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.

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Background

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).

Objective

The goal of this study is to examine the frequency and correlates of specific depressive symptoms in PD.

Method

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.

Results

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.

Conclusion

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.

Background

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.

Methods

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.

Results

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.

Limitations

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.

Conclusions

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.

Objective

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.

Method

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.

Results

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.

Conclusion

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.

Objective

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.

Method

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).

Results

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.

Conclusions

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.

Background

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.

Methods

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).

Results

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.

Conclusions

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.

Objective

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).

Methods

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.

Results

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.

Conclusions

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.

Objective

To investigate the validity of using electronic medical records (EMR) database in a large health organization for identifying patients with clinical depression.

Method

The Massachusetts General Hospital EMR system was used to generate a sample of primary care patients seen in the primary care clinic in 2007. Using this sample, the validity of using certain fields in the EMR database (i.e., billing diagnosis, problem list, and medication list) to identify patients with clinical depression was compared to primary care physician (PCP) assessment by a written questionnaire. Based on this standard, the sensitivity, specificity, positive predictive value, negative predictive value, and the areas under receiver operating characteristic curve (AUC) of three specific EMR fields – individually and in combination - were calculated to identify which EMR field best predicted PCP classification.

Results

The EMR fields “billing diagnosis,” “problem list,” and antidepressant in “medication list,” were all able to identify patients’ diagnosis of depression by their PCPs reasonably well. Having one or more “billing diagnosis” of depression had the highest sensitivity and highest AUC (77% sensitivity, 76% specificity, AUC 0.77) among any of the fields used alone.

Conclusion

The AUC for “billing diagnosis” of depression performed the best of the three single fields tested, with an AUC of 0.77, corresponding to a test with moderate accuracy. This analysis demonstrates that specific EMR fields can be used as a proxy for PCP assessment of depression for this EMR system. Limitations to our analysis include the physician response rate to our survey as well as the quality of the data, which is collected primarily for administrative and clinical purposes. When using administrative and clinical data in mental health studies, researchers must first assess the accuracy of choosing specific fields within their EMR system in order to determine the level of accuracy for them to be used as proxies for clinical diagnoses.

Objective

To examine the association between exposure to newer antidepressants and risk of gastrointestinal (GI) and other bleeding complications among individuals with major depressive disorder (MDD).

Design

This study uses an incident user cohort design to compare associations between incidence of vascular/bleeding events and the relative affinity (low, moderate or high) of the antidepressant for the serotonin transporter during an exposure risk period for each patient.

Setting

New England healthcare system electronic medical record database.

Participants

36 389 individuals with a diagnosis of MDD and monotherapy with a selective serotonin reuptake inhibitor, serotonin–norepinephrine reuptake inhibitor or other new-generation antidepressant were identified from among 3.1 million patients in a New England healthcare system.

Primary and secondary outcome measures

Rates of bleeding or other vascular complications, including acute liver failure, acute renal failure, asthma, breast cancer and hip fractures.

Results

601 GI bleeds were observed in the 21 462 subjects in the high-affinity group versus 333 among the 14 927 subjects in the lower affinity group (adjusted RR: 1.17, 95% CI 1.02 to 1.34). Similarly, 776 strokes were observed in the high-affinity group versus 434 in the lower affinity treatment group (adjusted RR: 1.18, 95% CI 1.06 to 1.32). No significant association with risk for a priori negative control outcomes, including acute liver failure, acute renal failure, asthma, breast cancer and hip fractures, was identified.

Conclusions

Use of antidepressants with high affinity for the serotonin transporter may confer modestly elevated risk for GI and other bleeding complications. While multiple methodologic limitations must be considered, these results suggest that antidepressants with lower serotonin receptor affinity may be preferred in patients at greater risk for such complications.

Article summary

Article focus

Previous reports have suggested that antidepressant use may contribute to dysfunction in platelet aggregation and increased risk for bleeding outcomes.

The authors hypothesised that antidepressants with higher affinity for the serotonin transporter would exhibit greater risk for these outcomes than those with lesser affinity.

