Psychosis and Inflammation

Dr. Weeks’ Comment:  Psychosis (i.e nervous breakdowns or  “going crazy”) is an inflammatory process. Take safe and effective anti-inflammatory agents to put out the fire. And if you are a pregnant woman or a lady intending to get pregnant,  eat an anti-inflammatory diet and eat the seeds.

Here are some scientific articles teaching you that you need anti-inflammation to get thinking clearly.

 

1.

Int J Neuropsychopharmacol. 2014 Oct 31. pii: pyu037. doi: 10.1093/ijnp/pyu037. [Epub ahead of print]

Pro-/Antiinflammatory Dysregulation in Early Psychosis: Results from a 1-Year Follow-Up Study.

 García-Bueno B1, et al

 Abstract

BACKGROUND:

Previous studies indicated a systemic deregulation of the pro-/antiinflammatory balance in subjects after 6 months of a first psychotic episode. This disruption was reexamined 12 months after diagnosis to identify potential risk/protective factors and associations with symptom severity.

METHODS:

Eighty-five subjects were followed during 12 months and the determination of the same pro-/antiinflammatory mediators was carried out in plasma and peripheral blood mononuclear cells. Multivariate logistic regression analyses were used to identify risk/protective factors. Multiple linear regression models were performed to detect the change of each biological marker during follow-up in relation to clinical characteristics and confounding factors.

RESULTS:

This study suggests a more severe systemic pro-/antiinflammatory deregulation than in earlier pathological stages in first psychotic episode, because not only were intracellular components of the inflammatory response increased but also the majority of soluble elements. Nitrite plasma levels and cyclooxygenase-2 expression in peripheral blood mononuclear cells are reliable potential risk factors and 15d-prostaglandin-J2 plasma levels a protection biomarker. An interesting relationship exists between antipsychotic dose and the levels of prostaglandin-E2 (inverse) and 15d-prostaglandin-J2 (direct). An inverse relationship between the Global Assessment of Functioning scale and lipid peroxidation is also present.

CONCLUSIONS:

Summing up, pro-/antiinflammatory mediators can be used as risk/protection biomarkers. The inverse association between oxidative/nitrosative damage and the Global Assessment of Functioning scale, and the possibility that one of the targets of antipsychotics could be the restoration of the pro-/antiinflammatory balance support the use of antiinflammatory drugs as coadjuvant to antipsychotics.

 

2.

J Affect Disord. 2014 Dec 12;174C:467-478. doi: 10.1016/j.jad.2014.12.015. [Epub ahead of print]

Taking the fuel out of the fire: Evidence for the use of anti-inflammatory agents in the treatment of bipolar disorders.

Ayorech Z1, Tracy DK2, Baumeister D3, Giaroli G1.

Abstract

BACKGROUND:

Inflammation has emerged as a potentially important factor – and thus putative pharmacological target – in the pathology of bipolar disorders. However to date no systematic evaluations of the efficacy of add on anti-inflammatory treatment for the depressive and manic episodes have been carried out.

METHODS:

Sixteen articles were ultimately identified – by computer searches of databases (including PsycINFO, MEDLINE, and EMBASE), supplemented by hand searches and personal communication – as meeting study inclusion criteria.

RESULTS:

Anti-manic effects were evaluated in two trials, one of adjunctive n-acetyl cysteine (NAC), one of omega-3 fatty acids (O3FA), and significant improvements only emerged for NAC. Celecoxib had a rapid but short-lived antidepressant effect. Despite limited effects of O3FA on symptoms, imaging data demonstrated alterations in neuronal functioning that might have longer-term therapeutic effects. Evidence was strongest for adjunctive NAC in bipolar depression though conclusions are limited by small sample sizes.

LIMITATIONS:

Definitive conclusions are limited by the paucity of data, small study sizes, and the variability in methodology used.

