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Objective Late-life depression has been associated with risk for cerebrovascular pathology, as demonstrated in neuroimaging studies of older depressed patients, as well as mood disorder following cerebrovascular accidents. However, more research is needed on neuroanatomical changes in late-life depression, where there has been no clearly documented link to brain injury. Such studies should examine morphological changes in medium and small sized vessels that supply the cortical gray and white matter. Methods The present study used a non-specific histological Nissl staining and a more vessel-specific immunolabeling with endothelial marker von Willebrand Factor (vWF) to estimate density and size of blood vessel segments in the orbitofrontal cortex of 16 older subjects with major depressive disorder (MDD) and 9 non-psychiatric comparison subjects. Results The density of Nissl-stained vessel segments and of segments with perivascular spaces was higher in subjects with MDD than in comparison subjects in gray (GM) and white matter (WM). In GM, the density of vWF-immunoreactive segments with cross-sectional areas greater than 800 µm2 was higher in MDD. In WM, only the density of vWF-immunoreactive segments with patent perivascular spaces and diameters larger than 60 µm was higher in subjects with MDD. Also in the WM, only subjects with late-onset MDD presented a significantly higher density of vWF-positive segments than comparison subjects. Conclusions In older subjects with MDD, there appear to be morphological changes that increase visibility of medium-sized vessel segments with some labeling techniques, and this increased visibility may be related to increased patency of perivascular spaces around arterioles. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Metabolomics is an emerging technology that allows researchers to characterize hundreds of small molecules that comprise the metabolome. We sought to determine metabolic differences in depressed and nondepressed participants. The sample consisted of a depressed group of patients with heart failure enrolled in an NIMH-supported clinical trial of sertraline versus placebo in depressed heart failure patients, and a nondepressed comparator group of heart failure patients. Plasma was obtained from blood samples provided by participants at baseline, and samples were profiled on GC-MS and LC-MS metabolomics platforms for biochemical content. A number of biochemicals were significantly different between groups, with depressed participants showing higher concentrations of several amino acids and dicarboxylic fatty acids. These results are consistent with prior findings where changes in neurotransmitter systems and fatty acid metabolism were shown to associate with the depressed state. It is unclear what role heart failure may have played in these differing concentrations. [ABSTRACT FROM AUTHOR]

Background: Cortical and subcortical hyperintensities in magnetic resonance imaging (MRI) scans are thought to represent areas of ischemic damage to brain tissue. Researchers have focused on the possible role these lesions may have in psychiatric disorders, including bipolar disorder. In 1997, the proposed 'vascular mania' diagnosis suggested utilizing not only the presence of strokes, but also confluent hyperintensities in its diagnostic criteria. This study was conducted to use meta-analytic techniques to investigate the association of hyperintensities and bipolar illness and to evaluate the current state of the literature. Methods: Using the PubMed and MEDLINE databases, we conducted a systematic literature search of studies investigating hyperintensities in subjects with bipolar disorder and controls or other psychiatric illnesses. We identified 44 publications from which 35 studies were included for review and 27 were selected for meta-analysis. Summary statistics of the prevalence were estimated through odds-ratios and confidence interval. Heterogeneity of the results across studies was tested using Q-statistics. Results: Meta-analysis identified an odds ratio of 2.5 (95% CI 1.9, 3.3) for hyperintensities in bipolar subjects compared to controls; however, there was significant heterogeneity among the studies (Q-statistics = 32; p = 0.04). This finding was most prominent for adolescents and children where the odds ratio was 5.7 (95% CI 2.3, 13.7). Deep white matter hyperintensities (odd ratio 3.2; 95% CI 2.2, 4.5) and subcortical grey matter hyperintensities (odds ratio 2.7; 95% CI 1.3, 2.9) were more strongly associated with bipolar subjects. There were no differences between bipolar subjects and controls for perivascular hyperintensities (odds ratio 1.3; 95% CI 0.8, 1.9). Though hyperintensities were numerically greater in bipolar subjects, meta-analysis did not demonstrate any significant differences between bipolar subjects and unipolar depression subjects (OR 1.6; 95% CI 0.9, 2.7) nor subjects with schizophrenia (OR 1.5; 95% CI 0.9, 2.7). Conclusions: This meta-analysis continues to support the association of bipolar disorder and hyperintensities, especially in the deep white matter and subcortical grey matter. It also highlights the increased incidence in children and adolescence with bipolar disorder. However, hyperintensities are not specific to bipolar disorder, but appear at similar rates in unipolar depression and schizophrenia. Thus, the role of hyperintensities in the pathogenesis, pathophysiology, and treatment of bipolar disorder remains unclear. Further studies are required that are large enough to decrease the heterogeneity of the samples and MRI techniques, assess size and location of hyperintensities, and the impact on treatment response. Coordination with newer imaging techniques, such as diffusion tensor imaging (DTI) may be especially helpful in understanding the pathology of these lesions. [ABSTRACT FROM AUTHOR]

