Effects Of Major Depressive Disorder Research Articles

Neural basis of the emotional Stroop interference effect in major depression

A mood-congruent sensitivity towards negative stimuli has been associated with development and maintenance of major depressive disorder (MDD). The emotional Stroop task assesses interference effects arising from the conflict of emotional expressions consistent with disorder-specific self-schemata and cognitive colour-naming instructions. Functional neuroimaging studies of the emotional Stroop effect advocate a critical involvement of the anterior cingulate cortex (ACC) during these processes. Subjects were 17 medication-free individuals with unipolar MDD in an acute depressive episode (mean age 39 years), and 17 age-, gender- and IQ-matched healthy volunteers. In an emotional Stroop task, sad and neutral words were presented in various colours, and subjects were required to name the colour of words whilst undergoing functional magnetic resonance imaging (fMRI). Overt verbal responses were acquired with a clustered fMRI acquisition sequence. Individuals with depression showed greater increases in response time from neutral to sad words relative to controls. fMRI data showed a significant engagement of left rostral ACC (BA 32) and right precuneus during sad words in patients relative to controls. Additionally, rostral ACC activation was positively correlated with latencies of negative words in MDD patients. Healthy controls did not have any regions of increased activation compared to MDD patients. These findings provide evidence for a behavioural and neural emotional Stroop effect in MDD and highlight the importance of the ACC during monitoring of conflicting cognitive processes and mood-congruent processing in depression.

Epidemiology of major depressive disorder in elderly Nigerians in the Ibadan Study of Ageing: a community-based survey

The growing populations of elderly people in sub-Saharan Africa are exposed to social changes with potential adverse effects on mental health. Our aim was to estimate the occurrence and effect of major depressive disorder in a large and representative community sample of elderly Africans. Face-to-face interviews with a representative sample of people aged 65 years and older (n=2152) were obtained by a multistage stratified sampling of households in the Yoruba-speaking areas of Nigeria (about 22% of the national population). Major depressive disorder was assessed with the WHO composite international diagnostic interview and diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Lifetime and 12-month prevalence estimates of major depressive disorder were 26.2% (95% CI 24.3-28.2) and 7.1% (5.9-8.3) respectively. Female sex (odds ratio [OR] 1.9) and increasing levels of urbanisation of residence (OR 1.4) were associated with this disorder. People with major depressive disorder had impaired quality of life and functioning in home, work, and social roles. Independent ratings of symptom severity confirmed the presence of clinically significant depression in 96.9% of those with diagnosis, and increasing symptom severity was associated with greater disability and poorer quality of life. Only about 37% of lifetime cases had received any treatment, and there was a mean delay of 5 years from onset of depression to receipt of first treatment. Low economic status (0.3) and rural residence (1.0) predicted no treatment. Major depressive disorder is common in elderly Nigerians and its occurrence is related to urbanisation. This disorder is a seriously disabling illness in this group but only a few sufferers have ever received treatment. Health-care services need to invest in effective treatment programmes for major depressive disorder.

Effects of major depressive disorder and attention-deficit/hyperactivity disorder on the outcome of treatment for cocaine dependence

Co-occurring psychiatric disorders have been associated with poor prognosis among substance-dependent patients, but few studies have examined this association among patients with cocaine dependence (CD). We compared baseline characteristics and treatment outcome between cocaine-dependent patients with major depressive disorder (MDD; n = 66), those with attention-deficit/hyperactivity disorder (ADHD; n = 53), and those with CD without comorbid disorders (CD alone; n = 48) who had been randomized to the placebo arms of clinical trials with venlafaxine, methylphenidate, and gabapentin, respectively. The three groups differed significantly in racial makeup, with more Caucasians and Hispanics among patients with MDD and those with ADHD but more African Americans among those with CD alone. The groups did not differ significantly in treatment retention, with retention rates ranging from 42% to 47%; neither did they differ in the rates of achieving 2 consecutive weeks of urinalysis-confirmed abstinence, with rates ranging from 40% to 50%. Using logistic regression for repeated measures with general estimating equations, modeling the likelihood of a cocaine-positive week over time in treatment, we found the diagnostic group to interact with the baseline level of cocaine use and time. Among cocaine-dependent patients who achieved abstinence at baseline, those with MDD and those with ADHD had better outcome over time as compared with patients with CD alone. However, among patients with cocaine-positive urine specimens at baseline, those with MDD and those with ADHD were associated with poor outcome as compared with patients with CD alone. The findings suggest that diagnosis and treatment of co-occurring disorders such as depression and ADHD may be important components of treatment planning for CD and that the baseline level of cocaine use should be included as a covariate in studies evaluating the impact of such treatment.

