Long-term outcome of lithium prophylaxis in bipolar disorder with mood-incongruent psychotic features: a prospective study

BACKGROUND: No study has assessed systematically up to now the long-term outcome of lithium prophylaxis in bipolar patients with vs. without mood-incongruent psychotic features. METHODS: All bipolar patients with mood-incongruent psychotic features who started lithium prophylaxis at a lithium clinic during 14 years were followed up prospectively for 5 years, along with a control group of non-psychotic bipolars. RESULTS: Psychotic patients were significantly less likely than controls to be still on lithium after 5 years, and to present a reduction of at least 50% of time spent in hospital during the lithium treatment period compared with a pre-treatment period of the same duration. The time to 50% risk of readmission was significantly increased among both groups during lithium treatment. 39.6% of prospective episodes in psychotic patients did not include mood-incongruent psychotic features. LIMITATIONS: This is a naturalistic study carried out at a lithium clinic. No control group of bipolar patients who did not receive lithium was available. CONCLUSIONS: Lithium exerts a significant impact on the course of bipolar disorder with mood-incongruent psychotic features, although this impact is less pronounced than in classical manic-depressive illness.     

Lithium, red blood cell choline and clinical state. A prospective study in manic-depressive patients

Red blood cell (RBC) choline and ergothioneine levels were measured after repeated sampling of bipolar manic-depressive patients over 11 months of lithium maintenance. In addition, blood levels were measured in healthy volunteers, newly hospitalised lithium-free patients and from patients prior to, and after, initiating lithium. RBC choline levels did not differ between normal volunteers and newly admitted lithium-free patients with either mania or depression. After 4 weeks of lithium treatment RBC choline levels increased 6-fold, whereas the levels of the closely related compound ergothioneine did not change. Significant changes in mood during lithium maintenance were not accompanied by changes in RBC choline levels. These data indicate that lithium produced a specific accumulation of choline in erythrocytes. However the increased levels appear to be unrelated to clinical state and do not distinguish lithium responders from non-responders     

Drug response patterns as a basis of nosology for the mood-incongruent psychoses (the schizophrenias)

Interaction of therapeutic drugs with a series of different biopathological substrates of psychosis might be expected to generate a series of different response patterns. Herein the authors suggest that multi-modal response patterns following lithium and neuroleptic treatment of psychotic patients may aid in resolving the heterogeneity of psychotic disorders and lead to a new nosology of the psychoses.     

Does maintenance lithium therapy prevent recurrences of mania under ordinary clinical conditions?

Mental-hospital admission rates in Edinburgh for mania, schizophrenia and psychotic depression were studied from 1970 to 1981, a 12-year period during which long-term lithium therapy was increasingly employed in affective illnesses. If this treatment had been effective admission and readmission rates for mania, and perhaps also for depression, should have fallen progressively. In fact, they rose steadily, while the admission rate for schizophrenia fell. These changes could not easily be attributed to changing diagnostic criteria, to the admission of milder affective illnesses, or to poor and deteriorating lithium surveillance. Their explanation is uncertain, but they cast some doubt on the efficacy of lithium prophylaxis in ordinary clinical practice.     

Early and late onset bipolar disorders: two different forms of manic-depressive illness?

BACKGROUND: Conflicting results in genetic studies of bipolar disorders may be due to the clinical and genetic heterogeneity of the disease. Age at onset of bipolar disorders may be a key indicator for identifying more homogeneous clinical subtypes. We tested whether early onset and late onset bipolar illness represent two different forms of bipolar illness in terms of clinical features, comorbidity and familial risk. METHODS: Among a consecutively recruited sample of 210 bipolar patients, we compared early onset (n=58) and late onset (n=39) bipolar patients; the cut-off points were age at onset before 18 years and after 40 years for the two subgroups. The subgroups were compared by independent t tests and a contingency table by raw chi-square test. Morbid risk among first-degree relatives was measured by the survival analysis method. RESULTS: The early onset group had the most severe form of bipolar disorder with more psychotic features (P=0.03), more mixed episodes (P=0.01), greater comorbidity with panic disorder (P=0.01) and poorer prophylactic lithium response (P=0.04). First degree relatives of early onset patients also had a higher risk of affective disorders (P=0.0002), and exhibit the more severe phenotype, i.e bipolar disorder. CONCLUSION: Our data suggest that early and late onset bipolar disorders differ in clinical expression and familial risk and may therefore be considered to be different subforms of manic-depressive illness.     

