Subclinical thyroid disease (SCTD) is defined as serum free T4 and free T3 levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and cardiovascular risk. Here, we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine t...

The clinical significance of subclinical thyroid dysfunction.

The Stanley Foundation Bipolar Treatment Outcome Network. II. Demographics and illness characteristics of the first 261 patients.

Objective: To describe the growth of developmental epidemiology in the past decade and to illustrate it with examples of recent studies. Method: A review of publications on developmental epidemiology in the past 10 years and a discussion of some key examples. Results: The authors describe how the interaction between developmental psychopathology and psychiatric epidemiology has produced developmental epidemiology, the study of patterns of distribution of psychiatric disorders in time as well as in space. They give two examples of the kinds of questions that developmental epidemiology can help to answer: (1) Is the prevalence of autism increasing? Does the use of vaccines explain the increase? (2) Is there an epidemic of child and adolescent depression? Finally, they describe two areas of science that are beginning to inform developmental epidemiology: molecular genetics and the use of biological measures of stress. Conclusions: While child and adolescent psychiatric epidemiology continues, as described in the first of these reviews, to address questions of prevalence and burden, it has also expanded into new areas of research in the past decade. In the next decade, longitudinal epidemiological data sets with their rich descriptive data on psychopathology and environmental risk over time and the potential to add biological measures will provide valuable resources for research into gene-environment correlations and interactions.

10-year research update review: the epidemiology of child and adolescent psychiatric disorders: II. Developmental epidemiology.

Background Low birth weight is a risk factor for coronary heart disease, diabetes, stroke and hypertension. Depression is highly associated with these conditions.

Aims To examine the association between birth weight and depression in late life.

Method A total of 882 singleton term births in the 1920s had contemporary records of birth weight and weight at 1 year. At 68 years all completed the Geriatric Depression Scale and 867 completed the Geriatric Mental State Examination. A logistic regression was used to analyse the associations between depression, birth weight and weight at 1 year while adjusting for known risk factors.

Results Current social class, social class at birth, recent bereavement, social isolation and physical illness increased the risk of depression. After adjusting for these and weight at 1 year, the odds ratios for depression among men, but not women, rose incrementally with decreasing birth weight (1.0, 12.8; for continuous variable, P <0.007).

Conclusions Foetal undernutrition predisposes men to depression in late adult life. If replicated, these results would suggest a neurodevelopmental aetiology of depression, possibly mediated by programming of the hypothalamic—pituitary—adrenal axis.

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Birth weight and the risk of depressive disorder in late life

Thyroid hormones play a critical role in the metabolic activity of the adult brain, and neuropsychiatric manifestations of thyroid disease have long been recognised. However, it is only recently that methodology such as functional neuroimaging has been available to facilitate investigation of thyroid hormone metabolism. Although the role of thyroid hormones in the adult brain is not yet specified, it is clear that without optimal thyroid function, mood disturbance, cognitive impairment and other psychiatric symptoms can emerge. Additionally, laboratory measurements of peripheral thyroid function may not adequately characterise central thyroid metabolism. Here, we review the relationship between thyroid hormone and neuropsychiatric symptoms in patients with primary thyroid disease and primary mood disorders.

The thyroid-brain interaction in thyroid disorders and mood disorders.

OBJECTIVE Cognitive and affective functioning is sensitive to changes in thyroid hormones. We have sought to determine: (1) the prevalence of thyroid function abnormalities in a psychiatric population on admission (as compared to the prevalence in a normal population), and (2) whether such thyroid function abnormalities are associated with the occurrence or development of cognitive and affective disorders.

DESIGN Serum was collected 2–3 weeks after hospitalization in 3 major clinics from 3756 psychiatric patients in 1987–1990, stored, and assayed in 1993 for the presence of antibodies against the TSH-receptor and thyroperoxidase (TPO-Ab) and for TSH levels. The psychiatric cohort was matched with a control population of healthy individuals living in the same area (n = 1877).

The prevalence study was followed by a case-control study involving patients from one clinic that had routinely assigned a DSM-IIIR classification to its patients. Cases were those admissions with thyroid abnormalities and three subgroups of cases were randomly formed demonstrating either TSH less than 0.4 mU/l (n = 44) or over 4.0 mU/l (n = 44), or TPO-Ab positivity (n = 50). Cases were compared to random controls from the same psychiatric population, viz patients without thyroid abnormalities (n = 83). Comparison was with respect to their psychiatric follow-up diagnosis (the investigator was blinded to the thyroid test results).

RESULTS Prevalence study. The percentage of patients positive for TSH-receptor-Ab was 0.26 (9/3504), for TPO-Ab was 10.0 (331/3316) and outside the TSH range of 0.4–4.0 mU/l was 10.0 ((332/3316): 5.9% (198/3316) >4.0 mU/l and 4.1% (134/3316) <0.4 mU/l). Abnormal total thyroxine levels were found in only 9.8% of subjects with abnormal TSH, indicating the predominantly subclinical character of the thyroid alteration. In comparison, the healthy area controls over 55 years of age showed the same prevalence of positive TPO-antibodies and TSH under 0.4 mU/l, but a higher prevalence of TSH over 4.0 mU/l.

Case-control study. In the case control analysis differences could not be noticed with regard to prevalences of dementia, schizophrenia or other psychiatric illnesses apart from the prevalence of affective disorders which were more prevalent in TPO-Ab positive patients and patients with a low serum TSH. Since prior use of lithium, carbamezapine, carbimazole and/or thyroxine could be a factor of importance in this association, analyses were also carried out excluding patients with such prior drug use. In these analyses affective disorders were still more prevalent in patients with a low serum TSH (particularly in males, 40% in cases vs 9% in controls, P   4.0 mU/l) and a subgroup of the affective disorders, viz with a rapid cycling of bipolar disorder (18% in cases vs 0% in controls, P < 0.001).

CONCLUSION Thoug h causal relations cannot be determined from this cross-sectional study, this admission survey found early forms of autoimmune thyroid disease, sometimes characterized only by TPO-Abs, highly significantly associated with rapid cycles of a bipolar disorder. It also found a weak association between subclinical hyperthyroidism (low serum TSH without TPO-Ab positivity) and affective disorder.

H. A. P. C. Oomen

Papers

The prevalence of affective disorder and in particular of a rapid cycling of bipolar disorder in patients with abnormal thyroid function tests