What is the genetic relationship between anxiety and depression?

Anxiety and depression share a long, close history in psychiatric nosology and treatment. The anxiety disorders, individually and as a group, exhibit remarkably high rates of comorbidity with each other and with major depression. Analyses done in large-scale epidemiologic surveys have identified major patterns of phenomenological overlap between these conditions. Researchers have tested hypotheses of shared genetic etiologies as a potential basis of this relationship. In general, available family studies have found mixed evidence for co-aggregation of anxiety and depressive disorders, while twin studies more definitively indicate that shared genetic risk factors largely account for this comorbidity. Some of this appears to be accounted for by genetic variation in personality traits that broadly predispose to anxiety and depression. Molecular genetic studies of these conditions, though too early to draw firm conclusions, thus far provide tentative support for specific genetic loci that may generally influence susceptibility across the anxiety-depressive spectrum.     

Is there a dose-effect relationship between the number of psychotherapy sessions and improvement of social functioning?

OBJECTIVES AND DESIGN This study describes a randomized controlled trial which aimed to evaluate whether 16 sessions of psychotherapy combined with pharmacotherapy is more effective in relieving depression and improving social functioning than 8 sessions of psychotherapy combined with pharmacotherapy. METHODS. Randomized controlled trial comparing two treatment conditions with different psychotherapy dosages in out-patients with major depression. All patients studied had a baseline score of at least 14 points on the 17-item Hamilton Depression Rating Scale (HDRS). The two conditions consisted of 8- or 16-session short psychodynamic supportive psychotherapy, both in combination with pharmacotherapy. Efficacy was assessed using the 17-item HDRS, the clinical global impression of severity and of improvement, the depression subscale of the Ninety Symptom Checklist, the Quality of Life Depression Scale, and the Groningen Social Disability Schedule. RESULTS. Social functioning improved significantly in both groups. No significant differences were found between 8 and 16 sessions with regard to social functioning. A significant advantage is found for patients in remission on 5 of the 11 dimensions in social functioning over patients not in remission. CONCLUSIONS. At the end of treatment, no clear differences are found between 8 or 16 sessions of psychotherapy - both combined with pharmacotherapy - with regard to severity of depression and social functioning. It is thus still unknown if patients with major depression show more improvement in social functioning and less symptoms of depression after 16 sessions of combined therapy than after 8 sessions. Currently, it seems that for major depression 8 sessions of combined therapy are equally effective as 16 sessions.     

What is relationship between the medial preoptic area,the organum vasculosum of the lamina terminalis and Kallmann syndrome?

The medial preoptic area is a structure located in the hypothalamic anteroventral third ventricle region, and is closely related to the olfactory brain development and sexual differentiation of the brain. The medial preoptic area surrounds the organum vasculosum of the lamina terminalis, and both structures are the main areas where synthesis of gonadotropin-releasing hormone occurs in the brain. Neurons synthesizing gonadotropin-releasing hormone migrate from the medial nasal epithelium to the rostral brain and reach the organum vasculosum of the lamina terminalis and the medial preoptic area. Kallmann syndrome is a genetic disorder which combines hypogonadotropic hypogonadism and anosmia. Hypogonadism is characterized by the absence or reduced levels of gonadotropin-releasing hormone and anosmia due to olfactory bulb aplasia. This paper speculates on the connection between the development of the medial preoptic area, the organum vasculosum of the lamina terminalis and olfactory bulbs with Kallmann syndrome, since the anteroventral third ventricle region is crucial for the normal development of these structures and its connection with the olfactory nerves and sexual maturation.     

A view of geriatrics through hormones. What is the relation between andropause and well-known geriatric syndromes?

Age related male hypogonadism, or “andropause”, is increasingly recognized as of frequent occurrence in older patients. Diagnosis requires both the presence of clinical symptoms and low testosterone levels. However, diagnosing andropause in this age group may be challenging since symptoms are frequently non specific and testosterone levels are influenced by a multitude of parameters such as lifestyle factors and chronic diseases. In this article we discuss the pathophysiology, definition and diagnostic difficulties of andropause in geriatric patients. Moreover, we review the relation between testosterone levels and frequent geriatric syndromes such as falls, osteoporosis, cognitive and mood disorders, anemia and cardiovascular disease. Finally, we examine the potential benefits and risks of testosterone replacement therapy in this age group.     

Does social support mediate the moderating effect of intrinsic religiosity on the relationship between physical health and depressive symptoms among Jews?