Cardiovascular Risk Factors May Moderate Pharmacological Treatment Effects in Major Depressive Disorder

An increased association between depression and cardiovascular disease, as well as cardiovascular risk factors, led to the "vascular depression" hypothesis. This subtype of depression is postulated to have a different clinical presentation and to be more treatment-resistant. In this study, we measured the impact of cardiovascular risk factors on the outcome of antidepressant treatment in major depressive disorder (MDD). We enrolled 348 MDD subjects, ages 19 to 65 years, in an 8-week treatment study with 20 mg fluoxetine per day. We recorded for each subject 6 cardiovascular risk factors: age (male > or =45, female > or =55), smoking, family history, hypertension, diabetes, hypercholesterolemia; and we defined a cardiovascular risk score (range, 0-6) by the number of risk factors present. Treatment outcome was measured as response (> or =50% improvement on the 17-item Hamilton Rating Scale for Depression [Ham-D-17]) and remission (final Ham-D-17< or =7). In logistic regression analyses, the cardiovascular risk score was significantly associated with treatment nonresponse and lack of remission when adjusting for age of onset of MDD and baseline severity of depression. The cardiovascular risk score remained significantly associated with treatment nonresponse when we additionally controlled for overall medical burden (measured with the Cumulative Illness Rating Scale). Among individual cardiovascular risk factors, elevated total cholesterol was a significant predictor of treatment nonresponse and lack of remission. Cardiovascular risk factors may have negative effects on the course of treatment in MDD. These results support the concept of "vascular depression" in younger subjects.

Dissociation of inflammatory markers and natural killer cell activity in major depressive disorder

Major depressive disorder is associated with increases in infectious disease risk as well as the incidence of inflammatory disorders. Declines of natural killer (NK) cell activity are reliably found in depression, whereas other studies report evidence of inflammation in depressed patients. The potential association between NK activity and circulating markers of immune activation has not been previously examined in the context of major depression. In this study, we measured levels of NK activity, circulating levels of interleukin-6 (IL-6), soluble interleukin-2 receptor, and acute phase proteins in 25 male patients with current major depressive disorder and 25 age, gender, and body weight comparable controls. As compared to controls, patients with major depressive disorder showed lower NK activity ( p = .05) and higher circulating levels of IL-6 ( p < .05). Levels of NK activity were not correlated with IL-6 or with other markers of immune activation. The independent effect of depression on inflammatory markers and natural killer immune responses has implications for understanding individual differences in the adverse health effects of major depressive disorder.

Depressive Symptoms Are Associated With Increased Systemic Vascular Resistance to Stress

