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Teaching Family Physicians About Mood Disorders: A Procedure Suite for Behavioral Medicine.

BACKGROUND AND OBJECTIVES: One of the skills required of family physicians is the ability to recognize and treat individuals suffering from mood disorders. This study represents an interdisciplinary residency training approach that (1) is unique in family practice residencies; (2) trains faculty, residents, and students in mood disorder recognition and treatment; (3) has been evaluated by the Residency Review Committee and found compatible with psychiatry training guidelines; and (4) is adaptable to varied settings. METHOD: Existing psychiatric education at an urban family practice residency program was evaluated. A new curriculum was developed to emphasize clinical interactions that would allow residents to model the behavior of family physicians who demonstrate interest and expertise in psychiatry. The centerpiece of this curriculum is a family-physician-led, multidisciplinary, in-house consultation service known as a mood disorders clinic (MDC). Educational effectiveness was evaluated by comparing resident identification rates of mood disorders before and after training. Educational utility was evaluated by implementation in a variety of settings. RESULTS: Fifty-one residents rotated through 1 or more of 3 practice sites during a 60-month period. Psychiatric diagnoses for the 187 patients who remained in treatment for complete clinical assessment included all major mood and anxiety disorders outlined in the DSM-IV. A wide variety of associated psychosocial problems were also identified. A significant difference (p <.05) was seen between the number of continuity patients diagnosed with psychiatric conditions by resident physicians before and after the training experience. CONCLUSION: Implementation of this intensive training experience resulted in subjective as well as objective enhancement of resident education by providing an intensive, focused educational experience in primary care psychiatry. This concept is adaptable to a variety of practice sites and educational levels. The MDC could become the hub of an integrated delivery system for mental health services in an ambulatory primary care setting.

Journal Article↗

Sleep disturbances and mood disorders: an epidemiologic perspective.

Epidemiologic studies of sleep disturbances and mood disorders that may provide more valid estimates of associations between these two conditions than clinical samples due to differential use of health care services. Increasing uniformity of questionnaires to assess sleep disturbances has decreased the variance in estimates of insomnia and hypersomnia within community samples. Women are more likely to report insomnia than men in every age group. There appear to be no clear racial or ethnic differences in rates of insomnia or hypersomnia. Several community-based studies have found that sleep disturbances are powerful risk factors for the development of new episodes of major depression in the following year. Individuals who report insomnia or poor quality sleep may be at higher risk for depression throughout their lifetime. Epidemiologic studies will be useful for developing the long-term perspective on the natural history of sleep disturbances and mood disorders and the consequences of treatment.

Adult↗

Has there been a decrease in the prevalence of mood disorders in HIV-seropositive individuals since the introduction of combination therapy?

PURPOSE: The aim of this study was to assess the prevalence of current mood disorders in HIV-seropositive patients treated with combined antiretroviral drug therapy including or not protease inhibitors. SUBJECTS AND METHODS: A random sample of 90 subjects consecutively attending, between February 1 and July 31, 1998, the outpatient unit of the Second Department of Infectious Diseases of the 'L. Sacco' Hospital in Milan was assessed by means of the Structured Clinical Interview for DSMIII-R (SCID) and the Zung Self-Rating Depression Scale (ZSDS). RESULTS: Twenty-three-point-three percent of the subjects were classified in CDC stage A, 32.3% in CDC stage B and 44.4% in CDC stage C. A DSMIII-R psychiatric diagnosis of current mood disorder was found in 4.4% of the recruited sample (dysthymia: 2.2%; adjustment disorder with depressed mood: 2.2%). CONCLUSIONS: Direct and indirect effect of new combination therapies, epidemiological changes in social groups affected by HIV and possible modifications in social perception of people with HIV infection may explain, at least in part, the decreased prevalence of current mood disorders observed in our study as compared to prevalence rates reported in the pre-HAART era.

Adult↗

[Does menstrual cycle affect mood disorders?].

