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Background Delirium is relatively common after lung transplantation, although its prevalence and prognostic significance have not been systematically studied. The purpose of the present study was to examine pretransplant predictors of delirium and the short-term impact of delirium on clinical outcomes among lung transplant recipients. Methods Participants underwent pretransplant cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status and the Trail Making Test. After transplant, delirium was assessed using the Confusion Assessment Method until discharge. Results Sixty-three patients were transplanted between March and November 2013, of which 23 (37%) developed delirium. Among transplanted patients, 48 patients completed pretransplant cognitive testing. Better pretransplant cognitive function was associated with lower risk of delirium (odds ratio, 0.69 [95% confidence interval 0.48, 0.99], P = .043); and demographic and clinical features including native disease ( P = .236), the Charlson comorbidity index ( P = .581), and the lung allocation score ( P = .871) were unrelated to risk of delirium, although there was a trend for women to experience delirium less frequently ( P = .071). The presence ( P = .006) and duration ( P = .027) of delirium were both associated with longer hospital stays. Conclusion Delirium occurs in more than one-third of patients after lung transplantation. Delirium was associated with poorer pretransplant cognitive functioning and longer hospital stays, after accounting for other medical and demographic factors.

To determine if the implementation of a hospital-specific alcohol withdrawal treatment pathway used in a medical-surgical patient population decreased hospital length of stay (LOS) compared with the standard of care.This retrospective observational study, conducted in a large academic tertiary care hospital, involved 582 subjects who met criteria for study inclusion, with 275 subjects in the 2010 cohort and 307 in the 2012 cohort. The Alcohol Withdrawal Project Team was formed with the goal of creating a standardized approach to the recognition and treatment of alcohol withdrawal at Duke University Hospital. The group created a computerized physician order entry alcohol withdrawal treatment pathway with 4 possible treatment paths chosen on the basis of current withdrawal symptoms, vital signs, and alcohol withdrawal history. The 4 treatment paths are 1 prophylaxis; 2 mild-to-moderate withdrawal; 3 moderate-to-severe withdrawal, and 4 severe withdrawal/alcohol withdrawal delirium. Each treatment path corresponds to a different lorazepam dose and dose schedule and symptom assessment. This pathway was implemented in the hospital at the end of 2011.Using a Cox proportional hazards model and adjusting for covariates, there was a 1 day [95% confidence interval (CI), 1-2 d] reduction in median hospital LOS between the 2010 and 2012 cohorts, 5 versus 4 days, respectively. The average ratio in hospital LOS between the 2 cohorts was 1.25 (95% CI, 1.25-1.67). The CI was estimated by bootstrapping and indicated a significantly longer LOS in the 2010 cohort compared with the 2012 cohort. Nonsignificant changes were found in the proportion of subjects admitted to the intensive care unit (24% in 2010 vs. 29.3% in 2012), LOS in the intensive care unit (7.1±8 d in 2010 vs. 5.6±6.9 d in 2012), and proportion of patients discharged with a diagnosis of delirium tremens (17.8% in 2010 vs. 15.3% in 2012).This study demonstrates the successful implementation of an alcohol withdrawal treatment pathway in a medical-surgical population hospitalized in a large tertiary care facility with significant impact on hospital LOS.

Baclofen, an agonist at the B subunit of gaba-aminobutyric acid receptor, possesses pharmacologic properties that may confer utility for the treatment of alcohol dependence. Research suggests that not only can it be useful in promoting maintenance of alcohol abstinence but also it may play a key role in decreasing alcohol cravings and anxiety often associated with alcohol dependence. To assess the benefit of baclofen for alcohol dependence, a review of the literature was conducted to identify published data investigating this off-label treatment. Four randomized controlled trials to date have been published and were included in this review. Although primary outcomes differ between studies, patients randomized to baclofen experience higher rates of abstinence from alcohol than those taking placebo in two of the trials. Secondary analyses indicate that baclofen is safe in patients with alcohol dependence, including those with moderate to severe liver cirrhosis, and may provide beneficial anxiolytic effects. Despite some positive data, the largest available randomized controlled trial failed to find any differences between baclofen and placebo. In all studies, individuals with severe medical comorbidities, seizure disorders, and psychiatric disorders were excluded from trials, which may limit external validity. In summary, there may be beneficial effects from using baclofen for the treatment of alcohol dependence; however, limited conclusions can be drawn from the small number of studies currently available for review. Larger well-designed trials are needed to further define baclofen’s role for the treatment of alcohol dependence.

