Heterozygous β-thalassaemia as a susceptibility factor in mood disorders: excessive prevalence in bipolar patients

BACKGROUND: Previous preliminary reports have suggested potential interactions between microcytic anaemia and mood disorders. In particular, heterozygous β-thalassaemia has been implicated in the bipolar spectrum. This study surveyed relevant haematological parameters in a large sample of psychiatric outpatients with the aim of clarifying previous observations. METHODS: Mean Corpuscular Volume (MCV) was analysed in 1014 consecutive patients diagnosed according to modified Research Diagnostic Criteria (RDC). Haemoglobin electrophoresis and/or chromatography was performed in blood samples from 143 patients with reduced MCV. Prevalence of heterozygous β-thalassaemia was estimated based on the rates of patients with reduced MCV and increased haemoglobin A(2 )concentration. RESULTS: MCV lower than 80 μ(3 )was found in greater proportions among bipolar compared with the remaining RDC subgroups (183/732 = 25.0% versus 51/282 = 18.1%; p = 0.02; relative risk = 1.38; Fisher's exact test). This difference can mainly be attributed to heterozygous β-thalassaemia, the estimated prevalence of which was 16.4% among bipolar and 9.9% among non-bipolar subgroups (p = 0.01; relative risk = 1.65). CONCLUSION: The results are consistent with the hypothesis that heterozygous β-thalassaemia might play a role as a susceptibility factor in bipolar spectrum disorders in specific populations

Psychotic mania in glucose-6-phosphate-dehydrogenase-deficient subjects

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been associated with acute psychosis, catatonic schizophrenia, and bipolar disorders by previous inconclusive reports. A particularly disproportionate rate of enzyme deficiency was found in manic schizoaffective patients from 662 lithium patients surveyed in Sardinia. The purpose of this study was to describe clinical characteristics which may be potentially associated with G6PD deficiency. METHODS: Characteristics of episodes, course of illness, family pattern of illness, laboratory tests, and treatment response of 29 G6PD-deficient subjects with a Research Diagnostic Criteria diagnosis of manic schizoaffective disorder were abstracted from available records. RESULTS: The most peculiar pattern was that of acute recurrent psychotic manic episodes, mostly characterized by loosening of associations, agitation, catatonic symptoms, and/or transient confusion, concurrent hyperbilirubinemia, positive psychiatric family history, and partial response to long-term lithium treatment. CONCLUSIONS: A relationship between psychiatric disorder and G6PD deficiency is to be searched in the bipolar spectrum, particularly among patients with a history of acute episodes with psychotic and/or catatonic symptoms or with transient confusion

Lithium treatment and thyroid abnormalities

BACKGROUND: Although the interactions between lithium treatment and thyroid function have long been recognised, their clinical relevance is still controversial. This paper sets out a review of the literature to date, considering that lithium still represents the gold standard among prophylactic treatments of manic-depression several decades after its introduction. METHOD: PubMed database was used to search for English-language articles relating to lithium treatment and thyroid function. As the amount of relevant papers totalled several hundreds, this review refers to previous reviews, especially with regard to older literature. Moreover, the authors particularly refer to a series of studies of thyroid function performed in a cohort of patients at different stages of lithium treatment, who were followed up by their group from 1989 onwards. RESULTS: The main findings from this review included: a) lithium definitely affects thyroid function as repeatedly shown by studies on cell cultures, experimental animals, volunteers, and patients; b) inhibition of thyroid hormone release is the critical mechanism in the development of hypothyroidism, goitre, and, perhaps, changes in the texture of the gland which are detected by ultrasonic scanning; c) compensatory mechanisms operate and prevent the development of hypothyroidism in the majority of patients; d) when additional risk factors are present, either environmental (such as iodine deficiency) or intrinsic (immunogenetic background), compensatory potential may be reduced and clinically relevant consequences may derive; e) hypothyroidism may develop in particular during the first years of lithium treatment, in middle-aged women, and in the presence of thyroid autoimmunity; f) thyroid autoimmunity is found in excess among patients suffering from affective disorders, irrespective of lithium exposure; g) in patients who have been on lithium for several years, the outcome of hypothyroidism, goitre, and thyroid autoimmunity do not much differ from those observed in the general population; h) hyperthyroidism and thyroid cancer are observed rarely during lithium treatment. RECOMMENDATIONS: Thyroid function tests (TSH, free thyroid hormones, specific antibodies, and ultrasonic scanning) should be performed prior to starting lithium prophylaxis. A similar panel should be repeated at one year. Thereafter, annual measurements of TSH may be sufficient to prevent overt hypothyroidism. In the presence of raised TSH or thyroid autoimmunity, shorter intervals between assessments are advisable (4–6 months). Measurement of antibodies and ultrasonic scanning may be repeated at 2-to-3-year intervals. The patient must be referred to the endocrinologist if TSH concentrations are repeatedly abnormal, and/or goitre or nodules are detected. Thyroid function abnormalities should not constitute an outright contraindication to lithium treatment, and lithium should not be stopped if a patient develops thyroid abnormalities. Decisions should be made taking into account the evidence that lithium treatment is perhaps the only efficient means of reducing the excessive mortality which is otherwise associated with affective disorders

