Chronic Depressive Episodes Research Articles

Possibilities and limitations of antidepressant use to correct depressive and negative symptoms in schizophrenia

The purpose of this review is to analyze approaches to the treatment of depressive and negative disorders in schizophrenia in terms of their level of efficacy and safety. Materials and Methods: A search was conducted for full-text articles published over the last 10 years in PubMed, Springer, Wiley Online Library, Taylor & Francis Online, APA PsycInfo, CORE, Science Direct, and eLIBRARY.RU databases. Several articles published previously to this period were also included into the review due to their high scientific value. Results: Our review suggests that antidepressants (ADs) are effective medications and they can be prescribed to correct depressive disorders and negative symptoms in patients with schizophrenia when used in combination with antipsychotics (АPs). However, when administering ADs and АPs combinations, it is important to consider the safety profile of these combinations as well as their tolerance. Negative symptoms of schizophrenia, including those induced by a number of АP, are less amenable to correction by АDs monotherapy, which requires a long period of АPs (on average - 8 weeks), which can be limited in the real life of the patient outside the hospital. Current approaches to the therapy of depressive disorders in patients suffering from schizophrenia vary from country to country. However, most of АDs used in clinical psychiatric practice are widely used in the comorbid state under consideration. Conclusion: The efficacy and safety of АDs of the different classes considered in this review depends on their mechanisms of action, duration of admission, type of АPs taken, and specific clinical situation (acute depressive disorder, major depressive episode, or chronic depressive episode). Most promising in clinical practice are serotonin–norepinephrine reuptake inhibitors (SNRIs) and dual ADs. The use of tricyclic antidepressants (TCAs) is limited due to a higher risk of adverse drug reactions (ADRs). The use of most selective serotonin reuptake inhibitors (SSRIs) is limited due to the risk of aggravation of hallucinations (this risk being higher for patients with visual hallucinations, and lower for those with auditory hallucinations) and\or iatrogenic psychosis. These ADRs may probably occur in patients suffering from schizophrenia due to their ideal "poor metabolizer" pharmacogenetic profile, since most of the drugs considered in this review have hepatic metabolism.

Cannabis and cannabidiol (CBD) for the treatment of fibromyalgia.

Fibromyalgia is a complex disease process that is as prevalent as it is poorly understood. Research into the pathophysiology is ongoing, and findings will likely assist in identifying new therapeutic options to augment those in existence today that are still insufficient for the care of a large population of patients. Recent evidence describes the use of cannabinoids in the treatment of fibromyalgia. This study provides a systematic, thorough review of the evidence alongside a review of the seminal data regarding the pathophysiology, diagnosis, and current treatment options. Fibromyalgia is characterized by widespread chronic pain, fatigue, and depressive episodes without an organic diagnosis, which may be prevalent in up to 10% of the population and carries a significant cost in healthcare utilization, morbidity, a reduced quality of life, and productivity. It is frequently associated with psychiatric comorbidities. The diagnosis is clinical and usually prolonged, and diagnostic criteria continue to evolve. Some therapies have been previously described, including neuropathic medications, milnacipran, and antidepressants. Despite some level of efficacy, only physical exercise has strong evidence to support it. Cannabis has been used historically to treat different pain conditions since ancient times. Recent advances allowed for the isolation of the active substances in cannabis and the production of cannabinoid products that are nearly devoid of psychoactive influence and provide pain relief and alleviation of other symptoms. Many of these, as well as cannabis itself, are approved for use in chronic pain conditions. Evidence supporting cannabis in chronic pain conditions is plentiful; however, in fibromyalgia, they are mostly limited. Only a handful of randomized trials exists, and their objectivity has been questioned. However, many retrospective trials and patient surveys suggest the significant alleviation of pain, improvement in sleep, and abatement of associated symptoms. Evidence supporting the use of cannabis in chronic pain and specifically in fibromyalgia is being gathered as the use of cannabis increases with current global trends. While the current evidence is still limited, emerging data do suggest a positive effect of cannabis in fibromyalgia. Cannabis use is not without risks, including psychiatric, cognitive, and developmental as well as the risks of addiction. As such, clinical judgment is warranted to weigh these risks and prescribe to patients who are more likely to benefit from this treatment. Further research is required to define appropriate patient selection and treatment regimens.

Recurrence and chronicity of major depressive disorder and their risk indicators in a population cohort.