Previous research in the general population suggests that intrinsic religiosity moderates (mitigates) the effect of poor physical health on depression. However, few studies have focused specifically on the Jewish community. We therefore examined these variables in a cross-sectional sample of 89 Orthodox and 123 non-Orthodox Jews. Based on previous research suggesting that non-Orthodox Judaism values religious mental states (e.g., beliefs) less and a collectivist social religiosity more, as compared to Orthodox Judaism, we hypothesized that the moderating effect of intrinsic religiosity would mediated by social support among non-Orthodox but not Orthodox Jews. As predicted, results indicated that the relationship between physical health and depression was moderated by intrinsic religiosity in the sample as a whole. Furthermore, this effect was mediated by social support among non-Orthodox Jews, but not among the Orthodox. The importance of examining religious affiliation and potential mediators in research on spirituality and health is discussed.     

Viewpoint: what is the best and most ethical model for the relationship between mainstream and alternative medicine: opposition, integration, or pluralism?

Despite radical improvements in medicine over the past 60 years, patients maintain multiple health care pathways that include high utilization of unconventional treatments. The authors examine three possible relationships between mainstream and alternative medicine: opposition, integration, and pluralism. Opposition, the traditional ethical position that the medical profession must eradicate unconventional medicine for the good of the patient, has withered away. Integration of mainstream and alternative medicine is increasingly advocated in tandem with hospital-based programs that amalgamate the use of conventional and alternative therapies. While advocates of integrative medicine often speak of "evidence-based" complementary and alternative medicine (CAM), integration fosters double standards for validating conventional and unconventional treatments. Integration also ignores unbridgeable epistemological beliefs and practices between mainstream and alternative medicine. Pluralism, which has been relatively ignored, calls for cooperation between the different medical systems rather than their integration. By recognizing the value of freedom of choice in medical options, pluralism is compatible with the principle of patient autonomy. Nonetheless, the pluralistic model does not amount to a relativistic stance according in which there would be no objective standards for comparing the therapeutic merit of conventional and CAM treatments. As an ethical model, pluralism realizes that physicians must be prepared to disagree with patient choices to pursue alternative therapies, and urge patients not to forgo medically indicated treatment. Pluralism encourages cooperation, research, and open communication and respect between practitioners despite the possible existence of honest disagreement, and preserves the integrity of each of the treatment systems involved.     

Is "relationship fear" unique to Japan? Symptom factors and patient clusters of social anxiety disorder among the Japanese clinical population

BACKGROUND: There have been only a limited number of cross-cultural studies of social anxiety disorder (SAD), especially as diagnosed with modern operationalized diagnostic criteria and as measured with recently developed assessment instruments. We examined the symptomatological structure and clinical subtypes of patients with DSM-IV SAD among the Japanese clinical population. METHODS: We performed confirmatory and exploratory factor analyses of the joint Social Interaction Anxiety Scale and Social Phobia Scale from 149 psychiatric patients diagnosed with SAD. Based on the derived symptom factors, we further ran cluster analysis to identify patient subgroups. RESULTS: Factor analyses revealed three factors which were named "scrutiny fears", "conversation fears" and "relationship fears". The first two appeared common to Western clinical populations but the third appeared unique to the Japanese. Cluster analysis based on these three factor scores yielded three subgroups, which were externally validated and which overall corresponded with mild, moderate and pervasive subtypes of social phobia. LIMITATIONS: Both factor analysis and cluster analysis employed in the present study are exploratory in nature. Further empirical examination in different settings and cultures is necessary to provide definitive answers. CONCLUSIONS: It is suggested that we may need three symptom subscales and three subtypes in order to better account for cultural variations in the presentation of SAD.     

Does number of lifetime traumas explain the relationship between PTSD and chronic medical conditions? Answers from the National Comorbidity Survey-Replication (NCS-R)

The present study sought to extend prior research by using data from the National Comorbidity Survey-Replication (NCS-R) to examine the relationship between number of lifetime traumas, posttraumatic stress disorder (PTSD) and 15 self-reported chronic medical conditions. The goal was to determine whether the commonly found relationship between PTSD symptomatology and physical health were better explained by the number of lifetime traumas experienced. The NCS-R is a representative US household survey that assessed lifetime experience of a variety of traumas, lifetime diagnosis of PTSD and 15 chronic medical conditions (e.g. pain conditions, cardiovascular disorders, etc.). Two major findings emerged: (1) there was a graded relationship between trauma exposure, PTSD, and the majority of chronic medical conditions where individuals with PTSD had the highest likelihood of chronic medical condition and non-traumatized individuals had the lowest risk and; (2) with the exception of headaches, the relationship between PTSD and chronic medical conditions was explained by the number of lifetime traumas experienced when analyses were subset to traumatized individuals. The present study supports prior research suggesting that multiple traumas have a cumulative effect on physical health. The impact of trauma on health may be independent of PTSD symptomatology.     

Might the inability to feel pleasure (anhedonia) explain the symptoms of major depression and schizophrenia, including unmotivated anxiety, delusions and hallucinations?

