odorants. Smell function and its aberrations are often overlooked in the literature on biomarkers of stress and anxiety. Taken together with the extant literature, these findings suggest that greater attention is warranted to characterize potential novel olfactory therapeutic targets-across the lifespan.

Insomnia severity during early abstinence is related to substance use treatment completion in adults enrolled in an intensive outpatient program.

BACKGROUND: Insomnia and other types of sleep disturbance are highly prevalent during withdrawal across many different types of substance use disorders (SUDs). It is largely unknown how sleep impacts SUD treatment outcomes, including treatment completion. METHODS: A retrospective chart review was conducted to obtain information about sleep disturbance and treatment completion in individuals beginning an intensive outpatient (IOP) SUD treatment program. Demographic data were collected along with number of sessions completed, treatment completion, comorbid psychiatric diagnosis, pertinent lab results, and scores on three self-reported measures of sleep: the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). RESULTS: Pertinent information was available for 110 individuals. The majority had clinically significant scores on the ISI and PSQI but not the ESS. ISI, but not PSQI or ESS, was associated with treatment completion, such that those with more insomnia were less likely to complete treatment. CONCLUSION: The high prevalence of insomnia symptoms and poor sleep quality coupled with the relationship between insomnia severity and treatment completion may indicate that more severe symptoms of insomnia are a risk factor for treatment completion and subsequent relapse across many substance types. Applying evidence-based insomnia interventions in SUD treatment programs may have meaningful implications for outcomes.

Exploratory Investigation of a Brief Cognitive Behavioral Intervention and Transcranial Direct Current Stimulation on Odor Sensitivity.

OBJECTIVE: Enhanced odor sensitivity is a phenomenon that potentially underlies conditions such as multiple chemical sensitivity (MCS). Currently, there are no treatments that have been shown to effectively decrease odor sensitivity. Given similarities of odor hypersensitivity/MCS to pain sensitization disorders such as fibromyalgia, there may be a potential for interventions that improve pain tolerance to modulate odor sensitivity. METHODS: This exploratory study randomized 72 healthy community adult volunteers to receive one of six treatments in between two assessments of thermal pain tolerance and odor threshold. Participants were randomized to receive either cathodal, anodal, or sham transcranial direct current stimulation (tDCS) aimed at dorsolateral prefrontal cortex. In addition, participants were provided a brief cognitive behavioral intervention (CBI) for pain consisting of task framing, cognitive restructuring, and distraction technique training, or a control intervention consisting of information about pain. RESULTS: Persons who received a brief CBI showed significantly increased odor thresholds (reduced sensitivity) during intervention (F (1,62) = 7.29, p = .009, ηp = .11), whereas the control intervention was not associated with altered odor thresholds. Moreover, in those who received brief CBI, more severe anxiety associated with larger reductions in odor sensitivity (ρ = .364, p = .035). There was no effect of tDCS (F (2,62) = .11, p = .90) nor interaction between tDCS and CBI (F (2,62) = .32, p = .73). CONCLUSIONS: Given the connection between anxiety and MCS, results suggest that CBT techniques for somatic processes may show promise in treating conditions characterized by increased sensitivity to odors (e.g., MCS).

Trauma management therapy with virtual-reality augmented exposure therapy for combat-related PTSD: A randomized controlled trial.

Virtual reality exposure therapy (VRET) realistically incorporates traumatic cues into exposure therapy and holds promise in the treatment of combat-related posttraumatic stress disorder (PTSD). In a randomized controlled trial of 92 Iraq and Afghanistan veterans and active duty military personnel with combat-related PTSD, we compared the efficacy of Trauma Management Therapy (TMT; VRET plus a group treatment for anger, depression, and social isolation) to VRET plus a psychoeducation control condition. Efficacy was evaluated at mid- and post-treatment, and at 3- and 6-month follow-up. Consistent with our hypothesis, VRET resulted in significant decreases on the Clinician Administered PTSD Scale and the PTSD Checklist-Military version for both groups. Also consistent with our hypothesis, significant decreases in social isolation occurred only for those participants who received the TMT group component. There were significant decreases for depression and anger for both groups, although these occurred after VRET and before group treatment. All treatment gains were maintained six-months later. Although not part of the original hypotheses, sleep was not improved by either intervention and remained problematic. The results support the use of VRET as an efficacious treatment for combat-related PTSD, but suggest that VRET alone does not result in optimal treatment outcomes across domains associated with PTSD.