Key messages

Use of antidepressants with higher affinity for the serotonin transporter was associated with modest but statistically significant increase in risk for gastrointestinal bleed and stroke.

Electronic medical record-based pharmacovigilance systems provide an opportunity to examine treatment risk in general clinical populations, in a more systematic fashion than traditional postmarketing surveillance.

Strengths and limitations of this study

A strength of this report, in addition to cohort size and generalisability, is the restriction to individuals with major depressive disorder, minimising risk for confounding by indication.

A key limitation is the absence of blood antidepressant levels or data on adherence, which might lead us to underestimate strength of effect.

Objective

Irritability is common during major depressive episodes, but its clinical significance and overlap with symptoms of anxiety or bipolar disorder remains unclear. We examined clinical correlates of irritability in a confirmatory cohort of Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study participants with major depressive disorder (MDD).

Method

Logistic regression was used to identify features associated with presence of irritability on the clinician-rated Inventory of Depressive Symptomatology.

Results

Of 2,307 study participants, 1067(46%) reported irritability at least half the time during the preceding week; they were more likely to be female, to be younger, to experience greater depression severity and anxiety, and to report poorer quality of life, prior suicide attempts, and suicidal ideation. Bipolar spectrum features were not more common among those with irritability.

Conclusion

Irritable depression is not a distinct subtype of MDD, but irritability is associated with greater overall severity, anxiety comorbidity, and suicidality.

Objective

We test the hypothesis that racial or ethnic differences exist in relapse rates to fluoxetine discontinuation in Major Depressive Disorder (MDD).

Method

Data are from a prospective study examining the relapse rates secondary to fluoxetine discontinuation in MDD. Subjects in the discontinuation phase consisted of 255 adults aged 18 to 65, 214 subjects who self-identified as Caucasian, 22 as African American, 13 as Latino American, and six as Asian American.

Results

In both the fluoxetine and placebo groups, no statistically significant differences emerged when comparing time to relapse for minority groups as compared to the Caucasian population. Adjusting for statistically significant predictors of relapse (symptom severity, neurovegetative symptom pattern, gender) and for educational level did not change the outcome of the survival analyses.

Conclusions

Although the size of minority groups in this sample was modest, in a randomized, controlled trial setting, minority and Caucasian patients may have similar rates of relapse in MDD. This finding reinforces the importance of maintenance treatment in relapse for both minority as well as Caucasian patients with MDD. Given the self-selecting nature of clinical trials, future studies are needed to further examine the potential influence of underlying cultural factors on clinical outcomes in minority populations.

Attentional bias for drug-related stimuli, as measured by emotional Stroop (ES) tasks, is predictive of treatment outcomes for tobacco smoking and other abused drugs. Characterizing relationships between smoking-related attentional bias and brain reactivity to smoking images may help in identifying neural substrates critical to relapse vulnerability. To this end, we investigated putative relationships between interference effects in an offline smoking ES task and functional MRI (fMRI) measures of brain reactivity to smoking vs neutral images in women smokers. Positive correlations were found between attentional bias and reactivity to smoking images in brain areas involved in emotion, memory, interoception, and visual processing, including the amygdala, hippocampus, parahippocampal gyrus, insula, and occipital cortex. These findings suggest that smokers with elevated attentional biases to smoking-related stimuli may more readily shift attention away from other external stimuli and toward smoking stimuli-induced internal states and emotional memories. Such attentional shifts may contribute to increased interference by smoking cues, possibly increasing relapse vulnerability. Treatments capable of inhibiting shifts to drug cue-induced memories and internal states may lead to personalized tobacco dependence treatment for smokers with high attentional bias to smoking-related stimuli.