Inability to enjoy normally pleasurable experiences (anhedonia) is a symptom common both to major depression and schizophrenia. It also regularly accompanies and follows stress, and its presence in the two mental illnesses could depend on the fact that both are facilitated and often preceded by stressful events. Anhedonia might possibly accompany stress because the loss of the pleasure of aiming for a goal and achieving it (including defending oneself and escaping from a danger) could lead to immobility, and immobility (playing dead) offers the extreme chance of safety when an animal is facing the worst possible stressful situation - being seized by a predator - as in this case any movement can further stimulate the predator’s aggressiveness.Perceiving and connecting sensory information also gives pleasure, and this appears to enhance the clarity of sensations and is an important factor in learning. We propose that anhedonia, by reducing or eliminating the pleasure, might jeopardize the usual appearance of the environment, which must not only be clearly perceived but also continuously interpreted (for instance a foreshortening, or something far off seen as small, must not be seen as a real deformation; the same holds for words, where the meaning has to be grasped from the single letters, and so on). Consequently, anhedonia could in some cases make the environment’s image strange, distorted and frightening, and this could cause anxiety, confusion, and give problems in contacts with people and things.As correct information about images and sounds can inhibit visual and auditory hallucinations (considering them, like delusions, as attempts to reconstruct and make sense again of a world that is becoming confused and alien), we propose that anhedonia, interfering with the correct perceiving and processing of sensations, may facilitate them.     

What is the real importance of evaluating the expression of c-erbB-2 (HER-2/neu) in carcinoma of the breast and prostate? (A short review)

This minireview covers the key data on biology and clinical implications of the c-erbB-2 oncogene in breast and prostate cancer. The aim was to provide basic information to practically oriented pathologists in order to make a reasonable application of methods for c-erbB-2 overexpression or amplification analysis. The clinical interpretation of c-erbB-2 abnormalities should reflect the complexity of c-erbB-2 mediated regulatory pathway and explain why tumours with overexpression/amplification of c-erbB-2 very often do not respond to therapy using Herceptin.     

Coping with unfair treatment at work--what is the relationship between coping and hypertension in middle-aged men and Women? An epidemiological study of working men and women in Stockholm (the WOLF study)

BACKGROUND: An important hypothesis in psychosomatic medicine is that exposure to psychosocial factors that arouse anger may accelerate the onset of hypertension, particularly if the subject is not allowed to show anger or to deal constructively with the factor that evoked it. For working men and women, being treated in an unfair way at work may be crucial. The present study was designed to answer the question whether the pattern of coping - primarily directed towards the aggressor (open) or directed inwards or towards others (covert) - is associated with hypertension among working men and women. STUDY GROUP: Five thousand seven hundred and twenty working men and women aged 15-64 participated in the study. The participation rate was 76%. METHODS: The coping pattern was studied by means of a Swedish version of a self-administered questionnaire that was originally introduced by Harburg et al. RESULTS: Significant results were confined to the age group 45-54. All analyses were adjusted for age and body mass index. Smoking habits and social class had no effect on the relationships. Low scores (lowest quartile) for open coping tended to be associated with an elevated prevalence ratio (PR) of hypertension both among men (PR 1.3, 95% confidence interval, CI, 0.9-1.7) and women (PR 1.4, 95% CI 1.0-2.0). High scores for covert coping (highest quartile) were associated with an elevated PR of hypertension among men (PR 1.6, 95% CI 1.2-2.2) but not in women. If the analysis was confined to cases without medication, the relationship between a high level of covert coping and high blood pressure was still significant for men. For women, however, no significant findings were made after this operation. Accordingly, the relationship between a low level of open coping and hypertension in women was confined to women with medication. Coping patterns were correlated with psychosocial work environment factors, in particular decision latitude. CONCLUSION: In men, covert coping was associated with prevalence of hypertension. In women, there tended to be a relationship between low scores for open coping and hypertension.     

Is dysfunction of the tissue plasminogen activator (tPA)-plasmin pathway a link between major depression and cardiovascular disease?