Objective Theories about the impact of stressful life events (SLE) in bipolar disorder have focused on their role early in the disease. Few studies have examined SLE in older bipolar patients. We wanted to assess the impact of SLE in late life bipolar disorder Methods We evaluated negative SLE experienced by older bipolar subjects compared with younger bipolar subjects and older controls for number, type, and their association with phase of illness, age of onset, and previous episodes. Results Both younger and older bipolar subjects have more SLE than similarly aged controls. There was no significant difference in the number of stressors that younger and older bipolar subjects experienced, based on mood state, previous episodes, or age-of-onset. Both older and younger depressed bipolar subjects reported more SLE in the previous 12 months compared with those in a manic state. Conclusions Negative SLE are much more prevalent in bipolar patients compared with age-matched controls, and continue to be frequent in later life. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Major depression in the elderly is associated with brain structural changes and vascular lesions. Changes in the subcortical regions of the limbic system have also been noted. Studies examining hippocampus volumetric differences in depression have shown variable results, possibly due to any volume differences being secondary to local shape changes rather than differences in the overall volume. Shape analysis offers the potential to detect such changes. The present study applied spherical harmonic (SPHARM) shape analysis to the left and right hippocampi of 61 elderly subjects with major depression and 43 non-depressed elderly subjects. Statistical models controlling for age, sex, and total cerebral volume showed a significant reduction in depressed compared with control subjects in the left hippocampus (F1,103 = 5.26; p = 0.0240) but not right hippocampus volume (F1,103 = 0.41; p = 0.5213). Shape analysis showed significant differences in the mid-body of the left (but not the right) hippocampus between depressed and controls. When the depressed group was dichotomized into those whose depression was remitted at time of imaging and those who were unremitted, the shape comparison showed remitted subjects to be indistinguishable from controls (both sides) while the unremitted subjects differed in the midbody and the lateral side near the head. Hippocampal volume showed no difference between controls and remitted subjects but nonremitted subjects had significantly smaller left hippocampal volumes with no significant group differences in the right hippocampus. These findings may provide support to other reports of neurogenic effects of antidepressants and their relation to successful treatment for depressive symptoms. [ABSTRACT FROM AUTHOR]