CONCLUSIONS:

Current evidence for aspirin or celecoxib is insufficient though further investigation of the potential of celecoxib in early illness onset is warranted. Variable evidence exists for add-on O3FA though an indication of short-term treatment effects on membrane fluidity and neuronal activity suggest longer follow-up assessment is needed. The strongest evidence emerged for NAC in depression and future studies must address the role of illness duration and patients׳ baseline medications on outcomes. Careful consideration of lithium toxicity in the elderly and renal impaired is essential.

 

3.

2014 Dec 18. pii: S0013-7006(14)00230-9. doi: 10.1016/j.encep.2014.10.007. [Epub ahead of print]

[Parvovirus B19 seroprevalence in a group of schizophrenic patients.]

[Article in French]

El Kissi Y1, Hannachi N2, Mtiraoui A3, Samoud S2, Bouhlel S3, Gaabout S3, Boukadida J2, Ben Hadj Ali B3.

Abstract

BACKGROUND:

Schizophrenia is a highly disabling chronic mental illness. It is considerded as a neuro-developpemental illness resulting from the interaction of genetic and environmental factors. Growing evidence supports the major role of prenatal infections and inflammation in the genesis of schizophrenia. The hypothesis including viral infections has been the subject of several studies and the role of parvovirus B19 (PB19) in the onset of the disease has been suggested. However, there is, up till now, no sero-epidemiological evidence of his involvement.

OBJECTIVE:

To determine the prevalence of parvovirus B19 (PB19) in schizophrenic patients and in control subjects and to examine clinical associations between viral prevalence, risk factors of infectious disease and clinical features.

METHOD:

We carried out a case-control seroepidemiological study in the Psychiatry department of Farhat-Hached general hospital of Sousse (Tunisia). We recruited108 schizophrenic patients and 108 healthy controls free from any psychotic disorder and matched for age and sex. We collected sociodemographic data, medical history, axis I comorbid disorders and infectious risk factors. We assessed patients for psychopathology and severity of illness using respectively the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impressions (CGI). For each study participant, blood sample was collected and levels of IgG and IgM anti-PB19 were measured using the ELISA technique.

RESULTS:

The prevalence of IgG antibodies to PB19 was significantly higher in schizophrenic patients than in controls (73.1% vs 60.2%; P=0.04). There were no statistical differences between the two groups regarding the prevalence of IgM antibodies to PB19. No association was found between viral prevalence and sociodemographic data, risk factors for infection or clinical characteristics. The presence of PB19 antibodies was associated with a lower score on the PANSS negative subscale (P=0.04). No other signficative association were found.

CONCLUSIONS:

In our study, prevalence of IgG antibodies to PB19 was significantly higher in schizophrenic patients than in controls. This finding supports the hypothesis of the involvement of PB19 in schizophrenia. Further studies including both virological and immunological aspects are needed to better clarify the etiopathogenic mechanisms of schizophrenia which would

 

4.

Int J Neuropsychopharmacol. 2014 Oct 31. pii: pyu042. [Epub ahead of print]

Effects of risperidone on cytokine profile in drug naïve first episode psychosis.

Noto C1, Ota VK2, Gouveia ES3, Rizzo LB4, Spindola LM2, Honda PH5, Cordeiro Q1, Belangero SI2, Bressan RA4, Gadelha A4, Maes M6, Brietzke E7.

Abstract

BACKGROUND:

There is robust evidence that schizophrenia is characterized by immune-inflammatory abnormalities, including variations on cytokines levels. The results of previous studies, however, are heterogeneous due to several confounding factors, as the effect of antipsychotic drugs. Therefore, research on drug naïve first episode psychosis (FEP) patients is essential to elucidate the role of immune processes in that disorder.

METHODS:

The aim of this study is to compare cytokines levels (IL-2, IL-10, IL-4, IL-6, IFN-Y, TNF-α and IL-17) in drug naïve FEP patients both before and after treatment with risperidone for 10 weeks and to investigate possible associations between cytokines levels and clinical response to treatment and presence of depressive symptoms. It this study, we included 55 drug naïve FEP patients who had repeated measurements of cytokines levels and 57 healthy controls.

