Depressed Probands Research Articles

Positive autobiographical memory deficits in youth with depression histories and their never-depressed siblings.

Impaired positive autobiographical memory (AM) is closely linked to emotional disorders. AM impairments are often found in depressed adults and may be related to thedifficulties such persons have in regulating their dysphoric mood. By contrast, less is known about AM disturbances among adolescents, or about the functional relationship of AM disturbances to early-onset depression. A high-risk family design served to compare four groups of youth who differed in depression histories and familial depression risk. Thirty-one currently depressed probands, 185 remitted probands, 204 never-depressed siblings of probands, and 180 healthy control youth were induced into a negative mood prior to recalling positive AMs via a novel memory elicitation procedure. Several positive AM characteristics were assessed. Relative to control youth, unaffected siblings and probands exhibited consistently impaired positive AMs. Moreover, wealso found some evidence that probands were more impaired than siblings, who were in turn more impaired than controls, consistent with a gradient effect. Positive AM disturbances may not only precede the onset of depression in vulnerable youth, but also continue to persist after remission of a depressive episode. Clinical and basic research implications of the findings are discussed. Positive AM impairments may betrait-like, persist in the euthymic phase of depression, and may serve as a risk marker for early-onset depression among vulnerable adolescents. Disturbances in positive AM may negatively impact the mood-regulatory functions of positive memory recall and contribute to persistent sadness and anhedonia, which are core features of depression. Our sample of currently depressed youth was relatively small, tempering ourconclusions. Although we collected data on some important covariates (e.g., socioeconomic status), we lacked information on other relevant variables such as youths' executive functioning orIQ.

BDNF Val66Met polymorphism and stressful life events in melancholic childhood-onset depression.

Brain-derived neurotrophic factor (BDNF) polymorphisms have been examined for their contribution toward depression with equivocal results. More homogeneous phenotypes might be used to improve our understanding of genetic liability to depression. The aim of our study was to (a) test for an association between the BDNF Val66Met polymorphism and childhood-onset melancholic depression and (b) to examine the interactive effects of stressful life events (SLE) and the Val66Met polymorphism on the risk of childhood-onset melancholic depression. A total of 583 depressed probands were involved in this study (162 of the melancholic subtype). Diagnoses were derived through the Interview Schedule for Children and Adolescents - Diagnostic Version and life event data were collected using an Intake General Information Sheet. Overall, 27.8% of the participants fulfilled the criteria for melancholy. In the melancholic group, the proportion of females was higher (53.1%), although there were more males in the overall depressed sample. We detected no significant differences in genotype or allele frequency between the melancholic and the nonmelancholic depressed group. The BDNF Val66Met polymorphism and SLE interaction was not significantly associated with the melancholy outcome. In our study, females were more prone to developing the early-onset melancholic phenotype. To our knowledge, this is the first study to investigate the differentiating effect of the genotype and the G×E interaction on the melancholic phenotype in a large sample of depressed young patients. We did not find an association between the melancholic subtype of major depression and the BDNF genotype and SLE interaction in this sample, which is representative of the Hungarian clinic-referred population of depressed youths.

Mood repair via attention refocusing or recall of positive autobiographical memories by adolescents with pediatric-onset major depression.

Impaired emotion regulation is increasingly recognized as a core feature of depressive disorders. Indeed, currently and previously depressed adults both report greater problems in attenuating sadness (mood repair) in daily life than healthy controls. In contrast, studies of various strategies to attenuate sad affect have mostly found that currently or previously depressed adults and controls were similarly successful at mood repair in the laboratory. But few studies have examined mood repair among depression-prone youths or the effects of trait characteristics on mood repair outcomes in the laboratory. Adolescents, whose first episode of major depressive disorder (MDD) had onset at age 9, on average (probands), and were either in remission or depressed, and control peers, watched a sad film clip. Then, they were instructed to engage in refocusing attention (distraction) or recalling happy memories. Using affect ratings provided by the youths, we tested two developmentally informed hypotheses about whether the subject groups would be similarly able to attenuate sadness via the two mood repair strategies. We also explored if self-reported habitual (trait) mood repair influenced laboratory performance. Contrary to expectations, attention refocusing and recall of happy memories led to comparable mood benefits across subjects. Control adolescents reported significantly greater reductions in sadness than did depressed (Cohen's d = .48) or remitted (Cohen's d = .32) probands, regardless of mood repair strategy, while currently depressed probands remained the saddest after mood repair. Habitual mood repair styles moderated the effects of instructed (state) mood repair in the laboratory. Whether depressed or in remission, adolescents with MDD histories are not as efficient at mood repair in the laboratory as controls. But proband-control group differences in mood repair outcomes were modest in scope, suggesting that the abilities that subserve affect regulation have been preserved in probands to some degree. Further information about the nature of mood repair problems among youths with depression histories would help to better understand the clinical course of MDD and to design personalized interventions for depression.