Delirium is common following lung transplant and is associated with poorer clinical outcomes. The extent to which intraoperative hemodynamic alterations may contribute to postoperative delirium among lung transplant recipients has not been examined.To examine the impact of intraoperative hemodynamic changes on neurobehavioral outcomes among lung transplant recipients.Intraoperative hemodynamic function during lung transplant was assessed in a consecutive series of patients between March and November 2013. Intraoperative cerebral perfusion pressure was assessed every minute in all patients. Following lung transplant, patients were monitored for the presence and severity of delirium using the Confusion Assessment Method and the Delirium Rating Scale until hospital discharge.Sixty-three patients received lung transplants, of whom 23 (37%) subsequently developed delirium. Lower cerebral perfusion pressure was associated with increased risk of delirium (odds ratio [OR], 2.08 per 10-mm Hg decrease; 95% confidence interval [CI], 1.02-4.24; P = 0.043), longer duration of delirium (OR, 1.7 d longer per 10-mm Hg decrease; 95% CI, 1.1-2.7; P = 0.022), and greater delirium severity (b = -0.81; 95% CI, -1.47 to -0.15; P = 0.017).Poorer cerebral perfusion pressure during lung transplant is associated with greater risk for delirium following transplant, as well as greater duration and severity of delirium, independent of demographic and medical predictors.

Background Postoperative delirium, a common complication in the elderly, can occur following any type of surgery and is associated with increased morbidity and mortality; it may also be associated with subsequent cognitive problems. Effective therapy for postoperative delirium remains elusive because the causative factors of delirium are likely multiple and varied. Methods Patients 65 yr or older undergoing elective knee arthroplasty were prospectively evaluated for postoperative Diagnostic and Statistical Manual of Mental Disorders-IV delirium. Exclusion criteria included dementia, mini-mental state exam score less than 24, delirium, clinically significant central nervous system/neurologic disorder, current alcoholism, or any serious psychiatric disorder. Delirium was assessed on postoperative days 2 and 3 using standardized scales. Patients' preexisting medical conditions were obtained from medical charts. The occurrence of obstructive sleep apnea was confirmed by contacting patients to check their polysomnography records. Data were analyzed using Pearson chi-square or Wilcoxon rank sum tests and multiple logistic regressions adjusted for effects of covariates. Results Of 106 enrolled patients, 27 (25%) developed postoperative delirium. Of the 15 patients with obstructive sleep apnea, eight (53%) experienced postoperative delirium, compared with 19 (20%) of the patients without obstructive sleep apnea (P = 0.0123, odds ratio: 4.3). Obstructive sleep apnea was the only statistically significant predictor of postoperative delirium in multivariate analyses. Conclusions This is the first prospective study employing validated measures of delirium to identify an association between preexisting obstructive sleep apnea and postoperative delirium.

The pharmacological properties of baclofen, a GABA(B) receptor agonist, have led to investigation of its use for the off-label treatment of alcohol dependence. Literature examining the role of baclofen in alcohol dependence suggests that it may be a useful medication in the treatment armamentarium with an additional benefit of promoting abstinence and reducing alcohol-associated cravings and anxiety. We conducted a systematic review of prospective, randomized controlled trials comparing baclofen with placebo for the treatment of alcohol dependence. Four randomized controlled trials were identified but only three met criteria for inclusion. The excluded trial was a post hoc analysis of data collected from an original trial whose primary outcome did not fit our inclusion criteria and was terminated prior to completion. Compared with placebo, subjects randomized to baclofen experienced higher rates of abstinence and lower anxiety scores; the effect of baclofen was statistically significant in two trials assessing patients with more severe alcohol dependence and non-significant in a trial of outpatients receiving concomitant manualized psychotherapy. Baclofen appeared to be safe, well tolerated and to have low addiction liability even in the setting of moderate-to-severe liver cirrhosis, a known complication of alcohol dependence. Though baclofen may hold promise, the different outcomes and sample populations of the three studies highlight the need for more research to better understand the appropriate target patient population to benefit from this medication. Questions still remain about optimal dosing and duration. There is not enough evidence to support the use of baclofen as a first-line treatment option, except for those alcohol-dependent patients with moderate-to-severe liver cirrhosis in whom other pharmacological treatments are not safe or practical.