OBJECTIVE: This paper will present a review of the literature on the relationship between the menstrual cycle and mood disorders. METHOD: We performed a MEDLINE search of the Turkish and English language literature for the years 1955-2005 using the following terms: depression, bipolar disorder, premenstrual syndrome, premenstrual exacerbation, premenstrual dysphoric disorder, menstrual cycle, and suicide. Earlier reports had shown higher psychiatric admission during premenstrual period of the menstrual cycle and higher prevalence of suicide attempts during specific phase of the menstrual cycle. RESULTS: Women of reproductive age with mental disorders may experience a fluctuating course of illness over the menstrual cycle. Some data suggest that for a subset of women there is a relationship between phases of the menstrual cycle and increased vulnerability for an exacerbation of ongoing mood disorders (especially major depressive episode) or the development of a new episode. The question of whether the direction of mood shifts in the course of bipolar disorder is associated with specific cycle phase has been raised, albeit with limited and inconsistent data. CONCLUSION: There are a limited number of studies to elucidate these relationships and most of them lack prospective assessments, include the small number of patients and use unreliable methods of determining menstrual-cycle phases. Additionally, many reports do not specify whether the exacerbations reflect an aggravation of the underlying mood disorder or a new subset of symptoms that occur only during certain phases of the menstrual cycle. Further studies should provide more information about the contribution of premenstrual fluctuation or worsening to increased illness severity of mood disorder and treatment resistance.

Adult↗

An update on regional brain volume differences associated with mood disorders.

PURPOSE OF REVIEW: Structural brain changes are apparent in some magnetic resonance imaging studies of patients with mood disorders, but results are inconsistent. The focus of this review is to examine whether there are demographic or clinical characteristics of people with mood disorders that are associated with regional brain volume changes. A systematic search of the literature in English, from January 2004 to July 2005, was performed on MEDLINE. References cited in all reports were searched iteratively to identify missing studies. RECENT FINDINGS: Recent studies have focused on factors that might help to reconcile the divergent reports of regional brain volume changes in major depressive disorder and bipolar disorder. Small hippocampal volumes are apparent in patients with recurrent major depressive disorder, but not generally reported early in the course of adult onset depression. Small hippocampal volumes may be apparent in patients with childhood onset illness. Small hippocampal volumes are infrequently reported in bipolar disorder, but studies to date have not accounted for illness history or treatment status. Changes in amygdala volumes are inconsistently reported in patients with major depressive disorder or bipolar disorder. There are relatively fewer reports of other brain regions, including the areas of the frontal cortex and striatum. An extensive preclinical literature suggests that various psychotropic medications may have neurotrophic and neuroprotective effects, making documentation of treatment history essential. SUMMARY: Patients' age, sex, age at onset of disease, course of illness and treatment status may affect the detection of regional brain volume changes in people with mood disorders.

Brain↗

Association study of MAO-A, COMT, 5-HT2A, DRD2, and DRD4 polymorphisms with illness time course in mood disorders.

The aim of our study was to investigate a possible influence of monoamine oxydase A (MAO-A), catechol-O-methyltransferase (COMT), serotonin receptor 2A (5-HT2A), dopamine receptor D2 (DRD2), and dopamine receptor D4 (DRD4) gene variants on timing of recurrence in mood disorders. Gene variants were determined using PCR-based techniques in 550 inpatients affected by recurrent mood disorders (major depressives: n = 212; bipolars: n = 338), rapid cycling mood disorder (n = 81), and 663 controls. We investigated possible genetic influences by comparing illness time course of subjects subdivided according to genotype using multivariate analysis of variance (MANOVA). We could not observe a significantly different time course. No demographic and clinical variables such as sex, age or polarity of onset, presence of psychotic features, genetic loading, or education level influenced the observed results. Our results suggest that MAO-A, COMT, 5-HT2A, DRD2, and DRD4 gene variants are not involved in susceptibility toward different time courses in mood disorders.

Adult↗

[A case of Neuro-Behçet's disease with early onset of bipolar mood disorder].

