Lifetime Depressive Episodes Research Articles

The effect of prolonged duration of untreated depression on antidepressant treatment outcome

BackgroundThe duration of untreated illness has been considered a likely predictor of the course of psychotic disorders. However, there is only sparse data concerning the influence of treatment delay on the outcome of mood disorders. The present study aimed to assess the effect of prolonged untreated depression on the outcome of antidepressant treatment. MethodPatients aged 18–70 years with recent onset of the first lifetime depressive episode were systematically recruited by the Danish Psychiatric Central Research Register during a 2-year period. A total number of 399 individuals out of 1006 potential participants in the Register were interviewed, and 270 fulfilled the inclusion criteria. The validity of the diagnosis, duration of untreated illness, remission on first-line antidepressant treatment and a number of covariates, including psychiatric co-morbidity, personality disorders and traits, stressful life events prior to onset, and family history of psychiatric illness, were assessed by structured interviews. ResultsThe remission rate was significantly decreased among patients with six months or more of untreated depression as compared to patients who were treated with antidepressant medication earlier after onset (21.1% versus 33.7%, OR=0.5, 95% CI 0.3 to 0.9, p=0.03). The negative influence of a prolonged DUI on the outcome did not seem confounded by any of a wide range of demographic and clinical variables. LimitationsThe outcome was evaluated retrospectively. The findings cannot be generalized to patients outside hospital settings. ConclusionInitiation of antidepressant treatment more than six months after onset of first episode depression reduces the chance of obtaining remission. The results emphasize the importance of early recognition and treatment of patients suffering from depression.

Depressive symptoms are associated with (sub)clinical psychotic symptoms in patients with non-affective psychotic disorder, siblings and healthy controls

Depression is a clinically relevant dimension, associated with both positive and negative symptoms, in patients with schizophrenia. However, in siblings it is unknown whether depression is associated with subclinical positive and negative symptoms. Method Depressive symptoms and their association with positive and negative symptoms were examined in 813 healthy siblings of patients with a non-affective psychotic disorder, 822 patients and 527 healthy controls. Depressive episodes meeting DSM-IV-TR criteria (lifetime) and depressed mood (lifetime) were assessed with the Comprehensive Assessment of Symptoms and History (CASH) in all three groups. In the patient group, the severity of positive and negative psychosis symptoms was assessed with the CASH. In the siblings and healthy controls, the severity of subclinical psychosis symptoms was assessed with the Community Assessment of Psychic Experiences (CAPE). Patients reported more lifetime depressed mood and more depressive episodes than both siblings and controls. Siblings had a higher chance of meeting lifetime depressive episodes than the controls; no significant differences in depressed mood were found between siblings and controls. In all three groups the number and duration of depressive symptoms were associated with (sub)clinical negative symptoms. In the patients and siblings the number of depressive symptoms was furthermore associated with (sub)clinical positive symptoms. Finally, lifetime depressed mood showed familial clustering but this clustering was absent for lifetime depressive episodes. These findings suggest that a co-occurring genetic vulnerability for both depressive and psychotic symptomatology exists on a clinical and a subclinical level.

Metabolic syndrome in bipolar disorders.

To review the data with respect to prevalence and risk factors of metabolic syndrome (MetS) in bipolar disorder patients. Electronic searches were done in PUBMED, Google Scholar and Science direct. From 2004 to June 2011, 34 articles were found which reported on the prevalence of MetS. The sample size of these studies varied from 15 to 822 patients, and the rates of MetS vary widely from 16.7% to 67% across different studies. None of the sociodemographic variable has emerged as a consistent risk factor for MetS. Among the clinical variables longer duration of illness, bipolar disorder- I, with greater number of lifetime depressive and manic episodes, and with more severe and difficult-to-treat index affective episode, with depression at onset and during acute episodes, lower in severity of mania during the index episode, later age of onset at first manic episode, later age at first treatment for the first treatment for both phases, less healthy diet as rated by patients themselves, absence of physical activity and family history of diabetes mellitus have been reported as clinical risk factors of MetS. Data suggests that metabolic syndrome is fairly prevalent in bipolar disorder patients.

