Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts.
The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort.
Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety.
The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.
We sought to examine the efficacy and safety of acamprosate augmentation of escitalopram in patients with concurrent major depressive disorder (MDD) and alcohol use disorders. Twenty-three adults (43% female; mean ± SD age, 46 ± 14 years) were enrolled and received 12 weeks of treatment with psychosocial support; escitalopram, 10 to 30 mg/d; and either acamprosate, 2000 mg/d (n = 12), or identical placebo (n = 11). Outcomes included change in clinician ratings of depressive symptoms, MDD response and remission rates, changes in frequency and intensity of alcohol use, retention rates, and adverse events. Twelve subjects (acamprosate, n = 7; placebo, n = 5) completed the study. There was significant mean reduction in ratings of depressive symptoms from baseline in both treatment arms (P < 0.05), with no significant difference between the groups. Those in the acamprosate group had a 50% MDD response rate and a 42% remission rate, whereas those in the placebo arm had a 36% response and remission rate (not significant). Those assigned to acamprosate had significant reduction in number of drinks per week and drinks per month during the trial, whereas those assigned to placebo demonstrated no significant change in any alcohol use parameter, but the between-group difference was not significant. There were no significant associations between change in depressive symptoms and change in alcohol use. Attrition rates did not differ significantly between the 2 arms. Acamprosate added to escitalopram in adults with MDD and alcohol use disorders was associated with reduction in the frequency of alcohol use. The present study was not powered to detect superiority versus placebo. Further study in a larger sample is warranted.
acamprosate; alcohol use disorder; AUD; depression; MDD; escitalopram
It has been suggested that patients with major depressive disorder (MDD) who display pretreatment features suggestive of bipolar disorder or bipolar spectrum features might have poorer treatment outcomes.
To assess the association between bipolar spectrum features and antidepressant treatment outcome in MDD.
Open treatment followed by sequential randomized controlled trials.
Primary and specialty psychiatric outpatient centers in the United States.
Male and female outpatients aged 18 to 75 years with a DSM-IV diagnosis of nonpsychotic MDD who participated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.
Open treatment with citalopram followed by up to 3 sequential next-step treatments.
Main Outcome Measures
Number of treatment levels required to reach protocol-defined remission, as well as failure to return for the postbaseline visit, loss to follow-up, and psychiatric adverse events. For this secondary analysis, putative bipolar spectrum features, including items on the mania and psychosis subscales of the Psychiatric Diagnosis Screening Questionnaire, were examined for association with treatment outcomes.
Of the 4041 subjects who entered the study, 1198 (30.0%) endorsed at least 1 item on the psychosis scale and 1524 (38.1%) described at least 1 recent manic-like/hypomaniclike symptom. Irritability and psychotic-like symptoms at entry were significantly associated with poorer outcomes across up to 4 treatment levels, as were shorter episodes and some neurovegetative symptoms of depression. However, other indicators of bipolar diathesis including recent maniclike symptoms and family history of bipolar disorder as well as summary measures of bipolar spectrum features were not associated with treatment resistance.
Self-reported psychoticlike symptoms were common in a community sample of outpatients with MDD and strongly associated with poorer outcomes. Overall, the data do not support the hypothesis that unrecognized bipolar spectrum illness contributes substantially to antidepressant treatment resistance.
Sleep disturbance (SD) has complex associations with depression, both preceding and following the onset and recurrence of depression. We hypothesized that students with depressive symptoms with SD would demonstrate a greater burden of comorbid psychiatric symptoms and functional impairment compared to students with depressive symptoms without SD.
During a mental health screening, 287 undergraduate students endorsed symptoms of depression (Beck Depression Inventory [BDI] ≥ 13) and filled out the following self-report measures: demographic questionnaire, BDI, Anxiety Symptom Questionnaire—intensity and frequency (ASQ), Beck Hopelessness Scale (BHS), Beck Anxiety Inventory (BAI), Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ), and the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ). SD was measured using the BDI sleep item #16 dichotomized (score 0: no SD; or score > 0: some SD).
Students with depressive symptoms and SD (n = 220), compared to those without SD (n = 67), endorsed significantly more intense and frequent anxiety and poorer cognitive and physical functioning. Students with depressive symptoms with and without SD did not significantly differ in depressive severity, hopelessness, or quality of life.
