Analyzing Non-verbal Behavior Throughout Recovery in a Sample of Depressed Patients Receiving Deep Brain Stimulation.

BACKGROUND: Traditional rating scales for depression rely heavily on patient self-report, and lack detailed measurement of non-verbal behavior. However, there is evidence that depression is associated with distinct non-verbal behaviors, assessment of which may provide useful information about recovery. This study examines non-verbal behavior in a sample of patients receiving Deep Brain Stimulation (DBS) treatment of depression, with the purpose to investigate the relationship between non-verbal behaviors and reported symptom severity. METHODS: Videotaped clinical interviews of twelve patients participating in a study of DBS for treatment-resistant depression were analyzed at three time points (before treatment and after 3 months and 6 months of treatment), using an ethogram to assess the frequencies of 42 non-verbal behaviors. The Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS-17) were also collected at all time points. RESULTS: Factor analysis grouped non-verbal behaviors into three factors: react, engage/fidget, and disengage. Two-way repeated measures ANOVA showed that scores on the three factors change differently from each other over time. Mixed effects modelling assessed the relationship between BDI score and frequency of non-verbal behaviors, and provided evidence that the frequency of behaviors related to reactivity and engagement increase as BDI score decreases. LIMITATIONS: This study assesses a narrow sample of patients with a distinct clinical profile at limited time points. CONCLUSIONS: Non-verbal behavior provides information about clinical states and may be reliably quantified using ethograms. Non-verbal behavior may provide distinct information compared to self-report.

Assessing Residents' Confidence in the Context of Pharmacotherapy Competence.

OBJECTIVE: We aimed to determine whether residents' confidence initiating medications increased with the number of times they prescribed individual medications and to quantify the relationship between prescription frequency and gains in confidence. METHODS: From July 2011 to June 2014, PGY-3 residents completed a survey of confidence levels at their psychopharmacology clinic orientation and then again 12 months later. The Emory Healthcare electronic medical record was used to identify all medications prescribed by each resident during their 12-month rotation and the frequency of these prescriptions. RESULTS: Confidence in initiating treatment with all medicines/medication classes increased over the 12-month period. For three of the medication classes for which residents indicated they were least confident at orientation, the number of prescriptions written during the year was significantly associated with an increase in confidence. CONCLUSIONS: Measuring resident confidence is a relevant and achievable outcome and provides data for educators regarding the amount of experience needed to increase confidence.

The Collaborative Cross, a community resource for the genetic analysis of complex traits.

The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

Peak window of suicides occurs within the first month of diagnosis: implications for clinical oncology.

OBJECTIVE: A diagnosis of cancer can provoke painful emotional reactions and possibly suicidal thoughts in a patient. Consequently, cancer patients carry a twofold increased lifetime risk of suicide. This risk is much higher within 1 year of diagnosis. However, it remains largely unknown whether suicide frequency remains constant within the first year. Therefore, we sought to characterize the distribution of suicides in order to potentially identify a clinically important window of peak suicide risk. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database for cancer patients 20 + years old with diagnosed with a single malignancy from 1973 to 2005 and known cause of death, including whether a patient committed suicide. Initial frequency analysis was performed to identify the period of maximum suicide risk. One-way ANOVA was performed to assess the relationship between year of diagnosis and suicide completions within 1 month of diagnosis. RESULTS: The cohort consisted of 3,678,868 patients. Of the total cohort, 0.2% (5875 patients) committed suicide, 36% (2111 patients) within 1 year of diagnosis. One in three (701 of the patients) who committed suicide in the first year did so within 1 month of diagnosis. No change in this distribution occurred over time. CONCLUSIONS: Cancer patients carry an increased risk of suicide. However, this risk peaks with the month following diagnosis. Clinicians should be aware of this increased risk and include assessments of mood state and suicidality at the time of initial diagnosis of the malignancy and be prepared to provide referral to mental health treatment providers.

Pharmaco-genetically guided treatment of recurrent rage outbursts in an adult male with 15q13.3 deletion syndrome.