Objectives The objective was to test the hypothesis that heart failure (HF) patients treated with sertraline will have lower depression scores and fewer cardiovascular events compared with placebo. Background Depression is common among HF patients. It is associated with increased hospitalization and mortality. Methods The SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial was a randomized, double-blind, placebo-controlled trial of sertraline 50 to 200 mg/day versus matching placebo for 12 weeks. All participants also received nurse-facilitated support. Eligible patients were age 45 years or older with HF (left ventricular ejection fraction ≤45%, New York Heart Association functional class II to IV) and clinical depression (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for current major depressive disorder). Those with significant cognitive impairment, psychosis, recent alcohol or drug dependence, bipolar or severe personality disorder, active suicidal ideation, and current antipsychotic or antidepressant medications were excluded. Primary end points were change in depression severity (Hamilton Depression Rating Scale total score) and composite cardiovascular status at 12 weeks. Results A total of 469 patients were randomized (n = 234 sertraline, n = 235 placebo). The mean ± SE change from baseline to 12 weeks in the Hamilton Depression Rating Scale total score was −7.1 ± 0.5 (sertraline) and −6.8 ± 0.5 (placebo) (p < 0.001 from baseline, p = 0.89 between groups, mean change between groups −0.4; 95% confidence interval: −1.7 to 0.92). The proportions whose composite cardiovascular score worsened, improved, or was unchanged were 29.9%, 40.6%, and 29.5%, respectively, in the sertraline group and 31.1%, 43.8%, and 25.1%, respectively, in the placebo group (p = 0.78). Conclusions Sertraline was safe in patients with significant HF. However, treatment with sertraline compared with placebo did not provide greater reduction in depression or improved cardiovascular status among patients with HF and depression. (Antidepressant Medication Treatment for Depression in Individuals With Chronic Heart Failure [SADHART-CHF]; [NCT00078286][1]) [1]: http://www.clinicaltrials.gov/ct2/show/NCT00078286?term=NCT00078286%26rank=1

Evidence is mixed for an association between serum insulin-like growth factor-I (IGF-I) levels and postoperative delirium (POD). The current study assessed preoperative serum IGF-I levels as a predictor of incident delirium in non-demented elderly elective knee arthroplasty patients. Preoperative serum levels of total IGF-I were measured using a commercially available Human IGF-I ELISA kit. POD incidence and severity were determined using DSM-IV criteria and the Delirium Rating Scale-Revised-98 (DRS-R98), respectively. Median IGF-I levels in delirious (62.6 ng/ml) and non-delirious groups (65.9 ng/ml) were not significantly different (p = 0.141). The ratio (95% CI) of geometric means, D/ND, was 0.86 (0.70, 1.06). The Hodges-Lehmann median difference estimate was 7.23 ng/mL with 95% confidence interval (−2.32, 19.9). In multivariate logistic regression analysis IGF-I level was not a significant predictor of incident POD after correcting for medical comorbidities. IGF-I levels did not correlate with DRS-R98 scores for delirium severity. In conclusion, we report no evidence of association between serum IGF-I levels and incidence of POD, although the sample size was inadequate for a conclusive study. Further efforts to investigate IGF-I as a delirium risk factor in elderly should address comorbidities and confounders that influence IGF-I levels.

