Publications by authors named "Lawrence H Price"

123 Publications

A pilot randomized controlled trial of smartphone-assisted mindfulness-based intervention with contingency management for smokers with mood disorders.

Exp Clin Psychopharmacol 2021 Jul 22. Epub 2021 Jul 22.

School of Nursing.

Cigarette smoking disproportionately affects individuals with mood disorders, but smoking cessation interventions have modest effects in this population. Home mindfulness practice during abstinence incentivized via contingency management (CM) may help those in affective distress quit smoking.

Method: Adult smokers receiving outpatient psychiatric treatment for mood disorders were randomized to receive a smartphone-assisted mindfulness-based smoking cessation intervention with contingency management (SMI-CM, = 25) or enhanced standard treatment (EST, = 24) with noncontingent rewards. Participants in SMI-CM were prompted to practice audio-guided mindfulness five times per day for 38 days (vs. no comparison intervention in EST), and received monetary incentives for carbon monoxide (CO) ≤ 6 ppm. The primary outcome was biochemically verified 7-day point prevalence abstinence rates 2, 4, and 13 weeks after a target quit day.

Results: Of the 49 participants, 63.3% were Latinx and 30.6% Black; 75.5% reported household incomes < $25,000. Abstinence rates for SMI-CM were 40.0%, 36.0%, and 16.0% versus 4.2%, 8.3%, and 4.2% in EST at weeks 2, 4, and 13. A generalized estimating equations (GEE) model showed significant overall differences in abstinence rates in SMI-CM versus EST (adjusted odds ratio [A] = 8.12, 95% CI = 1.42-46.6, = .019). Those who received SMI-CM reported significantly greater reduction in smoking-specific experiential avoidance from baseline to 3 days prior to quit date (β = -7.21, 95% CI = -12.1-2.33, = .006).

Conclusions: SMI-CM may increase cessation rates among smokers with mood disorders, potentially through reduced smoking-specific experiential avoidance. SMI-CM is a promising intervention, and warrants investigation in a fully powered randomized controlled trial (RCT). (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/pha0000506DOI Listing
July 2021

Sustained Care Smoking Cessation Intervention for Individuals Hospitalized for Psychiatric Disorders: The Helping HAND 3 Randomized Clinical Trial.

JAMA Psychiatry 2021 Aug;78(8):839-847

Tobacco Research and Treatment Center, Massachusetts General Hospital, Harvard Medical School, Boston.

Importance: Smoking among individuals with serious mental illness (SMI) represents a major public health problem. Intervening during a psychiatric hospital stay may provide an opportunity to aid engagement in smoking cessation treatment and facilitate success in quitting.

Objective: To examine the effectiveness of a multicomponent, sustained care (SusC) smoking cessation intervention in adults with SMI receiving inpatient psychiatric care.

Design, Setting, And Participants: The Helping HAND 3 randomized clinical trial compared SusC with usual care (UC) among individuals with SMI who smoked daily and were receiving inpatient psychiatric care in Austin, Texas, in a single hospital. The study was conducted from July 2015 through August 2019.

Interventions: The UC intervention involved brief smoking cessation information, self-help materials and advice from the admitting nurse, and an offer to provide nicotine replacement therapy during hospitalization. The SusC intervention included 4 main components designed to facilitate patient engagement with postdischarge smoking cessation resources: (1) inpatient motivational counseling; (2) free transdermal nicotine patches on discharge; (3) an offer of free postdischarge telephone quitline, text-based, and/or web-based smoking cessation counseling, and (4) postdischarge automated interactive voice response calls or text messages.

Main Outcomes And Measures: The primary outcome was biochemically verified 7-day point-prevalence abstinence at 6-month follow-up. A secondary outcome was self-reported smoking cessation treatment use at 1, 3, and 6 months after discharge.

Results: A total of 353 participants were randomized, of whom 342 were included in analyses (mean [SD] age, 35.8 [12.3] years; 268 White individuals [78.4%]; 280 non-Hispanic individuals [81.9%]; 169 women [49.4%]). They reported smoking a mean (SD) of 16.9 (10.4) cigarettes per day. Participants in the SusC group evidenced significantly higher 6-month follow-up point-prevalence abstinence rates than those in the UC group (8.9% vs 3.5%; adjusted odds ratio, 2.95 [95% CI, 1.24-6.99]; P = .01). The number needed to treat was 18.5 (95% CI, 9.6-306.4). A series of sensitivity analyses confirmed effectiveness. Finally, participants in the SusC group were significantly more likely to report using smoking cessation treatment over the 6 months postdischarge compared with participants in the UC group (74.6% vs 40.5%; relative risk, 1.8 [95% CI, 1.51-2.25]; P < .001).

Conclusions And Relevance: The findings of this randomized clinical trial provide evidence for the effectiveness of a scalable, multicomponent intervention in promoting smoking cessation treatment use and smoking abstinence in individuals with SMI following hospital discharge.

Trial Registration: ClinicalTrials.gov Identifier: NCT02204956.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.0707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100915PMC
August 2021

Do deviations from the 5 sessions per week schedule impact outcomes of transcranial magnetic stimulation for major depressive disorder?

Brain Stimul 2020 Nov - Dec;13(6):1491-1493. Epub 2020 Aug 6.

Butler Hospital TMS Clinic and Neuromodulation Research Facility, Providence, RI, USA; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA. Electronic address:

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http://dx.doi.org/10.1016/j.brs.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111778PMC
August 2020

Low-Dose Testosterone Augmentation for Antidepressant-Resistant Major Depressive Disorder in Women: An 8-Week Randomized Placebo-Controlled Study.

Am J Psychiatry 2020 10 14;177(10):965-973. Epub 2020 Jul 14.

Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (Dichtel, Kimball, Miller); Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston (Nyer, Mischoulon, Deckersbach, Dougherty, Yeung, Cassano, Hahn, Farabaugh, Pedrelli, Trinh, Dording, Cusin, Papakostas, Chang, Fisher, Shapero, Chen, Fava); Department of Psychiatry, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston (Brady); Biostatistics Center, Massachusetts General Hospital, Boston (Schoenfeld); Butler Hospital and Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Medicine, Brown University, Providence, R.I. (Carpenter, Tyrka, Price); Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston (Rao); Mayo Clinic Endocrine Laboratory, Rochester, Minn. (Singh).

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-Åsberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. The primary outcome of the fMRI substudy (N=20) was change in ACC activity.

Results: The participants' mean age 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.
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http://dx.doi.org/10.1176/appi.ajp.2020.19080844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748292PMC
October 2020

Molecular markers of neuroendocrine function and mitochondrial biogenesis associated with early life stress.

Psychoneuroendocrinology 2020 06 20;116:104632. Epub 2020 Feb 20.

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA; Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA.

Objective: Glucocorticoid receptor gene (NR3C1) promoter methylation influences cellular expression of the glucocorticoid receptor and is a proposed mechanism by which early life stress impacts neuroendocrine function. Mitochondria are sensitive and responsive to neuroendocrine stress signaling through the glucocorticoid receptor, and recent evidence with this sample and others shows that mitochondrial DNA copy number (mtDNAcn) is increased in adults with a history of early stress. No prior work has examined the role of NR3C1 methylation in the association between early life stress and mtDNAcn alterations.

Methods: Adult participants (n = 290) completed diagnostic interviews and questionnaires characterizing early stress and lifetime psychiatric symptoms. Medical conditions, active substance abuse, and prescription medications other than oral contraceptives were exclusionary. Subjects with a history of lifetime bipolar, obsessive-compulsive, or psychotic disorders were excluded; individuals with other forms of major psychopathology were included. Whole blood mtDNAcn was measured using qPCR; NR3C1 methylation was measured via pyrosequencing. Multiple regression and bootstrapping procedures tested NR3C1 methylation as a mediator of effects of early stress on mtDNAcn.

Results: The positive association between early adversity and mtDNAcn (p = .02) was mediated by negative associations of early adversity with NR3C1 methylation (p = .02) and NR3C1 methylation with mtDNAcn (p < .001). The indirect effect involving early adversity, NR3C1 methylation, and mtDNAcn was significant (95 % CI [.002, .030]).

Conclusions: NR3C1 methylation significantly mediates the association between early stress and mtDNAcn, suggesting that glucocorticoid receptor signaling may be a mechanistic pathway underlying mtDNAcn alterations of interest for future longitudinal work.
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http://dx.doi.org/10.1016/j.psyneuen.2020.104632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887859PMC
June 2020

Dose increase of S-Adenosyl-Methionine and escitalopram in a randomized clinical trial for major depressive disorder.

J Affect Disord 2020 02 31;262:118-125. Epub 2019 Oct 31.

Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. Electronic address:

Background: The optimal dose of S-adenosyl methionine (SAMe) for major depressive disorder (MDD) remains unclear. The objective of this analysis was to address whether a dose increase provided further improvement in cases of insufficient response using data from an existing randomized clinical trial.

Methods: Sixty-five patients with MDD who failed to respond to SAMe 1,600 mg/day, escitalopram 10 mg/day, or placebo for 6 weeks were treated with doubled doses of the allocated treatments for the following 6 weeks. Changes in 17-item Hamilton Depression Rating Scale, Inventory of Depressive Symptomatology-Self Rated, and Systematic Assessment for Treatment Emergent Events-Specific Inquiry were compared between the lower and higher dose treatments in each treatment group and among the higher dose treatments of SAMe, escitalopram, and placebo.

Results: Various depression severity scores decreased significantly for all three treatment arms during the higher dose treatment. No within-group and between-group differences were found in any of the efficacy measures when comparing the doses and treatments. There was a significant difference in reported abdominal discomfort among patients receiving the higher dose of SAMe (31.3%), compared to escitalopram (8.7%) and placebo (3.8%) (χ2=7.32, p = 0.026).

Limitations: The sample size was relatively small. The study duration for dose increase was relatively short.

Conclusions: Patients with MDD failing to respond to 1,600 mg/day of SAMe may improve after increasing the dose to 3,200 mg/day, but we cannot rule out the contribution of a placebo effect and time-related improvement. The risk of abdominal discomfort may be increased with higher doses of SAMe.
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http://dx.doi.org/10.1016/j.jad.2019.10.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917851PMC
February 2020

Neuroimmune signaling in neuropsychiatric disease.

Psychopharmacology (Berl) 2019 10;236(10):2855

Brown University, Warren Alpert Medical School, Butler Hospital, 345 Blackstone Blvd, Providence, RI, 02906, USA.

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http://dx.doi.org/10.1007/s00213-019-05355-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986316PMC
October 2019

Corrigendum to "Childhood maltreatment, behavioral adjustment, and molecular markers of cellular aging in preschool-aged children: A cohort study" [Psychoneuroendocrinology 107 (2019) 261-269].

Psychoneuroendocrinology 2019 Dec 8;110:104466. Epub 2019 Oct 8.

Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA. Electronic address:

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http://dx.doi.org/10.1016/j.psyneuen.2019.104466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848819PMC
December 2019

Adaptation of a sustained care cessation intervention for smokers hospitalized for psychiatric disorders: Study protocol for a randomized controlled trial.

Contemp Clin Trials 2019 08 15;83:18-26. Epub 2019 Jun 15.

