Comorbid Major Depression Research Articles

Agoraphobic behavior and panic attack: a study of male twins

We used data from 3372 pairs of male twins from the Vietnam Era Twin Registry to examine comorbidity and familial influences on the frequently observed association between agoraphobic behavior and panic. Due to low prevalence of DSM-III-R-defined panic disorder, we also examined subjects who had experienced at least one panic attack during their lives. Agoraphobic behavior among individuals with a history of panic attacks showed familial aggregation (odds ratio=5.7; P=.018). Probands with panic attacks and agoraphobic behavior and their co-twins had higher risk of major depression than probands without agoraphobic avoidance and their co-twins ( P=.01). Groups did not differ for alcohol dependence or antisocial personality. Agoraphobic behavior associated with panic attack is familial and associated with comorbid major depression. Agoraphobia following panic attack does not seem to reflect severity as agoraphobic behavior in the proband was unrelated to risk of panic attacks in the co-twin.

Alleles of a functional serotonin transporter promoter polymorphism are associated with major depression in alcoholics.

Serotonergic neurotransmission has been implicated in the pathogenesis of both alcohol dependence and mood disorders and may therefore be important in understanding the pathophysiology of comorbid alcohol dependence and major depression. Studies of the association of these disorders with a functional polymorphism in the promoter region of the gene encoding the serotonin transporter protein (locus SLC6A4) have yielded inconsistent results. Because the convergence of these disorders may provide a refined phenotype, we examined the association of serotonin (5-HT) transporter linked polymorphic region (5-HTTLPR) alleles to comorbid alcohol dependence and major depression. A sample of 296 European American and 16 African American patients with comorbid alcohol dependence and major depression was recruited from treatment studies. The control group included 260 European Americans and 43 African Americans; all were screened to exclude the presence of a mood or substance use disorder. DNA isolated from whole blood was polymerase chain reaction-amplified, and genotypes were assigned on the basis of agarose gel size fractionation. The frequency of the short allele in the patient group was in the range of those previously reported for samples with unipolar depression but was significantly more common than among controls (short allele frequency of cases, 45.8%; controls, 39.8%; chi(2)(1) = 4.02; p = 0.045). With respect to the frequency of the short allele at the SLC6A4 locus (5-HTTLPR), major depression in alcoholics is similar to major depression in nonalcoholics. Further efforts to characterize depressed alcoholics and to examine genetic predictors of response to antidepressant treatment seem warranted.

Two studies of psychiatric morbidity among motor vehicle accident survivors 1 year after the crash

We assessed the psychiatric co-morbidity associated with chronic posttraumatic stress disorder (PTSD) (1–2 years) secondary to personal injury motor vehicle accidents (MVAs) in two studies. In Study 1, we compared the results of SCID assessments for 75 treatment-seeking MVA survivors (51 with PTSD and 24 with symptoms but no PTSD). In Study 2, we compared similar results among 132 MVA survivors who had been followed prospectively for 12+ months after their accidents (19 with PTSD, 32 who had PTSD but who had remitted, and 81 who never met criteria for PTSD). We found comparable levels of current co-morbid major depression (53%), any mood disorder (62–68%), generalized anxiety disorder (26%) and any anxiety disorder (42%) for both groups of participants with chronic PTSD. These rates of co-morbidity were higher than those found in non-PTSD comparison groups with similar MVA histories.

Counterintuitive Antidepressant Properties of Slow rTMS Over the Left Frontal Cortex: A Possible Mechanism

Counterintuitive Antidepressant Properties of Slow rTMS Over the Left Frontal Cortex: A Possible Mechanism

Fluoxetine in the treatment of alcohol addicts with comorbid major depression

Fluoxetine in the treatment of alcohol addicts with comorbid major depression

Lifetime comorbidity of antisocial personality disorder and anxiety disorders among adults in the community