Objective We examined the relationship between 5HTTLPR genotype and volume of magnetic resonance imaging (MRI) brain lesions. Method We studied 217 older depressed patients and 141 individuals in the comparison group using a standard brain MRI protocol to calculate lesion volumes. Genotype at 5HTTLPR was determined for each subject. Results In age-adjusted models, the l/s genotype was associated with increased volume of total and white-matter lesions among depressed patients. This relationship lost significance in models controlling for reported hypertension. Conclusions The finding that 5HTTLPR heterozygotes have higher vascular lesion volumes may be related to development of hypertension. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACTBackgroundOrbitofrontal cortex (OFC) volumetric differences have been reported in depression, but in relatively small samples. Factors associated with these differences are not well described. We examined OFC volumes in a large sample of elderly depressed and non-depressed subjects, exploring the relationship between OFC volume, 5HTTLPRgenotype, apolipoprotein E (APOE) genotype and hyperintense lesion volume. We hypothesized that smaller OFC volume would be associated with depression, greater hyperintense lesion volume and severity, and APOE?4 or 5HTTLPRshort allele carriers.MethodA total of 226 depressed and 144 non-depressed older subjects completed 1?5 T magnetic resonance imaging (MRI) and genotyping. OFC volumes and lesion volumes were measured using standardized methods. Lesion severity was additionally rated using the Coffey rating scale. Differences between groups were compared while controlling for age, sex and total cerebral volume; separate models added lesion measures and genetic polymorphisms.ResultsDepressed subjects exhibited smaller OFC volumes. There was a trend for a negative association between white-matter lesion volume and OFC volume; however, rated white-matter lesion severity was significantly negatively associated with OFC volume. There was no association between gray-matter lesion measures or 5HTTLPRgenotype and OFC volume. Contrary to our hypothesis, subjects who were APOE?4 allele positive exhibited larger OFC volumes; in secondary analyses, this finding was limited to the non-depressed group.ConclusionsReduced OFC volumes are seen in depression and associated with greater severity of white-matter lesions. Healthy subjects who are APOE?4 allele positive exhibited larger OFC volumes. This finding should be examined in other populations. [ABSTRACT FROM AUTHOR]

Regulatory focus theory [Higgins, E. T. Beyond pleasure and pain. American Psychologist, 52, 1280-1300, 1997] postulates two social-cognitive motivational systems, the promotion and prevention systems, for self-regulation of goal pursuit. However, the neural substrates of promotion and prevention goal activation remain unclear. Drawing on several literatures, we hypothesized that priming promotion versus prevention goals would activate areas in the left versus right prefrontal cortex (PFC), respectively, and that activation in these areas would be correlated with individual differences in chronic regulatory focus. Sixteen participants underwent functional magnetic resonance imaging while engaged in a depth-of-processing task, during which they were exposed incidentally to their own promotion and prevention goals. Task-related cortical activation was consistent with previous studies. At the same time, incidental priming of promotion goals was associated with left orbital PFC activation, and activation in this area was stronger for individuals with a chronic promotion focus. Findings regarding prevention goal priming were not consistent with predictions. The data illustrate the centrality of self-regulation and personal goal pursuit within the multilayered process of social cognition. [ABSTRACT FROM AUTHOR]

Background Metabolomics, the global science of biochemistry, is an emerging field that enables detection and quantification of small molecules involved in metabolic and signaling pathways. Metabolic signatures for disease and its treatment could provide valuable biomarkers and insights about disease mechanisms. In this pilot study, we evaluate the potential of metabolomics in the study of older depressed patients. Methods We performed a metabolomic analysis of blood plasma from nine depressed, 11 remitted, and ten never-depressed older adults. Approximately 800 metabolites were analyzed, with comparisons made among the three groups. Results Metabolites that were altered in currently depressed patients when compared with controls included several fatty acids, glycerol and gamma-aminobutyric acid (GABA). Analyses comparing concentrations in remitted and currently depressed patients revealed a pattern of metabolite alterations similar to the control vs currently depressed analyses. One difference observed in the remitted patients relative to the depressed patients was elevation of the concentration of the ketone 3-hydroxybutanoic acid. Conclusion These observations suggest that the depressed state may be associated with alterations in the metabolism of lipids and neurotransmitters, and that treatment with antidepressants adjusts some of the aberrant pathways in disease so that the patients in remission have a metabolic profile more similar to controls than to the depressed population. These results will need to be examined and validated in larger longitudinal cohorts. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Decreased caudate volumes and increased white matter lesions (WMLs) are associated both with aging and late-life depression, but the relationship between the two is unclear. We examined the association between WML and caudate volume, hypothesizing there would be a negative association, which would be stronger for WMLs located in anterior regions. We additionally hypothesized that this association would be stronger in depressed subjects. Method This MRI study included 182 elderly depressed and 64 elderly control subjects. Our imaging analysis procedures divided the brain into anterior and posterior halves. WML volume in each half was calculated, as were left and right caudate volumes. A statistical model incorporating WML volumes, age, total brain volume, diagnosis, and gender was used to examine caudate volumes. Results WML volume was negatively associated with total and right caudate volume. This association was stronger for WMLs in the anterior half of the brain. Anterior WML volume was additionally negatively associated with right caudate volume in depressed subjects, but not in controls. Conclusions Using unadjusted levels of significance, WML volume is negatively associated with right caudate volume in both older populations, but with left caudate volume only in depressed individuals. When statistical corrections for multiple comparisons are used, the finding is limited to a negative association between WML volume and right caudate volume, primarily in depressed subjects. This study demonstrates one mechanism by which WMLs may disrupt frontostriatal circuits. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article summarizes the recommendations made by the interdisciplinary working group, formed by the National Heart, Lung and Blood Institute, concerning the assessment and treatment of depression in patients with coronary heart disease. These recommendations are intended to apply only to research including clinical trials, epidemiological studies and studies of mechanisms.

