Depression: Matthews K

Anderson IM, Ferrier IN, Baldwin RC, Cowen PJ, Howard L, Lewis G, Matthews K, McAllister-Williams RH, Peveler RC, Scott J, Tylee A. · Senior Lecturer and Honorary Consultant Psychiatrist, Neuroscience and Psychiatry Unit, University of Manchester, UK. · J Psychopharmacol. · Pubmed #18413657 No free full text.

Abstract: A revision of the 2000 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in May 2006. Key areas in treating depression were reviewed, and the strength of evidence and clinical implications were considered. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is provided, which identifies the quality of evidence to inform the recommendations, the strength of which are based on the level of evidence. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse, and stopping treatment.

Matthews K, Eljamel MS. · No affiliation provided · Br J Psychiatry. · Pubmed #12948985 links to  free full text

This publication has no abstract.

Matthews K, Christmas D, Swan J, Sorrell E. · Division of Pathology and Neuroscience, Department of Psychiatry, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · Neurosci Biobehav Rev. · Pubmed #15925695 No free full text.

Abstract: Animal models of human disease have proven of considerable value in elucidating basic pathophysiological mechanisms and in developing novel treatments. However, modelling human mental disorders in experimental animals is fraught with difficulties. Depression models generally lack both clinical and scientific credibility and have, thus far, failed to inform treatment strategies previously acquired through serendipity. The complexity and heterogeneity of the clinical states labelled 'depression' dictate that we continue to work with a crude and uninformative taxonomy within which 'core' clinical and pathophysiological features of depression are not clearly identified. Consequently, much of the neuroscience of animal modelling is framed around physiological and neurobiological phenomena that may be of relevance to only a minority of patients. Additionally, inferring pathophysiology from apparent treatment responses overestimates the efficacy of existing treatments and tends to ignore reliable demonstrations of the 'antidepressant effects' of non-pharmacological interventions. Whilst animal modelling remains a potentially important approach towards understanding neurobiological mechanisms in depression, we need to address the poverty of reliable clinical science that should inform model development.

Matthews K, Eljamel MS. · Ninewells Hospital and Medical School, Dundee, Scotland, UK. · Br J Psychiatry. · Pubmed #12724243 links to  free full text

Abstract: BACKGROUND: Despite the application of ablative neurosurgical treatments for intractable mental disorder throughout most of the past century, unequivocal evidence for efficacy has not been provided. AIMS: To review the status of ablative neurosurgery for mental disorder and to describe the activities of the Scottish national service. METHOD: Relevant literature is reviewed alongside a description of recent clinical activity. RESULTS: Neurosurgical treatment is offered to a small number of patients severely disabled by otherwise intractable mental disorder. There are inequalities in the strength of evidence to support the use of some of these procedures. The frequency and severity of adverse effects remains unclear. We are collecting data that should inform future practice. CONCLUSIONS: Modern neurosurgery can offer clinically meaningful symptom relief and improved function for 'untreatable' patients with chronic, severe depression and obsessive-compulsive disorder. However, follow-up studies of greater rigour are required. The potential role of non-ablative alternatives remains unclear.

Ridout N, O'Carroll RE, Dritschel B, Christmas D, Eljamel M, Matthews K. · Clinical and Cognitive Neurosciences, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK. · Neuropsychologia. · Pubmed #17327133 No free full text.

Abstract: Four patients that had received an anterior cingulotomy (ACING) and five patients that had received both an ACING and an anterior capsulotomy (ACAPS) as an intervention for chronic, treatment refractory depression were presented with a series of dynamic emotional stimuli and invited to identify the emotion portrayed. Their performance was compared with that of a group of non-surgically treated patients with major depression (n=17) and with a group of matched, never-depressed controls (n=22). At the time of testing, four of the nine neurosurgery patients had recovered from their depressive episode, whereas five remained depressed. Analysis of emotion recognition accuracy revealed no significant differences between depressed and non-depressed neurosurgically treated patients. Similarly, no significant differences were observed between the patients treated with ACING alone and those treated with both ACING and ACAPS. Comparison of the emotion recognition accuracy of the neurosurgically treated patients and the depressed and healthy control groups revealed that the surgically treated patients exhibited a general impairment in their recognition accuracy compared to healthy controls. Regression analysis revealed that participants' emotion recognition accuracy was predicted by the number of errors they made on the Stroop colour-naming task. It is plausible that the observed deficit in emotion recognition accuracy was a consequence of impaired attentional control, which may have been a result of the surgical lesions to the anterior cingulate cortex.