The association between lifetime anxiety disorders, conduct disorder (CD), and antisocial personality disorder (ASPD) among adults in the community was explored. Data were drawn from the National Comorbidity Survey ( n=5,877), a representative community sample of adults aged 15–54 in the 48 contiguous US states. Multiple logistic regression analyses were used to determine the association between anxiety disorders, CD and ASPD, and between the co-occurrence of anxiety disorders and ASPD in the likelihood of comorbid substance use and affective disorders, suicidal ideation (SI) and suicide attempt (SA). Out of the 3.3% of adults with ASPD, over half (54.33%) had a comorbid anxiety disorder (lifetime). Similarly, 42.31% of adults with a history of CD (9.4%) who did not meet criteria for ASPD had a lifetime anxiety disorder. Social phobia [OR=1.65 (1.01, 2.7)] and post-traumatic stress disorder [OR=2.28 (1.3, 4.0)] were associated with significantly increased odds of ASPD, after adjusting for differences in sociodemographic characteristics and other psychiatric comorbidity. Major depression was no longer significantly associated with ASPD after adjusting for anxiety disorders. The comorbidity of anxiety disorders and ASPD was associated with significantly higher odds of major depression, substance use disorders, and SI and SA compared with odds among those without both disorders. These data provide initial evidence of an association between PTSD and social phobia and an increased likelihood of ASPD among adults in the community, after adjustment for comorbid affective and substance use disorders. Adults with ASPD and comorbid anxiety had significantly higher levels of comorbid major depression, alcohol dependence, and substance dependence and substantially higher rates of lifetime suicidal ideation and suicide attempts compared to adults with ASPD or anxiety disorders alone or with neither disorder. Future studies are needed to replicate this finding using longitudinal data and to investigate the possible mechanisms of the observed links between anxiety disorders and ASPD.

Childhood adversities associated with major depression and/or anxiety disorders in a community sample of Ontario: Issues of co-morbidity and specificity

It has been well established that early adversity is a major risk factor for depression and for anxiety disorders in various populations and age groups. Few studies have considered the relative strength of these associations and the possible role of co-morbid depression/anxiety in understanding them. Using data from a large community sample of Ontario, Canada, we examined the relative strength of the associations between early physical abuse, sexual abuse, and/or parental strain with depression alone, anxiety alone, and co-morbid depression/anxiety. The current sample consisted of 6,597 individuals 15-64 years of age who were interviewed using the World Health Organization Composite International Diagnostic Interview (CIDI). Using a multivariate design, we compared early adversity scores across four diagnostic study groups including normal controls, individuals with major depression but no anxiety disorders, individuals with one or more anxiety disorders without major depression, and individuals with co-morbid major depression and anxiety. Individuals with past disorders were considered separately from those with current disorders. For both past and current disorders, highly significant differences in early adversity scores were found across the four study groups. A novel and robust finding, consistent across all analyses, was a marked association between early sexual abuse and co-morbid depression and anxiety but not the "pure" disorders. A strong association between early parental strain and major depression (independent of anxiety) was also found. The overall pattern of results suggest that there may be unique relationships linking particular adversities to particular manifestations of depression and anxiety disorders later in life. A particularly strong association between early sexual abuse and co-morbid depression/anxiety was found.

The role of serotonergic agents as treatments for alcoholism.

Serotonergic agents remain an important area of pharmacologic study as treatments for alcoholism. Selective serotonin reuptake inhibitors (SSRIs) do not appear to be efficacious at treating a heterogeneous alcoholic group. SSRIs may, however, possess utility in treating later-onset alcoholics and alcoholism that is complicated by co-morbid major depression. The 5-HT(1A) partial agonist, buspirone, does not appear to be an efficacious treatment for alcoholics without co-morbid disease. Buspirone may, however, possess some utility in treating alcoholics with co-morbid anxiety disorder. Ritanserin, a 5-HT(2) antagonist, does not appear to be an efficacious treatment for alcoholism at pharmacologically relevant clinical doses. Ondansetron, a 5-HT(3) antagonist, is an efficacious and promising medication for the treatment of earlier-onset alcoholism. The differential treatment effect of SSRIs and ondansetron among various subtypes of alcoholics is intriguing. Future research is needed to more clearly understand the biopsychosocial differences that typify a particular alcoholic subtype. This type of understanding could develop our ability to make reasonable predictions as to what alcoholic subtype would respond best to a particular serotonergic agent, which could then be provided.

Psychopharmacology of compulsive buying.

