History Of Recurrent Major Depression Research Articles

Relapse of Major Depression in Women Who Continue or Discontinue Antidepressant Medication During Pregnancy

Relapse of Major Depression in Women Who Continue or Discontinue Antidepressant Medication During Pregnancy

Behavioral activation system moderates self-referent processing following recovery from depression

Previous research has implicated the behavioral activation system (BAS) in depression. The relationship of BAS functioning to aspects of cognitive vulnerability to depression, however, is not known. Method The present study investigated associations among level of BAS functioning and the encoding and recall of positive and negative self-referent information in currently non-depressed participants with a history of recurrent major depression (recovered; RMD) and in never-depressed control participants (CTL). Participants completed self-report measures of levels of BAS and behavioral inhibition system (BIS) functioning. Following a negative mood induction, participants were presented with a series of positive and negative adjectives; they indicated which words described them and later recalled as many of the words as they were able. The relationship of BAS functioning to self-referent processing was dependent on participant group. Although lower BAS reward responsivity was associated with the endorsement and recall of fewer positive words across groups, the magnitude of these associations was stronger, and was only significant, within the RMD group. Furthermore, only for RMD participants was lower BAS reward responsivity associated with the endorsement of more negative words. These effects were not accounted for by depressive or anxiety symptoms, current mood, or level of BIS functioning. These results indicate that BAS functioning may be distinctively linked to negatively biased self-referent processing, one facet of cognitive vulnerability to depression, in individuals with a history of major depressive disorder. Enhancing BAS functioning may be important in buffering cognitive vulnerability to depression.

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.

History of Single Episode and Recurrent Major Depressive Disorder Among Smokers in Cessation Treatment

OBJECTIVES: Research and theory provide initial support for the potential utility in distinguishing between recurrent and single episode MDD smokers for cessation treatment. However, no study to date has examined differences in clinical presentation at the outset of treatment among these two groups and whether these clinical profiles are indicative of early cessation failure (smoking on quit day). METHODS: In a secondary analysis of a sample of 179 smokers entering cessation treatment, we examined baseline differences in dysfunctional attitudes, maladaptive coping, self-efficacy to manage negative affect, depressive symptoms, depressed mood, and experienced pleasure from life events between smokers with a history of recurrent major depression (MDD-R; 54.7%) and single episode major depression (MDD-S). RESULTS: Results showed that MDD-R smokers reported lower self-efficacy to cope with negative affect, greater depressive symptoms, and greater depressed mood than MDD-S smokers, although no differences were found on dysfunctional attitudes, avoidance coping, and level of experienced pleasure from daily life events. A greater number of MDD-R compared to MDD-S smokers were not abstinent on their quit day, however a history of recurrent MDD did not increase risk for early cessation failure. CONCLUSIONS: The findings indicate that although depressed mood, negative affect-regulation ability, and depression severity distinguish recurrent and single episode MDD smokers at the start of cessation treatment, these differences do not necessarily portend greater risk for cessation failure in the early stages of treatment.

FC05-03 Altered levels of neurotrophic factors in alzheimer's disease patients with a lifetimne history of depression

Aims:We have recently shown both increases in the number of neuropathological changes in Alzheimer's disease patients with a history of recurrent major depression, and evidence for Alzheimer's disease-related neuropathological changes in patients with geriatric major depression. However, the correlates and possible underlying mechanisms for these neuropathological changes in Alzheimer's disease patients as a function of depression remains to be studied.Method:Levels of several neurotrophic factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were measured in a sample of Alzheimer's disease patients with and without a lifetime history of major depressive disorder.Results:Alzheimer's disease patients with co-morbid depression showed lower levels BDNF (P < .001) and NGF (P < .001) than Alzheimer's disease patients without co-morbid depression. Results remained stable when controlling for age, gender, level of education, and other medical co-morbidities.Conclusion:In Alzheimer's disease, the presence of depression co-morbidity corresponds to decreases in neurotrophic factors beyond effects of age, education, and medical co-morbidities, suggesting that the previously described link between major depression and the neuropathological processes in Alzheimer's disease may be related to changes in neuronal survival mediated by neurotrophic factors.Funded by the National Institute on Aging (U01 AG016976 and NIA P01-AG05138) and NARSAD.