Odor sensitivity impairment: a behavioral marker of psychological distress?

OBJECTIVE: Enhanced odor sensitivity, particularly toward threat-related cues, may be adaptive during periods of danger. Research also suggests that chronic psychological distress may lead to functional changes in the olfactory system that cause heightened sensitivity to odors. Yet, the association between self-reported odor sensitivity, objective odor detection, and affective psychopathology is currently unclear, and research suggests that persons with affective problems may only be sensitive to specific, threat-related odors. METHODS: The current study compared adults with self-reported odor sensitivity that was described as functionally impairing (OSI; n = 32) to those who reported odor sensitivity that was non-impairing (OS; n = 17) on affective variables as well as quantitative odor detection. RESULTS: Increased anxiety sensitivity, trait anxiety, depression, and life stress, even while controlling for comorbid anxiety and depressive disorders, was found for OSI compared to OS. While OSI, compared to OS, demonstrated only a trend increase in objective odor detection of a smoke-like, but not rose-like, odor, further analysis revealed that increased detection of that smoke-like odor was positively correlated with anxiety sensitivity. CONCLUSION: These findings suggest that persons with various forms of psychological distress may find themselves significantly impaired by an intolerance of odors, but that self-reported odor sensitivity does not necessarily relate to enhanced odor detection ability. However, increased sensitivity to a smoke-like odor appears to be associated with sensitivity to aversive anxiogenic stimuli. Implications for the pathophysiology of fear- and anxiety-related disorders are discussed.

Web-based CBT for the prevention of anxiety symptoms among medical and health science graduate students.

Medical and health science graduate students report greater anxiety problems than the general population, but they are less likely to seek treatment due to cultural and logistical barriers. One preventative approach that overcomes these barriers is web-based cognitive behavioral therapy (webCBT). It is unknown whether webCBT is effective for preventing anxiety escalation within this population. A randomized controlled trial was conducted, comparing the effects of webCBT versus a control group (CG). Medical university students (n=594; Mage=27; 67% female; 80% Caucasian) completed online baseline measures and four assigned online activities. Measures were re-administered after approximately three months. There was a small interaction effect between time of assessment and treatment condition. Anxiety severity was lower in the webCBT (M[SD]=2.88[3.36]) versus CG condition (M[SD]=3.69 [3.35]) at follow-up. This effect was moderate for students with mild, versus minimal, anxiety at baseline. The proportion of students with possible anxiety disorder was lower in the webCBT (4.5%) versus CG (8.5%) condition, and the proportion of mildly anxious students with a clinically significant increase in symptoms was lower in the webCBT (10%) versus CG (20%) condition. WebCBT may aid in preventing anxiety escalation in this population, particularly for at-risk students who report mild anxiety symptoms.

Paradoxical olfactory function in combat veterans: The role of PTSD and odor factors.

Stress- and trauma-related disorders, including posttraumatic stress disorder (PTSD), are characterized by an increased sensitivity to threat cues. Given that threat detection is a critical function of olfaction and that combat trauma is commonly associated with burning odors, we sought a better understanding of general olfactory function as well as response to specific trauma-related (i.e. burning) odors in combat-related PTSD. Trauma-exposed combat veterans with (N = 22) and without (N = 25) PTSD were assessed for general and specific odor sensitivities using a variety of tools. Both groups had similar general odor detection thresholds. However, the combat veterans with PTSD, compared to combat veterans with comparable trauma exposure, but without PTSD, had increased ratings of odor intensity, negative valence, and odor-triggered PTSD symptoms, along with a blunted heart rate in response to burning rubber odor. These findings are discussed within the context of healthy versus pathological changes in olfactory processing that occur over time after psychological trauma.

