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Elevated sorbitol concentration in the cerebrospinal fluid of patients with mood disorders.

This study was undertaken to test the hypothesis that a specific pathophysiological mechanism of diabetic neuropathy, namely increased polyol pathway flux, could be operative in patients with bipolar and unipolar mood disorders. Numerous studies have shown abnormalities of carbohydrate metabolism, including high rates of diabetes mellitus, in patients with mood disorders. Several studies have found that peripheral neuropathy is a risk factor for depression in diabetics. Furthermore, increased polyol pathway flux results in elevated sorbitol concentrations in peripheral tissues and cerebrospinal fluid (CSF) of diabetics with neuropathy. The purpose of this study was to determine whether sorbitol concentration is elevated in the CSF of non-medically ill patients with mood disorders. Lumbar punctures were performed on 30 subjects - 10 with bipolar mood disorder, 10 with unipolar mood disorder, and 10 age-matched normal controls, and CSF sorbitol concentrations were measured, using a gas chromatographic-mass spectroscopic technique. The mean+/-standard deviation of CSF sorbitol concentrations differed among the three groups as follows: bipolar (22.9+/-4.6 micromoles/l) > unipolar (19.0+/-2.8 micromoles/l)>normal control (15. 6+/-1.9 micromoles/l). One-way ANOVA showed significant (P=0.0002) differences among the three groups. Post-hoc tests indicated a significant (P<0.05) difference between bipolars and normal controls, bipolars and unipolars, and unipolars and normal controls. Further investigation is needed to determine the pathophysiological significance of this novel finding of elevated sorbitol concentration in the CSF of patients with mood disorders.

Adult↗

Mood disorders affect drug treatment success of drug-dependent pregnant women.

This study examined the impact of co-occurring Axis I disorders on drug treatment outcomes of drug-dependent pregnant women. Participants (N = 106) were women who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for opioid dependence and were receiving methadone. Based on DSM-IV Axis I criteria, participants were categorized into three groups: (1) absence of mood/anxiety disorder (ND, n = 29), (2) primary mood disorder (MD, n = 39), or (3) primary anxiety disorder (AD, n = 38). Demographically, the groups were similar. The MD group was significantly more likely to be positive for drugs while in treatment compared with both the ND and AD groups. The MD and AD groups had more psychosocial impairment and higher incidence of suicidal ideation compared with the ND group. Interestingly, the AD group spent more days in treatment compared with the ND or MD group. These findings highlight the need to treat co-occurring Axis I disorders, particularly given the higher relapse risk for those with mood disorders.

Adult↗

Mood disorders: review of current diagnostic systems.

In their sections on mood disorders, both ICD-10 and DSM-IV represent considerable advances on ICD-9 in drawing affective disorders together in one section, distinguishing bipolar disorder from unipolar, including dysthymia and using clear definitions. Problems with ICD-10 include complexity, use of different clinical and research definitions, emphasis on single versus recurrent episodes and the lack of some clinically useful subtypes. DSM-IV is less complex but assigns separate unjustified categories of medical and substance-induced mood disorders, and fails to code its useful qualifiers. Both classifications preserve categories for psychotic depression and melancholia/somatic syndrome, which are better coded in ICD-10. The severity distinctions could usefully be extended to a milder category of minor depression. It is also recommended that the two classifications be brought together, with small differences in definitions ironed out and a single set used both clinically and for research, the simpler DSM-IV organisation, the omission of the categorisations of single versus recurrent and mood disorder due to general medical or substance abuse disorders, and the inclusion of coding for some subtypes such as seasonal and postpartum.

Bipolar Disorder↗

Can mood disorder in women with breast cancer be identified preoperatively?

