Serum and red cell folate and affective morbidity in lithium prophylaxis

Serum and red cell folate concentrations were estimated in 68 affective disorder patients taking lithium prophylactically, 65 of whom had bipolar disorder. The number of hospital admissions, the frequency of use of additional mood altering treatments and the Affective Morbidity Index were calculated for the 2 years of the study. Contrary to other findings, there were no differences between the folate concentrations for different severities of affective morbidity. These results question the rationale of prescribing folic acid preparations for lithium-treated bipolar disorder patients, but the authors indicate that folate concentrations may be low in lithium-treated unipolar depressives.     

Serum folate and homocysteine levels in patients with obsessive-compulsive disorder

Previous studies have shown that folate deficiency, increased homocysteine, impaired metylation have been identified in depressive disorder. Recently, growing research has resulted in the biological association between obsessive-compulsive disorder (OCD) and affective disorders. Therefore, in the present study it was evaluated whether or not folate and homocysteine levels changed. Serum folate and homocysteine concentrations were measured in 23 patients with OCD and in same number of controls. In addition, all patients were assessed by Yale-Brown Obsession Compulsion Scale (Y-BOCS). Serum folate values were significantly lower in OCD patients than in controls, while homocysteine concentrations were higher in patients compared with controls. Serum folate values were significantly and negatively related to Y-BOCS scores. Total serum homocysteine concentrations were positively correlated to Y-BOCS scores and the duration of illness. There was a trend toward a negative correlation between the concentrations of serum folate and homocysteine. In conclusion, we identified that a group of patients with OCD might have folate deficiency, higher homocysteine levels and probable impaired metylation and monoamine metabolism.     

Serum dopamine-beta-hydroxylase activity in clinical subtypes of depression

Serum dopamine-beta-hydroxylase (DBH) activity was determined in male adult psychiatric patients (n = 280) and age-matched male healthy controls (n = 100). Patients included in the study had no history of previous or current exposure to psychoactive drugs and were diagnosed according to Research Diagnostic Criteria. A significant decrease in serum DBH activity was noted in patients with psychotic major depressive disorder (n = 50) as compared with controls. In acute schizophrenics (n = 100), nonpsychotic major depressives (n = 45) and patients with manic disorder (n = 85), mean DBH activity did not differ significantly from the control values.     

Lithium and suicidal behavior in major affective disorder: a case-control study

OBJECTIVE: A number of studies have suggested that lithium may be particularly effective in reducing suicide risks among patients with major affective disorders. The design of many of these studies left them open to biases associated with treatment compliance, however. METHOD: Subjects were drawn from a naturalistic, long-term follow-up of patients with major affective disorders. Fifteen who committed suicide while receiving somatotherapy where matched to non-suicidal patients who were similarly receiving somatotherapy at the same point in follow-up. The same procedure was followed for 41 patients who made a serious suicide attempt during follow-up. RESULTS: Six (40.0%) of the patients who committed suicide, and eight (53.3%) of their controls, were thought to have been taking lithium in the preceding week. Among attempters and their controls, nine (22.0%) and eight (19.5%), respectively, were taking lithium. CONCLUSION: These results do not support previous suggestions that lithium has uniquely antisuicidal properties. Other existing datasets should be explored with this design to establish whether lithium does, or does not, offer special protection against suicide.     

Inositol augmentation of lithium or valproate for bipolar depression

OBJECTIVE: Despite promising new therapies, bipolar depression remains difficult to treat. Up to half of patients do not respond adequately to currently approved treatments. This study evaluated the efficacy of adjunctive inositol for bipolar depression. METHODS: Seventeen participants with DSM-IV criteria for bipolar depression and a 17-item Hamilton Rating Scale for Depression (HRSD) > or =15 on proven therapeutic levels of lithium or valproate for >2 weeks were randomized to receive double-blind inositol or placebo for 6 weeks. At the end of double-blind treatment, subjects were eligible for an 8-week open-label trial of inositol. RESULTS: Response was defined a priori as >50% reduction in the HRSD and a Clinical Global Impression of 1-2. Four of nine subjects (44%) on inositol and zero of eight subjects on placebo met response criteria (p = 0.053). There was no difference between groups in the average change score for the HRSD or Young Mania Rating Scale (YMRS). Response to inositol was highly variable. Of nine subjects randomized to inositol, two had >50% worsening in HRSD scores at the end of treatment, three had no change and four had >50% improvement. Those who had worsening in depressive symptoms on inositol had significantly higher scores at baseline on the YMRS total score and irritability, disruptive/aggressive behavior and unkempt appearance items. CONCLUSIONS: There was a trend for more subjects on inositol to show improvement in bipolar depression symptoms, but, on average, inositol was not more effective than placebo as an adjunct for bipolar depression. Baseline levels of anger or hostility may be predictive of clinical response to inositol.     