School of Nursing, The University of Texas at Austin, Austin, TX, United States of America. Electronic address:

Background: Individuals with serious mental illness (SMI) smoke at disproportionately higher rates than those without SMI, have lifespans 25-32 years shorter, and thus bear an especially large burden of tobacco-related morbidity and mortality. Several recent studies demonstrate that smokers with SMI can successfully quit smoking with adequate support. Further evidence shows that using technology to deliver sustained care interventions to hospitalized smokers can lead to smoking cessation up to 6 months after discharge. The current comparative effectiveness trial adapts a technology-assisted sustained care intervention designed for smokers admitted to a general hospital and tests whether this approach can produce higher cessation rates compared to usual care for smokers admitted to a psychiatric inpatient unit.

Methods: A total of 353 eligible patients hospitalized for psychiatric illness are randomized by cohort into one of two conditions, Sustained Care (SusC) or Usual Care (UC), and are followed for six months after discharge. Participants assigned to UC receive brief tobacco education delivered by a hospital nurse during or soon after admission. Those assigned to SusC receive a 40-min, in-hospital motivational counseling intervention. Upon discharge, they also receive up to 8 weeks of free nicotine patches, automated interactive voice response (IVR) telephone and text messaging, and access to cessation counseling resources lasting 3 months post discharge. Smoking cessation outcomes are measured at 1-, 3- and 6-months post hospital discharge.

Conclusion: Results from this comparative effectiveness trial will add to our understanding of acceptable and effective smoking cessation approaches for patients hospitalized with SMI.
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http://dx.doi.org/10.1016/j.cct.2019.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197194PMC
August 2019

Childhood maltreatment, behavioral adjustment, and molecular markers of cellular aging in preschool-aged children: A cohort study.

Psychoneuroendocrinology 2019 09 15;107:261-269. Epub 2019 May 15.

Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA. Electronic address:

Objective: Childhood maltreatment is a major risk factor for the development of behavioral problems and poor physical and mental health. Accelerated cellular aging, through reduced telomere length and mitochondrial dysfunction, may be a mechanism underlying these associations.

Methods: Families with (n = 133) and without (n = 123) child welfare documentation of moderate-severe maltreatment in the past six months participated in this study. Children ranged in age from 3 to 5 years, were racially and ethnically diverse, and 91% qualified for public assistance. Structured record review and interviews were used to assess a history of maltreatment and other adversities. Telomere length and mitochondrial DNA copy number (mtDNAcn) were measured from saliva DNA using real-time PCR. Measures were repeated at a six-month follow-up assessment. Repeated measures general linear models were used to examine the effects of maltreatment and other adversities on telomere length and mtDNAcn over time.

Results: Maltreatment and other adverse experiences were significant positive predictors of both telomere length and mtDNAcn over time. Internalizing and externalizing behavior problems were also both significantly associated with telomere length, but only internalizing symptoms were associated with mtDNAcn.

Conclusions: This is the first study to show that mtDNAcn is altered in children with stress and trauma, and the findings are consistent with recent studies of adults. Surprisingly, children who experienced moderate-severe levels of maltreatment in the prior six months had longer telomeres, possibly reflecting compensatory changes in response to recent trauma. Telomere length and mtDNAcn were also associated with behavioral problems, suggesting that these measures of cellular aging may be causally implicated in the pathophysiology of stress-related conditions.
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http://dx.doi.org/10.1016/j.psyneuen.2019.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839663PMC
September 2019

Anxiety Sensitivity is Associated with Lower Enjoyment and an Anxiogenic Response to Physical Activity in Smokers.

Cognit Ther Res 2019 Feb 27;43(1):78-87. Epub 2018 Jul 27.

Alpert Medical School of Brown University, Providence, Rhode Island.

Background: The subjective affective response to, and enjoyment of, physical activity are strong predictors of engagement in physical activity. Anxiety sensitivity, the fear of bodily sensations, is a cognitive factor that may inhibit the pleasurable affective experience of physical activity, possibly contributing to low levels of physical activity. The current study evaluated anxiety sensitivity in relation to PA enjoyment and affective experience before and after exercise in smokers.

Method: Participants were low-active treatment-seeking smokers ( = 201) enrolled in a smoking cessation intervention. At baseline, participants completed self -report assessments of anxiety sensitivity, cigarette dependence, and physical activity enjoyment. State affect was also reported before and after a submaximal exercise test to index pre-exercise activity affect and affective response to exercise.

Results: Anxiety sensitivity was significantly negatively correlated with physical activity enjoyment, specifically lower enjoyable physical feelings of physical activity. Anxiety sensitivity was significantly correlated with lower state mood and higher state anxiety prior to the submaximal exercise test, and higher anxiety immediately after the exercise test. Additionally, anxiety sensitivity predicted increased anxiety, but not lower mood, in response to the submaximal exercise test.

Conclusions: This is the first study to document an association of anxiety sensitivity with affective determinants of physical activity behavior in smokers. Anxiety sensitivity was associated with lower physical activity enjoyment, higher negative affect prior to after exercise testing, and an anxiogenic response to exercise. Future work is needed to understand how the current findings generalize beyond smokers.
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http://dx.doi.org/10.1007/s10608-018-9948-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502475PMC
February 2019

Anxiety sensitivity and daily cigarette smoking in relation to sleep disturbances in treatment-seeking smokers.

Cogn Behav Ther 2020 03 5;49(2):137-148. Epub 2019 Apr 5.

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.

Although the association between anxiety and sleep disturbance is well-documented, the underlying mechanisms are less clear. Anxiety sensitivity (AS), the fear of physiological arousal and bodily sensations, is a risk factor for anxiety and poor sleep. Smoking also contributes to poor sleep and may compound the effects of AS on sleep quality. This study evaluated the main and interactive effects of AS and cigarettes/day on sleep quality among smokers. Participants (n = 190) were adult treatment-seeking daily smokers who completed a baseline assessment as part of a larger smoking cessation trial. Sleep quality was self-reported. Results indicated that AS was significantly correlated with greater disturbance in sleep duration, subjective sleep quality, sleep onset latency, sleep disturbance, daytime dysfunction, and sleep medication use. There was a significant interaction between AS and cigarettes/day in terms of sleep onset latency, but not other sleep quality indices. AS was associated with significantly longer sleep onset latency minutes among heavier smokers, but not lighter smokers. Specifically, the association between AS and sleep onset latency was significant for those who smoked ≥ 33 cigarettes/day. AS is a psychological factor that may contribute to poor sleep quality, especially in heavy smokers, and thus may be a promising intervention target.
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http://dx.doi.org/10.1080/16506073.2019.1583277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778490PMC
March 2020

Development and Psychometric Evaluation of the Children's Yale-Brown Obsessive-Compulsive Scale Second Edition.