Swan J, Sorrell E, MacVicar B, Durham R, Matthews K. · Department of Psychiatry, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. <> · J Affect Disord. · Pubmed #15465585 No free full text.

Abstract: BACKGROUND: Failure to respond to antidepressant medication represents a major clinical problem. Few therapeutic interventions have been shown to benefit such individuals. METHOD: Patients attended a 12-session psychoeducational programme over a period of 10 weeks, with follow-up at 26 weeks. The main outcome measures were the self-report Beck Depression Inventory (BDI-II), the Global Severity Index (GSI) of the Brief Symptom Inventory (BSI) and the EuroQol 5D. RESULTS: Baseline assessments confirmed substantial chronicity and treatment resistance, high symptom burden and poor quality of life in the study cohort. Twenty-six week follow-up data were obtained from 34% of cohort. Completion of the course was associated with clinically significant changes in symptom burden. Sustained remission was achieved by 35% of completers. LIMITATIONS: We did not characterise the cohort using structured clinical interview and did not collect structured, objective ratings of mental health status. There was no control group. There was a high attrition rate and caution must be exercised in interpreting results. CONCLUSIONS: For a proportion of patients with chronic depressive episodes that have not responded to antidepressant treatments, the "Coping with Depression" psychoeducational group may confer sustained and meaningful benefit. Controlled studies are warranted.

Lewis TT, Everson-Rose SA, Colvin A, Matthews K, Bromberger JT, Sutton-Tyrrell K. · Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, New Haven, CT 06510, USA. · Psychosom Med. · Pubmed #19188530 No free full text.

Abstract: OBJECTIVE: To examine the cross-sectional associations among race, depressive symptoms, and aortic and coronary calcification in a sample of middle-aged women. Depressive symptoms have been associated with atherosclerotic indicators of coronary heart disease (CHD) in white women. Few studies have examined these associations in samples including African American women, or explored whether any observed associations differ by race. METHODS: Participants were 508 (38% African American, 62% white) women. Aortic and coronary calcification were measured by electron beam tomography and depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D). Multivariable linear and logistic regression models were conducted to test associations. RESULTS: In linear regression models adjusted for race, depressive symptoms were associated with a greater amount of aortic calcification (beta = 0.03, p = .01), and there was a significant race x depressive symptoms interaction (beta = 0.07, p = .006). Findings for depressive symptoms (odds ratio (OR) = 1.03, 95% Confidence Interval (CI) = 1.0-1.06, p = .07), and the race x depressive symptoms interaction (OR = 1.1, 95% CI = 1.01-1.18, p = .01) were similar in race-adjusted multinomial logistic regression models predicting high levels of aortic calcification. Race-specific models revealed a significant association between depressive symptoms and aortic calcification in African American, but not white women. Additional adjustments for education, study site, and CHD risk factors did not alter these results. Depressive symptoms were not associated with coronary calcification for women of either racial group. CONCLUSIONS: African American women may be particularly vulnerable to the effects of depressive symptoms on early atherosclerotic disease.

Bromberger JT, Kravitz HM, Matthews K, Youk A, Brown C, Feng W. · Departments of Epidemiology and Psychiatry, and Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. · Psychol Med. · Pubmed #18377672 No free full text.