Remitted major depression is characterized by reward network hyperactivation during reward anticipation and hypoactivation during reward outcomes

Although functional brain imaging has established that individuals with unipolar major depressive disorder (MDD) are characterized by frontostriatal dysfunction during reward processing, no research to date has examined the chronometry of neural responses to rewards in euthymic individuals with a history of MDD. A monetary incentive delay task was used during fMRI scanning to assess neural responses in frontostriatal reward regions during reward anticipation and outcomes in 19 participants with remitted major depressive disorder (rMDD) and in 19 matched control participants. During the anticipation phase of the task, the rMDD group was characterized by relatively greater activation in bilateral anterior cingulate gyrus, in right midfrontal gyrus, and in the right cerebellum. During the outcome phase of the task, the rMDD group was characterized by relatively decreased activation in bilateral orbital frontal cortex, right frontal pole, left insular cortex, and left thalamus. Exploratory analyses indicated that activation within a right frontal pole cluster that differentiated groups during reward anticipation predicted the number of lifetime depressive episodes within the rMDD group. Replication with larger samples is needed. Results suggest a double dissociation between reward network reactivity and temporal phase of the reward response in rMDD, such that rMDD is generally characterized by reward network hyperactivation during reward anticipation and reward network hypoactivation during reward outcomes. More broadly, these data suggest that aberrant frontostriatal response to rewards may potentially represent a trait marker for MDD, though future research is needed to evaluate the prospective utility of this functional neural endophenotype as a marker of MDD risk.

Phenomenology of psychotic mood disorders: Lifetime and major depressive episode features

The nosological and clinical implications of psychotic features in the course of mood disorders have been widely debated. Currently, no specification exists for defining a subgroup of lifetime Psychotic Mood Disorder (PMD) patients. A total of 2178 patients were examined, including subjects with Bipolar Disorder (BP) type I (n=519) and II (n=207) and Major Depressive Disorder (n=1452). Patients were divided between PMD (n=645) and non-psychotic Mood Disorders (MD) (n=1533) by the lifetime presence of at least one mood episode with psychotic features. Subjects having a depressive episode at the time of assessment were also examined: HAM-D and YMRS scores were compared between MD and PMD subjects, both with and without current psychotic features. A diagnosis of BP-I, a higher familial load for BP, a higher number of mood episodes lifetime, and a higher prevalence of OCD and somatic comorbidities were all associated to PMD. A diagnosis of BP (OR=4.48) was the only significant predictor for psychosis. PMD with non-psychotic depression were apparently less severe than MD patients and had a lower rate of "non-responders" to AD treatment. Sub-threshold manic symptoms and suicidal risk were also more pronounced among PMD. The lack of information about number and polarity of previous psychotic mood episodes may be the major limitations of our study. BP diagnosis is the most significant predictor for psychosis in mood disorders. Non-psychotic mood episodes in PMD patients may be characterized by a distinctive symptom profile and, possibly, a different response to treatment.

Early parental loss and depression history: Associations with recent life stress in major depressive disorder

Although exposure to early adversity and prior experiences with depression have both been associated with lower levels of precipitating life stress in depression, it is unclear whether these stress sensitization effects are similar for all types of stress or whether they are specific to stressors that may be particularly depressogenic, such as those involving interpersonal loss. To investigate this issue, we administered structured, interview-based measures of early adversity, depression history, and recent life stress to one hundred adults who were diagnosed with major depressive disorder. As predicted, individuals who experienced early parental loss or prolonged separation (i.e., lasting one year or longer) and persons with more lifetime episodes of depression became depressed following lower levels of life stress occurring in the etiologically-central time period of three months prior to onset of depression. Importantly, however, additional analyses revealed that these effects were unique to stressors involving interpersonal loss. These data highlight potential stressor-specific effects in stress sensitization and demonstrate for the first time that individuals exposed to early parental loss or separation, and persons with greater histories of MDD, may be selectively sensitized to stressors involving interpersonal loss.

Major depression and bipolar disorders in CADASIL: a study using the DSM-IV semi-structured interview

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microangiopathy characterized by migraine, cerebrovascular events, and cognitive impairment. Although recognized as a cardinal feature of the disease, psychiatric disturbances have rarely been the object of focused studies. We performed a structured evaluation of mood disorders in CADASIL. Twenty-three patients with CADASIL (five men and 18 women) were assessed by psychiatrists using the Structured Clinical Interview for the DSM-IV, clinician version. For the quantitative assessment of current mood disorder symptoms, the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Scale (YMRS) were used. A lifetime depressive episode was recorded in 17/23 (73.9%) patients with CADASIL. Six (26.1%) patients with CADASIL reported a current depressive episode. A diagnosis of manic lifetime episode was made in 6 (26.1%) patients with CADASIL. The HRSD mean score in patients with current depression was 9.1 ± SD 8.1. The YMRS mean score was 14.2 ± SD 4.1 for manic CADASIL. This study confirms that mood disorders are frequent in CADASIL. The use of a structured psychiatric interview outlines a frequency of depression higher than that previously reported but also reveals a considerable frequency of bipolar disorders. If confirmed in larger series, these data suggest that a greater attention should be paid to the psychiatric aspects in CADASIL.