No standard treatment exists for the DSM-IV Impulse Control Disorders, Not Elsewhere Classified, including Compulsive Buying Disorder. This paper reviews the suggested pharmacotherapies for this disorder and their theoretical basis. McElroy et al. first reported benefit from antidepressant therapy in three cases of Compulsive Buying Disorder with comorbid depression and anxiety. In a retrospective chart review, McElroy's group reported on 20 patients that benefited from antidepressants, often in combination with mood stabilizers. Lejoyeux reported on two patients in whom treatment of a comorbid mood disorder led to remission of compulsive buying behavior. Black reported fluvoxamine to be effective in patients without comorbid major depression, suggesting that improvement was independent of the treatment of mood symptoms. Kim reported improvement with naltrexone, an opioid antagonist, in a case series. Two double-blind placebo-controlled trials found fluvoxamine no better than placebo; however, in both studies patients kept shopping logs, which may have confounded the results. An open-label trial of citalopram and a double-blind crossover trial which excluded shopping logs both reported positive results. Twelve-month follow-up data for the open-label group found that remission rates at quarterly time points were independent of continuing drug therapy. The data reviewed above suggest that pharmacologic interventions may be effective for compulsive buying disorder. Whether pharmacological treatment is superior to placebo and whether it is more, less or equally effective compared to psychotherapeutic interventions remains to be established.

Lifetime rates of alcoholism in adults with anxiety, depression, or co-morbid depression/anxiety: a community survey of Ontario

Background: Separate lines of research have demonstrated strong associations linking alcohol misuse with major depression on the one hand, and anxiety disorders on the other. In the current study we examined the possible confounding and/or additive effects of co-morbid depression/anxiety in understanding these relationships. Methods: A total of 7195 individuals in Ontario, aged 15–64, were interviewed using the CIDI. Based on lifetime diagnoses, we compared rates of alcohol abuse/dependence in four groups consisting of normal controls, individuals with unipolar major depression but no anxiety disorders, individuals with one or more anxiety disorders without depression, and individuals with co-morbid major depression and anxiety. Age of onset of alcoholism in the four study groups was also compared. Results: In both genders, there were significantly higher rates of alcoholism in all three psychiatric groups relative to controls. In females only, there was also a significantly higher rate of alcoholism in the depressed/anxious group than in the pure anxious group. The age of onset of alcoholism was the same across all four study groups. Limitations: Due to limitations related to sample size, we combined subjects with various anxiety disorders into a single anxiety group and concurrent and sequential co-morbidity were not distinguished. Conclusions: Both gender effects and depression/anxiety co-morbidity may be important considerations in the design and interpretation of studies on alcohol misuse. This may be particularly relevant when considering the strength of the association between alcoholism and anxiety disorders in women. Depression and anxiety do not appear to influence the age of onset of alcoholism. Furthermore, no single temporal pattern of onset was identified in individuals with all three disorders, suggesting no obvious cause-effect relationship among them.

Shared genetic risk of major depression, alcohol dependence, and marijuana dependence: contribution of antisocial personality disorder in men.

Little is known about genetic factors that underlie the interrelationships among antisocial personality disorder (ASPD), major depression (MD), alcohol dependence (AD), and marijuana dependence (MJD). We examined the contribution of genetic effects associated with ASPD to the comorbidity of MD and substance use disorders. The Vietnam Era Twin Registry is a general population registry of male veteran twins constructed from computerized Department of Defense files and other sources. A telephone diagnostic interview was administered to eligible twins from the Registry in 1992. Of 5150 twin pairs who served on active military duty during the Vietnam era, 3360 pairs (1868 monozygotic and 1492 dizygotic) in which both members completed the pertinent diagnostic interview sections were included. The main outcome measures were lifetime DSM-III-R ASPD, MD, AD, and MJD. Structural equation modeling was performed to estimate additive genetic, shared environmental, and nonshared environmental effects common and specific to each disorder. The heritability estimates for lifetime ASPD, MD, AD, and MJD were 69%, 40%, 56%, and 50%, respectively. Genetic effects on ASPD accounted for 38%, 50%, and 58% of the total genetic variance in risk for MD, AD, and MJD, respectively. After controlling for genetic effects on ASPD, the partial genetic correlations of MD with AD and with MJD were no longer statistically significant. Genetic effects specific to MD and AD and familial effects specific to MJD remained statistically significant. Nonshared environmental contributions to the comorbidity in these disorders were small. In this sample, the shared genetic risk between MD and both AD and MJD was largely explained by genetic effects on ASPD, which in turn was associated with increased risk of each of the other disorders.

