vitamin-b-12 and Bipolar-Disorder

The single infusion of ketamine, an N-methyl-d-aspartic acid (NMDA) glutamate receptor antagonist, exerts a therapeutic effect in both unipolar and bipolar depression. Homocysteine (HCY) acts agonistically on the NMDA receptor, hyperhomocysteinemia is related to depression, and folic acid and vitamin B12 are associated with HCY system. We estimated the serum levels of these substances in 20 bipolar depressed patients before ketamine infusion. 10 patients responded favorably to this procedure, as their score on the Hamilton depression rating scale, compared to baseline, was reduced by more than 50%, after 7 days. The vitamin B12 level was significantly higher in "responders" compared to the remaining patients. No differences between the 2 groups were found with regard to HCY, folic acid levels and such clinical factors as age, duration of illness and duration of current episode. These preliminary data suggest that the vitamin B12 level may be connected with the efficacy of ketamine infusion in bipolar depression.

Topics: Adult; Aged; Bipolar Disorder; Excitatory Amino Acid Antagonists; Female; Folic Acid; Homocysteine; Humans; Infusions, Intravenous; Ketamine; Male; Middle Aged; Vitamin B 12

Topics: Adult; Amino Acid Metabolism, Inborn Errors; Bipolar Disorder; Gas Chromatography-Mass Spectrometry; Humans; Hyperhomocysteinemia; Male; Tandem Mass Spectrometry; Vitamin B 12

Deficiencies in both vitamin B12 and folate have been associated with depression. Recently, higher baseline vitamin B12 levels were observed in individuals with bipolar depression who responded to the antidepressant ketamine at 7 days post-infusion. This study sought to -replicate this result by correlating peripheral vitamin levels with ketamine's antidepressant efficacy in bipolar depression and major depressive disorder (MDD).. Baseline vitamin B12 and folate levels were obtained in 49 inpatients with treatment-resistant MDD and 34 inpatients with treatment-resistant bipolar depression currently experiencing a major depressive episode. All subjects received a single intravenous ketamine infusion. Post-hoc Pearson correlations were performed between baseline vitamin B12 and folate levels, as well as antidepressant response assessed by percent change in Hamilton Depression Rating Scale (HDRS) scores from baseline to 230 min, 1 day, and 7 days post-infusion.. No significant correlation was observed between baseline vitamin B12 or folate and percent change in HDRS for any of the 3 time points in either MDD or bipolar depression.. Ketamine's antidepressant efficacy may occur independently of baseline peripheral vitamin levels.

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Bipolar Disorder; Depressive Disorder, Major; Excitatory Amino Acid Antagonists; Female; Folic Acid; Humans; Ketamine; Male; Middle Aged; Psychiatric Status Rating Scales; Receptors, N-Methyl-D-Aspartate; Severity of Illness Index; Treatment Outcome; Vitamin B 12

The relationship between homocysteine (HCY) levels and cognitive impairments, particularly executive functions in bipolar disorder (BD), has recently been investigated. However, conflicting results were reported. The aim of the present study is to investigate changes in serum HCY, methionine, vitamine B12 and levels in BD patients are relative to controls and to investigate the relationship between HCY, methionine, vitamin B12, and folate levels and clinical features, cognitive functions and psychosocial functioning in euthymic BD patients and controls.. Sixty BD type I euthymic patients and twenty controls were assessed with Global Assessment of Functioning and a battery of neuropsychological tests including the Wisconsin card sorting test, the Rey's auditory verbal learning test, the Cancellation test, Trail making test A, Trail making test B, and the Stroop test. HCY, vitamin B12, methionine and folate levels were measured together after collecting blood samples from both patient and controls.. Mean serum methionine concentration was different between groups. Low serum methionine was found to be a predictor of BD. However, a statistically significant difference was not detected between groups for mean serum values of HCY, folate, or vitamin B12. HCY levels showed a positive correlation with illness duration, the number of total episodes, and the number of manic episodes. A significant correlation was not found between HCY, methionine, folate, B12 levels with cognitive functions and functioning in the BD group.. Low serum methionine was found to be a predictor of BD, a condition which can lead to a decrease in SAM synthesis and thus to a variety of complications in methylation reactions. Additional studies are needed to clarify the impact of single carbon metabolism on BD.

