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PubMed1998

Dopamine receptor D3 gene and response to lithium prophylaxis in mood disorders.

Lithium has established itself as an effective prophylactic agent in mood disorders, but not all patients respond to lithium therapy. It is probable that genetic factors play a substantial role in determining the differences in response to lithium. The aim of this study was to investigate the association between the dopamine receptor D3 (DRD3) gene and prophylactic efficacy of lithium in mood disorders. Fifty-five subjects affected by bipolar (n=43) and major depressive (n=12) disorder were followed prospectively for an average of 49 months and were also typed for their DRD3 variant, using polymerase chain reaction techniques. DRD3 variants were not associated with lithium outcome. Consideration of possible stratification effects, such as gender, polarity, family history, age at onset or duration of lithium treatment, also did not reveal any associations. DRD3 variants are not, therefore, a major factor influencing the prophylactic efficacy of lithium in mood disorders.

Journal Article↗

PubMed1980

Chronic mood disorders in depressed outpatient--diagnosis and response to pharmacotherapy.

The current study was devised to assess the utility of Research Diagnostic Criteria (RDC) categories used to classify minor mood disorders. Similar categories are to be used in the APA's Diagnostic and Statistical Manual, 3rd edition. The patient sample consisted of 64 consecutive admissions to a double-blind trial of amitriptyline, perphenazine and the combination as treatment for depression. Patients who met RDC for a current episode of major depressive disorder were given 4 weeks of pharmacotherapy as treatment. Chronic mood disorders were also assessed using RDC criteria. This evaluation revealed that only 34% met criteria for an episode of major depressive disorder alone, while 36% met criteria for intermittent depressive disorder, 14% for cyclothymic personality and 16% for labile personality in addition to being in a current major depressive episode. These 4 diagnostic subgroups were compared on demographic characteristics, childhood history, psychiatric history, presenting patterns of symptoms and social functioning, and response to treatment. Differences were noted in the subgroups in presenting symptom levels and residual impairment. However, there was no differential response to a brief course of antidepressant pharmacotherapy in patients with and without chronic minor mood disorders. Most patients showed an improvement during the brief course of treatment. Thus, the presence of a chronic minor mood disorder does not appear to be contraindication for use of medication in patients who also are currently experiencing a major depressive episode.

Adolescent↗

PubMed2000

The relation between anxiety and depressive symptoms in normal subjects and patients with anxiety and/or mood disorders.

OBJECTIVE: We investigated the associations between anxiety and depressive symptoms in normal subjects and patients with mood and/or anxiety disorders, using the Japaneses version of Spielberger's STAI and the Zung SDS. METHODS: The subjects for the present study were 60 normal subjects, 15 patients with anxiety disorders and, 12 patients with mood disorders meeting the DSM-IV diagnostic criteria. Informed consent was obtained from all subjects. RESULTS: 1) Both the mean total state-anxiety (S-anxiety) and trait-anxiety (T-anxiety) scores were significantly higher in patients with anxiety disorders and mood disorders than in normal subjects. 2) The mean total SDS score was significantly higher in patients with anxiety disorders and mood disorders than in normal subjects. 3) In normal subjects, there were significant positive correlations between the total T- and S-anxiety scores and total SDS scores. 4) In patients with anxiety disorders, there were significant positive correlations between the total T- and S-anxiety scores and total SDS scores. 5) In patients with mood disorders, there were nonsignificant positive correlations between the total T- and S-anxiety scores and total SDS scores. CONCLUSION: Our results might provide support for the existence of common underlying mechanisms to anxiety and depression.

Adult↗

PubMed2003

Predicting response to lithium in mood disorders: role of genetic polymorphisms.

Lithium is considered to be the first choice mood stabilizer in recurrent mood disorders. Its widespread and large-scale use is the result of its proven efficacy. In spite of this fact, patients have been observed to show a variable response to lithium treatment: in some cases it is completely effective in preventing manic or depressive relapses, while in other cases it appears to show no influence on the disease course. The possible definition of a genetic liability profile for adverse effects and efficacy will be of great help, as lithium therapy needs at least 6 months to be effective in stabilizing mood disorders. During the last few years, a number of groups have reported possible liability genes. Lithium long-term prophylactic efficacy has been associated with serotonin transporter protein, tryptophan hydroxylase and inositol polyphosphate 1-phosphatase variants. A number of other candidate genes and anonymous markers did not yield positive associations. Therefore, even if some positive results have been reported, no unequivocal susceptibility gene for lithium efficacy has been identified. Although the available data may not currently allow a meaningful prediction of lithium response, future research is aimed at the development of individualized treament of mood disorders, including the possibility of 'pharmacological genetic counseling'.

