Behavioral and metabolic effects of the atypical antipsychotic ziprasidone on the nematode Caenorhabditis elegans.

Atypical antipsychotics are associated with metabolic syndrome, primarily associated with weight gain. The effects of Ziprasidone, an atypical antipsychotic, on metabolic syndrome has yet to be evaluated. Here in, we evaluated lipid accumulation and behavioral changes in a new experimental model, the nematode Caenorhabditis elegans (C. elegans). Behavioral parameters in the worms were evaluated 24 h after Ziprasidone treatment. Subsequently, lipid accumulation was examined using Nile red, LipidTox green and BODIPY labeling. Ziprasidone at 40 µM for 24 h effectively decreased the fluorescence labeling of all markers in intestinal cells of C. elegans compared to control (0.16% dimethyl sulfoxide). Ziprasidone did not alter behaviors related to energetic balance, such as pharynx pumping, defecation cycles and movement. There was, however, a reduction in egg-production, egg-laying and body-length in nematodes exposed to Ziprasidone without any changes in the progression of larval stages. The serotoninergic pathway did not appear to modulate Ziprasidone's effects on Nile red fluorescence. Additionally, Ziprasidone did not alter lipid accumulation in daf-16 or crh-1 deletion mutants (orthologous of the transcription factors DAF-16 and CREB, respectively). These results suggest that Ziprasidone alters reproductive behavior, morphology and lipid reserves in the intestinal cells of C. elegans. Our results highlight that the DAF-16 and CREB transcription factors are essential for Ziprasidone-induced fat store reduction.

Is the serotonin transporter polymorphism (5-HTTLPR) a potential marker for suicidal behavior in bipolar disorder patients?

BACKGROUND: Suicide prediction is a huge challenge for mental health workers. Structured interviews based on epidemiological and clinical factors don't show effectiveness for suicide prevention. Biological markers, such as 5-HTTLPR, could help for identification of potential suicide attempters. METHODS: We evaluated 198 bipolar patients and 103 health controls, using a structured interview according to DSM-IV criteria. Genotyping, blind of clinical assessment for identification of S carriers and structured interviews were performed in order to describe clinical and epidemiological factors which could be associated with suicide behavior. Statistical analyses were calculated by the x(2) test and logistic regression model. RESULTS: We found that 26.77% and 16.67% had a lifetime history of non violent suicide attempt and violent suicide attempt, respectively. The clinical factors associated with violent and non violent suicide attempt had several differences. Violent suicide attempters had an earlier illness onset and had a higher number of psychiatric comorbidities (borderline personality disorder, panic disorder and alcoholism). The frequency of S allele carriers was higher only in those patients who had made a violent suicide attempt in their lifetime (x(2)=16.969; p=0.0001). In a logistic regression model including these factors, S allele carrier (5-HTTLPR) was the only factor associated with violent suicide attempt. LIMITATIONS: Sample size and retrospective assessment of suicide behavior history are the limitations of this study. CONCLUSIONS: Our study showed that serotonin polymorphism (5-HTTLPR) is strongly associated with violent suicidal behavior in BD patients. If confirmed, our results could be an important step to create a genetic tool for long-term suicide prediction.