Parental Depression Risk: Comparing Youth with Depression, Attention Deficit Hyperactivity Disorder and Community Controls

Objective: Family studies of youth with depression are reviewed and new data presented. Past studies suggest strong familiality of youth depression. However, few studies included direct interviews with fathers and both psychiatric and normal control groups. In this study, lifetime prevalences of parental Major Depressive Disorder (MDD), Recurrent Depression, Dysthymic Disorder (DD), Double Depression (MDD/DD) and Bipolar Disorder were compared for 6-18 year old youth with depression (n = 127), youth with ADHD without a depression history (n = 116), and community control youth (n = 78). Method: Parental diagnoses were made by diagnosticians blind to child diagnostic status using best estimate procedures based on the parent-interview SADS and the Family History Interview of Psychiatric Status from the other parent. Child diagnoses were based on K-SADS interviews conducted with both parent and child separately. Results: Both mothers and fathers of depressed probands were significantly more likely than mothers and fathers of the other proband groups to have a history of MDD and DD. Mothers of probands with MDD/DD had higher rates of MDD compared to mothers of other depressed probands. There were few cases of parental Bipolar Disorder and most occurred in parents of probands with depression. Conclusion: The current findings provide further evidence of the strong familiality of youth depression and highlight the need to evaluate parents when treating depressed youth. A comprehensive treatment approach may need to include a focus on obtaining treatment for and enhancing coping with parental depression.

Neuroanatomical Correlates of Religiosity and Spirituality

We previously reported a 90% decreased risk in major depression, assessed prospectively, in adult offspring of depressed probands who reported that religion or spirituality was highly important to them. Frequency of church attendance was not significantly related to depression risk. Our previous brain imaging findings in adult offspring in these high-risk families also revealed large expanses of cortical thinning across the lateral surface of the right cerebral hemisphere. To determine whether high-risk adults who reported high importance of religion or spirituality had thicker cortices than those who reported moderate or low importance of religion or spirituality and whether this effect varied by family risk status. Longitudinal, retrospective cohort, familial study of 103 adults (aged 18-54 years) who were the second- or third-generation offspring of depressed (high familial risk) or nondepressed (low familiar risk) probands (first generation). Religious or spiritual importance and church attendance were assessed at 2 time points during 5 years, and cortical thickness was measured on anatomical images of the brain acquired with magnetic resonance imaging at the second time point. Cortical thickness in the parietal regions by risk status. Importance of religion or spirituality, but not frequency of attendance, was associated with thicker cortices in the left and right parietal and occipital regions, the mesial frontal lobe of the right hemisphere, and the cuneus and precuneus in the left hemisphere, independent of familial risk. In addition, the effects of importance on cortical thickness were significantly stronger in the high-risk than in the low-risk group, particularly along the mesial wall of the left hemisphere, in the same region where we previously reported a significant thinner cortex associated with a familial risk of developing depressive illness. We note that these findings are correlational and therefore do not prove a causal association between importance and cortical thickness. A thicker cortex associated with a high importance of religion or spirituality may confer resilience to the development of depressive illness in individuals at high familial risk for major depression, possibly by expanding a cortical reserve that counters to some extent the vulnerability that cortical thinning poses for developing familial depressive illness.

Self-Mutilation and Suicide Attempts: Relationships to Bipolar Disorder, Borderline Personality Disorder, Temperament and Character

Self-mutilation has traditionally been associated with borderline personality disorder, and seldom examined separately from suicide attempts. Clinical experience suggests that self-mutilation is common in bipolar disorder. A family study was conducted on the molecular genetics of depression and personality, in which the proband had been treated for depression. All probands and parents or siblings were interviewed with a structured interview and completed the Temperament and Character Inventory. Fourteen per cent of subjects interviewed reported a history of self-mutilation, mostly by wrist cutting. Self-mutilation was more common in bipolar I disorder subjects then in any other diagnostic groups. In multiple logistic regression self-mutilation was predicted by mood disorder diagnosis and harm avoidance, but not by borderline personality disorder. Furthermore, the relatives of non-bipolar depressed probands with self-mutilation had higher rates of bipolar I or II disorder and higher rates of self-mutilation. Sixteen per cent of subjects reported suicide attempts and these were most common in those with bipolar I disorder and in those with borderline personality disorder. On multiple logistic regression, however, only mood disorder diagnosis and harm avoidance predicted suicide attempts. Suicide attempts, unlike self-mutilation, were not familial. Self-mutilation and suicide attempts are only partially overlapping behaviours, although both are predicted by mood disorder diagnosis and harm avoidance. Self-mutilation has a particularly strong association with bipolar disorder. Clinicians need to think of bipolar disorder, not borderline personality disorder, when assessing an individual who has a history of self-mutilation.