15q13.3 deletion syndrome (15q13.3DS) is a common recurrent genomic disorder associated with epilepsy, intellectual impairment, aggressive behavior, schizophrenia, and autism. A 39-year-old male presented with 15q13.3DS, epilepsy, intellectual impairment, psychosis, and recurrent episodes of aggressive rage. We hypothesized that the patient's aggressive behavior reflected deficits in α7 nicotinic cholinergic receptor (NChR)-mediated neurotransmission, arising from haploinsufficiency of the structural gene CHRNA7 due to the deletion. Treatment with the NChR allosteric modulator and acetylcholinesterase (AChE) inhibitor, galantamine, led to a dramatic decline in the frequency and intensity of rage outbursts, suggesting that enhancement of α7 NChR function can ameliorate 15q13.3DS-associated rage outbursts.

A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression.

OBJECTIVE: Patients (30-50%) with non-psychotic major depression will not respond despite an adequate trial of antidepressant medication. This study evaluated risperidone as an augmenting agent for patients who failed or only partially responded to an adequate trial of an antidepressant medication. METHOD: Ninety-seven patients with unipolar non-psychotic major depression who were not responsive to antidepressant monotherapy were randomized to risperidone (0.5-3mg/day) or placebo augmentation in a four-week, double-blind, placebo controlled treatment trial. The primary outcome measure was remission defined by a score of < or =10 on the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes measures were the Hamilton Rating Scale for Depression, the Clinician Global Impression of Severity scale and the overall satisfaction item of the Quality of Life and Enjoyment Questionnaire. RESULTS: Subjects in both treatment groups improved significantly over time. The odds of remitting were significantly better for patients in the risperidone vs. placebo arm (OR=3.33, p=.011). At the end of 4 weeks of treatment 52% of the risperidone augmentation group remitted (MADRS< or =10) compared to 24% of the placebo augmentation group (CMH(1)=6.48, p=.011), but the two groups were converging. Patients in the risperidone group also reported significantly more improvement in quality-of-life than patients in the placebo group. There were no between-group differences in the number of adverse events reported, however, weight gain was significantly higher in the group receiving risperidone. CONCLUSION: Augmentation of an antidepressant with risperidone for patients with difficult-to-treat depression leads to more rapid response and a higher remission rate and better quality-of-life.

Suicide pact by mutual simultaneous arm amputation.

BACKGROUND: Dyadic suicide pacts are cases in which two individuals (and very rarely more) agree to die together. These account for fewer than 1% of all completed suicides. OBJECTIVE: The authors describe two men in a long-term domestic partnership who entered into a suicide pact and, despite utilizing a high-lethality method (simultaneous arm amputation with a power saw), survived. METHOD: The authors investigated the psychiatric, psychological, and social causes of suicide pacts by delving into the history of these two participants, who displayed a very high degree of suicidal intent. Psychiatric interviews and a family conference call, along with the strong support of one patient's family, were elicited. RESULTS: The patients, both HIV-positive, showed high levels of depression and hopelessness, as well as social isolation and financial hardship. With the support of his family, one patient was discharged to their care, while the other partner was hospitalized pending reunion with his partner. DISCUSSION: This case illustrates many of the key, defining features of suicide pacts that are carried out and also highlights the nature of the dependency relationship.

Differential association of socioeconomic status in ethnic and age-defined suicides.

Suicide rates vary among racel- and age-defined groups, yet little is known about how suicide risk factors differentially impact individual groups. This study assessed differential associations of socioeconomic status among age- and race-defined groups of suicide victims. A database containing demographic information on declared suicides in Fulton County, GA, from 1 January 1988 through 31 December 2003 was combined with annual per capita income by zip code in Atlanta, GA. Analyses were performed to evaluate differential associations of socioeconomic status among age- and race-defined groups of suicide victims. Compared with the respective ethnic populations of Fulton County, white suicide victims lived in areas with lower per capita income ($51,232 vs. $35,893); African American suicide victims did not ($17,384 vs. $18,179). Elderly suicide victims (>or= 65 years) were more likely to live in the lowest per capita income areas compared with other age groups (OR 1.80, 95% C.I. 1.14, 2.84). Cox proportional hazards models showed increasing income increased the instantaneous risk of suicide among adolescents (HR 2.76; 95% C.I. 2.15, 3.53), particularly African American adolescents (HR 4.22; 95% C.I. 2.19, 8.11), and decreased risk among the elderly (HR 0.58; 95% C.I. 0.50, 0.68). Socioeconomic status had differential associations among age- and race-defined groups of suicide victims.