With the implementation of the Affordable Care Act (ACA), there will be a growing demand for mental health care in this country (Patient Protection and Affordable Care Act. U. S. Public Law 111-148-March 23, 2010). It is likely much of this care will continue to be delivered in the primary care setting and not in traditional outpatient psychiatric clinic sites. Primary care providers (PCPs) will be in the position to further expand their existing role as primary behavioral health providers. What does this mean for the future of psychiatry and how psychiatrists are trained?

Mental health and substance use disorders, or behavioral health (BH) disorders, are common and associated with significant morbidity, disability, and health-care costs. However, BH services are not adequate to meet this need. BH care in the general medical sector has increased substantially in the last decade. However, such care tends to lack adequate evidence-based mental health treatment despite a growing evidence base. Moreover, behavioral and medical conditions tend to co-occur, and thus, patients with combined needs are often seen in medical settings. BH and medical conditions are risk factors for one another, and each complicates the course and treatment of the other. Based on these observations, it is essential that we integrate mental health and medical care delivery to improve access, care, and reduce cost.

Despite strong evidence provided by genetic epidemiology of genetic involvement in the aetiology of bipolar and unipolar affective disorders, the exact nature of the predisposing gene(s) is still being investigated through linkage and association studies. The interaction of susceptibility genes and environmental factors in these diseases is also of fundamental importance and requires proper investigation. Interesting theories have recently been proposed examining the possible role of various chromosomal regions, candidate genes and mutations in affective disorders. Reliable multicentre-based methodology is currently being employed to examine these theories, with attention given to statistical analysis and the statistical power of the sample. The present article describes the European Collaborative Project on Affective Disorders (ECPAD) 'Interactions between genetic and psychosocial vulnerability factors', involving 15 European centres. A description is given of the association and family samples collected for the project and also the methodology used to analyse interactions in the gene-psychosocial environment. This material provides a powerful tool in the search for susceptibility genes in affective disorders and takes into account non-genetic aetiological factors.

Background Impaired psychological function is common among lung transplant candidates and may affect clinical outcomes following transplantation. Although numerous studies have examined the relationship between pretransplant depression, quality of life (QoL), and post-transplant outcomes, few have examined the relationship between depression and QoL shortly following transplantation and subsequent clinical outcomes. We therefore examined the association between depression, QoL, and short-term mortality in a consecutive series of lung transplant recipients. Methods Depression (Patient Health Questionnaire-9; Hospital Anxiety and Depression Scale; Centers for Epidemiologic Studies Depression Scale) and QoL (UCSD Shortness of Breath Questionnaire; Pulmonary Quality of Life Scale) were assessed prior to transplantation (median 0.9 months [IQR=1.6]) and again approximately 2 weeks following transplantation (median=0.5 months [IQR=0.5]), in a series of 66 patients transplanted between March 2013 and April 2014. The association between psychiatric diagnoses from participants’ comprehensive pretransplant assessment and mortality also was examined. Cox proportional hazards models were used to examine the association between depression, QoL, and mortality. Results During a median follow-up of 2.8 years (range 0.4-3.3), 21 patients died (32%). Greater depressive symptoms assessed shortly after transplant were associated with subsequent mortality (HR=2.17 [1.01, 4.67], P=.048), and this relationship persisted after controlling for primary graft dysfunction, duration of transplant hospitalization, and gender. In contrast, neither pretransplant depression, history of depression, nor QoL was associated with mortality. Conclusions Greater post-transplant depressive symptoms are independently associated with mortality among lung transplant recipients.