The naturalistic course of major depressive disorder (MDD) and risk indicators for recurrence and chronicity are best studied using a population sample without clear selection bias. However, such studies are scarce. This limits clinical decision-making concerning monitoring and maintenance treatment. Data were used from the Netherlands Mental Health Survey and Incidence Study-2, a psychiatric epidemiological cohort study among a representative adult population. Two groups at baseline were selected to study recurrence and chronicity of MDD at follow-up. Diagnoses were assessed with the Composite International Diagnostic Interview 3.0. Among remitted MDD cases (n=746), the cumulative recurrence rate was 4.3% at 5years, 13.4% at 10years and 27.1% at 20years. Time to recurrence was predicted by vulnerability characteristics (childhood abuse, negative life events, parental psychopathology), physical health, functioning, clinical characteristics of depression (previous episodes, severity, medication use), psychiatric comorbidity and mental health use. Among current MDD cases (n=242), 12% developed a chronic depressive episode over 6years. Chronic course was predicted by similar risk indicators as recurrence, except for vulnerability characteristics and physical health. These risk indicators may help to identify patients requiring monitoring and who could benefit from preventive interventions or maintenance treatment.

German general practitioners\u2019 self-reported management of patients with chronic depression

BackgroundPatients with chronic depression (persisting symptoms for ≥2 years) are a clinically relevant group with extensive (co)morbidity, high functional impairment and associated costs in primary care. The General Practitioner (GP) is the main health professional attending to these patients. The aim of this study was to examine the GPs’ perception on managing patients with chronic depression.MethodsWe performed an explorative cross-sectional study with a systematic sample of GPs in central Germany. Source of data was a written questionnaire (46 items). Descriptive analysis was carried out.ResultsTwo hundred twenty (out of 1000; 22%) GPs participated. 93% of the GPs distinguish between care for patients with chronic depression and acute depressive episode. 92% would recommend psychotherapeutic co-treatment to the chronically depressed patient. 52% of GPs would favour a general restraint on antidepressants (ADs) in older chronically depressed patients (≥ 75 years) whereas 40% suggest long-term pharmacotherapy. If severe physical comorbidity is present GPs would be restrictive in prescribing ADs (65%) or would urgently refer to specialist psychiatric services (40%). In case of a comorbid anxiety disorder 66% of the GPs would suggest a combined psycho- und pharmacotherapy. If a substance use disorder coexists 84% would prefer urgent referrals to specialist services.ConclusionsParticipating GPs report awareness towards chronic depression in their patients. Physical and mental comorbidity seem to play an important role in GPs’ treatment decisions.

Childhood neglect predicts the course of major depression in a tertiary care sample: a follow-up study

BackgroundThe course of depression is poorer in clinical settings than in the general population. Several predictors have been studied and there is growing evidence that a history of childhood maltreatment consistently predicts a poorer course of depression.MethodsBetween 2008 and 2012, we assessed 238 individuals suffering from a current episode of major depression. Fifty percent of these (N = 119) participated in a follow-up study conducted between 2012 and 2014 that assessed sociodemographic and clinical variables, the history of childhood abuse and neglect (using the Adverse Childhood Experience questionnaire), and the course of depression between baseline and follow-up interview (using the Life Chart method). The Structured Clinical Interview for DSM-IV-TR was used to assess diagnosis at baseline and follow-up interview. Statistical analyses used the life table survival method and Cox proportional hazard regression tests.ResultsAmong 119 participants, 45.4% did not recover or remit during the follow-up period. The median time to remission or recovery was 28.9 months and the median time to the first recurrence was 25.7 months. Not being married, a chronic index depressive episode, comorbidity with an anxiety disorder, and a childhood history of physical neglect independently predicted a slower time to remission or recovery. The presence of three or more previous depression episodes and a childhood history of emotional neglect were independent predictors of depressive recurrences.ConclusionsChildhood emotional and physical neglect predict a less favorable course of depression. The effect of childhood neglect on the course of depression was independent of sociodemographic and clinical variables.