Epidemiological, genetic and clinical studies have demonstrated an association between major depressive disorder (MDD) and cardiovascular disease (CVD). For example, MDD is a risk factor for the development of CVD, while around one fifth of patients with CVD have MDD and a significantly larger percentage have subsyndromal symptoms of depression. Furthermore, patients with CVD and depression have an increased risk of future cardiac events compared to similar cohorts without depression, independent of baseline cardiac dysfunction. Despite evidence that CVD and MDD are epidemiologically linked, the cause of this correlation is still unknown. Several risk factors including physical and psychological stress, smoking, physical inactivity and inflammation have been proposed to mediate the interaction between MDD and CVD. The tissue-type plasminogen activator (tPA)-plasminogen proteolytic cascade is widely expressed in the brain. Accumulating evidence from preclinical and clinical studies suggests that tPA and its inhibitor, plasminogen activator inhibitor-1, are related to stress reaction and depression. In addition, brain-derived neurotrophic factor (BDNF) is important for the pathogenesis of MDD and the tPA-plasminogen proteolytic cascade has been implicated in the cleavage of proBDNF to BDNF in the brain, by which the direction of BDNF action is controlled. Thus, it is proposed that tPA-plasmin pathway dysfunction may play a role in the link between MDD and CVD. Future study of the components in the tPA-plasminogen system in CVD patients comorbid with MDD may lead to new, potentially important insights into the link between MDD and CVD, and might also contribute to novel strategies for the management of these two common and devastating diseases.     

Maternal polymorphisms 677C-T and 1298A-C of MTHFR, and 66A-G MTRR genes: is there any relationship between polymorphisms of the folate pathway, maternal homocysteine levels, and the risk for having a child with Down syndrome?

This study was aimed at analyzing the effect of mutations in three non-synonymous SNP genes (677C > T and 1298A > C of the methylenetetrahydrofolate reductase (MTHFR) gene, and 66A > G in the MTRR gene) on total plasmatic homocysteine (Hcy), in 91 mothers of Down syndrome (DS) infants and 90 control mothers. The comparison of both groups of mothers is a new way to determine if those mutations and their interactions increase the risk for DS. Material came from the case-control network of the Spanish Collaborative Study of Congenital Malformations (ECEMC). Using a general lineal model in a backwards step, we performed the analyses including the different mutations, maternal age, the fact that each mother had a DS or a control infant, and all possible interactions of these variables, in the models, being maternal Hcy the continuous dependent variable. In another model, maternal folic acid intake during the third trimester of pregnancy was added. The results from both models were essentially the same: Hcy levels variability differs from case mothers to control ones, the presence of the MTHFR1298A > C polymorphism also affects significantly the Hcy variance, as it does the statistical interaction between the mutations MTRR66A > G and MTHFR1298A > C in the mother. In this sense, the interaction between different polymorphisms may totally modify their individual effects, and some of those effects are different in mothers of DS children and in controls' mothers. For instance, only two mutations in MTRR66 (GGAA) in mothers of control infants increase the reference maternal Hcy level in 4.66 units, and the individual effect of the genotype with only two mutations in the MTHFR1298 gene (AACC) increases the reference Hcy level in 12.74 units. However, the presence of the four mutations (GGCC) interacts giving a statistically significant decrease in 6.00 units in the level of Hcy in control mothers. On the contrary, in mothers of DS infants, the sole presence of two mutations in one of these two genes decreases the levels of Hcy (-2.31 units for GGAA genotype, and -3.43 units for AACC genotype), while the presence of the four mutations (GGCC) increases Hcy in 9.53 units. Taking into consideration that in the one-carbon metabolism cystathionine beta-synthase (CBS) catalyzes Hcy in an irreversible way, and that CBS gene is located in chromosome 21, fetuses and infants with DS have functional folate deficiency due to overexpression of CBS. This fact, as well as others influencing Hcy levels (such as nutrients interactions and lifestyle), together with the fetal genotype, suggest that their relationship with DS could be through an effect on fetal survival up to birth. Three possible mechanisms are considered by evaluating the results in the light of the present knowledge on cytology and molecular biology.     

To what extent are free testosterone (FT) values reproducible between the two Washingtons, and can calculated FT be used in lieu of expensive direct measurements?

Free testosterone (FT) measurement by equilibrium dialysis and liquid chromatography-tandem mass spectroscopy (LCMS/MS) is the "gold standard." We hypothesized that calculated FT values could substitute for measured values; compared FT results reported by Walter Reed Army Medical Center (WRAMC), Washington, DC, with results reported by the Seattle Veterans Affairs Health Care System, Seattle, WA, for 3 patient groups; and evaluated the calculated FT values by gold-standard measurements. Groups 1 and 2 included samples from 54 patients evaluated in Seattle and 94 evaluated at a primary care clinic in Alaska whose samples were analyzed in Seattle, respectively, whose care resulted in ordering an FT measurement. Group 3 included samples from 64 patients evaluated in endocrine WRAMC clinics. Calculated FT values between the 2 facilities demonstrated a strong correlation (R2 = 0.98) for all 212 patients. In a comparison of calculated FT values with measured levels, group 3 had an R2 = 0.93; however, samples with FT values less than 50 pg/mL had a poorer correlation (R2 = 0.45). Calculated FT values may accurately reflect and be substituted in the clinical setting for gold-standard values when levels are more than 50 pg/mL.