Recurrent Major Depression Research Articles

Perceived parenting and risk for major depression in Chinese women.

BackgroundIn Western countries, a history of major depression (MD) is associated with reports of received parenting that is low in warmth and caring and high in control and authoritarianism. Does a similar pattern exist in women in China?MethodReceived parenting was assessed by a shortened version of the Parental Bonding Instrument (PBI) in two groups of Han Chinese women: 1970 clinically ascertained cases with recurrent MD and 2597 matched controls. MD was assessed at personal interview.ResultsFactor analysis of the PBI revealed three factors for both mothers and fathers: warmth, protectiveness, and authoritarianism. Lower warmth and protectiveness and higher authoritarianism from both mother and father were significantly associated with risk for recurrent MD. Parental warmth was positively correlated with parental protectiveness and negatively correlated with parental authoritarianism. When examined together, paternal warmth was more strongly associated with lowered risk for MD than maternal warmth. Furthermore, paternal protectiveness was negatively and maternal protectiveness positively associated with risk for MD.ConclusionsAlthough the structure of received parenting is very similar in China and Western countries, the association with MD is not. High parental protectiveness is generally pathogenic in Western countries but protective in China, especially when received from the father. Our results suggest that cultural factors impact on patterns of parenting and their association with MD.

Childhood sexual abuse and the risk for recurrent major depression in Chinese women.

BackgroundStudies in Western countries have repeatedly shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in China?MethodThree levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 1970 clinically ascertained with recurrent MD and 2597 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression and regression coefficients by linear or Poisson regression.ResultsAny form of CSA was significantly associated with recurrent MD [OR 3.26, 95% confidence interval (CI) 1.95–5.45]. This association strengthened with increasing CSA severity: non-genital (OR 2.47, 95% CI 1.17–5.23), genital (OR 2.77, 95% CI 1.32–5.83) and intercourse (OR 13.35, 95% CI 1.83–97.42). The association between any form of CSA and MD remained significant after accounting for parental history of depression, childhood emotional neglect (CEN), childhood physical abuse (CPA) and parent–child relationship. Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes and an increased risk for generalized anxiety disorder (GAD; OR 1.92, 95% CI 1.39–2.66) and dysthymia (OR 2.16, 95% CI 1.52–3.09).ConclusionsIn Chinese women CSA is strongly associated with MD and this association increases with greater severity of CSA. Depressed women with CSA have an earlier age of onset, longer depressive episodes and increased co-morbidity with GAD and dysthymia. Although reporting biases cannot be ruled out, our results are consistent with the hypothesis that, as in Western countries, CSA substantially increases the risk for MD in China.

The relationship between neuroticism, major depressive disorder and comorbid disorders in Chinese women

ObjectiveThe personality trait of neuroticism is a risk factor for major depressive disorder (MDD), but this relationship has not been demonstrated in clinical samples from Asia.MethodsWe examined a large-scale clinical study of Chinese Han women with recurrent major depression and community-acquired controls.ResultsElevated levels of neuroticism increased the risk for lifetime MDD (with an odds ratio of 1.37 per SD), contributed to the comorbidity of MDD with anxiety disorders, and predicted the onset and severity of MDD. Our findings largely replicate those obtained in clinical populations in Europe and US but differ in two ways: we did not find a relationship between melancholia and neuroticism; we found lower mean scores for neuroticism (3.6 in our community control sample).LimitationsOur findings do not apply to MDD in community-acquired samples and may be limited to Han Chinese women. It is not possible to determine whether the association between neuroticism and MDD reflects a causal relationship.ConclusionsNeuroticism acts as a risk factor for MDD in Chinese women, as it does in the West and may particularly predispose to comorbidity with anxiety disorders. Cultural factors may have an important effect on its measurement.

Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms

Because of the high costs associated with ascertainment of families most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. While microsatellite markers spaced every 10 centimorgans typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carry out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 SNPs. Of the ~1100 families, 972 were informative for further analyses and mean information content was 0.86 after pruning for LD. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with Bipolar II disorder (BPII) and 702 subjects with Recurrent Major Depression. Three affection status models were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus Recurrent Major Depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (Nonparametric Pairs Lod 3.4 for rs1046943 at 119 cM) and 9q21 (Nonparametric Pairs Lod 3.4 for rs722642 at 78 cM) using only BPI and SA, BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis we observed 59 parametric lods of 2 or greater, many of which are likely to be close to maximum possible scores. While some linkage findings may be false positives the results could help prioritize the search for rare variants using whole exome or genome sequencing.