In Search of Endophenotypes for Suicidal Behavior

In Search of Endophenotypes for Suicidal Behavior

Familial Aggregation of Suicide Explained by Cluster B Traits: A Three-Group Family Study of Suicide Controlling for Major Depressive Disorder

There is substantial evidence suggesting that suicide aggregates in families. However, the extent of overlap between the liability to suicide and psychiatric disorders, particularly major depressive disorder, remains an important issue. Similarly, factors that account for the familial transmission of suicidal behavior remain unclear. Thus, through direct and blind assessment of first-degree relatives, the authors conducted a family study of suicide by examining three proband groups: probands who committed suicide in the context of major depressive disorder, living depressed probands with no history of suicidal behavior, and psychiatrically normal community comparison probands. Participants were 718 first-degree relatives from 120 families: 296 relatives of 51 depressed probands who committed suicide, 185 relatives of 34 nonsuicidal depressed probands, and 237 relatives of 35 community comparison subjects. Psychopathology, suicidal behavior, and behavioral measures were assessed via interviews. The relatives of probands who committed suicide had higher levels of suicidal behavior (10.8%) than the relatives of nonsuicidal depressed probands (6.5%) and community comparison probands (3.4%). Testing cluster B traits as intermediate phenotypes of suicide showed that the relatives of depressed probands who committed suicide had elevated levels of cluster B traits; familial predisposition to suicide was associated with increased levels of cluster B traits; cluster B traits demonstrated familial aggregation and were associated with suicide attempts among relatives; and cluster B traits mediated, at least in part, the relationship between familial predisposition and suicide attempts among relatives. Analyses were repeated for severity of attempts, where cluster B traits also met criteria for endophenotypes of suicide. Familial transmission of suicide and major depression, while partially overlapping, are distinct. Cluster B traits and impulsive-aggressive behavior represent intermediate phenotypes of suicide.

From psychoanalysis to epidemiology: autobiographical notes

From psychoanalysis to epidemiology: autobiographical notes

A twin study of smoking, nicotine dependence, and major depression in men

This study examined the nature of the relationship among lifetime major depression, smoking, and nicotine dependence. Subjects were 8,169 male twins from the Vietnam Era Twin Registry. Biometrical modeling demonstrated a genetic influence on daily smoking, nicotine dependence, and major depression, and a family environmental influence on daily smoking. Genetic factors influencing nicotine dependence also strongly influenced major depression. We also compared probands with a history of major depression (n = 398) from pairs discordant for major depression, their nondepressed cotwins (n = 364), and controls (n = 1,863) on a number of secondary smoking outcomes. Major depression was associated with current daily smoking and certain nicotine withdrawal symptoms. Individuals with a familial vulnerability for major depression, even without a personal history of major depression, were more likely to smoke despite a serious illness and to report nervousness, restlessness, difficulty concentrating, and depressed mood during past quit attempts. Among the 237 monozygotic pairs discordant for major depression, depressed probands were more likely to have a lifetime history of nicotine dependence than were cotwins. Findings extend Kendler and colleague's (1993) study of female twins by demonstrating in men that shared genetic factors predispose not only to major depression and daily smoking but also to major depression and nicotine dependence.

Homing in on Depression Genes

Homing in on Depression Genes

Regional Patterns of Brain Activity in Adults With a History of Childhood-Onset Depression: Gender Differences and Clinical Variability

The study investigated the hypothesis that EEG asymmetry scores (indicating higher right and lower left frontal brain activity) are associated with vulnerability to negative mood states and depressive disorders. Gender and clinical history variables were examined as factors that may influence the relation between EEG and depression. EEG measures of asymmetrical alpha frequency (7.5-12.5 Hz) suppression were analyzed in 55 young adults with a documented clinical history of childhood-onset depression and 55 comparison subjects with no history of major psychopathology. EEG patterns were examined in relation to operational diagnoses of mental disorders during childhood and adulthood. Differences in EEG asymmetry between childhood depression probands and comparison subjects varied with gender, diagnostic history, and current symptoms. Women with childhood depression had higher right midfrontal alpha suppression, and men with childhood depression had higher left midfrontal alpha suppression, relative to comparison subjects. At all scalp sites, women showed greater alpha power than men. Probands with a bipolar spectrum course had the most extreme midfrontal asymmetry. Frontal asymmetry was more extreme in probands with current depressive symptoms than in those without current symptoms. Regional brain activity is influenced by gender and variability in clinical course. The findings have implications for investigating brain correlates of mood disorder and may help to develop more refined phenotypes.