RESULTS:

We found that FEP patients had significantly higher IL-6, IL-10 and TNF-α levels than healthy controls. After risperidone treatment, these three cytokines and additionally IL-4 decreased significantly. No significant difference was found between the post-treatment cytokines levels in FEP patients and in healthy controls, suggesting that these alterations in cytokine profile are a state marker of FEP. No significant association was found between risperidone-induced changes in cytokines and the clinical response to treatment or the presence of depression. There was a significant inverse association between the risperidone-induced changes in IL-10 and the negative symptoms.

CONCLUSION:

In conclusion, our results show a specific cytokine profile in FEP patients (monocytic and regulatory T cell activation) and suggest immunoregulatory effects of risperidone treatment, characterized by suppressant effects on monocytic, Th2 and T regulatory functions.

 

5.

J Psychiatr Res. 2014 Nov 11;60C:163-169. doi: 10.1016/j.jpsychires.2014.10.011. [Epub ahead of print]

Stress biomarkers as predictors of transition to psychosis in at-risk mental states: Roles for cortisol, prolactin and albumin.

Labad J1, Stojanovic-Pérez A2, Montalvo I3, Solé M2, Cabezas A2, Ortega L2, Moreno I2, Vilella E2, Martorell L2, Reynolds RM4, Gutiérrez-Zotes A2.

Abstract

Stress and inflammation are thought to play a role in the risk of developing a psychotic disorder. We aimed to identify stress-related biomarkers for psychosis transition in help-seeking individuals with an at-risk mental state (ARMS). We studied 39 ARMS subjects who were attending an Early Intervention Service. We included a control group of 44 healthy subjects (HS) matched by sex and age. Stressful life events and perceived stress were assessed. Stress-related biomarkers were determined in serum (cortisol, prolactin, C-reactive protein and albumin), plasma (fibrinogen) or saliva (morning cortisol, cortisol awakening response). All ARMS were followed-up at our Unit for at least one year. We divided the ARMS group into two subgroups based on the development of a psychotic disorder (ARMS-P, N = 10) or not (ARMS-NP, N = 29). ARMS-P reported more stressful life events and perceived stress than HS and ARMS-NP groups. In relation to baseline stress biomarkers, ARMS-P subjects had increased prolactin and lower albumin levels in serum, when compared to ARMS-NP and HS groups. These results did not change when repeated in a subsample of antipsychotic-naïve ARMS subjects. We also found significant differences between groups in the cortisol secretion after awakening. In a multinomial logistic regression adjusting for age, sex and life stress, prolactin was a predictor of psychosis transition whereas albumin levels had a protective effect. Our study underscores the role of stress and stress-related biomarkers (cortisol awakening response, prolactin and albumin) in the pathogenesis of psychosis.

 

6.

Schizophr Bull. 2015 Jan;41(1):85-93. doi: 10.1093/schbul/sbu157. Epub 2014 Nov 9.

Imaging Neuroinflammation in Gray and White Matter in Schizophrenia: An In-Vivo PET Study With [18F]-FEPPA.

Kenk M1, Selvanathan T1, Rao N1, Suridjan I1, Rusjan P1, Remington G1, Meyer JH1, Wilson AA1, Houle S1, Mizrahi R2.