Poor Neonatal Adaptation After in Utero Exposure to Duloxetine

Back to table of contents Previous article Next article Letters to the EditorFull AccessPoor Neonatal Adaptation After in Utero Exposure to DuloxetineROY EYAL M.D.DEBORAH YAEGER M.D.,ROY EYAL M.D.Search for more papers by this authorDEBORAH YAEGER M.D.Search for more papers by this author,Published Online:1 May 2008https://doi.org/10.1176/appi.ajp.2008.07071194AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To The Editor: Risk-benefit analysis is central when forming a treatment plan for pregnant women with mental illness. This task is further complicated by limited data pertaining to the effects of antidepressants on the fetus, neonate, and child. To our knowledge, this is the first case report of in utero exposure to duloxetine.“Ms. A” was a 36-year-old Caucasian female with a history of recurrent major depression, anorexia, and chronic neck pain. When she sought psychiatric consultation at 34 weeks’ gestation, she was 1) in complete remission, 2) being treated by an anesthesiologist, 3) and receiving monotherapy duloxetine (90 mg/day). She was educated about neonatal behavioral syndrome, and duloxetine was subsequently decreased to 60 mg/day.The child was delivered without complication at 38 weeks. Upon delivery, she was blue, with minimal respiratory effort and oxygen saturations in the 80s. Her Apgar scores were 7 and 9. After birth, she was transferred to the neonatal intensive care unit because she continued to require oxygen. The child was started on antibiotics while possible causes of transient tachypnea were assessed. Basic laboratory examination, blood gas, echocardiogram, and chest and abdominal x-rays were all normal on day 1. Breast feeding was discouraged because of concerns of exposure to duloxetine, and the mother was advised to switch to sertraline. Antibiotic treatment was discontinued after blood cultures remained negative.On day 3, the child was weaned to room air but developed “jerky rhythmic movements,” or “twitchiness.” An electroencephalogram (EEG) showed nonspecific encephalopathic findings. The child did have episodes of shaking, and the EEG revealed no correlated changes. Phenobarbital was started, and despite a high blood level the following day, the child continued to experience occasional twitching. Head computed tomography, magnetic resonance imaging, and lumbar puncture were all normal. A repeat EEG conducted at 7 days was suggestive of subclinical seizures. A follow-up EEG at 7 weeks was normal. Phenobarbital was discontinued, and the child was diagnosed with tremors and neonatal seizures associated with neonatal behavior syndrome. At age 2, the child is healthy with consistently normal neurobehavioral development. This case demonstrates the syndrome referred to as poor neonatal adaptation or neonatal behavioral syndrome, characterized by jitteriness, poor muscle tone, weak cry, respiratory distress, hypoglycemia, low Apgar score, and seizure (1) . These symptoms start within hours, generally require only supportive care, and end within 1 to 2 weeks. The syndrome may occur in up to 30% of infants with selective serotonin reuptake inhibitor exposure (2) , with a risk ratio of approximately 3.0 (3) or higher for premature infants (4) . The mechanism underlying the syndrome is unclear. A dose of fluoxetine or nursing may decrease symptoms assuming they stem from withdrawal. Reports indicate a higher risk with exposure to paroxetine and venlafaxine, agents with the shortest half-lives, but data are very limited pertaining to newer antidepressants such as duloxetine, mirtazapine, and bupropion. Better characterization of poor neonatal adaptation and its etiology could reduce invasive procedures and inform the difficult decisions in treating mental illness during pregnancy. Los Angeles, Calif.The authors report no competing interests.This letter (doi: 10.1176/appi.ajp.2008.07071194) was accepted for publication in January 2008.