J Am Acad Child Adolesc Psychiatry 2019 01 25;58(1):92-98. Epub 2018 Oct 25.

Baylor College of Medicine, Houston, TX.

Objective: To develop and examine the psychometric properties of the Children's Yale-Brown Obsessive-Compulsive Scale Second Edition (CY-BOCS-II) in children and adolescents with obsessive-compulsive disorder (OCD).

Method: Youth with OCD (N = 102; age range 7-17 years), who were seeking treatment from 1 of 2 specialty OCD treatment centers, participated in the study. The CY-BOCS-II was administered at an initial assessment, and measures of OCD symptom severity, anxiety and depressive symptoms, behavioral and emotional problems, and global functioning were administered. Inter-rater and test-retest reliabilities were assessed on a subsample of participants (n = 50 and n = 31, respectively) approximately 1 week after intial assessment.

Results: The CY-BOCS-II demonstrated moderate-to-strong internal consistency (α = 0.75-0.88) and excellent inter-rater (intraclass correlation coefficient = 0.86-0.92) and test-retest (intraclass correlation coefficient = 0.95-0.98) reliabilities across all scales. Construct validity was supported by strong correlations with clinician-rated measures of OCD symptom severity and moderate correlations with measures of anxiety symptoms. Exploratory factor analysis showed a 2-factor structure, which was generally inconsistent with its adult counterpart, the Yale-Brown Obsessive-Compulsive Scale Second Edition.

Conclusion: Initial findings support the CY-BOCS-II as a reliable and valid measure of obsessive-compulsive symptoms in youth.
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http://dx.doi.org/10.1016/j.jaac.2018.05.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309898PMC
January 2019

Time-lagged predictors of daily medication nonadherence beliefs during the month post-hospital discharge in patients with psychotic-spectrum disorders.

Psychiatry Res 2018 12 21;270:253-256. Epub 2018 Sep 21.

Department of Psychiatry & Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI, USA.

We used ecological momentary assessment (EMA) to examine the period following hospitalization when risk for medication nonadherence is highest among patients with psychotic-spectrum disorders. EMA data were collected daily via smartphones from 23 patients with psychotic-spectrum disorders (totaling 1149 surveys) in the month immediately following discharge. Nonadherence beliefs significantly correlated with percentage of medication doses. Time-lagged increases in irritability, sadness, life dissatisfaction, functional impairment, and previous day missed medication dose predicted subsequent increases in nonadherence beliefs over time. Future research should study mobile interventions that target the factors found to predict nonadherence beliefs to improve post-hospital recovery.
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http://dx.doi.org/10.1016/j.psychres.2018.09.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292726PMC
December 2018

Mechanisms of Perceived Treatment Assignment and Subsequent Expectancy Effects in a Double Blind Placebo Controlled RCT of Major Depression.

Front Psychiatry 2018 7;9:424. Epub 2018 Sep 7.

Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

It has been suggested that patients' perception of treatment assignment might serve to bias results of double blind randomized controlled trials (RCT). Most previous evidence on the effects of patients' perceptions and the mechanisms influencing these perceptions relies on cross-sectional associations. This re-analysis of a double blind, placebo controlled RCT of pharmacological treatment of major depression set out to gather longitudinal evidence on the mechanism and effects of patients' perceived treatment assignment in the pharmacological treatment of major depression. One-hundred eighty-nine outpatients with DSM-IV diagnosed major depression were randomized to SAMe 1,600-3,200 mg/d, escitalopram 10-20 mg/days, or placebo for 12 weeks. Data on depressive symptoms (17-item Hamilton Depression Scale; HDRS-17), adverse events and patients' perceived treatment assignment was collected at baseline, week 6, and week 12. The re-analysis focused on = 166 (out of the originally included 189 participants) with available data on perceived treatment assignment. As in the parent trial, depressive symptoms (HDRS-17) significantly decreased over the course of 12 weeks and there was no difference between placebo, SAMe or escitalopram. A significant number of patients changed their perceptions about treatment assignment throughout the trial, especially between baseline and week 6. Improvement in depressive symptoms, but not adverse events significantly predicted perceived treatment assignment at week 6. In turn, perceived treatment assignment at week 6, but not actual treatment, predicted further improvement in depressive symptoms at week 12. The current results provide longitudinal evidence that patients' perception of treatment assignment systematically change despite a double blind procedure and in turn might trigger expectancy effects with the potential to bias the validity of an RCT. Parent study grant number: R01 AT001638 Parent study ClinicalTrials. gov Identifier: NCT00101452.
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http://dx.doi.org/10.3389/fpsyt.2018.00424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137256PMC
September 2018

5 Hz Repetitive transcranial magnetic stimulation for posttraumatic stress disorder comorbid with major depressive disorder.

J Affect Disord 2018 08 5;235:414-420. Epub 2018 Apr 5.

Butler Hospital, Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, United States; Center for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, RI, United States.

Background: Standard clinical protocols for repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder (MDD) apply 10 Hz pulses over left prefrontal cortex, yet little is known about the effects of rTMS in more diagnostically complex depressed patients.