Abstract

Neuroinflammation and abnormal immune responses have been implicated in schizophrenia (SCZ). Past studies using positron emission tomography (PET) that examined neuroinflammation in patients with SCZ in vivo using the translocator protein 18kDa (TSPO) target were limited by the insensitivity of the first-generation imaging agent [(11)C]-PK11195, scanners used, and the small sample sizes studied. Present study uses a novel second-generation TSPO PET radioligand N-acetyl-N-(2-[(18)F]fluoroethoxybenzyl)-2-phenoxy-5-pyridinamine ([(18)F]-FEPPA) to evaluate whether there is increased neuroinflammation in patients with SCZ. A cross-sectional study was performed using [(18)F]-FEPPA and a high-resolution research tomograph (HRRT). Eighteen patients with SCZ with ongoing psychotic symptoms and 27 healthy volunteers (HV) were recruited from a tertiary psychiatric clinical setting and the community, respectively. All participants underwent [(18)F]-FEPPA PET and magnetic resonance imaging, and PET data were analyzed to obtain [(18)F]-FEPPA total volume of distribution (V T) using a 2-tissue compartment model with an arterial plasma input function, as previously validated. All subjects were classified as high-, medium- or low-affinity [(18)F]-FEPPA binders on the basis of rs6971 polymorphism, and genotype information was incorporated into the analyses of imaging outcomes. No significant differences in neuroinflammation indexed as [(18)F]-FEPPA V T were observed between groups in either gray (F (1,39) = 0.179, P = .674) or white matter regions (F (1,38) = 0.597, P = .445). The lack of significant difference in neuroinflammation in treated patients with SCZ in the midst of a psychotic episode and HV suggests that neuroinflammatory processes may take place early in disease progression or are affected by antipsychotic treatment.

 

7.

Int J Tryptophan Res. 2014 Sep 16;7:15-22. doi: 10.4137/IJTR.S16800. eCollection 2014.

Imbalanced kynurenine pathway in schizophrenia.

Kegel ME1, Bhat M2, Skogh E3, Samuelsson M3, Lundberg K3, Dahl ML4, Sellgren C5, Schwieler L1, Engberg G1, Schuppe-Koistinen I2, Erhardt S1.

 

Abstract

Several studies suggest a role for kynurenic acid (KYNA) in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN). Here we investigate the levels of QUIN in cerebrospinal fluid (CSF) of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22) and those of controls (n = 26) were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36). CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls (P = 0.027). In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.

 

8.

2014 Dec;50:210-9. doi: 10.1016/j.psyneuen.2014.08.016. Epub 2014 Sep 2.

Suicidal patients are deficient in vitamin D, associated with a pro-inflammatory status in the blood.

Grudet C1, Malm J2, Westrin A3, Brundin L4.

Abstract

BACKGROUND:

Low levels of vitamin D may play a role in psychiatric disorders, as cross-sectional studies show an association between vitamin D deficiency and depression, schizophrenia and psychotic symptoms. The underlying mechanisms are not well understood, although vitamin D is known to influence the immune system to promote a T helper (Th)-2 phenotype. At the same time, increased inflammation might be of importance in the pathophysiology of depression and suicide. We therefore hypothesized that suicidal patients would be deficient in vitamin D, which could be responsible for the inflammatory changes observed in these patients.

METHODS:

We compared vitamin D levels in suicide attempters (n=59), non-suicidal depressed patients (n=17) and healthy controls (n=14). Subjects were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and went through a structured interview by a specialist in psychiatry. 25(OH)D2 and 25(OH)D3 were measured in plasma using liquid-chromatography-mass-spectrometry (LC-MS). We further explored vitamin D’s association with plasma IL-1β, IL-6 and TNF-α.

RESULTS:

Suicide attempters had significantly lower mean levels of vitamin D than depressed non-suicidal patients and healthy controls. 58 percent of the suicide attempters were vitamin D deficient according to clinical standard. Moreover, there was a significant negative association between vitamin D and pro-inflammatory cytokines in the psychiatric patients. Low vitamin D levels were associated with higher levels of the inflammatory cytokines IL-6 and IL-1β in the blood.

CONCLUSION:

The suicide attempters in our study were deficient in vitamin D. Our data also suggest that vitamin D deficiency could be a contributing factor to the elevated pro-inflammatory cytokines previously reported in suicidal patients. We propose that routine clinical testing of vitamin D levels could be beneficial in patients with suicidal symptoms, with subsequent supplementation in patients found to be deficient.

 

9.

Am J Psychiatry. 2014 Sep;171(9):901-5. doi: 10.1176/appi.ajp.2014.14060749.

