A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression

Human milk has a higher concentration of nucleotides than bovine milk which is the source of most infant formulas. As the composition of human milk is considered the 'gold standard,' an increasing number of infant formulas are supplemented with nucleotides. This review summarises the biology of human milk nucleotides and evaluates the studies which investigated the clinical benefits of feeding infants with nucleotide-supplemented formulas. Although dietary nucleotides have been suggested to have beneficial gastrointestinal and immunological effects, nucleotide-supplemented formula feeding has not been shown to confer the same benefits as breast feeding, and randomised controlled trials have yet to prove that healthy term infants fed nucleotide-supplemented formulas compared to those fed nonsupplemented formulas, have accelerated physical growth and neurological development, better growth and development of their gastrointestinal tract resulting in improved digestive and absorptive functions, enhanced development of their immune system resulting in increased resistance to infection and lower bacterial and viral infection rates during infancy, and a more favourable intestinal microflora associated with a lower rate of infectious diarrhoea. However, a randomised controlled trial has reported that term infants with severe intrauterine growth retardation do have better catch-up growth with nucleotide supplementation. The hypothesis that nucleotides are semi-essential nutrients needs to be further studied, in particular in the presence of prematurity, fetal growth retardation, intestinal injury and limited nutrient intake. As no deleterious effects have been reported with the use of nucleotide-supplemented formulas, the first of which was introduced over 30 years ago, such products are considered safe when nucleotides are supplemented to an amount equivalent to the free nucleotide concentration of human milk. More basic and clinical research studies are awaited to further define the biology and role of human milk nucleotides, and to critically assess the potential benefits and appropriate level of nucleotide supplementation of infant formula.     

Recurrence in major depression: A conceptual analysis.

[Correction Notice: An erratum for this article was reported in Vol 118(4) of Psychological Review (see record 2011-23298-002). An incorrect version of Figure 2 was published, and Figure 3 was published in color instead of Figure 4. Also, in Table 1, the acronym “(FLED)” should not have been included in the Recurrence section, under Confusion to avoid, following “Not to be confused with a first lifetime recurrence.” All versions of this article have been corrected.] Theory and research on major depression have increasingly assumed a recurrent and chronic disease model. Yet not all people who become depressed suffer recurrences, suggesting that depression is also an acute, time-limited condition. However, few if any risk indicators are available to forecast which of the initially depressed will or will not recur. This prognostic impasse may be a result of problems in conceptualizing the nature of recurrence in depression. In the current paper we first provide a conceptual analysis of the assumptions and theoretical systems that presently structure thinking on recurrence. This analysis reveals key concerns that have distorted views about the long-term course of depression. Second, as a consequence of these theoretical problems we suggest that investigative attention has been biased toward recurrent forms of depression and away from acute, time-limited conditions. Third, an analysis of how these theoretical problems have influenced research practices reveals that an essential comparison group has been omitted from research on recurrence: people with a single lifetime episode of depression. We suggest that this startling omission may explain why so few predictors of recurrence have as yet been found. Finally, we examine the reasons for this oversight, document the validity of depression as an acute, time-limited disorder, and provide suggestions for future research with the goal of discovering early risk indicators for recurrent depression. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

The latent symptom structure of the Beck Depression Inventory–II in outpatients with major depression.

The Beck Depression Inventory–II (BDI–II) is a self-report instrument frequently used in clinical and research settings to assess depression severity. Although investigators have examined the factor structure of the BDI–II, a clear consensus on the best fitting model has not yet emerged, resulting in different recommendations regarding how to best score and interpret BDI–II results. In the current investigation, confirmatory factor analysis was used to evaluate previously identified models of the latent symptom structure of depression as assessed by the BDI–II. In contrast to previous investigations, we utilized a reliably diagnosed, homogenous clinical sample, composed only of patients with major depressive disorder (N = 425)—the population for whom this measure of depression severity was originally designed. Two 3-factor models provided a good fit to the data and were further evaluated by means of factor associations with an external, interviewer-rated measure of depression severity. The results contribute to a growing body of evidence for the Ward (2006) model, including a General (G) depression factor, a Somatic (S) factor, and a Cognitive (C) factor. The results also support the use of the BDI–II total scale score. Research settings may wish to model minor factors to remove variance extraneous to depression where possible. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of DSM-III-R chronic major depression and major depression superimposed on dysthymia (double depression): Validity of the distinction.