NOT ALL MONOAMINE OXIDASE INHIBITORS ARE CREATED EQUAL

To the Editor: Refractory depression is commonly encountered in psychiatric practice; it has been estimated that up to 15% of patients will fail to respond to aggressive treatment with multiple agents.1 Refractory depression is especially problematic for older patients, who are unable to withstand the ravages of a severe and prolonged depression as well as younger individuals;2, 3 it is common for such patients to be left with permanent disabilities even after finally treating the depression. Monoamine oxidase inhibitors (MAOIs) have been available since the late 1950s and have proved to be effective in up to 50% of patients with refractory depression.4, 5 The older MAOIs are infrequently used now, mainly because of their potentially fatal interactions with a variety of medications and foods; although Food and Drug Administration approval of transdermal selegiline has engendered some renewed interest, many psychiatrists are inexperienced with these valuable drugs. Because MAOIs are usually reserved for refractory depression, the question of whether a patient that fails one agent might respond to another is an important one but one that has never been addressed in the literature. Two elderly patients who failed to respond to phenelzine but had a rapid and dramatic improvement when switched to tranylcypromine are reported here. An 80-year-old man presented with an 8-month history of severe major depression with prominent somatic and nihilistic delusions. Over the subsequent 4 months of treatment, he failed to respond to multiple trials of antidepressants, augmenting strategies, and a course of nine bilateral electroconvulsive treatments. Ultimately, a trial of phenelzine was initiated and titrated to a maximal dosage of 75 mg per day; this was ineffective. Lithium was added, also with no effect. After 5 weeks, phenelzine was discontinued and tranylcypromine substituted, titrating to a maximal dosage of 60 mg per day. This resulted in a dramatic improvement in his depressive symptoms within approximately 10 days; he developed some subtle confusion, which resolved on discontinuation of lithium. His depression remained in full remission on tranylcypromine monotherapy until his death from congestive heart failure 5 years later. A 76-year-old man with a 13-year history of recurrent major depression with prominent somatic delusions had initially responded to electroconvulsive therapy and phenelzine but had eventually become refractory to both. His depression remained in remission for the following 5 years on lithium monotherapy but then recurred and again proved to be refractory to phenelzine in doses as high as 90 mg per day with continued lithium augmentation. Phenelzine was washed out and tranylcypromine substituted at a final dosage of 40 mg per day. His response to tranylcypromine was dramatic, with complete resolution of all depressive symptoms within 12 days; he developed moderate delirium that completely resolved with reduction of his lithium dosage. Both of these patients suffered from highly morbid, refractory depression, and their response to a second MAOI was gratifying. Because of their interactions with many antidepressants, switching to a non-MAOI strategy would have been much more cumbersome (although a wash-out period between MAOIs may be necessary as well6) and perhaps less effective. Although the past 5 decades have witnessed extraordinary progress in psychopharmacology, older medications should not be forgotten. Financial Disclosure: The Editor in Chief has determined that the author has no conflict of interest related to this letter. Author Contributions: Jonathan T. Stewart was responsible for the entire content of the letter. Sponsor's Role: None.

Antidepressant Use in the Postpartum Period: Practical Considerations

A 30-year-old woman, 6 weeks postpartum, is referred by her obstetrician for possible postpartum depression. The patient noted onset of symptoms 2 days after delivery of her son; describing the onset, she said she felt as if curtain descended upon her. Her symptoms include low mood, tearfulness, decreased sleep and appetite, significant weight loss, and anhedonia. She feels she cannot care for her son properly and has intrusive thoughts that some unspecified harm may come to him. She adamantly denies thoughts of hurting herself or her son but worries constantly that something bad will happen. At night, she feels restless and frequently checks that the baby is still breathing. Her concentration is poor, and she often does not shower or take care of household duties, but she does care for her son. On examination, the patient appears sad and anxious, with psychomotor retardation. She denies a previous psychiatric history. Her family history is notable for bipolar I disorder in a paternal uncle and a grandfather. She is breastfeeding. A 27-year-old woman with a history of recurrent major depression since age 18 presents for a consultation during her second trimester of pregnancy. The patient has a history of nonresponse to selective serotonin reuptake inhibitors (SSRIs) and has been hospitalized twice for severe depressive episodes. During the second hospitalization, at age 25, she required six ECT treatments. Since that time, she has been maintained with good results on 75 mg daily of nortriptyline. Her treating psychiatrist recommended that she continue taking the nortriptyline during the pregnancy, which she has done.