Animals↗

PubMed1990

Relationship of mood disorders to violence.

Past research on the relationship between mood disorders and violent behavior has been inconsistent, sometimes finding a relationship between the two and sometimes finding no relationship. Any relationship is arguably complex, and this area of research would benefit from attempts to clarify the relationship. This paper addresses the issue of complexity by examining the relationship between specific mood disorder categories and symptoms and six conceptually different indicators of violent behavior. Relationships are analyzed in logistic regression models where demographic and problem drinking variables are included to control variation that may be accounted for by these factors. The study uses a sample of 1140 recently incarcerated male felons. Psychiatric disorder diagnoses are based on the Diagnostic Interview Schedule. There is evidence of a direct relationship between a lifetime diagnosis of dysthymia and an arrest or incarceration history for robbery as well as with multiple incidents of fighting since age 18. Recurrent depression was significantly associated with a robbery incarceration history. Depression symptoms (regardless of whether a disorder diagnosis was made) were associated with multiple incidents of fighting since age 18. Manic symptoms were inconsistently associated with "expressive" violence and a number of mood disorder/violence models showed no significant relationship between the two.

Adult↗

PubMed1990

Psychobiological indices of bipolar mood disorder: future trends in nursing care.

Recent research on the various biological indices of bipolar mood disorder reveals a complex framework for the understanding of this psychobiological disorder. Four major constructs emerge from the professional literature to form the basis of the current understanding of and approaches to bipolar disorder. The first construct is that of biological rhythms and mood disorders. From this perspective, time is considered as a biological dimension evidenced by biological rhythms. Disruption of certain internal circadian rhythms yields behavioral change and symptoms of psychobiological disequilibrium. Concepts inherent in this particular construct include sleep, effect of light on mood pattern, and possible biochemical indices of mood modulation such as melatonin or phenylethylamine. The second construct attempts to explore the linkage between biochemical brain function and aberrant mood behavior. This information bifurcates into two major categories: (1) effects of psychopharmacological substances on neurotransmitter synthesis and release; and (2) implications of dietary influences on neurotransmitter activity and the psychobiological ramifications of such activity on the clinical understanding of the behavioral disorder. An eclectic set of concepts form the third construct in the framework presented here. These concepts address other possible etiological or mitigating biological influences on bipolar mood states. Such influences include, but are not limited to, limbic seizure activity, neuroendocrine dysfunction, and organic substrates of bipolar states such as various malignancies. The final construct explores the role of genetics in either the predisposition to or the emergence of bipolar mood disordered states. This report will focus on a review of the aforementioned constructs, pointing to significant research and narrative professional publications. In addition, the presentation will address the application of the nursing process to psychobiological aspects of bipolar mood disorder, specifically circadian rhythmicity disturbance and dietary influences on neurotransmission.

Affect↗

PubMed2003

Association study of a brain-derived neurotrophic-factor genetic polymorphism and mood disorders, age of onset and suicidal behavior.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin growth factor family, has been implicated in both mood disorders and suicidal behavior. This study has examined the association between the BDNF gene Val66Met polymorphism and mood disorders, age of onset and suicidal behavior in a Chinese sample population. The genotype and allele frequencies for the BDNF gene Val66Met polymorphism did not differ comparing depression groups (total, bipolar disorder or major depression) and control subjects. Furthermore, it was not demonstrated that this BDNF polymorphism was associated with age of onset or suicidal history in our mood disorder patients. Based on these results, it seems reasonable to suggest that this polymorphism is unlikely to play a major role in the genetic susceptibility to mood disorders. Given the fact that the positive association between BDNF gene Val66Met polymorphism and bipolar disorder has only been demonstrated for a Caucasian population but not for a Japanese analog or our Chinese sample, it appears likely that this association is ethnicity dependent.

Adult↗

PubMed2000

Linkage of mood disorders with D2, D3 and TH genes: a multicenter study.