Long-Term Outcomes of Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression.

OBJECTIVE: Deep brain stimulation of the subcallosal cingulate (SCC DBS) has been studied as a potential treatment for severe and refractory major depressive disorder since 2005. The authors used an open-label, long-term follow-up design to examine participants enrolled in a clinical trial of SCC DBS for treatment-resistant depression. METHODS: Long-term outcome data were collected for 28 patients (20 with major depressive disorder and seven with bipolar II disorder; one patient in the major depression subgroup was later reclassified as having bipolar II disorder) receiving SCC DBS for 4-8 years. RESULTS: Response and remission rates were maintained at ≥50% and ≥30%, respectively, through years 2-8 of the follow-up period. Three-quarters of all participants met the treatment-response criterion for more than half of their duration of participation in the study, with 21% of all patients demonstrating continuous response to treatment from the first year onward. Of 28 participants, 14 completed ≥8 years of follow-up, 11 completed ≥4 years, and three dropped out before 8 years. The procedure itself was generally safe and well tolerated, and there were no side effects of acute or chronic stimulation. The rate of medical or surgical complications was consistent with the rate observed in studies of DBS for other indications. There were no suicides. CONCLUSIONS: In >8 years of observation, most participants experienced a robust and sustained antidepressant response to SCC DBS.

And now, transcriptomics.

In this issue of Neuron, report different patterns of 5-HT2C pre-mRNA editing in suicide victims, as compared to controls. Treatment of mice with fluoxetine alters the pattern of 5-HT2C transcript editing in the direction opposite that observed for suicide victims. The authors speculate on a possible serotonergic mechanism controlling 5-HT2C pre-mRNA editing.

Genetic regulation of hypothalamic cocaine and amphetamine-regulated transcript (CART) in BxD inbred mice.

Cocaine and Amphetamine-Regulated Transcript (CART) peptides are implicated in a wide range of behaviors including in the reinforcing properties of psychostimulants, feeding and energy balance and stress and anxiety responses. We conducted a complex trait analysis to examine natural variation in the regulation of CART transcript abundance (CARTta) in the hypothalamus. CART transcript abundance was measured in total hypothalamic RNA from 26 BxD recombinant inbred (RI) mouse strains and in the C57BL/6 (B6) and DBA/2J (D2) progenitor strains. The strain distribution pattern for CARTta was continuous across the RI panel, which is consistent with this being a quantitative trait. Marker regression and interval mapping revealed significant quantitative trait loci (QTL) on mouse chromosome 4 (around 58.2 cM) and chromosome 11 (between 20-36 cM) that influence CARTta and account for 31% of the between strain variance in this phenotype. There are numerous candidate genes and QTL in these chromosomal regions that may indicate shared genetic regulation between CART expression and other neurobiological processes referable to known actions of this neuropeptide.

Depression, desperation, and suicidal ideation in college students: results from the American Foundation for Suicide Prevention College Screening Project at Emory University.

The objective of this investigation was to examine suicidal ideation and depression in undergraduate college students who participated in the American Foundation for Suicide Prevention-sponsored College Screening Project at Emory University. The principal measure of depressive symptoms was the nine-item depression module from the Patient Health Questionnaire (PHQ-9). Additional questions were focused on current suicidal ideation, past suicide attempts, and episodes of deliberate self-harm and on symptoms of anxiety and distress. Seven hundred and twenty-nine students participated over a 3-school-year interval (2002-2005). Most notably, 11.1% of the students endorsed current (past 4 weeks) suicidal ideation and 16.5% had a lifetime suicide attempt or self-injurious episode. Students with current suicidal ideation had significantly higher depression symptom severity than those without suicidal ideation (t = -9.34, df = 706, P<.0001, d = 1.9), and 28.5% of the students with PHQ-9 scores of 15 or higher reported suicidal ideation compared to 5.7% of those with lower scores (chi(2) = 56.29, df = 1, P<.0001, two-tailed). Suicidal ideation was prominently associated with symptoms of desperation (odds ratio 2.6, 95% CI 1.5-4.6, P<.001). The vast majority of students with moderately severe to severe depression (85%) or current suicidal ideation (84%) were not receiving any psychiatric treatment at the time of assessment. These results suggest that there is a strong relationship between severity of depressive symptoms and suicidal ideation in college students, and that suicidal feelings and actions are relatively common in this group. This underscores the need to provide effective mental health outreach and treatment services to this vulnerable population. As this analysis was based on data collected at a single institution, the results may not be representative of all college students or young adults.