Post-vasectomy depression: a case report and literature review

Vasectomy is a commonly performed and relatively safe procedure, with low reported rates of psychological morbidity, though there is some variability across studies. Depression following a vasectomy is relatively infrequent. A married man aged 30 developed a chronic depressive episode, lasting four years and resistant to an adequate trial of fluoxetine, following a vasectomy. His depression was heralded by a post-operative panic attack, and was accompanied by medically unexplained symptoms and the attribution of all his symptoms to the procedure – a belief that was shared by his family. Psychological complications of vasectomy have generally been studied under four heads: sexual dysfunction, effects on marital relationships, chronic post-operative pain, and other complications including anxiety and depression. These complications have generally been reported at higher rates in developing countries, and are linked to poor knowledge about the procedure and inadequate pre-operative counseling. The implications of the existing literature for the patient's current complaints, and the mechanisms and risk factors involved, are discussed in the light of existing research. Suggestions for the prevention and treatment of post-vasectomy depression are also outlined.

Religious involvement in major depression: Protective or risky behavior? The relevance of bipolar spectrum

BackgroundReligiosity has been reported to be inversely related to depression and to suicide as well, but there is a lack of studies on its impact on bipolar disorder and especially, on depressed patients belonging to the bipolar spectrum. MethodsAs part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 234 (55.2%) could be classified as with high religious involvement (HRI), and 190 (44.8%) as with low religious involvement (LRI), on the basis of their ratings on the Duke Religious Index (DRI). ResultsCompared to LRI, HRI patients did not differ with respect to their religious affiliation but had a later age at onset of their affective illness with more hospitalizations, suicide attempts, associated hypomanic features, switches under antidepressant treatment, prescription of tricyclics, comorbid obsessive compulsive disorder, and family history of affective disorder in first-degree relatives. The following independent variables were associated with religious involvement: age, depressive temperament, mixed polarity of first episode, and chronic depression. The clinical picture of depressive patients with HRI was evocative of chronic mixed depressive episodes described in bipolar III patients within the spectrum of bipolar disorders. LimitationsRetrospective design, recall bias, lack of sample homogeneity, no assessment of potential protective and risk factors, and not representative for all religious affiliations. ConclusionsIn depressive patients belonging to the bipolar spectrum, high religious involvement associated with mixed features may increase the risk of suicidal behavior, despite the existence of religious affiliation.

2795 – Delusional social isolation: criteria attempts for psychotic depression and late paranoid schizophrenia

Introduction Chronic social isolation in the elderly may be related with diverse psychiatric disorders: chronic depressive episode, paranoia-type personality, and late non-schizophrenic psychosis. Objectives In order to separate psychotic depression and non-schizophrenic psychosis with depressive mood, there is a need for more clearly defined criteria. Methods We report the case of a 68 yrs. women living alone at home for more than twenty years, with a complete social isolation for two years. This behaviour was found associated with severe delusion: she unreasonably felt persecuted by her flat's owner and she dissimulated an extensive basocellular carcinoma on her face threatening her life. A history of a short depressive episode at the time of her divorce was only found, as she demonstrated at initial assessment many paranoia personality traits. A review of literature on this disorders’ association was therefore undertaken. Results Evolution after admission revealed the lack of effectiveness of antipsychotic treatment on delusion, but some efficiency of antidepressant. Nevertheless, personality traits remained unaffected by care. Literature on the association between mood disorders and non-schizophrenic psychosis is rare, and we suggest some criteria that may account for psychotic depression and be useful to treatment choice. Conclusions In the absence of a history of chronic mood or psychotic disorder, it is hypothesised that paranoia symptoms may account more for a psychotic depression than for late paranoid schizophrenia. This may have consequences for therapeutic strategy.

SEROTONIN TRANSPORTER LENGTH POLYMORPHISM, CHILDHOOD MALTREATMENT, AND CHRONIC DEPRESSION: A SPECIFIC GENE-ENVIRONMENT INTERACTION

Key questions about the interaction between the serotonin transporter length polymorphism (5-HTTLPR) and stress in the etiology of depression remain unresolved. We test the hypotheses that the interaction is restricted to childhood maltreatment (as opposed to stressful events in adulthood), and leads to chronic depressive episodes (as opposed to any onset of depression), using gold-standard assessments of childhood maltreatment, severe life events, chronic depression, and new depressive onsets. In a risk-enriched sample of 273 unrelated women, childhood maltreatment was retrospectively assessed with the Childhood Experience of Care and Abuse (CECA) interview and 5-HTTLPR was genotyped. A subset of 220 women was followed prospectively for 12 months with life events assessed with the Life Events and Difficulties (LEDS) interview. Any chronic episode of depression (12 months or longer) during adulthood and onset of a major depressive episode during a 12-month follow-up were established with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview. The short alleles of 5-HTTLPR moderated the relationship between childhood maltreatment and chronic depression in adulthood, reflected in a significant gene-environment interaction (RD = 0.226, 95% CI: 0.076-0.376, P = .0032). 5-HTTLPR did not moderate the effects of either childhood maltreatment or severe life events on new depressive onsets. The short variant of the serotonin transporter gene specifically sensitizes to the effect of early-life experience of abuse or neglect on whether an adult depressive episode takes a chronic course. This interaction may be responsible for a substantial proportion of cases of chronic depression in the general population.