Outcome of lithium prophylaxis: a prospective follow-up of affective disorder patients assigned to high and low serum lithium levels

The purpose of the study was to examine the outcome of long-term lithium treatment in consecutively admitted affective disorder patients assigned to high and low serum lithium levels. A total of 91 patients were diagnosed according to DSM-III criteria and randomly allocated to two open treatment groups in which prophylactic lithium was administered in high (serum lithium 0.8-1.0 mmol L^-1) and low (serum lithium 0.5-0.8 mmol L^-1) doses, respectively. The patients were followed for 2 years or until discontinuation of lithium treatment or readmission to hospital for recurrence of affective illness. The main outcome of the treatment groups was compared with Kaplan-Meier survival curves and by Cox regression analysis. A total of 31 patients (34%) completed 24 months of prophylactic lithium treatment without recurrence and readmission to hospital. In total, 18 patients (20%) suffered a recurrence on lithium, and 42 patients (46%) discontinued lithium or were lost to follow-up. No effect of treatment group was seen, either for the total patient group or for the large subgroup of bipolar patients when analysed separately. A number of patients did not maintain their original assignment to the high serum lithium levels group. The results were analysed both according to assignment and according to actual serum lithium levels. Abuse of alcohol or medication was associated with a poor outcome. Only one third of the patients completed 2 years of lithium prophylaxis successfully. No difference in the protection against recurrences was observed between patients maintained on high and low serum lithium levels.     

Prevalence of winter depression in Denmark

An unselected cohort of 3556 subjects in Copenhagen was asked to complete the Seasonal Pattern Assessment Questionnaire (SPAQ) for estimating the presence of seasonal affective disorders (SAD or winter depression). Completed questionnaires were received from 1794 subjects in total. About 12% of the respondents had a Global Seasonality Score (GSS) high enough to indicate the presence of SAD. Among those respondents without SAD, women and younger people were found to be much more sensitive to seasonal and weather changes than men and older people, respectively.     

Personality and personality disorders among patients with major depression in combination with dysthymic or cyclothymic disorders

Personality traits and personality disorders in 298 consecutive outpatients with pure major depression, major depression with dysthymic or cyclothymic disorder, pure dysthymic or cyclothymic disorder and other disorders were investigated. Patients with dysthymic or cyclothymic disorders alone or in combination with major depression showed more self-doubt, insecurity, sensitivity, compliance, rigidity and emotional instability. They were more schizoid, schizotypal, borderline and avoidant according to MCMI and had a higher prevalence of DSM-III Axis II diagnoses, and more borderline, avoidant, and passive-aggressive personality disorders, as measured by SIDP. All in all, dramatic and anxious clusters of personality disorders were more frequent among patients with dysthymic-cyclothymic disorders in addition to major depression than among patients with major depression only. The findings elucidated the close connection between the more chronic affective disorders and the personality disorders, irrespective of any concomitant diagnosis of major depression.     

Mortality during initial and during later lithium treatment

We have previously shown that the mortality of patients with recurrent affective disorders in long-term lithium treatment is not higher than that of the general population. In the present study on 471 patients from Denmark and Germany, we examined mortality during the initial year of lithium treatment and during later lithium treatment. During initial lithium treatment, the total mortality was twice as high as in the general population (difference not significant) and the mortality due to suicide 16 times higher. During later lithium treatment, the mortality rates did not differ from those in the general population. Our results indicate that patients with frequent, often severe recurrences, those chosen for prophylactic lithium treatment, are at risk of high mortality, which then diminishes as the prophylactic action of the treatment takes effect.     

A prevalence study of folate deficiency in a psychiatric in-patient population

Controlled clinical trials in the UK have shown folate deficiency in psychiatric patients, and it has been suggested that such deficiency is most likely to occur among patients with affective disorders. Studies have led to the use of folate as an adjunct to therapy in such patients. The present paper describes a preliminary investigation into the red cell folate status of psychiatric patients in a general hospital unit compared with age- and sex-matched healthy controls, using up-to-date assays and strict entry criteria and overall improved methods on previous studies. The study showed that, although there is a trend for psychiatric patients to have lower serum folate levels than controls, there is no statistically significant difference in folate levels as measured by red cell folate, a more reliable measure of folate status, between healthy controls and psychiatric patients, and all but one of the patients had normal haematological indices.     

Life satisfaction and adjustment in lithium-treated affective patients in remission

The aim of this study was to assess life satisfaction and adjustment of lithium-treated affective patients in remission. Scores of life satisfaction and adjustment in four areas were obtained for two experimental groups of 50 unipolars and 50 bipolars and for two control groups of 50 healthy individuals and 50 patients with personality disorders. Subjects' self-assessments and psychiatrists' evaluation were rated using a modification of Cantril's ladder device. No significant differences were found between affective patients and healthy controls regarding life satisfaction and adjustment, whereas psychiatric controls scored significantly less on most indices. Moreover, the treating psychiatrists rated affective patients significantly higher than psychiatric controls and perceived them as actualizing their potential to a greater degree. Thus, it is concluded that neither the affective illness nor lithium as a prophylactic agent interfered with the patients' feelings of satisfaction or with manifest functioning while in remission.     