Objective/hypothesis: Posttraumatic stress disorder (PTSD) is commonly comorbid with MDD, and while rTMS has been shown to alleviate PTSD symptoms in preliminary studies, ideal parameters remain unclear. We conducted a prospective, open-label study of 5 Hz rTMS for patients with comorbid PTSD + MDD and hypothesized stimulation would reduce symptoms of both disorders.

Methods: Outpatients (N = 40) with PTSD + MDD and at least moderate global severity were enrolled. 5 Hz rTMS included up to 40 daily sessions followed by a 5-session taper. Symptoms were measured using the PTSD Checklist (PCL-5) and Inventory of Depressive Symptomatology, Self-Report (IDS-SR). Baseline-to-endpoint changes were analyzed.

Results: The intent-to-treat population included 35 participants. Stimulation significantly reduced PTSD symptoms (PCL-5 baseline mean ± SD score 52.2 ± 13.1 versus endpoint 34.0 ± 21.6; p < .001); 23 patients (48.6%) met a pre-defined categorical PTSD response criteria. MDD symptoms also improved significantly (IDS-SR, baseline 47.8 ± 11.9 to endpoint 30.9 ± 18.9; p < .001); 15 patients (42.9%) demonstrated categorical response and 12 (34.3%) remitted. PTSD and MDD symptom change was highly correlated (r = 0.91, p < .001).

Limitations: Unblinded single-arm study, with modest sample size.

Conclusion: Significant and clinically meaningful reductions in both MDD and PTSD symptoms were observed following stimulation. The preliminary efficacy of 5 Hz rTMS for both symptom domains in patients with comorbid disorders supports future controlled studies.
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http://dx.doi.org/10.1016/j.jad.2018.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567988PMC
August 2018

The effects of early life stress on reward processing.

J Psychiatr Res 2018 06 13;101:80-103. Epub 2018 Feb 13.

Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.

Early life stress (ELS), in the form of childhood maltreatment, abuse, or neglect, increases the risk for psychiatric sequelae later in life. The neurobiology of response to early stress and of reward processing overlap substantially, leading to the prediction that reward processing may be a primary mediator of the effects of early life stress. We describe a growing body of literature investigating the effects of early life stressors on reward processing in animals and humans. Despite variation in the reviewed studies, an emerging pattern of results indicates that ELS results in deficits of ventral striatum-related functions of reward responsiveness and approach motivation, especially when the stressor is experienced in early in development. For stressors experienced later in the juvenile period and adolescence, the animal literature suggests an opposite effect, in which ELS results in increased hedonic drive. Future research in this area will help elucidate the transdiagnostic impact of early life stress, and therefore potentially identify and intervene with at-risk youth, prior to the emergence of clinical psychopathology.
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http://dx.doi.org/10.1016/j.jpsychires.2018.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889741PMC
June 2018

Rationale, design and pilot feasibility results of a smartphone-assisted, mindfulness-based intervention for smokers with mood disorders: Project mSMART MIND.

Contemp Clin Trials 2018 03 27;66:36-44. Epub 2017 Dec 27.

University of Texas at Austin, United States.

Background: Although individuals with psychiatric disorders are disproportionately affected by cigarette smoking, few outpatient mental health treatment facilities offer smoking cessation services. In this paper, we describe the development of a smartphone-assisted mindfulness smoking cessation intervention with contingency management (SMI-CM), as well as the design and methods of an ongoing pilot randomized controlled trial (RCT) targeting smokers receiving outpatient psychiatric treatment. We also report the results of an open-label pilot feasibility study.

Methods: In phase 1, we developed and pilot-tested SMI-CM, which includes a smartphone intervention app that prompts participants to practice mindfulness, complete ecological momentary assessment (EMA) reports 5 times per day, and submit carbon monoxide (CO) videos twice per day. Participants earned incentives if submitted videos showed CO≤6ppm. In phase 2, smokers receiving outpatient treatment for mood disorders are randomized to receive SMI-CM or enhanced standard treatment plus non-contingent CM (EST).

Results: The results from the pilot feasibility study (N=8) showed that participants practiced mindfulness an average of 3.4times/day (≥3min), completed 72.3% of prompted EMA reports, and submitted 68.0% of requested CO videos. Participants reported that the program was helpful overall (M=4.85/5) and that daily mindfulness practice was helpful for both managing mood and quitting smoking (Ms=4.50/5).

Conclusions: The results from the feasibility study indicated high levels of acceptability and satisfaction with SMI-CM. The ongoing RCT will allow evaluation of the efficacy and mechanisms of action underlying SMI-CM for improving cessation rates among smokers with mood disorders.
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http://dx.doi.org/10.1016/j.cct.2017.12.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841579PMC
March 2018

Effects of Negative Affect, Urge to Smoke, and Working Memory Performance (n-back) on Nicotine Dependence.

Subst Use Misuse 2018 06 29;53(7):1177-1183. Epub 2017 Nov 29.

c Department of Psychiatry and Human Behavior , Alpert Medical School of Brown University , Providence , Rhode Island , USA.

Background: Three key domains including negative emotionality, incentive salience, and executive function form the core functional elements of addictive behaviors. Variables related to these broader domains have been studied extensively in relation to one another; however, no studies to date, have examined models including variables from all three domains, in relation to nicotine dependence.

Method: Smokers (N = 117), 65.8% female, 78% white, mean age of 44.4 (SD = 10.8), enrolled in a smoking cessation program completed measures of negative affect (a component of negative emotionality), urge to smoke (incentive salience), and working memory (WM; a core executive function), during a baseline assessment period prior to initiating treatment.

Results: Negative affect was associated with greater urge to smoke, and this elevated urge to smoke was associated with higher levels of nicotine dependence. Further, a significant moderated mediation indicated that WM moderated the relationship between increased urge to smoke and nicotine dependence. For those with low to average WM, urge to smoke was significantly related to nicotine dependence; however, for those with higher WM (+1 SD), urge to smoke stemming from negative affect was not associated with nicotine dependence.

