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Background: There is an urgent need to identify interventions to reduce suicidality. We investigated the antisuicidal effects of intravenous (IV) ketamine and intranasal (IN) esketamine among patients with treatment-resistant depression (TRD) in a historical cohort study., Methods: The Quick Inventory of Depressive Symptomatology self-report (QIDS-SR) question 12 was used to measure suicidal ideation (SI). Cox proportional hazards models were used to evaluate associations between the number of treatments to response and baseline SI (yes, Q12 > 0 versus no, Q12 = 0), adjusting for covariates and modified baseline QIDS-SR score. We evaluated associations between the number of treatments to a 50 % reduction in SI score between IV and IN treatment., Results: Fifty-two adults (62.5 % female, median age 49.1 years) received IV ketamine (71 %, n = 37) or IN esketamine (29 %, n = 15). Eighty-one percent of patients reported SI at baseline. Among those with baseline SI, 60 % had improved SI scores while 38 % did not change, and among those with no SI, 80 % did not change. After adjusting for covariates, the hazard ratios (HR) of response were significantly lower among those with baseline SI (HR = 0.36, 95 % CI, 0.14-0.92, p = 0.03). The number of treatments to achieve a 50 % reduction in SI score did not depend on group (IN esketamine vs. IV ketamine HR = 0.74 [95 % CI, 0.27-2.05]; p = 0.57)., Limitations: Small sample size and lack of a placebo group., Conclusions: This study suggests that patients with baseline suicidal ideation require more treatments to achieve a response with ketamine or esketamine. The antisuicidal response seemed similar between IV ketamine and IN esketamine., Competing Interests: Declaration of competing interest Dr. Singh has received research grant support from Mayo Clinic, the National Network of Depression Centers (NNDC) Momentum grant, and BD2 (Breakthrough Discoveries for thriving with bipolar disorder). Dr. Vande Voort has received grant-in-kind support from Assurex Health (unrelated to this study). Dr. Kung received payment for a recorded CME presentation about transcranial magnetic stimulation by Psychopharmacology Institute. Dr. Frye reports Grant Support from Assurex Health, Mayo Foundation, CME/Travel/Honoraria from Carnot Laboratories and American Physician Institute, and Financial Interest/Stock ownership/Royalties with Chymia LLC. Other authors report no potential conflicts of interest. Funding sources had no influence on the work reported., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Sleep disturbances are highly prevalent in depressive episodes and are linked to higher mood severity and suicidal behaviors. Slow wave sleep (SWS) and REM sleep are compromised in depression. Current evidence suggests that rapid antidepressant effects of intravenous (IV) ketamine in patients with treatment-resistant depression (TRD) is mediated by its effects on SWS and REM sleep. Sleep phenotypes may help predict ketamine response., Method: In this observational study, we investigated differences in rates of response among sleep phenotypes defined by QIDS-SR in a cohort of patients with TRD (n = 52) treated with IV ketamine or intranasal (IN) esketamine. Also, we explored a neurovegetative symptoms of atypical depression (NVSAD) phenotype and its association between response and change in QIDS-SR following the treatment with IV ketamine/IN esketamine., Results: 94 % of patients reported sleep difficulties and 62 % reported more than one sleep phenotype with middle and early insomnia being the most prevalent. Individuals with baseline hypersomnia showed higher response rates and more pronounced improvements on their QIDS-SR score. Additionally, 15 % of patients presented with NVSAD phenotype; the majority of whom achieved response and had higher reductions on QIDS-SR. A trend towards faster response was identified for hypersomnia and atypical depression phenotypes., Limitations: Observational study design and lack of a placebo group., Conclusions: Our data indicate that patients with TRD who have baseline hypersomnia and atypical depression features experienced a more substantial reduction in depressive symptoms and are more likely to achieve response with ketamine/esketamine. This could serve as a future predictor for clinical response., Competing Interests: Declaration of competing interest BS has received research grant support from the Mayo Clinic, the NNDC Momentum grant (unrelated to this study) and BD2 (Breakthrough Discoveries for thriving with bipolar disorder). JLVV has received grant-in-kind support from Assurex Health (unrelated to this study). Dr. Kung received payment for a recorded CME presentation about transcranial magnetic stimulation by Psychopharmacology Institute. Other authors report no potential conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania., (© 2024. The Author(s).)