The significance of psychotic features in manic episodes: a report from the NIMH collaborative study

BACKGROUND: Psychotic features in the context of major depressive syndromes have correlates in symptom severity, acute treatment response and long-term prognosis. Little is known as to whether psychotic features have similar importance when they occur within manic syndromes. METHODS: These data derive from a multi-center, long-term follow-up of patients with major affective disorder. Raters conducted follow-up interviews at 6-month intervals for the first 5 years and annually thereafter. A sub-set of probands participated in a family study in which all available, adult, first-degree relatives were interviewed as well. RESULTS: Of 139 who entered the study in an episode of mania, 90 patients had psychotic features. Symptom severity ratings at intake were more severe for this group. Though time to first recovery and time to first relapse did not distinguish the groups, psychotic features were associated with a greater number of weeks ill during follow-up and the strength of this association was similar to that seen for psychotic features within depressed patients described in an earlier publication. Patients with psychotic mania at intake did not differ significantly from those with nonpsychotic mania by response to acute lithium treatment, suicidal behavior during follow-up, or risks for affective disorder among first-degree relatives. Psychotic features within manic syndromes were not associated with high psychosis ratings during follow-up. In contrast, when psychotic features accompanied depressive syndromes, they strongly predicted the number of weeks with psychosis during follow-up, particularly among individuals whose episodes at intake were less acute. CONCLUSIONS: As with major depressive syndromes, psychotic features in mania are associated with greater symptom severity and higher morbidity in the long-term. Psychotic features are much less predictive of future psychosis when they occur within a manic syndrome than when they occur within a depressive syndrome.     

The pharmacotherapy of major depressive syndrome Part 1: Treatment of acute depression

After listing the diagnostic criteria for major depressive syndrome (which comprises involutional melancholia, manic-depressive illness, and psychotic depressive reaction), the authors offer guidelines for choosing among the tricyclic antidepressants, monoamine oxidase inhibitors, psychomotor stimulants, lithium, and other agents for these conditions. The relatively lengthy course of an acute depressive episode, they suggest, allows time to find the most effective drug for each patient.     

Lithium prophylaxis and the kidney

We reviewed the records of 44 patients under age 55 with bipolar affective disorder, who were without known systemic illness and receiving lithium prophylactically for a minimum of 6 months. We systematically collected all demographic, family history, and clinical side-effect data. In addition, laboratory results of renal function were complied. Polyuria was the earliest and most frequent of lithium therapy. Patients receiving other psychotropic medication, plus lithium, showed a significant increased prevalence of polyuria particularly after 3 months of exposure to medication, as compared to patients receiving lithium alone. The onset of polyuria was correlated with duration of lithium treatment and patient's age at initiation of therapy.Our data suggest that polypharmacy, duration of exposure to lithium ion and patient age each predict the development of delayed polyuria, a symptom consistent with interstitial nephritis.     

Cycloid psychosis: a clinical and nosological study

BACKGROUND: Despite its clinical relevance, the diagnosis of cycloid psychosis has been relatively neglected in the psychiatric literature and in the current nosological systems. This study examined the clinical validity and nosological status of the cycloid psychosis concept. METHOD: Six-hundred and sixty psychotic in-patients were assessed for psychosis-related variables and diagnosed according to DSM-III-R, DSM-IV, ICD-10 and the Perris & Brockington criteria forcycloid psychosis. The cycloid psychosis diagnosis (N = 68, 10.3%) was examined in regard to its discriminant validity, concordance with other psychotic disorders, and predictive validity in relation to schizophrenia and psychotic mood disorders. To address putative heterogeneity within cycloid psychosis, affective (N = 38) and non-affective (N = 30) subgroups were examined. RESULTS: Cycloid psychosis had good discriminant validity regarding other psychoses (95% of correctly classified cases) and poor concordance with individual diagnoses from the formal diagnostic systems (K < 0.22). Cycloid patients had levels of psychotic, disorganization and first-rank symptoms comparable to schizophrenia, and levels of affective symptoms in-between schizophrenia and mood disorders. Regarding most clinical variables and morbidity risk of mood disorders, cycloid psychosis was closer to mood disorders. Cycloid psychosis had higher psychosocial stressors than schizophrenia and mood disorders. Affective and non-affective groups of cycloid psychosis differed in a number of variables indicating an overall better outcome for the non-affective group. CONCLUSIONS: Cycloid psychosis does not correspond closely to any DSM-III-R, DSM-IV or ICD-10 category of psychosis, and more specifically this nosological concept is not well represented by the different formal definitions of remitting psychotic disorders. Cycloid psychosis seems to be an heterogeneous condition in that affective and non-affective subgroups can be differentiated.     

