Does unilateral dopamine deficit contribute to depression?

A system of emotional control of behavior is believed to be lateralized to the right hemisphere. Given that dopaminergic pathways are involved in affective behavior, depression, which is recognized as an integral part of Parkinson's disease, may be associated with a dopamine imbalance. The present study examined this hypothesis in patients with unilateral symptomatology indicating either left hemisphere parkinsonism (LHP) or right hemisphere parkinsonism (RHP). Sixteen patients were tested on a battery of neuropsychological tests and several scales for evaluating mood. The two groups did not differ significantly on either cognitive or emotional measures. However, RHP patients rated themselves higher on the Present Scale of Cantril, and showed some neglect of the left visual field, as compared to LHP patients.     

Genetic susceptibility in thyroid autoimmunity

The autoimmune thyroid diseases (AITD) include Graves' disease (GD) which manifests in hyperthyroidism and Hashimoto's thyroiditis (HT), manifesting as hypothyroidism. Genetic susceptibility in combination with external factors (e.g. dietary iodine) are believed to initiate the autoimmune response to thyroid antigens in AITD. Indeed, there is solid epidemiological data to support a strong genetic influence on the etiology of AITD including family and twin studies. Recently, there has been significant progress toward the identification of the AITD susceptibility genes. Several loci (genetic regions) that are linked with AITD have been mapped and in some of these loci putative AITD susceptibility genes have been identified. Some of these loci predispose to a single phenotype (GD or HT), while other loci are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg) and it is likely that the final disease phenotype is a result of an interaction between these loci, as well as environmental influences.     

Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute Gi/o- coupled receptor activation inhibits the activity of several AC isozymes, including Ca2+/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute Mu-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of Gbetagamma subunits (Gbetagamma scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that Gbetagamma is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.     

Two-year evaluation of the logic model for developing a psycho-oncology service

OBJECTIVE: The objective of this study was to test whether reorganizing a psycho-oncology service in a planned and focused manner would maximize the achievement of coherent developmental goals. METHODS: The logic model, a strategic program development tool, was used in the context of a public psychiatry fellowship to analyze and plan the organizational objectives of a psycho-oncology service. To assess the efficacy of the logic model, a two-year prospective evaluation of the model's outcome measures was performed. RESULTS: The psycho-oncology service was systematically reorganized through use of the logic model. Qualitative and quantitative data identified the degree of goal achievement. Most of the short- and medium-term clinical, educational, and research goals, as measured by outcome measures, had been realized at the two-year point. CONCLUSIONS: The logic model facilitated the effective reorganization of a psycho-oncology program by analyzing the existing service, developing pertinent goals, and then measuring goal attainment. These findings will be useful to psychiatric services interested in rational program development and service delivery, especially in small and medium hospitals with limited resources.     

Novelty seeking and harm avoidance in Parkinson's disease: effects of asymmetric dopamine deficiency

OBJECTIVES: Although changes in novelty seeking and harm avoidance have been reported among patients with Parkinson's disease (PD), the findings regarding the neurochemical correlates of such changes are inconsistent. This study was designed to examine the hypothesis that different patterns of motor and neurochemical asymmetry in PD may have contributed to the conflicting results. METHODS: Forty PD patients (divided into two groups according to initial asymmetry in dopamine deficit: left hemisphere, n = 22; right hemisphere, n = 18) and 17 age matched healthy controls completed the Tridimensional Personality Questionnaire (Cloninger, 1987). RESULTS: Only patients with greater dopamine loss in the left hemisphere showed reduced novelty seeking, whereas only patients with reduced dopamine in the right hemisphere reported higher harm avoidance than matched healthy controls. Novelty seeking was not associated with disease duration, current motor symptoms, or medication, whereas harm avoidance was significantly correlated only with the severity of bradykinesia and depression. CONCLUSIONS: Approach and avoidance reflect different patterns of dopaminergic asymmetry. Whereas reduced novelty seeking reflects deficit in the mesolimbic branch of ascending dopamine transmission in the left hemisphere, increased harm avoidance is associated with greater dopamine loss in the right striatum.     

The contribution of immune regulatory and thyroid specific genes to the etiology of Graves' and Hashimoto's diseases

The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine) are believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT) and some are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg). Most likely these loci interact and their interactions may influence disease phenotype and severity.     

A C/T single nucleotide polymorphism at the tyrosine kinase domain of the insulin receptor gene is associated with polycystic ovary syndrome

OBJECTIVE: To examine whether the insulin receptor (INSR) gene contributes to genetic susceptibility to the polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Academic endocrinology clinic. PATIENT(S): Ninety-nine women with PCOS as defined by the National Institutes of Health consensus and polycystic ovaries on ultrasonography, and 136 healthy controls. MAIN OUTCOME MEASURE: Frequency of genotypes of a single nucleotide polymorphism of the INSR gene in patients and controls. RESULT(S): After stratification of participants by body mass index, the frequency of the uncommon T allele of the INSR single nucleotide polymorphism was significantly increased in lean patients with PCOS (body mass index < or =27 kg/m2) compared with lean controls (relative risk, 2.1). CONCLUSION(S): The INSR gene is a susceptibility gene for PCOS among lean patients with PCOS. It remains to be determined whether the exon 17 C/T single nucleotide polymorphism is the susceptibility single nucleotide polymorphism for PCOS or whether it is in linkage disequilibrium with another INSR gene polymorphism.