Background: Dysregulation of central nervous system serotonergic (5-HT) activity is implicated in behavioral states and psychological traits associated with depression and aggression, with some studies suggesting possible gender-related differences. Purpose: This study examined the relation of free plasma tryptophan (TRP) to aggression and depression in a sample of 138 nonsmoking adults recruited from the general community. It was hypothesized that TRP would be associated with anger, hostility, and aggression. Methods: To minimize effects of diurnal variation and menstrual cycle, fasting blood samples were collected in the morning, and, for women, during the follicular phase of the menstrual cycle. Participants were administered questionnaires following blood draw. Plasma TRP was determined by high performance liquid chromatography. Results: In women, but not men, higher levels of TRP were associated with trait hostility, propensity for anger, a tendency to express anger outwardly, and an antagonistic interpersonal style. For men and women, greater severity of depressive symptoms, anger, and the verbal expression of anger were associated with higher TRP. These associations were independent of age, body mass index, fasting albumin, and race and ethnicity. Conclusions: These data suggest that in women, but not men, higher plasma levels of TRP, the precursor to 5-HT, are associated with anger-hostility-aggression and that these associations are independent of various potential confounds. Implications of these observations to studies employing acute TRP depletion studies are discussed. [ABSTRACT FROM AUTHOR]

The article cites a study which focused on acute psychotic disorder after gastric bypass surgery. Gastric bypass surgery is considered a safe procedure. However, fatal psychiatric complications associated with weight reduction and hyperemesis at a rapid rate, can occur after gastric bypass surgery. These complications may appear to be non-threatening, and clinical presentations vary from neurological abnormalities to psychiatric manifestations. Such variability is considered to be related to the individual vulnerability of the central nervous system to nutritional decline.

Background Larger gray matter (GM) volume in healthy children is correlated with higher IQ. Children with neurofibromatosis type 1 (NF1) have larger brains, their magnetic resonance images frequently show T2-weighted hyperintensities, and their IQs are lower. Objectives To confirm the hypotheses that (1) children with NF1 have larger GM and white matter volumes, (2) the greatest volume differences are in the frontal and parietal regions and in children with NF1 with hyperintensities, and (3) GM volume is inversely related to IQ in children with NF1. Design Wechsler Intelligence Scale for Children–Third Edition IQ testing and measurement of cerebral volumes and hyperintensities in brain magnetic resonance images were performed on 36 children with NF1 and on 36 matched relatives who served as control subjects. Results Gray matter and white matter volumes were significantly larger in children with NF1. The greatest difference was observed in cerebral white matter volume, predominantly in the frontal lobes, whereas the greatest difference in GM volume was in the temporal, parietal, and occipital regions. In controls, IQ was significantly related to GM volume, but in children with NF1, IQ was not inversely associated with GM volume, although IQs of children with NF1 were significantly lower. Conclusions Children with NF1 do not have the normal relationship between GM volume and IQ. Larger GM volume in the posterior brain regions and larger white matter volumes in the frontal brain regions contribute to the larger brain volume in children with NF1. [ABSTRACT FROM AUTHOR]