College students with depressive symptoms with SD may experience a greater burden of comorbid anxiety symptoms and hyperarousal, and may have impairments in functioning, compared to students with depressive symptoms without SD. These findings require replication. Depression and Anxiety 00:1–8, 2013.
sleep; depression; anxiety; hopelessness; functioning; quality of life; college students; mental health screening; hyperarousal
Suicide among college students is a significant public health concern. Although suicidality is linked to depression, not all depressed college students experience suicidal ideation (SI). The primary aim of this study was to determine potential factors that may distinguish college students with depressive symptoms with and without SI.
A total of 287 undergraduate college students with substantial depressive symptoms (Beck Depression Inventory [BDI] total score >13) with and without SI were compared across psychiatric and functional outcome variables. Independent sample t tests were conducted for each outcome variable using the suicide item of the BDI as a dichotomous (ie, zero vs nonzero score) grouping variable.
Relative to students with substantial depressive symptoms without SI, those with SI were more symptomatic overall, having significantly higher levels of depressive symptoms, hopelessness, and anxiety. However, contrary to our expectations, nonsuicidal and suicidal students did not differ on measures of everyday functioning (ie, cognitive and physical functioning and grade point average).
Our findings suggest that SI among college students is associated with increased subjective distress but may not adversely impact physical or cognitive functioning or academic performance.
suicide; depression; college students; anxiety; undergraduate; hopelessness
Among college students alcohol consumption is associated with other high-risk behaviors that can lead to short- and long-term negative health consequences. Identification of college students consuming alcohol who are at high risk for problems may have important public health implications. This study examines the ability of the CHQ compulsive use of alcohol item to detect high-risk behaviors relative to other screening measures and its association with different dimensions of compulsive drinking. Three hundred thirty-two college students completed measures on compulsive drinking and hazardous behaviors. Results showed that among male students the CHQ compulsive use of alcohol item was not sensitive to detect hazardous alcohol consumption but co-occurred with the use of illicit drugs. Among female students it was sensitive to detect heavy drinking but not alcohol or drug problems. Among college students compulsive use of alcohol corresponds to an urge to consume alcohol that may be associated with use of illicit drugs in male students, with heavy drinking in female students and with substance use problems. This study suggest that the CHQ compulsive use of alcohol item should not be used as a stand-alone screening for alcohol or drug problems but it could be considered a marker for at-risk behaviors.
College students; Compulsive drinking; Risky behaviors; Alcohol; Drug use
It has been suggested that there is a mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with antidepressant response, and poorer outcomes among NSAID-treated patients were reported in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. To attempt to confirm this association in an independent population-based treatment cohort and explore potential confounding variables, the authors examined use of NSAIDs and related medications among 1,528 outpatients in a New England health care system.
Treatment outcomes were classified using a validated machine learning tool applied to electronic medical records. Logistic regression was used to examine the association between medication exposure and treatment outcomes, adjusted for potential confounding variables. To further elucidate confounding and treatment specificity of the observed effects, data from the STAR*D study were reanalyzed.
NSAID exposure was associated with a greater likelihood of depression classified as treatment resistant compared with depression classified as responsive to selective serotonin reuptake inhibitors (odds ratio=1.55, 95% CI=1.21–2.00). This association was apparent in the NSAIDs-only group but not in those using other agents with NSAID-like mechanisms (cyclooxygenase-2 inhibitors and salicylates). Inclusion of age, sex, ethnicity, and measures of comorbidity and health care utilization in regression models indicated confounding; association with outcome was no longer significant in fully adjusted models. Reanalysis of STAR*D results likewise identified an association in NSAIDs but not NSAID-like drugs, with more modest effects persisting after adjustment for potential confounding variables.
These results support an association between NSAID use and poorer antidepressant outcomes in major depressive disorder but indicate that some of the observed effect may be a result of confounding.
A subset of patients undergoing initial antidepressant treatment experience worsening of symptoms, including thoughts of suicide or suicidal behavior. The present study explores whether this subset of patients is also more likely to experience recurrence or worsening of these symptoms during a second treatment trial with a different antidepressant.
We examined data collected between July 2001 and September 2006 from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a multicenter effectiveness study of outpatients with major depressive disorder diagnosed by a DSM-IV checklist. In that study, subjects who did not remit with citalopram treatment were randomized among next-step treatment options. The main outcome measure for this post hoc analysis, presence of suicidal thoughts and behaviors, was assessed using the suicide item on the 16-item Quick Inventory of Depressive Symptomatology—Self-Rated. Logistic regression was used to examine association between emergence or worsening of these symptoms with the first-step (level 1) citalopram treatment and emergence or worsening with next-step (level 2) pharmacologic or psychosocial treatment, including augmentation with bupropion or buspirone; switch to sertraline, venlafaxine, or bupropion; or addition of or switch to cognitive therapy.