Intravenous haloperidol can increase the risk for corrected QT (QTc) interval prolongation, torsades de pointes (TdP) and sudden death.The purpose of this study was to examine the effects of implementation of a computerized physician order entry (CPOE) set on adherence to monitoring parameters, maximum and cumulative doses, and identification or mitigation of risk factors for QTc prolongation in patients prescribed intravenous haloperidol.A retrospective cohort study of medically ill hospitalized inpatients prescribed intravenous haloperidol was conducted. Data were collected for two distinct 1-year time periods: the pre-CPOE set period (30 June 2007 through 30 June 2008) and the post-CPOE set period (1 January 2009 through 1 January 2010). The CPOE set was implemented on 1 October 2008.A total of 151 subjects were included; 84 subjects were in the pre-CPOE set group and 67 subjects were in the post-CPOE set group. Following CPOE set implementation, subjects in the post-CPOE group, compared with the pre-CPOE group, were more likely to receive a 24-hour cumulative dose of intravenous haloperidol2 mg (Fisher's exact test; p 0.048), have a baseline ECG (Fisher's exact test; p = 0.045), have a follow-up ECG within 24 hours of intravenous haloperidol administration (Fisher's exact test; p = 0.009) and have a magnesium value assessed at the time of intravenous haloperidol administration (Fisher's exact test; p = 0.004).This study reports on the successful implementation of a CPOE set designed to improve the safety of intravenous haloperidol administration in medically ill patients.

Objective This study examines the efficacy of clonidine in smoking cessation and the influence of gender, history of major depression, and measures of nicotine dependence. Methods The study was designed as a 10-week double-blind randomized comparison stratified for gender and major depression. Three hundred subjects who smoked cigarettes heavily were enrolled in the study. Abstinence from smoking was evaluated by self-report and verified by serum cotinine levels. Results Gender, major depression recurrent type, and measures of nicotine addiction were risk factors for treatment failure. There was no clonidine effect in men, but there was a modest effect in women (odds ratio, 2.01; 95% confidence interval, 1.00 to 4.10) that was most pronounced (odds ratio, 8.5; 95% confidence interval, 1.67 to 43.62) among women with the highest risks. Conclusion Measures of addiction and major depression predict treatment failure. Together they are stronger predictors of outcome than drug. Clonidine is a limited aid in cessation, and drug effects come primarily from women at high risk for treatment failure. An increased risk for psychiatric complications after smoking cessation was apparent among smokers with histories of major depression, particularly bipolar disease. Clinical Pharmacology and Therapeutics (1993) 54, 670–679; doi:10.1038/clpt.1993.205

This article reviews data on the cardiovascular effects of tricyclic antidepressants. While cardiotoxic in overdose, at therapeutic doses tricyclics exhibit relatively benign cardiovascular effects in depressed patients without preexisting cardiac disease, with the exception of orthostatic hypotension. They have been shown to delay conduction, manifested by prolonged PR, QRS and QT intervals on the standard ECG. Depressed patients with conduction disease, particularly bundle branch block, when treated with TCAs at therapeutic plasma levels, are at a higher risk of developing symptomatic A-V block than patients free of conduction disorders. Tricyclic antidepressants have been found to reduce ventricular arrhythmias, a property shared with type 1A antiarrhythmic compounds. Recently, a variety of type 1 antiarrhythmics has been shown to increase mortality in post-MI patients. The implications this may have for the TCA treatment of post-myocardial infarction depressed patients needs further study. The newer n...

The objective was to test the hypothesis that heart failure (HF) patients treated with sertraline will have lower depression scores and fewer cardiovascular events compared with placebo.Depression is common among HF patients. It is associated with increased hospitalization and mortality.The SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial was a randomized, double-blind, placebo-controlled trial of sertraline 50 to 200 mg/day versus matching placebo for 12 weeks. All participants also received nurse-facilitated support. Eligible patients were age 45 years or older with HF (left ventricular ejection fractionor =45%, New York Heart Association functional class II to IV) and clinical depression (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for current major depressive disorder). Those with significant cognitive impairment, psychosis, recent alcohol or drug dependence, bipolar or severe personality disorder, active suicidal ideation, and current antipsychotic or antidepressant medications were excluded. Primary end points were change in depression severity (Hamilton Depression Rating Scale total score) and composite cardiovascular status at 12 weeks.A total of 469 patients were randomized (n = 234 sertraline, n = 235 placebo). The mean +/- SE change from baseline to 12 weeks in the Hamilton Depression Rating Scale total score was -7.1 +/- 0.5 (sertraline) and -6.8 +/- 0.5 (placebo) (p0.001 from baseline, p = 0.89 between groups, mean change between groups -0.4; 95% confidence interval: -1.7 to 0.92). The proportions whose composite cardiovascular score worsened, improved, or was unchanged were 29.9%, 40.6%, and 29.5%, respectively, in the sertraline group and 31.1%, 43.8%, and 25.1%, respectively, in the placebo group (p = 0.78).Sertraline was safe in patients with significant HF. However, treatment with sertraline compared with placebo did not provide greater reduction in depression or improved cardiovascular status among patients with HF and depression. (Antidepressant Medication Treatment for Depression in Individuals With Chronic Heart Failure [SADHART-CHF]; NCT00078286).