This article reports on preliminary findings describing microstructural abnormalities in the white matter of cortical areas thought to be associated with bipolar disorder. In all, 14 patients with bipolar disorder and 21 nonpsychiatrically ill control subjects underwent MR imaging including a diffusion tensor imaging (DTI) pulse sequence (six directions, b=1000 mm2/s). DTI data were analyzed on a workstation using a program that allowed calculation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within the following three white matter fiber tracts bilaterally: the orbital frontal cortex, and the superior and middle frontal gyri. These values were compared across patient groups. The left and right orbital frontal white matter exhibited significantly higher ADC values in bipolar subjects than control subjects on both the left (p=0.028) and right (p=0.011). Microstructural changes in the white matter of the orbital frontal areas as reflected by increased ADC values appear to be associated with bipolar disorder. Further research is needed to better understand the interaction of microstructural changes and bipolar symptoms and whether these changes are specific to bipolar disorder.Neuropsychopharmacology (2005) 30, 2225–2229. doi:10.1038/sj.npp.1300802; published online 29 June 2005 [ABSTRACT FROM AUTHOR]

Objective: In a platelet/endothelial biomarker substudy of the Sertraline Anti- Depressant Heart Attack Randomized Trial (SADHART), the authors sought to determine whether plasma levels of sertraline and its primary metabolite N-desmethylsertraline affect the release of platelet/endothelial biomarkers. Method: Fifty-five acute coronary syndrome patients with depression were randomly assigned to receive sertraline (N= 23) or placebo (N=32). Twenty-six serial plasma samples collected at week 6 (N= 12) and week 16 (N=14) were analyzed. Platelet factor 4 (PF4), ²-thromboglobulin (13-TG), platelet/eridothelial cell adhesion molecule 1 (PECAM-1), P-selectin, thromboxane B2 (TxB2), prostacyclin (6-keto- PGF1±), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin were measured by enzyme-linked immunosorbent assay. Concentrations of sertraline and N-des- methylsertraline were determined by liquid chromatography with fluorescence detection in autologous samples. Results: Strong, mostly time-dependent negative correlations were found for the plasma levels of sertraline and N-des- methylsertraline with PF4 (week 6: r=-0.69 and -0.33, respectively; week 16: r-0.63 for both), ²-TG (week 6: r=-0.43 and -0.29; week 16: r=-0,66 and -0.57), PECAM-1 (week 6: r=-0.82 and -0.49; week 16: r= -0.60 for both), P-selectin (week 6: r=-0.82 and -0.49; week 16: r=-0.73 and -0.43), and TxB2 (week 6: r=-0.66 and -0.59; and week 16: r=-0.64 and -0.41), Regression analysis revealed some borderline correlations for endothelial markers such as 6- keto- PGF1± and E-selectin and a positive correlation for VCAM-1. Conclusions: This is the first documented evidence that plasma release of platelet/endothelial biomarkers is directly related to the levels of sertraline and N- desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. The clinical significance of these findings should be assessed in the setting of a randomized clinical trial. [ABSTRACT FROM AUTHOR]

Context Polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) influence transcription and may play a role in the pathogenesis and course of depression. Recent research demonstrates that specific polymorphisms may be associated with differences in hippocampal volumes in subjects with depression. Objective To examine associations between 5-HTTLPR genotype and hippocampal volumes in elderly control subjects and elderly subjects classified as having early or late onset of depression. Design Cohort study examining baseline characteristics. Participants Subjects were community dwelling and 60 years or older. Using a definition of early-onset depression as depression first occurring at 50 years or younger, we examined 72 subjects with early-onset depression, 63 subjects with late-onset depression, and 83 healthy control subjects. Main Outcome Measures All subjects underwent genotyping for the 5-HTTLPR and underwent brain magnetic resonance imaging. Analyses of hippocampal volumes were controlled for total cerebral volume, age, and sex. Results The interaction between diagnosis and 5-HTTLPR genotype was statistically significant for the right hippocampus (P = .04). Subjects with late-onset depression who were homozygous for the long (L) allele (L /L genotype) had significantly smaller right hippocampal volumes than did L /L subjects with early-onset depression (P = .046) or L /L control subjects (P = .01). Post hoc analyses showed that later age of depression onset was associated with smaller hippocampal volumes in subjects with the L /L genotype, but earlier age of onset was associated with smaller hippocampal volumes in subjects who were homozygous for the short (S) allele (S/S genotype). Conclusions Subjects with late-onset depression who were homozygous for the L allele exhibited smaller hippocampal volumes than other groups. Genotype also mediated the effect of age of onset on hippocampal volumes. Our findings differ from previous work; however, we examined an older and larger cohort of subjects than previous studies. Possible explanations for these findings include interactions between the serotonergic system and neurotrophic factors or cortisol response to stresses, each of which may affect hippocampal volumes. [ABSTRACT FROM AUTHOR]