A sib-pair study of psychoticism, life events and depression

The Psychoticism (P) scale of the Eysenck Personality Questionnaire (EPQ) (Eysenck & Eysenck, 1975) was originally proposed as a measure of the predisposition to psychotic breakdown, however, subsequent research has suggested that the P-scale is measuring a thoughtless and reckless personality. This study aims to further examine the construct of P, its relation to the experience of adversity and the development of depression. One hundred and eight depressed probands and their nearest aged siblings were compared to 105 control probands and their nearest aged siblings. All were interviewed using the Schedule for the Clinical Assessment of Neuropsychiatry (Wing, Babor, Brugha et al., 1990) and the Life Events and Difficulties Schedule (Brown & Harris, 1978). Subjects also completed the Beck Depression Inventory (BDI) (Beck, 1961) and the EPQ at the time of interview. It was found that four factors underlie the P-scale, namely Cruel/ Hostile, Anti-social, Impulsiveness, Recklessness/Fecklessness. The P-scale is familial and scores correlate positively with severe and threatening life events and BDI score at the time of interview. It is concluded that high P-scale scorers are predisposed to personality traits that are associated with an excess of severe and threatening life events, which in turn can lead to the development of depression.

Recurrence of depression in those with prepubertal onset was associated with higher rates of depression in relatives

Wickramaratne PJ, Greenwald S, Weissman MM. Psychiatric disorders in the relatives of probands with prepubertal-onset or adolescent-onset major depression. J Am Acad Child Adolesc Psychiatry2000 Nov; 39 : 1396 –405....

The Cardiff Depression Study: a sib-pair study of dysfunctional attitudes in depressed probands and healthy control subjects.

Current cognitive theories propose that depression develops as a result of the interaction between dysfunctional cognitive schemata and environmental stressors. There is also consistent evidence of a substantial genetic contribution to depression. This study examines the familiality and stability of dysfunctional attitudes and attempts to distinguish whether they reflect trait vulnerability to depression or the state of being depressed. The 24-item Dysfunctional Attitude Scale (DAS-24) was completed by 108 depressed probands and their nearest-aged siblings and 105 healthy control probands and their nearest-age siblings, at the time of a semi-structured clinical interview and 10-12 months later. Subjects also completed self-report measures of depressed mood on both occasions. Measures of clinical depression were significantly correlated with DAS scores. At retest, DAS scores remained elevated despite improvement in mood, giving support for earlier findings, that dysfunctional attitudes remain active following recovery. The dependency subscale (DAS-D) of the DAS showed modest familiality, although there were no significant differences for DAS-D scores between the two groups of siblings. In a multiple regression analysis, current mood-state was the overwhelming predictor of DAS scores. However for DAS-D, gender as well as current mood influenced scores on this subscale. Although there was modest evidence for temporal stability and familiality for some DAS-24 subscale scores, dysfunctional attitudes were predominantly influenced by current low mood, and therefore reflect the state of being depressed rather than a familial vulnerability trait underpinning depression.

The Cardiff sib-pair study: suicidal ideation in depressed and healthy subjects and their siblings.

Depression is associated with high rates of suicidal ideation, which varies in intensity from transient thoughts of wishing to be dead to the making of plans and, Finally, to attempts to kill oneself. There is limited evidence from family, twin, and adoption studies that completed suicide is familial and has a genetic etiological component. However, it is unclear whether suicidal ideation is also familial. The familiality of suicidal ideation has been examined in the subjects who participated in the Cardiff Depression Study, namely, 108 depressed probands. their nearest-aged siblings, and 105 healthy control subjects and their siblings. The study showed that 66% of depressed subjects had experienced suicidal ideation in the week prior to the interview, and that this was significantly associated with recurrent illness. Suicidal ideation was not shown to be familial. However, somewhat surprisingly, 6% of healthy, never-depressed subjects admitted to having had transient suicidal thoughts. Suicidal ideation was significantly associated with high neuroticism and psychoticism scores and severe threatening life events.