Background

Ethnic minorities with depression are more likely to seek mental health care through primary care providers (PCPs) than mental health specialists. However, both provider and patient-specific challenges exist. PCP-specific challenges include unfamiliarity with depressive symptom profiles in diverse patient populations, limited time to address mental health, and limited referral options for mental health care. Patient-specific challenges include stigma around mental health issues and reluctance to seek mental health treatment. To address these issues, we implemented a multi-component intervention for Asian American and Latino American primary care patients with depression at Massachusetts General Hospital (MGH).

Methods/Design

We propose a randomized controlled trial to evaluate a culturally appropriate intervention to improve the diagnosis and treatment of depression in our target population. Our goals are to facilitate a) primary care providers' ability to provide appropriate, culturally informed care of depression, and b) patients' knowledge of and resources for receiving treatment for depression. Our two-year long intervention targets Asian American and Latino American adult (18 years of age or older) primary care patients at MGH screening positive for symptoms of depression. All eligible patients in the intervention arm of the study who screen positive will be offered a culturally focused psychiatric (CFP) consultation. Patients will meet with a study clinician and receive toolkits that include psychoeducational booklets, worksheets and community resources. Within two weeks of the initial consultation, patients will attend a follow-up visit with the CFP clinicians. Primary outcomes will determine the feasibility and cost associated with implementation of the service, and evaluate patient and provider satisfaction with the CFP service. Exploratory aims will describe the study population at screening, recruitment, and enrollment and identify which variables influenced patient participation in the program.

Discussion

The study involves an innovative yet practical intervention that builds on existing resources and strives to improve quality of care for depression for minorities. Additionally, it complements the current movement in psychiatry to enhance the treatment of depression in primary care settings. If found beneficial, the intervention will serve as a model for care of Asian American and Latino American patients.

Trial Registration

ClinicalTrials.gov: NCT01239407

Background

Chinese American patients with Major Depressive Disorder (MDD) tend to underutilize mental health services and are more likely to seek help in primary care settings than from mental health specialists. Our team has reported that Culturally Sensitive Collaborative Treatment (CSCT) is effective in improving recognition and treatment engagement of depressed Chinese Americans in primary care. The current study builds on this prior research by incorporating telemedicine technology into the CSCT model.

Methods/Design

We propose a randomized controlled trial to evaluate the acceptability and effectiveness of a telepsychiatry-based culturally sensitive collaborative treatment (T-CSCT) intervention targeted toward Chinese Americans. Patients meeting the study's eligibility criteria will receive either treatment as usual or the intervention under investigation. The six-month intervention involves: 1) an initial psychiatric interview using a culturally sensitive protocol via videoconference; 2) eight scheduled phone visits with a care manager assigned to the patient, who will monitor the patient's progress, as well as medication side effects and dosage if applicable; and 3) collaboration between the patient's PCP, psychiatrist, and care manager. Outcome measures include depressive symptom severity as well as patient and PCP satisfaction with the telepsychiatry-based care management service.

Discussion

The study investigates the T-CSCT model, which we believe will increase the feasibility and practicality of the CSCT model by adopting telemedicine technology. We anticipate that this model will expand access to culturally competent psychiatrists fluent in patients' native languages to improve treatment of depressed minority patients in primary care settings.

Trial Registration

NCT00854542

BACKGROUND

Although research suggests depression is common among individuals with Parkinson’s disease (PD), it is unclear how to best assess depression in PD (dPD). We wanted to examine the prevalence of dPD using different definitions of depression, as well as examine factors associated with dPD.

METHODS

One hundred fifty-eight individuals (68% male; age 66.8 ± 9.6 SD) with a primary diagnosis of PD were assessed for depression using the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS) in an outpatient setting at the Movement Disorders Clinic at Massachusetts General Hospital. We defined depression using 4 thresholds based on the HANDS and whether or not an individual was ever on an antidepressant regimen. We also examined potential predictors of the presence of dPD.

RESULTS

The prevalence of depression among study participants ranged from 11% to 57%, depending on which of the 4 definitions of depression was applied. Younger age and longer duration of PD predicted a relatively higher prevalence of depression. Having a history of depression prior to onset of PD also was predictive of dPD.