Of 1,240 subjects entering level 2 with a score less than 3 on the suicide item, 102 (8.2%) experienced emergence or worsening of suicidal thoughts or behaviors. Emergence or worsening at level 1 was strongly associated with reemergence or worsening at level 2 (crude OR=4.00 [95% CI, 2.45–6.51], adjusted OR=2.95 [95% CI, 1.76–4.96]). Overall magnitude of risk was similar among next-step pharmacologic augmentation versus switching.
These results suggest that individuals who experience emergence or worsening of suicidal thoughts or behaviors with one antidepressant treatment may warrant closer follow-up during the next-step treatment, as these symptoms may recur regardless of which modality is selected.
Previous functional neuroimaging studies have identified a network of brain regions that process aversive stimuli, including anger. A polymorphism near the cyclic adenosine monophosphate response element binding protein gene (CREB1) has recently been associated with greater self-reported effort at anger control as well as risk for antidepressant treatment–emergent suicidality in men with major depressive disorder, but its functional effects have not been studied.
To determine whether this genetic variant is associated with altered brain processing of and behavioral avoidance responses to angry facial expressions.
Design and Participants
A total of 28 white participants (mean age, 29.2 years; 13 women) were screened using the Structured Clinical Interview for DSM-IV to exclude any lifetime Axis I psychiatric disorder and were genotyped for rs4675690, a single-nucleotide polymorphism near CREB1.
Main Outcome Measures
Blood oxygenation level–dependent signal by functional magnetic resonance imaging in the amygdala, insula, anterior cingulate, and orbitofrontal cortex during passive viewing of photographs of faces with emotional expressions. To measure approach and avoidance responses to anger, an off-line key-press task that traded effort for viewing time assessed valuation of angry faces compared with other expressions.
The CREB1-linked single-nucleotide polymorphism was associated with significant differential activation in an extended neural network responding to angry and other facial expressions. The CREB1-associated insular activation was coincident with activation associated with behavioral avoidance of angry faces.
A polymorphism near CREB1 is associated with responsiveness to angry faces in a brain network implicated in processing aversion. Coincident activation in the left insula is further associated with behavioral avoidance of these stimuli.
This study aimed to investigate the psychometric properties of the Chinese translations of the Quick Inventory of Depressive Symptomatology (QIDS16), including the Clinician-Rated (QIDS-C16), Self-report (QIDS-SR16), and Interactive Voice Response (QIDS-SR-IVR16) formats. Thirty depressed Chinese Americans were assessed with Chinese translations of the QIDS-SR16, QIDS-SR-IVR16, and QIDS-C16. Cronbach alpha estimates of internal scale consistency on the QIDS-SR16, QIDS-SR-IVR16, and QIDS-C16 were 0.70, 0.74, and 0.79, respectively. Intercorrelations among the measures were QIDS-SR16 and QIDS-SR-IVR16, r = 0.79; QIDS-SR16 and QIDS-C16, r = 0.61; and QIDS-SR-IVR16 and QIDS-C16, r = 0.69 (all p values < 0.01). The areas under the curve for the receiver operating characteristics of the QIDS-SR16 and QIDS-SR-IVR16 were 0.78 (95% confidence interval, 0.61–0.95) and 0.81 (95% confidence interval, 0.65–0.96), respectively. The respective screening sensitivities/specificities were 0.73/0.74 and 0.86/0.58. The Chinese translations of the QIDS16 have adequate psychometric properties and may be useful tools for depression screening.
Depression; Chinese; psychometrics; severity of illness index; psychiatric status rating scales
Reactivity to smoking-related cues may play a role in the maintenance of smoking behavior and may change depending on smoking status. Whether smoking cue-related functional MRI (fMRI) reactivity differs between active smoking and extended smoking abstinence states currently is unknown.
We used fMRI to measure brain reactivity in response to smoking-related versus neutral images in 13 tobacco-dependent subjects prior to a smoking cessation attempt and again during extended smoking abstinence (52 ± 11 days) aided by nicotine replacement therapy.