Perinatal Sleep Problems: Causes, Complications, and Management.

Changes in sleep are ubiquitous in the perinatal period and it is important to be able to determine when these changes are significant enough to indicate sleep deficiency associated with increased risk for poor maternal and infant outcomes. Guidelines for identifying sleep deficiency include insomnia symptoms, excessively shortened sleep duration, and perception of insufficient or nonrestful sleep. Causes and complicating factors related to such sleep problems have been well-documented and are used to tailor behavioral and pharmacologic treatments for women who are pregnant or in the early postpartum period.

Preliminary evidence for differential olfactory and trigeminal processing in combat veterans with and without PTSD.

Structural and functional changes in the olfactory system are increasingly implicated in the expression of PTSD. Still, very little is known about the neurobiological networks of trauma-related odor sensitivity or how they relate to other objective and subjective measures of olfaction and PTSD. The purpose of this study was to replicate prior findings and further characterize olfactory function in trauma-exposed combat veterans with and without PTSD. We also sought to extend this area of research by exploring the effects of time since the combat-related index trauma (TST) on post-trauma olfactory function, as well as by correlating odor-elicited brain activity to general olfactory ability and odor-elicited PTSD symptoms. Participants included combat veterans with PTSD (CV+PTSD; n = 21) or without any psychiatric disorder (CV-PTSD; n = 27). TST was coded as greater (n = 24) or less (n = 24) than 5 years. There were main effects and/or interaction for PTSD-status and TST across several parameters of olfactory function: odor detection, odor identification, ratings for trauma-related odor intensity and triggered PTSD symptoms, and trauma odor-elicited brain activation. Overall, results suggest olfactory impairment in chronic PTSD, but not necessarily in the earlier stages of the disorder, although some early-stage olfactory findings may be predictive of later olfactory impairment. Results also suggest that trauma-exposed individuals who never develop PTSD may demonstrate olfactory resiliency. Finally, results highlight a potentially unique role of trigeminal odor properties in the olfactory-PTSD relationship.

An examination of sleep quality in veterans with a dual diagnosis of PTSD and severe mental illness.

Poor sleep quality is one of the most frequently reported symptoms by veterans with Posttraumatic Stress Disorder (PTSD) and by veterans with severe mental illness (SMI; i.e., schizophrenia spectrum disorders, bipolar disorder, major depression with or without psychotic features). However, little is known about the compounding effects of co-occurring PTSD/SMI on sleep quality in this population. Given the high rates of comorbidity and poor functional outcomes associated with sleep dysfunction, there is a need to better understand patterns of poor sleep quality in this population. The present study provides a description of sleep quality in veterans with a dual diagnosis of PTSD/SMI relative to veterans with PTSD only. Results indicated that, despite similar reports of PTSD symptom severity between the groups, veterans with PTSD/SMI reported higher levels of poor sleep quality than veterans only diagnosed with PTSD. Specifically, veterans with PTSD/SMI reported significantly greater difficulties with sleep onset and overall more sleep disturbance than their non-SMI counterparts. Implications of the findings are discussed within the context of an existing model of insomnia and suggest that more comprehensive sleep assessment and the provision of targeted sleep interventions may be helpful for those with a dual diagnosis of PTSD/SMI.

Depression-Specific Outcomes After Treatment of Chronic Rhinosinusitis.