The Hospital Anxiety and Depression (HAD) scale, a self-report questionnaire, was tested as a method of identifying mood disorder among patients with operable breast cancer during the year after diagnosis. In a cohort of 91 patients anxiety and depression were assessed preoperatively, and at 3 and 12 months post-operatively, using a standardised psychiatric interview and diagnostic rating criteria. The patients also completed the HAD scale at each assessment. Fifty out of 91 (55%) patients were full or borderline cases of depression and/or anxiety at one or more assessment points. Using a receiver operator characteristic curve analysis, the optimum threshold for the preoperative HAD scale total score to identify psychiatric disorder either preoperatively or at 3 and 12 months post-operatively was 11. With this threshold 70% of both full and borderline cases occurring at any of the assessment points were correctly identified. The false-positive rate was 12%. This approach was particularly sensitive to full cases, correctly identifying 90% of them. The potential for the preoperative HAD scale total score to identify mood disorder in the year after diagnosis was influenced by age. Among women aged less than 50 years, a preoperative HAD scale total score > or = 11 provided a highly sensitive indicator of mood disorder (full and borderline cases) at any time in the year after diagnosis (sensitivity = 90%). The false-positive rate was 40%. Among women older than 50 who experienced a mood disorder, only 57% were correctly identified by a HAD scale total score of > or = 11 (sensitivity = 57%). However, the false-positive rate among older women was low (3%). This simple preoperative screening approach can be used to identify patients who have or are at high risk of developing severe mood disorder in the year after diagnosis. The HAD scale is also sensitive to the detection of borderline mood disorder in patients under the age of 50. It is a specific screening tool among patients over 50, but is not sensitive to the detection of borderline mood disorder in this age group.

Adult↗

Critical role of brain-derived neurotrophic factor in mood disorders.

The purpose of this review is to integrate what is currently known about the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of mood disorders including major depressive disorder (MDD) and bipolar disorder (BD). We reviewed the pre-clinical and clinical papers demonstrating that BDNF plays a role in the pathophysiology of mood disorders and in the mechanism of action of therapeutic agents. Pre-clinical studies suggest that the expression of BDNF might be a downstream target of antidepressant treatments and mood stabilizers such as lithium and valproate, and that BDNF exerts antidepressant activity in animal models of depression. Furthermore, BDNF protects against stress-induced neuronal damage, and it might affect neurogenesis in the hippocampus, which is thought to be involved in the pathogenesis of mood disorders. Clinical studies have demonstrated that serum levels of BDNF in drug-naive patients with MDD are significantly decreased as compared with normal controls, and that BDNF might be an important agent for therapeutic recovery from MDD. Moreover, recent findings from family-based association studies have suggested that the BDNF gene is a potential risk locus for the development of BD. These findings suggest that BDNF plays a critical role in the pathophysiology of mood disorders and in the activity of therapeutic agents in patients with mood disorders. New agents capable of enhancing BDNF levels may lead aid the development of novel therapeutic drugs for patients with mood disorders.

Animals↗

Antidepressant drugs and cytokines in mood disorders.

This article reviews recent developments in cytokine research that pertain to pharmacological treatment of mood disorders such as antidepressants and lithium. We review the possible involvement of cytokines in mood disorders and their role in the therapeutic effects of antidepressant drugs. Growing evidence suggests that specific cytokines signal the brain to generate neurochemical, neuroimmune, neuroendocrine and behavior changes. An imbalance of cytokines within the central nervous system (CNS), or even systemically, may play a role in the pathophysiology of mood disorders. Modulation of these cytokines by chronic antidepressant treatment may result in restored balance. However, the effect of antidepressants on cytokines is still unclear both in clinical and preclinical research due to limited data. Further research is needed to clarify the involvement of cytokines in mood disorders. Understanding this relationship may lead to rational, therapeutic improvements in antidepressant and mood stabilizing drugs.

Animals↗

The application of mindfulness-based cognitive interventions in the treatment of co-occurring addictive and mood disorders.

This article reviews the theory, clinical application, and empirical findings on mindfulness-based cognitive therapy (MBCT) for mental health and addictive disorders. Expanding upon the research demonstrating the efficacy of cognitive-behavioral therapy (CBT) for addiction, this article develops and explores the rationale for combining mindfulness-based interventions with evidence-based CBTs in treating addictive disorders, with an emphasis on substance use disorders with co-occurring mood disorders. This article proposes that deficits in affect--regulation related to the behavioral and emotional effects of neurobiological changes that occur with long-term substance abuse--pose a unique set of challenges in early recovery. Prolonged use of addictive substances impairs the brain pathways that mediate certain affect regulation functions. These functions involve attention and inhibitory control, the saliency of and response to addictive versus natural reward stimuli, and the ability to detach or maintain perspective in response to strong emotional states. In treating this affective dysregulation, which can contribute to the vulnerability to relapse in the early stages of recovery, the affect-regulation-specific focus of MBCT adds a valuable element to augment CBT for addiction. Summarizing magnetic resonance imaging and positron emission tomography findings on the effects of MBCT and the neurobiology of drug addiction, this article outlines directions for further research on potential benefits of MBCT for the recovering individual. Finally, this article describes a structured protocol, developed at the Mount Sinai School of Medicine in New York City, which combines CBT with mindfulness-based intervention, for the treatment of affect-regulation issues specific to co-occurring addictive and mood disorders.