Risk factors for postoperative depression in 150 subjects treated for drug-resistant focal epilepsy

The primary goal was to identify risk factors for post-surgical depression in subjects operated on for drug-resistant epilepsy. Secondary goals were to confirm the high rate of depression in subjects suffering from epilepsy (prior to surgery) and to look for first post-surgical depressive episode. Case series study of 150 subjects surgically treated for partial epilepsy (side of surgery: 72 right, 78 left; site of surgery: 97 Unilobar Temporal, 17 Unilobar Frontal, 14 Posterior, 22 Multilobar). All subjects routinely had three psychiatric evaluations: before surgery (baseline) and at 6 and 12 months after surgery. Psychiatric diagnoses were made according to DSM-IV-TR criteria. Bivariate (Fisher exact test and Kruskal-Wallis rank sum test) and multivariate (logistic regression model fitting) analyses were performed. Thirty-three (22%) subjects had post-surgical depressive episodes, 31 of them in the first 6 months. Fourteen out of 33 experienced depression for the first time. Post-surgical depressive episodes are not associated with gender, outcome on seizures, side/site of surgical resection, histological diagnosis, psychiatric diagnoses other than depression. Depressive episodes before surgery and older age at surgery time are risk factors for post-surgical depression (p= 0.0001 and 0.01, respectively, at logistic regression analysis). No protective factors were identified. Our data show that lifetime depressive episodes and older age at surgery time are risk factors for postsurgery depression. Moreover, a prospective study could be useful in order to assess whether depression is really a consequence of surgery.

Comorbid Anxiety in Children and Adolescents With Bipolar Spectrum Disorders

Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder. We aimed to examine the prevalence and correlates of comorbid anxiety disorders among youth with bipolar disorder. As part of the Course and Outcome of Bipolar Youth study, 446 youth, ages 7 to 17 years, who met DSM-IV criteria for bipolar I disorder (n = 260) or bipolar II disorder (n = 32) or met operationalized criteria for bipolar disorder not otherwise specified (n = 154) were included. Subjects were evaluated for current and lifetime Axis I psychiatric disorders at intake using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime version, and standardized instruments were used to assess functioning and family history. Forty-four percent (n = 194) of the sample met DSM-IV criteria for at least 1 lifetime anxiety disorder, most commonly separation anxiety (24%) and generalized anxiety disorders (16%). Nearly 20% met criteria for 2 or more anxiety disorders. Overall, anxiety disorders predated the onset of bipolar disorder. Subjects with bipolar II disorder were more likely than subjects with bipolar I disorder or bipolar disorder not otherwise specified to have a comorbid anxiety disorder. After adjusting for confounding factors, youth with bipolar disorder with anxiety were more likely to have bipolar II disorder; longer duration of mood symptoms; more severe ratings of depression; and family history of depression, hopelessness, and somatic complaints during their worst lifetime depressive episode than those without anxiety. Comorbid anxiety disorders are common in youth with bipolar disorder, and they most often predate bipolar disorder onset. Bipolar II disorder, a family history of depression, and more severe lifetime depressive episodes distinguish youth with bipolar disorder with comorbid anxiety disorders from those without. Careful consideration should be given to the assessment of comorbid anxiety in youth with bipolar disorder.