Open-Label Evaluation of Venlafaxine Sustained Release in Outpatients with Generalized Anxiety Disorder with Comorbid Major Depression or Dysthymia: Effectiveness, Tolerability and Predictors of Response

In a setting of routine clinical practice, 32 outpatients with generalized anxiety disorder (GAD) and major depression (MD) (n = 21) or dysthymia (n = 11), according to DSM-IV criteria, were consecutively treated with flexible dosages of sustained-release venlafaxine (SR-VF) for at least 8 weeks. In a 16-week follow-up, SR-VF daily dose could be modified on the basis of the therapeutic response and of the side effect profile. Symptomatological modifications were explored by means of the Clinical Global Impression (CGI) scale, Hamilton Rating Scale for Depression (HAM-D), and Hamilton Anxiety Scale (HAM-A). SR-VF was well tolerated and only 2 patients interrupted the treatment before 24 weeks; the mean final dose ± SD was 135.5 ± 71.8 mg (range 75–225); in 26 (81.2%) patients, a statistically significant response was observed in depressive symptomatology within the first 8 weeks. The mean total score of HAM-D showed a significant reduction during the first 8 weeks of treatment, while the mean total score of HAM-A did not present a significant reduction until week 24. In patients with MD, a statistically significant response was observed after the first 8 weeks, while the reduction of the anxiety scores required more time and, in some cases, did not appear at all. Conversely, in patients with GAD and dysthymia, anxious and depressive symptomatology improved simultaneously. Stepwise multiple regression indicated that the improvement of depression is negatively related to a high score of CGI anxiety severity, and the improvement of anxiety is related to the presence of dysthymia and, to a lesser extent, to a short duration of the illness. Our data confirm the effectiveness and tolerability of SR-VF in mixed anxiety-depressive states. The differential response suggests a pathophysiologic and clinical distinction between GAD with comorbid MD or dysthymia.

Distinguishing generalized anxiety disorder from major depression: prevalence and impairment from current pure and comorbid disorders in the US and Ontario.

Estimation of comparative disease burden in epidemiological surveys is complicated by the fact that high comorbidities exist among many chronic conditions. The easiest way to take comorbidity into consideration is to distinguish between pure and comorbid conditions and to evaluate the incremental effects of comorbid conditions in prediction equations. This approach is illustrated here in an analysis of the effects of pure and comorbid major depression (MD) and generalized anxiety disorder (GAD) on a number of different measures of role impairment in the US National Comorbidity Survey (NCS) and the Mental Health Supplement to the Ontario (Canada) Health Survey (the Supplement). Pure MD and pure GAD were found to have roughly equal independent associations with role impairments. The incremental effects of having comorbid MD and GAD were found to vary depending on the outcome under investigation. The paper closes with a discussion of the methodological complexities associated with generalizing to comorbidities that involve rare conditions or more than two disorders.

Repetitive Transcranial Magnetic Stimulation Treatment of Comorbid Posttraumatic Stress Disorder and Major Depression

Twelve patients with comorbid posttraumatic stress disorder (PTSD) and major depression underwent repetitive transcranial magnetic stimulation (rTMS) to left frontal cortex as an open-label adjunct to current antidepressant medications. rTMS parameters were as follows: 90% of motor threshold, 1 Hz or 5 Hz, 6,000 stimuli over 10 days. Seventy-five percent of the patients had a clinically significant antidepressant response after rTMS, and 50% had sustained response at 2-month follow-up. Comparable improvements were seen in anxiety, hostility, and insomnia, but only minimal improvement in PTSD symptoms. Left frontal cortical rTMS may have promise for treating depression in PTSD, but there may be a dissociation between treating mood and treating core PTSD symptoms.

5-HT1A dysfunction in borderline personality disorder.

