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What is the place of psychological treatments in mood disorders?

While psychotherapy has many applications for mood disorders, this paper focuses on those psychotherapies (cognitive behaviour therapy or CBT, and interpersonal psychotherapy or IPT) that have been manualized, extensively evaluated, and positioned as definitive therapies for unipolar depressive disorders. This paper suggests some reasons as to why their role and utility remain unclear. First, despite many randomized controlled efficacy studies, differentiation from other psychotherapies or control interventions appears to occur only when the actual control treatment possesses few therapeutic ingredients. Second, their testing as if they have universal application for non-specific diagnostic entities (e.g. major depression), in trials where there is a high rate of non-specific responsivity to intervention, has limited our capacity to identify the circumstances in which such treatments have specific benefits. Thus, many of the limitations to the knowledge base more reflect limitations reflecting the current evaluation of all antidepressant therapies rather than being unique to the psychotherapies. This paper argues for a change in the paradigms for evaluating the psychotherapies, and argues for a 'horses for courses' approach for conceptualizing the roles of the psychotherapies in managing mood disorders, rather than any model assuming their universal application.

Antidepressive Agents↗

Association study between cannabinoid receptor gene (CNR1) and pathogenesis and psychotic symptoms of mood disorders.

Cannabis can induce mood change and sometimes psychotic symptoms in normal persons. In brain, the main active ingredient of cannabis acts via the cannabinoid CB1 receptor (CNR1) which is located on chromosome 6q14-15. Linkage studies have suggested the presence of a bipolar disorder susceptibility locus on chromosome 6q. In this population based association study, we tested the hypothesis that a microsatellite polymorphism in the promoter region of the CNR1 gene confers susceptibility to mood disorders and psychotic features. We genotyped the CNR1 gene is 154 mood disorder patients and 165 normal controls. The results showed that the triplet repeat polymorphism in the promoter region of the CNR1 gene was not likely to be involved in the pathogenesis or in the psychotic symptoms of mood disorders.

Adult↗

Pharmacologic treatment of mood disorders in acquired immune deficiency syndrome (AIDS).

Mood disorders in HIV are common and can impact on the course of the illness. With the increasing use of newer psychopharmacologic and antiviral medications, clinicians need to take precautions while prescribing them. This paper gives an overview of the most recent literature describing the pharmacologic treatment of mood disorders in HIVpositive patients. The authors of this paper focus on antidepressants, mood stabilizers, neuroleptics, and psychostimulants, as well as on areas of controversy. The authors' own clinical experiences are also included.

Acquired Immunodeficiency Syndrome↗

Cognitive and neurological impairment in mood disorders.

Disorders of mood are accompanied by a range of cognitive and neurological impairments. Similar types of cognitive deficits are shared by patients with unipolar depression and bipolar disorder. Given the disparate clinical nature of these two disorders, it is interesting and informative to understand that they share common impairments in cognition. Neuro-imaging studies indicate that these impairments in both patient populations may be subserved by disruptions of the dorsal lateral and ventral medial PFC. An important problem that remains for clinicians is that some neurological symptoms are linked specifically to the adverse pharmacological effects of antidepressant agents, mood stabilizers, and neuroleptic agents. Research has shown a relation between mood and cognitive ability. Studies also have shown an association between mood and specific types of neurological dysfunction. Although few studies have examined all three symptom domains within one investigation, preliminary reports indicate that mood, cognition, and motor function may be linked to one another by complex mechanisms. Moreover, either type of abnormality that persists in the euthymic state suggests that a fundamental neural dysfunction is unaffected by treatment with existing means. Understanding the neural mechanisms that underlie mood, cognition, and movements may help to devise better treatments that do not influence cognitive or neurological functions,yet treat mood successfully.

Attention↗

Lifetime co-morbidities between social phobia and mood disorders in the US National Comorbidity Survey.