The deleterious effects of major depressive disorder on cardiovascular (CV) functioning are well known. However, the etiologic mechanisms underlying this association are incompletely understood. In the current study, subjects with varying degrees of depressive symptoms performed a stress task while CV reactivity was measured. We hypothesized that high levels of depressive symptoms would be associated with altered CV reactivity. Ninety-one healthy volunteer subjects performed reactivity testing while measures of impedance cardiography and autonomic nervous system function were obtained. Subjects completed the Center for Epidemiological Studies Depression Scale (CES-D) and were categorized into either the high depressive (i.e., CES-D > or =16) or low depressive (i.e., CES-D <16) symptoms group. Task performance was associated with increases in systemic vascular resistance (SVR) (p = .001), mean arterial pressure (p = .001), and heart rate (p = .005), and decreases in cardiac output (p = .001), heather index (p = .001), and stroke volume (p = .05). After controlling for screening mean arterial pressure, an interaction effect of stress by mood group on SVR (p = .01) was observed; subjects with high amounts of depressive symptoms manifested significantly greater SVR at baseline and in response to a stressor task than did subjects with low amounts of depressive symptoms. These results suggest a mechanism that may partially explain the increased CV morbidity associated with depressive symptoms. In future studies, it may be useful to examine if treatment of depressive symptoms alters CV reactivity.

Lower hippocampal volume in patients suffering from depression: a meta-analysis.

A number of studies have used magnetic resonance imaging to examine volumetric differences in temporal structures in subjects suffering from major depressive disorder. Studies have reported lower hippocampal and amygdala volume, but results have been inconsistent. The authors were interested, therefore, in examining these studies in the aggregate in order to determine whether hippocampal volume is lower in major depressive disorder. They also examined factors that may contribute to the disparate results in the literature. A meta-analysis was conducted of studies that used magnetic resonance imaging to assess the volume of the hippocampus and related structures in patients with major depressive disorder. Patients were seen to have lower hippocampal volume relative to comparison subjects, detectable if the hippocampus was measured as a discrete structure. Although the effect of major depressive disorder on amygdala volume remains to be conclusively established, inclusion of the amygdala with the hippocampus appears to have decreased the likelihood of detecting volumetric differences in either structure. Slice thickness or other scan parameters did not account for a substantive amount of the variance in results, whereas clinical variables of the populations studied, such as duration of illness or presence of abuse, may account for much of the discrepancy between findings.

Meta-analysis of placebo rates in major depressive disorder trials.

Placebo effects in major depressive disorder (MDD) have received much interest in the medical literature. However, few quantitative analyses have been done in homogeneous populations. To determine efficacy rates for placebo in patients with MDD; to quantify the correlation between efficacy and publication year, as well as between placebo and drug response rates. Searching MEDLINE (1966-December 2000), EMBASE (1998-February 2001), HealthSTAR (1975-December 2000), and Cochrane (1980-December 2000) databases, randomized, placebo-controlled trials were retrieved including patients with MDD as defined by Diagnostic and Statistical Manual of Mental Disorders, 3rd and 4th editions criteria, Hamilton Rating Scale for Depression score >/=18 or Montgomery-Asberg Depression Rating Scale score >/=16, reporting successes as 50% decreases in scores after 6-8 weeks of treatment. Response rates were summarized using a random effects meta-analysis for per protocol (PP) and intent-to-treat (ITT) results. We included 24 of 134 potential studies examining 4459 patients, 1786 on placebo and 2673 on an antidepressant. Placebo response rates were 45.5% (PP) and 26.9% (ITT). Correlations were significant between year and rates (PP rho 0.448, p = 0.042; ITT rho 0.557; p = 0.006), but not for active drugs. Placebo and drug rates were correlated (PP r 0.397, p = 0.020; ITT r 0.539; p = 0.002). These placebo rates confirm those reported previously, but were from a homogeneous population. Although statistically significant, the correlation between drug and placebo rates was lower than others reported. During the study period, placebo rates increased linearly; active drugs did not. Correlations between placebo and drug response rates reflected moderate to strong effect sizes. We suggest that current methodology has been unsuccessful in achieving unbiased double-blind conditions not influenced by extra-trial factors, including time.

Effects of major depression on remission and relapse of substance dependence.