Priming the brain for psychosis: maternal inflammation during fetal development and the risk of later psychiatric disorder.

Cannon M, Clarke MC, Cotter DR.

 

10.

Int J Neuropsychopharmacol. 2014 Oct 31. pii: pyu037. doi: 10.1093/ijnp/pyu037. [Epub ahead of print]

Pro-/Antiinflammatory Dysregulation in Early Psychosis: Results from a 1-Year Follow-Up Study.

 García-Bueno B1, et al

Abstract

BACKGROUND:

Previous studies indicated a systemic deregulation of the pro-/antiinflammatory balance in subjects after 6 months of a first psychotic episode. This disruption was reexamined 12 months after diagnosis to identify potential risk/protective factors and associations with symptom severity.

METHODS:

Eighty-five subjects were followed during 12 months and the determination of the same pro-/antiinflammatory mediators was carried out in plasma and peripheral blood mononuclear cells. Multivariate logistic regression analyses were used to identify risk/protective factors. Multiple linear regression models were performed to detect the change of each biological marker during follow-up in relation to clinical characteristics and confounding factors.

RESULTS:

This study suggests a more severe systemic pro-/antiinflammatory deregulation than in earlier pathological stages in first psychotic episode, because not only were intracellular components of the inflammatory response increased but also the majority of soluble elements. Nitrite plasma levels and cyclooxygenase-2 expression in peripheral blood mononuclear cells are reliable potential risk factors and 15d-prostaglandin-J2 plasma levels a protection biomarker. An interesting relationship exists between antipsychotic dose and the levels of prostaglandin-E2 (inverse) and 15d-prostaglandin-J2 (direct). An inverse relationship between the Global Assessment of Functioning scale and lipid peroxidation is also present.

CONCLUSIONS:

Summing up, pro-/antiinflammatory mediators can be used as risk/protection biomarkers. The inverse association between oxidative/nitrosative damage and the Global Assessment of Functioning scale, and the possibility that one of the targets of antipsychotics could be the restoration of the pro-/antiinflammatory balance support the use of antiinflammatory drugs as coadjuvant to antipsychotics.

 

 

11.

J Affect Disord. 2014 Dec 12;174C:467-478. doi: 10.1016/j.jad.2014.12.015. [Epub ahead of print]

Taking the fuel out of the fire: Evidence for the use of anti-inflammatory agents in the treatment of bipolar disorders.

Ayorech Z1, Tracy DK2, Baumeister D3, Giaroli G1.

Abstract

BACKGROUND:

Inflammation has emerged as a potentially important factor – and thus putative pharmacological target – in the pathology of bipolar disorders. However to date no systematic evaluations of the efficacy of add on anti-inflammatory treatment for the depressive and manic episodes have been carried out.

METHODS:

Sixteen articles were ultimately identified – by computer searches of databases (including PsycINFO, MEDLINE, and EMBASE), supplemented by hand searches and personal communication – as meeting study inclusion criteria.

RESULTS:

Anti-manic effects were evaluated in two trials, one of adjunctive n-acetyl cysteine (NAC), one of omega-3 fatty acids (O3FA), and significant improvements only emerged for NAC. Celecoxib had a rapid but short-lived antidepressant effect. Despite limited effects of O3FA on symptoms, imaging data demonstrated alterations in neuronal functioning that might have longer-term therapeutic effects. Evidence was strongest for adjunctive NAC in bipolar depression though conclusions are limited by small sample sizes.

LIMITATIONS:

Definitive conclusions are limited by the paucity of data, small study sizes, and the variability in methodology used.

CONCLUSIONS:

Current evidence for aspirin or celecoxib is insufficient though further investigation of the potential of celecoxib in early illness onset is warranted. Variable evidence exists for add-on O3FA though an indication of short-term treatment effects on membrane fluidity and neuronal activity suggest longer follow-up assessment is needed. The strongest evidence emerged for NAC in depression and future studies must address the role of illness duration and patients׳ baseline medications on outcomes. Careful consideration of lithium toxicity in the elderly and renal impaired is essential.