Discuss the interplay of depression and ischemic heart disease. Studies demonstrate high prevalence of depression and its negative impact among patients with ischemic heart disease.Results extend previous findings among men, demonstrating a significant increase in mortality and cardiovascular events among depressed women. Sertraline, citalopram and mitrazapine have been shown to be safe and well tolerated in patients with ischemic heart disease. Sertraline and citalopram have demonstrated efficacy for treating depression in such patients. Mirtazapine did not have significant efficacy on post-myocardial infarction depression. Cognitive-behavioral therapy and interpersonal therapy have not been found to have a significant treatment effect. Treating depression may have an impact on cardiovascular morbidity and mortality, but this has not yet been adequately studied. Studies to date lack sufficient statistical power to fully examine the impact of interventions for depression on cardiovascular outcomes.Cardiologists encounter depression among 25-30% of their patients with ischemic heart disease. Depression is an independent risk factor for poor prognosis among ischemic heart disease patients, at a level comparable to several conventional cardiac risk factors. Adequate treatment of depression may improve the poor prognosis of depressed patients with ischemic heart disease.

To the Editor: Levocarnitine is utilized for valproic acid overdose to prevent the formation of hepatotoxic metabolites. Levocarnitine has been shown to reduce phosphorus levels. We present a case where levocarnitine was administered for valproic acid toxicity and may have contributed to hypophosphatemia. Levocarnitine (L-carnitine) may be utilized for acute toxicity in valproic acid (VPA) overdose. It is primarily metabolized in the liver via glucuronidation and also undergoes mitochondrial beta-oxidation and microsomal omega-oxidation. In overdose, a shift in metabolism to the omega-oxidative pathway occurs, yielding the hepatotoxic metabolite 2-propyl-4-pentanoic acid. L-carnitine acts as a cofactor for VPA metabolism, increasing beta-oxidation of VPA and limiting hepatotoxic metabolites. 1

Polysomnograms of most homeothermic species distinguish two states, rapid eye movement (REM) and non-REM (NREM) sleep. These alternate several times during the night for reasons and following rules that remain poorly understood. It is unknown whether each state has its own function and regulation or whether they represent two facets of the same process. The present study compared the mean REM/NREM sleep ratio and the mean number of NREM-REM sleep cycles across 3 consecutive nights. The rationale was that, if REM and NREM sleep are tightly associated, their ratio should be comparable whatever the cycle frequency in the night. Twenty-six healthy subjects of both sexes were recorded at their home for 4 consecutive nights. The correlation between the REM/NREM sleep ratio and the number of cycles was highly significant. Of the two sleep components, REM sleep was associated to the number of cycles, whereas NREM sleep was not. This suggests that the relationship between REM sleep and NREM sleep is rather weak within cycles, does not support the concept of NREM-REM sleep cycles as miniature units of the sleep process, and favors the concept of distinct mechanisms of regulation for the two components.