Abstract: BACKGROUND: Little is known about factors that predict first lifetime episodes of major depression in middle-aged women. It is not known whether health-related factors and life stress pose more or less of a risk to the onset of clinical depression than does the menopausal transition. METHOD: The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) was used to assess diagnoses of lifetime, annual and current major depression in a community-based sample of premenopausal or early perimenopausal African American and White women. Menstrual cycle characteristics, psychosocial and health-related factors, and blood samples for assay of reproductive hormones were obtained annually. Two hundred and sixty-six women without a history of major depression at baseline constituted the cohort for the current analyses. RESULTS: Over 7 years of follow-up, 42 (15.8%) women met criteria for a diagnosis of major depression. Frequent vasomotor symptoms (VMS; hot flashes and/or night sweats) (HR 2.14, p=0.03) were a significant predictor of major depression in univariate analyses. After simultaneous adjustment for multiple predictors in Cox proportional hazards analyses, frequent VMS were no longer significant; lifetime history of an anxiety disorder (HR 2.20, p=0.02) and role limitations due to physical health (HR 1.88, p=0.07) at baseline and a very stressful life event (HR 2.25, p=0.04) prior to depression onset predicted a first episode of major depression. CONCLUSIONS: Both earlier (e.g. history of anxiety disorders) and more proximal factors (e.g. life stress) may be more important than VMS in contributing to a first episode of major depression during midlife.

Matthews K, Coghill D, Rhodes S. · Section of Psychiatry and Behavioural Sciences, Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · J Affect Disord. · Pubmed #18367251 No free full text.

Abstract: BACKGROUND: Neuropsychological impairment has been demonstrated in adults with depression. Whether depression arising during adolescence is associated with similar changes is unknown. We describe the neuropsychological functioning of a referred sample of medication-naïve adolescent girls meeting criteria for a diagnosis of Depressive Episode (ICD-10). METHODS: A cross-sectional study of 28 girls (ages 12-16); 14 with depression, 14 healthy controls matched for age, IQ and socio-economic status. Neuropsychological testing was conducted using the CANTAB automated test battery. RESULTS: Depressed adolescent girls showed performance deficits on visual memory tasks (Pattern Recognition, Delayed Matching to Sample and Paired Associates Learning), one measure of motor speed and on a test of Spatial Working Memory. LIMITATIONS: A restricted range of neuropsychological testing was performed on a female-only sample of modest size. CONCLUSIONS: Depressive episodes in adolescent girls are associated with neurocognitive deficits similar to those previously defined in adult populations and these impairments can be detected prior to exposure to psychotropic drugs. Neuropsychological impairment may be an important, neglected clinical feature in adolescent depression.

Wilkie MJ, Smith G, Day RK, Matthews K, Smith D, Blackwood D, Reid IC, Wolf CR. · Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. · Pharmacogenomics J. · Pubmed #18253134 No free full text.

Abstract: The majority of antidepressant drugs act by increasing synaptic serotonin levels in the brain. Genetic variation in serotonin-related genes may therefore influence antidepressant efficacy. In this study, nine polymorphisms in four serotonin receptor genes (HTR1B, HTR2A, HTR5A and HTR6) and the serotonin transporter gene (SLC6A4) were analysed to investigate their influence on antidepressant response in a well-characterized unipolar depressive population (n=166) following a protocolized treatment regimen. 5-HTTLPR short-allele homozygotes were significantly associated with both remission (odds ratios (OR)=4.00, P=0.04) and response (OR=5.06, P=0.02) following second switch treatment, with a similar trend observed following initial treatment and paroxetine therapy. Following initial treatment, unipolar patients homozygous for the SLC6A4 intron 2 repeat polymorphism were significantly associated with lack of remission (OR=0.38, P=0.02) and lack of response (OR=0.42, P=0.01). Additionally, the HTR2A C(1354)T polymorphism showed an association with remission (OR=7.50, P=0.002) and response (OR=5.25, P=0.01) following paroxetine therapy. These results suggest that genetically determined variation in serotonin receptor genes makes a significant contribution to the efficacy of commonly prescribed antidepressant drugs.

Adler N, Singh-Manoux A, Schwartz J, Stewart J, Matthews K, Marmot MG. · Department of Psychiatry, University of California at San Francisco, San Francisco, CA 94118, USA. · Soc Sci Med. · Pubmed #18180089 No free full text.