Lower cortisol levels predict recurrence in remitted patients with recurrent depression: A 5.5 year prospective study

Major Depressive Disorder (MDD) is a highly recurrent disease. Stress-responsive system dysfunction seems to persist after remission. In patients with more chronic and recurrent depressive episodes, state related HPA-axis dysregulation might be a risk factor for prospective recurrence. This study examines the predictive effect of cortisol on consecutive episodes in remitted recurrently depressed patients.Cortisol was assessed in saliva in remitted recurrently depressed patients (n=55) that were followed up prospectively for 5.5 years after remission. Recurrence was assessed using a well validated structured interview.Lower mean morning cortisol levels predicted earlier time to recurrence over 5.5 year after correction for residual symptoms (p=0.015). Residual symptoms and childhood trauma slightly confounded the association between cortisol and recurrence. Lower cortisol levels were associated with having experienced traumatic childhood life events (42.3% in patients with lower cortisol versus 19.2% in patients with higher cortisol).Our study provides further support for the predictive role over 5.5 year of HPA axis dysregulation, i.e. lower morning cortisol levels, of recurrence in recurrently depressed patients. Childhood trauma is associated to having lower cortisol levels. It might have long term consequences for dealing with stress and the HPA-axis.

AS36-02 - Chronic course of depression in the general population

Introduction The prevalence and course of chronic major depressive disorders (MDD) in the general population has rarely been assessed. Objectives to gain a better understanding of the prevalence, course and the familial aggregation of MDD with at least one episode exceeding a duration of two years. Aims to assess 1) the prevalence; 2) course characteristics and comorbidity with other psychiatric disorders and 3) cardiovascular risk factors (CVRFs) and 4) the familial aggregation of chronic MDD in subjects with chronic MDD. Methods The sample stems from a large community survey carried out in the city of Lausanne, Switzerland. Subjects were aged from 35 to 65 years (n = 3717, 53.1% females, mean age: 50.9 years). They all underwent a physical examination of CVRFs and a psychiatric evaluation using the semi-structured Diagnostic Interview for Genetic Studies. Results 1) Approximately 15% of the sample reported at least one chronic depressive episode and 6% were in a chronic depressive episode at the time of the interview; about a 6 th of them had episodes longer than 10 years; 2) compared to non-chronic MDD, MDD with chronic depressive episodes was associated with low socio-demographic level, comorbidity with anxiety disorders and almost all variables indicating poor course, but not with CVRFs except for inactivity; 4)there was no evidence for familial aggregation of chronic MDD. Conclusions As expected, MDD with chronic episodes revealed a strong association to indicators of poor course. However, with the exception of inactivity they do not seem to be associated with CVRF.

Dysthymic Disorder and Other Chronic Depressions

Chronic forms of depression have been closely studied over the last three decades, and it is now widely recognized that these conditions are better classified under the umbrella of affective disorders rather than characterological or personality disorders. Chronic depressive disorders include dysthymic disorder, chronic major depressive episode, major depressive episode superimposed on dysthymic disorder (double depression), as well as recurrent major depressive disorder without full interepisode recovery. Chronic forms of depression are prevalent in the general population, and even those with low grade severity can lead to significant functional impairment, occupational dysfunction, suicide attempts, and worse prognosis. Given the obvious potential for deleterious effects, chronic forms of depression should be promptly recognized and aggressively treated. Clinical benefit from using psychopharmacologic agents alone or in combination with psychotherapy for the treatment of chronic depression has been demonstrated. In this article the authors review pertinent clinical and diagnostic aspects in chronic depressive disorders as well as their treatment.

Bipolar disorder and comorbid obsessive-compulsive disorder is associated with higher rates of anxiety and impulse control disorders.