The effects of major depressive disorder (MDD) on the course of substance dependence may differ depending on the temporal relationship of depression to dependence. We investigated the effects of MDD on the outcome of substance dependence under 3 circumstances: (1) lifetime onset of MDD prior to lifetime onset of dependence onset, (2) current MDD occurring during a period of abstinence, and (3) current MDD during substance use that exceeded the expected effects of intoxication or withdrawal. A sample of 250 inpatients with DSM-IV cocaine, heroin, and/or alcohol dependence were followed up at 6, 12, and 18 months. The Psychiatric Research Interview for Substance and Mental Disorders (PRISM) was used to make DSM-IV diagnoses. Using Cox proportional hazards models, stable remissions (those lasting at least 26 weeks) from DSM-IV cocaine, heroin, and/or alcohol dependence and from use were studied, as well as subsequent relapses of dependence and use. Patients with current substance-induced MDD were less likely to remit from dependence (adjusted hazards ratio, 0.11) than patients with no baseline MDD. A history of MDD prior to lifetime onset of substance dependence also reduced the likelihood of remission relative to the absence of such a history (adjusted hazard ratio, 0.49). Major depressive disorder during sustained abstinence predicted dependence relapse (adjusted hazards ratio, 3.07) and substance use after hospital discharge compared with those without abstinence MDD (adjusted hazards ratio, 1.45). The timing of depressive episodes relative to substance dependence served as an important factor in the remission and relapse of substance dependence and substance use.

Effect of major depression on cognitive performance among treatment-seeking adolescents

We investigated the association between cognitive performance and major depressive disorder (MDD) in adolescents seeking outpatient treatment. We used several tests comparing cognitive capacities between 16 adolescents with MDD and 25 adolescents not diagnosed as suffering from psychiatric illness according to the Structured Clinical Interview for DSM-III-R (SCID). No difference in neuropsychological test performance was found between adolescents with MDD and those without psychiatric diagnosis. Logistic regression analysis showed the only independent factor associated with MDD to be Emotional Tone (S2; odds ratio 1.13). The specific effects of MDD on the adolescents were restricted to the emotional area and were expressed as a broad deterioration in psychosocial functioning.

Effect of Major Depression on the Self-Image of Adolescent Boys and Girls

We investigated the specific impact of major depressive disorder (MDD) on the self-image of adolescent boys and girls seeking outpatient treatment. We used the Offer Self-Image Questionnaire (OSIQ) to compare 68 adolescents with MDD and 39 adolescents with no diagnosis of psychiatric illness according to the Structural Clinical Interview for DSM-III-R (SCID). Self-image among MDD patients was in general poorer than in the comparison group and was particularly expressed as dissatisfaction with life and an impaired mastery of the environment. Logistic regression analysis showed S2 (Emotional Tone) to be an independent factor associated with MDD (OR 1.15). In girls S2 was also independently associated with MDD (OR 1.14). The effect of MDD on self-image was more negative in girls than in boys and the self-image pattern differed between the sexes.

Childhood Depression and Adult Personality Disorder

This study extends previous findings of the risks posed by childhood major depressive disorder and other psychopathological features for later personality disorder (PD) in a random sample of 551 youths. Self-reports and mother reports were used to evaluate DSM-III-R (Axes I and II) psychiatric disorders at mean ages of 12.7, 15.2, and 21.1 years. Logistic regression was used to examine the independent effects of major depressive disorder in childhood or adolescence on 10 PDs in young adulthood. Odds of dependent, antisocial, passive-aggressive, and histrionic PDs increased by more than 13, 10, 7, and 3 times, respectively, given prior major depressive disorder. Those effects were independent of age, sex, disadvantaged socioeconomic status, a history of child maltreatment, nonintact family status, parental conflict, preexisting PD in adolescence, and other childhood or adolescent Axis I psychopathological features, including disruptive and anxiety disorders. In addition, odds of schizoid and narcissistic PD increased by almost 6 times and odds of antisocial PD increased by almost 5 times given a prior disruptive disorder, and odds of paranoid PD increased by 4 times given a prior anxiety disorder. Personality disorders may represent alternative pathways of continuity for major depressive disorder and other Axis I disorders across the child-adult transition.

