Frontal D2/3 Receptor Availability in Schizophrenia Patients Before and After Their First Antipsychotic Treatment: Relation to Cognitive Functions and Psychopathology.

BACKGROUND: We have previously reported associations between frontal D2/3 receptor binding potential positive symptoms and cognitive deficits in antipsychotic-naïve schizophrenia patients. Here, we examined the effect of dopamine D2/3 receptor blockade on cognition. Additionally, we explored the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms. METHODS: Twenty-five antipsychotic-naïve first-episode schizophrenia patients were examined with the Positive and Negative Syndrome Scale, tested with the cognitive test battery Cambridge Neuropsychological Test Automated Battery, scanned with single-photon emission computerized tomography using the dopamine D2/3 receptor ligand [(123)I]epidepride, and scanned with MRI. After 3 months of treatment with either risperidone (n=13) or zuclopenthixol (n=9), 22 patients were reexamined. RESULTS: Blockade of extrastriatal dopamine D2/3 receptors was correlated with decreased attentional focus (r = -0.615, P=.003) and planning time (r = -0.436, P=.048). Moreover, baseline frontal dopamine D2/3 binding potential and positive symptom reduction correlated positively (D2/3 receptor binding potential left frontal cortex rho = 0.56, P=.003; D2/3 receptor binding potential right frontal cortex rho = 0.48, P=.016). CONCLUSIONS: Our data support the hypothesis of a negative influence of D2/3 receptor blockade on specific cognitive functions in schizophrenia. This is highly clinically relevant given the well-established association between severity of cognitive disturbances and a poor functional outcome in schizophrenia. Additionally, the findings support associations between frontal D2/3 receptor binding potential at baseline and the effect of antipsychotic treatment on positive symptoms.

Well-being and depression in individuals with subclinical hypothyroidism and thyroid autoimmunity - a general population study.

BACKGROUND: The association between subclinical hypothyroidism (SCH), with and without raised thyroid peroxidase antibodies (anti-TPO), and well-being or depression is still controversial, in spite of many studies on the topic. AIMS: In this large general population study of 8214 individuals, we aim to clarify the significance of elevated levels of anti-TPO as a marker of poor well-being and depression in euthyroid individuals and individuals with SCH. METHODS: In participants from the Danish General Suburban Population Study (GESUS), serum thyroid stimulating hormone (TSH), total triiodothyronine (tT3), free thyroxine (fT4) and anti-TPO was measured. Prevalence of poor well-being and depression was measured using the WHO-5 Well-being questionnaire and WHO MDI [Major (ICD-10) Depression Inventory] questionnaire. RESULTS: Raw score for well-being or depression overall and stratified for sex was not more significantly different in euthyroid individuals than in individuals with SCH, with or without high anti-TPO, except that euthyroid women with elevated anti-TPO had better well-being (P = 0.03) compared with euthyroid women with anti-TPO within the reference range. CONCLUSION: Elevated anti-TPO levels cannot be used as a general marker of poor well-being or depression in the general population.