Issler CK, Monkul ES, Amaral JAMS, Tamada RS, Shavitt RG, Miguel EC, Lafer B. Bipolar disorder and comorbid obsessive-compulsive disorder is associated with higher rates of anxiety and impulse control disorders. Although bipolar disorder (BD) with comorbid obsessive-compulsive disorder (OCD) is highly prevalent, few controlled studies have assessed this comorbidity. The objective of this study was to investigate the clinical characteristics and expression of comorbid disorders in female BD patients with OCD. We assessed clinically stable female outpatients with BD: 15 with comorbid OCD (BD+OCD group) and 15 without (BD/no-OCD group). All were submitted to the Structured Clinical Interview for DSM-IV, with additional modules for the diagnosis of kleptomania, trichotillomania, pathological gambling, onychophagia and skin picking. The BD+OCD patients presented more chronic episodes, residual symptoms and previous depressive episodes than the BD/no-OCD patients. Of the BD+OCD patients, 86% had a history of treatment-emergent mania, compared with only 40% of the BD/no-OCD patients. The following were more prevalent in the BD+OCD patients than the BD/no-OCD patients: any anxiety disorder other than OCD; impulse control disorders; eating disorders; and tic disorders. Female BD patients with OCD may represent a more severe form of disorder than those without OCD, having more depressive episodes and residual symptoms, and being at a higher risk for treatment-emergent mania, as well as presenting a greater anxiety and impulse control disorder burden.

Functional disability as an explanation of the associations between chronic physical conditions and 12-month major depressive episode

Background The link between physical conditions and mental health is poorly understood. Functional disability could explain the association of physical conditions with major depressive episode (MDE) as an intermediary factor. Methods Data was analyzed from a subsample ( N = 8796) of the European Study of the Epidemiology of Mental Disorders (ESEMeD), a cross-sectional general population survey. MDE during the last 12 months was assessed using a revision of the Composite International Diagnostic Interview (CIDI 3.0). Lifetime chronic physical conditions were assessed by self-report. Functional disability was measured using a version of the World Health Organization Disability Assessment Schedule (WHODAS). The associations of physical conditions with MDE and explanation by functional disability were quantified using logistic regression. Results All physical conditions were significantly associated with MDE. The increases in risk of MDE ranged from 30% for allergy to amply 100% for arthritis and heart disease. When adjusted for physical comorbidity, associations decreased and were no longer statistically significant for allergy and diabetes. Functional disability explained between 17 and 64% of these associations, most substantially for stomach or duodenum ulcer, arthritis and heart disease. Limitations Due to the cross-sectional nature of the study the temporal relationship of the variables could not be assessed and the amount of explanation cannot simply be interpreted as the amount of mediation. Conclusions Our findings suggest that the association of chronic physical conditions with MDE is partly explained by functional disability. Such explanation is more pronounced for pain causing conditions and heart disease. Health professionals should be particularly aware of the increased risk of depressive disorder when patients experience disability from these conditions.

Child-specific and family-wide risk factors using the retrospective Childhood Experience of Care & Abuse (CECA) instrument: A life-course study of adult chronic depression — 3

Background An earlier paper [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007a-this issue. Development of a retrospective interview measure of parental maltreatment using the Childhood Experience of Care & Abuse (CECA) instrument — a life-course study of adult chronic depression — 1. J. Affect. Disord. doi:10.1016/j.jad.2007.05.022] documented an association between parental maltreatment and risk of adult chronic depression. This paper explores the contribution of other child-specific factors (e.g. conduct problems) and family-wide factors (e.g. parental discord). Methods Data are derived from an enquiry of 198 women largely comprising of adult sister pairs. Data was collected by semi-structured interviews covering a wide range of parental behaviour and childhood behaviour. Results Parental maltreatment emerged as channelling the effect of family-wide factors on risk of adult chronic depression, but with a child's conduct problems and shame-withdrawal partly mediating this link. A child's depression before 17, although correlated with parental maltreatment, did not appear to play a significant role in adult depression. This core model is supplemented by analyses exploring the mechanisms involved. A mother's rejection/physical abuse and her depression via her lax control, for example, account for the link of parental maltreatment with conduct problems. Also ‘rebelliousness’ of a child relates to the chances of her low affection moving to rejection. “Rebelliousness” also appears to play a role in why the paired sisters so often had a different experience of maltreatment. Limitations The data is collected retrospectively — but see [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007b-this issue. Validity of retrospective measures of early maltreatment and depressive episodes using the Childhood Experience of Care and Abuse (CECA) instrument — A life-course study of adult chronic depression — 2. J. Affect. Disord. doi:10.1016/j.jad.2007.06.003]. Conclusions Child-specific factors play a major role in the origins of adult chronic depressive episodes. This, however, is fully consistent with an equally significant contribution from family-wide factors. The crucial point is that the link of the latter with such depression appears to be indirect and mediated very largely by parental maltreatment.