BACKGROUND: General population data were used to study co-morbidities between lifetime social phobia and mood disorders. METHODS: Data come from the US National Comorbidity Survey (NCS). RESULTS: Strong associations exist between lifetime social phobia and major depressive disorder (odds ratio 2.9), dysthymia (2.7) and bipolar disorder (5.9). Odds ratios increase in magnitude with number of social fears. Reported age of onset is earlier for social phobia than mood disorders in the vast majority of co-morbid cases. Temporally-primary social phobia predicts subsequent onset of mood disorders, with population attributable risk proportions of 10-15%. Social phobia is also associated with severity and persistence of co-morbid mood disorders. CONCLUSIONS: Social phobia is a commonly occurring, chronic and seriously impairing disorder that is seldom treated unless it occurs in conjunction with another co-morbid condition. The adverse consequences of social phobia include increased risk of onset, severity and course of subsequent mood disorders. Early outreach and treatment of primary social phobia might not only reduce the prevalence of this disorder itself, but also the subsequent onset of mood disorders.

Adolescent↗

Future therapeutic targets in mood disorders: the glucocorticoid receptor.

BACKGROUND: The hypercortisolaemia and dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis associated with mood disorders have been attributed to a breakdown in the glucocorticoid-receptor-mediated negative feedback mechanism regulating HPA activity. Reinstating normal feedback may be therapeutic in mood disorders. AIMS: To review the evidence for the involvement of the glucocorticoid receptor in the pathogenesis and treatment of mood disorders. METHOD: Medline and hand searches were carried out, selecting literature relevant to psychiatrists and psychopharmacologists. RESULTS: A dysfunction in glucocorticoid receptors is integral to the HPA abnormalities of mood disorders. Antidepressant and mood-stabilising drugs can up-regulate glucocorticoid receptors, restoring glucocorticoid function. Preliminary clinical studies targeting the glucocorticoid receptor are encouraging. CONCLUSIONS: Drugs designed specifically to up-regulate glucocorticoid receptors may be integral to future strategies in treating mood disorders.

Antidepressive Agents↗

New insights into the nature and heterogeneity of mood disorders.

Emerging research findings in mood disorders continue to provide support for multifactorial etiology. The present review considers the role of familial and developmental factors, gender, life circumstances, and biological precipitants in pathogenesis and discusses how they might, hypothetically, interact with other psychological and biological traits in giving rise to clinical heterogeneity. Special consideration is given to the pathoplastic influence of characterologic and temperamental traits, in view of their current clinical visibility.

Adult↗

Natural history and preventative treatment of recurrent mood disorders.

This chapter focuses on recent developments in our understanding of the etiology, epidemiology, and treatment of recurrent mood disorders. It addresses the changing relationship between endogenous and exogenous factors over time in the etiology of mood episodes. In the area of epidemiology, the chapter presents new information on the prevalence of various subtypes and male/female differences in lifetime risk. Complications of the mood disorders, such as suicide, and important comorbidities, including alcoholism and substance abuse, are discussed. In the area of treatment, the life-long nature of many of the mood disorders is described, as is the consequent role of the primary care physician in their management. The evidence for the efficacy of the depression-specific psychotherapies, cognitive therapy and interpersonal therapy, is reviewed. Current issues in the pharmacotherapy of mood disorders are discussed, including the relative efficacy of the older antidepressants versus the newer selective serotonin reuptake inhibitors (SSRIs) and the treatment of various subtypes of mood disorders, including dysthymia, chronic depression, and atypical depression. Finally, the chapter describes recent advances in the treatment of bipolar disorder.

Alcoholism↗

Circumscribed numerical deficit of dorsal raphe neurons in mood disorders.