Affect↗

Impaired neuropsychological performance in euthymic patients with recurring mood disorders.

BACKGROUND: Both patients suffering from schizophrenia and patients suffering from recurring mood disorder show cognitive impairments as established by a variety of neuropsychological tests. The aim of the present study was to investigate the neuropsychological performance of euthymic patients who had recurring mood disorder and the possible relationship between episodes of hospitalization and cognitive impairments. METHOD: Twenty-six euthymic patients with a DSM-III-R recurring mood disorder diagnosis were investigated by using the Synonym Reasoning and Block-Test Battery and a part of the Halstead-Reitan Test Battery. RESULTS: An overall lowered performance in the test results was found. There was a significant positive relationship between four different tests and the number of hospitalization episodes; the patients with impaired cognitive functioning had significantly more hospitalization episodes than patients with normal cognitive functioning. CONCLUSION: The results suggest that a subgroup of patients with recurring mood disorder are defined by more relapses and episodes of hospitalization and show cognitive dysfunctions even when euthymic.

Adult↗

Association study of adenosine A2a receptor (1976C>T) genetic polymorphism and mood disorders and age of onset.

Evidence suggests that the adenosine A2a receptor (A2aAR) may be implicated in the pathogenesis of mood disorders. We tested the hypothesis that the A2aAR 1976C>T genetic variant confers susceptibility to mood disorders by comparing 192 mood disorder patients and 216 normal controls. The distribution of the A2aAR genotypes and alleles did not differ significantly comparing the two groups, suggesting that it is unlikely that the A2aAR 1976C>T polymorphism plays a major role in the development of mood disorders.

Age of Onset↗

Familial pathways to early-onset suicide attempt: risk for suicidal behavior in offspring of mood-disordered suicide attempters.

BACKGROUND: Although adoption, twin, and family studies have shown that suicidal behavior is familial, the risk factors for familial transmission from parent to child remain unclear. METHODS: A high-risk family study was conducted comparing the offspring of 2 mood-disordered groups: suicide attempters and nonattempters. Recruited from 2 sites, probands were 81 attempters and 55 nonattempters, with 183 and 116 offspring, respectively. Offspring were assessed by investigators masked to proband status. Probands and offspring were assessed with respect to psychopathologic findings, suicide attempt history, impulsive aggression, and exposure to familial environmental stressors. RESULTS: Offspring of attempters had a 6-fold increased risk of suicide attempts relative to offspring of nonattempters. Familial transmission of suicide attempt was more likely if (1) probands had a history of sexual abuse and (2) offspring were female and had a mood disorder, substance abuse disorder, increased impulsive aggression, and a history of sexual abuse. CONCLUSIONS: The offspring of mood-disordered suicide attempters are at markedly increased risk for suicide attempts themselves. Familial transmission of suicidal behavior in families with mood disorders almost always requires transmission of a mood disorder and is also related to the offspring's impulsive aggression and the familial transmission of sexual abuse. Early treatment of mood disorders and targeting impulsive aggression and sexual trauma may be helpful in the prevention and treatment of suicidal behavior in families with mood disorders.

Adolescent↗

Health-related quality of life (HRQOL), activity of daily living (ADL) and depressive mood disorder in temporal lobe epilepsy patients.