Abstract: Socioeconomic status (SES) is related to health in every industrialized society where it has been studied. Indicators include educational attainment, occupational status, and income. Subjective social status (SSS), a summative judgment of one's socioeconomic position across these dimensions, also appears to be associated with health status. The current study examines whether SSS has similar associations with SES indicators and with health outcomes among British civil servants (participants in the Whitehall-II study), and U.S. whites and blacks (participants in the CARDIA study). The comparisons shed light on social status in the U.S. and England and on the applicability of findings from Whitehall-II to both whites and blacks in the U.S. Parallel analyses in each group examined (1) the extent to which income, education, and occupational status determine SSS ratings, (2) the association of SSS with hypertension, depression, and global health, and (3) the extent to which adjustment for education, occupation and income individually and collectively reduce the association of SSS and health outcomes. As predicted, occupation is a more important determinant of SSS in Whitehall-II than in CARDIA; adjustment for occupation reduces the association between SSS and health outcomes more for the Whitehall-II participants -- especially males -- than for CARDIA participants. Among the latter, education and income play relatively greater roles. Socioeconomic factors do not predict SSS scores for blacks as well as they do for the other two groups. SSS is significantly related to global health and depression in all groups and to hypertension in all groups except black males. Overall, relationships of SSS and health were stronger for Whitehall-II and white CARDIA participants than for blacks in CARDIA.

Schlaepfer TE, Frick C, Zobel A, Maier W, Heuser I, Bajbouj M, O'Keane V, Corcoran C, Adolfsson R, Trimble M, Rau H, Hoff HJ, Padberg F, Müller-Siecheneder F, Audenaert K, Van den Abbeele D, Matthews K, Christmas D, Stanga Z, Hasdemir M. · Departments of Psychiatry, University Hospital, Bern, Switzerland. · Psychol Med. · Pubmed #18177525 No free full text.

Abstract: BACKGROUND: Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression. METHOD: An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically. RESULTS: The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (> or = 50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%). CONCLUSIONS: VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European study.

Steele JD, Christmas D, Eljamel MS, Matthews K. · Department of Mental Health, University of Aberdeen, Royal Cornhill Hospital, Aberdeen, United Kingdom. · Biol Psychiatry. · Pubmed #17916331 No free full text.

Abstract: BACKGROUND: Anterior cingulotomy (ACING) is a neurosurgical treatment for chronic refractory depression, pain, and obsessive-compulsive disorder. Anterior cingulotomy involves the placement of bilateral lesions in the anterior cingulate under stereotactic guidance. Although a long-established therapeutic intervention, the optimal location and volume of lesions are not known, but it is generally believed that efficacious lesions interrupt the fibers of the cingulum bundle. METHODS: Using T2-weighted magnetic resonance imaging, we tested the hypothesis that lesions placed more anteriorly would be associated with a better clinical response. We also tested a secondary hypothesis that a superior clinical response would be associated with larger lesion volumes. RESULTS: When assessed 12 months following surgery, a superior clinical response was associated with more anterior lesions but, unexpectedly, with smaller lesion volumes. Specifically, the best clinical response was associated with total (right plus left hemisphere) lesion volumes of 1000 to 2000 mm(3) centered at Montreal Neurological Institute (MNI) coordinates (+/- 9,19,30). CONCLUSIONS: There is considerable evidence from neuroimaging studies that more rostral areas within the anterior cingulate cortex are functionally and structurally abnormal in patients with major depressive disorder. Anteriorly placed ACING lesions would target and modify function within such regions. It should not be assumed that larger lesions are associated with a better response. These findings of relationships between lesion characteristics and clinical response argue against the suggestion that ACING represents a placebo treatment.

Wilkie MJ, Smith D, Reid IC, Day RK, Matthews K, Wolf CR, Blackwood D, Smith G. · Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK. · Pharmacogenet Genomics. · Pubmed #17460549 No free full text.