Does the method of data collection affect the reporting of depression in the relatives of depressed probands?

Background: Data is usually collected from different sources in family studies in depression. We sought to determine what effect different methods of data collection had on the reporting of the lifetime prevalence of depression in the relatives of depressed probands. Method: We examined the psychiatric histories of 519 first-degree relatives of a consecutive series of 89 hospitalised depressed probands to ascertain their lifetime prevalence of RDC Major Depression. These data on relatives were obtained either directly with the SADS-L ( n=116), indirectly with the Family History RDC (FH-RDC) ( n=283) or by examining the casenotes of the probands ( n=120). Results: The method of data collection had a marked effect on the reported prevalence of depression, with direct interview being much more sensitive in detecting the less severe forms of the illness. The lifetime prevalence of hospitalised depression in relatives, however, was unaffected by the method of the data collection. Variation in lifetime prevalence of depression between the SADS-L and FH-RDC appeared to be due mainly to differences in the sensitivity of the instrumentation rather than to biases in sampling. Conclusion: We confirm that indirect sources of family information have reduced sensitivity for the detection of depression in relatives compared with direct interview. Limitations: The numbers of relatives directly interviewed were small and the probands represented a severely affected sample which limits the generalisability of the findings. Clinical relevance: Combining data from different methods of collection in family studies is therefore problematic unless a narrow definition of caseness is used (e.g. depression requiring hospitalisation).

Association studies of bipolar disorder at the human serotonin transporter gene (hSERT; 5HTT).

The human serotonin transporter gene (hSERT) is a strong candidate for involvement in the pathogenesis of mood disorder and, using a UK Caucasian case-control sample, Collier et al found a significant association between bipolar disorder and the 12 allele of the VNTR polymorphism in intron 2 of this gene. In a European collaborative sample, Collier et al found a significant association between affective disorder and a functional deletion polymorphism in the promoter of hSERT. We have undertaken association studies using these polymorphisms in a British Caucasian sample comprising 171 DSM-IV bipolar probands, 80 DSM-IV major depression probands and 121 unrelated controls matched to bipolar probands for age, sex and ethnicity. We found no association between the promoter deletion and affective disorder but our findings with the VNTR polymorphism are similar to those of Collier and colleagues: we found a significant excess of the 12 repeat allele in bipolar probands (P = 0.031, one-tall) with a suggestion of a gene dosage effect (using genotypes bearing no 12 repeat allele as baseline, the increased risks conferred by genotypes bearing 12 repeat alleles were: heterozygote, OR = 1.24; homozygote, OR = 1.76). Our findings add to the evidence that variation at or near hSERT influences susceptibility to bipolar disorder in the British Caucasian population.

Eye-tracking dysfunction in offspring from the New York High-Risk Project: diagnostic specificity and the role of attention

Eye tracking abnormalities were studied in the offspring of schizophrenic, unipolar depressed and bipolar probands from the New York High-Risk Project to examine their familial specificity. Offspring of schizophrenic and depressed probands both had significant global performance deficits based on spectral purity measurements, but only the offspring of schizophrenic probands had an increased rate of intrusive anticipatory saccades. The greater specificity of high anticipatory saccade rate than global performance impairment suggests that this eye movement abnormality may provide a more specific biological marker of risk for schizophrenia than the global measure of eye tracking performance used in this study. Attention facilitation effectively normalized all performance deficits in the offspring of schizophrenic patients, suggesting that a problem sustaining focused visual attention may contribute to eye tracking deficits observed in the relatives of schizophrenic probands.

Psychiatric disorders in the relatives of depressed probands II. Familial loading for comorbid non-depressive disorders based upon proband age of onset

This study examined familial loading for non-depressive disorders in first-degree relatives (FDRs) of early- (< 20 years of age) and adult-onset (⩾ 20 years of age) depressed probands. Our previous work, which demonstrated that FDRs of early-onset probands have higher rates of major depression as compared to FDRs of adult-onset probands, has not yet examined risk for non-depressive disorders in FDRs. In this paper, we focus on best-estimate diagnoses of anxiety disorders, alcoholism, and antisocial personality conducted on 639 first-degree relatives. The FDRs of early-onset probands had significantly higher rates of comorbid transmission of alcoholism and depression, and antisocial personality and depression, respectively. Significant co-transmission of anxiety disorders and depression was found in the FDRs of both early- and adult-onset probands. Future genetic studies of depression, especially early-onset depression, should hence broaden their definitions of phenotypes to include comorbid disorders when searching for the etiology of this complex disorder.