In vivo pharmacological evaluations of novel olanzapine analogues in rats: a potential new avenue for the treatment of schizophrenia

Olanzapine (Olz) is one of the most effective antipsychotic drugs commonly used for treating schizophrenia. Unfortunately, Olz administration is associated with severe weight gain and metabolic disturbances. Both patients and clinicians are highly interested in the development of new antipsychotics which are as effective as atypical antipsychotics but which have a lower propensity to induce metabolic side effects. In the present study, we examined two new derivatives of Olz; OlzEt (2-ethyl-4-(4′-methylpiperazin-1′-yl)-10Hbenzo[b]thieno[2,3-e][1,4]diazepine), and OlzHomo (2-ethyl-4-(4′-methyl-1′,4′-diazepan-1′-yl)-10H-benzo[b]thieno[2,3-e] [1,4]diazepine), for their tendency to induce weight gain in rats. Weight gain and metabolic changes were measured in female Sprague Dawley rats. Animals were treated orally with Olz, OlzEt, OlzHomo (3 or 6 mg/kg/day), or vehicle (n = 8), three times daily at eight-hour intervals for 5 weeks. Furthermore, a phencyclidine (PCP)-treated rat model was used to examine the prevention of PCP-induced hyperlocomotor activity relevant for schizophrenia therapy. Male Sprague Dawley rats were pre-treated with a single dose (3 mg/kg/day) of Olz, OlzEt, OlzHomo, or vehicle (n = 12), for 2 weeks. Locomotor activity was recorded following a subcutaneous injection with either saline or PCP (10 mg/kg). Olz was found to induce weight gain, hyperphagia, visceral fat accumulation, and metabolic changes associated with reduced histamatergic H1 receptor density in the hypothalamus of treated rats. In contrast, OlzEt and OlzHomo presented promising antipsychotic effects, which did not induce weight gain or fat deposition in the treated animals. Behavioural analysis showed OlzEt to attenuate PCP-induced hyperactivity to a level similar to that of Olz; however, OlzHomo showed a lower propensity to inhibit these stereotyped behaviours. Our data suggest that the therapeutic effectiveness of OlzHomo may be delivered at a higher dose than that of Olz and OlzEt. Overall, OlzEt and OlzHomo may offer a better pharmacological profile than Olz for treating patients with schizophrenia. Clinical trials are needed to test this hypothesis

KLINIK PSIKOFARMAKOLOJI BULTENI-BULLETIN OF CLINICAL PSYCHOPHARMACOLOGY

Objectives: Evidence from clinical, pharmacological and animal studies, have led to neurodevelopment, neurodegeneration, and dopamine hypotheses, and to the investigation of BDNF as a potential candidate molecule in the pathophysiology of schizophrenia, The aim of this study is to investigate the BNDF levels of schizophrenic patients with depression and compare them with major depression patients and controls in order to understand the nature of depressive symptoms seen in schizophrenia. Methods: The BDNF levels of eight schizophrenic patients with depressive symptomatology (SD) were compared with two control groups. The first group consisted of major depressed patients (MDD) (n=24) and the second was the healthy control group (n=26). Results: SD group had BDNF levels similar to control group and MDD group had significantly lower levels than the other two groups. Conclusion: This difference of BDNF levels between schizophrenia with depression group and major depression group supports the hypothesis of distinct etiologies

Needs of patients with Schizophrenia and their predictors

Objective: The aim of this study was to explore the needs of patients with schizophrenia and to determine the sociodemographic and clinical variables associated with these needs. Method: The study was carried out with 94 patients diagnosed with schizophrenia and their primary caregivers. The diagnoses were established based on DSM-IV-TR (American Psychiatric Association 1994) criteria. The patients' needs were evaluated with the Camberwell Assessment of Needs Scale (CAN), which reflects both the patient and the caregiver views on needs and problems. In addition, the Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, the Personal and Social Performance Scale, the Quality of Life Scale for Schizophrenia and the Perceived Family Burden Scale were used as data collection tools. Results: 'Psychotic symptoms' stood out as the most prevalent need to be met. 'Money' and 'intimate relations' were determined as the needs that the patients suffered most from. Being female, being married, living with families, having high school or higher education were found less associated with the needs. The variables explained 45.1% of the variance in predicting needs and 23.4% in predicting unmet needs. The Calgary Depression Scale for Schizophrenia and Perceived Family Burden Scale were significant predictors for patients and the PANSS-Positive Symptoms Scale for caregivers. Conclusion: Any treatment targeting solely the symptoms proves to be insufficient for patients with schizophrenia. Treatment planning should focus on the needs of patients and the needs identified by patients should be at the center of the treatment. A 'needs assessment' will make an important contribution not only to the planning of individual treatments but also to the planning of a community mental health services scheme and increasing its effectiveness. © 2018, Turkish Association of Nervous and Mental Health