The nosology of chronic depression has become increasingly complex since the publication of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R; American Psychiatric Association, 1987), but there are few data available to evaluate the validity of the distinctions between the subtypes of chronic depression. The validity of the distinction between DSM-III-R chronic major depression (CMD) and major depression superimposed on dysthymia (double depression, DD) was examined. Participants were 635 patients with chronic depression in a 12-week trial of antidepressant medications. Patients with CMD, DD, and a 3rd group with a chronic major depressive episode superimposed on dysthymia (DD/CMD) were compared on demographic and clinical characteristics, family history, and response to treatment. Few differences were evident, although the depression of patients with DD/CMD tended to be more severe. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Beta-adrenoceptor-linked protein kinase A (PKA) activity in human fibroblasts from normal subjects and from patients with major depression

Human fibroblasts from normal subjects and from patients with major depression are cultured and their beta-adrenoreceptor-cyclic AMP-protein kinase A (PKA) system characterized. The results indicate that the beta-adrenoreceptor-mediated activation of PKA in the 900 g supernatant fraction of human fibroblasts is mediated via beta-adrenoreceptors. The activation of PKA by isoproterenol is very rapid with maximal stimulation occurring at 5 seconds. The time course of PKA activation by isoproterenol in fibroblasts from patients with major depression is identical to that in fibroblasts from normal subjects but the magnitude of activation is significantly reduced in fibroblasts from patients with major depression. Dose-response curves on cyclic AMP mediated activation of PKA confirmed the previously reported reduction in activation of PKA in patients with major depression but demonstrated that this reduction occurs without a change in the EC50 values of cyclic AMP (approximately 20 nmol/L). The blunted beta-adrenoceptor-linked PKA responses in patients with major depression occur without a change in the expression of the PKA catalytic subunit C alpha. The studies suggest that the beta-adrenoceptor-coupled adenylate cyclase PKA system in human fibroblasts may represent a valid model to explore possible abnormalities in the fine tuning of the beta-adrenergic transduction cascade in patients with affective disorders.     

Efficacy of venlafaxine and placebo during long-term treatment of depression: a pooled analysis of relapse rates

An assay was developed for the specific detection of Salmonella enterica serotype Enteritidis, using a novel application of the polymerase chain reaction (PCR). This PCR assay is based on the mismatch amplification mutation assay, an allele-specific reaction, and can discriminate Enteritidis from all other salmonella. PCR primers were selected to amplify a 351-base pair (bp) DNA fragment from the salmonella plasmid virulence A (spv A) gene of Enteritidis. A single base difference at position 272 is present between the nucleotide sequence of the spvA gene of Enteritidis and other salmonellae. The downstream PCR primer, that encompasses position 272 of the Enteritidis spvA gene, was designed to contain a single base mismatch at the penultimate position, resulting in a 1-base mismatch with Enteritidis and a 2-base mismatch with other salmonellae that harbour the virulence plasmid. The upstream primer was completely homologous with the region immediately 5' to the spvA gene. When these primers were used and the annealing and extension reactions were performed at the same temperature, the PCR assay was specific for Enteritidis; no PCR product was detected for 40 other serotypes and 28 different genera examined. In pure culture, 120 colony forming units (c.f.u.) could be detected; a PCR product was observed from template derived from a 5 h enrichment broth culture of chicken seeded with 1 c.f.u. per gram of Enteritidis. This PCR assay is specific, reproducible, and less time consuming than the standard bacteriological methods used to detect Enteritidis.     

Personality disorders in adolescents with major depression, substance abuse disorders, and coexisting major depression and substance use disorders.

This study examined the presence of personality disorders in adolescent inpatients with major depression (MDD; n?=?45), substance use disorders (SUD; n?=?27), or both disorders combined (MDD-SUD; n?=?42). A consecutive series of patients were given structured diagnostic interviews for Axes I and II disorders. The groups did not differ with regard to age, gender, ethnicity, socioeconomic status, psychiatric history, or global assessment of functioning. Borderline personality disorder was diagnosed more frequently in the MDD-SUD group than in the MDD or SUD groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treatment of major depressive disorder in older adult outpatients with brief psychotherapies.