Evidence that major depression can be a significant hindrance to smoking cessation prompted this examination of the usefulness of sertraline as a cessation aid for smokers with a history of major depression. Specifically, sertraline's efficacy for smoking abstinence and its effects on withdrawal symptoms were evaluated.The study design included a 1-week placebo washout, a 9-week double-blind, placebo-controlled treatment phase followed by a 9-day taper period, and a 6-month drug-free follow-up. One hundred thirty-four smokers with a history of major depression were randomly assigned to receive sertraline (N=68) or matching placebo (N=66); all received intensive individual cessation counseling during nine clinic visits.Sertraline treatment produced a lower total withdrawal symptom score and less irritability, anxiety, craving, and restlessness than placebo. However, the abstinence rates did not significantly differ between treatment groups: 28.8% (19 of 66) for placebo and 33.8% (23 of 68) for sertraline at the end of treatment and 16.7% (11 of 66) for placebo and 11.8% (eight of 68) for sertraline at the 6-month follow-up. No moderating effects of single or recurrent major depression, depressed mood at baseline, nicotine dependence level, or gender were observed.Sertraline did not add to the efficacy of an intensive individual counseling program in a double-blind, placebo-controlled study. However, given that the end-of-treatment abstinence rate for the placebo group was much higher than expected, it is unclear whether a ceiling effect of the high level of psychological intervention received by all subjects prevented an adequate test of sertraline.

Summary Background Smokers with a history of major depression who attempt to stop smoking have a higher risk of failure than non-depressed smokers. Anecdotal and post-hoc data suggest that those who successfully abstain are at increased risk of depression compared with individuals who continue to smoke. However, these studies confound effects of abstinence and history of depression. We aimed to assess whether there is an increased risk of depression and for how long that increase lasts. Methods We enrolled 100 smokers (>pack per day) with a history of major depression, but who were currently free from major depression and had not been on antidepressant medicine for at least 6 months, in a 2-month smoking-cessation trial. The primary outcome was recurrence of major depression, which we assessed by structured clinical interviews 3 and 6 months after the end of treatment. We verified smoking status by serum-sample cotinine concentrations. Findings 76 participants (42 successful abstainers, 34 smokers) were followed up. 13 abstainers and two smokers had an episode of major depression (odds ratio 7·17 [95% CI 1·5–34·5]; Kaplan-Meier survival curve, log-rank statistic 9·11 [p = 003]). Risk of major depression was similar between the first and second 3 months of follow-up. Interpretations Smokers with a history of depression who abstain from smoking are at significantly increased risk of developing a new episode of major depression. This risk remains high for at least 6 months.

Anterior spinal artery syndrome is rare in children. In adults, where it is observed most frequently after resection of thoracoabdominal aortic aneurysms, spinal magnetic resonance imaging is considered the first-line investigation to confirm the clinical diagnosis. A 3-year-old male who presented with this syndrome after palliative cardiac surgery for a complex cardiac malformation associated with aortic coarctation is presented. Clinical diagnosis of anterior horn cell impairment below the L2 level was confirmed by electromyography and F-wave studies. Sparing of dorsal sensory tracts was documented by normal somatosensory-evoked potentials, which confirmed the anterior localization of the lesion. Spinal magnetic resonance imaging performed on day 15 and day 105 after surgery was normal. Neurologic deficits, including flaccid paraplegia, remained stable except for the reappearance of patellar reflexes on day 83. Neurophysiologic conduction studies were consistent with lower motoneuron loss. In this patient, magnetic resonance imaging was less sensitive in demonstrating spinal cord lesion than clinical neurophysiology. Somatosensory-evoked potentials failed to detect the insult. Prevention may therefore require other neurophysiologic monitoring techniques.

The identification of genes responsible for mood disorders will contribute to significant advances in the awareness of diagnosis (diagnostic process and early recognition), pathophysiology, epidemiology and treatment issues. During the past two decades, the search for genes for mood disorders has mainly contributed to better understand and confirm the genetic complexities inherent to these disorders. The large amount of results available and the difficulty to digest them corroborate this observation. The major contribution of these findings should be integrated in the context of the world-wide efforts to identify the thousands of genes of the human genome. Some of these genes may be identified within the next decade. Several consistent hypotheses are currently being tested and will, hopefully, speed up the process of narrowing the important regions when the complete genome map will be available. The most promising chromosomal regions have been localized on chromosomes 4, 5, 11, 12, 18, 21 and X. A number of candidate genes have also been investigated, some of these are directly linked to neurobiological hypotheses of the aetiology of affective disorders. In parallel, specific hypotheses have been implicated, such as anticipation and dynamic mutations. Further research should concentrate on these hypotheses and confirm positive findings through interdisciplinary and multicenter projects.