BACKGROUND: Neurocircuits comprising limbic, striato-pallidal and thalamo cortical brain areas are assumed to be involved in the pathophysiology of mood disorders. All these brain regions receive serotonergic afferents arising from the rostral raphe, mainly the dorsal raphe. Although serotonergic systems appear to be involved in the pathology of mood disorders, there is uncertainty as to whether structural alterations in raphe nuclei exist alongside a functional dysregulation of the serotonergic system. METHODS: In the brains of 12 patients with mood disorders (major depressive disorder N= 6, bipolar disorder N = 6) and 12 normal subjects we performed a morphometric post-mortem study on neuronal morphology in all subnuclei of the dorsal raphe nucleus using Nissl stained 20 microm axial serial sections of the brainstem. RESULTS: The number of neurones of the ventrolateral subnucleus of the dorsal raphe was reduced by 31 % in patients with mood disorders compared with non-psychiatric control subjects. Ventrally located subnuclei of the rostral dorsal raphe (ventrolateral, ventral, interfascicular) taken together also showed a smaller number of neurones. Neurone numbers of the dorsal and the caudal subnucleus and volumes of all single subnuclei appeared to be unchanged. Analysis of morphological neuronal types revealed a smaller number of triangular neurones in the ventrolateral subnucleus. Numbers of ovoid and round neurones in the ventrolateral subnucleus also showed a trend to reduction. No correlation was found between neurone numbers in any subnucleus of the dorsal raphe and duration of illness. Neurone numbers did not differ in any subnucleus between patients with unipolar and those with bipolar affective disorder. CONCLUSIONS: Results indicate that patients with primary mood disorders have a circumscribed numerical neuronal deficiency in the dorsal raphe. This structural deviation may contribute to impaired serotonergic innervation of brain regions which are involved in the pathology of mood disorders.

Adult↗

Regulation of cellular plasticity cascades in the pathophysiology and treatment of mood disorders: role of the glutamatergic system.

There is increasing evidence from a variety of sources that mood disorders are associated with regional reductions in brain volume, as well as reductions in the number, size, and density of glia and neurons in discrete brain areas. Although the precise pathophysiology underlying these morphometric changes remains to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. In this context, it is noteworthy that a growing body of data suggests that the glutamatergic system--which is known to play a major role in neuronal plasticity and cellular resilience--may be involved in the pathophysiology and treatment of mood disorders. Preclinical studies have shown that the glutamatergic system represents targets (often indirect) for the actions of antidepressants and mood stabilizers. There are a number of glutamatergic "plasticity enhancing" strategies that may be of considerable utility in the treatment of mood disorders. Among the most immediate ones are NMDA antagonists, inhibitors of glutamate-release agents, and AMPA potentiators; this research progress holds much promise for the development of novel therapeutics for the treatment of severe, refractory mood disorders.

Animals↗

Child and adolescent antecedents of adult mood disorders.

PURPOSE OF REVIEW: Developmental information such as childhood risk factors and childhood precursors of adult mood disorders may have implications for etiologic theory, clinical practice and preventive intervention. From a developmental point of view, mood disorders are of particular interest because of the complex interplay of psychological, social and biological components across time. Identifying different developmental trajectories of mood disorders may yield insights that are relevant to the etiology. RECENT FINDINGS: Findings demonstrate a clear association between early mood problems and onset of mood disorders in adult life. Childhood environmental risks are associated with increased risk of depression in adulthood. There is a lack of studies that have tested the role of gene-environment correlation and the role of gene-environment interaction in the development of depression from childhood into adulthood. A promising line of research comes from studies looking into the biological modifications of the developing brain as a result of early adverse experiences, especially alterations in the corticotropin-releasing factor system, which may lead to increased responsiveness to stress. SUMMARY: To better understand the complex interplay between nature and nurture in the development of mood disorders in adults, future studies should ideally consider well measured risk environments in genetic sensitive designs. It is equally important that future studies should also consider both age differences in causal processes and gender differences in effects. Such an approach calls for research in which (molecular) genetic and psychosocial research is well integrated in prospective epidemiological strategies.

Journal Article↗

Monoamine oxidase genes polymorphisms and mood disorder.

We investigated a genetic association between mood disorders (bipolar and unipolar) and the alleles of monoamine oxidase (MAO) A and B (MAOA and MAOB). One hundred and twelve unrelated Japanese patients (60 bipolar, 52 unipolar) and 100 controls were genotyped for three markers of MAOA and for one marker of MAOB. No statistically significant difference in the distribution of the alleles existed between cases and controls. Therefore, our results did not support the involvement of the alleles at MAOA and MAOB in the etiology of mood disorder.