Topics: Bipolar Disorder; Case-Control Studies; Cognition; Folic Acid; Homocysteine; Humans; Methionine; Psychiatric Status Rating Scales; Severity of Illness Index; Vitamin B 12

Depression may be associated with elevated homocysteine (HCY) levels. Procedures aiming at its decrease, i.e. supplementation with folic acid or vitamin B12, have antidepressant effect. Both depression and elevated HCY can increase cardiovascular risk. In this study, clinical and biochemical factors, including markers of endothelial function, in relation to hyperhomocysteinemia, in patients with bipolar depression during acute episode were studied.. One hundred and twelve patients (24 male, 88 female), aged 20-78 (mean 51 ± 14 years), with depressive episode in the course of bipolar mood disorder have been included. The assays were made of serum concentrations of HCY, vitamin B12, folic acid as well as markers of endothelial function such as E-selectin and intracellular adhesion molecule-1 (ICAM-1).. Hyperhomocysteinemia (>15 mM) was found in 50 patients (45%), significantly more frequently in male (67%) than in female subjects (39%). Female patients with hyperhomocysteinemia were significantly older than the remaining ones. A significant inverse correlation between HCY level and concentration of folic acid and vitamin B12 as well as with E-selectin and ICAM-1 was observed.. The results point to a significant prevalence of hyperhomocysteinemia in bipolar depressed patients during an acute episode. They also corroborate the correlation between increased concentration of HCY and lower level of vitamin B12 and folic acid. An unexpected finding of negative correlation of HCY level with markers of endothelial functions in such patients is discussed in view of current concepts of the role of HCY in various conditions.

Topics: Adult; Aged; Biomarkers; Bipolar Disorder; E-Selectin; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Intercellular Adhesion Molecule-1; Male; Middle Aged; Vitamin B 12; Young Adult

The aim of the present study was to investigate hyperhomocysteinemia in Tunisian bipolar I patients according to 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism.. The subjects consisted of 92 patients with bipolar I disorder diagnosed according to DSM-IV, and 170 controls. Plasma total homocysteine, folate and vitamin B12 were measured. MTHFR C677T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism.. Compared with controls, patients had a significantly higher homocysteine level (16.4 ± 9.8 vs 9.6 ± 4.5 µmol/L; P < 0.001) and a significantly lower folate level (3.2 ± 0.9 vs 6.5 ± 3.2 µg/L; P < 0.001). C677T MTHFR polymorphism genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for MTHFR C677T genotypes, hypofolatemia, hypovitamin B12 and for potential confounding factors, the odds ratio (OR) of hyperhomocysteinemia associated with bipolar disorder remained significant (OR, 5.53; 95% confidence interval: 1.92-15.86; P = 0.001). In patients, there was no significant change in hyperhomocysteinemia, hypofolatemia and hypovitamin B12 with regard to the clinical and therapeutic characteristics, whereas the highest prevalence of hyperhomocysteinemia was found in depressive patients and when illness duration was >12 years. Hypofolatemia was seen in all patients on lithium and in the majority of patients on carbamazepine, and the highest prevalence of hypovitamin B12 was noted in patients taking carbamazepine.. Hyperhomocysteinemia was more frequent in bipolar I patients independent of C677T polymorphism. Patients had reduced levels of folate, which modulates homocysteine metabolism. Indeed, this finding indicates that folate supplementation may be appropriate for bipolar patients with hyperhomocysteinemia.

Topics: Adult; Bipolar Disorder; Case-Control Studies; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Methylenetetrahydrofolate Dehydrogenase (NAD+); Middle Aged; Odds Ratio; Polymorphism, Genetic; Tunisia; Vitamin B 12

A manic episode in old age presents a diagnostic challenge to the clinician due to the different symptomatology often difficult to distinguish from delirium, dementia, agitated depression and psychosis. To complicate matters further, a first episode of mania in later life is very often based on underlying physical and cerebral pathology ('secondary mania'). Many causes of 'secondary mania', including neurological, systemic or endocrine diseases, infections, intoxications, apnoea, post-thoracic surgery and vitamin B12 deficiency have been described to date, but there have been no reports on subdural haematomas in this context. However, the elderly are more prone to subdural haematomas following head trauma than younger patients. We present two case reports of older patients with a first manic episode in later life probably caused by subdural haematomas. A first episode of mania in later life always requires thorough assessment of the patient to determine physical and cerebral pathology.