Prolonged Impairment in Inhibition and Semantic Fluency in a Follow-up Study of Recurrent Major Depression

Several studies have demonstrated impaired performance in inhibition and semantic fluency in the acute phase of illness in patients with recurrent major depression. However, few studies have investigated these functions longitudinally, focusing on how these impairments relate to symptoms over time. The present longitudinal study investigated whether the specific impairment in inhibition and semantic fluency seen in the acute phase of Major Depressive Disorder (MDD) was prolonged or normalized with symptom reduction in a 9-month follow-up. Twenty recurrent major depressive patients and 19 control subjects were included in the study. Inhibition and semantic fluency were investigated using tests from the Delis-Kaplan Executive Function System. The results show that the patient group still had significantly lower scores in inhibition and semantic fluency compared with the control group despite significant symptom reduction. Further, the results show that impaired inhibition in the acute phase was strongly correlated with impaired inhibition in the follow-up, suggesting that the inability to inhibit may represent a trait marker in recurrent MDD.

A follow‐up case–control association study of tractable (druggable) genes in recurrent major depression

The High-Throughput Disease-specific target Identification Program (HiTDIP) aimed to study case-control association samples for 18 common diseases. Here we present the results of a follow-up case-control association study of HiTDIP in major depressive disorder (MDD). The HiTDIP in MDD was conducted in a sample of 974 cases of recurrent MDD of white German origin collected at the Max-Planck Institute (MP-GSK) and 968 ethnically matched controls screened for lifetime absence of depression. Six genes were identified as of interest for a follow-up, based on the strength of the association and based on the interest as potential candidate target for developing new treatment for depression: Solute Carrier Family 4 Member 10 (SLC4A10), Dipeptidyl Peptidase IV (DPP4), Dopamine Receptor D3 (DRD3), Zinc Finger Protein 80 (ZNF80), Nitric Oxide Synthase 2A (NOS2A) and Peroxisome Proliferator-Activated Receptor-Gamma, Coactivator 1, Alpha (PPARGC1A). Within the current study, we attempted to follow-up these findings in a sample from the UK, the Depression Case Control (DeCC) sample consisting of 1,196 cases and 842 screened controls, phenotyped using exactly the same methods as the MP-GSK sample. Performing Cochran-Mantel-Haenzel statistics to test for genotypic and/or allelic differences between the DeCC and MP-GSK samples, we found no significant differences, thus being able to combine the two samples for association testing. In the combined sample of 2,170 MDD cases and 1,810 controls, there were positive findings in the Nitric Oxide Synthase 2A (NOS2A) gene both using single SNP analysis and haplotype analysis.

A genome-wide significant linkage for severe depression on chromosome 3: the depression network study.

The purpose of this study was to find loci for major depression via linkage analysis of a large sibling pair sample. The authors conducted a genome-wide linkage analysis of 839 families consisting of 971 affected sibling pairs with severe recurrent major depression, comprising waves I and II of the Depression Network Study cohort. In addition to examining affected status, linkage analyses in the full data set were performed using diagnoses restricted by impairment severity, and association mapping of hits in a large case-control data set was attempted. The authors identified genome-wide significant linkage to chromosome 3p25-26 when the diagnoses were restricted by severity, which was a maximum LOD score of 4.0 centered at the linkage marker D3S1515. The linkage signal identified was genome-wide significant after correction for the multiple phenotypes tested, although subsequent association mapping of the region in a genome-wide association study of a U.K. depression sample did not provide significant results. The authors report a genome-wide significant locus for depression that implicates genes that are highly plausible for involvement in the etiology of recurrent depression. Despite the fact that association mapping in the region was negative, the linkage finding was replicated by another group who found genome-wide-significant linkage for depression in the same region. This suggests that 3p25-26 is a new locus for severe recurrent depression. This represents the first report of a genome-wide significant locus for depression that also has an independent genome-wide significant replication.

Interleukin-1beta Promoter (−31T/C and −511C/T) Polymorphisms in Major Recurrent Depression

To elucidate a genetic predisposition to major depressive disorder, we investigated two polymorphisms (−31T/C and −511C/T) in the interleukin-1beta promoter region in patients who suffered from major recurrent depression. The aim of the current work was to compare alleles and genotype layout between patients with major recurrent depression and healthy people. We would like to indicate such combination of genotypes which corresponds with major recurrent depression. Correlations between genotypes for analyzed polymorphisms and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset were investigated as well. The study group consisted of 94 patients diagnosed with major recurrent depression. The control group included 206 healthy individuals. Both groups involved representatives of Caucasian population. Genotyping of polymorphisms was performed by using PCR-RFLP technique. A specific haplotype, composed of the C allele at −31 and the T allele at −511, has a tendency to have a statistically significant difference (p = 0.064) between patients and control group. Correspondence analysis revealed that genotype T/T at −31 and genotype C/C at −511 are associated with major recurrent depression. No association was found between genotypes for studied polymorphic sites and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset.

False recognition in women with a history of childhood emotional neglect and diagnose of recurrent major depression

While previous research has suggested that adults with a history of childhood sexual abuse may be more prone to produce false memories, little is known about the consequences of childhood neglect on basic memory processes. For this reason, the authors investigated how a group of women with a history of childhood emotional neglect (CEN) and diagnosed with recurrent Major Depressive Disorder (MDD) performed on the Deese-Roediger-McDermott paradigm in comparison to control groups. The results indicated that women with MDD and CEN were actually less prone to produce false memories relative to both women with MDD but no CEN and healthy women without MDD and any form of childhood maltreatment. These findings were explained in terms of the inability to extract/retrieve gist memories that support false recognition of critical lures, an explanation that seems to fit well with emerging MRI findings linking childhood neglect to reduced volume of brain regions associated to memory function.

Methylphenidate for Chronic Migraine and Cluster-Type Headaches: A Case Report

Objective: To report the successful treatment of a case of chronic, treatment-resistant migraine and cluster headaches that started after an accidental exposure to toxic gas in a patient with recurrent major depression, hypersomnia, and chronic fatigue. Case Summary: A 50-year-old female presented with a 32-year history of recurrent major depression, hypersomnia, and chronic fatigue in addition to migraine and cluster headaches that started after accidental exposure to toxic gas during an army training exercise. The frequent and severe headaches led to discharge from the army and to the patient's being fired from multiple jobs due to repeated absences. She became depressed, with hypersomnia and chronic fatigue, spending most of the day in bed for about 2 decades. This also interfered with her partner relationship. She had received tricyclic antidepressants (TCAs), anticonvulsants, triptans, migraine agents, nonsteroidal antiinflammatory drugs, and biofeedback for the headaches, all without lasting benefit. Medications for depression had included TCAs, serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors without resolution of chronic depression. Treatment for depression and fatigue began with titration of citalopram to 60 mg daily, followed by titration of bupropion SA to 300 mg in the morning and 150 mg in the afternoon. Her mood improved; however, the hypersomnia and fatigue remained along with the chronic migraine and cluster headaches. Methylphenidate immediate release was added to reduce the hypersomnia and fatigue, and her headaches markedly decreased. The patient apparently stopped taking the prescribed methylphenidate due to medication name confusion with medroxyprogesterone, and the migraine and cluster headaches returned to their prior level of severity. Methylphenidate was retitrated to 15 mg twice/day with resolution of the chronic migraine and cluster headaches, hypersomnia, and fatigue. Discussion: The literature on the use of methylphenidate, a methyl α-phenyl-2-piperidineacetate hydrochloride, for headache treatment and prophylaxis consists of 1 other case report. Methylphenidate stimulates the central nervous system, increasing norepinephrine and dopamine levels by impeding uptake and increasing release. By augmenting dopamine and norepinephrine levels in the medial prefrontal cortex and hypothalamus, methylphenidate may modulate depression and somnolence. Methylphenidate may also alter brain stem serotoninergic action, resulting in methylphenidate-mediated analgesia, perhaps modulating headache symptoms. Conclusions: Methylphenidate may have an application as a third- or fourth-tier medication for headache treatment and prophylactic action in selected treatment-resistant cases. Response appears to be dose-related.

Tinnitus as a Symptom of Psychotic Depression Successfully Treated With Electroconvulsive Therapy

We present the case of a 51-year-old woman with recurrent major depression with psychotic features including severe tinnitus. Her tinnitus resolved with successful treatment of her depressive episode with electroconvulsive therapy. We review the literature on electroconvulsive therapy and tinnitus.

P01-211 - Selective effect of paternal age on age-of-onset in bipolar i disorder

ObjectiveThe study investigated the effect of the parental age on the age-of-onset (AO) in bipolar I disorder (BPI) in connection with proband gender and family history for major psychoses in a directly interviewed sample of 530 BPI probands.MethodAll 530 probands, 73.0% of their first-degree and 22.62% of their second-degree relatives were administered the DIGS and FIGS interviews. The family history (FH) method was used for unavailable relatives. The impact of parental age on proband early/late AO was evaluted through logistic regressions. The commingling analysis (SAGEv6.1-software) was used to determine the cut-off age separating the early/late AO.ResultsWe evidenced a significant influence of the paternal age ≥ 35 years on AO in BPI disorder in the total sample (p = 0.023) and in some subgroups defined by positive/negative FH for major psychoses: the sporadic group (p = 0.035) and the group with FH of recurrent unipolar major depression (Mdd-RUP) (p = 0.041). No effect of the paternal/maternal age on disease AO was found in patients with FH of bipolar/schizoaffective disorders/schizoprenia (BP/SA/SCZ). The global significant effect of the advancing paternal age on the decreasing proband AO was generated by female patients (p = 0.022). No effect of the paternal/maternal age on disease AO was found in male patients. Paternal age was older in fathers of sporadic cases and of cases with FH of Mdd-RUP than in cases with FH of BP/SA/SCZ (p = 0.011).ConclusionWe evidenced a selective effect of the advancing paternal age on bipolar onset depending on offspring gender and type of FH for major psychoses.

Are atypical depression, borderline personality disorder and bipolar II disorder overlapping manifestations of a common cyclothymic diathesis?

The constructs of atypical depression, bipolar II disorder and borderline personality disorder (BPD) overlap. We explored the relationships between these constructs and their temperamental underpinnings. We examined 107 consecutive patients who met DSM-IV criteria for major depressive episode with atypical features. Those who also met the DSM-IV criteria for BPD (BPD+), compared with those who did not (BPD-), had a significantly higher lifetime comorbidity for body dysmorphic disorder, bulimia nervosa, narcissistic, dependent and avoidant personality disorders, and cyclothymia. BPD+ also scored higher on the Atypical Depression Diagnostic Scale items of mood reactivity, interpersonal sensitivity, functional impairment, avoidance of relationships, other rejection avoidance, and on the Hopkins Symptoms Check List obsessive-compulsive, interpersonal sensitivity, anxiety, anger-hostility, paranoid ideation and psychoticism factors. Logistic regression revealed that cyclothymic temperament accounted for much of the relationship between atypical depression and BPD, predicting 6 of 9 of the defining DSM-IV attributes of the latter. Trait mood lability (among BPD patients) and interpersonal sensitivity (among atypical depressive patients) appear to be related as part of an underlying cyclothymic temperamental matrix.

Phenomenological differences between acute and chronic forms of major depression in inpatients

Background. Chronic forms of depression are highly prevalent especially in inpatient settings. Defined only by episode duration greater than 2 years, heterogeneous diagnoses like dysthymic disorder, double depression, major depression and recurrent major depression are included. Chronic depression is considered difficult to treat, although its distinguishing characteristics remain unclear. Aims. The purpose of the present study was empirically to approach proposed differences between acute and chronic forms of depression. Methods. 80 psychiatric inpatients positively screened for depression and diagnosed with the Composite International Diagnostic Interview (CIDI), completed a set of questionnaires regarding symptom severity (a simplified version of the Beck Depression Inventory), dysfunctional attitudes (Dysfunctional Attitudes Scale), ruminative response style (Response Styles Questionnaire, Why Ruminate Scale) and interpersonal problems (Inventory of Interpersonal Problems; IIP). Results. 30 patients were diagnosed with chronic forms of depression; 34 patients with acute depression. Patients did not differ regarding symptom severity, ruminative response styles, all but one subscales of the IIP or presence of comorbid post-traumatic stress disorder. However, chronic depression did show higher dysfunctional attitudes than acute depression, and reported higher rates of socially avoidant behavior. Conclusions. In line with previous findings, acute and chronic forms of depression differed in dysfunctional attitudes, which might actually reflect a distinguishing pattern of chronicity. Chronic depression patients also reported higher socially avoidant behavior, which might be crucial to focus in treatment. Surprisingly, other variables that are assumed to characterize chronic depression could not be confirmed as distinguishing features. Future research should take etiological aspects into account.

Recurrent major depression, ataxia, and cardiomyopathy: association with a novel POLG mutation?

At present, more than 100 disease mutations in mitochondrial DNA polymerase γ (POLG) have been indentified that are causally related to an array of neuropsychiatric diseases affecting multiple systems. Both autosomal recessive and autosomal dominant forms can be delineated, the latter being associated with Parkinsonism and depressive or psychotic syndromes. In this report, a middle-aged female patient with recurrent major depression with melancholic features, slowly progressive gait instability, and dilated cardiomyopathy is described. Detailed diagnostic evaluation was performed to elucidate the supposed relationship between ataxia, cardiomyopathy, and major depression with melancholia. After extensive genetic and metabolic investigation, a nucleotide substitution c.2207 A→G in the POLG gene resulting in amino acid change Asn 736Ser in exon 13 was demonstrated. This mutation was considered to be compatible with a mitochondrial disorder and implicated in the pathophysiology of the neuropsychiatric syndrome. It is concluded that this novel POLG mutation forms the most parsimonious etiological explanation for the here-described combination of ataxia, major depression, and cardiomyopathy. Therefore, in patients with a complex neuropsychiatric presentation, extensive diagnostic analysis is warranted, including the search for mitochondriopathies, in order to avoid unnecessary delay of adequate treatment.

Recurrence in major depression: A conceptual analysis.

Theory and research on major depression have increasingly assumed a recurrent and chronic disease model. Yet not all people who become depressed suffer recurrences, suggesting that depression is also an acute, time-limited condition. However, few if any risk indicators are available to forecast which of the initially depressed will or will not recur. This prognostic impasse may be a result of problems in conceptualizing the nature of recurrence in depression. In the current paper we first provide a conceptual analysis of the assumptions and theoretical systems that presently structure thinking on recurrence. This analysis reveals key concerns that have distorted views about the long-term course of depression. Second, as a consequence of these theoretical problems we suggest that investigative attention has been biased toward recurrent forms of depression and away from acute, time-limited conditions. Third, an analysis of how these theoretical problems have influenced research practices reveals that an essential comparison group has been omitted from research on recurrence: people with a single lifetime episode of depression. We suggest that this startling omission may explain why so few predictors of recurrence have as yet been found. Finally, we examine the reasons for this oversight, document the validity of depression as an acute, time-limited disorder, and provide suggestions for future research with the goal of discovering early risk indicators for recurrent depression.

Unexplained Somatic Symptoms during Major Depression: Prevalence and Clinical Impact in a National Sample of Italian Psychiatric Outpatients

Background: The aim of this study was to explore the prevalence and impact of unexplained somatic symptoms during major depression. Sampling and Methods: A total of 560 consecutive outpatients with a major depressive episode according to the DSM-IV (text revision) were evaluated in 30 psychiatric facilities throughout Italy. ‘Unexplained’ somatic symptoms were evaluated using the 30-item Somatic Symptoms Checklist (SSCL-30). Somatic symptoms were considered explained if they were best accounted for as coming from a concomitant physical illness or side effects. Patients evaluated their own mood symptomatology using the Zung questionnaires for depression and anxiety and the Hypomania Checklist-32. Results: According to the SSCL-30, only 90 subjects (16.1%) had no unexplained somatic symptoms, while 231 (41.3%) had 1–5 unexplained symptoms and 239 (42.7%) had more than 5. Asthenia was the most commonly observed unexplained somatic symptom (53% of patients). Unexplained somatic symptoms were more common in females and among those suffering from major depression and depression not otherwise specified rather than in patients with recurrent major depression and bipolar disorders. No relationship between unexplained somatic symptoms and hypomanic features was observed. Conclusions: The presence of a large number of unexplained somatic symptoms is associated with more severe depression and higher rates of misdiagnosis and inappropriate treatment.