Adult↗

Evidence of association between gamma-aminobutyric acid type A receptor genes located on 5q34 and female patients with mood disorders.

Pharmacological evidence suggests the involvement of gamma-aminobutyric acid (GABA) perturbation in the etiology of mood disorders. A linkage study has detected chromosomal area 5q34, where GABA type A (GABA(A)) receptor subunit genes are mapped, as a susceptibility region for mood disorders, making these genes compelling candidates for such diseases. Our prior quantitative trait loci (QTL) analysis of mouse depression models identified a QTL on mouse chromosome 11, a genomic region whose human synteny includes 5q34. This further supports a contribution from GABA(A) receptors to a predisposition towards mood disorder. In the present study, we examined GABA(A) receptor alpha1 (GABRA1), alpha6 (GABRA6) and gamma2 (GABRG2) subunit genes on 5q34. Polymorphisms on GABRA1 and GABRA6 genes displayed significant associations with mood disorders in female patients. These data offer genetic support for a role of GABA(A) receptor genes in susceptibility to mood disorders.

Adult↗

Sad, glad, or mad hearts? Epidemiological evidence for a causal relationship between mood disorders and coronary artery disease.

OBJECTIVE: To examine the epidemiological evidence to determine if there is sufficient support for the hypothesis that mood disorders convey a risk factor in the pathogenesis of coronary artery disease (CAD). METHOD: Based on a review of the related research on Type A behavioral pattern (TABP) and other variables such as anger and hostility and their relationship to coronary artery disease (CAD), the findings were analyzed to ascertain any clinical patterns or similarities between behaviors of Type A and those in mood disorders. Using the given epidemiological criteria for a causal relationship, the association between the mood and coronary artery disease was explored. RESULTS: There are similar symptoms and behaviors noted among Type A, manic, cyclothymic and hyperthymic individuals. There is sufficient historical and contemporaneous epidemiological evidence to support the notion that mood disorders confer risk for CAD, but it is premature to describe it as a causative factor. Depressive symptoms and general mood disorders emerged as toxic risk factors for CAD. LIMITATION: This article presents only a selective literature review, and it is limited by an epidemiological analyses of secondary sources. The impact of this limitation on the interpretation of the analyses is discussed. CLINICAL RELEVANCE: Patients require scrupulous clinical assessment for the presence of mood disorders including subtype; the stakes are high, since their cardiac health status may depend upon it. Pathophysiological pathways may play a covariate role in both mood and coronary disease, and some tentative hypotheses regarding the role of catchecholamines and cortisol are explored. CONCLUSIONS: There is evidence to justify studying the role of mood as a covariate risk factor in the pathogenesis of CAD. Implications for mental health, public health, primary care practice, and psychometric measurement are discussed. The hypothesis that mood disorders are a cause of CAD requires further research.

Coronary Disease↗

Serotonin transporter binding in patients with mood disorders: a PET study with [11C](+)McN5652.

BACKGROUND: Several lines of studies have suggested the involvement of serotonin transporter (5-HTT) in the pathophysiology of mood disorders. The aim of this study was to examine whether 5-HTT binding was altered in patients with mood disorders using positron emission tomography (PET). METHODS: Thirteen antidepressant-naive or -free patients with mood disorders and 21 age-matched healthy control subjects participated in this study. The patients consisted of 7 with major depressive disorder (MDD) and 6 with bipolar disorder (BD). Positron emission tomography scans were performed using a selective ligand for 5-HTT, [11C](+)McN5652. The uptake was quantified in the thalamus and midbrain by graphical method with reference tissue, and binding potential (BP) was used for the index of 5-HTT binding. RESULTS: Binding potential in the thalamus was significantly increased in patients with mood disorders as compared to control subjects, whereas BP in the midbrain did not differ between the groups. Subgroup comparison showed that MDD patients had significantly higher BP in the thalamus compared to control subjects. Binding potential of the thalamus was higher by approximately 22% in the combined patients and 23% in MDD patients relative to control subjects. CONCLUSIONS: These findings may suggest the possibility of altered 5-HTT in patients with mood disorders. Functional abnormality in the thalamus may be involved in the pathophysiology of mood disorders.