Abstract: OBJECTIVE: Recent evidence suggests that signalling cascades located downstream of monoamine receptors are altered following antidepressant treatment. Our objective was to investigate whether genetic polymorphisms in genes involved in these signalling cascades influenced antidepressant efficacy. METHODS: Polymorphisms in the G-protein beta subunit GNB3, the cAMP response element binding protein 1 gene (CREB1), the brain derived neurotrophic factor (BDNF) and CREB binding protein (CREBBP) were studied in well characterised unipolar (n=166) and early onset (n=102) depressive populations and correlated with treatment response. RESULTS: The GNB3 C825T polymorphism, which results in a 41 amino acid deletion, was significantly associated with lack of remission (OR=0.18, P=0.02) and lack of response (OR=0.26, P=0.03) following 2nd switch treatment. A cytosine deletion 16 base pairs from the start of exon 8 in CREB1 was found more frequently in remitters and responders to 2nd switch antidepressant drug therapy, although these differences failed to reach significance. Polymorphisms detected BDNF (G196A) and CREBBP (T651 C) did not appear to influence antidepressant response. CONCLUSIONS: These results suggest that inheritance of the GNB3C825T allele may significantly influence antidepressant response and emphasises the potential importance of polymorphisms in genes in signalling cascades activated by commonly prescribed antidepressants.

Cyranowski JM, Bromberger J, Youk A, Matthews K, Kravitz HM, Powell LH. · Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. · Arch Sex Behav. · Pubmed #15483368 No free full text.

Abstract: We examined the association between lifetime depression history and sexual function in a community-based sample of midlife women. Specifically, 914 women aged 42-52 who were participants in the Study of Women's Health Across the Nation completed a self-report assessment of their sexual behaviors, sexual desire, sexual arousal, and sexual satisfaction over the past 6 months. On the basis of the Structured Clinical Interview for the DSM-IV , participants were categorized into 1 of 3 lifetime major depressive disorder (MDD) history groups: no MDD history, single episode MDD, and recurrent MDD. In line with previous reports, women with a history of recurrent MDD reported experiencing less frequent sexual arousal, less physical pleasure, and less emotional satisfaction within their current sexual relationships. Although the groups did not differ in their reported frequency of sexual desire or partnered sexual behaviors, lifetime depression history was associated with increased rates of self-stimulation (masturbation). Associations between lifetime depression history and lower levels of physical pleasure within partnered sexual relationships and higher rates of masturbation remained significant following control for current depressive symptoms, study site, marital status, psychotropic medication use, and lifetime history of anxiety or substance abuse/dependence disorder. Future research is needed to characterize the temporal and etiologic relationships among lifetime depressive disorder, current mood state, and sexual function in women across the lifespan.

Stewart CA, Petrie RX, Balfour DJ, Matthews K, Reid IC. · Department of Psychiatry, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K. · Biol Psychiatry. · Pubmed #15050869 No free full text.

Abstract: BACKGROUND: There is a long-standing clinical awareness of the significance of adverse early experiences and subsequent stress in the evolution of psychiatric disorder. METHODS: We investigated the impact of a single episode of preweaning maternal separation on in vivo electrophysiologic responses in the hippocampus of the mature rat after repeated exposure to an open elevated platform. RESULTS: Only rats that had experienced both maternal separation followed by stressful platform exposure when mature had significantly increased granule cell response to perforant path stimulation, compared with control rats. Rats exposed to either maternal separation or the elevated platform in adulthood alone did not differ significantly from control rats. CONCLUSIONS: Adverse early experience seems to induce functional changes in the hippocampus that remain latent until activated by stress in adulthood. Such electrophysiologic changes might represent a neural substrate for vulnerability to stress-associated psychopathology.