Study Objectives: It is unknown whether sleep quality improvements after repetitive transcranial magnetic stimulation (rTMS) are inherent to the intervention or related to improvements in depressive symptoms. This retrospective study examined sleep quality in patients with major depressive disorder before and after treatment with rTMS, adjusting for age, sex, sedative-hypnotic use, number of rTMS treatments, depression severity, and changes in depressive symptoms., Methods: Adults with major depressive disorder underwent a 6-week course of 10 Hz rTMS over the left dorsolateral prefrontal cortex. Patients completed the Patient Health Questionnaire-9 depression rating scale and the Pittsburgh Sleep Quality Index before and after treatment. To limit confounding, analysis of depressive symptoms occurred without item 3 (the sleep item) of the Patient Health Questionnaire-9., Results: Twenty-one patients completed the study, with a mean (± standard deviation) baseline Pittsburgh Sleep Quality Index score of 12.0 (± 3.8), compared to 10.5 (± 4.3) posttreatment ( P = .01). The mean baseline Patient Health Questionnaire-9 score without item 3 was 17.3 (± 3.0), compared to 12.2 (± 4.9) posttreatment ( P = .0001). Pittsburgh Sleep Quality Index and modified Patient Health Questionnaire-9 changes were uncorrelated in nonadjusted and adjusted linear regression models and in the Spearman rank-order correlation., Conclusions: Mood and sleep quality improved independently after rTMS treatment, even after adjusting for age, sex, sedative-hypnotic use, number of rTMS treatments, and depression severity. These findings suggest that rTMS exerts direct effects on both mood and sleep in patients with major depressive disorder., Citation: Collins AR, Cheung J, Croarkin PA, Kolla BP, Kung S. Effects of transcranial magnetic stimulation on sleep quality and mood in patients with major depressive disorder. J Clin Sleep Med. 2022;18(5):1297-1305., (© 2022 American Academy of Sleep Medicine.)

Background: Intravenous Ketamine has shown robust antidepressant efficacy although other routes of administration are currently needed. We conducted a systematic review and meta-analysis of studies evaluating the efficacy and tolerability of oral ketamine for depression., Methods: A comprehensive search of major electronic databases from inception to April 2020 was performed. Studies of oral ketamine for depression, from case series to randomized clinical trials, were eligible. Randomized controlled trials were included in a meta-analysis, focusing on response, remission, time to effect, and side effects., Results: A total of 917 articles were identified with 890 studies screened, yielding a total of 10 studies included in our systematic review.Three randomized controlled trials (RCTs) (N = 161, mean age 37.9 ± 9.5 years, 58.6% females) were included in the meta-analysis. Pooled analysis suggested a significant antidepressant effect of oral ketamine (SMD: -0.75; 95% CI: -1.08, -0.43; p<0.0001; I 2 = 0%) although remission rates (RR:2.77; 95% CI:0.96, 8.00; p = 0.06) and response rates (RR:2.58; 95% CI:0.94,7.08; p = 0.07) were marginal compared to placebo at the endpoint. Oral ketamine antidepressant effects seemed to take effect at the 2nd week (SMD: -0.71; 95% CI: -1.08, -0.35; p = 0.001; I 2 = 0%). There were no significant differences in the overall side-effects between oral ketamine and the placebo group (RR 1.28, 95% CI: 0.89-1.83; p = 0.19)., Conclusion: This focused meta-analysis of oral ketamine suggests a marginal efficacy for major depressive disorder without increased risk of adverse events. Further larger sample studies are needed to confirm these preliminary findings, analyzing differential response/remission rates by affective disorder, optimal dosing strategies, and its long-term effects., Competing Interests: Financial Disclosures Dr. Singh received research time support from Medibio. It is unrelated to the current study. Dr. Singh reports grant support from Mayo Clinic. Dr. Frye reports grant support from Assurex Health, Mayo Foundation, Medibio. Consultant (Mayo)—Actify Neurotherapies, Allergan, Intra-Cellular Therapies, Inc., Janssen, Myriad, Neuralstem Inc., Takeda, Teva Pharmaceuticals. He reports CME/Travel/Honoraria from the American Physician Institute, CME Outfitters, Global Academy for Medical Education. Dr. Vande Voort has received supplies and genotyping services from Assurex Health, Inc. for investigator-initiated studies. Other authors have none to declare. All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 1964–2019 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Objective: Stress is associated with the onset, maintenance, and recurrence of depression. This study investigated the feasibility of stress management and resiliency training (SMART) for enhancing resiliency in a group of patients with major depressive disorder., Methods: In an open-label study, patients with major depressive disorder were invited to participate in an adjunctive 8-week group therapy of