CONCLUSIONS

Depression appears to be relatively common among individuals with PD, and history of depression, younger age, and longer PD duration may be factors associated with dPD.

Objective

To assess the relationship between early changes in anxiety/somatization symptoms and treatment outcome among MDD subjects during a 12-week trial of fluoxetine. We also examined the relationship between anxious depression and treatment response.

Methods

510 MDD patients received 12 weeks of fluoxetine with flexible dosing (target dosages: 10 mg/day (week 1), 20 mg/day (weeks 2–4), 40 mg/day (weeks 4–8), and 60 mg/day (weeks 5–12)). We assessed the relationship between early changes in HAMD-17- anxiety/somatization factor items and depressive remission, as well as whether anxious depression at baseline predicted remission at study endpoint. . Baseline HAMD-17 scores were considered as covariates and the Bonferroni correction (p ≤ .008) was used for multiple comparisons.

Results

Adjusting for baseline HAMD-17 scores, patients who experienced greater early improvement in somatic symptoms (gastrointestinal) were significantly more likely to attain remission (HAMD-17 < 8) at endpoint than those without early improvement (p = .006). Early changes in the remaining items did not predict remission, nor did anxious depression at baseline.

Conclusions

Among the anxiety/somatization factor items, only early changes in somatic symptoms (gastrointestinal) predicted remission. Future studies are warranted to further investigate this relationship, as well as that between anxious depression and treatment outcome.

Adverse events during selective serotonin reuptake inhibitor (SSRI) treatment are frequent and may lead to premature treatment discontinuation. If attrition is associated with early worsening of side effects or the frequency, intensity, or burden of side effects, interventions to maximize retention could be focused on patients with these events. Outpatient participants (n=265) with nonpsychotic major depressive disorder entered an 8-week trial with an SSRI. At baseline and week 2, specific side effects were evaluated with the Systematic Assessment for Treatment Emergent Events – Systematic Inquiry, and at week 2 the Frequency, Intensity, and Burden of Side Effects Rating globally assessed side effects. Attrition was defined by those participants who left treatment after week 2 but before week 8. No specific week 2 side effect, either treatment emergent or with worsening intensity, was independently associated with attrition. Global ratings of side effect frequency, intensity, or burden at week 2 were also not associated with subsequent attrition. Neither global ratings nor specific side effects at week 2 were related to patient attrition during SSRI treatment. Other factors appear to contribute to patient decisions about continuing with treatment.

Objective

Presymptomatic individuals with the Huntingtin (HTT) CAG expansion mutation that causes Huntington’s disease may have higher levels of depressive symptoms than healthy comparison populations. However, the prevalence of HTT CAG repeat expansions among individuals diagnosed with major depressive disorder has not been established.

Method

This was a case-control genetic association study of HTT CAG allele size in two discovery cohorts of individuals with major depressive disorder and comparison subjects without major depression as well as a replication cohort of individuals with major depression and comparison subjects without major depression.

Results

CAG repeat lengths of 36 or greater were observed in six of 3,054 chromosomes from individuals with major depression, compared with none of 4,155 chromosomes from comparison subjects. In a third cohort, one expanded allele was observed among 1,202 chromosomes in the major depression group, compared with none of 2,678 chromosomes in comparison subjects. No clear pattern of clinical features was shared among individuals with the expanded repeats.

Conclusions

In clinical populations of individuals diagnosed with major depression, approximately 3 in 1,000 carried expanded HTT CAG alleles.

Attentional bias for drug-related stimuli, as measured by emotional Stroop (ES) tasks, is predictive of treatment outcomes for tobacco smoking and other abused drugs. Characterizing relationships between smoking-related attentional bias and brain reactivity to smoking images may help identify neural substrates critical to relapse vulnerability. To this end, we investigated putative relations between interference effects in an offline smoking ES task and functional MRI (fMRI) measures of brain reactivity to smoking versus neutral images in women smokers. Positive correlations were found between attentional bias and reactivity to smoking images in brain areas involved in emotion, memory, interoception, and visual processing including the amygdala, hippocampus, parahippocampal gyrus, insula, and occipital cortex. These findings suggest that smokers with elevated attentional biases to smoking-related stimuli may more readily shift attention away from other external stimuli and toward smoking stimuli-induced internal states and emotional memories. Such attentional shifts may contribute to increased interference by smoking cues, possibly increasing relapse vulnerability. Treatments capable of inhibiting shifts to drug cue-induced memories and internal states may lead to personalized tobacco dependence treatment for smokers with high attentional bias to smoking-related stimuli.