The association between lithium carbonate and smooth pursuit eye tracking among first-episode patients with psychotic affective disorders

The association between treatment with lithium carbonate and smooth pursuit eye tracking performance was investigated in first-episode patients with psychotic affective disorders. The horizontal pursuit performance of patients with major depression and bipolar disorder who were receiving lithium carbonate was contrasted with that of patients not receiving lithium carbonate. In addition, the accuracy and quality of pursuit eye tracking was examined in bipolar patients whose lithium status changed from the time of initial testing to the time of retest 10 months later. For the combined group of depressed and bipolar patients, treatment with lithium carbonate was not associated with worse pursuit performance. Bipolar disordered patients on lithium did not differ in tracking proficiency from those not on lithium; bipolar patients whose lithium status changed from intake to retest also did not display a significant change in pursuit performance.     

Seasonality of the episodes of recurrent affective psychoses: Possible prophylactic interventions

This study is an attempt to ascertain whether evidence for seasonal variations of the episodes of recurrent affective psychoses can be found in patients in Greece. Due allowance has been made for the fact that different socio-cultural and above all climatological factors prevail in Greece as opposed to other countries, which might be relevant in the phenomenon of seasonality.The seasonal distribution of the psychotic episodes, either depressive or manic, has been examined for 533 patients with various forms of affective psychoses, admitted to and treated in the State Mental Hospital of Athens, Greece, during the last 50 years.Statistically significant seasonal variation with peaks in spring was found for both depressive and manic episodes of various subgroups of patients, divided according to the I.C.D.-9.     

A longitudinal record study of renal function in patients treated with lithium

We reviewed hospital charts of 62 patients receiving long-term lithium therapy in an attempt to see if renal function deteriorated in association with lithium treatment. We found no association between duration of lithium treatment of up to four years and change in BUN or creatinine or the development of proteinuria. There was a nonsignificant tendency for cases showing a rise in BUN from index to follow-up to have had a chart record of lithium intoxication, but these same cases tended to have a lower follow-up creatinine. There was a tendency for older patients to have higher BUN and creatinine at follow-up than at index, but there was no association between this and duration of lithium treatment.     

Are childhood psychiatric histories of bipolar adolescents associated with family history, psychosis, and response to lithium treatment?

OBJECTIVE: To examine if childhood psychiatric diagnoses are associated with family history, psychosis, age, and lithium response. METHOD: Associations among variables, and their contributions to explaining lithium response were examined in 48 bipolar adolescents enrolled in a study of lithium. RESULTS: Presence of a childhood diagnosis was not associated with family psychiatric history or lithium response. Subjects with psychotic features, however, were less likely to have a childhood psychiatric diagnosis, were older, and had a poorer response rate to lithium than subjects without psychosis. DISCUSSION: Heterogeneity within bipolar adolescents may be based on clinical features such as psychosis rather than childhood or family history alone.     

Lithium + L-tryptophan compared with amitriptyline in endogenous depression

Endogenously depressed in-patients were treated for four weeks with either lithium + L-tryptophan (N = 22) or amitriptyline (N = 21) in an open study. Before and weekly during treatment the patients were evaluated by means of Hamilton rating scale, and blood samples were collected for determination of serum concentration of lithium, or amitriptyline and nortriptyline. Both groups responded significantly and the two treatments were not significantly different in antidepressive efficacy. No significant correlation could be demonstrated between clinical improvement and steady-state serum drug levels. From this study it appears that lithium combined with L-tryptophan may be effective in the treatment of endogenous depression.     