12

2014 Dec 18. pii: S0013-7006(14)00230-9. doi: 10.1016/j.encep.2014.10.007. [Epub ahead of print]

[Parvovirus B19 seroprevalence in a group of schizophrenic patients.]

[Article in French]

El Kissi Y1, Hannachi N2, Mtiraoui A3, Samoud S2, Bouhlel S3, Gaabout S3, Boukadida J2, Ben Hadj Ali B3.

Abstract

BACKGROUND:

Schizophrenia is a highly disabling chronic mental illness. It is considerded as a neuro-developpemental illness resulting from the interaction of genetic and environmental factors. Growing evidence supports the major role of prenatal infections and inflammation in the genesis of schizophrenia. The hypothesis including viral infections has been the subject of several studies and the role of parvovirus B19 (PB19) in the onset of the disease has been suggested. However, there is, up till now, no sero-epidemiological evidence of his involvement.

OBJECTIVE:

To determine the prevalence of parvovirus B19 (PB19) in schizophrenic patients and in control subjects and to examine clinical associations between viral prevalence, risk factors of infectious disease and clinical features.

METHOD:

We carried out a case-control seroepidemiological study in the Psychiatry department of Farhat-Hached general hospital of Sousse (Tunisia). We recruited108 schizophrenic patients and 108 healthy controls free from any psychotic disorder and matched for age and sex. We collected sociodemographic data, medical history, axis I comorbid disorders and infectious risk factors. We assessed patients for psychopathology and severity of illness using respectively the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impressions (CGI). For each study participant, blood sample was collected and levels of IgG and IgM anti-PB19 were measured using the ELISA technique.

RESULTS:

The prevalence of IgG antibodies to PB19 was significantly higher in schizophrenic patients than in controls (73.1% vs 60.2%; P=0.04). There were no statistical differences between the two groups regarding the prevalence of IgM antibodies to PB19. No association was found between viral prevalence and sociodemographic data, risk factors for infection or clinical characteristics. The presence of PB19 antibodies was associated with a lower score on the PANSS negative subscale (P=0.04). No other signficative association were found.

CONCLUSIONS:

In our study, prevalence of IgG antibodies to PB19 was significantly higher in schizophrenic patients than in controls. This finding supports the hypothesis of the involvement of PB19 in schizophrenia. Further studies including both virological and immunological aspects are needed to better clarify the etiopathogenic mechanisms of schizophrenia which would be helpful.

 

Int J Neuropsychopharmacol. 2014 Oct 31. pii: pyu042. [Epub ahead of print]

Effects of risperidone on cytokine profile in drug naïve first episode psychosis.

Noto C1, Ota VK2, Gouveia ES3, Rizzo LB4, Spindola LM2, Honda PH5, Cordeiro Q1, Belangero SI2, Bressan RA4, Gadelha A4, Maes M6, Brietzke E7.

Author information

 

 

Abstract

BACKGROUND:

There is robust evidence that schizophrenia is characterized by immune-inflammatory abnormalities, including variations on cytokines levels. The results of previous studies, however, are heterogeneous due to several confounding factors, as the effect of antipsychotic drugs. Therefore, research on drug naïve first episode psychosis (FEP) patients is essential to elucidate the role of immune processes in that disorder.

METHODS:

The aim of this study is to compare cytokines levels (IL-2, IL-10, IL-4, IL-6, IFN-Y, TNF-α and IL-17) in drug naïve FEP patients both before and after treatment with risperidone for 10 weeks and to investigate possible associations between cytokines levels and clinical response to treatment and presence of depressive symptoms. It this study, we included 55 drug naïve FEP patients who had repeated measurements of cytokines levels and 57 healthy controls.

