Variations in anxiety-related behavior are associated with individual allostatic set-points in ch... more Variations in anxiety-related behavior are associated with individual allostatic set-points in chronically stressed rats. Actively offensive rats with the externalizing indicators of sniffling and climbing the stimulus and material tearing during 10 days of predator scent stress had reduced plasma corticosterone, increased striatal glutamate metabolites, and increased adrenal 11-dehydrocorticosterone content compared to passively defensive rats with the internalizing indicators of freezing and grooming, as well as to controls without any behavioral changes. These findings suggest that rats that display active offensive activity in response to stress develop anxiety associated with decreased allostatic set-points and increased resistance to stress.
Schizophrenia (SCZ) is a devastating mental disorder with poorly defined underlying molecular mec... more Schizophrenia (SCZ) is a devastating mental disorder with poorly defined underlying molecular mechanisms. The gut microbiome can modulate brain function and behaviors through the microbiota-gut-brain axis. Here, we found that unmedicated and medicated patients with SCZ had a decreased microbiome α-diversity index and marked disturbances of gut microbial composition versus healthy controls (HCs). Several unique bacterial taxa (e.g., Veillonellaceae and Lachnospiraceae) were associated with SCZ severity. A specific microbial panel (Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae) enabled discriminating patients with SCZ from HCs with 0.769 area under the curve. Compared to HCs, germ-free mice receiving SCZ microbiome fecal transplants had lower glutamate and higher glutamine and GABA in the hippocampus and displayed SCZ-relevant behaviors similar to other mouse models of SCZ involving glutamatergic hypofunction. Together, our findings suggest that t...
To examine the association between antidepressant use and weight gain, as well as the interaction... more To examine the association between antidepressant use and weight gain, as well as the interaction with lifestyle factors. Longitudinal study. We used data from 2334 adults from two stages (4.4 years apart) of the North West Adelaide Health Study, including validated diet and lifestyle questionnaires, measured body weight and linked pharmaceutical prescription data. Body weight change. 188 (8.1%) participants had a mean annual number of 1-2 antidepressant prescriptions, and 212 (9.1%) had over two prescriptions. The mean annual weight gain was 0.12, 0.18 and 0.28 kg in non-users, low (1-2 prescriptions/year) and high (>2 prescriptions/year) antidepressant users, respectively. In multivariable regression models, antidepressant use was positively associated with weight gain: high antidepressant users gained an extra 0.22 (95% CI 0.00 to 0.44) kg per year. This association was mainly due to selective serotonin reuptake inhibitor (SSRI) use. High SSRI users gained 0.48 (95% CI 0.20 to...
Earlier we had found that the CYP2C9*2 allelic frequency was lower in Mexican-Americans living in... more Earlier we had found that the CYP2C9*2 allelic frequency was lower in Mexican-Americans living in California than in Spaniards (SP). This was assumed to be related to the low CYP2C9*2 and *3 allele frequencies in Orientals. This study was therefore aimed at analyzing whether there were also differences in CYP2C9 allele frequencies between Mexican-Tepehuanos (MT) and Mexican-Mestizos (MM) living in northwestern Mexico and SP. The CYP2C9*2 frequency was expected to be lower in the indigenous MT than in the two other groups, and lower in MM than in SP as in our earlier study. CYP2C9 genotypes and allele frequencies of two populations of healthy volunteers, MT (n=99) and MM (n=102), were compared with a population of SP (n=327). The data were also compared with our previously published population of Mestizo-Mexican-Americans (MA). The CYP2C9 genotypes among the studied populations were in equilibrium. The frequencies of CYP2C9*2 were 0.01, 0.07, 0.08, and 0.16 for MT, MM, MA, and SP sub...
Progress in neuro-psychopharmacology & biological psychiatry, Jan 15, 2007
Modulations of serotonergic and noradrenergic systems are thought to be critical to the therapeut... more Modulations of serotonergic and noradrenergic systems are thought to be critical to the therapeutic effect of most antidepressants, and their efficacies have been shown to depend on a functional polymorphism within the promoter region of the serotonin transporter gene (5-HTTLPR). Mirtazapine has a dual-action profile, combining the enhancement of the noradrenergic neurotransmitter system with specific actions on particular serotonergic receptor subtypes. The goal of this study was to elucidate whether the 5-HTTLPR polymorphism is associated with the mirtazapine antidepressant response in subjects with major depressive disorder (MDD). One hundred and one MDD patients were evaluated during 4 weeks of mirtazapine treatment. The severity of depression was assessed with the 21-item Hamilton Depression Rating scale, and the 5-HTTLPR genotypes in the patients were determined using the polymerase chain reaction. Our results showed that responses at the 2nd and 4th weeks were significantly b...
... le substrate fo r in d u cing d epression -like sympto ms in ro d en ts. Anhed o nia is the m... more ... le substrate fo r in d u cing d epression -like sympto ms in ro d en ts. Anhed o nia is the m arked ly d imin ished interest o r p leasu ... s re-sem b lin g th ose ob served in dep ression . Anhed onia-like behaviors are reversed by ch ron ic but n o t acu te antidepressant treatm ent. ...