Antenatal Depression: Navigating the Treatment Dilemmas

“Ms. A” was a 35-year-old married Caucasian health care professional with a history of recurrent major depressive disorder that responded well to treatment with a selective serotonin reuptake inhibitor (SSRI). She discontinued her antidepressant prior to conception for a planned pregnancy because she did not want to expose her baby to medication. She soon relapsed, and by the first trimester of her pregnancy, she was in a major depressive episode. Her symptoms included anhedonia, tearfulness, irritability, insomnia, and diminished appetite. She presented for participation in an open-label pilot trial of omega-3 fatty acids for antenatal major depressive disorder (1). At intake, after hearing the risks and benefits of available treatment options, Ms. A declined antidepressant medication and a referral for psychotherapy and consented to participate in the study of omega-3 fatty acids, which she started at 16 weeks’ gestation. She was assessed every 2 weeks throughout pregnancy. At 8 weeks she had not responded to omega-3 fatty acids and was again presented with other treatment options, including medication and psychotherapy. She again declined these treatments and continued to do so throughout the remainder of her pregnancy. She was concerned about the safety of medications in pregnancy and believed that taking medication would make her a bad mother. She also declined referral for psychotherapy, stating that she was “too busy.”

Increased 5-HT 2A Receptor Binding in Euthymic, Medication-Free Patients Recovered From Depression: A Positron Emission Study With [ 11 C]MDL 100,907

A previous positron emission tomography (PET) study reported increased serotonin 5-HT(2A) receptor binding in unmedicated depressed patients with high scores on the Dysfunctional Attitudes Scale. The purpose of the present study was to use the highly selective 5-HT(2A) receptor ligand [(11)C]MDL 100,907 in a PET imaging paradigm to assess 1) 5-HT(2A) receptor binding potential in euthymic subjects with a history of recurrent depression and 2) the relationship between receptor binding and scores on the Dysfunctional Attitudes Scale. Cortical 5-HT(2A) receptor binding was measured in 20 unmedicated, fully recovered unipolar depressed patients and 20 age- and gender-matched comparison subjects. Regional estimates of binding potential were obtained using a reversible plasma input function compartmental model and the cerebellum as a reference region to estimate the free and non-specifically bound [(11)C]MDL 100,907 in brain tissue. Relative to the comparison subjects, the recovered depressed patients demonstrated significantly higher 5-HT(2A) receptor binding potential in the frontal cortex (mean increase: 19%), parietal cortex (mean increase: 25%), and occipital cortex (mean increase: 19%). 5-HT(2A) receptor binding potential correlated negatively with age in both patients and comparison subjects and positively with the Dysfunctional Attitudes Scale in the recovered patients. These findings should be considered preliminary but suggest that recovered subjects with a history of recurrent major depression have elevated binding potential of cortical 5-HT(2A) receptors. The correlation of increased 5-HT(2A) receptor binding potential with increased scores on Dysfunctional Attitudes Scale supports earlier work suggesting that increased 5-HT(2A) receptor availability characterizes a group of depressed patients with high levels of dysfunctional attitudes.

Increased 5-HT<char aid="99820963" id="sub">2A</char> Receptor Binding in Euthymic, Medication-Free Patients Recovered From Depression: A Positron Emission Study With [<char aid="99820964" id="sup">11</char>C]MDL 100,907

Objective: A previous positron emission tomography (PET) study reported increased serotonin 5-HT 2A receptor binding in unmedicated depressed patients with high scores on the Dysfunctional Attitudes Scale. The purpose of the present study was to use the highly selective 5-HT 2A receptor ligand [ 11 C]MDL 100,907 in a PET imaging paradigm to assess 1) 5-HT 2A receptor binding potential in euthymic subjects with a history of recurrent depression and 2) the relationship between receptor binding and scores on the Dysfunctional Attitudes Scale. Method: Cortical 5-HT 2A receptor binding was measured in 20 unmedicated, fully recovered unipolar depressed patients and 20 age- and gender-matched comparison subjects. Regional estimates of binding potential were obtained using a reversible plasma input function compartmental model and the cerebellum as a reference region to estimate the free and non-specifically bound [ 11 C]MDL 100,907 in brain tissue. Results: Relative to the comparison subjects, the recovered depressed patients demonstrated significantly higher 5-HT 2A receptor binding potential in the frontal cortex (mean increase: 19%), parietal cortex (mean increase: 25%), and occipital cortex (mean increase: 19%). 5-HT 2A receptor binding potential correlated negatively with age in both patients and comparison subjects and positively with the Dysfunctional Attitudes Scale in the recovered patients. Conclusions: These findings should be considered preliminary but suggest that recovered subjects with a history of recurrent major depression have elevated binding potential of cortical 5-HT 2A receptors. The correlation of increased 5-HT 2A receptor binding potential with increased scores on Dysfunctional Attitudes Scale supports earlier work suggesting that increased 5-HT 2A receptor availability characterizes a group of depressed patients with high levels of dysfunctional attitudes.