Examined (a) whether older adults in a current major depressive episode would improve systematically when treated with short-term psychotherapies and (b) if they would respond differentially to treatment approaches emphasizing the importance of either cognitive, behavioral, or relational/insight factors in the therapy process. 30 elderly outpatients (aged 59–80 yrs) were assigned to 1 of the 3 individual treatment conditions for 16 sessions over a 12-wk period. Evaluation (Hamilton Rating Scale for Depression, Beck Depression Inventory, and Self-Rating Depression Scale) occurred before and after therapy and at 4 times during a 1-yr follow-up. Comparable improvement in depressive symptoms was seen from pre- to posttest for Ss in all 3 treatment conditions. However, improvement during the 1-yr follow-up was maintained more effectively by Ss treated with behavioral or cognitive therapy than with relational/insight therapy. Results indicate that brief psychotherapies can be effective in the treatment of elderly depressives and that structured therapies may be more beneficial than nonstructured relationally oriented therapy during a treatment-free follow-up period. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A twin study of generalized anxiety disorder and major depression

Previous analyses with a sample of female twins sampled from the general population in Virginia have suggested that generalized anxiety disorder (GAD) and major depression (MD) share their genetic determinants but have partly different environmental determinants. The goal of this report is to examine whether these findings apply to samples that include male as well as female twins and contain high proportions of subjects who had been hospitalized for MD. The subjects were ascertained through two different sources: (i) index probands were ascertained through the Swedish Psychiatric Twin Registry for a diagnosis of unipolar or bipolar affective illness; (ii) control twin probands were ascertained through the Swedish Twin Registry. Subjects were sent questionnaires for the assessment of lifetime history of GAD and MD. Positing multinormal distribution of the liability for GAD and MD, we fitted bivariate models to examine the sources of comorbidity. The full model included additive genetic effects, shared environment and individual-specific environment, as well as scalar and non-scalar sex limitations and different thresholds across genders. The best-fitting model included: (i) a genetic correlation of unity; (ii) no common environment; (iii) an individual-specific environmental correlation of 0.28; (iv) different thresholds across genders, but neither scalar nor non-scalar sex-limitations. A model that included additive and dominant genetic effects and individual-specific environment, with correlation of unity for both additive and dominant genetic effects, provided an equivalent fit. These analyses confirm that GAD and MD share the same genetic factors but that their environmental determinants are mostly distinct. Moreover, the present report supports the feasibility of combining clinical ascertained and general-population samples into a single bivariate analysis.     

Double-blind comparison of bupropion sustained release and sertraline in depressed outpatients

BACKGROUND: A sustained-release formulation of bupropion (bupropion SR), developed with an improved pharmacokinetic profile to permit less frequent dosing than the immediate-release form, has not been evaluated in active comparator trials. This randomized, double-blind, parallel-group trial was conducted to compare the efficacy and safety of bupropion SR and sertraline. METHOD: Outpatients with moderate to severe major depressive disorder (DSM-IV) received bupropion SR (100-300 mg/day) or sertraline (50-200 mg/day) for 16 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Clinical Global Impressions scale for Severity of Illness (CGI-S), and for Improvement (CGI-I) were completed, and adverse events were assessed in the clinic periodically throughout treatment. Patients' orgasm function was also assessed. RESULTS: Mean HAM-D, HAM-A, CGI-I, and CGI-S scores improved over the course of treatment in both the bupropion SR group and the sertraline group; no between-group differences were observed on any of the scales. Orgasm dysfunction was significantly (p < .001) more common in sertraline-treated patients compared with bupropion SR-treated patients. The adverse events of nausea, diarrhea, somnolence, and sweating were also experienced more frequently (p < .05) in sertraline-treated patients. No differences were noted between the two treatments for vital signs and weight. CONCLUSION: This double-blind comparison of bupropion SR and sertraline demonstrates that bupropion and sertraline are similarly effective for the treatment of depression. Both compounds were relatively well tolerated, and orgasm dysfunction, nausea, diarrhea, somnolence, and sweating were reported more frequently in sertraline-treated patients.     

A comparison of fluvoxamine and fluoxetine in the treatment of major depression

Two monoclonal antibodies (MAbs) to human placenta laminin (pl-LAM), 1D8 (IgG1) and 6G5 (IgG2b) were generated and shown by ELISA and immunoblot analysis to recognize only native pl-LAM, but not denatured, reduced pl-LAM or mouse EHS laminin. Intact pl-LAM was easily isolated and purified in large scale from human placenta by 1D8-conjugated affinity chromatography. Electrophoretic analysis of the purified pl-LAM revealed the presence of a major 750-kDa component composed of 320-, 220-, and 200-kDa polypeptides and a minor 800-kDa component composed of 320-, 240-, and 220-kDa polypeptides. Neither molecule had a 400-kDa component corresponding to the A chain. It has already been shown that the 320-kDa polypeptide is identical to the M chain of human merosin (Hori et al. J. Biochem. 1994;116:1212-1219). Electron microscopy revealed that isolated merosin was composed of three short arms and one long arm. By immunohistochemistry, MAbs showed positive staining in human adult kidney and liver. These results indicate that these MAbs recognize only native merosin and can be used to study merosin structure and function by rapid purification of native merosin and by immunohistochemical analysis.     

Reversible hepatotoxicity of paroxetine in a patient with major depression

Selective serotonin reuptake inhibitors (SSRIs) are becoming widely used because of their favorable side-effect profile and their safety in overdose. We report about a patient with recurring major depression (DSM-IIIR) who was treated with paroxetine and developed a severe hepatotoxic reaction, which was reversed after withdrawal of the drug. Individual, patient-related causes for this side-effect were not found. To our knowledge, this is the first published case of a probably paroxetine-induced severe hepatotoxicity. Hepatotoxicity should be taken into account as a rare complication that may occur not only with tricyclic antidepressants (TCAs) but also with SSRIs.     

A double-blind multicenter trial comparing sertraline and citalopram in patients with major depression treated in general practice

The purpose of this double-blind, multicenter trial was to compare the efficacy and safety of sertraline (50-150 mg/day) with those of citalopram (20-60 mg/day) in patients with major depression in general practice during 24 weeks of treatment. The patients were assessed using the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impressions of severity and improvement scales. Observed and spontaneously reported adverse events were recorded and side-effects were assessed by means of the UKU Side-Effect Scale. Altogether 400 patients were randomized into the study. A total of 308 patients completed the 24-week study in accordance with the protocol. A significant reduction in the total Montgomery-Asberg Depression Rating Scale scores was observed in both treatment groups as early as 2 weeks, with no statistically significant differences between the drugs. In the intention to treat-last observation carried forward analysis 76% responded to treatment in the sertraline and 81% in the citalopram group. The final mean doses were 82 mg/day (64% higher than baseline) in the sertraline group and 34 mg/day (70% higher than baseline) in the citalopram group. The response rate in completers in accordance with protocol was 90% in the sertraline group and 93% in the citalopram group. The side-effects were those usually seen, and both sertraline and citalopram were considered to be well tolerated. It was concluded that patients with major depression in general practice respond well to 24 weeks of treatment with sertraline or citalopram. With regard to efficacy, no statistically significant differences were found between the drugs.     

Plasma levels of arginine vasopressin elevated in patients with major depression

Mentally healthy subjects show increased plasma concentrations of the neuropeptides, arginine vasopressin (AVP) and oxytocin (OT), under conditions of stress, but data are lacking about plasma concentrations of AVP and OT in patients with major depression. We thus assessed plasma concentrations of AVP and OT in patients with major depression (n = 52) and healthy controls (n = 37). Mean plasma AVP concentrations were higher in the group of depressed patients than in controls. A subgroup of 16 patients showed very high levels of plasma AVP, but no other feature differentiating this subgroup from the other patients was found. In-patients showed higher plasma AVP levels than out-patients, and melancholic patients had higher plasma AVP levels than did nonmelancholic patients. Plasma AVP levels were slightly related to psychomotor retardation and significantly inversely to neuroticism. Patients' plasma OT concentrations had a wider range than in controls. AVP and AVP-mediated functions may be a factor in the clinical picture of depression, possibly by influencing the activity of the hypothalamic-pituitary-adrenal axis.     