In this report, we describe a case of Neuro-Behçet's disease with early onset of bipolar mood disorder. A 53-year-old man with neuropathy including dysphasia and dyslalia developed bipolar mood disorder with anxiety, agitation, depressive mood, talkativeness, hyperkinesias, and appetite rise, and soon exhibited severe personality deterioration. Oral aphthae, cell proliferation and elevated IL-6 levels in spinal fluid, and the patient's clinical downhill course with remission and relapse in spite of good reaction to steroid preparation indicated the possibility of Neuro-Behçet's disease. Brain MRI showed clear swelling of the brain stem area, especially in the pons, in the active phase with low signal in T1-weighted images contrasting with clear high signal in T2-weighted images and FLAIR. At the time of remission, atrophy of the brain stem was shown. These findings were consistent with the view reported in recent years concerning the brain image of Neuro-Behçet's disease, which seemed to be useful for the differential diagnosis. This case manifested two outstanding clinical features. First, it showed bipolar mood swing or mixed state distinguishable from disinhibition or euphoria in deteriorated personality, which is common in this condition. A clear bipolar mood disorder has not been described until now in Neuro-Behçet's disease. Second, subclinical dysthymia or hypomanic phase occurred before clear onset of the disease. In Neuro-Behçet's disease, it is currently considered that psychiatric symptoms may appear in the early stage, but there is controversy as to whether they can precede the other symptoms. Our case indicated very early onset of psychiatric symptoms in this condition.

Behcet Syndrome↗

Baseline cerebral hypermetabolism associated with carbamazepine response, and hypometabolism with nimodipine response in mood disorders.

BACKGROUND: Positron emission tomography (PET) studies have reported baseline (medication free) differences between mood disorder patients and healthy control subjects, but relatively little is known about relationships between baseline PET scans and treatment responses. Carbamazepine (CBZ) and to a more limited extent nimodipine (NIMO) seem useful in mood disorders. We explored whether baseline regional cerebral glucose metabolism (rCMRglu) could discriminate CBZ and NIMO responders from nonresponders and healthy control subjects. METHODS: In refractory mood disorder patients, we examined relationships between responses to these drugs, assessed by Clinical Global Impression-Improvement scores, and baseline rCMRglu, determined with fluorine-18 deoxy-glucose and PET. RESULTS: CBZ responders had baseline left insular hyper-metabolism compared to healthy control subjects and nonresponders, whereas nonresponders had widespread (including left insular) hypometabolism. Degree of CBZ response correlated with baseline paralimbic (including insula) and prefrontal hypermetabolism. In responders but not nonresponders, CBZ decreased widespread metabolism, with the degree of decrease in left insula correlating with response. In contrast, NIMO responders but not nonresponders had baseline widespread (including left insular) hypometabolism. Left prefrontal and left insular baseline hypometabolism, but not metabolic changes with treatment correlated with degree of NIMO response. CONCLUSIONS: These data suggest that baseline anterior paralimbic and prefrontal hypermetabolism may be associated with CBZ response, and hypometabolism with NIMO response. Based on these preliminary data, further exploration of relationships between baseline PET scans and treatment responses is indicated.

Adult↗

Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders.

We previously reported an association between the functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR) and the prophylactic efficacy of lithium in a sample of 201 Italian subjects affected by Mood disorders. The aim of the present study was to replicate analyses on an independent sample. In total, 83 subjects affected by Bipolar disorder were recruited in the Mood Disorders Clinic of the Eginition Hospital of the Athens University, Medical School Department of Psychiatry. All patients were administered with lithium as prophylactic therapy and they were prospectively observed for at least 3 years. Subjects were typed for their SERTPR variant using polymerase chain reaction techniques. SERTPR variants were associated with lithium outcome among those subjects who had few manic episodes before lithium treatment and, as a trend, among subjects who received a high daily dose of lithium (> or =1200 mg/die). In both cases, subjects with the l/l variant showed a higher probability to develop an illness episode within 3 years of prophylactic treatment with lithium. The present study confirmed our previous observation of a better response of SERTPR*l/s carriers, but could not confirm a poor efficacy in subjects with the SERTPR*s/s genotype. Notwithstanding the conflicting results, SERTPR variants are a possible liability factor for lithium long-term efficacy in mood disorders. Further studies on independent and large samples are required to determine the reliability and direction of the possible association between SERTPR variants and lithium outcome.