Pre-quit smoking cue induced fMRI activity patterns paralleled those reported in prior smoking cue reactivity fMRI studies. Greater fMRI activity was detected during extended smoking abstinence than during the pre-quit assessment subcortically in the caudate nucleus and cortically in prefrontal (BA 6, 9, 44, 46), primary somatosensory (BA 1,2,3), temporal (BA 22, 41, 42), parietal (BA 7, 40) anterior cingulate (BA 24, 32), and posterior cingulate (BA 31) cortex.
These data suggest that during extended smoking abstinence, fMRI reactivity to smoking versus neutral stimuli persists in brain areas involved in attention, somatosensory processing, motor planning, and conditioned cue responding. In some brain regions, fMRI smoking cue reactivity is increased during extended smoking abstinence in comparison to the pre-quit state, which may contribute to persisting relapse vulnerability.
abstinence; addiction; caudate nucleus; fMRI; nicotine
Relapse to smoking is common after initial abstinence with pharmacotherapy and behavioral support and represents a major clinical challenge. Although mechanisms underlying relapse to smoking have not been elucidated, preclinical studies suggest that glutamate receptors may be involved. We sought to test a selective antagonist of the glycine coag-onist site on the glutamate N-methyl-d-aspartate receptor, GW468816, for prevention of relapse in recently abstinent smokers. To do so, we enrolled 264 healthy female smokers in an open 8-week smoking cessation intervention with behavioral therapy and a standard dose of transdermal nicotine replacement therapy with taper and additional gum or lozenge as needed for nicotine withdrawal symptoms. Ninety-eight participants achieved 7-day point prevalence abstinence and were randomized into a 5-week double-blind, placebo-controlled, relapse-prevention trial of GW468816 (200 mg/d) and then followed for 60 days after randomization. There was no effect of treatment on abstinence rates at the end of treatment (χ2 [1, n = 96] = 0.168, p = 0.838), on the rates of relapse (χ2 [1, n = 98] = 0.031, p = 1.000) or lapse (χ2 [1, n = 62] = 0.802, p = 0.423), or on time to relapse (χ2 [1, n = 98) = 0.001, p = 0.972). No significant relationships were detected between plasma GW468816 concentrations and abstinence, time to relapse, or self-reported craving. In conclusion, despite promising preclinical data that support the use of a selective NMDA glycine site antagonist for prevention of relapse to smoking, we observed no effect of GW468816 on relapse or lapse rates, time to relapse, or craving compared to placebo.
nicotine; smoking cessation; NMDA; glutamate; relapse prevention; glycine
Bereavement-related depression is excluded from a diagnosis of major depressive episode (MDE) in DSM-IV unless the syndrome is prolonged or complicated. The objective of this study is to assess the validity of the bereavement exclusion by comparing characteristics of bereavement-related episodes that are excluded from a diagnosis, and bereavement-related episodes that qualify for a diagnosis (complicated bereavement), to MDE.
We used data from two waves of the National Epidemiologic Survey on Alcohol and Related Conditions to compare bereavement-excluded depression and complicated bereavement to MDE with respect to indicators of pre-existing risk for psychopathology (antecedent indicators) and indicators of disorder severity (consequent indicators).
Compared to individuals with MDE, individuals with bereavement-excluded depression had lower risks of pre-existing psychiatric disorders (e.g., 0.44 lower odds of social phobia, P=0.006), fewer depressive episodes (recurrence rate 0.37 times lower, P<0.001), less impairment, an 0.18 times lower odds of seeking treatment (P<0.001), and a lower risk of psychiatric disorders during a 3-year follow-up period. Unexpectedly, this same pattern of differences was observed between individuals with complicated bereavement and MDE.
Despite the presence of a clinically significant depressive episode, bereavement-excluded depression is in many ways less indicative of psychopathology than MDE. However, complicated bereavement was more similar to bereavement-excluded depression than to MDE. We therefore question whether the DSM-IV criteria validly distinguish between non-disordered loss reactions (bereavement-excluded depression), pathological loss reactions (complicated bereavement), and non-loss related MDE.