SMART (from June 2017 to June 2018) that encompassed attention training and practice of gratitude, compassion, higher meaning, acceptance, and forgiveness. The primary outcome measure was baseline-to-endpoint change in resilience as measured by the Connor Davidson Resilience Scale (CD-RISC). Secondary outcome measures included baseline-to-endpoint change in stress using the Perceived Stress Scale (PSS) and in depression using the 17-item Hamilton Depression Rating Scale (HDRS-17) and 9-item Patient Health Questionnaire (PHQ-9)., Results: Twenty-three participants enrolled in the study (mean ± SD age = 46 ± 13 years, female = 91%). Baseline ratings of mood were of mild-to-moderate symptom severity (mean HDRS-17 score = 14.5 and PHQ-9 score = 12), resilience (mean CD-RISC score = 53.8), and perceived stress (mean PSS score = 23.5). Of the participants, 74% were study completers (attended ≥ 6 sessions). In an intention-to-treat analysis, at study endpoint there was a significant improvement in resilience (mean CD-RISC score = 61.1, P = .03), reduction in perceived stress (mean PSS score = 19.4, P = .002), and improvement in depression (mean HDRS-17 score = 9.1 and PHQ-9 score = 7.6, both P < .001)., Conclusions: A resilience training program focused on wellness is feasible for patients who are currently symptomatic with major depressive disorder. A larger randomized controlled trial is needed to establish efficacy of this intervention and explore the long-term impact of stress management and resilience training in depression., Trial Registration: ClinicalTrials.gov identifier: NCT03275961., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

Study Objectives: Sleep disruption is a significant symptom of major depressive disorder (MDD). To our knowledge, no prior work has examined the impact of repetitive transcranial magnetic stimulation (rTMS) on sleep disturbances in adolescents with MDD., Methods: Seventeen adolescents with treatment-resistant depression received 30 daily sessions of 10-Hz rTMS applied to the left dorsolateral prefrontal cortex (L-DLPFC). Clinical symptoms were assessed at baseline; after 10, 20, and 30 treatments; and at a 6-month follow-up visit. Insomnia was measured with a 3-item subscale of the Quick Inventory of Depressive Symptomatology-Adolescent (17 Item)-Self Report (QIDS-A 17 -SR). Hypersomnia was measured with a single QIDS-A 17 -SR item. Depression severity was rated with the Children's Depression Rating Scale, Revised (CDRS-R). The effect of rTMS on sleep was examined via linear mixed model analyses, with fixed effects of time (as a proxy of treatment), depression severity, age, and hypnotic medication use., Results: No significant main effect of time was observed on the insomnia subscale (F 4,43.442  = 1.078, p = 0 .379). However, there was a significant main effect of time on the QIDS-A 17 -SR hypersomnia score (F 4,46.124  = 2.733, p = 0 .040), with significant improvement from baseline to treatment 10 (p adj  = 0.019) and from baseline to 6-month follow-up (p adj  = 0.044). In exploratory sensitivity analyses, response/nonresponse to rTMS for overall depressive symptoms had no significant effect on sleep outcomes., Conclusions: rTMS may have intrinsic effects on hypersomnia apart from its antidepressant effects in depressed adolescents. Future work should utilize sham controls and objective, quantitative measurements of sleep architecture to assess effects of rTMS in depressed adolescents., Clinical Trial Registry: Clinicaltrials.gov identifiers are NCT00587639, NCT01502033, NCT01804270., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Previous research suggests that electroconvulsive therapy (ECT)-the criterion standard for the treatment of severe depression-is not as effective when the patient has comorbid borderline personality disorder (BPD). The ECT outcomes of patients with and without BPD were compared in a retrospective chart review to test this claim., Methods: We enrolled 137 patients with a diagnosis of major depressive disorder who completed the McLean Screening Instrument for Borderline Personality Disorder. Twenty-nine patients had positive screening scores for BPD. The difference in Patient Health Questionnaire (PHQ-9) scores before and after ECT was compared between patients with and without BPD. Follow-up PHQ-9 scores determined after treatment were collected and analyzed., Results: Electroconvulsive therapy equally improved symptoms of depression as measured by PHQ-9 score in both patients who screened positive and patients who screened negative for BPD. No difference in the increase in PHQ-9 scores between these 2 groups was noted 1 month after treatment (P = 0.19)., Conclusions: These data showed that a positive BPD screen does not necessarily predict a poorer response to ECT, nor does it predict greater symptom recurrence after ECT. This does not suggest that ECT is necessarily an appropriate treatment for major depressive disorder in patients with a comorbid BPD, given the limitations of screening instruments.