Deep Brain Stimulation for OCD and Major Depression

Back to table of contents Previous article Next article Letter to the EditorFull AccessDeep Brain Stimulation for OCD and Major DepressionBRUNO AOUIZERATE, M.D., Ph.D., CORINNE MARTIN-GUEHL, M.D., Ph.D., EMMANUEL CUNY, M.D., DOMINIQUE GUEHL, M.D., Ph.D., HELENE AMIEVA, Ph.D., ABDELHAMID BENAZZOUZ, Ph.D., COLETTE FABRIGOULE, Ph.D., BERNARD BIOULAC, M.D., Ph.D., JEAN TIGNOL, M.D., and PIERRE BURBAUD, M.D., Ph.D., BRUNO AOUIZERATESearch for more papers by this author, M.D., Ph.D., CORINNE MARTIN-GUEHLSearch for more papers by this author, M.D., Ph.D., EMMANUEL CUNYSearch for more papers by this author, M.D., DOMINIQUE GUEHLSearch for more papers by this author, M.D., Ph.D., HELENE AMIEVASearch for more papers by this author, Ph.D., ABDELHAMID BENAZZOUZSearch for more papers by this author, Ph.D., COLETTE FABRIGOULESearch for more papers by this author, Ph.D., BERNARD BIOULACSearch for more papers by this author, M.D., Ph.D., JEAN TIGNOLSearch for more papers by this author, M.D., and PIERRE BURBAUDSearch for more papers by this author, M.D., Ph.D., Bordeaux, FrancePublished Online:1 Nov 2005https://doi.org/10.1176/appi.ajp.162.11.2192AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Deep brain stimulation has been proposed to alleviate treatment-resistant obsessive-compulsive disorder (OCD) (1). We examined the long-term efficacy of deep brain stimulation of the ventral caudate nucleus in a case of primary, severe, and intractable OCD with concomitant major depression.We previously reported the case of Mr. A, a 56-year-old man suffering from a severely disabling and refractory form of OCD that began over 4 decades before (2). He mainly experienced somatic obsessions concerning potential disturbances in bodily functioning, especially regarding his arms, fingers, legs, and gastrointestinal tract, and his mental capacities, with compulsive verification of functioning, comprising repetitive voluntary movements, controlled intake of foods according to their purgative properties, and repeated mental acts of questioning. Aggressive obsessions with fear of embarrassing thoughts about his children occurred, although considerably less frequently. OCD coexisted only with a lifetime history of recurrent major depression. Mr. A’s written informed consent had been obtained before his participation in the study. Psychiatric assessments included the Yale-Brown Obsessive Compulsive Scale, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Global Assessment of Functioning (GAF) scale. Neuropsychological assessments consisted of a wide range of tests primarily exploring memory and executive functions (2). These evaluations were performed independently and blindly, regarding stimulation settings. No pharmacological and/or psychological treatment was administered postoperatively.We previously reported that deep brain stimulation of the ventral caudate nucleus progressively improved Mr. A’s depressive and anxiety symptoms until remission was achieved at 6 months (Hamilton depression scale score ≤7 and Hamilton anxiety scale score ≤10) (2). There was also a marked but delayed reduction in OCD symptom severity on the Yale-Brown Obsessive Compulsive Scale from a baseline score of 25 to 10 and 14 at 12 and 15 months after deep brain stimulation, respectively. His level of functioning on the GAF scale gradually increased from 35 to 60 over the first 15 months of the postoperative period (2). Failure of the pulse generator battery, which was discovered after a clinical impairment, did not affect depressive and anxiety symptom intensity but worsened his obsessive-compulsive manifestations, especially his somatic preoccupations and the related checking compulsions (Yale-Brown Obsessive Compulsive Scale score=21), with a slight deterioration of global functioning (GAF scale score=55) at 18 months. A return to remission levels of OCD (Yale-Brown Obsessive Compulsive Scale score <16) was observed 3 months after replacement of the generator and remained stable until the end of the 27-month follow-up (final Yale-Brown Obsessive Compulsive Scale score=12). This was paralleled by an improvement in psychosocial functioning (final GAF scale score=65). Of interest, no neuropsychological alteration or any adverse clinical effect was reported.Thus, this finding strengthens our previous report, suggesting that deep brain stimulation of the ventral caudate nucleus could be a promising strategy for the treatment of refractory cases of both OCD and major depression.