Objective: In this study, we examined 204 older depressed individuals for up to 64 months to determine factors related to depression outcome. We hypothesized that both presence of vascular brain lesions seen on baseline magnetic resonance imaging (MRI) scans and lower baseline social support measures would be related to worse depression outcome.Method: At study entry, all subjects were at least 59 years old, had a diagnosis of major depression, and were free of other major psychiatric illness and primary neurological illness, including dementia and stroke. Depression was diagnosed via structured interview and clinical assessment by a geriatric psychiatrist who completed a Montgomery Asberg Depression Rating Scale (MADRS) to determine severity of depression. Subjects provided self-report data on social support variables and ability to perform basic and instrumental activities of daily living (ADL, IADL). All subjects agreed to have a baseline standardized MRI brain scan. Ratings of severity of hyperintensities were determined for the periventricular white matter, deep white matter, and subcortical gray matter by two readers who decided by consensus. Treatment was provided by geropsychiatrists following clinical guidelines. Using mixed models to analyze the data, we determined the effect of a variety of demographic, social and imaging variables on the trajectory of MADRS score, the outcome variable of interest.Results: MADRS scores decreased steadily over time. In a final HLM model, in which time since entry, a baseline time indicator, age, gender, education and Mini-mental State Examination score were controlled, subjective social support, instrumental ADL impairment, subcortical gray matter severity, and the interactions of time with social network and with subcortical gray matter lesions remained significantly associated with MADRS score.Conclusions: Both social and biological factors at baseline are associated with longitudinal depression severity in geriatric depression. [ABSTRACT FROM AUTHOR]

Examines the biological and social predictors of long-term geriatric depression outcome. Hypothesis that both the presence of vascular brain lesions seen on baseline magnetic resonance imaging scans and lower baseline social support measures would be related to worse depression outcome; Other factors related to the occurrence of depression in the elderly.

