In vitro studies have demonstrated possible neuroprotective effects of the following pro-inflammatory cytokines: IL-6, IL-1β and TNF-α against glutaminergic excitotoxicity in brain through different pathways.

In the current study, we aim to correlate level of the above pro-inflammatory cytokines in serum with glutamate levels in head of caudate nucleus measured using Proton Magnetic Resonance Spectroscopy (1H-MRS) in patients with obsessive-compulsive disorder (OCD), a neuropsychiatric illness with possible multifactorial aetiology including immunological and excitotoxic factors.

Thirty psychotropic-naïve patients with OCD and an equal number of gender and age-matched normal controls were recruited in the study. A detailed psychiatric assessment was carried out including sociodemographic and clinical variables. A 3T MR imaging and spectroscopy session was carried out in head of caudate nucleus. Further, absolute quantification of glutamate level was obtained using LC model. Simultaneously, 5 mL of blood sample was collected and assayed for the above pro-inflammatory cytokines (Siemens, Immulite™). The level of glutamate was correlated with the cytokine levels in patients with OCD.

The level of Glx was significantly higher in patients with OCD as compared to controls (P < 0.05). The Glx level negatively correlated with two of the three pro-inflammatory cytokines: IL-6 and TNF-α (r = −0.807; r = −0.838; P < 0.05) while no significant correlation was demonstrated with IL-1β.

The findings provide preliminary evidence regarding possible neuroprotective effects of pro-inflammatory cytokines against glutaminergic excitotoxicity in patients with OCD. Further studies including patients with other psychiatric illnesses as controls are required for confirmation of the above findings.

The authors have not supplied their declaration of competing interest.

A large number of studies have reported that the prolactin concentration was significantly increased in the Taq1A A1 allele carriers because several reports revealed that individuals with the DRD2 Taq1A A1 allele have a reduced density of brain D2 receptors.

The main aim of this study was to identify the impact of pharmacogenetic markers associated with prolactin concentration in risperidone-treated children and adolescents with autism spectrum disorders.

One hundred and forty-seven children and adolescents with autism, aged 3 to 19, received risperidone. The clinical data of patients were recorded from medical records. Prolactin levels were measured by chemiluminescence immunoassay. Three CYP2D6 single nucleotide polymorphisms (SNPs), CYP2D6*4 (1846G>A), *10 (100C>T), and *41 (2988G>A), one gene deletion (*5), and DRD2 Taq1A (rs1800497) polymorphism were genotyped by TaqMan real-time PCR.

The three common allelic frequencies were CYP2D6*10 (55.10%), *1 (32.65%) and *5 (6.12%), respectively. Patients were grouped according to their CYP2D6 genotypes. The DRD2 genotype frequencies were Taq1A A2A2 (38.77%), A1A2 (41.50%), and A1A1 (19.73%), respectively. There were statistically significant differences in prolactin level of patients among the three groups (P = 0.033). The median prolactin level in patients with DRD2 Taq1A A2A2 (17.80 ng/mL) was significantly higher than A1A2 (17.10 ng/mL) and A1A1 (12.70 ng/mL).

DRD2 Taq1A A2A2 polymorphisms may be a critical role in an influence prolactin elevation during risperidone treatment in ASD.

The authors have not supplied their declaration of competing interest.

The determination of the accurate CYP2D6 genotyping is essential in the clinical setting and individualization of drug therapy.

In this study, was to apply the Luminex xTAG technology to detect significant CYP2D6 polymorphisms and copy number variation, including assessment the relationship of CYP2D6 polymorphisms and risperidone plasma concentration in autism spectrum disorder children (ASD) treated with risperidone.

All 84 ASD patients included in this study had been receiving risperidone at least for 1 month. The CYP2D6 genotypes were determined by luminex assay. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured using LC/MS/MS.

Among the 84 patients, the most common genotype was CYP2D6*1/*10 (26.19%). The most common allele was CYP2D6*10 (51.79%) and the second most allele was CYP2D6*1 (27.98%). There were 46 (55.42%) classified as EM, 33 (39.76%) as IM, and 4 (4.82%) as UM. The plasma concentration of risperidone and risperidone/9-hydroxyrisperidone ratio in the patients were significant differences among the CYP2D6 predicted phenotype group (P = 0.001 and P < 0.0001, respectively). Moreover, the plasma concentration of risperidone and risperidone/9-hydroxyrisperidone ratio in the patients with CYP2D6 activity score 0.5 were significantly higher than those with the CYP2D6 activity score 2.0 (P = 0.004 and P = 0.002, respectively).