Personality disorders in patients with winter depression

Sixty-six patients satisfying the criteria for seasonal affective disorder (SAD) winter depression type (n= 57) or subsyndromal SAD (n= 9), were interviewed in a nondepressed state with the Structured Interview for DSM-III-R Personality Disorders (SIDP-R). Twenty-three percent of the patients in the SAD sample met DSM-III-R criteria for one or more categorical diagnosis of personality disorder (PD). Disorders in cluster C occurred in 18% of the sample, while 12% had cluster B PDs and 5% a cluster A disorder. The relative number of positive criteria, as a dimensional measure of PD, were higher for all cluster C disorders than for any PD in the other clusters. Our data indicate that the pattern of personality disorders in patients with winter SAD are similar to that previously reported for outpatients with non-SAD major depression. We explored the relationship between lifetime severity and clinical manifestation of SAD and dimensional measures of PD with multiple regression analyses. No significant association was found. This is in accordance with the hypothesis that the two disorders are distinct conditions with independent causes.     

Mood-independent aberrancies in associative processes in bipolar affective disorder: an apparent stabilizing effect of lithium

Forty-eight patients from an affective disorders clinic were tested twice with a word association test. They gave significantly fewer repetitions of common responses than did 29 normal controls. This difference was not related to subgroup diagnosis (bipolar I, bipolar II, unipolar, schizoaffective, and cyclothymic personality), to mood state at the time of testing, or to cycling frequency. The total number of repeated responses was directly correlated with serum lithium level (r = 0.44, p less than 0.01, especially in those judged good lithium responders (r = 0.71, p less than 0.05). This finding may reflect a normalizing effect of lithium on associative processes in affective illness.     

Antithyroid antibodies in major depression

Antithyroid antibodies were measured in 58 patients with unipolar major depressive disorder. None of the patients had received prior lithium treatment. Five patients had antimicrosomal and antithyroglobulin antibodies. The prevalence rate of detectable antibody titers approximates that found in normal subjects. The presence of detectable antibody titers was not related to abnormal thyroid function tests. The implications of these findings are discussed.     

Carbamazepine versus lithium in the prophylaxis of bipolar affective disorder.

A 12-month double-blind trial of carbamazepine vs lithium, given as sole treatment for the prophylaxis of bipolar affective disorder, was carried out in 31 patients. All were previously stable on lithium; 15 were switched over to carbamazepine and 16 remained on lithium. Although the overall relapse rate was similar in the 2 groups (6 on carbamazepine, 8 on lithium), nearly all the relapses in carbamazepine occurred in the first month, probably precipitated by lithium withdrawal. Two patients on carbamazepine developed a rash and were withdrawn. More side effects were noted during the early stages on carbamazepine. Patients on lithium tended to gain weight (+4 kg) compared with carbamazepine (-3.1 kg). It is concluded that carbamazepine is as effective as lithium in the prophylaxis of bipolar affective disorder; changeover from lithium to carbamazepine should be done slowly.     

Lithium discontinuers. I. Clinical characteristics and outcome

Eleven patients with major affective disorder (DSM-III) were investigated after a mean of 6.7 years on lithium prophylaxis and reinvestigated 7 years later, at which time they had discontinued lithium for a mean 2.3 years. Outcome was assessed by the Comprehensive Psychopathological Rating Scale, by relapse frequencies, by need for psychotropic medication and for inpatient treatment. The study period was associated with an increase in the rated score for depression, as previously observed also in lithium discontinuers. Although the relapse frequencies remained largely unchanged, a significantly increased number of inpatient treatment days indicated considerably more severe episodes after the discontinuation of lithium. Long periods without lithium were associated with higher doses of neuroleptic drugs.     

重性抑郁障碍或双相障碍患者抑郁发作伴随躁狂症状的临床特征

目的:了解重性抑郁障碍(MDD)或双相障碍抑郁发作患者出现躁狂症状的频率和程度。方法:对52例经简明国际神经精神访谈(MINI)、符合《美国精神障碍诊断与统计手册》第4版(DSMIV)重性抑郁障碍或双相障碍抑郁发作的患者,采用情感障碍评估量表(ADE)评估患者本次抑郁发作中出现的躁狂症状。结果:52例患者中有36例重性抑郁障碍,16例为双相障碍抑郁发作。至少有1条躁狂症状的患者达86.5%(n=45),至少有3条躁狂症状的患者占32.7%(n=17),而没有任何躁狂症状的患者仅占13.5%(n=7)。结论:抑郁发作患者大多存在不同程度的躁狂症状,及时识别这些症状,对诊断与治疗有指导意义。情感障碍评估量表是一个值得应用的评估情感发作的工具。