5-HTTLPR polymorphism and anxious preoccupation in early breast cancer patients.

BACKGROUND: Difficulties in coping with cancer, and the accompanying anxious and depressive symptoms, have been shown to affect the mood and the quality of life in breast cancer patients. 5-Hydroxytryptamine Transporter Gene-linked Polymorphic Region (5-HTTLPR) functional polymorphism of serotonin transporter has been shown to influence the adaptation to stressful life events. The aim of this prospective study was therefore to examine the association of 5-HTTLPR with the mental adaptation to cancer diagnosis and treatment. PATIENTS AND METHODS: Forty eight consecutive patients with early mammary carcinoma were evaluated at enrolment and at follow up after one and three months. The patients were characterized psychometrically using the Hospital Anxiety and Depression Scale (HADS) and the Mini-Mental Adjustment to Cancer Scale (Mini-MAC); 5-HTTLPR allelic variants were determined using PCR-based techniques. RESULTS: In women with early breast cancer, the mental adaptation to the disease was associated with high scores of avoidance and anxious preoccupation of Mini-MAC, which decreased with time at follow up. Anxious preoccupation decreased with time less in patients with the S/S and S/L genetic variant of 5-HTTLPR as compared with the L/L carriers (p=0.023), indicating gene - environment interactions. CONCLUSIONS: These results indicate that the characterization of 5-HTTLPR allows the identification of breast cancer patients in greater risk of mental suffering, for which specific intervention may be focused; in case of drug therapy, they provide indications for the choice of most appropriate agent in a pharmacogenetic perspective.

Psychological response to cancer: role of 5-HTTLPR genetic polymorphism of serotonin transporter.

BACKGROUND: 5-HTTLPR genetic polymorphism of serotonin transporter (SERT) and stressful life events facilitate depression. The aim of this investigation was therefore to determine the correlations between SERT polymorphism and mental adjustment to cancer. PATIENTS AND METHODS: Breast cancer patients early after surgery, and subjects with various advanced tumours were recruited, evaluated using the Mini Mental Adjustment to Cancer Scale and Hospital Anxiety and Depression Scale (HADS), and genotyped. RESULTS: In early breast cancer patients (n=53), hopelessness-helplessness (HH) and anxious preoccupation (AP) significantly correlated with depression and anxiety; avoidance (AV) correlated with anxiety. Advanced cancer patients (n=73) displayed similar correlations, and a negative correlation of HADS depression with fighting spirit (FS) and AV. The stratification for 5-HTTLPR showed that early breast cancer carriers of the L/L variant displayed a significant correlation between HH and depression. CONCLUSION: Among early breast cancer patients, a specific set, characterized by their 5-HTTLPR variant, display differential correlations between HH and depression, with possible implications for treatment options.

Clinical experience with risperidone in the treatment of behavioral and psychological symptoms of dementia.

Dementia is a neuropsychiatric disorder characterized by cognitive impairment and behavioral and psychological symptoms. The efficacy and tolerability of risperidone for treating dementia-associated psychological and behavioral disturbances were evaluated in a study of 135 patients aged 60-85 years with DSM-IV diagnoses of Alzheimer's disease. All were treated with risperidone at a starting dose of 0.5 mg once daily at bedtime. After the first 3 days of therapy the dosage was increased to 1 mg in 2 doses (morning and evening), then a further 0.5 mg was added (alternatively in the morning and in the evening) every three days until attenuation of the psychiatric symptoms. The response to treatment was evaluated for a period of 12 weeks by the Neuropsychiatric Inventory (NPI) and the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). Both NPI and BEHAVE-AD were administered at the baseline visit, and after 4 and 12 weeks of therapy. Tolerability was assessed by the incidence of clinically evident side effects. The mean dose at endpoint was 1 mg/day of risperidone. The mean NPI score was 28.80+/-13.92 at start, 15.55+/-11.25 after 4 weeks and 8.30+/-7.00 at endpoint. The reduction in mean scores at 4 and 12 weeks was statistically significant in most of the Neuropsychiatric Inventory items, except for appetite disorders (p<0.0001). The mean BEHAVE-AD score was 20.44+/-3.92 at start, 13.50+/-11.39 after 4 weeks and 8.03+/-7.80 at endpoint. All the items showed a statistically significant improvement after 4 and 12 weeks (p<0.0001). The results were better at 12 than at 4 weeks. In our elderly patients with dementia low-dose risperidone was well tolerated and associated with reductions in BPSD, in particular agitation, aggression, irritability, delusions, sleep disorders, anxiety and phobias.