RESULTS:

We found that FEP patients had significantly higher IL-6, IL-10 and TNF-α levels than healthy controls. After risperidone treatment, these three cytokines and additionally IL-4 decreased significantly. No significant difference was found between the post-treatment cytokines levels in FEP patients and in healthy controls, suggesting that these alterations in cytokine profile are a state marker of FEP. No significant association was found between risperidone-induced changes in cytokines and the clinical response to treatment or the presence of depression. There was a significant inverse association between the risperidone-induced changes in IL-10 and the negative symptoms.

CONCLUSION:

In conclusion, our results show a specific cytokine profile in FEP patients (monocytic and regulatory T cell activation) and suggest immunoregulatory effects of risperidone treatment, characterized by suppressant effects on monocytic, Th2 and T regulatory functions.

 

J Psychiatr Res. 2014 Nov 11;60C:163-169. doi: 10.1016/j.jpsychires.2014.10.011. [Epub ahead of print]

Stress biomarkers as predictors of transition to psychosis in at-risk mental states: Roles for cortisol, prolactin and albumin.

Labad J1, Stojanovic-Pérez A2, Montalvo I3, Solé M2, Cabezas A2, Ortega L2, Moreno I2, Vilella E2, Martorell L2, Reynolds RM4, Gutiérrez-Zotes A2.

Author information

 

 

Abstract

Stress and inflammation are thought to play a role in the risk of developing a psychotic disorder. We aimed to identify stress-related biomarkers for psychosis transition in help-seeking individuals with an at-risk mental state (ARMS). We studied 39 ARMS subjects who were attending an Early Intervention Service. We included a control group of 44 healthy subjects (HS) matched by sex and age. Stressful life events and perceived stress were assessed. Stress-related biomarkers were determined in serum (cortisol, prolactin, C-reactive protein and albumin), plasma (fibrinogen) or saliva (morning cortisol, cortisol awakening response). All ARMS were followed-up at our Unit for at least one year. We divided the ARMS group into two subgroups based on the development of a psychotic disorder (ARMS-P, N = 10) or not (ARMS-NP, N = 29). ARMS-P reported more stressful life events and perceived stress than HS and ARMS-NP groups. In relation to baseline stress biomarkers, ARMS-P subjects had increased prolactin and lower albumin levels in serum, when compared to ARMS-NP and HS groups. These results did not change when repeated in a subsample of antipsychotic-naïve ARMS subjects. We also found significant differences between groups in the cortisol secretion after awakening. In a multinomial logistic regression adjusting for age, sex and life stress, prolactin was a predictor of psychosis transition whereas albumin levels had a protective effect. Our study underscores the role of stress and stress-related biomarkers (cortisol awakening response, prolactin and albumin) in the pathogenesis of psychosis.

 

 

Schizophr Bull. 2015 Jan;41(1):85-93. doi: 10.1093/schbul/sbu157. Epub 2014 Nov 9.

Imaging Neuroinflammation in Gray and White Matter in Schizophrenia: An In-Vivo PET Study With [18F]-FEPPA.

Kenk M1, Selvanathan T1, Rao N1, Suridjan I1, Rusjan P1, Remington G1, Meyer JH1, Wilson AA1, Houle S1, Mizrahi R2.

Author information

 

 