Olson MB, Kelsey SF, Matthews K, Shaw LJ, Sharaf BL, Pohost GM, Cornell CE, McGorray SP, Vido D, Bairey Merz CN. · Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. · Eur Heart J. · Pubmed #12919775 links to  free full text

Abstract: AIMS: Our goal was to evaluate health-related quality of life (QOL) in women undergoing angiography for suspected ischaemia. METHODS AND RESULTS: QOL measurements were obtained in 406 women with chest pain symptoms in the Women's Ischemia Syndrome Evaluation (WISE). QOL measures included a general rating (GR), Duke Activity Status Index (DASI), and the Beck Depression Inventory (BDI). Higher scores on the GR and DASI are indicative of better QOL and functioning. Higher scores on the BDI indicate more symptoms of depression. Women were stratified by the presence and absence of obstructive angiographic coronary artery disease (CAD) and by the presence and absence of myocardial ischaemia. Women with angiographic obstructive CAD had lower DASI and higher BDI scores compared to women without obstructive CAD (both P<0.05). Stratification by the presence and absence of ischaemia demonstrated that women with ischaemia had better QOL, evidenced by higher GR QOL scores and lower BDI scores (both P<0.05) than women without ischaemia. Symptoms of angina were significant independent predictors of QOL scores (P<0.001). CONCLUSIONS: Chest pain symptoms have a significant impact on health-related QOL in women undergoing coronary angiography for suspected myocardial ischaemia andare more important determinants of QOL than the underlying conditions of CAD or ischaemia.

Rutledge T, Matthews K, Lui LY, Stone KL, Cauley JA. · Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Psychosom Med. · Pubmed #12883123 links to  free full text

Abstract: OBJECTIVE: To assess the relationship between social network size and prospective mortality risk among a large sample of older, Caucasian women. METHOD: The study included 7524 Caucasian community-dwelling women, age 65 or older (mean age = 74.1), who participated from four U.S. communities. Study participants completed a protocol that included anthropomorphic and health assessments at baseline and the Lubben Social Network Scale at year 2. We followed participants for an average of 6 years after they had completed the year-2 assessment. We used hospital records and a copy of the participant's official death certificate to document mortality and cause of death in accordance to ICD-9 revision codes. RESULTS: A total of 1451 deaths (19.3% of sample) were observed over follow-up, 215 (3.4%) due to cardiovascular causes. Higher social network scores were a robust predictor of lower multivariate-adjusted mortality (RR = 0.92, 95% CI = 0.86-0.98), controlling for age, comorbid disease, body mass, smoking, depression, and education. However, social network benefits were attenuated after controlling for marital status. Married participants showed lower total (RR = 0.83, 95% CI = 0.74-0.94) and CVD (RR = 0.59, 95% CI = 0.43-0.81) covariate-adjusted death rates compared with unmarried participants. CONCLUSIONS: Social network scores and marriage were each associated with reduced prospective mortality risk among older women. The relationships shown here suggest that much of the protection afforded by larger social networks in older women results from marriage rather than other forms of social relationships. Mechanisms at the physiological or behavioral level explaining social relationship benefits remain important areas for future research.

Matthews K, Robbins TW. · Department of Psychiatry, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · Neurosci Biobehav Rev. · Pubmed #12732222 No free full text.

Abstract: Depression is a major public health concern, representing one of the most significant causes of disability and morbidity. Despite significant advances in the definition of specific cognitive, emotional and neural dysfunctions that are associated with depression, there has been frustratingly little progress in the elucidation of plausible aetiological and pathophysiological mechanisms. The complex, multi-system dysfunctions of depressive illness do not lend themselves to hypothesis-driven, systematic manipulation in patients. For this reason, there is a need to develop valid and reliable models of affective psychopathology in laboratory animals. In this paper, we review briefly some of our previous work demonstrating that a specific periodic neonatal maternal separation procedure leads to a robust constellation of behavioural changes in the adult rat that resemble core aspects of human depressive psychopathology. We also present data from a study of the adult effects of the same manipulation on electrical intracranial self-stimulation behaviour. These data further support the hypothesis that it is possible to model vulnerability to anhedonia in the adult rat by manipulation of early experience.