Methylphenidate May Treat Apathy Independent of Depression

To report a case of apathy treated with methylphenidate in which improvement in apathy was independent of improvement of depression. A 47-year-old woman with a 20-year history of recurrent major depression was diagnosed as having significant apathy with lack of initiative and motivation. Over the course of a 4-week treatment regimen with methylphenidate, her apathy, as measured by the Apathy Evaluation Scale, improved, with her score decreasing from 57 to 31. During this period, her depression, as assessed by the 21-item Hamilton Rating Scale for Depression, remained unchanged. Our report of improvement of apathy with methylphenidate is consistent with other reports in the literature, although previous studies have not specifically used the rating scales to assess apathy. Even though this patient had experienced apathy for a long time, it had not been detected due to lack of direct questioning. In this case, as noted, the improvement of apathy was independent of improvement in depression. A high degree of suspicion and specific inquiry is required for identification of apathy. Once detected, methylphenidate may be beneficial in its treatment, a strategy that may work independently of augmentation of antidepressants.

Coronary and Aortic Calcification in Women With a History of Major Depression

Although depression is a well-documented risk factor for clinical heart disease, its association with subclinical atherosclerosis is unclear. We hypothesized that middle-aged women with a history of recurrent major depression would show evidence of atherosclerosis. Coronary and aortic calcification was measured by electron beam tomography in 58 African American and 152 white healthy middle-aged women. Women were administered the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and a self-report measure of current depressive symptoms. Coronary calcification was found in 103 women (49%) and aorta calcification in 144 women (54%); high calcification scores were set at approximately 75% of the sample distribution (ie, at >/=10 for the coronary calcium score [n = 49 women] and at >100 for the aorta calcium score [n = 53 women]). Women with a history of recurrent major depression (n = 53) were more likely to have any coronary calcification or calcification in the high category at either site compared with women with a history of a single episode of depression or no depression. After stepwise forward adjustment for cardiovascular risk factors and sociodemographic characteristics, a history of recurrent major depression, compared with a single episode or no history, was associated with odds ratios (ORs) of 2.46 (95% confidence interval [CI], 1.06-5.67) for any coronary calcification, 2.71 (95% CI, 1.08-6.81) for high coronary calcification, and 3.39 (95% CI, 1.34-8.63) for high aortic calcification. Further adjustments for waist-hip ratio reduced the association between history of recurrent depression and any calcification (OR, 2.24; 95% CI, 0.94-5.32) and high calcification (OR, 2.31; 95% CI, 0.89-5.99). In this sample of asymptomatic middle-aged women without known coronary disease, recurrent major depression was independently associated with coronary and aortic calcification. Waist-hip ratio in part mediated the association. Our findings suggest that recurrent major depression may be a risk factor for early atherosclerosis in women.

Who Benefits from More Structured Depression Treatment?