Familial transmission of panic disorder: effect of major depression comorbidity.

This study assesses the effect of major depressive disorder (MDD) comorbidity on familial transmission of panic disorder (PD). The following questions are addressed: (1) is PD familial, i.e., do relatives of patients with PD show an increased risk for PD? (2) do PD and MDD share a common diathesis, i.e., do relatives of patients with PD without MDD show an increased risk for MDD? (3) is lifetime comorbid PD with MDD conjointly familial, i.e., do relatives of patients with PD and MDD show an increased risk for the combined syndrome? Subjects were: (1) 152 relatives of 54 anxiety clinic patients with PD and MDD; (2) 193 relatives of 72 patients with PD without MDD; (3) 231 relatives of 77 not ill controls. Relatives were interviewed by clinicians, and best estimate DSM-III-R diagnoses were formulated by senior staff. Relatives of PD with MDD (13%) and PD without MDD probands (9%) showed significantly higher rates of PD than relatives of controls (3%). Relatives of PD with MDD probands (37%) showed significantly higher rates of MDD than relatives of PD without MDD (24%) and controls (21%), with no difference between the latter two groups. Relatives of PD with MDD probands (9%) showed significantly higher rates of PD with MDD than relatives of PD without MDD (3%) and controls (1%). We conclude that: (1) PD is familial; (2) PD in the absence of MDD does not incur increased risk of MDD to relatives; and (3) PD with MDD may represent a distinct, complex syndrome.

Anger attacks in unipolar depression, Part 1: Clinical correlates and response to fluoxetine treatment

Anger attacks are sudden, intense spells of anger associated with a surge of autonomic arousal including such symptoms as tachycardia, sweating, flushing, and a feeling of being out of control. The purpose of this study was to determine whether depressed patients with and without anger attacks exhibit distinct psychological characteristics and whether these attacks respond to treatment with fluoxetine. The Anger Attacks Questionnaire, the Hamilton Rating Scale for Depression, the Symptom Questionnaire, and the Cook-Medley Hostility Scale were among the scales administered at the Depression Research Program of the Clinical Psychopharmacology Unit at the Massachusetts General Hospital to 127 medication-free outpatients with major depression and to 85 of these patients after 8 weeks of open treatment with a fixed dose (20 mg/day) of fluoxetine. At baseline, 44% of the depressed outpatients reported having anger attacks; these patients had significantly higher scores on measures of anxiety, somatization, and state and trait hostility than did the subjects who did not exhibit such attacks. After treatment, there were significant reductions in these measures, and the anger attacks disappeared in the majority (71%) of the patients who had previously reported them. There was a trend toward greater overall clinical improvement for patients with anger attacks than for patients without them. This study identified a subgroup of highly irritable and hostile depressed patients who report the presence of anger attacks and have a psychological profile distinct from that of depressed patients without anger attacks. Furthermore, fluoxetine treatment appears to be beneficial in reducing anger and hostility in these patients.

The use of conditional probabilities to examine age-period-cohort data: further evidence for a period effect in major depressive disorder

There is growing evidence that rates of major depression have been increasing over this century, with successive birth cohorts showing increased lifetime risks and earlier ages of onset. In this paper, we describe and compare onset rates in six birth cohorts of first degree relatives of probands with affective disorders from the NIMH Collaborative Study, using graphs of conditional probabilities of first onset. There is evidence of a period effect and age-period interaction for both men and women.

Depressive illness and learning difficulties: research needs and practical implications.

Major depressive disorder (MDD) in children is a subject of much recent interest in psychiatry. In addition to the direct effects of MDD on learning and cognition in general, some investigators have suggested that there may be relationships of MDD to learning disabilities in general or to dysfunction to the right hemisphere of the brain in particular. In this report I briefly review the basis for these ideas, suggest some testable hypotheses, and discuss the potential implications of the hypotheses for educators and mental health professionals.