Variations in anxiety-related behavior are associated with individual allostatic set-points in ch... more Variations in anxiety-related behavior are associated with individual allostatic set-points in chronically stressed rats. Actively offensive rats with the externalizing indicators of sniffling and climbing the stimulus and material tearing during 10 days of predator scent stress had reduced plasma corticosterone, increased striatal glutamate metabolites, and increased adrenal 11-dehydrocorticosterone content compared to passively defensive rats with the internalizing indicators of freezing and grooming, as well as to controls without any behavioral changes. These findings suggest that rats that display active offensive activity in response to stress develop anxiety associated with decreased allostatic set-points and increased resistance to stress.
Schizophrenia (SCZ) is a devastating mental disorder with poorly defined underlying molecular mec... more Schizophrenia (SCZ) is a devastating mental disorder with poorly defined underlying molecular mechanisms. The gut microbiome can modulate brain function and behaviors through the microbiota-gut-brain axis. Here, we found that unmedicated and medicated patients with SCZ had a decreased microbiome α-diversity index and marked disturbances of gut microbial composition versus healthy controls (HCs). Several unique bacterial taxa (e.g., Veillonellaceae and Lachnospiraceae) were associated with SCZ severity. A specific microbial panel (Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae) enabled discriminating patients with SCZ from HCs with 0.769 area under the curve. Compared to HCs, germ-free mice receiving SCZ microbiome fecal transplants had lower glutamate and higher glutamine and GABA in the hippocampus and displayed SCZ-relevant behaviors similar to other mouse models of SCZ involving glutamatergic hypofunction. Together, our findings suggest that t...
To examine the association between antidepressant use and weight gain, as well as the interaction... more To examine the association between antidepressant use and weight gain, as well as the interaction with lifestyle factors. Longitudinal study. We used data from 2334 adults from two stages (4.4 years apart) of the North West Adelaide Health Study, including validated diet and lifestyle questionnaires, measured body weight and linked pharmaceutical prescription data. Body weight change. 188 (8.1%) participants had a mean annual number of 1-2 antidepressant prescriptions, and 212 (9.1%) had over two prescriptions. The mean annual weight gain was 0.12, 0.18 and 0.28 kg in non-users, low (1-2 prescriptions/year) and high (>2 prescriptions/year) antidepressant users, respectively. In multivariable regression models, antidepressant use was positively associated with weight gain: high antidepressant users gained an extra 0.22 (95% CI 0.00 to 0.44) kg per year. This association was mainly due to selective serotonin reuptake inhibitor (SSRI) use. High SSRI users gained 0.48 (95% CI 0.20 to...
Earlier we had found that the CYP2C9*2 allelic frequency was lower in Mexican-Americans living in... more Earlier we had found that the CYP2C9*2 allelic frequency was lower in Mexican-Americans living in California than in Spaniards (SP). This was assumed to be related to the low CYP2C9*2 and *3 allele frequencies in Orientals. This study was therefore aimed at analyzing whether there were also differences in CYP2C9 allele frequencies between Mexican-Tepehuanos (MT) and Mexican-Mestizos (MM) living in northwestern Mexico and SP. The CYP2C9*2 frequency was expected to be lower in the indigenous MT than in the two other groups, and lower in MM than in SP as in our earlier study. CYP2C9 genotypes and allele frequencies of two populations of healthy volunteers, MT (n=99) and MM (n=102), were compared with a population of SP (n=327). The data were also compared with our previously published population of Mestizo-Mexican-Americans (MA). The CYP2C9 genotypes among the studied populations were in equilibrium. The frequencies of CYP2C9*2 were 0.01, 0.07, 0.08, and 0.16 for MT, MM, MA, and SP sub...
Progress in neuro-psychopharmacology & biological psychiatry, Jan 15, 2007
Modulations of serotonergic and noradrenergic systems are thought to be critical to the therapeut... more Modulations of serotonergic and noradrenergic systems are thought to be critical to the therapeutic effect of most antidepressants, and their efficacies have been shown to depend on a functional polymorphism within the promoter region of the serotonin transporter gene (5-HTTLPR). Mirtazapine has a dual-action profile, combining the enhancement of the noradrenergic neurotransmitter system with specific actions on particular serotonergic receptor subtypes. The goal of this study was to elucidate whether the 5-HTTLPR polymorphism is associated with the mirtazapine antidepressant response in subjects with major depressive disorder (MDD). One hundred and one MDD patients were evaluated during 4 weeks of mirtazapine treatment. The severity of depression was assessed with the 21-item Hamilton Depression Rating scale, and the 5-HTTLPR genotypes in the patients were determined using the polymerase chain reaction. Our results showed that responses at the 2nd and 4th weeks were significantly b...
... le substrate fo r in d u cing d epression -like sympto ms in ro d en ts. Anhed o nia is the m... more ... le substrate fo r in d u cing d epression -like sympto ms in ro d en ts. Anhed o nia is the m arked ly d imin ished interest o r p leasu ... s re-sem b lin g th ose ob served in dep ression . Anhed onia-like behaviors are reversed by ch ron ic but n o t acu te antidepressant treatm ent. ...
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