Background Decreased caudate volumes have been noted in unipolar depressed subjects, especially in the elderly and those with cognitive impairment. No differences have been noted in initial studies of multi-aged bipolar subjects; however, this region has not been examined in older bipolar subjects. Methods We examined the caudate nuclei volumes of 36 older bipolar subjects (mean age 58) and 35 older controls (mean age 62) using logistic regression analyses to control for age and gender differences. Differences between late- and early-onset (age-of-onset before age 45) bipolar subjects were also examined, as well as the effect of length of illness. Results The right caudate was noted to be smaller in older bipolar subjects compared with older controls when controlled for sex and age (p = 0.0448). No differences were noted in overall brain volume nor lateral ventricular volume between the bipolar and control subjects. Late-onset bipolar subjects had a decrease in brain volume (p = 0.035) compared with early-onset bipolar subjects. Late-onset bipolar subjects had a decrease in the right (p = 0.044) and total (p = 0.04) caudate size compared with older controls. Conclusions Right caudate volume is decreased in older bipolar subjects compared to controls. Bipolar subjects with late-onset illness have significantly decreased right and total caudate volumes compared to controls. This is affected by neither the length of illness nor the age of onset. Late-onset bipolar subjects have decreased total brain volume compared with early-onset bipolar subjects. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Context: Zonisamide is a marketed antiepileptic drug that has serotonergic and dopaminergic activity in addition to blockade of sodium and calcium channels. Weight loss was an adverse effect associated with zonisamide treatment in epilepsy clinical trials. Objective: To evaluate the efficacy of zonisamide for weight loss in obese adults. Design and Setting: Sixteen-week randomized, double-blind, placebo-controlled trial with an optional single-blind extension of the same treatment for another 16 weeks, conducted at Duke University Medical Center from March 2001 to March 2002. Participants: Fifty-five (92%) women and 5 (8%) men (mean [SE] body mass index, 36.3 [0.5]; mean age, 37.0 (1.0) years). Interventions: Patients were randomly assigned to receive zonisamide (n = 30) or placebo (n = 30). All participants were prescribed a balanced hypocaloric diet (500 kcal/d deficit) and compliance was monitored with self-rated food diaries. Zonisamide therapy was started at 100 mg/d orally, with gradual increase to 400 mg/d and further increase to 600 mg/d for patients losing less than 5% of body weight at the end of 12 weeks. Placebo dosing was identical. Main Outcome Measure: Change in body weight. Results: Of the 60 randomized patients, 51 completed the 16-week acute phase. In an intent-to-treat analysis using the available data for all randomized participants with the last observation carried forward, the zonisamide group lost more body weight than the placebo group (mean [SE], 5.9 [0.8] kg [6.0% loss] vs 0.9 [0.4] kg [1.0% loss]; t = 5.5; P<.001) during the 16-week period. A longitudinal mixed-model regression for weight change controlling for age, race, sex, body mass index, and percent body fat estimated that zonisamide treatment over the 16-week study duration was associated with significantly greater weight loss than was placebo (t = 6.4; P<.001). Seventeen (57%) of 30 in the zonisamide group and 3 (10%) of 30 in the placebo group lost at least 5% of body weight... [ABSTRACT FROM AUTHOR]

Objective: The role of social support in bipolar disorder is poorly understood. It is known that young and middle-aged patients with impaired social support are more likely to be treatment resistant and have increased hospitalization. However, the role of social support in elderly patients with bipolar disorder has not been studied. Our purpose was to evaluate social support in older adults with bipolar disorder compared with peer controls and younger bipolar patients. In addition, we looked at the role of social support in the age of illness onset. Methods: We evaluated social support of 29 older subjects with bipolar disorder (age 50 or older) and 56 younger subjects with bipolar disorder using the Duke Social Support Index, comparing them to non-psychiatric, peer controls. Using logistic regression we then examined the relationship of demographic, social support factors, and age of onset. Results: Both older and younger bipolar subjects perceived their social support as inadequate (OR=14.98; OR=9.05) compared with similar aged controls. Younger bipolar subjects also had less social interactions than younger controls (OR=4.63). These findings remained significant when controlled for gender, marital status, race, and education. No significant differences were noted between early-onset and late-onset bipolar subjects. Conclusions: Older and younger bipolar patients have decreased perceptions of social support than older controls. No effect was found based on the age of illness onset. In addition, younger subjects had less social interactions than peer controls. [ABSTRACT FROM AUTHOR]

Volumetric neuroimaging is increasingly being used by researchers of affective disorders to assess potential involvement of different brain structures in mood regulation and to test neuroanatomic models of mood disorders. In unipolar depression, findings suggest abnormalities in the frontal lobe (particularly the subgenual prefrontal cortex), basal ganglia (particularly the caudate and putamen), cerebellum, and hippocampus/amygdala complex. In bipolar disorder, abnormalities in the third ventricle, frontal lobe, cerebellum, and possibly the temporal lobe are noted. We review the findings for the various regions of the brain, and discuss the implications on the understanding of mood disorders. Directions for future research in volumetric imaging is then discussed. [ABSTRACT FROM AUTHOR]