Specificity of depression following an acute coronary syndrome to an adverse outcome extends over five years

Many studies have demonstrated that depression is associated with a worse cardiovascular outcome and increased risk of death in those experiencing an acute coronary syndrome (ACS). Recent studies have suggested, however, that any association is strongly influenced by the timing of the depression, with post-ACS depression providing the greatest risk. Establishing any timing impact should assist etiological clarification. We initially recruited 489 subjects hospitalized for an ACS, assessed lifetime and current depression, and then – at 1 and 12 months – assessed subsequent depression. Subjects were followed for up to 5 years to assess cardiovascular outcome and the impact of depression at differing time points, with three defined poor outcome categories (i.e. cardiac admission and/or cardiac rehospitalization). While outcome was associated with a number of non-depression variables, a poor outcome was most clearly associated with depressive episodes emerging at the time of the ACS but with some risk affected by episodes that commenced prior to the ACS and being persistent. Neither lifetime depressive episodes nor transient depressive episodes occurring around the baseline ACS event appeared to provide any risk. Study findings indicate that any differential deleterious impact of post-ACS depression has both short-term and longer-term outcomes, and, by implicating the centrality of post-ACS depression, should assist studies seeking to identify causal explanations.

The catechol-O-methyl transferase (COMT) gene and its potential association with schizophrenia: Findings from a large German case-control and family-based sample

The aim of the present study was to investigate possible associations between schizophrenia and 13 SNP markers in COMT. No association was observed in 631 cases, 207 nuclear families, and 776 controls. A cognitive performance phenotype (Trail Marking Test) was available for a subgroup of the patients. No association was found between the 13 markers and this phenotype. Four clinically-defined subgroups (early age at onset, negative symptoms, family history of schizophrenia, and life-time major depressive episode) were also investigated. Associations were observed for 3 of these subgroups, although none withstood correction for multiple testing. COMT does not appear to be a risk factor for schizophrenia in this population.

A population-based analysis of distinguishers of bipolar disorder from major depressive disorder

BackgroundMany people with bipolar disorder (BD) in the community are misdiagnosed with major depressive disorder (MDD). A probabilistic model has been proposed to assist in the identification of BD among patients with depressive symptoms, however there are limited population-based data on the key distinguishers of BD from MDD. The objective of this study was to identify distinguishers of BD from MDD in a population-based sample. MethodsPopulation-based data were extracted from the Canadian Community Health Survey: Mental Health and Well-Being. Sociodemographic variables, clinical variables, and depressive symptomatology were compared between subjects with BD (N=467) and MDD (N=4145). Logistic regression analysis was used to identify significant correlates of BD, and areas under the receiver operating characteristic curves (AUCs) were determined for each model. ResultsBD and MDD subjects differed across a number of characteristics. Clinical variables significantly associated with BD included greater number of lifetime depressive episodes, earlier age of first depressive episode, lifetime anxiety disorder, problematic substance use, and lifetime suicide attempt. Symptoms significantly more common during a major depressive episode among BD subjects included agitation, suicidal ideation, anxious symptoms, and irritability. AUCs for these models ranged from 0.72 to 0.81. LimitationsData were not available for all potential distinguishers; subgroups of BD could not be determined; cross-sectional data. ConclusionsThese population-based results reinforce the effort to establish a generalizable probabilistic model that incorporates clinical and symptom variables in order to assist clinicians in the diagnostic assessment of BD.

Unmet Need for Treatment of Major Depression in the United States

This study examined the extent and correlates of perceived unmet need for treatment among individuals with depression in the U.S. general population. Analyses were based on a representative sample of 6,510 adult participants in the 2005 and 2006 National Surveys on Drug Use and Health who reported a major depressive episode in the past 12 months. A total of 3,568 (62.4%) participants had sought mental health treatment in the past 12 months, and 2,942 (37.6%) had not; 34.9% and 26.8% of these groups, respectively, reported unmet need for treatment. In both groups, older age was associated with a lower likelihood of reporting unmet need for treatment, whereas greater distress and impairment and higher education were associated with a greater likelihood of reporting unmet need. Among treatment seekers, treatment from general medical providers was associated with greater likelihood of unmet need, and more outpatient visits and insurance coverage for the full year were associated with a lower likelihood of unmet need. The most common reason for not seeking needed treatment was a concern about costs (cited as a reason by 46.0% of the total sample). Even though rates of treatment seeking have increased, many persons with major depression continue to experience unmet need for treatment, which in this study was mainly attributable to concerns about treatment costs.

Depressive illness burden associated with complex polypharmacy in patients with bipolar disorder: findings from the STEP-BD.