Age of Onset↗

Interaction between serotonin transporter gene, catechol-O-methyltransferase gene and stressful life events in mood disorders.

It is well established that stress is a risk factor for onset of mood disorders. Emerging evidence suggests that genetic vulnerability may also moderate individual responsiveness to stress. The most compelling evidence regards the polymorphism within the promoter region of the serotonin transporter gene (SERTPR), which has been reported to moderate the risk for depression, in conjunction with life stressors. In the present paper we analysed SERTPR in the onset of mood disorders, along with adverse life events, and other candidate genes: the serotonin receptor 1A (5-HT1A), the dopamine receptor D4 (DRD4) and the catechol-O-methyltransferase (COMT). The sample was composed of 686 Italian subjects, affected by major depression and bipolar disorder. Patients were asked to report about life stressors within the year preceding onset of their first mood-disorder episode and genotyped. A 'case-only' design was employed to investigate the interaction between genes and stressors. COMT was associated with depression following exposure to stressors (chi2=13.05, d.f.=2, p=0.0015) and SERTPR also showed a positive association (chi2=6.70, d.f.=2, p=0.035), mainly among women and among major depressives. The interaction between COMT and SERTPR was also significant (p=0.0005). In our retrospective study SERTPR is hypothesized to lead to the onset of major depression via its influence on reaction to adversities, particularly in females. Moreover, COMT was risk factor for onset of both major depression and bipolar disorder, in conjunction with adversities.

Adult↗

Magnetic resonance spectroscopic studies of pediatric mood disorders: a selective review.

PURPOSE OF REVIEW: This review article presents a summary of the recent magnetic resonance spectroscopic studies of pediatric mood disorders. RECENT FINDINGS: Magnetic resonance imaging is a promising tool for investigating the biologic substrates of neuropsychiatric disorders without the use of ionizing radiation. This novel technique has been recently applied to pediatric patients with mood disorders. Structural, chemical, and functional abnormalities in pediatric patients with mood disorders have been reported. SUMMARY: To date, only modest numbers of pediatric studies using magnetic resonance imaging have been conducted. Most of these studies have small sample sizes and heterogeneous subject groups. These studies have provided important information regarding the underlying neuro-circuitry and pathophysiology of these complex and disabling disorders, however.

Brain↗

Reliability of diagnosis in mood disorders.

The reliability of diagnosing mood disorders is reviewed for previous and current versions of the American Psychiatric Association's DMS. Reliability is shown to improve with the increasing specificity of diagnostic criteria. The new specifiers for the course of major depression in relation to dysthymia also are shown to be reliable.

Adult↗

Genetics of mood disorders--an overview. Part one.

Mood disorders are severe and common psychiatric diseases with two main clinical forms: Bipolar disorder, type 1 (BP1), and Unipolar disorder (UP). This paper provides an overview of the Literature on genetics of BP1 and UP disorders. We described the problems of diagnostic definitions, and statistical methods for studying the genetic etiology of these disorders. Epidemiological and quantitative genetic studies are reviewed. Interactions of susceptibility genes and environmental factors in this disorders are also fundamental and has to be properly investigated. The understanding of genetic aspects of BP1 and UP disorders has benefited from recent findings with DNA markers. Therefore we also provide an overview of linkage and association studies that reveal several chromosomal regions, candidate genes and dynamic mutations which may play role in BP1 and UP disorders.

Bipolar Disorder↗

Neurotransmitter receptor-mediated activation of G-proteins in brains of suicide victims with mood disorders: selective supersensitivity of alpha(2A)-adrenoceptors.

