Low plasma concentrations of N-methyl-d-aspartate receptor subunits as a possible biomarker for psychosis.

BACKGROUND: N-methyl-d-aspartate receptor (NMDAR) has been largely implicated in the neurobiology of schizophrenia and other psychosis. Aiming to evaluate their potential as peripheral biomarkers for psychosis, we quantified the plasma concentrations of NR1 and NR2 NMDAR subunits of first-episode psychosis patients in their first contact with mental health services due to psychotic symptoms, compared with siblings and matched community-based controls. METHODS: The quantifications of NR1 and NR2 plasma concentrations were performed by ELISA. Data were analysed by nonparametric tests and Receiver Operating Curve (ROC) analysis. RESULTS: We included 166 first-episode psychosis patients (mean age = 30.3 ±â€¯12.2 years; 64% men), with the diagnosis of schizophrenia spectrum (n = 84), bipolar disorder (n = 51) and psychotic depression (n = 31), 76 siblings (mean age = 31.5 ±â€¯11.0 years; 30.3% men) and 166 healthy community-based controls (mean age = 31.4 ±â€¯12.0 years; 63.9% men). NMDAR subunits were significantly lower in patients compared with siblings and controls (p < 0.001), except by NR1 plasma concentrations of bipolar patients compared with siblings and controls. NR1 plasma concentrations lower than 17.65 pg/ml (AUC = 0.621) showed sensitivity of 42.8%, specificity of 84.3%, positive predictive value (PPV) of 73.2% and negative predictive value (NPV) of 59.6%. Individuals with NR2 plasma concentrations lower than 2.92 ng/ml (AUC = 0.801) presented a 10.61-fold increased risk of psychosis, with a sensibility of 71.9%, specificity of 80.6%, PPV of 79.0% and NPV of 73.9%. CONCLUSIONS: This is the first study reporting the measurement and the reduction of NR1 and NR2 NMDAR subunits plasma concentrations in psychiatric disorders. In particular, the NR2 subunit may be a possible plasma biomarker for psychosis.

The response of social anxiety disorder patients to threat scenarios differs from that of healthy controls

The objective of the present study was to evaluate the response of social anxiety disorder (SAD) patients to threat scenarios. First-choice responses to 12 scenarios describing conspecific threatening situations and mean scores of defensive direction and defensive intensity dimensions were compared between 87 SAD patients free of medication and 87 matched healthy controls (HC). A significant gender difference in the first-choice responses was identified for seven scenarios among HCs but only for two scenarios among SAD patients. A significantly higher proportion of SAD patients chose "freezing" in response to "Bush" and "Noise" scenarios, whereas the most frequent response by HCs to these scenarios was "check out". SAD males chose "run away" and "yell" more often than healthy men in response to the scenarios "Park" and "Elevator", respectively. There was a positive correlation between the severity of symptoms and both defensive direction and defensive intensity dimensions. Factorial analysis confirmed the gradient of defensive reactions derived from animal studies. SAD patients chose more urgent defensive responses to threat scenarios, seeming to perceive them as more dangerous than HCs and tending to move away from the source of threat. This is consistent with the hypothesis that the physiopathology of anxiety disorders involves brain structures responsible for defensive behaviors.

The response of social anxiety disorder patients to threat scenarios differs from that of healthy controls.

The objective of the present study was to evaluate the response of social anxiety disorder (SAD) patients to threat scenarios. First-choice responses to 12 scenarios describing conspecific threatening situations and mean scores of defensive direction and defensive intensity dimensions were compared between 87 SAD patients free of medication and 87 matched healthy controls (HC). A significant gender difference in the first-choice responses was identified for seven scenarios among HCs but only for two scenarios among SAD patients. A significantly higher proportion of SAD patients chose "freezing" in response to "Bush" and "Noise" scenarios, whereas the most frequent response by HCs to these scenarios was "check out". SAD males chose "run away" and "yell" more often than healthy men in response to the scenarios "Park" and "Elevator", respectively. There was a positive correlation between the severity of symptoms and both defensive direction and defensive intensity dimensions. Factorial analysis confirmed the gradient of defensive reactions derived from animal studies. SAD patients chose more urgent defensive responses to threat scenarios, seeming to perceive them as more dangerous than HCs and tending to move away from the source of threat. This is consistent with the hypothesis that the physiopathology of anxiety disorders involves brain structures responsible for defensive behaviors.

Defensive responses to threat scenarios in Brazilians reproduce the pattern of Hawaiian Americans and non-human mammals.

A former study with scenarios conducted in Hawaii has suggested that humans share with non-human mammals the same basic defensive strategies - risk assessment, freezing, defensive threat, defensive attack, and flight. The selection of the most adaptive strategy is strongly influenced by features of the threat stimulus - magnitude, escapability, distance, ambiguity, and availability of a hiding place. Aiming at verifying if these strategies would be consistent in a different culture, 12 defensive scenarios were translated into Portuguese and adapted to the Brazilian culture. The sample consisted of male and female undergraduate students divided into two groups: 76 students, who evaluated the five dimensions of each scenario and 248 medical students, who chose the most likely response for each scenario. In agreement with the findings from studies of non-human mammal species, the scenarios were able to elicit different defensive behavioral responses, depending on features of the threat. "Flight" was chosen as the most likely response in scenarios evaluated as an unambiguous and intense threat, but with an available route of escape, whereas "attack" was chosen in an unambiguous, intense and close dangerous situation without an escape route. Less urgent behaviors, such as "check out", were chosen in scenarios evaluated as less intense, more distant and more ambiguous. Moreover, the results from the Brazilian sample were similar to the results obtained in the original study with Hawaiian students. These data suggest that a basic repertoire of defensive strategies is conserved along the mammalian evolution because they share similar functional benefits in maintaining fitness.

Defensive responses to threat scenarios in Brazilians reproduce the pattern of Hawaiian Americans and non-human mammals

A former study with scenarios conducted in Hawaii has suggested that humans share with non-human mammals the same basic defensive strategies - risk assessment, freezing, defensive threat, defensive attack, and flight. The selection of the most adaptive strategy is strongly influenced by features of the threat stimulus - magnitude, escapability, distance, ambiguity, and availability of a hiding place. Aiming at verifying if these strategies would be consistent in a different culture, 12 defensive scenarios were translated into Portuguese and adapted to the Brazilian culture. The sample consisted of male and female undergraduate students divided into two groups: 76 students, who evaluated the five dimensions of each scenario and 248 medical students, who chose the most likely response for each scenario. In agreement with the findings from studies of non-human mammal species, the scenarios were able to elicit different defensive behavioral responses, depending on features of the threat. "Flight" was chosen as the most likely response in scenarios evaluated as an unambiguous and intense threat, but with an available route of escape, whereas "attack" was chosen in an unambiguous, intense and close dangerous situation without an escape route. Less urgent behaviors, such as "check out", were chosen in scenarios evaluated as less intense, more distant and more ambiguous. Moreover, the results from the Brazilian sample were similar to the results obtained in the original study with Hawaiian students. These data suggest that a basic repertoire of defensive strategies is conserved along the mammalian evolution because they share similar functional benefits in maintaining fitness.