Many patients with bipolar disorder receive multi-drug treatment regimens, but the distinguishing profiles of patients who receive complex pharmacologies have not been established. Prescribing patterns of lithium, anticonvulsants, antidepressants, and antipsychotics were examined for 4,035 subjects with bipolar disorder (DSM-IV) immediately prior to entering the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Subjects were recruited for participation across 22 centers in the United States between November 1999 and July 2005. The quality receiver operating characteristic (ROC) method was used to develop composite profiles of patients receiving complex regimens (p < .01 for all iterations). Use of 3 or more medications occurred in 40% of subjects, while 18% received 4 or more agents. Quality ROC analyses revealed that subjects had a 64% risk for receiving a complex regimen (> or = 4 medications) if they had (1) ever taken an atypical antipsychotic, (2) > or = 6 lifetime depressive episodes, (3) attempted suicide, and (4) an annual income > or = $75,000. Complex polypharmacy was least often associated with lithium, divalproex, or carbamazepine and most often associated with atypical antipsychotics or antidepressants. Contrary to expectations, a history of psychosis, age at onset, bipolar I versus II subtype, history of rapid cycling, prior hospitalizations, current illness state, and history of alcohol or substance use disorders did not significantly alter the risk profiles for receiving complex regimens. Complex polypharmacy involving at least 4 medications occurs in approximately 1 in 5 individuals with bipolar disorder. Use of traditional mood stabilizers is associated with fewer cotherapies. Complex regimens are especially common in patients with substantial depressive illness burden and suicidality, for whom simpler drug regimens may fail to produce acceptable levels of response. clinicaltrials.gov Identifier: NCT00012558.

Community Participation and the Emergence of Late-Life Depressive Symptoms: Differences between Women and Men

To understand the role of community participation in prevention of first lifetime depressive episode in older women and men. We used data from the Wisconsin Longitudinal Study to identify variables that predicted risk for the emergence of depressive symptoms and tested a hypothesis that community participation would protect women from depression more than it would protect men. The sample was drawn from Wisconsin high school graduates who were approximately 64-66 years of age in the 2003-2005 data collection period (n = 2546 with complete data meeting inclusion criteria.) The sample consisted of persons who had no evidence of current or prior lifetime depression in the 1993 data collection period. The emergence of high depressive symptoms was examined for women and men as a function of community participation and other covariates, including social support. The emergence of depressive symptoms for both sexes was predicted by poorer reported health status and higher levels of subthreshold depressive symptoms during the previous interview. For men, additional risk factors were pain and low income. For women, additional risks were widowhood, lower education, and lower community participation. Community participation, in the form of volunteering, religious attendance, and engagement in community organizations, is related to reduced risk of first-time depressive symptoms among older women.

Personality and risk for depression in a birth cohort of 70-year-olds followed for 15 years

The association between personality traits and the first lifetime onset of clinically significant depression has not been studied in older adults. Experienced psychiatrists conducted interviews and chart reviews at baseline and throughout the 15-year follow-up period. Survival analyses were conducted on the presence/absence of a DSM-III-R mood disorder at follow-up. There were 59 cases of first lifetime episodes of depression. Analyses showed that Neuroticism [hazard ratio (HR) per one point increase in the Maudsley Personality Inventory (MPI)=1.05, 95% confidence interval (CI) 1.02-1.08] but not Extroversion (HR 1.02, 95% CI 0.97-1.06) amplified risk for mood disorder. This prospective study on a randomly sampled birth cohort of older adults showed that Neuroticism confers risk for a first lifetime episode of clinically significant depression. Findings have implications for understanding the etiology of late-life depression (LLD) and could also aid in the identification and treatment of people at risk.

A Comparison of Factors Associated With Substance-Induced Versus Independent Depressions

This article expands on the results from a 1997 report from the Collaborative Study on the Genetics of Alcoholism (COGA), using a new phase of the protocol to evaluate the prevalence and characteristics of substance-induced and independent major depressive episodes (MDEs) in a population of alcoholics and nonalcoholics. Data were evaluated from Phase II of the six-center-wide COGA investigation using information gathered beginning in January 1997. Data were generated through face-to-face evaluations using the updated version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA-II) interview, with distinctions between substanceinduced and independent MDEs based on the chronology of development of full depressive syndromes. The analyses focused on the 2,548 men and women who were divided into 351 individuals who had only an independent MDE (Group 1), 238 subjects who experienced only substance-induced MDEs, and 1,959 individuals with no MDE history. The two MDE groups were similar in age, marital status, and religion; but those with substance-induced depressions (Group 2) were more likely to be original alcoholic probands, be males, be nonwhite, and have less education. They were also more likely to have alcohol, drug, or antisocial personality diagnoses and to report higher maximum drinks. In addition, only Group 2 subjects reported an elevated family history of alcohol diagnoses compared with the nondepressed Group 3. Subjects with independent MDEs were different from the comparison Group 3 regarding the family histories of independent MDEs. However, symptoms during the worst depressive episode were quite similar across Groups 1 and 2. This study corroborates a high rate of substance-induced MDEs among alcoholics, with these disorders explaining about half of the lifetime depressive episodes. The results also support the validity of the distinction between substance-induced and independent depressions regarding external validators of gender, substance-use patterns, and family histories of independent MDEs.