We determined the interrelations of chronological age, age at seizure onset, duration of seizure disorder, cognitive functioning (IQ), scales of activities of daily living, depressive mood disorder and measures of health-related quality of life (HRQOL). Furthermore, we investigated the association of the laterality of seizure onset zone and absence/presence of hippocampal atrophy and/or sclerosis (HA/HS) with measures of HRQOL, activities of daily living (ADL) and depressive mood disorder. In the setting of pre-surgical epilepsy evaluation, a sample of 56 patients with temporal lobe epilepsy (TLE) was studied using the Bonner Skalen für Epilepsie (BPSE) and the depression inventory D-S of von Zerssen. Patients reported high levels of dependency on others and poor coping capabilities. Our data also showed specific ADL-behaviour suggesting social withdrawal and isolation. Our results indicate emotional impairment as a major problem in TLE, because 45% of our patients scored in the depressive range of the D-S depression scale. Depression score was found to be a powerful predictor of self-reported quality of life after adjusting for seizure-related variables, demographic variables and cognitive functioning (IQ). The only scale showing a significant laterality effect was ADL-home. No relationship between the dependent measures of HRQOL, ADL-social, ADL-cultural, depressive mood disorder and laterality of the epileptogenic zone or absence/presence of HA/HS was found. HRQOL and depressive mood disorder are strongly interrelated indicating that patients with depressive symptoms report lower quality of life and specific patterns of ADL. HRQOL, ADL and depressive mood disorder are largely independent of biological markers such as laterality of seizure onset zone and absence/presence of HA/HS in TLE.

Activities of Daily Living↗

Mechanisms of action in the prevention of recurrent mood disorders.

BACKGROUND: Since long-term treatment is a need in many patients with mood disorders, knowledge on mechanisms of action in the prevention of recurrence is of major relevance. METHODS: Follow-up studies, which are best suited to prove the linkage of causal factors and mechanisms with the clinical course of the disorders, are rare. Another approach to search for preventive mechanisms is to address actions of pharmacological agents, which are effective in prophylactic treatment of mood disorders. Studies over the past several years have indicated that intracellular signaling cascades mediate long-term pharmacological effects via modulation of transcription factors and gene expression of neurotrophic and neuroprotective factors which may interfere with recurrence of affective illness. RESULTS: The impact of treatment on stress responsive systems varies with different therapeutic strategies and the relevance of a treatment-related modification of stress reliability for the course of the disease is not clear. Functional and structural actions of mood stabilizers and of antidepressants on mood-relevant anatomical circuits and modulation of chronobiological alterations also appear to be involved in preventive mechanisms in mood disorders. Moreover, cognitive mediators of prophylactic effects have been described. CONCLUSION: Combined clinical and biological studies should assess the relevance of those modes of action for the long-term course of mood disorders.

Antidepressive Agents↗

Quantitative regional cerebral flow measured by Tc-99M HMPAO SPECT in mood disorder.

Depressed (n = 14) and remitted (n = 9) patients with mood disorder, patients with depressive disorder not otherwise specified (NOS; n = 10) and normal subjects (n = 8) underwent non-invasive and quantitative measurement of cerebral blood flow using HMPAO and SPECT in a resting state. The mean and regional cerebral blood flow (CBF) in twelve ROIs were compared among the four groups and correlations between CBF and the depressive symptoms were studies. The CBF was computed using graphical analysis on the SPECT console after a bolus injection of Tc-99m HMPAO and radionuclide angiography. The depressed group had significantly lower mCBF in the bilateral hemisphere and rCBF in all except one of the ROIs than the NOS and normal group. Significant negative correlations were found between the Hamilton scale for depression and rCBF in the bilateral lower frontal cortex after correcting for age in the mood disorder. Parallel analysis using both the quantitative and semiquantitative methods revealed that the former provided more global reduction of CBF in mood disorder. These results indicate that mean and regional CBF measured by this non-invasive method contributes to the objective evaluation of depressive symptoms. Negative correlations between HRSD and rCBF in the frontal regions indicate that frontal hypoactivity is closely related to depressive symptoms.

Adult↗

[Classification of mood disorders in adults].

The two main classifications of mood disorders currently used are the American system, DSM, the fourth edition of which came out in 1994, and the International Classification of Diseases, the tenth edition of which was published in 1993. These classifications are based on the following broad principles: simple description with no hypothetical aetio-pathogenic discussion, distinction between the various clinical forms in accordance with variety and intensity of symptoms, co-existence of other more or less serious somatic disorders, individual identification of bipolar forms, etc. The key changes made in the classification of mood disorders between the revised version of DSMIII published in 1987 and DSM-IV published in 1994 suggest that a greater degree of concordance in diagnosis between different practitioners may be expected in future. In addition, certain changes such as the therapeutic decision-trees will most likely have an impact on practice. In this way, further details are added to the clinical criteria of duration or description of the clinical features seen, thereby allowing a clearer distinction to be made between normality and the onset of the pathology in question. Regarding bipolar disorders, the general organisation of the classification and the terminology used have been extensively revised, with the distinction between types I and II becoming official. Furthermore, differentiation between certain aspects of depression emphasises the frequency of certain clinical particularities, either in the onset or during the course of these disorders. This is true of melancholic, catatonic and atypical features specifiers (i.e. with mood reactivity and interpersonal rejection sensitivity), post-partum onset specifier, seasonal pattern specifier and rapid-cycling specifier. Finally, a certain number of specifications are proposed allowing the postulation of notions of complete or partial cure between episodes in case of recurrence.