Background: The purpose of this study was to identify specific pharmacokinetic (PK) and pharmacodynamics (PD) factors that affect the likelihood of treatment remission with a serotonin norepinephrine reuptake inhibitor (SNRI) in depressed patients whose initial selective serotonin reuptake inhibitor (SSRI) failed., Methods: Multiple logistic regression modeling of PK and PD variation hypothesized to contribute to SNRI (i.e. duloxetine or venlafaxine) treatment remission in prior SSRI (i.e. citalopram or escitalopram) failure was conducted on 139 subjects from the Pharmacogenomics Research Network (PGRN) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies. Depressive symptoms were assessed with the Quick Inventory of Depressive Symptomatology Clinician-rated (QIDS-C 16 )., Results: Venlafaxine-XR remission was associated with a significant interaction between CYP2D6 ultra-rapid metabolizer (URM) phenotype and SLC6A4 5-HTTLPR L/L genotype. A similar significant interaction effect was observed between CYP2D6 URM and SLC6A2 G1287A GA genotype. Stratifying by transporter genotypes, venlafaxine-XR remission was associated with CYP2D6 URM in patients with SLC6A4 L/L (p = 0.001) and SLC6A2 G1287A GA genotypes., Limitations: The primary limitation of this post hoc study was small sample size., Conclusion: Our results suggest that CYP2D6 ultra-rapid metabolizer status contributes to venlafaxine-XR treatment remission in MDD patients; in particular, there is a PK-PD interaction with treatment remission associated with CYP2D6 URM phenotype and SLC6A4 5-HTTLPR L/L or SLC6A2 G1287A G/A genotype, respectively. These preliminary data are encouraging and support larger pharmacogenomics studies differentiating treatment response to mechanistically different antidepressants in addition to further PK-PD interactive analyses., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Electroconvulsive therapy (ECT) is an effective treatment for depression, but the standard 2 to 3 times weekly treatment course results in a total treatment duration of >2 weeks. We explored the viability of decreasing treatment duration by using daily right unilateral ultrabrief (RULUB) ECT instead of standard bitemporal (BT) ECT., Methods: This study involved a retrospective review of records of inpatients 18 to 64 years of age who were treated between 2012 and 2017 at a large tertiary ECT center. Lead placement/technique, treatment duration (days from first to last ECT), number of ECT treatments, and scores on the Patient Health Questionnaire-9 (PHQ-9), and the Hamilton Depression Rating Scale (HamD-24) were collected. Statistical analysis was performed using 1-way analysis of variance and t tests., Results: Of 214 patients, 112 started daily RULUB ECT (86 were completers and 26 were eventually switched to BT), and 83 started and completed BT ECT. Daily RULUB completers finished their course of ECT 6.5 days faster than those who received BT ECT (11.7 vs. 18.2 d, P<0.0001), while the number of ECT treatments did not significantly differ between the 2 groups (daily RULUB 8.6 treatments vs. BT 8.3 treatments, P=0.4402). There were no significant differences in the final PHQ-9 or HamD-24 depression scores between the 2 groups. One case of significant cognitive impairment was observed in the daily RULUB group., Conclusions: Daily RULUB ECT compared with BT ECT allowed depression to be treated faster and with similar efficacy. Randomized controlled trials, which include the use of formal cognitive and physical side effect measures, are needed to further explore the viability of daily RULUB ECT.