Depression; bereavement; validity
Both the 17-item Hamilton Rating Scale for Depression (HRSD17) and 30-item Inventory of Depressive Symptomatology – Clinician-rated (IDS-C30) contain a subscale that assesses anxious symptoms. We used classical test theory and item response theory methods to assess and compare the psychometric properties of the two anxiety subscales (HRSDANX and IDS-CANX) in a large sample (N = 3453) of outpatients with non-psychotic major depressive disorder in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Approximately 48% of evaluable participants had at least one concurrent anxiety disorder by the self-report Psychiatric Diagnostic Screening Questionnaire (PDSQ). The HRSDANX and IDS-CANX were highly correlated (r = 0.75) and both had moderate internal consistency given their limited number of items (HRSDANX Cronbach’s alpha = 0.48; IDS-CANX Cronbach’s alpha = 0.58). The optimal threshold for ascribing the presence/absence of anxious features was found at a total score of eight or nine for the HRSDANX and seven or eight for the IDS-CANX. It would seem beneficial to delete item 17 (loss of insight) from the HRSDANX as it negatively correlated with the scale’s total score. Both the HRSDANX and IDS-CANX subscales have acceptable psychometric properties and can be used to identify anxious features for clinical or research purposes.
depression; anxiety; rating scales; STAR*D; measurement-based care
Background. This pilot study examined the feasibility and efficacy of providing Qigong treatment in a health center to Chinese Americans with major depressive disorder (MDD). Methods. Fourteen Chinese Americans with MDD were enrolled, and they received a 12-week Qigong intervention. The key outcome measurement was the 17-item Hamilton Rating Scale for Depression (HAM-D17); the Clinical Global Impressions-Severity (CGI-S) and -Improvement (CGI-I), the Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF), and the Multidimensional Scale of Perceived Social Support (MSPSS) were also administered. Positive response was defined as a decrease of 50% or more on the HAM-D17, and remission was defined as HAM-D17 ≤ 7. Patients' outcome measurements were compared before and after the Qigong intervention. Results. Participants (N = 14) were 64% female, with a mean age of 53 (±14). A 71% of participants completed the intervention. The Qigong intervention resulted in a positive treatment-response rate of 60% and a remission rate of 40% and statistically significant improvement, as measured by the HAM-D17, CGI-S, CGI-I, Q-LES-Q-SF, and the family support subscale of the MSPSS. Conclusions. The Qigong intervention provided at a health care setting for the treatment of primary care patients with MDD is feasible. Further studies with larger sample sizes are warranted.
The objective of this manuscript is to report associations between baseline depressive severity and (1) baseline sociodemographic and clinical characteristics, (2) treatment outcomes, and (3) differential outcomes for three treatment groups. Six hundred and sixty-five outpatients with nonpsychotic, major depressive disorder were prospectively randomized to treatment with either a selective serotonin reuptake inhibitor (SSRI) monotherapy (escitalopram plus placebo) or one of two antidepressant medication combinations (bupropion-sustained release plus escitalopram, or venlafaxine-extended release plus mirtazapine). For purposes of these analyses, participants were divided into four groups based on baseline severity by the 16-item Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR16) total score: mild (0–10) [N=81], moderate (11–15) [N=238], severe (16–20) [N=260] and very severe (21–27) [N=67]. Treatment outcomes at 12 and 28 weeks were compared among the four severity groups. A history of childhood neglect and/or abuse was strongly associated with the severity of adult depression (1/2 of participants in the very severy group versus 1/5–1/4 of those in the mild group reported abuse and/or neglect). The degree of suicidality (e.g., 15/.4% of the very severe group ever attempted suicide versus none in the mild group), the number of suicide attempts (e.g., mean of .41 +/− 1.99 suicide attempts in the severe group versus o.o +/−0.0 in the mild group) and severity of suicidality (e.g., 9.2% of participants in very severe group had a plan or made a gesture versus 5.6% in moderate group and none in the mild group) were increased in more severe groups. Participants with a greater baseline depressive severity reported significantly more psychiatric comorbitities (e..g. [at p < 0.05] increased rates of agoraphobia, bulimia, generalized anxiety, hypocondriasis, panic disorder, post-traumatic stress disorder, social phobia and somatoform disorder, with 23.9 % of participants in the very severe group having reported four or more psychiatric disorders versus 1.2% of the mild group). Combination medication treatments were no more effective in treating severe depressions than was SSRI monotherapy. Remission (61.7% of participants in the mild group achieved remission versus 28.4% in the very severe group) is more difficult to achieve in more severe groups than is response (48.8% of participants in the mild group achieved response versus 58.2% in the very severe group) (p < 0.03) . These data may help us to understand the impact of baseline features on antidepressant medication effectiveness and to inform the personalization of depression treatment across the spectrum of depressive severity.
Depression; abuse; suicide; combination treatment severity; response; remission
The co-occurrence of substance use disorder (SUD) and major depressive disorder (MDD) is common and is often thought to impair response to antidepressant therapy. These patients are often excluded from clinical trials, resulting in a significant knowledge gap regarding optimal pharmacotherapy for the treatment of MDD with concurrent SUD.
In the Combining Medications to Enhance Depression Outcomes study, 665 adult outpatients with chronic and/or recurrent MDD were prospectively treated with either escitalopram monotherapy (escitalopram and placebo) or an antidepressant combination (venalfaxine-XR and mirtazapine or escitalopram and bupropion-SR). Participants with MDD and concurrent SUD (13.1%) were compared to those without SUD (86.9%) on sociodemographic and clinical characteristics at baseline and treatment response at 12-week and 28-week endpoints.
The participants with MDD and SUD were more likely to be male and have current suicidal thoughts/plans, and had a greater lifetime severity and number of suicide attempts, and a higher number of concurrent Axis I disorders, particularly concurrent anxiety disorders. There were no significant differences between the MDD with or without SUD groups in terms of dose, time in treatment, response or remission at week 12 and 28. Furthermore, no significant differences in response or remission rates were noted between groups on the basis of the presence or absence of SUD and treatment assignment.
Although significant baseline sociodemographic and clinical differences exist, patients with MDD and concurrent SUD are as likely to respond and remit to a single or combination antidepressant treatment as those presenting without SUD.
major depressive disorder; substance use disorder; dual diagnosis; combination antidepressants; treatment outcome
Tobacco smoking is the leading preventable cause of death in the developed world. Identifying risk factors for smoking may lead to more effective treatments. Genome wide association studies revealed a relationship between development of nicotine dependence and a single-nucleotide polymorphism (SNP, rs16969968) of the nicotine acetylcholine receptor (nAChR) alpha-5 subunit gene (CHRNA5). The relationship between this SNP and other factors contributing to smoking behavior such as smoking cue reactivity is unclear.
We assessed the role of rs16969968 on brain functional MRI (fMRI) reactivity to smoking cues by studying nicotine dependent women with the nicotine dependence ‘risk’ allele (A allele, N=14) and without the ‘risk’ allele (G/G smokers, N=10). Nicotine dependence severity, as assessed with the Fagerstrom test for nicotine dependence, smoking pack-years, and expired carbon monoxide levels, were equivalent in these groups.
We observed a group difference in fMRI reactivity; women without the A allele (G/G smokers) showed greater fMRI reactivity to smoking images in brain areas related to memory and habitual behavior such as the hippocampus and dorsal striatum.
Our finding suggests that nicotine-dependent smokers lacking the rs16969968 A allele are more likely to recall smoking-related memories and engage in habitual responding to smoking cues than A allele smokers. Although more studies are necessary to determine the mechanism underlying and significance of this cue reactivity difference, these data suggest that smokers may develop and remain nicotine dependent due to different factors including genetics and cue reactivity. This finding may have implications for personalizing smoking treatment.
Tobacco smoking; fMRI; CHRNA5; nicotine dependence; dorsal striatum
Depressive symptoms are common in Parkinson’s disease (PD); however, it is unclear whether there are specific depressive symptom patterns in patients with PD and co-morbid depression (dPD).
The goal of this study is to examine the frequency and correlates of specific depressive symptoms in PD.
A sample of 158 individuals with PD completed the self-rated Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS). By multiple-regression analysis, the authors examined the association between HANDS total and subscale scores and various demographic variables.
The frequency of depression was 37% (N=58). Patients with a history of depression before PD had significantly more serious depression than those who had no such history. Of those who were more depressed, the most common symptoms of depression endorsed were low energy, difficulty with concentration/making decisions, feeling blue, feeling hopeless, and having poor sleep.
There is a relatively high prevalence of dPD. Items on the HANDS that discriminated best between depressed and nondepressed subjects with PD included feeling blue, feeling hopeless, feeling worthless, lack of interest, and self-blame. It remains to be defined whether dPD should be understood primarily as a psychological reaction to a physical disability or perceived impending one, or as a direct expression of the neuropathology of PD.