Course and Severity of Maternal Depression: Associations with Family Functioning and Child Adjustment.

Number of lifetime episodes, duration of current episode, and severity of maternal depression were investigated in relation to family functioning and child adjustment. Participants were the 151 mother-child pairs in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) child multi-site study. Mothers were diagnosed with Major Depressive Disorder; children (80 males and 71 females) ranged in age from 7 to 17 years. Measures of child adjustment included psychiatric diagnoses, internalizing and externalizing symptoms, and functional impairment. Measures of family functioning included family cohesion, expressiveness, conflict, organization, and household control; parenting measures assessed maternal acceptance and psychological control. Children of mothers with longer current depressive episodes were more likely to have internalizing and externalizing symptoms, with this association being moderated by child gender. Mothers with more lifetime depressive episodes were less likely to use appropriate control in their homes.

Eating disorders and illness burden in patients with bipolar spectrum disorders

Objectives The objectives of the study were to evaluate the clinical significance of lifetime eating disorder comorbidity in a well-defined sample of patients with bipolar spectrum disorders and to describe cognitive correlates of disordered eating in this group. Method Twenty-six bipolar patients with a lifetime history of a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)–defined eating disorder (n = 17) or a clinically significant subthreshold eating disorder (n = 9) (ED group) were compared with 46 bipolar patients with no history of an eating disorder (no-ED group) on demographic and clinical characteristics at study presentation, history of bipolar illness, and other psychiatric comorbidity. Measures included the Structured Clinical Interview for the DSM-IV Axis I Disorders, the Clinical Global Impression–Severity Scale–Bipolar Version (CGI-S-BP), and the Eating Disorder Examination. Height and weight were recorded to calculate body mass index. Results Patients in the ED group were heavier and were rated as more symptomatic on the CGI-S-BP than were patients in the no-ED group. The ED group also had a higher number of lifetime depressive episodes and greater psychiatric comorbidity, excluding eating and mood disorders. Finally, after controlling for body mass index and CGI-S-BP rating, patients in the ED group had significantly higher Eating Disorder Examination Restraint, Eating Concern, Shape Concern, Weight Concern, and Global scores than did patients in the no-ED group. Conclusions These findings highlight the need for a renewed emphasis on the evaluation and management of weight and eating in the mood disorders. In particular, this research suggests that eating disorder comorbidity may be a marker for increased symptom load and illness burden in bipolar disorder.

Stressful life events and depressive problems in early adolescent boys and girls: The influence of parental depression, temperament and family environment

Background Stressful life events increase the probability of depressive problems in early adolescence. Several genetic and environmental risk factors may change individual sensitivity to the depressogenic effect of these events. We examined modification by parental depression and gender, and mediation of the former by temperament and family environment. Methods Data were collected as part of a longitudinal cohort study of (pre)adolescents ( n = 2127). During the first assessment wave at approximately age 11, we assessed parental depression, family functioning, perceived parenting behaviours, and temperamental frustration and fearfulness. At the second wave, about two and a half years later, stressful life events between the first and second assessment were assessed. Depressive problems were measured at both waves. Results Adolescents with parents who had a (lifetime) depressive episode were more sensitive to the depressogenic effect of stressful events than adolescents without depressed parents. Furthermore, girls are more sensitive to these effects than boys. The modifying effect of parental depression was not mediated by temperament, family functioning and perceived parenting. Limitations Life events were assessed without consideration of contextual information. Depressive problems were measured by questionnaires that did not directly represent DSM-IV criteria. The measure of parental depression was unspecific regarding severity and timing of depressive episodes. Conclusion The results suggest that gender and parental depression are associated with increased sensitivity to depression after experiencing stressful life events during adolescence.