This clinical review considers the different symptomatic forms of bipolar disorders and the influence of the clinical subtype on treatment. Therapy is required both to manage the various types of acute episodes of mania or depression and to prevent recurrence. For the latter purpose, continuous long-term or even lifetime prophylaxis may be required, continuing on after control of the acute episode. In this context, the roles and potential side-effects of lithium, divalproex sodium and carbamazepine, alone and in combination, are summarized, along with the proper use of antipsychotic drugs. The selection of mood-stabilizing agent or drug combination depends on the clinical manifestations of bipolar disorder, family history and previous treatment history of the patient. Particular caution must be exercised in those with a history of antidepressant-induced switches; many such patients appear prone to course aggravation and even rapid-cycling and will often need combined mood-stabilizer combinations.

Objective: Two smoking cessation studies provided venues to 1) look for differences in affective symptoms between cigarette smokers with and without a history ofmajor depression or other psychiatric diagnoses who were not currently depressed and 2) evaluate the efficacy offluoxetine in ameliorating affective symptoms in smokers with a history ofmajor depression but not currently depressed. Method: Part I: Three hundred sixty-eight smokers who enrolled in a smoking cessation treatment study completed baseline self-rating scales. The relationship between the scale scores and a history of major depression and other psychiatric diagnoses was examined. Part II: Thirty-nine smokers with a history ofmajor depression were enrolled in a randomized, double-blind study that examined the utility offluoxetine as an aid to smoking cessation. Self-rated scales were compared at baseline and after 3 weeks of medication treatment before the attempt to quit. Results: A history of major depression had significant main effects across all scale scores; subjects with such a history rated themselves as more symptomatic. The effects ofother psychiatric diagnoses were neither as pervasive nor as robust. There were no differences in baseline scores between the fluoxetine- and placebo-treated groups and no change within the placebo group after 3 weeks. There was significant improvement f rom baseline in several subscale scores for the group treated with fluoxetine. However, comparison ofthe score changes for the placebo and fluoxetine groups did not show a statistically significant difference, which limited the ability to conclude that active treatment was better than placebo. Conclusions: Subjects with a history of major depression, but without current affective illness, reported themselves to be more symptomatic than those without such a history. Furthermore, in a group of smokers with a history of major depression, affective symptoms, without concurrent syndromal illness, may be ameliorated by treatment with fluoxetine. (Am J Psychiatry 1995; 152:398-403)

Thirty-two patients with a DSM-III-R diagnosis of panic disorder (PD) were administered the Parental Bonding Instrument (PBI), a 25-item self-report questionnaire devised to evaluate parental rearing practices. Compared with 32 matched healthy controls, PD patients scored both their parents as being significantly less caring and more overprotective. Moreover, the consistency of parental attitudes between the 2 parents was significantly lower, indicating lesser uniformity in the rearing patterns.

Tyrosine hydroxylase (TH), the rate-limiting enzyme in the metabolism of catecholamines, is considered a candidate gene in bipolar affective disorder (BPAD) and has been the subject of numerous linkage and association studies. Taken together, most results do not support a major gene effect for the TH gene in BPAD. Genetic and phenotypic heterogeneity may partially explain the difficulty of confirming the exact role of this gene using both association and linkage methods. Four hundred one BPAD patients and 401 unrelated matched controls were recruited within a European collaborative project (BIOMED1 project in the area of brain research, European Community grant number CT 92-1217, project leader: J. Mendlewicz) involving 14 centers for a case-control association study with a tetranucleotide polymorphism in the TH gene. Patients and controls were carefully matched for geographical origin. Phenotypic heterogeneity was considered and subgroup analyses were performed with relevant variables: age at onset, family history, and diagnostic stability. No association was observed in the total sample or for subgroups according to age at onset (n = 172), family history alone (n = 159), or high degree of diagnostic stability and a positive family history (n = 131). The results of this association study do not confirm the possible implication of TH polymorphism in the susceptibility to BPAD.