An interactive web-based method of outreach to college students at risk for suicide.

OBJECTIVE AND PARTICIPANTS: From 2002 to 2005, the authors tested an interactive, Web-based method to encourage college students at risk for suicide to seek treatment. METHODS: The authors invited students at 2 universities to complete an online questionnaire that screened for depression and other suicide risk factors. Respondents received a personalized assessment and were able to communicate anonymously with a clinical counselor online. At-risk students were urged to attend in-person evaluation and treatment. RESULTS: A total of 1,162 students (8% of those invited) completed the screening questionnaire; 981 (84.4%) were designated as at high or moderate risk. Among this group, 190 (19.4%) attended an in-person evaluation session with the counselor, and 132 (13.5%) entered treatment. Students who engaged in online dialogues with the counselor were 3 times more likely than were those who did not to come for evaluation and enter treatment. CONCLUSIONS: The method has considerable promise for encouraging previously untreated, at-risk college students to get help.

Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions.

BACKGROUND: The dissociative anesthetic agent ketamine is increasingly being utilized to treat depression, despite not having FDA (Food and Drug Administration) approval for this indication. There are many questions about the potential risks of this treatment and hence the proper setting and degree of monitoring required to ensure patient safety. There is limited data about the cardiovascular safety of ketamine when administered at subanesthetic doses to treat depression. METHODS: 66 patients in the Department of Psychiatry at Emory University received a total of 684 ketamine infusions between 2014 and 2016. Ketamine was dosed at 0.5 mg/kg body weight and infused over 40 min. Blood pressure was measured every 10 min during the infusions and every 15 min thereafter. RESULTS: Mean age of the patients was 56.7 years, 87.9% had unipolar depression and 36.1% had essential hypertension. No infusions were discontinued due to instability of vital signs, adverse physiological consequences or acute psychotomimetic effects. The biggest increases in blood pressure were measured at 30 min (systolic 3.28 mmHg, diastolic 3.17 mmHg). Hypertensive patients had higher blood pressure peaks during the infusions. Blood pressures returned to baseline during post-infusion monitoring. There was no development of tolerance to the blood pressure elevating effects of ketamine between the first and sixth infusions. LIMITATIONS: This is a single site, retrospective analysis, of patients who were spontaneously seeking clinical care. CONCLUSIONS: The blood pressure changes observed when ketamine is administered over 40 min at 0.5 mg/kg for the treatment of depression are small, well tolerated and clinically insignificant.

Cocaine and alcohol use preceding suicide in African American and white adolescents.

The goal of this investigation was to determine whether cocaine and ethanol use was a differentiating factor between African American and white teenage suicide victims. This is a retrospective analysis of medical examiner's records of all completed suicides in Fulton County, GA from 01/1989 to 12/2003, and included 1296 cases. There were 79 suicide victims aged 19 and younger during the study interval, and of this group, 49 (62%) were African American, 26 (33%) were white, and 4 (5%) other race, compared to adults (20 years) where 28.5% were African American, 68.6% white and 2.9% other race (chi(2)=42.678, d.f.=2, p<0.0001). Of the black teenaged victims, 82.2% had no cocaine or alcohol detected at autopsy, while 41.7% of the white victims were positive for one or both substance (chi(2)=4.633, d.f.=1, p=0.04). Only 8.9% of the black teenage suicide victims had used cocaine prior to death compared to 28% of the whites (chi(2)=4.432; d.f.=1; p<0.04). The suicide rate (suicide/100,000/year) for black teens was 5.48 compared to 4.16 for whites, but the rate of cocaine positive teen suicides was 1.12 for whites and 0.45 for blacks. The pattern of cocaine use changes dramatically in the adult group, with 27% of African American suicide victims compared to 7.7% of whites being positive (chi(2)=73.272; d.f.=1; p<0.001). Use of intoxicating substances does differentiate teenage suicide victims, as only a small proportion of black teenagers had used cocaine or alcohol prior to death compared to almost half of all whites.

Genetic analysis of the hypothalamic neurotensin system.