Background: Little is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression., Methods: Twelve subjects with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5mg/kg, administered over 100min). Those who remitted during acute-phase treatment received continuation-phase treatment that consisted of 4 weekly ketamine infusions, followed by 4 weeks of post-continuation phase follow-up (during which no further ketamine infusions were administered). Clinical measures were assessed at baseline, at 24h following each infusion, at the last acute-phase observation, and during continuation and post-continuation follow-up (acute phase remitters only)., Results: Of the 12 enrollees, 5 (41.7%) remitted and 7 (58.3%) responded to ketamine treatment during the acute-phase. All five subjects who remitted during the acute-phase experienced further depressive symptom improvement during continuation-phase treatment. Four subjects lost remission status during the post-continuation phase, but all were still classified as positive treatment responders at the end of the post-continuation phase. Adverse effects were generally mild and transient during acute- and continuation-phase treatment; however, one subject developed behavioral outbursts and suicide threats during follow-up while hospitalized, and one subject died by suicide several weeks after the end of follow-up., Limitations: This was an uncontrolled feasibility study with a small sample size., Conclusions: The continuation-phase administration of ketamine at weekly intervals to patients with treatment-resistant depression who remitted during acute-phase ketamine treatment can extend the duration of depressive symptom remission. The antidepressive effect of ketamine persisted for several weeks after the end of continuation-phase treatment. Our results highlight the need for close monitoring of subjects who are at high baseline risk for suicide but do not respond clinically to ketamine. CLINICALTRIALS., Gov Identifier: NCT02094898., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: The aims of this naturalistic study are to examine psychiatric rehospitalization rates in geriatric compared to nongeriatric patients who receive electroconvulsive therapy (ECT) and to characterize the sustained effectiveness of ECT for treatment of depression., Methods: Retrospective review of electronic medical records at a tertiary care center for patients with major depressive disorder who received an acute course of ECT at an index psychiatric hospitalization over a 5-year period. Data for subsequent psychiatric and primary care encounters were ascertained by chart review. Outcomes of interest included between-group differences in rates of psychiatric rehospitalization, time to rehospitalization, rates of other types of clinical follow-up care, and effect of demographic variables on clinical outcome., Results: Of 482 total patients, there were 210 (44%) geriatric patients (≥65 years). These patients experienced lower overall rates of psychiatric rehospitalization after ECT (6.2% vs 22%; P < 0.0001) compared to the nongeriatric group. Cox proportional hazard models indicated that older age, assessed both as a dichotomous and continuous variable, was associated with lower risk of rehospitalization. The majority (76.9%) of detected rehospitalizations among geriatric patients occurred within 6 months. In comparison, rates of outpatient primary care and psychiatric follow-up after ECT did not differ as a function of age., Conclusions: Our findings suggest that geriatric patients with major depression receive greater long-term benefit from an acute course of ECT than do nongeriatric patients. Much more research is needed on this topic to rigorously evaluate the long-term efficacy of ECT in geriatric populations.

Right unilateral ultrabrief (RUL-UB) pulse width electroconvulsive therapy (ECT) has attracted much research attention recently due to its smaller effect on memory than is associated with other forms of ECT, such as bitemporal placement or unilateral standard pulse width. However, RUL-UB has demonstrated slower antidepressant efficacy in comparison to the other techniques. One method to enhance the speed of response to RUL-UB ECT is administration of 5 times a week (termed "daily") treatments as opposed to the more standard twice or thrice weekly schedule. In this open label study, we treated 20 depressed patients with daily RUL-UB treatments for up to 2 weeks (ie, 10 treatments) using standardized assessments of depression and retrograde amnesia. Response and remission rates were commensurate with those reported in other recent studies using this technique with twice or thrice weekly treatment frequencies, and there was no clinically significant effect on retrograde memory function. We conclude that daily administration of RUL-UB ECT may shorten the duration of the course of ECT treatments without compromising cognition. A randomized trial comparing this technique to a thrice weekly schedule of RUL-UB treatments is indicated.