Although there is a strong relationship between depression and smoking, most nicotine dependence treatment trials exclude depressed smokers. Our objective was to determine if bupropion improves abstinence rates and abstinence-associated depressive symptoms when added to transdermal nicotine replacement therapy (NRT) and group cognitive behavioral therapy (CBT) in smokers with unipolar depressive disorder (UDD). Adult smokers with current (n=90) or past (n=109) UDD were randomly assigned to receive bupropion or placebo added to NRT and CBT for 13 weeks. In the primary analysis, with dropouts considered smokers, 36% (35/97) of those on bupropion and 31% (32/102) on placebo attained biochemically-validated 7-day point-prevalence abstinence at end of treatment (NS). Because of a high drop out rate (50%) and a significant difference in abstinence status at dropout by treatment group, a traditional intent-to-treat (ITT) analysis with last observation carried forward imputation of abstinence status was performed. In this secondary analysis, 56% (54/97) of those on bupropion and 41% (42/102) on placebo met criteria for abstinence at end of trial, Chi2=4.18, p=0.04. NRT usage and absence of a co-morbid anxiety disorder predicted abstinence. Abstinence was associated with increased depressive symptoms, regardless of bupropion treatment. Thus, in the primary analysis, bupropion neither increased the efficacy of intensive group CBT and NRT for smoking cessation in smokers with UDD nor prevented abstinence-associated depressive symptoms. Bupropion appeared to provide an advantage for smoking cessation for those who remained in the trial. The dropout rate was high and was characterized by higher prevalence of current comorbid anxiety disorder. Given the high abstinence rate achieved with CBT plus NRT, a ceiling effect related to the high level of intervention received by all subjects may have prevented an adequate test of bupropion.
Depression; Major Depressive Disorder; Unipolar Depressive Disorder; Nicotine; Smoking Cessation; Bupropion; Cognitive Behavioral Therapy; Nicotine Replacement Therapy; Relapse
Growing data suggest that complicated grief (CG) may be common in clinical care settings, but there are few prior reports about CG in outpatients presenting with primary mood disorders.
The present study examined rates of bereavement and threshold CG symptoms (defined as a score ≥ 25 on the Inventory of Complicated Grief scale) in 111 outpatients with major depressive disorder (MDD) and 142 healthy controls participating in a study of stress and depression. Clinical and demographic characteristics were also compared for bereaved individuals with CG (MDD + CG) to those without (MDD – CG). Participants completed structured diagnostic interviews as well as measures of CG, depression, anxiety, exposure to traumatic events, and perceived social support.
Lifetime history of a significant loss did not differ for the MDD and control groups (79.3% vs. 76.1%), but bereaved participants with MDD had higher rates of threshold CG (25.0% vs. 2.8%). Amongst those with MDD, CG was associated with a higher prevalence of lifetime alcohol dependence, greater exposure to traumatic events, and lower perceived social support. Depressed women, but not men, with CG also had higher rates of panic disorder, social anxiety disorder, and posttraumatic stress disorder.
Our findings are limited by the lack of a clinician confirmatory assessment of CG diagnosis, absence of complete information about the nature and timing of the loss, and relatively narrow generalizability.
We found high rates of CG in a group of psychiatric outpatients with chronic MDD, suggesting that patients with depression should be routinely screened for CG.
complicated grief; bereavement; traumatic grief; prolonged grief; major depression
The question addressed is whether a mortality risk associated with depression in a 1952 representative sample of Stirling County adults changed in a new sample of 1970 and whether there was a change in relationships to cigarette smoking and alcoholism.
Sample members were interviewed about depression and cigarette smoking. General physicians were interviewed by psychiatrists regarding alcoholism. Information about death as of December 31, 1992 was provided by Statistics Canada. Proportional hazards models were fitted in the two samples to assess the mortality risks associated with depression among men and women over 20 years of follow-up, and additionally among men with heavy smoking and alcoholism. Specific causes of death were investigated.
Hazard ratios representing the association between depression and premature death among men were 2.6 (95%CI 1.4 to 4.9) and 2.8 (95%CI 1.5 to 5.1) respectively in the 1952 and 1970 samples for the first 10 years of follow-up. Hazard ratios for women were 1.4 (95%CI 0.6 to 3.2) and 1.2 (95%CI 0.5 to 2.9). The risk associated with depression among men was independent of alcoholism and heavy smoking. Depression and alcoholism were significantly associated with death due to external causes and to circulatory disease; heavy smoking with malignant neoplasms.