Validity of retrospective measures of early maltreatment and depressive episodes using the Childhood Experience of Care and Abuse (CECA) instrument — A life-course study of adult chronic depression — 2

Background A previous paper, using data collected retrospectively from sister pairs, reported substantial associations of adult depressive episodes lasting at least 12 months with childhood maltreatment [Brown, G.W., Craig, T.K.J., Harris, T.O. Handley, R.V. & Harvey, A.L. 2007a-this issue. Development of a retrospective interview measure of parental maltreatment using the Childhood Experience of Care & Abuse (CECA) instrument — a life-course study of adult chronic depression — 1. J. Affect. Disord. doi:10.1016/j.jad.2007.05.022]. Risk was far less when depressive episodes of any duration were considered. This paper considers how much scientific weight can be placed on these findings in the light of doubt often expressed about retrospective collection of childhood and adult data. Methods The retrospectively gathered material was obtained from adult sister pairs within 5 years of age, comprising a high-risk series ( n = 118) where the first sister was selected as likely to have experienced childhood abuse or neglect, and a comparison series ( n = 80) where she was selected at random. Current age ranged between early 20s and 50s. Data was collected by semi-structured interviews, using investigator-based ratings covering a wide range of parental behaviour and childhood behaviour. Results A series of analyses failed to reveal evidence of significant bias in the collection of material about adult depression or parental maltreatment. There was, however, some evidence of under reporting. Limitations Conclusions from such analyses can only be judged in terms of degree of plausibility. Conclusions Nothing emerged to suggest the presence of significant bias in the aetiological findings of our earlier paper. There is evidence of some underreporting of both early adverse experience and adult depressive episodes, but this is unlikely to threaten the conclusions drawn about the link of parental maltreatment with adult chronic depressive episodes.

Development of a retrospective interview measure of parental maltreatment using the Childhood Experience of Care and Abuse (CECA) instrument — A life-course study of adult chronic depression — 1

Background Childhood maltreatment among women is related to risk of adult depression and particularly an episode taking a chronic course. This paper explores the aspects of parental behaviour involved. Methods An expanded version of CECA (Childhood Experiences of Care and Abuse), a retrospective interview-based instrument covering neglect as well as various forms of abuse is used to develop a new index of parental maltreatment. Data are derived from an enquiry of sister pairs between early 20s and 50s, comprising a high-risk series ( n = 118) where the first sister was selected as likely to have experienced childhood abuse or neglect, and a comparison series ( n = 80) where she was selected at random. Results Adverse maternal behaviour emerges as of critical importance for the link with adult chronic depression. Maternal lack of affection (‘neglect’) and maternal rejection (‘emotional abuse’) form the core of an index of parental maltreatment, and it is concluded that persistent rejection, particularly from a mother, appears to be the core experience of importance. The findings of behavioural genetics that the experience of siblings of parents in ordinary families often differs have been found to hold for the more extreme behaviour involved in maltreatment. Difference between siblings in risk of later chronic depression is entirely related to such experience. Limitations The study is based on retrospective questioning of adult women. Our next paper considers the possible threats to validity involved [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007a. Validity of retrospective measures of early maltreatment and depressive episodes using CECA (Childhood Experience of Care and Abuse) — a life-course study of adult chronic depression — 2. J. Affect. Disord. doi:10.1016/j.jad.2007.06.003]. Conclusions Parental maltreatment emerges as a critical determinant of later chronic depressive episodes among adult women.