IMPORTANCE: Depression is frequently undiagnosed in patients with chronic rhinosinusitis (CRS) and affects quality of life, productivity, and health care use. OBJECTIVE: To examine depression-specific outcomes after medical or surgical treatment of CRS. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional, prospective study of patients with refractory CRS treated at tertiary academic rhinology centers was performed from March 1, 2011, to November 1, 2015. Data analysis was performed from October 1, 2015, to November 1, 2015. INTERVENTIONS: Patients self-selected to undergo continued medical management or endoscopic sinus surgery for refractory CRS. MAIN OUTCOMES AND MEASURES: Patients completed the 22-item Sinonasal Outcome Test (SNOT22), Rhinosinusitis Disability Index (RSDI), Pittsburgh Sleep Quality Index (PSQI), and missed productivity and medication use questionnaires before and at least 6 months after treatment. Computed tomography and endoscopy scoring were performed with reviewers masked to patient-reported data. Depression-specific outcomes were recorded using the 2-item Patient Health Questionnaire (PHQ2). RESULTS: Baseline data were available on 685 patients, with 167 (24.4%) having depression according to the PHQ2 scores. The mean (SD) age of the patients was 50.5 (15.0) years, and 332 (48.4%) were male. Revision surgery status was the only baseline factor associated with depression (53.9% vs 38.0%, P < .001). Patients with depression had worse baseline SNOT22 (mean, 64.5 vs 47.6), PSQI (mean, 12.8 vs 8.4), productivity (mean, 22.8 vs 5.2 days missed), and medication use scores for oral antibiotics (mean, 23.8 vs 14.8) and oral corticosteroids (mean, 17.8 vs 9.9) (P < .001 for all). Medical and surgical treatments had similar outcomes for patients with depression with mean improvement in the PHQ2 scores from 3.96 to 1.91 (P < .001), and 110 of 167 patients (65.9%) categorized as having depression at baseline were categorized as not having depression after treatment. Improvements in the PHQ2 scores were associated with improvements in the SNOT22, PSQI, oral antibiotic use, and productivity scores (P ≤ .001 for all). CONCLUSIONS AND RELEVANCE: Depression is a common comorbidity in patients with CRS and affects numerous quality-of-life and health care outcomes. There are few objective baseline factors to aid physicians in identifying depression in patients with CRS. Medical and surgical treatments for CRS improve depression and related clinical outcomes.

Depression in chronic rhinosinusitis: A controlled cohort study.

BACKGROUND: Depression in patients with chronic rhinosinusitis (CRS) is underdiagnosed but significantly impacts treatment outcomes and health care utilization. OBJECTIVE: To compare undiagnosed depression in a CRS cohort with a healthy, non-CRS control cohort. METHODS: A case-control study of patients with symptomatic CRS and a non-CRS control cohort was performed. Demographic and comorbidity factors were correlated to depression-specific outcomes by using the Beck Depression Inventory II (BDI). RESULTS: We enrolled 42 patients with CRS and 88 control patients with no history of CRS. Physician-diagnosed depression was equivalent in CRS and control patients (6% and 9%, respectively). BDI-detected depression was higher among patients with CRS compared with controls (31% versus 14.8%, respectively; p = 0.031). BDI scores were higher in patients with CRS even when controlling for comorbid asthma, allergy, and aspirin sensitivity. When examined by polyp status, the patients without polyps had more depression than did the controls (38% versus 14.8%; p = 0.048). The somatic subscale scores of the BDI were worse in patients with CRS (p = 0.004), whereas the cognitive subscale trended toward significance (p = 0.081). CONCLUSION: Depression may be more common in CRS than previously recognized, especially in patients without polyps. Somatic subscale scores of the BDI are increased in CRS and may impact future treatment outcomes.

Burning odor-elicited anxiety in OEF/OIF combat veterans: Inverse relationship to gray matter volume in olfactory cortex.

Despite the anatomical overlap between the brain's fear/threat and olfactory systems, a very limited number of investigations have considered the role of odors and the central olfactory system in the pathophysiology of PTSD. The goal of the present study was to assess structural differences in primary and secondary olfactory cortex between combat veterans with and without PTSD (CV + PTSD, CV-PTSD, respectively). An additional goal was to determine the relationship between gray matter volume (GMV) in olfactory cortex and the distressing properties of burning-related odors. A region of interest voxel-based morphometric (VBM) approach was used to measure GMV in olfactory cortex in a well-characterized group of CV + PTSD (n = 20) and CV-PTSD (n = 25). Prior to the MRI exam, combat-related (i.e., burning rubber) and control odors were systematically sampled and rated according to their potential for eliciting PTSD symptoms. Results showed that CV + PTSD exhibited significantly reduced GMV in anterior piriform (primary olfactory) and orbitofrontal (secondary olfactory) cortices compared to CV-PTSD (both p < .01). For the entire group, GMV in bilateral anterior piriform cortex was inversely related to burning rubber odor-elicited memories of trauma (p < .05). GMV in orbitofrontal cortex was inversely related to both clinical and laboratory measures of PTSD symptoms (all p < .05). In addition to replicating an established inverse relationship between GMV in anxiety-associated brain structures and PTSD symptomatology, the present study extends those findings by being the first report of volumetric decreases in olfactory cortex that are inversely related to odor-elicited PTSD symptoms. Potential mechanisms underlying these findings are discussed.