Background

Developing means to identify smokers at high risk for relapse could advance relapse prevention therapy. We hypothesized that functional magnetic resonance imaging (fMRI) reactivity to smoking-related cues, measured prior to a quit attempt, could identify smokers with heightened relapse vulnerability.

Methods

Twenty-one nicotine-dependent women underwent fMRI prior to quitting smoking, during which smoking-related and neutral images were shown. These smokers also were tested for possible attentional biases to smoking-related words using a computerized emotional Stroop (ES) task previously found to predict relapse. Smokers then made a quit attempt and were grouped based on outcomes (abstinence versus slip: smoking 1 cigarette after attaining abstinence). Pre-quit fMRI and ES measurements in these groups were compared.

Results

Slip subjects had heightened fMRI reactivity to smoking-related images in brain regions implicated in emotion, interoceptive awareness, and motor planning and execution. Smoking cue-induced insula and dorsal anterior cingulate cortex (dACC) reactivity correlated with an attentional bias to smoking-related words. A discriminant analysis of ES and fMRI data predicted outcomes with 79% accuracy. Additionally, smokers who slipped had decreased fMRI functional connectivity between an insula-containing network and brain regions involved in cognitive control, including the dACC and dorsal lateral prefrontal cortex, possibly reflecting reduced top-down control of smoking-related cue-induced emotions.

Conclusions

These findings suggest that the insula and dACC are important substrates of smoking relapse vulnerability. The data also suggest that relapse-vulnerable smokers can be identified prior to quit attempts, which could enable personalized treatment, improve tobacco-dependence treatment outcomes, and reduce smoking-related morbidity and mortality.

Irritability is a diagnostic symptom of child-adolescent but not adult major depressive disorder (MDD) in both the DSM-IV and ICD-10 systems. We explore the importance of irritability for sub-typing adult DSM-IV MDD in the National Comorbidity Survey Replication (NCS-R), a national US adult household survey. The WHO Composite International Diagnostic Interview (CIDI) was used to assess prevalence of many DSM-IV disorders in the lifetime and in the year before interview (12-month prevalence). MDD was assessed conventionally (i.e., requiring either persistent sadness or loss of interest), but with irritability included as one of the Criterion A symptoms. We also considered the possibility that irritability might be a diagnostic symptom of adult MDD (i.e., detect cases who had neither sad mood nor loss of interest). Twelve-month MDD symptom severity was assessed with the Quick Inventory of Depressive Symptomatology and role impairment with the Sheehan Disability Scale. After excluding bipolar spectrum disorders, irritability during depressive episodes was reported by roughly half of respondents with lifetime DSM-IV MDD. Irritability in the absence of either sad mood or loss of interest, in comparison, was rare. Irritability in MDD was associated with early age-of-onset, lifetime persistence, comorbidity with anxiety and impulse-control disorders, fatigue and self-reproach during episodes, and disability. Irritability was especially common in MDD among respondents in the age range 18–44 and students. Further investigation is warranted of distinct family aggregation, risk factors, and treatment response. Consideration should also be given to including irritability as a non-diagnostic symptom of adult MDD in DSM-V and ICD-11.

Background

Previous studies of major depressive disorder (MDD) have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN), and medial forebrain bundle (MFB).

Methodology/Principal Findings

We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI) in 22 MDD subjects and compared them with 22 matched healthy control subjects. Fractional anisotropy (FA) values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity.

Conclusions/Significance

These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression.