Correction to Kanayama et al. (2007).

Reports an error in "Testosterone supplementation for depressed men: Current research and suggested treatment guidelines" by Gen Kanayama, Revital Amiaz, Stuart Seidman and Harrison G. Pope Jr. (Experimental and Clinical Psychopharmacology, 2007[Dec], Vol 15[6], 529-538). In the "Recent Studies" section (pp. 531-532), citations to Pope and Katz (2003) should have been to Pope, Kanayama, Cohane, Siegel, and Hudson (2003) to reflect the following source, which was omitted from the reference list: "Pope, H. G., Jr., Kanayama, G., Cohane, G., Siegel, A., & Hudson, J. I. (2003). Testosterone gel supplementation for men with refractory depression: A randomized placebo-controlled trial. American Journal of Psychiatry, 160, 105-111". (The following abstract of the original article appeared in record 2007-18976-003.) Several lines of accumulating evidence suggest that testosterone might be effective for the treatment of depression, especially in older men who exhibit low testosterone levels. However, despite the potential promise of this approach, the available literature of controlled studies of testosterone in depression remains extremely limited. Therefore, testosterone treatment of depression must still be considered an experimental procedure. At the present state of research, it appears that testosterone might most likely show benefit as an augmentation strategy in men who exhibit low or borderline testosterone levels and who show only a partial response to conventional antidepressants. In this article, we provide some suggested practical guidelines for the treatment of such individuals. However, it should be recognized that these suggestions are tentative and will likely require revision as additional data become available. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Testosterone supplementation for depressed men: Current research and suggested treatment guidelines.

[Correction Notice: An erratum for this article was reported in Vol 16(2) of Experimental and Clinical Psychopharmacology (see record 2008-03846-010). In the "Recent Studies" section (pp. 531-532), citations to Pope and Katz (2003) should have been to Pope, Kanayama, Cohane, Siegel, and Hudson (2003) to reflect the following source, which was omitted from the reference list: "Pope, H. G., Jr., Kanayama, G., Cohane, G., Siegel, A., & Hudson, J. I. (2003). Testosterone gel supplementation for men with refractory depression: A randomized placebo-controlled trial. American Journal of Psychiatry, 160, 105-111".] Several lines of accumulating evidence suggest that testosterone might be effective for the treatment of depression, especially in older men who exhibit low testosterone levels. However, despite the potential promise of this approach, the available literature of controlled studies of testosterone in depression remains extremely limited. Therefore, testosterone treatment of depression must still be considered an experimental procedure. At the present state of research, it appears that testosterone might most likely show benefit as an augmentation strategy in men who exhibit low or borderline testosterone levels and who show only a partial response to conventional antidepressants. In this article, we provide some suggested practical guidelines for the treatment of such individuals. However, it should be recognized that these suggestions are tentative and will likely require revision as additional data become available. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age-associated testosterone decline in men: clinical issues for psychiatry

OBJECTIVE: The author summarizes current knowledge about the diagnosis and treatment of testosterone decline in healthy aging men and the associated clinical issues for psychiatry. METHOD: A MEDLINE search was conducted in which the search terms "male climacteric," "male menopause," "andropause," "viropause," "low-testosterone syndrome," and "testosterone replacement therapy" were used. Literature published before 1966 was identified by reviewing the reference lists of later publications. RESULTS: Manifestations of testosterone deficiency have included depression, anxiety, irritability, insomnia, weakness, diminished libido, impotence, poor memory, reduced muscle and bone mass, and diminished sexual body hair. Although testosterone levels decline with age, there is great interindividual variability, and the connection between serum testosterone levels and clinical psychiatric signs and symptoms is not clear-cut, since other hormonal changes are implicated as well. Testosterone replacement therapy may offer hypogonadal men benefit, but long-term studies on its efficacy and safety are lacking. Comprehensive biopsychosocial assessment should be a routine part of the evaluation of complaints of low-testosterone syndrome in men. CONCLUSIONS: Testosterone decline/deficiency is not a state strictly analogous to female menopause and may exhibit considerable overlap with primary and other secondary psychiatric disorders.     

Characterization of the proliferation state in canine mammary tumors by the standardized AgNOR method with postfixation and immunohistologic detection of Ki-67 and PCNA

Recently, there have been some reports that changes in serum lipid composition may be related to suicide, major depression and immune-inflammatory responses. Findings from our laboratory suggest that major depression is accompanied by reduced formation of cholesteryl esters and perhaps by impairment of reverse cholesterol transport. The latter is reportedly accompanied by lower serum high-density lipoprotein cholesterol (HDL-C). The aim of this study was to examine whether (i) major depression is accompanied by lower serum HDL-C or by abnormal levels of serum total cholesterol, triglycerides, low-density lipoprotein-C (LDL-C) or vitamin E, (ii) suicidal attempts are related to lower serum HDL-C and (iii) there are significant associations between serum HDL-C and immune/inflammatory markers. A total of 36 subjects with major depression, of whom 28 patients showed treatment resistance, as well as 28 normal control subjects, had blood sampled for the assay of the above lipids, serum zinc (Zn), albumin (Alb) and flow cytometric determination of the T-helper/T-suppressor (CD4+/CD8+) T-cell ratio. In total, 28 depressed subjects had repeated measures of these variables both before and after treatment with antidepressants. Serum HDL-C and total cholesterol, as well as the HDL-C/cholesterol ratio, were significantly lower in subjects with major depression than in normal controls. Serum HDL-C levels were significantly lower in depressed men who had at some time made serious suicidal attempts than in those without such suicidal behaviour. Treatment with antidepressants for 5 weeks did not significantly alter either serum HDL-C or other lipid variables. Serum HDL-C levels were significantly and negatively correlated with the (CD4+/CD8+) T-cell ratio, and positively correlated with serum Alb and Zn. These results suggest that (i) lower serum HDL-C levels are a marker for major depression and suicidal behaviour in depressed men, (ii) lower serum HDL-C levels are probably induced by the immune/inflammatory response in depression and (iii) there is impairment of reverse cholesterol transport from the body tissues to the liver.     

Exercise as a mediator of psychological and nutritional effects of testosterone therapy in HIV+ men

PURPOSE: The purpose of this study was to determine whether exercise mediates the psychological and nutritional effects of testosterone therapy in men with symptomatic HIV illness, low serum testosterone, and clinical symptoms of hypogonadism. METHODS: A 12-wk open trial of biweekly intramuscular testosterone injections was conducted, with 54 men completing the trial and exercise assessments. Most (71%) men were diagnosed with AIDS; 41% had a CD4 < 50. One-third of the men were diagnosed with major depression, and nearly half had some evidence of wasting. Twenty-nine men (54%) engaged in exercise (predominantly resistance training) during the trial. Exercisers did not differ from nonexercisers on any measure of psychological well being or nutritional status at baseline. RESULTS: After 12 wk of testosterone treatment, those who exercised showed significant improvement in mood (Hamilton Rating Scale for Depression; HAM-D) and overall distress (Brief Symptom Inventory; BSI) (P < 0.000 for both), as well as a significant increase in body cell mass (P < 0.01) and lean body mass (mean increase of 2.6 kg; P < 0.000) as measured by bioelectric impedance analysis. In contrast, nonexercisers showed improvement on the HAM-D (P < 0.000), but not the BSI or measures of nutritional status. CONCLUSION: These findings indicate that exercise may be an important adjunct to testosterone therapy in the treatment of psychological distress and wasting symptoms in men with symptomatic HIV illness.     

Psychoneuroendocrinology of depression. Hypothalamic-pituitary-gonadal axis

Women are more susceptible than men to depression, particularly during periods of rapid fluctuation of gonadal hormones, such as premenstrually, postpartum, and during the climacteric. This review summarizes the evidence for the association of depression with abnormalities in reproductive hormones. Although there are similarities in stress hormones changes between depressed women and women with stress-related amenorrhea, no abnormalities in LH activity have been documented in depression. Similarly no abnormalities in LH, estradiol, or progesterone have been documented in premenstrual syndrome (PMS), although complete elimination of monthly cycling with leuprolide improves mood. Some studies have suggested beneficial effects of estrogen on mood in postmenopausal women but as yet there have been no adequately controlled studies of estrogen treatment of either premenopausal or postmenopausal women.     

Maternal depressive disorder and contextual risk: contributions to the development of attachment insecurity and behavior problems in toddlerhood

Research has shown that offspring of depressed caregivers are at increased risk for maladaptive development and emotional difficulties. Specifically, infants and toddlers of depressed mothers have been shown to evidence higher percentages of insecure attachments and more behavioral difficulties than offspring of nondisordered mothers. However, even in studies that reveal significant differences between children of depressed and nondepressed caregivers, a substantial number of children with depressed caregivers do not evidence dysfunction. Such findings have resulted in increased attention to the broader social context in which children of depressed mothers develop. This investigation examined the direct influences of maternal depression on child development, as well as the role of contextual risks that may be particularly heightened in families with depressed parents. Toddlers with depressed mothers evidenced significantly more insecure attachments than did toddlers with nondisordered mothers, and this difference was not accounted for by contextual risk. In predicting child behavior problems, contextual risk was found to mediate the relation between maternal depression and child behavior problems. Father-report data on child behavior corroborated the mother report data. Results are discussed in terms of the diversity of functioning in offspring of depressed caregivers that can be attributed to varied levels of contextual risk accompanying depression.     

Responses to depression and their effects on the duration of depressive episodes.

Proposes that the ways people respond to their own symptoms of depression influence the duration of these symptoms. People who engage in ruminative responses to depression, focusing on their symptoms and the possible causes and consequences of their symptoms, will show longer depression than people who take action to distract themselves from their symptoms. Ruminative responses prolong depression because they allow the depressed mood to negatively bias thinking and interfere with instrumental behavior and problem-solving. Laboratory and field studies directly testing this theory have supported its predictions. The author discusses how response styles can explain the greater likelihood of depression in women than men, then integrates this response styles theory with studies of coping with discrete events. The response style theory is compared to other theories of the duration of depression. Finally, suggestions are made that may help a depressed person to stop engaging in ruminative responses and on how response style for depression may develop. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Consequences of major and minor depression in later life: a study of disability, well-being and service utilization

BACKGROUND: The consequences of major depression for disability, impaired well-being and service utilization have been studied primarily in younger adults. In all age groups the consequences of minor depression are virtually unknown. In later life, the increased co-morbidity with physical illness may modify the consequences of depression, warranting special study of the elderly. With rising numbers of elderly people, excess service utilization by depressed elderly represents an increasingly important issue. METHODS: Based on a large, random community-based sample of older inhabitants of the Netherlands (55-85 years), the associations of major and minor depression with various indicators of disability, well-being and service utilization were assessed, controlling for potential confounding factors. Depression was diagnosed using a two-stage screening design. Diagnosis took place in all subjects with high depressive symptom levels and a random sample of those with low depressive symptom levels. The study sample consists of all participants to diagnostic interviews (N = 646). RESULTS: As in younger adults, associations of both major and minor depression with disability and well-being remained significant after controlling for chronic disease and functional limitations. Adequate treatment is often not administered, even in subjects with major depression. As the vast majority of those depressed were recently seen by their general practitioners, treatment could have been provided in most cases. Bivariate analyses show that major and minor depression are associated with an excess use of non-mental health services, underscoring the importance of recognition. In multivariate analyses the evidence of excess service utilization was less compelling. CONCLUSIONS: Both major and minor depression are consequential for well-being and disability, supporting efforts to improve the recognition and treatment in primary care. However, controlled trials are necessary to assess the impact this may have on service utilization.     

Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial

A decline in testicular function is recognized as a common occurrence in older men. However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines. This study was undertaken to examine the year-long effects of testosterone administration in this patient population. Fifteen hypogonadal men (mean age 68 +/- 6 yr) were randomly assigned to receive a placebo, and 17 hypogonadal men (mean age 65 +/- 7 yr) were randomly assigned to receive testosterone. Hypogonadism was defined as a bioavailable testosterone <60 ng/dL. The men received injections of placebo or 200 mg testosterone cypionate biweekly for 12 months. The main outcomes measured included grip strength, hemoglobin, prostate-specific antigen, leptin, and memory. Testosterone improved bilateral grip strength (P < 0.05 by ANOVA) and increased hemoglobin (P < 0.001 by ANOVA). The men assigned to testosterone had greater decreases in leptin than those assigned to the control group (mean +/- SEM: -2.0 +/- 0.9 ng/dL vs. 0.8 +/- 0.7 ng/dL; P < 0.02). There were no significant changes in prostate-specific antigen or memory. Three subjects receiving placebo and seven subjects receiving testosterone withdrew from the study. Three of those seven withdrew because of an abnormal elevation in hematocrit. Testosterone supplementation improved strength, increased hemoglobin, and lowered leptin levels in older hypogonadal men. Testosterone may have a role in the treatment of frailty in males with hypogonadism; however, older men receiving testosterone must be carefully monitored because of its potential risks.     

Testosterone treatment in men with erectile disorder and low levels of total testosterone in serum

Since decreased serum levels of testosterone (T) do not necessarily predict good outcome of testosterone treatment for erectile disorder, the purpose, of this study was to determine which men with erectile disorder and decreased serum levels might benefit from treatment. From a sample of 31 men (mean age = 39 years), 15 (48%) with erectile disorder and decreased serum levels of T responded well after 8 weeks of testosterone treatment (100 mg of testosterone propionate in the sustained-release form given im once a week). Good treatment outcome was associated with several variables, but only high levels of luteinizing hormone (LH) and low values of the T/LH (testosterone/LH) ratio consistently emerged as significant correlates and/or predictors of effective treatment. Levels of LH above 7.5 IU/L or the values of the T/LH ratio equal to or below 0.87 nmol/IU in patients with erectile disorder and decreased serum levels of T suggest that testosterone treatment may be effective.     

Osteoporosis in men. New insights into aetiology, pathogenesis, prevention and management

Osteoporosis is increasingly recognised in men. Low bone mass, risk factors for falling and factors causing fractures in women are likely to cause fractures in men. Bone mass is largely genetically determined, but environmental factors also contribute. Greater muscle strength and physical activity are associated with higher bone mass, while radial bone loss is greater in cigarette smokers or those with a moderate alcohol intake. Sex hormones have important effects on bone physiology. In men, there is no abrupt cessation of testicular function or 'andropause' comparable with the menopause in women; however, both total and free testosterone levels decline with age. A common secondary cause of osteoporosis in men is hypogonadism. There is increasing evidence that estrogens are important in skeletal maintenance in men as well as women. Peripheral aromatisation of androgens to estrogens occurs and osteoblast-like cells can aromatise androgens into estrogens. Human models exist for the effects of estrogens on the male skeleton. In men aged > 65 years, there is a positive association between bone mineral density (BMD) and greater serum estradiol levels at all skeletal sites and a negative association between BMD and testosterone at some sites. It is crucial to exclude pathological causes of osteoporosis, because 30 to 60% of men with vertebral fractures have another illness contributing to bone disease. Glucocorticoid excess (predominantly exogenous) is common. Gastrointestinal disease predisposes patients to bone disease as a result of intestinal malabsorption of calcium and colecalciferol (vitamin D). Hypercalciuria and nephrolithiasis, anticonvulsant drug use, thyrotoxicosis, immobilisation, liver and renal disease, multiple myeloma and systemic mastocytosis have all been associated with osteoporosis in men. It is possible that low-dose estrogen therapy or specific estrogen receptor-modulating drugs might increase BMD in men as well as in women. In the future, parathyroid hormone peptides may be an effective treatment for osteoporosis, particularly in patients in whom other treatments, such as bisphosphonates, have failed. Men with idiopathic osteoporosis have low circulating insulin-like growth factor-1 (IGF-1; somatomedin-1) concentrations, and IGF-1 administration to these men increases bone formation markers more than resorption markers. Studies of changes in BMD with IGF-1 treatment in osteoporotic men and women are underway. Osteoporosis in men will become an increasing worldwide public health problem over the next 20 years, so it is vital that safe and effective therapies for this disabling condition become available. Effective public health measures also need to be established and targeted to men at risk of developing the disease.     

Relationship of age, age at onset, and sex to depression in older adults

The authors investigated the relationships among factors of age, age at onset, and sex in depressed older adults. A group of 96 outpatients (mean age, 60) diagnosed with late-(LOD) and early-onset (EOD) major depression were assessed for severity of depression and underwent magnetic resonance imaging (MRI). The MRI scans were rated for severity of white-matter hyperintensities (WMH) and ventricle-to-brain ratio (VBR). LOD was associated with increased amounts of WMH, larger VBR, and history of hypertension. Men were more severely depressed than women, with higher rates of neurovegetative signs and history of smoking. Age correlated with increased VBR and WMH, history of hypertension, history of percipitants for the current episode, and lack of social support. Results suggest that a subgroup of men may be more at risk for LOD associated with WMH and that sex and age at onset need to be considered in future studies.     

Insulin-like growth factor-I (IGF-I) plasma concentrations are increased in depressed patients

There is some evidence that the somatotrophic system in depression, as assessed by basal growth hormone (GH) concentrations and by GH releasing hormone (GHRH) challenge, might be dysfunctional. However, the rather limited data have been inconclusive so far and plasma concentrations of both insulin-like growth factor-1 (IGF-I) and binding proteins (IGFBP 1 to IGFBP-6) have not been measured simultaneously in depressed patients. We studied 24 severely depressed patients and 33 healthy controls and estimated 24-hour mean plasma cortisol, six-hour evening mean plasma growth hormone (GH), morning plasma IGF-I, IGFBP 2 and 3 and GH-binding protein (GH-BP). Twenty-four-hour mean cortisol (306 +/- 69 vs. 196 +/- 30 nmol/l, p < .001) and IGF-I (157 +/- 40 vs. 120 +/- 33 micrograms/l, p < .01) plasma concentrations were found to be significantly increased in depressed patients, while there was no difference in GH or binding proteins between both groups. MANOVA analysis revealed age and diagnosis to have main effects upon plasma IGF-I. Especially young age and a diagnosis of major depression are associated with higher plasma IGF-I. After treatment only patients in remission had attenuated IGF-I plasma concentrations. We conclude that plasma IGF-I is increased in acutely depressed patients similar to other states of hypercortisolemia.     

Gender-sensitive recommendations for assessment and treatment of depression in men.

Psychologists increasingly recognize depression as a serious, albeit often undiagnosed, condition in men. In fact, undiagnosed and untreated depression in men may be one reason why many more men than women commit suicide. However, because of cultural conditioning that discourages expression of depressed mood in men, assessment as well as treatment of depression in men are sometimes difficult. Use of gender-sensitive assessment strategies and interventions will assure that more men will be identified and treated for depression. This article integrates scientific findings related to depression in men with specific gender-sensitive assessment and psychotherapeutic intervention strategies designed to enhance psychologists' skills in working with this significant problem in men. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blunted Cortisol Response to Awakening in Mild to Moderate Depression: Regulatory Influences of Sleep Patterns and Social Contacts.