Topics: Aged; Bipolar Disorder; Craniocerebral Trauma; Diagnosis, Differential; Female; Hematoma, Subdural, Acute; Humans; Male; Vitamin B 12; Vitamin B 12 Deficiency

Studies have found elevated plasma homocysteine (Hcy) levels in bipolar disorder (BD). We investigated serum Hcy levels in euthymic BD patients, and its relationship with cognitive and psychosocial functioning.. Sixty-five BD type I euthymic patients and 49 healthy controls were assessed using a neuropsychological test battery. Hcy levels were measured using an HPLC method with fluorescence detection.. The mean Hcy levels were 1.37 mg/L for BD patients and 1.30 mg/L for healthy controls (P=0.342), male patients showing higher Hcy levels as compared to females (P=0.009). Older patients, those with later illness onset, and patients taking more medications showed higher Hcy levels, but no significant correlation was found with psychosocial functioning. Patients with "elevated" Hcy levels performed significantly worse on all neurocognitive tests, and in patients we found significant associations between Hcy levels and number of perseverations on the SCT (r=0.248, P=0.047), and number of moves on the ToH (r=0.265, P=0.033); however, a linear regression model revealed that Hcy was not a significant predictor of neurocognitive test performance.. Our findings suggest that increased homocysteinemia may play a role in the pathophysiology of neurocognitive deficits in BD, with a higher impact among older patients, or who had a delayed onset of illness.

Topics: Adult; Age Factors; Bipolar Disorder; Cognition Disorders; Demography; Diagnostic and Statistical Manual of Mental Disorders; Dysthymic Disorder; Female; Folic Acid; Homocysteine; Humans; Male; Neuropsychological Tests; Severity of Illness Index; Sex Factors; Vitamin B 12

We investigated the effect of polymorphic variants of c.1298A>C (Glu429Ala) and c.677C>T (Ala222Val) in methylenetetrahydrofolate (MTHFR) gene on the total homocysteine (tHcy), folate and B12 levels in patients with bipolar disorder, first-degree relatives of patients, and controls. The c.677C>T and c.1298A>C polymorphisms in MTHFR were determined by polymerase chain reaction-restriction fragment length polymorphism in 197 bipolar patients, 278 relatives and 238 controls. tHcy and folate and vitamin B12 levels were measured by Fluorescence Polarization Immunoassay and Electrochemiluminescence, respectively. The tHcy was significantly increased in patients and relatives. In contrast, folate and B12 were significantly lower in patients and relatives. Gender was not considered as a significant determinant in the multivariate analysis. Genotypes of c.1298A>C and c.677C>T were correlated with tHcy, folate and B12. Patients and relatives carrying TT and/or AA and AC genotypes had elevated tHcy and reduced folate and B12 levels. High tHcy but low folate and vitamin B12 levels may be a risk factor for development of bipolar disorder.

Topics: Adult; Analysis of Variance; Bipolar Disorder; Family; Female; Fluorescence Polarization Immunoassay; Folic Acid; Gene Frequency; Genotype; Homocystine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Vitamin B 12

Topics: Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Brain; Female; Folic Acid; Haloperidol; Homocystine; Humans; Lithium Carbonate; Magnetic Resonance Imaging; Middle Aged; Neuropsychological Tests; Vitamin B 12

We have previously reported that homocysteine levels are elevated in euthymic bipolar patients with functional deterioration. The current study was designed to extend this finding by examining the relationship between neuropsychological functioning and homocysteine levels in euthymic bipolar patients.. Fifty-seven euthymic bipolar outpatients were assessed for serum levels of homocysteine, folic acid, and vitamin B-12 and administered a battery of neuropsychological tests.. We found that male bipolar subjects showed higher average homocysteine levels than a comparison group of normal subjects, that poorer functioning on a task of executive function (Wisconsin Card Sort) was related to higher homocysteine levels, and that folic acid or vitamin B-12 levels did not significantly affect neuropsychological functioning.. These results, while suggesting some relationship between higher homocysteine levels, bipolar illness, and impairment in cognitive function do not establish any causative effects.. The findings of this study confirm that in euthymic bipolar patients, higher homocysteine levels are associated with poorer performance in some neuropsychological tests. Treatment trials will be required before it will be known if the putative decrements in the executive function of bipolar patients can be reversed, or at least retarded, if homocysteine levels are reduced (as, for example, by dietary addition of B vitamin supplements).

Topics: Adolescent; Adult; Bipolar Disorder; Cognition; Cognition Disorders; Dysthymic Disorder; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Neuropsychological Tests; Severity of Illness Index; Vitamin B 12

Divalproex (DVP) is increasingly prescribed to children and adolescents in psychiatric practices. Among the hematologic adverse effects of DVP, decreased platelet count is well described in the medical literature. However, to date, few studies describe the occurrence of macrocytosis as an adverse effect of divalproex. We report two cases of pediatric patients who developed macrocytosis and decreasing platelet counts secondary to DVP treatment. Because macrocytosis remained an asymptomatic nonprogressive condition for our patients, we support the recommendation for closer surveillance of the patients' complete blood counts for development of anemia in addition to thrombocytopenia.

