Early antipsychotic intervention and schizophrenia

Yang, Yao-Hsu; Lu, Chao; Lo, Shih-Mao; Peng, Chia-Ho; Liu, Yia-Ping

doi:10.1016/j.mehy.2015.05.014

Cited by 4 publications

(4 citation statements)

References 32 publications

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“…One example, among many, of a cognitive mechanism preserved across species, is that of sensorimotor gating, the ability to filter out irrelevant from relevant information. This phenomenon, present in humans (Hashimoto, 2005;Witten et al, 2016), rodents (Ma et al, 2015;Yang et al, 2015) and zebrafishes (Burgess and Granato, 2007;Knogler and Drapeau, 2014), can be disrupted in all three species with a dopamine agonist (Burgess and Granato, 2007;Larrauri et al, 2015;Talledo et al, 2009), thus mimicking the deficit seen in patients with schizophrenia. The abnormal response can further be reversed by antipsychotic agents in these three species (Burgess and Granato, 2007;Csomor et al, 2014;Zangrando et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

True alignment of preclinical and clinical research to enhance success in CNS drug development: a review of the current evidence

Goetghebeur

Swartz

2016

J Psychopharmacol

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Central nervous system pharmacological research and development has reached a critical turning point. Patients suffering from disorders afflicting the central nervous system are numerous and command significant attention from the pharmaceutical industry. However, given the numerous failures of promising drugs, many companies are no longer investing in or, indeed, are divesting from this therapeutic area. Central nervous system drug development must change in order to develop effective therapies to treat these patients. Preclinical research is a cornerstone of drug development; however, it is frequently criticised for its lack of predictive validity. Animal models and assays can be shown to be more predictive than reported and, on many occasions, the lack of thorough preclinical testing is potentially to blame for some of the clinical failures. Important factors such as translational aspects, nature of animal models, variances in acute versus chronic dosing, development of add-on therapies and understanding of the full dose-response relationship are too often neglected. Reducing the attrition rate in central nervous system drug development could be achieved by addressing these important questions before novel compounds enter the clinical phase. This review illustrates the relevance of employing these criteria to translational central nervous system research, better to ensure success in developing new drugs in this therapeutic area.

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Section: Introductionmentioning

confidence: 99%

True alignment of preclinical and clinical research to enhance success in CNS drug development: a review of the current evidence

Goetghebeur

Swartz

2016

J Psychopharmacol

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“…The animals were kept in a temperature–(22 ±4°C) and humidity–controlled (50±20%) room under a 12-h light/dark cycle (lights on from 07:00 to 19:00) and given ad libitum access to a standard laboratory chow diet (Ralston Purina, St. Louis, MO, USA) and sterile water. At their age of postnatal days 77–79 [ 13 ], rats in each rearing condition were randomly assigned to one of the two managements (sham control vs. 5-HT depletion surgery), thus made it totally 4 groups (SOC-sham, IR-sham, SOC-depletion, IR-depletion, N=8 for each) to enter the behavioral protocol (7 days after the surgery) for measuring their ASR and PPI under different doses of 8-OH-DPAT. Locomotor activity was also monitored in both SOC and IR rats under 5-HT depleted condition.…”

Section: Methodsmentioning

confidence: 99%

Effects of 5HT1A Activation on Gating Profile Following 5HT Depletion in Rats Lacking Social Attachment Since Weanling