Cognitive-behavioral therapy of panic disorder with secondary major depression: A preliminary investigation.

Controlled studies indicate that cognitive-behavioral therapy eliminates panic attacks in greater than 80% of patients who suffer from panic disorder. However, because most of the screening procedures used in those studies called for excluding patients who were depressed, a question arises as to the extent to which these results apply to patients who are clinically depressed in addition to having panic attacks. An attempt was made in the present study to determine whether or not panic patients who are clinically depressed could be treated as successfully as those who are not clinically depressed. Two multiple baseline A-A–1-A-B across-Ss designs were used, 1 to test 8 panic Ss with major depression and the 2nd to test 7 panic Ss without major depression. In baseline (A), Ss monitored their panic attacks daily. During the A–1 phase, a program of information on panic attacks presented as psychotherapy was instituted to assess the effects of nonspecific factors, followed by a 2nd baseline phase (A). Cognitive-behavioral therapy (B) was then introduced. Results showed that cognitive-behavioral therapy was significantly superior to information-based therapy in the reduction of panic attacks. No significant differences were found between depressed and nondepressed patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychopathology in children of parents with opiate dependence and/or major depression

OBJECTIVE: To evaluate psychiatric disorders and impairment in school-age and adolescent children of opiate-dependent patients. METHOD: One hundred fourteen children, aged 6 to 17 years, of 69 white methadone maintenance patients with (n = 30) and without (n = 39) major depression were evaluated for DSM-III-R diagnoses by the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic version and best estimate, and by measures of functioning (Children's Global Assessment Scale, Social Adjustment Inventory for Children and Adolescents, WISC, Peabody Picture Vocabulary Test), and compared with children of historical controls without substance abuse history. RESULTS: Sons of opiate addicts with major depression were at increased risk for conduct disorder and global, social, and intellectual impairment compared with sons of opiate addicts without major depression and/or sons of controls with neither drug dependence nor depression. Sons of opiate addicts without major depression differed little from controls. Daughters of opiate addicts did not differ from controls in rates of disorders but had poorer social adjustment and nonverbal intelligence. CONCLUSIONS: Children of opiate-dependent patients, particularly sons of addicts with depression, may be at risk for a developmental path toward antisocial personality and poor social and intellectual functioning. Treatment settings such as methadone maintenance might afford an opportunity for primary and secondary prevention, both through early detection of childhood disorders and treatment of parental drug dependence and psychopathology.     

A test-retest study of cerebral blood flow during somatosensory stimulation in depressed patients with schizophrenia and major depression

Six depressed patients with schizophrenia and 6 depressed patients with major depression were investigated before and during somatosensory stimulation (SS) with Tc-99m HMPAO SPECT. 8 controls were investigated only under resting conditions. The results can be summarized as follows: 1. Both psychiatric patient groups were hypofrontal (dorsolateral prefrontal cortex) compared to controls. 2. Hypofrontality was further enhanced by SS, significantly only in affective psychoses in the right inferior frontal lobe and in the right frontal hemisphere in total, in schizophrenia in the left dorsolateral prefrontal cortex. 3. Within the frontal lobes different regions were affected by SS in the two diagnostic groups. 4. In the right inferior parietal lobe SS response was significantly different in the two illnesses with schizophrenia showing a relative decrease, affective psychoses showing a relative increase of activity. 5. SS produced an increase of cerebral blood flow in subcortical regions (statistically significant contralateral to SS in thalamus and basal ganglia, ipsilateral to SS in cerebellum), a pattern which was common to all psychiatric patients. 6. Somatosensory cortex flow was not changed by SS. In conclusion, we could not fully confirm our hypotheses that similar blood flow abnormalities in different illnesses during SS are only caused by similarities in depressive psychopathology. Instead, depressed patients with schizophrenia were different from depressed patients with major depression in showing decreased activity in interrelating brain regions participating in an attentional network.     

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