Abstract

Neuroinflammation and abnormal immune responses have been implicated in schizophrenia (SCZ). Past studies using positron emission tomography (PET) that examined neuroinflammation in patients with SCZ in vivo using the translocator protein 18kDa (TSPO) target were limited by the insensitivity of the first-generation imaging agent [(11)C]-PK11195, scanners used, and the small sample sizes studied. Present study uses a novel second-generation TSPO PET radioligand N-acetyl-N-(2-[(18)F]fluoroethoxybenzyl)-2-phenoxy-5-pyridinamine ([(18)F]-FEPPA) to evaluate whether there is increased neuroinflammation in patients with SCZ. A cross-sectional study was performed using [(18)F]-FEPPA and a high-resolution research tomograph (HRRT). Eighteen patients with SCZ with ongoing psychotic symptoms and 27 healthy volunteers (HV) were recruited from a tertiary psychiatric clinical setting and the community, respectively. All participants underwent [(18)F]-FEPPA PET and magnetic resonance imaging, and PET data were analyzed to obtain [(18)F]-FEPPA total volume of distribution (V T) using a 2-tissue compartment model with an arterial plasma input function, as previously validated. All subjects were classified as high-, medium- or low-affinity [(18)F]-FEPPA binders on the basis of rs6971 polymorphism, and genotype information was incorporated into the analyses of imaging outcomes. No significant differences in neuroinflammation indexed as [(18)F]-FEPPA V T were observed between groups in either gray (F (1,39) = 0.179, P = .674) or white matter regions (F (1,38) = 0.597, P = .445). The lack of significant difference in neuroinflammation in treated patients with SCZ in the midst of a psychotic episode and HV suggests that neuroinflammatory processes may take place early in disease progression or are affected by antipsychotic treatment.

 

Int J Tryptophan Res. 2014 Sep 16;7:15-22. doi: 10.4137/IJTR.S16800. eCollection 2014.

Imbalanced kynurenine pathway in schizophrenia.

Kegel ME1, Bhat M2, Skogh E3, Samuelsson M3, Lundberg K3, Dahl ML4, Sellgren C5, Schwieler L1, Engberg G1, Schuppe-Koistinen I2, Erhardt S1.

Author information

 

 

Abstract

Several studies suggest a role for kynurenic acid (KYNA) in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN). Here we investigate the levels of QUIN in cerebrospinal fluid (CSF) of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22) and those of controls (n = 26) were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36). CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls (P = 0.027). In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.

 

  1. 2014 Dec;50:210-9. doi: 10.1016/j.psyneuen.2014.08.016. Epub 2014 Sep 2.

Suicidal patients are deficient in vitamin D, associated with a pro-inflammatory status in the blood.

Grudet C1, Malm J2, Westrin A3, Brundin L4.

Author information

 

 

Abstract

BACKGROUND:

Low levels of vitamin D may play a role in psychiatric disorders, as cross-sectional studies show an association between vitamin D deficiency and depression, schizophrenia and psychotic symptoms. The underlying mechanisms are not well understood, although vitamin D is known to influence the immune system to promote a T helper (Th)-2 phenotype. At the same time, increased inflammation might be of importance in the pathophysiology of depression and suicide. We therefore hypothesized that suicidal patients would be deficient in vitamin D, which could be responsible for the inflammatory changes observed in these patients.

METHODS:

We compared vitamin D levels in suicide attempters (n=59), non-suicidal depressed patients (n=17) and healthy controls (n=14). Subjects were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and went through a structured interview by a specialist in psychiatry. 25(OH)D2 and 25(OH)D3 were measured in plasma using liquid-chromatography-mass-spectrometry (LC-MS). We further explored vitamin D’s association with plasma IL-1β, IL-6 and TNF-α.

RESULTS:

Suicide attempters had significantly lower mean levels of vitamin D than depressed non-suicidal patients and healthy controls. 58 percent of the suicide attempters were vitamin D deficient according to clinical standard. Moreover, there was a significant negative association between vitamin D and pro-inflammatory cytokines in the psychiatric patients. Low vitamin D levels were associated with higher levels of the inflammatory cytokines IL-6 and IL-1β in the blood.

CONCLUSION:

The suicide attempters in our study were deficient in vitamin D. Our data also suggest that vitamin D deficiency could be a contributing factor to the elevated pro-inflammatory cytokines previously reported in suicidal patients. We propose that routine clinical testing of vitamin D levels could be beneficial in patients with suicidal symptoms, with subsequent supplementation in patients found to be deficient.

 

Am J Psychiatry. 2014 Sep;171(9):901-5. doi: 10.1176/appi.ajp.2014.14060749.

Priming the brain for psychosis: maternal inflammation during fetal development and the risk of later psychiatric disorder.

Cannon M, Clarke MC, Cotter DR.

 

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