This article uses data from two studies that have demonstrated the overall effectiveness of Collaborative Care interventions to evaluate factors associated with poor outcomes overall (general prognostic factors) and factors associated with greater or lesser effects of treatment (differential treatment effects). Adult primary care patients initiating antidepressant treatment for major depression were randomized to usual care or to Collaborative Care, a structured depression treatment program that included planned, proactive and coordinated care with a health care team and informed, activated patients (n = 156, mean age = 43, 85% white). Response to treatment was defined as a 50% or greater reduction in depression at four months. High neuroticism and a history of recurrent major depression (3+ episodes) or dysthymia predicted poor outcomes in general. While the magnitude of the intervention effects differed, frequently cited predictors of persistence of depression (age, gender, depression severity, medical and psychiatric comorbidity) were not significantly associated with greater or lesser benefit from Collaborative Care (no differential treatment effects). Results demonstrate the robustness of intervention effects across numerous groups at risk for persistence of depression. These findings suggest that at the time of diagnosis it is not possible to predict who is most likely to benefit from Collaborative Care. Instead, outcomes of treatment should be routinely monitored among depressed patients to ensure optimal response.

Influence of synaptic serotonin level on [ 18F]altanserin binding to 5HT 2 receptors in man

The feasibility of in vivo serotonin 5HT 2 receptor binding measurement using [ 18F]altanserin as a radioligand has been well established. In this study, the postsynaptic receptor binding potential of this ligand was examined as a possible indicator of synaptic serotonin content after pharmacological challenge. Studies were performed in 11 subjects with a history of recurrent major depression. Six of them received serotonergic antidepressive treatment at the time of the experiment, the other five patients were untreated. Two PET measurements were carried out in each subject within 2 or 3 days. Before one of the measurements, 25 mg of the serotonin re-uptake inhibitor clomipramine were given intravenously, the other measurement was done without pharmacological challenge. The data were analyzed using non-linear least-square regression and Logan's graphical method. In the whole group of subjects, binding potential and distribution volume of altanserin decreased following clomipramine challenge. The decrease was between 14 ( P=0.03) and 23% ( P=0.004). This effect was mainly seen in subjects not on antidepressive medication. Clomipramine challenge probably increased the synaptic serotonin level, which competed with altanserin leading to the lowered binding potential. The paradigm might, thus, be useful to estimate serotonin release in vivo. Pretreatment with serotonergic antidepressants reduces the effect of clomipramine.

Depression Duration But Not Age Predicts Hippocampal Volume Loss in Medically Healthy Women with Recurrent Major Depression

This study takes advantage of continuing advances in the precision of magnetic resonance imaging (MRI) to quantify hippocampal volumes in a series of human subjects with a history of depression compared with controls. We sought to test the hypothesis that both age and duration of past depression would be inversely and independently correlated with hippocampal volume. A sample of 24 women ranging in age from 23 to 86 years with a history of recurrent major depression, but no medical comorbidity, and 24 case-matched controls underwent MRI scanning. Subjects with a history of depression (post-depressed) had smaller hippocampal volumes bilaterally than controls. Post-depressives also had smaller amygdala core nuclei volumes, and these volumes correlated with hippocampal volumes. In addition, post-depressives scored lower in verbal memory, a neuropsychological measure of hippocampal function, suggesting that the volume loss was related to an aspect of cognitive functioning. In contrast, there was no difference in overall brain size or general intellectual performance. Contrary to our initial hypothesis, there was no significant correlation between hippocampal volume and age in either post-depressive or control subjects, whereas there was a significant correlation with total lifetime duration of depression. This suggests that repeated stress during recurrent depressive episodes may result in cumulative hippocampal injury as reflected in volume loss.

Charles Bonnet Syndrome with Peripheral and Central Findings

The Charles Bonnet syndrome comprises complex vivid visual hallucinations without significant psychopathology or disturbed consciousness and has been known for several hundred years. A consensus is lacking whether eye and brain disease are necessary or exclusionary criteria for this syndrome. We describe the recent onset of complex and vivid visual hallucinations in a 73-year-old man with macular degeneration and a history of recurrent major depression. We discuss ophthalmologic and radiographic findings in the context of syndrome cause.

Charles Bonnet Syndrome with Peripheral and Central Findings

The Charles Bonnet syndrome comprises complex vivid visual hallucinations without significant psychopathology or disturbed consciousness and has been known for several hundred years. A consensus is lacking whether eye and brain disease are necessary or exclusionary criteria for this syndrome. We describe the recent onset of complex and vivid visual hallucinations in a 73-year-old man with macular degeneration and a history of recurrent major depression. We discuss ophthalmologic and radiographic findings in the context of syndrome cause.