Conclusions: To our knowledge, this is the first reported relationship between negative affect, urge to smoke, WM, and nicotine dependence. Although preliminary, results indicate that WM may moderate the relationship between urge to smoke associated with negative affect and nicotine dependence. Treatments targeting WM may be particularly useful for individuals with average to low WM who experience urge to smoke related to negative affect.
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http://dx.doi.org/10.1080/10826084.2017.1400569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376498PMC
June 2018

The Role of Physical Activity Enjoyment on the Acute Mood Experience of Exercise among Smokers with Elevated Depressive Symptoms.

Ment Health Phys Act 2017 Mar 10;12:37-43. Epub 2017 Feb 10.

Butler Hospital, Providence, Rhode Island.

Problem: Depressive symptoms are consistently shown to be related to poor smoking cessation outcomes. Aerobic exercise is a potential treatment augmentation that, given its antidepressant and mood enhancing effect, may bolster cessation outcomes for smokers with elevated depressive symptoms. Lower enjoyment of physical activity may inhibit the acute mood enhancing effects of aerobic exercise. The current study investigated the associations between depressive symptoms, physical activity enjoyment and the acute mood experience from exercise among low-active smokers with elevated depressive symptoms.

Method: Daily smokers with elevated depressive symptoms (N=159; = 45.1, = 10.79; 69.8% female) were recruited for a randomized controlled exercise-based smoking cessation trial. Participants self-reported levels of depressive symptoms, physical activity enjoyment, and rated their mood experience (assessed as "mood" and "anxiety") before and after a standardized aerobic exercise test.

Results: Hierarchical regression analysis revealed that depressive symptom severity accounted for significant unique variance in physical activity enjoyment ( =.041, = -2.61, = .010), beyond the non-significant effects of gender and level of tobacco dependence. Additionally, physical activity enjoyment was a significant mediator of the association between depressive symptom severity and acute mood experience ("mood" and "anxiety") following the exercise test.

Conclusions: Physical activity enjoyment may explain, at least in part, how depressive symptom severity is linked to the acute mood experience following a bout of activity. Interventions that target increasing physical activity enjoyment may ultimately assist in enhancing the mood experience from exercise, and therefore improve smoking cessation likelihood, especially for smokers with elevated depressive symptoms.
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http://dx.doi.org/10.1016/j.mhpa.2017.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625337PMC
March 2017

Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder.

Biol Psychiatry 2018 02 8;83(3):263-272. Epub 2017 Aug 8.

Butler Hospital Mood Disorders Research Program and Neuromodulation Research Facility, Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island.

Background: Repetitive transcranial magnetic stimulation (TMS) therapy can modulate pathological neural network functional connectivity in major depressive disorder (MDD). Posttraumatic stress disorder is often comorbid with MDD, and symptoms of both disorders can be alleviated with TMS therapy. This is the first study to evaluate TMS-associated changes in connectivity in patients with comorbid posttraumatic stress disorder and MDD.

Methods: Resting-state functional connectivity magnetic resonance imaging was acquired before and after TMS therapy in 33 adult outpatients in a prospective open trial. TMS at 5 Hz was delivered, in up to 40 daily sessions, to the left dorsolateral prefrontal cortex. Analyses used a priori seeds relevant to TMS, posttraumatic stress disorder, or MDD (subgenual anterior cingulate cortex [sgACC], left dorsolateral prefrontal cortex, hippocampus, and basolateral amygdala) to identify imaging predictors of response and to evaluate clinically relevant changes in connectivity after TMS, followed by leave-one-out cross-validation. Imaging results were explored using data-driven multivoxel pattern activation.

Results: More negative pretreatment connectivity between the sgACC and the default mode network predicted clinical improvement, as did more positive amygdala-to-ventromedial prefrontal cortex connectivity. After TMS, symptom reduction was associated with reduced connectivity between the sgACC and the default mode network, left dorsolateral prefrontal cortex, and insula, and reduced connectivity between the hippocampus and the salience network. Multivoxel pattern activation confirmed seed-based predictors and correlates of treatment outcomes.

Conclusions: These results highlight the central role of the sgACC, default mode network, and salience network as predictors of TMS response and suggest their involvement in mechanisms of action. Furthermore, this work indicates that there may be network-based biomarkers of clinical response relevant to these commonly comorbid disorders.
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http://dx.doi.org/10.1016/j.biopsych.2017.07.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679924PMC
February 2018

Development and preliminary pilot evaluation of a brief tablet computer intervention to motivate tobacco quitline use among smokers in substance use treatment.

Am J Addict 2017 Sep 11;26(6):587-594. Epub 2017 Aug 11.

Merrill-Palmer Skillman Institute and Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Michigan.

Background And Objectives: The majority of individuals in substance use disorder (SUD) treatment also smoke cigarettes; yet, the availability of smoking cessation services in SUD treatment remains limited. In this study, we developed and piloted a brief intervention for smokers in SUD treatment intended to motivate engagement in tobacco quitline treatment (TIME-TQ).

Methods: First, we interviewed 19 smokers in SUD treatment to inform the development of TIME-TQ (Phase 1). Second, we delivered a prototype TIME-TQ to 16 smokers in the same SUD treatment program and followed them for 3 months post-discharge (Phase 2).

Results: Feedback from Phase 1 participants was used to refine response choices and video segments included in the prototype TIME-TQ. Phase 2 participants rated TIME-TQ high on relevance, interest, respectfulness, and helpfulness. Additionally, they reported significant increases in readiness to quit and perceived importance of quitting after receiving TIME-TQ. A total of 8 of the 16 accepted a quitline referral, and 8 of 13 reached for follow-up (four referral acceptors, four decliners) reported efforts to quit or reduce smoking during the follow-up period. However, only three received quitline counseling and none achieved a sustained period of abstinence.