Bipolar disorder and antithyroid antibodies: review and case series

Mood disorders and circulating thyroid antibodies are very prevalent in the population and their concomitant occurrence may be due to chance. However, thyroid antibodies have been repeatedly hypothesized to play a role in specific forms of mood disorders. Potentially related forms include treatment-refractory cases, severe or atypical depression, and depression at specific phases of a woman's life (early gestation, postpartum depression, perimenopausal). With regard to bipolar disorder, studies of specific subgroups (rapid cycling, mixed, or depressive bipolar) have reported associations with thyroid antibodies. Offspring of bipolar subjects were found more vulnerable to develop thyroid antibodies independently from the vulnerability to develop psychiatric disorders. A twin study suggested thyroid antibodies among possible endophenotypes for bipolar disorder. Severe encephalopathies have been reported in association with Hashimoto's thyroiditis. Cases with pure psychiatric presentation are being reported, the antithyroid antibodies being probably markers of some other autoimmune disorders affecting the brain. Vasculitis resulting in abnormalities in cortical perfusion is one of the possible mechanisms

Affective psychosis, Hashimoto's thyroiditis, and brain perfusion abnormalities: case report

BACKGROUND: It has recently become evident that circulating thyroid antibodies are found in excess among patients suffering from mood disorders. Moreover, a manic episode associated with Hashimoto's thyroiditis has recently been reported as the first case of bipolar disorder due to Hashimoto's encephalopathy. We report a case in which Hashimoto's thyroiditis was suspected to be involved in the deteriorating course of mood disorder and discuss potential pathogenic mechanisms linking thyroid autoimmunity with psychopathology. CASE PRESENTATION: A 43-year-old woman, with a history of recurrent depression since the age of 31, developed manic, psychotic, and soft neurological symptoms across the last three years in concomitance with her first diagnosis of Hashimoto's thyroiditis. The patient underwent a thorough medical and neurological workup. Circulating thyroperoxidase antibodies were highly elevated but thyroid function was adequately maintained with L-thyroxine substitution. EEG was normal and no other signs of current CNS inflammation were evidenced. However, brain magnetic resonance imaging evidenced several non-active lesions in the white matter from both hemispheres, suggestive of a non-specific past vasculitis. Brain single-photon emission computed tomography showed cortical perfusion asymmetry particularly between frontal lobes. CONCLUSION: We hypothesize that abnormalities in cortical perfusion might represent a pathogenic link between thyroid autoimmunity and mood disorders, and that the rare cases of severe Hashimoto's encephalopathy presenting with mood disorder might be only the tip of an iceberg.

PW08-03 The use of drugs for mood disorders in Italy: Preliminary results

Background:Some community surveys in Italy have shown that a proportion of subjects without lifetime psychiatric diagnosis (anxiety/depression) used antidepressants. The prescription of AD in bipolar depression appears to be another largely underestimated problem in the clinical practice and is difficult to recognise by means of traditional epidemiological methods (lay interview and structured diagnostic tools).Objectives:The purpose is to use defined and validated international semi-structured interview as diagnostic instrument administered by expert clinicians to evaluate appropriateness and amount of over and under prescription of psychotropic drugs in different Italian community areas. The focus is on general antidepressant use and use in subjects with bipolar disorder and in subsyndromal depression.Methods:Study design: Community survey. Study population: sample randomly drawn, after stratification by sex and age, from the adult population of Municipal records in 6 Italian Regions: about 4000 persons will be interviewed. Tools: Questionnaire on psychotropic drugs consumption, prescription, health services utilisation;diagnostic Structured Clinical Interview np version;Mood Disorders Questionnaire; Short Form Health Survey. Ethical aspects: a signed informed consent for each candidate. The study was approved by the ethical committee of theItalain National Health Institute.Expected results:The study aims to identify the frequency of over and under prescription of psychotropic drugs in different Italian regions and the determinants of prescription related to physicians, patients, comorbidity and symptoms and to establish the basis for a cohort prospective study to assess the future changes

The Use of Antidepressant Drugs and the Lifetime Prevalence of Major Depressive Disorders in Italy

BACKGROUND: The increased use of antidepressant drugs (ADs) improved the response to the needs of care although some community surveys have shown that subjects without lifetime psychiatric diagnosis (anxiety/depression) used ADs. OBJECTIVES: To evaluate the appropriateness and amount of prescription of psychotropic drugs in people with lifetime diagnosis of Major Depressive Disorder (MDD) by means of community survey with a semi-structured interview as a diagnostic instrument, administered by clinicians. METHODS: STUDY DESIGN: community survey. STUDY POPULATION: samples randomly drawn, after stratification from the adult population of municipal records. Sample size: 4.999 people were drawn in 7 centres of 6 Italian regions. TOOLS: questionnaire on psychotropic drug consumption, prescription, health services utilization; Structured Clinical Interview for DSM-IV modified (ANTAS); Training: interviewers were trained psychologists or medical doctors. RESULTS: 3.398 subjects were interviewed (68% of the recruited sample). The lifetime prevalence of DSM-IV MDD was 4.3% in males and 11.5% in females; antidepressant drugs were taken by 4.7% of subjects, 2.9% male and 5.9% female. 38% of males and 57% of females with lifetime diagnosis of MDD were taking ADs. CONCLUSIONS: Compared with studies using lay interviewers and structured tools the prevalence of the MDD was quite lower; ADs use was higher and tallied well with the data regarding antidepressant sales in Italy; the correspondence between lifetime diagnosis of MDD and ADs use was closer