Abnormalities in the density of neuroreceptors that regulate norepinephrine and serotonin release have been repeatedly reported in brains of suicide victims with mood disorders. Recently, the modulation of the [(35)S]GTPgammaS binding to G-proteins has been introduced as a suitable measure of receptor activity in postmortem human brain. The present study sought to evaluate the function of several G-protein coupled receptors in postmortem brain of suicide victims with mood disorders. Concentration-response curves of the [(35)S]GTPgammaS binding stimulation by selective agonists of alpha(2)-adrenoceptors, 5-HT(1A) serotonin, mu-opioid, GABA(B), and cholinergic muscarinic receptors were performed in frontal cortical membranes from 28 suicide victims with major depression or bipolar disorder and 28 subjects who were matched for gender, age and postmortem delay. The receptor-independent [(35)S]GTPgammaS binding stimulation by mastoparan and the G-protein density were also examined. The alpha(2A)-adrenoceptor-mediated stimulation of [(35)S]GTPgammaS binding with the agonist UK14304 displayed a 4.6-fold greater sensitivity in suicide victims than in controls, without changes in the maximal stimulation. No significant differences were found in parameters of 5-HT(1A) serotonin receptor and other receptor-mediated [(35)S]GTPgammaS binding stimulations. The receptor-independent activation of G-proteins was similar in both groups. Immunoreactive densities of G(alphai1/2)-, G(alphai3)-, G(alphao)-, and G(alphas)-proteins did not differ between suicide victims and controls. In conclusion, alpha(2A)-adrenoceptor sensitivity is increased in the frontal cortex of suicide victims with mood disorders. This receptor supersensitivity is not related to an increased amount or enhanced intrinsic activity of G-proteins. The new finding provides functional support to the involvement of alpha(2)-adrenoceptors in the pathogenesis of mood disorders.

Adult↗

Alcohol dependence and mood disorders.

This article explores the complex relationships between alcohol dependence and mood disorders. Although many alcoholics present with substance-induced depressions, once appropriate methodological controls are used, there does not appear to be a significant relationship between independent unipolar depression and alcohol dependence. However, the data support a small, but significant, relationship between bipolar manic-depressive disease and alcoholism. The literature does not support the relevance of self-medication as a course of alcoholism, unless one includes the use of alcohol to alleviate alcohol-induced psychological and neurochemical perturbations. The clinical importance of distinguishing between substance-induced and independent mood disorders is reviewed.

Affective Symptoms↗

Dopamine receptor D4 gene is associated with delusional symptomatology in mood disorders.

Disturbances of the dopaminergic neurotransmitter system have been implicated in the pathogenesis of depressive symptoms. Many studies have, however, failed to detect any association between genetic markers for the dopamine system and mood disorders. A possible reason for this may lie in the definition of phenotype, which is traditionally based on psychiatric diagnosis. In this study, we investigated the possibility that functional variants of the dopamine D4 receptor (DRD4) gene might be associated with depressive symptomatology in a sample of mood disorder subjects. Seventy-nine inpatients affected by bipolar (n=37) and major depressive (n=42) disorder (DSM-IV) were assessed at admission by the Hamilton Depression Rating Scale and were typed for DRD4 variants at the third exon using polymerase chain reaction (PCR) techniques. DRD4 was associated with delusional symptoms (F=5.56; d.f.=2,145; P=0.005), with DRD4*7 exhibiting higher scores when compared to DRD4*4 (P=0.006) variants. Polarity of mood disorder did not influence results significantly. The findings are in accordance with our previous report of an association of the DRD4 gene with delusional symptomatology of major psychoses. DRD4*7 should, therefore, be considered a liability factor for delusional symptoms in mood disorders.

Adult↗

S100B is increased in mood disorders and may be reduced by antidepressive treatment.

Previous studies have reported alterations of glial cells and particularly astrocytes in mood disorders. Therefore, serum concentration of the astrocytic marker S100B was ascertained with an immunoluminometric assay in 20 patients with mood disorder and 12 healthy age-matched controls. Serum S100B was elevated in major depression (median after admission 410 ng/l, at discharge < 100 ng/l) and mania (130, 160 ng/l), when compared with controls (< 100 ng/l; rho< 0.01). Antidepressive treatment reduced S100B in conjunction with severity of depressive symptoms ( rho< 0.01). The severity of depression (Hamilton Depression Rating Scale) was positively correlated with S100B (r(s) = 0.51, rho< 0.005). Elevated serum S100B during depressive and manic episodes of mood disorders may indicate alterations of astrocytes, which are reversed by antidepressive treatment.

Adult↗