A comparison of the familiality of chronic depression in recurrent early-onset depression pedigrees using different definitions of chronicity

BackgroundThe study of chronicity in the course of major depression has been complicated by varying definitions of this illness feature. Because familial clustering is one component of diagnostic validity we compared family clustering of chronicity as defined in the DSM-IV to that of chronicity determined by an assessment of lifetime course of depressive illness. MethodsIn 1750 affected subjects from 652 families recruited for a genetic study of recurrent, early-onset depression, we applied several definitions of chronicity. Odds ratios were determined for the likelihood of chronicity in a proband predicting chronicity in an affected relative. ResultsThere was greater family clustering of chronicity as determined by assessment of lifetime course (OR=2.54) than by DSM-IV defined chronic major depressive episode (MDE) (OR=1.93) or dysthymic disorder (OR=1.76). In families with probands who had preadolescent onset of MDD, familiality was increased by all definitions, with a much larger increase observed for chronicity by lifetime course (ORs were 6.14 for lifetime chronicity, 2.43 for chronic MDE, and 3.42 for comorbid dysthymic disorder). Agreement between these definitions of chronicity was only fair. LimitationsThe data used to determine chronicity were collected retrospectively and not blindly to relatives' status, and assessment of lifetime course was based on global clinical impressions gathered during a semi-structured diagnostic interview. Also, it can be difficult to determine whether individuals with recurrent major depressive episodes who frequently experience long periods of low grade depressive symptoms meet the strict timing requirements of DSM-IV dysthymic disorder. ConclusionsAn assessment of lifetime symptom course identifies a more familial, and thus possibly a more valid, type of chronic depression than the current DSM-IV categories which are defined in terms of particular cross-sectional features of illness.

Long-term outcome of antidepressant-refractory depression: The relevance of unrecognized bipolarity

Background The long-term outcome of antidepressant-refractory depression is not well known. Therefore, the present study investigated the long-term outcome of 26 antidepressant-refractory patients with depression, whom we had studied and treated in 1995. Methods Before being classified as nonresponse, these patients had been treated adequately with at least two tricyclic or heterocyclic antidepressants (a minimum of the equivalent of 150mg of imipramine for 4 weeks). In 1995, 21 of 26 patients were diagnosed with unipolar depression, while 5 were diagnosed with bipolar depression. Mean follow-up was 5.7 years (range: 1–7 years) and changes in diagnosis, remission and treatment efficacy were evaluated. Results Following the long-term follow-up, 13 patients achieved full remission and demonstrated high social functioning (mean GAF score, 91). A further four depressed patients experienced full remission; however, subsequent recurrence was observed. In total, 17 of 26 patients experienced remission at least once during the long-term follow-up period despite the chronic depressive episodes observed at study entry. Adjuvant treatment with lithium, dopamine receptor agonists or thyroid hormone was effective for promoting full remission. Among the 21 patients initially diagnosed with unipolar depression in 1995, diagnoses were changed to bipolar disorder in 5 cases. Limitations This naturalistic study had a relatively small sample size and treatment was not controlled. Conclusions Long-term follow-up revealed that a substantial proportion of antidepressant-refractory depression is comprised of bipolar disorders. In addition, augmentation therapies are effective for promoting full remission among chronically depressed patients without a risk of serious side effects.

Ten-Year Prospective Follow-Up Study of the Naturalistic Course of Dysthymic Disorder and Double Depression

Objective: The purpose of this study was to describe the 10-year course and outcome of dysthymic disorder. Method: The authors conducted a naturalistic, prospective, longitudinal follow-up of 97 adults with early-onset dysthymic disorder and 45 adults with nonchronic major depressive disorder selected from consecutive admissions to several outpatient facilities. Follow-up data were obtained for 90% of the cohort. Assessments were conducted at baseline, 30, 60, 90, and 120 months. Measures included the Longitudinal Interval Follow-Up Evaluation and the Hamilton Depression Rating Scale. Results: The Kaplan-Meier estimated recovery rate from dysthymic disorder was 73.9%, with a median time to recovery of 52 months. Among patients who recovered, the estimated risk of relapse into another period of chronic depression was 71.4%. Chronic depressive relapses took a variety of forms and were not limited to dysthymia. Nonetheless, the distinction between chronic and nonchronic forms of depression was relatively stable over the follow-up period. Mixed-effects models indicated that patients with dysthymic disorder experienced a significantly slower rate of improvement in symptoms over time and exhibited significantly greater depression at the 10-year point, compared to patients with nonchronic major depression. Conclusions: Dysthymic disorder has a protracted course and is associated with a high risk of relapse. The nature of chronic depressive episodes varies over time within individuals, indicating that the various manifestations of chronic depression in DSM-IV do not represent distinct disorders. However, the distinction between chronic and nonchronic forms of depression is relatively stable and may provide a useful basis for subtyping in genetic and neurobiological research.