BACKGROUND: It has been suggested that the dopaminergic system is involved in the pathophysiology of mood disorders. We conducted a multicenter study of families with mood disorders, to investigate a possible linkage with genes coding for dopamine receptor D2, dopamine receptor D3 and tyrosine hydroxylase (TH). METHODS: Twenty three mood disorder pedigrees collected within the framework of the European Collaborative Project on Affective Disorders were analyzed with parametric and non-parametric linkage methods. Various potential phenotypes were considered, from a narrow (only bipolar as affected) to a broad (bipolar+major depressive+schizoaffective disorders) definition of affection status. RESULTS: Parametric analyses excluded linkage for all the candidate genes, even though small positive LOD (Limit of Detection) scores were observed for TH in three families. Non-parametric analyses yielded negative results for all markers. CONCLUSION: The D2 and D3 dopamine receptors were, therefore, not a major liability factor for mood disorders in our sample, whereas TH may play a role in a subgroup of patients.

Bipolar Disorder↗

PubMed1993

Lessons from a mood disorders unit.

Specialist treatment centres, such as the Mood Disorders Unit (MDU) at Prince Henry Hospital, Sydney, have developed in response to the high prevalence of mood disorders and their frequent persistence and treatment resistance. The MDU's assessment and treatment of patients from a state-wide catchment area and its teaching and research effectiveness are reviewed. Of 479 patients assessed between 1985 and 1989, there were 304 with primary depressive disorders, of whom 154 were followed up by clinical assessment at 52 weeks and 231 by telephone interview at 3 1/2 years. At intake, 59% were tertiary referral patients and 88% were from outside the local area. Two-thirds were recovered 3 1/2 years later, despite the disorders having been generally severe and protracted. Treatment modality was associated primarily with diagnosis, but also with age and somewhat with the patient's personality and consultant psychiatrists' preferences. No consistent predictors of outcome were discerned. Specialist tertiary referral centres, such as the MDU, contribute significantly to treatment success, especially of difficult cases, and enrich teaching and research.

Adjustment Disorders↗

PubMed2002

Decreased cerebral haemodynamic response to cognitive and physiological tasks in mood disorders as shown by near-infrared spectroscopy.

BACKGROUND: Hypofrontality has been demonstrated in mood disorders by functional brain imaging methods such as positron emission tomography. However, the neurobiological basis of hypofrontality has not been well clarified. Near-infrared spectroscopy (NIRS) is a non-invasive technique for continuous monitoring of alterations in oxygenated (oxyHb) and deoxygenated (deoxyHb) haemoglobin using near-infrared light, which penetrates biological tissues. METHODS: We used NIRS during cognitive and physiological tasks to investigate alterations of haemoglobin oxygenation in the frontal region of euthymic patients with mood disorders (major depressive disorder (MD) and bipolar disorder (BP)) and in controls. RESULTS: The increase of oxyHb during a verbal fluency task was significantly less in the MD and the BP groups than in the controls. The MD group showed a significantly smaller decrease of oxyHb during hyperventilation than the controls. The BP group also showed a similar trend. CONCLUSIONS: These findings suggest that the hypofrontality in mood disorders may be associated with a poor response in the cerebral blood vessels to neuronal and chemical stimuli.

Adult↗

PubMed2001

Dermatoglyphic analysis in Malay subjects with bipolar mood disorder.

Dermatoglyphic is the study of the epidermal ridges and the pattern formed by them. It may be pointed out that genetic factors have a large share in determining the variations in dermatoglyphics. It is however, suggested by evidence that bipolar mood disorder factors are determined more by genetic factors than by the environmental factors. The experiment has been undertaken to look for the effects of the bipolar mood disorder on dermatoglyphics. The dermatoglyphic characteristics of subjects with bipolar mood disorder when compared with control group revealed significant differences. The radial loop were increased in bipolar mood disorder, but there were little changes in 'atd' angles between normal and bipolar mood disorder.

Bipolar Disorder↗

PubMed1989

The association of physical illness and environmental factors with mood disorder in adolescents.