Cortisol is elevated during severe depression. However, some studies of outpatients suggest reduced cortisol levels, either basal or poststress. More definite evidence of this phenomenon is needed, and correlates that may explain the disparate findings should be identified. Women from the community (37 depressed and 36 nondepressed) completed electronic diaries in order to help researchers assess the cortisol awakening response (CAR), sleep, and social contacts. Depressed women had a blunted CAR compared with nondepressed women. Among the nondepressed but not among depressed women, time of waking, and number of social contacts (especially positive ones) were independently associated with CAR. These psychosocial factors may contribute to a normal CAR, but their regulatory influence may become disrupted during mild to moderate clinical depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age and emotional response to the Northridge earthquake: A longitudinal analysis.

Cross-sectional studies have found older adults to have lower levels of emotional distress after natural disasters. The maturation hypothesis suggests that older adults are less reactive to stress events, whereas the inoculation hypothesis argues that prior experience with disaster is protective. One hundred and sixty-six adults aged 30 to 102 were interviewed regarding the 1994 Northridge earthquake. Longitudinal data were available on depressed mood before and after the earthquake. The maturation hypothesis was generally not supported. The young–old were least depressed; however, this age difference was present prior to the earthquake. The old–old showed lowest levels of earthquake-specific rumination, but age did not buffer the relationship between damage exposure and rumination. The inoculation hypothesis was supported for depressed mood. Prior earthquake experience was related to lower postearthquake depression scores. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in unipolar depression: Evidence and theory.

A large body of evidence indicates that women are more likely than men to show unipolar depression. Five classes of explanations for these sex differences are examined and the evidence for each class is reviewed. Not one of these explanations adequately accounts for the magnitude of the sex differences in depression. Finally, a response set explanation for the sex differences in depression is proposed. According to this explanation, men are more likely to engage in distracting behaviors that dampen their mood when depressed, but women are more likely to amplify their moods by ruminating about their depressed states and the possible causes of these states. Regardless of the initial source of a depressive episode (i.e., biological or psychological) men's more active responses to their negative moods may be more adaptive on average than women's less active, more ruminative responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparative studies of the biological distinction between unipolar and bipolar depressions

Although unipolar depression and bipolar depression are considered distinct entities both by clinicians and researchers, it is not clear whether a pathophysiological distinction, which is the bridge between etiology and treatment, exists between these two conditions. The objective of this paper was to systematically review the studies that examined the biological differences between unipolar and bipolar depression. Using computerized Medline and manual searches, we located and reviewed studies that directly compared patients with unipolar depression with bipolar depressed patients on at least one biological variable. The results showed that patients with bipolar depression had lower levels of urinary NE and its metabolites and lower platelet MAO activity, and higher platelet free and stimulated intracellular calcium levels compared with unipolar depressed patients, but none of the variables examined appeared to differentiate the two groups consistently. We discuss some of the methodological flaws that might have contributed to this, and suggest that further studies should control for such confounding variables.     

Raising questions about antidepressants

Antidepressant medication has apparently become the most popular treatment for depression in the USA. Several beliefs about the efficacy of antidepressant medications prevail among mental health professionals and the public. This paper explores relevant research data and raises questions about these beliefs. Many of the common beliefs about these medications are not adequately supported by scientific data. The following issues are raised: (1) industry-funded research studies which result in negative findings sometimes do not get published; (2) placebo washout procedures may bias results in some studies; (3) there are serious questions about the integrity of the double-blind procedure; (4) the 'true' antidepressant drug effect in adults appears to be relatively small; (5) there is minimal evidence of antidepressant efficacy in children; (6) side effects are fairly common even with the newer antidepressants; (7) combining medications raises the risk for more serious complications; (8) all antidepressants can cause withdrawal symptoms; (9) genetic influences on unipolar depression appear to be weaker than environmental influences; (10) biochemical theories of depression are as yet unproven; (11) biological markers specific for depression have been elusive; (12) dosage and plasma levels of antidepressants have been minimally related to treatment outcome; (13) preliminary evidence suggests that patients who improve with cognitive-behavioral psychotherapy show similar biological changes as those who respond to medication, and (14) the evidence suggests that psychological interventions are at least as effective as pharmacotherapy in treating depression, even if severe, especially when patient-rated measures are used and long-term follow-up is considered.