A number of challenge studies have reported abnormalities of serotonergic function in borderline personality disorder (BPD). There are, however, problems with the pharmacological probes used in these studies since fenfluramine and m-CPP are not only serotonergic agents but also induce release of catecholamines, particularly dopamine. Therefore, we tested whether subjects with BPD showed a blunted prolactin (PRL) response to flesinoxan, a highly potent and selective 5-HT1A agonist. Flesinoxan challenge test was carried out in 20 BPD in-patients and 20 healthy controls matched for gender but not for age. Since 16 BPD in-patients exhibited major depressive co-morbidity, a group of 20 depressed in-patients matched for gender but not for age was also included. BPD in-patients exhibited blunted PRL responses as compared to controls, whereas depressed in-patients did not differ from controls. Moreover, PRL responses were lower among BPD in-patients than among depressed in-patients. Among the BPD in-patients, PRL responses to flesinoxan were lower in patients with past history of suicide attempts (N = 8) than in those with a negative history. The results show major involvement of serotonergic function in BPD and are consistent with previous studies linking lower serotonergic activity with impulsivity. More particularly, our data suggest that BPD is characterized by lower 5-HT1A receptor sensitivity. Moreover, the data support the involvement of 5-HT1A activity in suicidal behaviour. However, this conclusion is limited because other hormonal responses such as ACTH and cortisol were not assessed, and because BPD was assessed by a self-report questionnaire and not a structured clinical interview.

Major Depressive Disorder and Health Care Costs in Multiple Sclerosis

Multiple Sclerosis (MS) is associated with elevated levels of depressive symptoms and an elevated frequency of depressive disorders. Depressive disorders, in general, are associated with substantial direct and indirect economic costs, and have been shown to increase the costs associated with the management of medical conditions in a variety of clinical settings. However, the impact of depressive disorders on costs associated with MS have not been evaluated. The objective of this study was to evaluate this association. The Composite International Diagnostic Interview (CIDI) was used to identify subjects with major depressive disorder in a sample who had earlier been selected for a broader economic evaluation of the costs associated with MS. Costs were measured in two ways: retrospectively (by questionnaire covering a 2-year period) and prospectively (using a 6-month diary). The proportion of subjects reporting any costs and the proportion exceeding various cost thresholds were calculated in subjects with and without lifetime major depression. These proportions were compared using exact statistical tests and confidence intervals. Non-parametric (rank sum) tests were used to compare median costs. Of 136 subjects, 31 had a lifetime history of major depression. MS-related expenses evaluated retrospectively (e.g., house and vehicle alterations and purchases) did not differ depending on major depression status. In the prospective analysis, subjects with lifetime major depression were more likely to purchase vitamins, herbs, and naturopathic remedies (p < 0.01) and more likely to incur costs associated with utilization of services provided by alternative practitioners (p = 0.04). Other differences (e.g., in mental health care, medical specialists, general practitioner visits) were not observed. Contrary to expectation, this study did not find increased direct medical costs in persons with comorbid major depressive disorder and multiple sclerosis. Persons with comorbid MS and (lifetime) major depression did not incur greater costs or utilize more services. The Canadian health care system is guided by principles of universality and is publicly funded and administered, however, the lack of an impact of major depression on utilization may reflect limited access to services. The lack of an association between costs and major depression may or may not be generalizable to health care systems in other countries.

A controlled evaluation of cognitive behaviorial therapy for posttraumatic stress in motor vehicle accident survivors

Seventy-eight motor vehicle accident survivors with chronic (greater than 6 months) PTSD, or severe sub-syndromal PTSD, completed a randomized controlled comparison of cognitive behavioral therapy (CBT), supportive psychotherapy (SUPPORT), or a Wait List control condition with two detailed assessments. Scores on the CAPS showed significantly greater improvement for those in CBT in comparison to the Wait List and to the SUPPORT conditions. The SUPPORT condition in turn was superior ( p=0.012) to the Wait List. Categorical diagnostic data showed the same results. An analysis of CAPS scores including drop-outs ( n=98) also showed CBT to be superior to Wait List and to SUPPORT with a trend for SUPPORT to be superior to Wait List. The CBT condition led to significantly greater reductions in co-morbid major depression and GAD than the other two conditions. Results held up well at a 3-month follow-up on the two active treatment conditions.

