Negative Correlation between Negative Symptoms of Schizophrenia and Testosterone Levels

Goyal, Ruchi; Sagar, Rajesh; Ammini, AC; Khurana, Madan Lal; Alias, Aliza

doi:10.1196/annals.1314.042

Cited by 75 publications

(49 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our findings provide evidence that gonadal hormones are also important in the NOR task in males and that androgens may play especially critical roles in its modulation in this sex. Further, our findings of abnormally low values of the DI with GDX that are attenuated by replacement with TP but not E are an intriguing fit with clinical evidence of diminished recognition memory in cases of hypogonadism (Salminen et al, 2004;Salminen et al, 2005) and NOR deficits of schizophrenia in male patients (Heckers et al, 2000), which are a part of the cluster of negative, prefrontal cortically mediated symptoms in this disease for which severity has also been directly linked to decreased circulating testosterone levels (Akhondzadeh et al, 2006;Goyal et al, 2004;Huber et al, 2005;Ko et al, 2007;Shirayama et al, 2002;Taherianfard and Shariaty, 2004).…”

Section: Hormone Sensitivity Of the Nor Task: Comparison To Previous supporting

confidence: 50%

Effects of gonadectomy and hormone replacement on a spontaneous novel object recognition task in adult male rats

Aubele

Kaufman²,

Montalmant

et al. 2008

Hormones and Behavior

101

View full text Add to dashboard Cite

Recent studies in adult male rats have shown that gonadal hormones influence performance on certain working memory and other types of cognitive tasks that are sensitive to lesions of the medial and/or orbital prefrontal cortices. This study asked whether gonadal hormone modulation of prefrontal cortical function in males also extends to the perirhinal division of the rat prefrontal cortex. Specifically, sham-operated control, gonadectomized, and gonadectomized rats supplemented with testosterone propionate or estradiol were tested on a spontaneous novel object recognition task, a paradigm where performance has been shown to be impaired by perirhinal cortical lesions. Using analyses of variance, regression analyses and post-hoc testing to evaluate group differences, it was found that during both the sample and test trials of the task all four groups spent similar absolute and proportional amounts of time ambulating, rearing, stationary, and exploring the two objects present. All groups also explored each of the two identical objects present during sample trials equally. However, during the test trials, only the control and gonadectomized rats given testosterone showed the expected increase in exploration of the novel objects presented, whereas the gonadectomized and gonadectomized, estradiol-supplemental groups continued to explore the novel and familiar objects equally. That regression analyses also identified significant correlations between low bulbospongiosus muscle weight and impaired novel vs. familiar object discrimination further indicates that gonadectomy in adult male rats adversely affects spontaneous novel object recognition in an androgen-sensitive, estrogen-insensitive manner.

show abstract

Section: Hormone Sensitivity Of the Nor Task: Comparison To Previous supporting

confidence: 50%

Effects of gonadectomy and hormone replacement on a spontaneous novel object recognition task in adult male rats

Aubele

Kaufman²,

Montalmant

et al. 2008

Hormones and Behavior

101

View full text Add to dashboard Cite

show abstract

“…NS levels have been correlated to the severity of symptoms in schizophrenic patients (Akhondzadeh et al, 2006;Goyal et al, 2004;Shirayama et al, 2002). This possibility is supported by the notion that environmental stress, a major factor in the etiology of psychosis (Howes et al, 2004), has been shown to affect the metabolism of several NSs (Barbaccia et al, 2001).…”

Section: Introductionsupporting

confidence: 54%

“…Similarly, testosterone, but not DHT, increases PPI in rats (Van den Buuse and Eikelis, 2001). Testosterone levels are also inversely correlated to the incidence of negative symptoms in schizophrenia and to the poverty of clinical outcome (Akhondzadeh et al, 2006;Goyal et al, 2004). The participation of other NSs, such as glucocorticoids, in the effects of 5AR inhibitors cannot be completely ruled out, in view of their major role in stress and psychosis (Wada et al, 2001).…”

Section: -A-reductase Inhibitors In Models Of Psychosis M Bortolato mentioning

confidence: 99%

“…For instance, synthetic androgens might also induce and precipitate psychotic-like abnormalities (Trenton and Currier, 2005). Conversely, testosterone and dehydroepiandrosterone may have antipsychotic potential (Strous, 2005;Strous et al, 2003;Van den Buuse and Eikelis, 2001) and their levels are typically low in schizophrenia patients (Goyal et al, 2004;Huber et al, 2005;Taherianfard and Shariaty, 2004).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Bortolato