Topics: Anemia, Macrocytic; Anticonvulsants; Bipolar Disorder; Child; Dose-Response Relationship, Drug; Erythrocyte Indices; Female; Folic Acid; Follow-Up Studies; Humans; Platelet Count; Thrombocytopenia; Valproic Acid; Vitamin B 12

Topics: Adult; Bipolar Disorder; Diagnosis, Differential; Diet, Vegetarian; Female; Humans; India; Peripheral Nervous System Diseases; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

A twenty-one-year-old female known to suffer from bipolar type I disorder developed features of a pseudodementia. Following prompt initial response to treatment with antidepressants, there was an early recurrence of cognitive impairment. Blood investigations confirmed a macrocytic anaemia and vitamin B12 and folate deficiencies. There was dramatic resolution of cognitive impairment after vitamin replacement. This suggested the occurrence of a reversible nutritional dementia and reinforced the need to rule out secondary organic causes of psychiatric symptoms even in patients previously diagnosed with a primary psychiatric disorder.

Topics: Adult; Bipolar Disorder; Dementia; Female; Folic Acid; Folic Acid Deficiency; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Bipolar Disorder; Body Temperature Regulation; Circadian Rhythm; Combined Modality Therapy; Drug Administration Schedule; Humans; Male; Phototherapy; Sleep Stages; Vitamin B 12

Topics: Bipolar Disorder; Crohn Disease; Humans; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Bipolar Disorder; Depressive Disorder; Humans; Male; Middle Aged; Neurocognitive Disorders; Paranoid Disorders; Vitamin B 12; Vitamin B 12 Deficiency

Red cell folate and vitamin B12 estimations were performed on 243 successively admitted in-patients at a District General Hospital Psychiatric Unit and 42 out-patients (29 attending a lithium clinic). Patients were classified into five diagnostic groups. The mean ages of the manic and schizophrenic patients were lower than of the depressed or euthymic patients but age was not correlated with red cell folate or serum B12 levels in any group. There were 89 (31%) patients with red cell folate below 200 ng/ml and 35 (12%) with concentrations below 150 ng/ml. Significantly more of these low-folate patients were in-patients than out-patients. The mean red cell folate in the depressed patients was significantly lower than in the euthymic, manic and schizophrenic groups. Alcoholics had a similar mean red cell folate to depressed patients which was not quite significantly lower than the other groups. The mean serum B12 level in the alcoholics was, however, significantly raised. There were no significant differences in red cell folate or serum B12 between lithium-treated and untreated euthymic patients. The highest proportions of values below 200 ng/ml and 150 ng/ml were found in depressed and alcoholic patients. Endogenous depressives had the highest percentage of values below 150 ng/ml (folate-deficient) of all psychiatric groups and alcoholic patients. The significance of these findings is discussed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alcoholism; Bipolar Disorder; Depressive Disorder; Erythrocytes; Female; Folic Acid; Folic Acid Deficiency; Humans; Male; Mental Disorders; Middle Aged; Schizophrenia; Vitamin B 12

This chart review study examined the serum vitamin B12 and folate status of 102 geriatric patients newly admitted to a private psychiatric hospital. Only 3.7% were B12 deficient and 1.3% were folate deficient; 4% were anemic. Nevertheless, those with below-median values of both vitamins had significantly lower Mini-Mental State scores than patients higher in one or both vitamins. Patients with "organic psychosis" with a negative family history for psychiatric disorder had significantly lower B12 levels than those with a positive family history. In major depression, folate levels correlated negatively with age at onset of psychiatric illness and length of hospitalization. These data suggest that (1) biochemically interrelated vitamins such as B12 and folate may exert both a separate and a concomitant influence on affect and cognition; (2) poorer vitamin status may contribute to certain geropsychiatric disorders that begin at a later age and lack a familial predisposition.

Topics: Affective Disorders, Psychotic; Aged; Aged, 80 and over; Bipolar Disorder; Cognition Disorders; Depressive Disorder; Female; Folic Acid; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Neurocognitive Disorders; Retrospective Studies; Vitamin B 12

A case of mania apparently secondary to vitamin B12 deficiency appeared without other overt clinical features of pernicious anemia and resolved with B12 replacement. Six months later, the patient was receiving monthly B12 injections and his mental status remained normal.

Topics: Aged; Bipolar Disorder; Humans; Male; Neurocognitive Disorders; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Bipolar Disorder; Chronic Disease; Depression; Gastrointestinal Diseases; Humans; Malabsorption Syndromes; Psychosurgery; Psychotic Disorders; Schizophrenia; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6 Deficiency

Topics: Adult; Aged; Biological Assay; Bipolar Disorder; Chlorpromazine; Depressive Disorder, Major; Female; Humans; Lactobacillus; Male; Middle Aged; Phenothiazines; Schizophrenia; Thioridazine; Trifluoperazine; Vitamin B 12