Discontinuation of antipsychotic drug therapy

When an antipsychotic medication is discontinued, the possible withdrawal symptoms include psychotic relapse, medical complaints, and dyskinetic movements. Psychotic relapse, if it occurs, may be delayed for months or years and can be detected by close patient follow-up. Medical symptoms, such as nausea, Vomiting, and dizziness, are time-limited. Tardive dyskinesia may appear during or after drug withdrawal, but this problem is not necessarily permanent. To minimize symptoms, antipsychotic drugs should be tapered gradually, and patients on an antiparkinsonism medication should continue it for at least a week after the antipsychotic drug is stopped.     

Neonaticides may be more preventable and heterogeneous than previously thought – neonaticides in Finland 1980–2000

Summary Neonaticide is a sad and infrequent crime with possibly a high level of underreporting. The aim of this study was to examine the circumstances of neonaticide, and whether there are subtypes of offenders, or suggestions for prevention. The study was retrospective and register-based using comprehensive nation-wide material of all cases of suspected neonaticide during 1980–2000 in Finland. Out of the 50 suspected cases, 32 women were included in the final analyses as neonaticide offenders. Most women (91%) had concealed their pregnancy, which was not the first for 66%. Most (66%) were not quite sure why they had offended, and the most frequent (63%) method of operation was neglect. Four women were diagnosed psychotic and formed a specific group. We concluded that there might be specific subgroups of offenders – even though our small population limited conclusions. Furthermore, prevention might be heightened. We call for international joint projects for enlarged material to enable grouping, as well as education and discussion among the public and the professionals to prevent neonaticide, unify its jurisprudence and improve the treatment of the offenders.     

神经精神病学临床评定表(SCAN)在精神分裂症临床表型界定中的应用

目的：使用半定式诊断工具神经精神病学临床评定表(SCAN)进行有关精神分裂症临床表型界定方面的探索。方法：对初步诊断为精神分裂症的住院患者使用SCAN核实ICD-10诊断，共收集80例，采用SCAN诊断软件辅助诊断并得出症状组和症状群资料，用主成分分析等方法进行处理。结果：根据对SCAN症状群的主成分分析，精神分裂症的临床相可以划分为以精神病性症状、阴性症状和抑郁症状为主的三个维度；而精神病性症状内部可以区分出特征性幻听、思维障碍和被动体验、怪异妄想以及非特异性病理症状四个维度的划分。结论：根据精神分裂症临床相的维度划分，提出按照操作性标准(如一级症状)、阴性症状和情感症状三级标准划分临床表型的假说。     

Trace lithium in mood disorders.

BACKGROUND: Variations in trace (endogenous) lithium exchanges have been postulated to play a role in the pathophysiology of affective diseases. This prospective study aimed to check whether plasma, erythrocytes and urine trace lithium levels were altered in mood disorders. METHODS: Trace lithium was determined by atomic absorption spectrophotometry in patients without mood stabilizing drugs or somatic diseases, hospitalized for bipolar affective disorders, major depressive episodes, and other psychiatric disorders with depressive features. Patients admitted for psychotic disorders without mood alterations and healthy volunteers served as controls. RESULTS: There were no differences in trace lithium status between the groups. Erythrocytes/plasma ratios appeared higher than described on therapeutic lithium (1.6+/-0.7, N = 199). LIMITATIONS: The study had sufficient power to detect clinically significant differences in whole body lithium handling between the groups. However, it did not address alterations of lithium exchanges across neuronal membranes or the blood-brain barrier. CONCLUSIONS: Alterations of membrane exchanges hypothetically associated with mood disorders are not reflected in plasma or erythrocytes trace lithium levels. The occurrence of mood disorders seems not to be related to abnormalities in endogenous lithium.     

Proposed delusional depression subtypes: preliminary evidence from a retrospective study of phenomenology and treatment course

An analysis of the phenomenology and treatment course of 52 subjects with delusional depression suggests that there may be various subtypes: bipolar, early-onset unipolar and possibly a late-onset unipolar. The bipolar subgroup tended to relapse in different but always psychotic directions, and was resistant to lithium carbonate treatment alone. Treatment refractoriness, delusional depressive recurrences, and a dementia-like presentation were associated with a small late-onset subgroup. A high rate of delusionally depressive relapses also characterized the early-onset unipolar group, however, patients with single episodes were found only in this subgroup.