Frau

Orrù

et al. 2008

Neuropsychopharmacol

View full text Add to dashboard Cite

Recent evidence indicates that neuroactive steroids may participate in the pathogenesis of schizophrenia spectrum disorders, yet the mechanisms of this involvement are elusive. As 5-a-reductase (5AR) is the rate-limiting enzyme of one of the two major metabolic pathways in brain steroidogenesis, we investigated the effects of its blockade in several rat models of psychotic-like behavior. The 5AR inhibitor finasteride (FIN, 60 or 100 mg/kg, intraperitoneal, i.p.) dose-and time-dependently antagonized prepulse inhibition (PPI) deficits induced by apomorphine (APO, 0.25 mg/kg, subcutaneous, s.c.) and d-amphetamine (AMPH, 5 mg/kg, s.c.), in a manner analogous to haloperidol (HAL, 0.1 mg/kg, i.p.) and clozapine (CLO, 5 mg/kg, i.p.). Similar results were observed with the other 5AR inhibitors dutasteride (DUT, 40 or 80 mg/kg, i.p.) and SKF 105111 (30 mg/kg, i.p.). FIN (60 or 100 mg/kg, i.p.) also reduced hyperlocomotion induced by AMPH (1 or 3 mg/kg, s.c.) and attenuated stereotyped behaviors induced by APO (0.25 mg/kg, s.c.). Nevertheless, FIN (100 mg/kg, i.p.) did not reverse the PPI disruption induced by the N-methyl-d-aspartate receptor antagonist dizocilpine (0.1 mg/kg, s.c.). FIN (60-300 mg/kg, i.p.) induced no catalepsy in either the bar test or the paw test. Our results suggest that 5AR inhibitors elicit antipsychotic-like effects in animals and may be proposed as a putative novel target in the management of psychotic disorders.

show abstract

“…For example, DHEAS exhibited memory-enhancing, antidepressant, anxiolytic, and antiaggression effects in animal experiments (Compagnone and Mellon, 2000). Clinical studies reported an improvement in negative symptoms in schizophrenia patients after application of DHEAS or its precursor dehydroepiandrosterone (Strous et al, 2003;Goyal et al, 2004). However, the mechanism underlying the psychotropic effects of DHEAS remains to be studied.…”

mentioning

confidence: 99%

Neuroactive Steroid Dehydroepiandrosterone Sulfate Inhibits 5-Hydroxytryptamine (5-HT)-Evoked Glutamate Release via Activation of σ-1 Receptors and Then Inhibition of 5-HT₃Receptors in Rat Prelimbic Cortex

Dong

Zhu²,

Dong³

et al. 2009

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Dehydroepiandrosterone sulfate (DHEAS) is one of the most important neuroactive steroids. The present study examined the effect of DHEAS on spontaneous and evoked glutamate release in the pyramidal cells of layers V and VI of the rat prelimbic cortex by using whole-cell patch-clamp recordings in slices and further investigated its mechanism. The results showed that DHEAS at 1 M had no effect on spontaneous glutamate release but inhibited 5-hydroxytryptaime (5-HT)-evoked glutamate release. The concentration-response relationship of this effect of DHEAS was U-shaped with a maximum at 1 M, and this inhibition seemed to have some extent of selectivity for the 5-HT-evoked glutamate release because it had no effects on high K ϩ -, electrical stimulus-, and dopamineevoked releases. Further study showed that DHEAS inhibited the 5-HT 3 receptor agonist evoked-glutamate release but had no effect on the 5-HT 2A/2C receptor agonist-evoked release. Moreover, the 5-HT 3 receptor antagonist could block the effect of DHEAS on the 5-HT-evoked glutamate release. The mechanism study showed that the -1 receptor antagonist could block the effect of DHEAS and that the -1 receptor agonist could mimic the effect of DHEAS on 5-HT 3 receptor agonistevoked glutamate release and intrasynaptosomal Ca 2ϩ increase. These results suggest that DHEAS can inhibit 5-HTevoked glutamate release via activation of the -1 receptor and then inhibition of the 5-HT 3 receptor in the pyramidal cells of the prelimbic cortex.

show abstract

Negative Correlation between Negative Symptoms of Schizophrenia and Testosterone Levels

Cited by 75 publications

References 14 publications

Effects of gonadectomy and hormone replacement on a spontaneous novel object recognition task in adult male rats

Effects of gonadectomy and hormone replacement on a spontaneous novel object recognition task in adult male rats

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Neuroactive Steroid Dehydroepiandrosterone Sulfate Inhibits 5-Hydroxytryptamine (5-HT)-Evoked Glutamate Release via Activation of σ-1 Receptors and Then Inhibition of 5-HT₃Receptors in Rat Prelimbic Cortex

Contact Info

Product

Resources

About

Negative Correlation between Negative Symptoms of Schizophrenia and Testosterone Levels

Cited by 75 publications

References 14 publications

Effects of gonadectomy and hormone replacement on a spontaneous novel object recognition task in adult male rats

Effects of gonadectomy and hormone replacement on a spontaneous novel object recognition task in adult male rats

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Neuroactive Steroid Dehydroepiandrosterone Sulfate Inhibits 5-Hydroxytryptamine (5-HT)-Evoked Glutamate Release via Activation of σ-1 Receptors and Then Inhibition of 5-HT3Receptors in Rat Prelimbic Cortex

Contact Info

Product

Resources

About

Neuroactive Steroid Dehydroepiandrosterone Sulfate Inhibits 5-Hydroxytryptamine (5-HT)-Evoked Glutamate Release via Activation of σ-1 Receptors and Then Inhibition of 5-HT₃Receptors in Rat Prelimbic Cortex