Whooley MA, Kiefe CI, Chesney MA, Markovitz JH, Matthews K, Hulley SB, Anonymous00057. · Department of Veterans Affairs Medical Center, 4150 Clement St (Mail Stop 111A1), San Francisco, CA 94121. · Arch Intern Med. · Pubmed #12456234 links to  free full text

Abstract: BACKGROUND: Previous studies have suggested an association between depression and low socioeconomic status, but few have empirically examined the effect of depressive symptoms on income and employment over time. OBJECTIVE: To determine whether depressive symptoms are associated with subsequent unemployment or loss of family income. METHODS: We performed a prospective cohort study of 5115 adults aged 18 to 30 years. These participants included approximately equal numbers of African Americans and whites and men and women from 4 cities in the United States who completed the 1990-1991 examination of the Coronary Artery Risk Development in Young Adults (CARDIA) study. For this analysis, we included 2334 participants who were employed full or part time and who reported an annual family income of $25 000 or more. Participants completed the Center for Epidemiologic Studies Depression Scale and were considered to have depressive symptoms if they scored 16 or higher on the 60-point scale. We evaluated self-reported unemployment and annual family income during 5 years of follow-up. RESULTS: Thirty-three percent (118/354) of participants with depressive symptoms (Center for Epidemiologic Studies Depression Scale score >/=16) in 1990-1991 and 21% (335/1581) of participants without substantial depressive symptoms (Center for Epidemiologic Studies Depression Scale score <16) reported new unemployment during the subsequent 5 years (odds ratio, 1.9; 95% confidence interval, 1.4-2.4; P<.001). This association remained strong after adjusting for potential confounding variables, including marital status, education, history of unemployment, current part-time (vs full-time) employment, and cigarette smoking (odds ratio, 1.6; 95% confidence interval, 1.2-2.0; P =.001). Seventeen percent (62/371) of participants with depressive symptoms and 7% (113/1631) of participants without substantial depressive symptoms in 1990-1991 reported that their family income had decreased below $25 000 by 1995-1996 (odds ratio, 2.7; 95% confidence interval, 1.9-3.8; P<.001). This association also remained strong after adjusting for potential confounding variables (odds ratio, 1.9; 95% confidence interval, 1.3-2.7; P<.001). CONCLUSIONS: Depressive symptoms are associated with subsequent unemployment and loss of family income among working young adults. Socioeconomic indicators, such as income and employment, should be considered in evaluating the potential benefits of treatment for patients with depressive symptoms.

Matthews K, Cauley J, Yaffe K, Zmuda JM. · University of Pittsburgh, Pennsylvania 15213, USA. · J Am Geriatr Soc. · Pubmed #10323642 No free full text.

Abstract: BACKGROUND: The purpose of this study was to evaluate the cross-sectional and longitudinal association of oral estrogen replacement therapy (ERT) and cognitive function in an older, nondemented sample of women. METHODS: In a prospective cohort of 9651 white women aged 65 years and older enrolled in the Study of Osteoporotic Fractures, a modified Mini-Mental Status Exam (mMMSE), and digit symbol substitution and Trails B tests were administered twice, 4 to 6 years apart. History and current use of oral ERT was documented. Age, educational attainment, and activity limitations were the primary covariates in the analyses; in addition, stroke and depression scores were adjusted in subsets of women with available data. RESULTS: Current and past users of ERT had better initial scores on the mMMSE than did never users, P < .05 and .001, respectively, with better scores for current estrogen hormone users being most apparent among the older and less educated women. The percentages of women scoring < or = 23 of a possible 26 on the mMMSE were 14.3 for current users, 14.5 for past users, and 20.5 for never users, P < .001. However, only past users exhibited smaller declines upon retesting in mMMSE and Trails B performance, P < .05, than did never users. Educational attainment predicted both initial test scores and change scores and was, next to age, the most powerful predictor of cognitive function. CONCLUSIONS: Current oral ERT does not protect against age-related declines in cognitive function in older nondemented women, whereas formal education does protect, even though it had been completed many years earlier. The influence of education in late-life on cognitive function should be tested.