Conclusions And Scientific Significance: Our results suggest that TIME-TQ activated these patients to quit smoking, but our referral method (standard fax referral) was unsuccessful in helping participants fully engage in quitline treatment or achieving a period of abstinence.

Scientific Significance: We are now conducting an RCT to evaluate TIME-TQ with a revised referral procedure intended to increase treatment engagement and, ultimately, abstinence rates. (Am J Addict 2017;26:587-594).
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http://dx.doi.org/10.1111/ajad.12559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892843PMC
September 2017

Anxiety sensitivity predicts increased perceived exertion during a 1-mile walk test among treatment-seeking smokers.

J Behav Med 2017 Dec 27;40(6):886-893. Epub 2017 Apr 27.

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, 02906, USA.

Smoking increases risk of early morbidity and mortality, and risk is compounded by physical inactivity. Anxiety sensitivity (fear of anxiety-relevant somatic sensations) is a cognitive factor that may amplify the subjective experience of exertion (effort) during exercise, subsequently resulting in lower engagement in physical activity. We examined the effect of anxiety sensitivity on ratings of perceived exertion (RPE) and physiological arousal (heart rate) during a bout of exercise among low-active treatment-seeking smokers. Adult daily smokers (n = 157; M  = 44.9, SD = 11.13; 69.4% female) completed the Rockport 1.0 mile submaximal treadmill walk test. RPE and heart rate were assessed during the walk test. Multi-level modeling was used to examine the interactive effect of anxiety sensitivity × time on RPE and on heart rate at five time points during the walk test. There were significant linear and cubic time × anxiety sensitivity effects for RPE. High anxiety sensitivity was associated with greater initial increases in RPE during the walk test, with stabilized ratings towards the last 5 min, whereas low anxiety sensitivity was associated with lower initial increase in RPE which stabilized more quickly. The linear time × anxiety sensitivity effect for heart rate was not significant. Anxiety sensitivity is associated with increasing RPE during moderate-intensity exercise. Persistently rising RPE observed for smokers with high anxiety sensitivity may contribute to the negative experience of exercise, resulting in early termination of bouts of prolonged activity and/or decreased likelihood of future engagement in physical activity.
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http://dx.doi.org/10.1007/s10865-017-9853-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659951PMC
December 2017

Distress Tolerance Treatment for Weight Concern in Smoking Cessation Among Women: The WE QUIT Pilot Study.

Behav Modif 2017 07 27;41(4):468-498. Epub 2016 Dec 27.

1 Alpert Medical School of Brown University, Providence, RI, USA.

Fear of gaining weight after quitting cigarette smoking is a major barrier to smoking cessation among women. Distress tolerance, which refers to one's ability and willingness to tolerate physical and emotional discomfort, predicts successful behavior change. Novel interventions rooted in Acceptance and Commitment Therapy (ACT) have emerged that aim to increase distress tolerance and engagement in values-oriented behavior. In this study, we developed a 9-week, group-based distress tolerance intervention for weight concern in smoking cessation among women (DT-W). Using an iterative process, we piloted DT-W with two small groups ( n = 4 and n = 7) of female weight-concerned smokers. Results indicated that we successfully established the feasibility and acceptability of DT-W, which was well-attended and well-received. Biochemically verified 7-day point-prevalence abstinence rates at post-intervention, 1, 3, and 6 months were 64%, 36%, 27%, and 27%, respectively. We are now evaluating DT-W in a randomized controlled trial.
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http://dx.doi.org/10.1177/0145445516683500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453845PMC
July 2017

Early life stress predicts thalamic hyperconnectivity: A transdiagnostic study of global connectivity.

J Psychiatr Res 2016 08 13;79:93-100. Epub 2016 May 13.

Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, USA.

Early life stress (ELS) is an established risk factor for psychiatric illness and is associated with altered functional connectivity within- and between intrinsic neural networks. The widespread nature of these disruptions suggests that broad imaging measures of neural connectivity, such as global based connectivity (GBC), may be particularly appropriate for studies of this population. GBC is designed to identify brain regions having maximal functional connectedness with the rest of the brain, and alterations in GBC may reflect a restriction or broadening of network synchronization. We evaluated whether ELS severity predicted GBC in a sample (N = 46) with a spectrum of ELS exposure. Participants included healthy controls without ELS, those with at least moderate ELS but without psychiatric disorders, and a group of patients with ELS- related psychiatric disorders. The spatial distribution of GBC peaked in regions of the salience and default mode networks, and ELS severity predicted increased GBC of the left thalamus (corrected p < 0.005, r = 0.498). Thalamic connectivity was subsequently evaluated and revealed reduced connectivity with the salience network, particularly the dorsal anterior cingulate cortex (corrected p < 0.005), only in the patient group. These findings support a model of disrupted thalamic connectivity in ELS and trauma-related negative affect states, and underscore the importance of a transdiagnostic, dimensional neuroimaging approach to understanding the sequelae of trauma exposure.
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http://dx.doi.org/10.1016/j.jpsychires.2016.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894492PMC
August 2016

Editorial: Reporting guidelines for psychopharmacology.

Psychopharmacology (Berl) 2016 Apr;233(7):1131-4

Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.

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http://dx.doi.org/10.1007/s00213-016-4252-7DOI Listing
April 2016

Depression and telomere length: A meta-analysis.

J Affect Disord 2016 Feb 2;191:237-47. Epub 2015 Dec 2.

Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.

Background: Several recent studies have investigated the relationship between telomere length and depression with inconsistent results. This meta-analysis examined whether telomere length and depression are associated and explored factors that might affect this association.

Methods: Studies measuring telomere length in subjects with clinically significant unipolar depression were included. A comprehensive search strategy identified studies in PubMed, MEDLINE, PsycINFO, Global Health, The Cochrane Library, and Web of Science. A structured data abstraction form was used and studies were appraised for inclusion or exclusion using a priori conditions. Analyses were conducted using standardized mean differences in a continuous random effects model.

