The most effective treatment for hepatitis C virus (HCV) is interferon-alpha (IFN) therapy in combination with ribavirin. Although symptoms of depression are among the most common side effects of IFN therapy in treating patients with HCV, the mechanisms by which IFN produces these neuropsychiatric side effects remain unclear. In the brain, IFNs are involved in a number of regulatory functions, including but not limited to regulation of the endocrine system via the hypothalamic-pituitary-adrenal and -thyroid axes. The purpose of this study was to assess the effect of IFN therapy on thyroid function and to characterize the relationship between thyroid dysfunction and major depressive disorder during IFN therapy in patients with hepatitis C. Thirty-three patients with HCV were administered the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis I Disorders (SCID) and completed the Beck Depression Inventory (BDI). Patients were on IFN for an average of 6 to 12 months depending on their viral genotype. Serum samples were collected at baseline, during and after IFN therapy, and measured for free thryoxine (FT4) and TSH levels. Patients who developed IFN-induced depression were treated with selective serotonin reuptake inhibitor antidepressants. Only one patient developed transient IFN-induced overt hypothyroidism, but he did not develop depression. Analysis of variance showed that there were no significant differences in either FT4 or TSH serum levels between patients who developed major depressive disorder (MDD) (no.= 10) during IFN therapy and those who did not (no.=23). These results illustrate the frequency and severity of depressive symptoms associated with IFN therapy and the apparent absence of a relationship between IFN-induced MDD and changes in thyroid function.

Adult↗

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Gender differences in the brain: are they relevant to the pathogenesis of schizophrenia?

Gender differences are present in the clinical expression of schizophrenia, age of onset, course of illness, and response to pharmacologic treatment. These differences are not surprising in view of the normal gender differences in brain growth, differentiation, adult brain structure, and neurochemistry. The present review examines what is presently known about brain gender differences, and whether this information is consistent with the published reports of brain functional and morphological abnormalities in schizophrenia. Whether gender differences in the brain can explain the gender differences in clinical aspects of the disorder remains unknown.

Brain↗

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Prophylactic treatment of depression induced by interferon-alpha.

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Aged↗

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Resistance to thyroid hormone: implications for neurodevelopmental research on the effects of thyroid hormone disruptors.

Thyroid hormones are essential for normal behavioral, intellectual, and neurological development. Congenital hypothyroidism, if not treated, can result in irreversible mental retardation, whereas thyroid diseases with more moderate impairment of thyroid function, such as resistance to thyroid hormone, cause less severe intellectual and behavioral abnormalities, including attention deficit hyperactivity disorder. There is increasing evidence that exposure to certain synthetic compounds, including dioxins and polychlorinated biphenyls (PCBs), during the perinatal period can also impair learning, memory, and attentional processes in offspring. Animal and human studies suggest that exposure to these environmental toxicants impair normal thyroid function. Although the precise mechanisms of action of the adverse effects these toxicants have on neurodevelopment have not yet been elucidated, it is possible that they are partially or predominantly mediated by alterations in hormone binding to the thyroid hormone receptor. The convergence of studies that examine the neurodevelopmental consequences of moderate impairment of thyroid function, such as is found in resistance to thyroid hormone, with those studies that demonstrate the adverse behavioral and cognitive effects of perinatal exposure to dioxins and PCBs serves to generate new hypotheses to test in a research setting. Such studies may provide new insights into the basic pathogenesis of developmental neurotoxicity following exposure to thyroid-disrupting synthetic compounds.

Animals↗

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Relationship between prior course of illness and neuroanatomic structures in bipolar disorder: a preliminary study.

OBJECTIVE: In this preliminary study, we examined the relationships between prior course and severity of illness and size of the hippocampus, temporal lobes, and third and lateral ventricles in patients with bipolar disorder. BACKGROUND: The few studies that have investigated relationships between course of illness measures and neuroanatomic structures in patients with bipolar disorder found divergent results. METHOD: Twenty-six outpatients, who met Diagnostic and Statistical Manual, Third Edition - Revised (DSM-III-R) criteria for bipolar disorder, received a magnetic resonance imaging (MRI) scan, from which volumes of the temporal lobes, hippocampi, third ventricle, and areas of the lateral ventricles were calculated. Prior course of illness variables were determined using the NIMH Life-Chart Method and were correlated to the volumetric measures of neuroanatomic structures using multiple regression analyses. RESULTS: A longer duration of illness was paradoxically associated with a larger left temporal lobe volume whether patients with a history of substance abuse were removed from the analyses. CONCLUSIONS: Additional studies are needed to both replicate and further examine the association of prior course of illness and larger hippocampal and ventricular volumes in bipolar disorder.

Adult↗

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Networking: tactic for the Supreme Court case.

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Humans↗