To assess the clinical utility of ketamine as an anesthetic agent for electroconvulsive therapy (ECT), based upon recent findings that ketamine may have antidepressant properties. Depressed ECT patients were randomly assigned to receive anesthesia with either ketamine or methohexital. Outcome measures included assessments of depressive severity, cognition, post-anesthesia side effects, and hemodynamics. Twenty one patients were treated with ketamine and 17 with methohexital. There were no significant differences in depression or cognitive outcomes between the two drugs. Additionally, there were no measures of post-anesthesia tolerability or hemodynamics which favored ketamine. Ketamine anesthesia does not accelerate the antidepressant effect of ECT or diminish the cognitive side effects, at least as measured in this study. Furthermore, there is no apparent benefit of ketamine for speed or quality of post-ECT recovery, and it is associated with higher systolic blood pressures after the treatments. Ketamine is associated with longer motor seizure duration than methohexital., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The effectiveness of psychotherapies, such as interpersonal and social rhythm therapy (IPSRT), is supported by randomized controlled trials. These trials provide minimal direction regarding feasibility of psychotherapy delivery models. The study purpose was to identify factors facilitating implementation and sustainability of an IPRST group for patients with bipolar disorder. Qualitative data were assessed by the normalization process model (NPM). The results demonstrate feasibility of implementation with experienced clinicians, program coordination, and leadership support. Sustainability challenges include aftercare groups, space, and clinician time. The NPM provides a useful framework for evaluation of factors influencing the feasibility of psychotherapy delivery models., (© 2013.)

Background: Single infusions of ketamine have been used successfully to achieve improvement in depressed patients. Side effects during the infusions have been common. It is not known whether serial infusions or lower infusion rates result in greater efficacy., Methods: Ten depressed patients were treated with twice weekly ketamine infusions of ketamine 0.5 mg/kg administered over 100 min until either remission was achieved or four infusions were given. Side effects were assessed with the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). Patients were followed naturalistically at weekly intervals for four weeks after completion of the infusions., Results: Five of 10 patients achieved remission status. There were no significant increases on the BPRS or YMRS. Two of the remitting patients sustained their improvement throughout the four week follow-up period., Conclusions: Ketamine infusions at a lower rate than previously reported have demonstrated similar efficacy and excellent tolerability and may be more practically available for routine clinical care. Serial ketamine infusions appear to be more effective than a single infusion. Further research to test relapse prevention strategies with continuation ketamine infusions is indicated.

Background: The short form of the indel promoter polymorphism (5HTTLPR) of the serotonin transporter gene (SLC6A4) and a history of child abuse have been reported to be associated with an increased risk for the development of depression. A child abuse history has also been associated with more rapid heart rate reactions., Methods: A retrospective chart review identified 282 patients with major depression who had been hospitalized and genotyped for the 5HTTLPR polymorphism. A subgroup of 185 females of European ancestry was also identified and analyzed. While hospitalized, heart rate was measured. Child abuse history was documented during the diagnostic evaluation. Analyses of the relationship between 5HTTLPR genotype, history of child abuse, and admission heart rate were conducted., Results: No main effect on heart rate from the 5HTTLPR genotype or a child abuse history was demonstrated for the entire sample or the subgroup of female patients. However, a genotype-by-abuse interaction was associated with resting heart rate on admission to the hospital (P<.05). Depressed patients, who were homozygous for the long allele and who had been abused, had a heart rate on hospital admission, which was statistically higher than patients with the same genotype but who had not been abused. These findings were consistent both for the 282 patients (7.2 bpm higher) as well as for the subgroup of 185 female patients of European ancestry (9.6 bpm higher)., Conclusions: A 5HTTLPR genotype interaction of elevated heart rate with a history of child abuse was demonstrated in depressed psychiatric inpatients., (© 2010 Wiley-Liss, Inc.)