Adult↗

Burden, reward and family functioning of caregivers for relatives with mood disorders: 1-year follow-up.

BACKGROUND: Longitudinal caregiver studies of patients with mood disorders report no consistent pattern in burden over time. This naturalistic study of caregivers of patients with mood disorders assesses caregiver perceptions of burden, reward and family functioning at hospitalization and at 1 year follow-up. METHODS: Thirty-nine caregivers of patients with mood disorders were recruited during their relative's in-patient psychiatric hospitalization. Caregivers were given an assessment packet to complete at the time of enrollment and identical assessment packets were mailed to the caregivers at 1 year. RESULTS: Caregivers of bipolar disorder relatives reported less reward, more subjective burden and worse family functioning than depression caregivers, at recruitment. Bipolar caregivers showed a significant reduction in burden 1 year after their relative was discharged from the hospital, whereas depression caregivers showed no change at 1 year. At 1 year, overall family functioning was unchanged and was in the unhealthy range in all dimensions except for behavior control. Limitations of the study include the small sample size, the selective recruitment from a hospital setting where family members did not actively seek out help and the high drop-out rate. CONCLUSIONS: Caregivers of relatives with mood disorders show a different pattern of burden and reward, over time, depending on the patient diagnosis. In all cases, however, family functioning was significantly impaired. CLINICAL RELEVANCE: Short-term family interventions can be offered at the time of hospitalization to try to reduce caregiver burden and increase caregiver reward.

Activities of Daily Living↗

Tyrosine hydroxylase gene associated with depressive symptomatology in mood disorder.

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of dopamine and norepinephrine. It may be involved in the pathophysiology of psychiatric disorders and positive associations have been reported for TH gene markers in mood disorders. While most replications failed to confirm the initial findings, other papers suggested a potential role of this gene in the etiology of mood disorders. Among the many different reasons for a lack of consistent replications, a critical role is played by the "correct" phenotype identification. Actually, up to now the only classification criteria has been the psychiatric diagnosis, but within the same psychiatric diagnoses the symptomatologic presentation may vary dramatically depending upon severity, presence of psychotic features or other psychopathologic traits. Thus, the aim of our study is to evaluate a possible association for TH gene with symptomatology in a sample of subjects affected by mood disorders. We have developed a phenotype definition based on the observed symptomatology divided into the four factors "Excitement," "Depression," "Delusion," and "Disorganization." Our sample includes 46 mood disorder subjects, investigated by the OPCRIT (operational criteria checklist for psychotic illness) checklist for their symptomatological pattern and typed for TH variants by polymerase chain reaction (PCR) amplification. Depressive factor was associated with TH variants (F = 4.79, df = 4, 87, P = 0.006), with TH*2 subjects presenting lower depressive scores. Subjects with genotype TH*2/2 were the only ones in the sample to report mild depressive episodes. TH variants may be related with depressive symptomatology in subjects affected by mood disorders.

Alleles↗

Seasonality of birth in patients with mood disorders in Japan.

BACKGROUND: Findings about seasonality of birth in individuals with mood disorders have been inconsistent. METHODS: Data were collected from the governmental statistics, the Patient Survey in Japan in 1996. The number of patients with mood disorders was 13,969. We obtained information about each patient's date of birth, sex, and diagnosis according to ICD-10. Distributions of monthly birth numbers of patients with mood disorders were compared to those of the general population. RESULTS: Birth excess was observed from winter to early-spring in both sexes, compared to births of the general population. The magnitude of the excess was larger in females than in males. Although the same tendencies were observed in patients with bipolar disorder and depressive disorder, the differences were more marked in females. LIMITATIONS: Insufficient birth data in the general population before 1940 and hospital diagnosis. CONCLUSION: Among Japanese patients with mood disorders, there are excess births from winter to early-spring, compared to the general population. This difference is more marked in females than in males.

Adult↗