Tai

Ko²,

Lin

et al. 2018

Psychiatry Investig

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Objective Central 5-HT1A receptor is involved in the modulation of sensorimotor gating function. However, its precise role is not clearly defined in developmentally social deprived (isolation rearing, IR) rats featured with impaired sensorimotor gating ability. We therefore aimed to examine the effects of 5HT1A activation on acoustic startle response (ASR) and prepulse inhibition (PPI) in IR rats in a condition of compromised presynaptic 5-HT functions. Methods Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletor, 5,7-DHT. Seven days later rats entered a protocol of 8-OH-DPAT, a 5-HT1A agonist, in which locomotor activity, ASR and PPI and their tissue levels of 5-HT were measured. Results Our results found that both IR and 5,7-DHT decreased the tissue concentration of 5-HT. IR-induced hyperactivity and gating impairment were unaffected by 5-HT depletion. 8-OH-DPAT strengthened the ASR in IR but not SOC rats and the drug-reduced PPI could be adjusted by 5,7-DHT pretreatment. 8-OH-DPAT at 100 μg/kg enhanced PPI in 5-HT-depleted SOC rats. However for IR rats, 8-OH-DPAT strengthened PPI in sham rats but downgraded it in depletion condition. Conclusion The integrity of central 5-HT system is important to 5-HT1A-modulated sensorimotor gating in isolation-reared rats.

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“…Previously we demonstrated that risperidone was more beneficial when administering earlier (i.e., adolescence) than later (i.e., young adulthood) in correcting the impairment of PPI in SIR rats [5]. In the present study, SIR rats that received risperidone intervention at different age would be measured for their metabolic parameters [blood pressure, body weight, plasma levels of triglyceride, total cholesterol (TC), high-density lipoprotein (HDL), lowdensity lipoprotein (LDL) and glucose].…”

Section: Introductionmentioning

confidence: 93%

“…However, high risk of metabolic abnormalities and its associated adverse cardiovascular effects leads to poor drug compliance and increased mortality rate [3,4]. It raises the concerns about the pros and cons of SGAs [5].…”

Section: Introductionmentioning

confidence: 99%

Effects of Early Risperidone Treatment on Metabolic Parameters in Socially Isolated Rats—Implication of Antipsychotic Intervention across Developmental Stages of Schizophrenia

Tzeng¹,

Yang²,

Lin³

et al. 2023

J. Integr. Neurosci.

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Background: Second-generation antipsychotics (SGAs) is thought responsible for the metabolic abnormalities of schizophrenic patients, however, some untreated schizophrenic patients had already developed problems with glucose metabolism. The present study examined the hypothesis that schizophrenia itself but not risperidone, an extensively employed SGA, is accountable for metabolic abnormalities. Methods: A 56-day risperidone regimen (1 mg/kg/day) was employed for rats of social isolation rearing (SIR) beginning at different developmental stage (28 or 56 days after weaning, i.e., adolescent and young adulthood, respectively). Metabolic parameters including body weight, systolic blood pressure (SBP), triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and plasma glucose were measured at baseline, 28, and 56 days of the regimen. Oral glucose tolerance test (OGTT) was performed at the end of the regimen. Insulin function was evaluated by area under the curve (AUC) of OGTT, homeostasis model assessment-insulin resistance (HOMA-ir), and Matsuda index. Results: Our results demonstrated that: (i) SIR rats presented higher body weight, plasma triglyceride, and HOMA-ir than social controls. (ii) Higher insulin resistance was specifically presented in young adult rather than adolescent SIR rats. (iii) Adolescent drugged rats showed a lower level of LDL in day 28 of the regimen than young adult. Risperidone led to a lower LDL level in only young adult IR rats in day 56 than undrugged rats. (iv) SIR-induced dysregulation of insulin can be reversed by chronic risperidone treatment beginning at adolescence but not young adulthood. Conclusions: Our findings support the primary role of schizophrenia in metabolic abnormalities and risperidone appear beneficial when administered earlier.

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Early antipsychotic intervention and schizophrenia

Cited by 4 publications

References 32 publications

True alignment of preclinical and clinical research to enhance success in CNS drug development: a review of the current evidence

True alignment of preclinical and clinical research to enhance success in CNS drug development: a review of the current evidence

Effects of 5HT1A Activation on Gating Profile Following 5HT Depletion in Rats Lacking Social Attachment Since Weanling

Effects of Early Risperidone Treatment on Metabolic Parameters in Socially Isolated Rats—Implication of Antipsychotic Intervention across Developmental Stages of Schizophrenia

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