This study on adolescents focuses on the association of psychological distress and mood disorder with illness and environmental sources of distress. The subjects were 505 high school students--346 boys and 159 girls. Psychological distress and mood disorder were measured with the Brief Symptom Inventory of Derogatis. To a significant degree, both were predicted by nonfebrile physical illness and life events. However, illness had a significantly stronger effect on girls than boys. In both sexes, feelings about school and home were significant predictors of psychological distress and mood disorder, but feelings about school were much less positive than feelings about home.

Adolescent↗

PubMed1999

Serotonin transporter gene not associated with psychotic symptomatology of mood disorders.

A functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has been recently reported to be associated with mood disorders. In the present study we investigated the possible influence of 5-HTTLPR on the symptomatology of mood disorders. Two hundred and thirty inpatients affected by mood disorders (160 bipolar and 70 major depressive disorder) were assessed by the Operational Criteria checklist for psychotic illness (OPCRIT) and were also typed for the 5-HTTLPR variants using PCR techniques. Mania, Depression, Delusion and Disorganization were the four symptomatologic factors used as phenotype definition. 5-HTTLPR variants were not associated with these symptomatologic factors, and consideration of possible stratification effects, such as sex, age of onset and polarity, did not reveal any association either. The serotonin transporter gene does not, therefore, appear to be associated with the symptomatology of mood disorders.

Adult↗

PubMed2006

Distribution of serotonin transporter labeled fibers in amygdaloid subregions: implications for mood disorders.

BACKGROUND: The serotonin transporter 5-HTT mediates responses to serotonin reuptake inhibitors (SSRIs), a mainstay treatment in mood disorders. The amygdala, a key emotional processing center, has functional abnormalities in mood disorders, which resolve following successful SSRI treatment. To better understand the effects of SSRIs in mood disorders, we examined the distribution of 5-HTT labeled fibers relative to specific nuclear groups in the amygdala. METHODS: Immunocytochemical techniques were used to chart 5-HTT labeled fibers in the amygdala in coronal sections through the brain of six adult Macaques. Nissl staining was used to define nuclear groups in the amygdala. RESULTS: The serotonin transporter 5-HTT is distributed heterogeneously in the primate amygdala, with the lateral subdivision of the central nucleus, intercalated cell islands, amygdalohippocampal area, and the paralaminar nucleus showing the heaviest concentrations. CONCLUSIONS: 5HTT-labeled fibers are very densely concentrated in output regions of the amygdala. High concentrations of 5-HTT-positive fibers in the central nucleus indicate that tight regulation of serotonin is critical in modulating fear responses mediated by this nucleus. High concentrations of 5-HTT-labeled fibers in the intercalated islands and parvicellular basal nucleus/paralaminar nucleus, which contain immature -appearing neurons, suggest a potential trophic role for serotonin in these subregions.

Amygdala↗

PubMedDate not supplied

[Prophylactic treatment of mood disorders: cost effectiveness analysis comparing lithium and carbamazepine].

Economic impact of lithium therapy has seldom been assessed, economic comparisons with alternative mood stabilizers are almost non existent. This economic evaluation of preventive treatment of mood disorders recurrences (whether unipolar or bipolar) compared lithium with carbamazepine, through data from a randomized controlled clinical trial. A retrospective analysis of medical files of index patients is included in this trial, with experts' global ratings. A brief survey checked for representativity of in-patients length of stay. The model compared two cohorts of patients followed-up for two years after prophylactic treatment had begun. Rates of recurrence and direct medical costs related to mood disorders (prophylactic treatment, treatment of recurrences and serious adverse effects) were assessed. Data extrapolation was necessary because of variable lengths of follow-up during the trial and was based on medical review of index patients. Assessment of consumed health care resources were derived from the available database of the clinical trial, when necessary practice guidelines and experts' opinions were added to the model. Costs were valued according to available french unit costs (Vidal, NGAP, and Comptes de la santé). Analysis only included direct costs. An estimate of mean cost of care of 15,404 French francs per year per patient was calculated. The components of health costs show that in-patient costs are the most important part of annual medical costs for mood disorders (70% of the total costs). Prophylactic medication costs accounted for only 6.9% of total costs. Comparison of prophylactic alternatives gave lithium a clinical benefit with 27% fewer recurrences than carbamazepine. Lithium led to an economic benefit of 4,280 French francs per year of treatment for a single patient. Robustness of this finding was assessed through a sensitivity analysis on estimate of length of stay. Total costs of treatment would be equal between lithium and carbamazepine if length of stay in hospital for lithium patients was increased by 51%. According to the cost-effectiveness analysis developed in this study, lithium should stay the "gold standard" of prophylactic treatment of recurrent mood disorders, and has both clinical and economic advantages compared to carbamazepine.