Acoustic Neuroma Identified After Electroconvulsive Therapy in a Patient With Recurrent Major Depression and Undifferentiated Somatoform Disorder

Little is known about the safety of electroconvulsive therapy (ECT) in patients with brain tumors, especially in patients with acoustic neuroma, which is difficult to diagnose early. For patients with somatoform disorder, physicians may alter the sensitivity to the somatic complaints, making it even more difficult to make an early diagnosis of "silent" brain tumors. This report describes a rare case involving treatment of refractory major depression and somatoform disorder that developed into increased intracranial pressure after ECT, possibly due to an undiagnosed acoustic neuroma. It is suggested that for patients with refractory major depression with somatoform disorders, the threshold of suspicion for silent tumors should be lowered and pre-ECT brain imaging study should be performed, specifically when the pattern of symptoms of the central nervous system-related somatoform syndrome changes.

Deep Brain Stimulation for Treatment-Resistant Depression

Brian did reasonably well for about 3 years, with occasional worsening of depressive symptoms but generally with good functioning, when he developed his current major depressive episode. This was his most severe episode to date, with active suicidal ideation with a plan (but no immediate intent) to shoot himself. Over the next year, he had a number of treatments, among them multiple antidepressant medications, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, mirtazapine, tricyclic antidepressants, and tranylcypromine, as well as augmentation with lithium, thyroid hormone, buspirone, atypical antipsychotics, anticonvulsants, stimulants, light therapy, and ongoing psychotherapy. No treatment was able to achieve remission or a persistent clinically signifi cant reduction in symptoms. Given his degree of treatment resistance and continued overall deterioration, including increased suicidal ideation, he was referred for ECT. He achieved a good response (50%‐60% symptom reduction) with eight highdose right unilateral ECT treatments. ECT was delivered concurrently with ongoing medications, and attempts were made to optimize medications during and after ECT. However, Brian relapsed in about 6 weeks, and repeat ECT (including four right unilateral and eight bitemporal treatments delivered concurrently with ongoing medications) was unsuccessful in achieving signifi cant symptom reduction but was associated with notable cognitive impairment.

Effectiveness of psychotherapeutic, pharmacological, and combined treatments for chronic depression: a systematic review (METACHRON).

BackgroundChronic depressions represent a substantial part of depressive disorders and are associated with severe consequences. Several studies were performed addressing the effectiveness of psychotherapeutic, pharmacological, and combined treatments for chronic depressions. Yet, a systematic review comparing the effectiveness of multiple treatment options and considering all subtypes of chronic depressions is still missing.Methods/DesignAim of this project is to summarize empirical evidence on efficacy and effectiveness of treatments for chronic depression by means of a systematic review. The primary objectives of the study are to examine, which interventions are effective; to examine, if any differences in effectiveness between active treatment options exist; and to find possible treatment effect modifiers. Psychotherapeutic, pharmacological, and combined treatments will be considered as experimental interventions and no treatment, wait-list, psychological/pharmacological placebo, treatment as usual, and other active treatments will be seen as comparators. The population of patients will include adults with chronic major depression, dysthymia, double depression, or recurrent depression without complete remission between episodes. Outcomes of the analyses are depressive symptoms, associated consequences, adverse events, and study discontinuation. Only randomized controlled trials will be considered.DiscussionGiven the high prevalence and serious consequences of chronic depression and a considerable amount of existing primary studies addressing the effectiveness of different treatments the present systematic review may be of high relevance. Special attention will be given to the use of current methodological standards. Findings are likely to provide crucial information that may help clinicians to choose the appropriate treatment for chronically depressed patients.