The mortality associated with depression did not change over the period of 1952 to 1970. Depressed men experienced a significant mortality risk that was not matched among depressed women and also was not due to alcoholism and heavy smoking.
Mortality Risks; Depression; Alcoholism; Smoking; Sex differences; Epidemiology; Time-trends; Proportional hazards models
Maternal major depressive disorder is an established risk factor for child psychopathology. The authors previously reported that 1 year after initiation of treatment for maternal depression, children of mothers whose depression remitted had significantly improved functioning and psychiatric symptoms. This study extends these findings by examining changes in psychiatric symptoms, behavioral problems, and functioning among children of depressed mothers during the first year after the mothers' remission from depression.
Children were assessed at baseline and at 3-month intervals with the Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime Version, the Child Behavior Checklist, and the Children's Global Assessment Scale for 1 year after their mothers' remission or for 2 years if the mothers did not remit. The authors compared children of early remitters (0–3 months; N=36), late remitters (3–12 months; N=28), and nonremitters (N=16).
During the postremission year, children of early-remitting mothers showed significant improvement on all outcomes. Externalizing behavioral problems decreased in children of early- and late-remitting mothers but increased in children of nonremitting mothers. Psychiatric symptoms decreased significantly only in children of mothers who remitted, and functioning improved only in children of early-remitting mothers.
Remission of mothers' depression, regardless of its timing, appears to be related to decreases in problem behaviors and symptoms in their children over the year after remission. The favorable effect of mothers' remission on children's functioning was observed only in children of early-remitting mothers.
Cigarette smoking is the leading preventable cause of death. Unfortunately, the majority of smokers who attempt to quit smoking relapse within weeks. Abnormal dorsal anterior cingulate cortex (dACC) function may contribute to tobacco smoking relapse vulnerability. Growing evidence suggests that glutamate neurotransmission is involved in mediating nicotine dependence. We hypothesized that prior to a cessation attempt, dACC glutamate levels would be lower in relapse vulnerable smokers.
Proton magnetic resonance spectra (MRS) were obtained from dACC and a control region, the parieto-occipital cortex (POC), using two-dimensional J-resolved MRS at 4 Tesla and analyzed using LCModel. Nine nicotine-dependent women were scanned prior to making a quit attempt. Subjects then were divided into two groups; those able to maintain subsequent abstinence aided by nicotine replacement therapy (NRT) and those who slipped while on NRT (smoked any part of a cigarette after attaining at least 24 hours of abstinence).
Slip subjects exhibited significantly reduced dACC MRS glutamate (Glu/Cr) levels (p<0.03) compared to abstinent subjects. This effect was not observed in the POC control region.
Our preliminary findings suggest that dACC Glu levels as measured with MRS may help identify and/or be a biomarker for relapse vulnerable smokers. Future research following up on these findings may help clarify the role of dACC Glu in smoking dependence that may lead to new treatment strategies.
dorsal anterior cingulate cortex; glutamate; relapse; smoking; spectroscopy; nicotine
To assess whether early changes in HAM-D-17 anxiety/somatization items predict remission in two controlled studies of hypericum perforatum (St. John’s wort) versus an SSRI for major depressive disorder (MDD).
The Hypericum Depression Trial Study Group (NIMH) study randomized 340 subjects to hypericum, sertraline, or placebo for 8 weeks. The MGH study randomized 135 subjects to hypericum, fluoxetine, or placebo for 12 weeks. We examined whether remission was associated with early changes in anxiety/somatization symptoms.
In the NIMH study, significant associations were observed between remission and early improvement in the anxiety-psychic item (sertraline arm), somatic-gastrointestinal item (hypericum arm), and somatic symptoms-general (placebo arm). None of the three treatment arms of the MGH study showed significant associations between anxiety/somatization symptoms and remission. When both study samples were pooled, we found associations for anxiety-psychic (SSRI arm), somatic-gastrointestinal and hypochondriasis (hypericum arm), and anxiety-psychic and somatic symptoms-general (placebo arm). In the entire sample, remission was associated with improvement in the anxiety-psychic, somatic-gastrointestinal, and somatic symptoms-general items.
The number and type of anxiety/somatization items associated with remission varied depending on the intervention. Early scrutiny of the HAM-D-17 anxiety/somatization items may help predict remission of MDD.
Depression; Antidepressants; St. John’s wort; Anxiety; Predictors; Remission