The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults.

Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor+picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multisensory, but not unisensory cues, was significantly related to participants' level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving.

Differential odor sensitivity in PTSD: Implications for treatment and future research.

BACKGROUND: Given that odors enhance the retrieval of autobiographical memories, induce physiological arousal, and trigger trauma-related flashbacks, it is reasonable to hypothesize that odors play a significant role in the pathophysiology of posttraumatic stress disorder (PTSD). For these reasons, this preliminary study sought to examine self-reported, odor-elicited distress in PTSD. METHODS: Combat veterans with (N=30) and without (N=22) PTSD and healthy controls (HC: N=21), completed an olfactory questionnaire that provided information on the hedonic valence of odors as well as their ability to elicit distress or relaxation. RESULTS: Two main findings were revealed: Compared to HC, CV+PTSD, but not CV-PTSD, reported a higher prevalence of distress to a limited number of select odors that included fuel (p=.004), blood (p=.02), gunpowder (p=.03), and burning hair (p=.02). In contrast to this increased sensitivity, a blunting effect was reported by both groups of veterans compared to HC that revealed lower rates of distress and relaxation in response to negative hedonic odors (p=.03) and positive hedonic odors (p<.001), respectively. LIMITATIONS: The study is limited by its use of retrospective survey methods, whereas future investigations would benefit from laboratory measures taken prior, during, and after deployment. CONCLUSION: The present findings suggest a complex role of olfaction in the biological functions of threat detection. Several theoretical models are discussed. One possible explanation for increased sensitivity to select odors with decreased sensitivity to other odors is the co-occurrence of attentional bias toward threat odors with selective ignoring of distractor odors. Working together, these processes may optimize survival.

Oscillating Square Wave Transcranial Direct Current Stimulation (tDCS) Delivered During Slow Wave Sleep Does Not Improve Declarative Memory More Than Sham: A Randomized Sham Controlled Crossover Study.

BACKGROUND: A 2006 trial in healthy medical students found that anodal slow oscillating tDCS delivered bi-frontally during slow wave sleep had an enhancing effect in declarative, but not procedural memory. Although there have been supporting animal studies, and similar findings in pathological groups, this study has not been replicated, or refuted, in the intervening years. We therefore tested these earlier results for replication using similar methods with the exception of current waveform (square in our study, nearly sinusoidal in the original). OBJECTIVE/HYPOTHESIS: Our objective was to test the findings of a 2006 trial suggesting bi-frontal anodal tDCS during slow wave sleep enhances declarative memory. METHODS: Twelve students (mean age 25, 9 women) free of medical problems underwent two testing conditions (active, sham) in a randomized counterbalanced fashion. Active stimulation consisted of oscillating square wave tDCS delivered during early Non-Rapid Eye Movement (NREM) sleep. The sham condition consisted of setting-up the tDCS device and electrodes, but not turning it on during sleep. tDCS was delivered bi-frontally with anodes placed at F3/F4, and cathodes placed at mastoids. Current density was 0.517 mA/cm(2), and oscillated between zero and maximal current at a frequency of 0.75 Hz. Stimulation occurred during five-five minute blocks with 1-min inter-block intervals (25 min total stimulation). The primary outcomes were both declarative memory consolidation measured by a paired word association test (PWA), and non-declarative memory, measured by a non-dominant finger-tapping test (FTT). We also recorded and analyzed sleep EEG. RESULTS: There was no difference in the number of paired word associations remembered before compared to after sleep [(active = 3.1 ± 3.0 SD more associations) (sham = 3.8 ± 3.1 SD more associations)]. Finger tapping improved, (non-significantly) following active stimulation [(3.6 ± 2.7 SD correctly typed sequences) compared to sham stimulation (2.3 ± 2.2 SD correctly typed sequences)]. CONCLUSION: In this study, we failed to find improvements in declarative or performance memory and could not replicate an earlier study using nearly identical settings. Specifically we failed to find a beneficial effect on either overnight declarative or non-declarative memory consolidation via square-wave oscillating tDCS intervention applied bi-frontally during early NREM sleep. It is unclear if the morphology of the tDCS pulse is critical in any memory related improvements.