This study used B x D recombinant inbred mice to detect and localize genes that control the hypothalamic neurotensin (NT) system. Abundance of transcripts that encode NT and NT receptors 1, 2, and 3 (NTR1, NTR2, and NTR3) in total hypothalamic RNA was the quantitative trait measured. Analysis of transcript abundance data revealed associations with quantitative trait loci (QTL) for NT transcript abundance (NTta) on chromosome 1, 3, 6, 7, 8, and 9; for NTR1ta on chromosome 3, 8, 12, and X; for NTR2ta on chromosome 2, 4, 9, 10, 12, 13, and 17; for NTR3ta on chromosome 1, 7, 11, and 12. NTta QTL on chromosomes 3, 7, and 8 coincide with QTL previously identified that impact NT peptide content and NTR2ta QTL on chromosome 2 and 12 coincide with genes previously associated with NTR2 receptor abundance. The NTta, NTR1ta, and NTR3ta QTL were not linked to their respective structural genes, but there is a highly significant (p<0.001) association for NTR2ta on chromosome 12 that includes the Ntsr2 structural gene. There are areas of potential shared genetic regulation between NTta and NTR3ta on chromosome 1 and 7 and for all three receptors on proximal chromosome 12. The NTta QTL on chromosome 9 includes the dopamine D2 receptor (Drd2) gene and QTL involved in responses to dopaminergic agents (Hts), antipsychotics (Hpic1) and cocaine (Cocrb8), and ethanol (Etohc3). These results further strengthen the hypothesis that the NT system is involved in mediating the actions of antipsychotic agents and drugs of abuse.

Use of Expert Consultation in a Complex Case of Neuroleptic Malignant Syndrome Requiring Electroconvulsive Therapy.

Our team at Emory University Hospital contacted experts at the National Network of Depression Centers (NNDC) for clinical guidance concerning a patient with schizophrenia hospitalized in the intensive care unit with a complex case of prolonged delirium secondary to neuroleptic malignant syndrome (NMS). Through the NNDC, leading psychiatrists across the United States with expertise in electroconvulsive therapy (ECT) provided us with treatment strategies based on experience in our area of concern. This report describes our use of ECT to treat severe NMS in this patient with schizophrenia, utilizing the recommendations made by the NNDC's ECT experts concerning electrode position, number and frequency of treatments, and selection of anesthetic induction agents. This case report highlights the utility of expert consultation in the treatment of rare diseases and provides guidance on how to treat NMS in the intensive care unit setting.

Time-dependent effects of dexamethasone plasma concentrations on glucocorticoid receptor challenge tests.

Glucocorticoid challenge tests such as the dexamethasone suppression test (DST) and the combined dexamethasone/corticotropin-releasing hormone (dex-CRH) test are considered to be able to sensitively measure hypothalamic-pituitary-adrenal (HPA) axis activity in stress-related psychiatric and endocrine disorders. We used mass-spectrometry to assess the relationship of plasma dexamethasone concentrations and the outcome of these tests in two independent cohorts. Dexamethasone concentrations were measured after oral ingestion of 1.5mg dexamethasone in two cohorts that underwent a standard (dexamethasone at 23:00h) as well as modified (18:00h) DST and dex-CRH test. The first study population was a case/control cohort of 105 depressed patients and 133 controls in which peripheral blood mRNA expression was also measured. The second was a cohort of 261 depressed patients that underwent a standard dex-CRH test at baseline and after 12 weeks' treatment with cognitive-behavioral therapy or antidepressants. Dexamethasone concentrations explained significant proportions of the variance in the DST in both the first (24.6%) and the second (5.2%) cohort. Dexamethasone concentrations explained a higher proportion of the variance in the dex-CRH test readouts, with 41.9% of the cortisol area under the curve (AUC) in the first sample and 24.7% in the second sample. In contrast to these strong effects at later time points, dexamethasone concentrations did not impact cortisol or ACTH concentrations or mRNA expression 3hours after ingestion. In the second sample, dexamethasone concentrations at baseline and week 12 were highly correlated, independent of treatment type and response status. Importantly, a case/control effect in the Dex-CRH test was only apparent when controlling for dexamethasone concentrations. Our results suggest that the incorporation of plasma dexamethasone concentration or measures of earlier endocrine read-outs may help to improve the assessment of endocrine dysfunction in depression.