Influence of gender on attention deficit hyperactivity disorder in children referred to a psychiatric clinic.

The substantial discrepancy in the male-to-female ratio between clinic-referred (10 to 1) and community (3 to 1) samples of children with attention deficit hyperactivity disorder (ADHD) suggests that gender differences may be operant in the phenotypic expression of ADHD. In this study the authors systematically examined the impact of gender on the clinical features of ADHD in a group of children referred to a clinic. The study included 140 boys and 140 girls with ADHD and 120 boys and 122 girls without ADHD as comparison subjects. All subjects were systematically assessed with structured diagnostic interviews and neuropsychological batteries for subtypes of ADHD as well as emotional, school, intellectual, interpersonal, and family functioning. Girls with ADHD were more likely than boys to have the predominantly inattentive type of ADHD, less likely to have a learning disability, and less likely to manifest problems in school or in their spare time. In addition, girls with ADHD were at less risk for comorbid major depression, conduct disorder, and oppositional defiant disorder than boys with ADHD. A statistically significant gender-by-ADHD interaction was identified for comorbid substance use disorders as well. The lower likelihood for girls to manifest psychiatric, cognitive, and functional impairment than boys could result in gender-based referral bias unfavorable to girls with ADHD.

Generalized anxiety disorder: prevalence, burden, and cost to society.

Generalized anxiety disorder (GAD) is a prevalent and disabling disorder characterized by persistent worrying, anxiety symptoms, and tension. It is the most frequent anxiety disorder in primary care, being present in 22% of primary care patients who complain of anxiety problems. The high prevalence rate of GAD in primary care (8%) compared to that reported in the general population (12-month prevalence 1.9-5.1%) suggests that GAD patients are high users of primary care resources. GAD affects women more frequently than men and prevalence rates are high in midlife (prevalence in females over age 35: 10%) and older subjects but relatively low in adolescents. The natural course of GAD can be characterized as chronic with few complete remissions, a waxing and waning course of GAD symptoms, and the occurrence of substantial comorbidity particularly with depression. Patients with GAD demonstrate a considerable degree of impairment and disability, even in its pure form, uncomplicated by depression or other mental disorders. The degree of impairment is similar to that of cases with major depression. GAD comorbid with depression usually reveals considerably higher numbers of disability days in the past month than either condition in its pure form. As a result, GAD is associated with a significant economic burden owing to decreased work productivity and increased use of health care services, particularly primary health care. The appropriate use of psychological treatments and antidepressants may improve both anxiety and depression symptoms and may also play a role in preventing comorbid major depression in GAD thus reducing the burden on both the individual and society.

The Comorbidity of Major Depression and Anxiety Disorders: Recognition and Management in Primary Care.

BACKGROUND: Depressive and anxiety disorders commonly occur together in patients presenting in the primary care setting. Although recognition of individual depressive and anxiety disorders has increased substantially in the past decade, recognition of comorbidity still lags. The current report reviews the epidemiology, clinical implications, and management of comorbidity in the primary care setting. METHOD: Literature was reviewed by 2 methods: (1) a MEDLINE search (1980-2001) using the key words depression, depressivedisorders, and anxietydisorders; comorbidity was also searched with individual anxiety diagnoses; and (2) direct search of psychiatry, primary care, and internal medicine journals over the past 5 years. RESULTS: Between 10% and 20% of adults in any given 12-month period will visit their primary care physician during an anxiety or depressive disorder episode (although typically for a nonpsychiatric complaint); more than 50% of these patients suffer from a comorbid second depressive or anxiety disorder. The presence of depressive/anxiety comorbidity substantially increases medical utilization and is associated with greater chronicity, slower recovery, increased rates of recurrence, and greater psychosocial disability. Typically, long-term treatment is indicated, although far less research is available to guide treatment decisions. Selective serotonin reuptake inhibitor antidepressants are the preferred treatment based on efficacy, safety, and tolerability criteria. Knowledge of their differential clinical and pharmacokinetic profiles can assist in optimizing treatment. CONCLUSION: Increased recognition of the high prevalence and negative psychosocial impact of depression and anxiety disorder comorbidity will lead to more effective treatment. While it is hoped that early and effective intervention will yield long-term benefits, research is needed to confirm this.