Olfactory cue reactivity in nicotine-dependent adult smokers.

Cue-elicited reactivity is a significant factor in relapse during smoking quit attempts. Previous research has focused primarily on visual smoking cues, with very limited research examining reactivity to olfactory triggers. Twenty-six adult non-treatment-seeking, nicotine-dependent smokers were exposed to 7 odorants during a cue-reactivity session measuring heart rate, skin conductance, and subjective craving. Cues included 2 cigarette odors (fresh tobacco and cigarette smoke), 2 odors previously identified as smoking-related (freshly mowed grass and coffee), 2 odors previously identified as unrelated to smoking (lavender and burned rubber), and 1 odorless control (propylene glycol). Pairwise comparisons demonstrated that subjective intensity of craving was significantly higher following exposure to the fresh tobacco odor compared with the odorless control (p < .01). A significant main effect for cue type on a physiological measure of arousal was also revealed, with a fresh tobacco odor-elicited significant increase in skin conductance level compared with the odorless control. However, no main effect of cue type on heart rate was found (p = .25). The results of the present study indicate that cigarette odor is an effective olfactory cue that heightens both subjective craving and increases skin conductance in smokers. Future research is needed to evaluate whether avoidance of these odors, or extinction of responses to them, can reduce relapse risk during smoking quit attempts.

Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: an open label pilot study.

Previous studies have demonstrated that combined total sleep deprivation (Wake therapy), sleep phase advance, and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N = 10, Mean age = 44 ± 16.4 SD, 6F) with unipolar depression. In addition to standard of care, they received open label Triple Chronotherapy. Participants underwent one night of total sleep deprivation (33-36 h), followed by a three-night sleep phase advance along with four 30-min sessions of bright light therapy (10,000 lux) each morning. Primary outcome measures included the 17 item Hamilton depression scale (HAM17), and the Columbia Suicide Severity Rating Scale (CSSRS), which were recorded at baseline prior to total sleep deprivation, and at protocol completion on day five. Both HAM17, and CSSRS scores were greatly reduced at the conclusion of the protocol. HAM17 scores dropped from a mean of 24.7 ± 4.2 SD at baseline to a mean of 9.4 ± 7.3 SD on day five (p = .002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5 ± 8.5 SD at baseline to a mean of 7.2 ± 5.5 SD on day five (p = .01). The results of this small pilot trial demonstrate that adjunctive Triple Chronotherapy is feasible and tolerable in acutely suicidal and depressed inpatients. Limitations include a small number of participants, an open label design, and the lack of a comparison group. Randomized controlled studies are needed.

Optogenetic stimulation of MCH neurons increases sleep.

Melanin concentrating hormone (MCH) is a cyclic neuropeptide present in the hypothalamus of all vertebrates. MCH is implicated in a number of behaviors but direct evidence is lacking. To selectively stimulate the MCH neurons the gene for the light-sensitive cation channel, channelrhodopsin-2, was inserted into the MCH neurons of wild-type mice. Three weeks later MCH neurons were stimulated for 1 min every 5 min for 24 h. A 10 Hz stimulation at the start of the night hastened sleep onset, reduced length of wake bouts by 50%, increased total time in non-REM and REM sleep at night, and increased sleep intensity during the day cycle. Sleep induction at a circadian time when all of the arousal neurons are active indicates that MCH stimulation can powerfully counteract the combined wake-promoting signal of the arousal neurons. This could be potentially useful in treatment of insomnia.