The effect of the family history of diabetes on glucose metabolism of the patients recieving atypical antipsychotics [Atipik antipsikotik kullanan hastalarda ailede diyabet öykü sü olmasinin glukoz metabolizmasi üzerine olan etkisi]

Objective: Diabetes is observed 2-3 times more frequently in schizophrenic patients with comparison to the general population. Recently, many publications have reported diabetes related to atypical antipsychotics. Risk factors such as age, ethnicity, overweight, duration of obesity, physical activity, and family history of diabetes seem to help development of diabetes. This study aims to investigate how the glucose metabolism is affected from familial history of diabetes which is a risk factor for the disease. Method: Seventy patients who have a diagnosis of schizophrenia or other psychotic disorders and are treated with atypical antipsychotics for at least one year were recruited for the study. The patients were divided into two groups defined as those with or without a family history of diabetes. In order to evaluate the glucose metabolism fasting blood glucose, oral glucose tolerance, blood insuline, c-peptide, hemoglobine A1c, leptin and ghrelin levels were measured. Results: The results of the comparison of fasting blood glucose, oral glucose tolerance, blood insuline, c-peptide, hemoglobine A1c, leptin and ghrelin levels between two patient groups with and without family history of diabetesonly ghrelin levels were found to be statistically higher in the group of patients with a history of diabetes in their family; no other parameters have statistically significant differencesbetween two groups. Conclusion: Having a family history of diabetes may increase the probabality of disturbance in glucose metabolism of the patients receiving atypical antipsychotics. It would be reasonable to evaluate the risk factors prior to the treatment and routinely review the parameters required to evaluate the metabolic side effects in clinical follow-ups

The effect of theory of mind capacities of mothers of patients with schizophrenia on the severity of the diseases

Objective: Studies conducted with patients with schizophrenia and first-degree relatives show that, the pathology in theory of mind may be related to the risk of psychosis. The theory of mind capacities of the mothers may be effective in the prognosis of schizophrenia. The purpose of this study is to examine the effects of theory of mind capacities of patient mothers on the severity of the disease. Method: The study was conducted with 34 schizophrenic patients and their mothers, and 31 healthy mothers. Sociodemographic data was captures for all groups. In addition, PANSS was collected from patients and Reading the Mind in the Eyes Test was collected from the each patient mother. Results: There was no statistically significant difference between the age and education levels of the groups. The mothers of patients with schizophrenia performed significantly worse in the Reading the Mind in the Eyes Test than the control group. There was an inverse correlation between theory of mind capacity and the medication dose, PANSS general condition and PANSS total score. Discussion: The significant difference between the groups suggests that the impairment in the function of the theory of mind can be regarded as an endo-phenotype for schizophrenia. The low theory of mind capacities of the mothers of schizophrenia patients can cause the mothers to misunderstand the feelings of their patient which could lead to increase in disease severity and drugs use. © 2018 Turkish Association of Nervous and Mental Health

Cortisol response to stress in schizophrenia: Associations with oxytocin, social support and social functioning

Previous studies reported attenuated cortisol reactivity as one explanation for poor social functioning in schizophrenia. Recent research has demonstrated that both glucocorticoid and oxytocin systems are central to stress regulation. Here, we studied the associations between basal oxytocin, stress-induced cortisol levels, and social functioning and social support in schizophrenia. A mock job interview was used as an ecologically-valid social stressor in 32 schizophrenia patients. Blood samples were taken before and after stress induction to assess basal oxytocin and cortisol levels. In addition social functioning and social support scales were collected. Patients were divided into cortisol responders and non-responders according to percentage change following stress induction. Our findings revealed a possible subgroup of patients who did not exhibit attenuated cortisol responses. Importantly, cortisol responders had generally better social functioning, but perceived social support was not different between groups. There was also no evidence of a relationship between cortisol and oxytocin. This study highlights the heterogeneity of cortisol responses to stress in a schizophrenia population, and the importance of the relationship between social functioning and cortisol reactivity. These findings could be relevant when considering therapeutic interventions that manipulate endocrinology in order to improve real-world functioning. © 2018 Elsevier B.V