Results: Thirty-eight studies (N=34,347) met the inclusion criteria. The association between depression and telomere length was significant, with a Cohen's d effect size of -0.205 (p<0.0001, I(2)=42%). Depression severity significantly associated with telomere length (p=0.03). Trim and fill analysis indicated the presence of publication bias (p=0.003), but that the association remained highly significant after accounting for the bias. Subgroup analysis revealed depression assessment tools, telomere measurement techniques, source tissue and comorbid medical conditions significantly affected the relationship.

Limitations: Other potentially important sub-groups, including antidepressant use, have not been investigated in sufficient detail or number yet and thus were not addressed in this meta-analysis.

Conclusions: There is a negative association between depression and telomere length. Further studies are needed to clarify potential causality underlying this association and to elucidate the biology linking depression and this cellular marker of stress exposure and aging.
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http://dx.doi.org/10.1016/j.jad.2015.11.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760624PMC
February 2016

5Hz Repetitive transcranial magnetic stimulation to left prefrontal cortex for major depression.

J Affect Disord 2015 Nov 17;186:13-7. Epub 2015 Jul 17.

Butler Hospital Mood Disorders Research Program, Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, United States.

Background: Repetitive transcranial magnetic stimulation (rTMS) to left prefrontal cortex at 10Hz is the most commonly utilized protocol for major depressive disorder (MDD). Published data suggests that left sided 5Hz rTMS may be efficacious and well tolerated.

Objective: We analyzed outcomes in a naturalistic cohort of MDD patients who could not tolerate 10Hz rTMS and were routinely switched to 5Hz. We hypothesized that the efficacy of 5Hz rTMS would be equivalent to 10Hz.

Methods: Records were reviewed for patients (n=98) who received 15 or more acute rTMS treatments. The sample was split based upon the frequency (10 or 5Hz) at which the majority of treatments were delivered. The Inventory of Depressive Symptoms (IDS-SR) and 9-Item Patient Health Questionnaire (PHQ-9) were used to evaluate outcomes.

Results: Baseline IDS-SR was higher in the 5Hz (n=27) than in the 10Hz (n=71) group (p<.05), as was frequency of comorbid anxiety (p=.002). Depression outcomes did not differ between groups, and there were no differences in response or remission rates (all p>.1). Statistical power was sufficient to detect small group differences (d=.26).

Limitations: Open-label data in a naturalistic setting.

Conclusion: Outcomes associated with 5Hz rTMS did not differ from 10Hz, despite higher baseline depressive symptom severity and anxiety in 5Hz patients. 5Hz stimulation may be an alternative treatment option for patients unable to tolerate 10Hz rTMS.
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http://dx.doi.org/10.1016/j.jad.2014.12.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565741PMC
November 2015

Association of telomere length and mitochondrial DNA copy number in a community sample of healthy adults.

Exp Gerontol 2015 Jun 3;66:17-20. Epub 2015 Apr 3.

Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, USA.

Cellular aging plays a role in longevity and senescence, and has been implicated in medical and psychiatric conditions, including heart disease, cancer, major depression and posttraumatic stress disorder. Telomere shortening and mitochondrial dysfunction are thought to be central to the cellular aging process. The present study examined the association between mitochondrial DNA (mtDNA) copy number and telomere length in a sample of medically healthy adults. Participants (total n=392) were divided into 4 groups based on the presence or absence of early life adversity and lifetime psychopathology: No Adversity/No Disorder, n=136; Adversity/No Disorder, n=91; No Adversity/Disorder, n=46; Adversity/Disorder, n=119. Telomere length and mtDNA copy number were measured using quantitative polymerase chain reaction. There was a positive correlation between mtDNA and telomere length in the entire sample (r=0.120, p<0.001) and in each of the four groups of participants (No Adversity/No Disorder, r=0.291, p=0.001; Adversity/No Disorder r=0.279, p=0.007; No Adversity/Disorder r=0.449, p=0.002; Adversity/Disorder, r=0.558, p<0.001). These correlations remained significant when controlling for age, smoking, and body mass index and establish an association between mtDNA and telomere length in a large group of women and men both with and without early adversity and psychopathology, suggesting co-regulation of telomeres and mitochondrial function. The mechanisms underlying this association may be important in the pathophysiology of age-related medical conditions, such as heart disease and cancer, as well as for stress-associated psychiatric disorders.
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http://dx.doi.org/10.1016/j.exger.2015.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459604PMC
June 2015

Telomeres, early-life stress and mental illness.

Adv Psychosom Med 2015 30;34:92-108. Epub 2015 Mar 30.

Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, R.I., USA.

Telomeres are structures of tandem TTAGGG repeats that are found at the ends of chromosomes and preserve genomic DNA by serving as a disposable buffer to protect DNA termini during chromosome replication. In this process, the telomere itself shortens with each cell division and can consequently be thought of as a cellular 'clock', reflecting the age of a cell and the time until senescence. Telomere shortening and changes in the levels of telomerase, the enzyme that maintains telomeres, occur in the context of certain somatic diseases and in response to selected physical stressors. Emerging evidence indicates that telomeres shorten with exposure to psychosocial stress (including early-life stress) and perhaps in association with some psychiatric disorders. These discoveries suggest that telomere shortening might be a useful biomarker for the overall stress response of an organism to various pathogenic conditions. In this regard, telomeres and their response to both somatic and psychiatric illness could serve as a unifying stress-response biomarker that crosses the brain/body distinction that is often made in medicine. Prospective studies will help to clarify whether this biomarker has broad utility in psychiatry and medicine for the evaluation of responses to psychosocial stressors. The possibility that telomere shortening can be slowed or reversed by psychiatric and psychosocial interventions could represent an opportunity for developing novel preventative and therapeutic approaches.
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http://dx.doi.org/10.1159/000369088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476498PMC
June 2015
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