Adult↗

Molecular analysis, mutation screening, and association study of adenylate cyclase type 9 gene (ADCY9) in mood disorders.

Chromosome 16p13 has been shown to display modest linkage signals for mood disorders in a number of studies. An interesting candidate gene in this region is the adenylate cyclase (AC) type 9 gene (ADCY9). ACs are critical in neuronal signaling, and perturbation of brain AC activity has been reported in mood disorder postmortem brains. ACs may also act as targets of antidepressants. Two distinct length transcripts for the ADCY9 gene have been reported, but molecular mechanisms are unknown. To investigate the potential role of ADCY9 in mood disorders, we clarified alternative poly(A) sites for the two mRNA species, delineated the exon-intron structure, and screened the gene for genetic variants. The two transcripts encoded by ADCY9 shared the first 10 exons, but exon 11 was shorter in one of the mRNA species. Seven single nucleotide polymorphisms, including a missense mutation and one polymorphic microsatellite repeat in the 3'-UTR, were identified. However, a case-control study using the missense polymorphism, 2316A>G (Ile772Met), and the tetranucleotide repeat (TTTA)n showed no significant association with mood disorders in Japanese samples. The DNA polymorphisms detected in this study can be tested in other ethnic samples and/or other psychiatric diseases.

Adenylyl Cyclases↗

Psychoeducation for caregivers of patients with chronic mood disorders.

Caregivers of patients with mood disorders report high levels of caregiver burden and poor family functioning. This study assessed the impact of educating caregivers about their symptoms and about community resources. Depressive symptoms were reported by 74% of caregivers, but only 37% of these caregivers accepted a referral and only 6% followed through. Similarly, of those with poor family functioning, 44% were offered a referral, 22% accepted, but only 5% followed through. Overall, 82% reported that the psychoeducational packet was useful.

Caregivers↗

Genetic factors and treatment of mood disorders.

OBJECTIVES: This paper reviews the pharmacogenetics of mood disorders. METHODS: We have searched the literature for published studies and abstracts relevant for genetic effects in acute antidepressant treatment and in long-term prophylactic treatment. RESULTS: The most promising findings to date show an association of the serotonin transporter (5-HTT) gene and the response to serotonin reuptake inhibitors. Genetic factors also appear to play a significant role in the outcome of long-term lithium treatment. The phenotype of lithium-responsive bipolar disorder is associated with stronger genetic effects as well as with an increased phenotypic homogeneity. CONCLUSIONS: Genetic factors likely influence treatment response in mood disorders. Clarifying their precise role will have implications for treatment as well as for understanding the pathophysiological mechanisms of these disorders.

Antidepressive Agents↗

Initiation of daily smoking and nicotine dependence in schizophrenia and mood disorders.

This study replicates, using more refined methodology, the indications of prior studies that patients with schizophrenia show a greater frequency of tobacco smoking than patients with mood disorders. The sample included 66 patients with schizophrenia and 51 patients with a mood disorder who were admitted at a state hospital in Kentucky. The control group included 404 community subjects. Ever daily smoking was studied using logistic regression. Survival analyses of age of onset of daily smoking (AODS) were performed controlling for several variables including education level. Nicotine dependence was measured with a scale. The prevalence of ever and current daily smoking was respectively 92 and 83% for patients with schizophrenia, 78 and 65% for patients with mood disorders, and 47 and 26% for controls. Before the age of 20, the three populations appear to have a similar risk of smoking initiation. However, after the age of 20, the initiation rate of daily smoking for patients with schizophrenia was higher than in patients with a mood disorder, or controls. Among daily smokers, there were no differences in nicotine dependence between patients with schizophrenia and those with a mood disorder. Schizophrenia was associated with a greater probability of ever daily smoking than mood disorders and with higher rates of initiation of daily smoking after 20 years old.

Adult↗