Adult↗

PubMed2006

MDR1 gene polymorphism in Japanese patients with schizophrenia and mood disorders including depression.

P-Glycoprotein (ABCB1-type P-gp), a membrane protein encoded by the multi drug resistant gene (MDR1), expressing on the blood brain barrier protects the brain from many drugs including dexamethasone. Psychiatric disorders, schizophrenia and depression, have known to have abnormal hypothalamus-pituitary-adrenal (HPA) activity, which is assessed by non-suppression of cortisol in dexamethasone suppression test. The poor response to dexamethasone in these patients' population suggested the impaired activity on dexamethasone penetration into the brain via P-gp, which was associated with MDR1 polymorphisms. We, therefore, examined five SNPs of the MDR1 gene, -1517 T>C (promoter), -41 A>G (intron -1), -129 T>C (exon 1b), 2677 G>A,T (exon 21) and 3435 C>T (exon 26), in Japanese patients with schizophrenia (n=121) and mood disorders (n=62), and compared with the control subjects (n=160). The frequency of MDR1 mutant alleles at -1517, -41 and -129 in patients with mood disorders was significantly lower (2.4, 5.6, 2.4%, respectively) than those of controls (7.8, 13.7, 7.8%, respectively) (p<0.05). The frequencies of MDR1 2677 G/A and A/A genotype in mood disorders was significantly higher (17.7, 6.5%, respectively) than controls (11.2, 0%, respectively) (p<0.05). The 2677A allele frequency in mood disorders (20.2%) was significant higher than controls (10.9%) (p<0.05). Haplotype of 129-2677-3435 (T-A-C) in mood disorders was significantly higher (14.4%) than controls (8.0%) (p<0.05). There was no significant difference in allele and genotype frequencies between the patients with schizophrenia and controls. These findings suggested that predispose to mood disorders, not schizophrenia, was associated with possible alteration of P-gp activities corresponding MDR1 polymorphism at least partly.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1990

Plasma GABA in mood disorders.

Plasma levels of gamma-aminobutyric acid (GABA) were determined in 68 healthy controls and in 133 patients with mood disorder. Plasma GABA levels were significantly lower in the patients with mood disorder compared to controls. Levels of plasma GABA were similar among diagnostic groups (primary unipolar depression, bipolar depression, mania, and secondary depression). No differences in plasma GABA were found in patients classified according to family history, nor were any correlations found between plasma GABA levels and severity of depression as determined by the 17-item Hamilton Rating Scale for Depression. These findings support the notion that low plasma GABA may represent a biological marker for mood disorder.

Affective Disorders, Psychotic↗

PubMed1993

Family functioning and suicidal behavior in adolescent inpatients with mood disorders.

OBJECTIVE: This study was designed to identify family and parental characteristics associated with suicidal behavior (active intent, gesture, attempt) among adolescent inpatients with mood disorders. METHOD: Subjects were 32 suicidal adolescent inpatients with mood disorders, 32 nonsuicidal adolescent inpatients with mood disorders, and 38 normal comparison adolescents. A group comparison design was used. Adolescent measures were the Family Assessment Device and two semistructured interviews (Hamilton Rating Scale for Depression, Social Adjustment Inventory for Children and Adolescents). Parent measures were the Symptom Checklist-90 and the Social Adjustment Scale-Self Report. RESULTS: Fathers of suicidal adolescents reported more depression and family unit problems than did fathers of nonsuicidal and normal comparison adolescents, even after controlling for adolescents' depression severity. Suicidal adolescents, in turn, reported less active and communicative relationships with fathers. Differences among suicidal and nonsuicidal adolescents' perceptions of general family functioning were not significant after controlling for adolescents' depression severity. CONCLUSIONS: Findings highlight the importance of treating the depressed and potentially suicidal adolescent within the family system and attending to the nature and quality of adolescents' relationships with fathers as well as with mothers. Findings also highlight interactions between suicidal adolescents' depression severity and their negative perceptions of family functioning.

Adolescent↗