A consensus conference on the use of placebo in mood disorder studies consisted of expert presentations on bioethics, biostatistics, unipolar depression, and bipolar disorder. Work groups considered evidence and presented statements to the group. Although it was not possible to write a document for which there was complete agreement on all issues, the final document incorporated input from all authors. There was consensus that placebo has a definite role in mood disorder studies. Findings of equivalence between a new drug and standard treatment in active control studies is not evidence of efficacy unless the new drug is also significantly more effective than placebo. Add-on studies in which patients are randomized to standard therapy plus the investigational drug or standard therapy plus placebo are especially indicated for high-risk patients. Mood disorders in elderly and pediatric patients are understudied, and properly designed trials are urgently needed. Research is needed on the ethical conduct of studies to limit risks of medication-free intervals and facilitate poststudy treatment. Patients must fully understand the risks and lack of individualized treatment involved in research. [ABSTRACT FROM AUTHOR]

Psychiatric inpatients (N = 343) admitted to an affective-disorders unit were administered a self-rating Trauma Questionnaire (TQ) to evaluate life history of traumatic experiences. Eighty four percent of the sample identified at least one traumatic-event category (M = 2.72 categories/patient). Symptoms consistent with posttraumatic stress disorder (PTSD) were highly prevalent. However, only six patients received a chart diagnosis of posttraumatic stress disorder. Female patients evidenced more PTSD symptoms than males, in contrast to an equal number of event categories identified by the two sexes. Age correlated negatively with number of symptoms endorsed. Implications for trauma screening in affective-disorder patients are discussed. [ABSTRACT FROM AUTHOR]

The literature suggests that bipolar elders with early and late onset of the disorder present with different demographic, family history, and psychosocial profiles, which are less well characterized than those for elderly unipolar patients. In this cross-sectional clinical survey, we assessed subjects (n = 74) from the NIMH Clinical Research Center for the Study of Depression in Later Life at Duke University who had a consensus diagnosis of bipolar depression; the primary assessment instrument was the Duke Depression Evaluation Schedule. We found that bipolar subjects with later age of onset reported less family history of psychiatric problems, more comorbid vascular disease, and more instrumental and subjective social support. Stressful life events were more frequent among bipolar subjects with earlier age of depressive symptom onset. This study suggests that early-onset disorder may be characterized by a psychosocial component, whereas organic factors may be particularly important to late-onset bipolar disorder. Depression and Anxiety 7:76–82, 1998. © 1998 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Examines the relationship between age at onset of first depressive episode and clinical features in elderly depressed patients. Loss of interest in usual activities; Number of depressive episodes; Lack of a clearly defined cutoff point between late and early onset.

Hyperintense signal areas (HSA) on T[sub 2]-weighted brain magnetic resonance imaging (MRI) may reflect subtle cerebro-vascular insufficiency and are common in elderly depressives. We hypothesized that these HSAs may indicate a vascular etiology for depression in late life, and that patients with late-onset major depression (MDD) would therefore more often show HSAs than comparably aged recurrent depressives. We reviewed the brain MR1 findings of a consecutive series of inpatients aged 50 or over who were treated for MDD during an 18-morith period. Patients with Parkinsonߣs or other brain diseases predisposing to depression were not considered. Twenty-seven (82%) of 33 patients with depression first apparent in late life and nine (64%) of 14 patients with earlier-onset, recurrent depression showed HSAs. This difference did not reach statistical significance. It was not attributable to the older mean age of the late-onset group. These rates are in accord with an 86% rate reported in a series of patients referred for ECT (Coffey et al., 1988) They are much higher than the 20–30% figure for comparably aged normals (Bradley, 1984: Kirkpatrick and Hayman, 1987). HSAs were common in this series of elderly, depressed inpatients, regardless of age of onset of illness. [ABSTRACT FROM AUTHOR]

Elderly patients are particularly sensitive to the neurologic side effects of psychotropic medications. This increased sensi tivity may be related to brain structural changes associated with aging. In this pilot study, the authors report on the oc currence of caudate hyperintensities, using brain magnetic resonance imaging, in seven elderly depressed subjects who developed neuroleptic-induced parkinsonism. Caudate hyperintensities were not observed in any of the seven healthy elderly controls examined. These results suggest that caudate hyperintensities may render some elderly depressed pa tients susceptible to neuroleptic-induced parkinsonism. (J Geriatr Psychiatry Neurol 1991;4:86-89). [ABSTRACT FROM PUBLISHER]