The present study suggests that it would be ideal to identify the CYP2D6 genotype of patients before prescribing and administering risperidone. Furthermore, the use of CYP2D6 gene scoring system to determine an individual's metabolic capacity may become an essential tool for a more rational and safer drug administration.

The authors have not supplied their declaration of competing interest.

A critical need exists for progress in the characterization of targets for pro-cognitive drug discovery. We previously demonstrated that Telmisartan (TLM), an angiotensin type 1 receptor (AT1) blocker and partial agonist of peroxisome proliferator-activated receptor gamma (PPARγ), alleviates cognitive decline in chronically stressed rats. Understanding of mechanistic background of this phenomenon is hampered by both dual binding sites of TLM and limited data on the molecular consequences of central AT1 blockade and PPARγ activation.

To discriminate molecular effects of AT1 blockade and PPARγ activation in stress induced memory impairment.

In this study, we investigated mechanism of neuroprotection provided by TLM in chronic psychological stress.

We analyzed BDNF gene expression in the hippocampus (HIP) and medial prefrontal cortex (mPFC) in chronically restrained stressed Wistar rats (2.5 h, 21 days), repeatedly treated with TLM (1 mg/kg), GW9662 (0.5 mg/kg) – a selective PPARγ receptor antagonist, or both in combination. TATA box binding protein (Tbp) was an internal control for expression studies.

Alterations of mRNA expression of BDNF are shown on Figs. 1 and 2.

AT1 receptor blockade restores cognitive functions in chronically stressed subjects, which is associated with changes in primarily cortical gene expression.

The authors have not supplied their declaration of competing interest.

The pattern of changes can be related with the differences between perioperative expectations and real long-term outcomes. Correlations between changes seen in BDI and SF36 scores with age can be considered as a confirmatory evidence for this idea.

All cases showed an insignificant gradual decline in digit span test, which may be independent of the surgical procedure. Although the COWA test could not prove a significant deterioration in verbal fluency but a slight decline after one year was obvious, in addition to one patient who turned aphasic during this period.

The outcomes showed that the benefits of DBS outweigh the slight risk of developing depression.

The authors have not supplied their declaration of competing interest.

MDD is a common, chronic and recurrent illness .it is essential to reach full remission in acute treatment. tDCS is a non-invasive brain stimulation that uses direct electrical currents to stimulate specific parts of the brain.

Is to assess the effectiveness of tDCS in patients with treatment resistance MDD.

Eighty outpatients of a psychiatric clinic were selected. Subjects meet (DSM-IV) diagnostic criteria for MDD. All patients had failed to respond to at least two standard antidepressant medication, in the current episode. Patients with bipolar depressive disorder, MDD with psychotic and atypical features, other psychiatric disorders, sever medical condition, acute suicidality and pregnancy were excluded. All patients received stable drug regimens for at least two weeks before enrollment and drug dosages remained unchanged throughout the study. They revised 8 stimulation sessions, using a 2 mA current, for 20 minutes, in 8 consecutive days. The anodal electrode was placed over the left DLPFC. Cathode electrode over the right supraorbital region. Mood was evaluated with 21-item Hamilton Rating Depression Scale and the Beck Depression Inventory.

We designed a pretest–posttest study and evaluate depression at baseline (pre-intervention), immediately after 8 sessions (post-intervention) and two months after treatment onset (follow-up).

There is a significant difference between Pre- vs. post-intervention (FBDI = 246.58, P < 0.001; FHRSD = 214.56, P < 0.001) and pre vs. Follow-up intervention (FBDI = 323.10, P < 0.001; FHRSD = 150.96, P < 0.001).

It can be said that tDCS had effective and enduring variation (P post vs. follow-up > 0.05) in improving the clinical symptoms of MDD.

The authors have not supplied their declaration of competing interest.

Limitations of available treatment methods of dementia imply constant need to search for new, supplementary therapy strategies. There is a consensus that vascular lesions, oxidative stress, inflammatory processes and abnormal neurotransmission are associated with dementia. Due to the anti-inflammatory (modification of pro-inflammatory cytokines concentration), antioxidative effect of cryogenic temperatures as well as the hormonal and lipid changes, they may play an important role in preventing or inhibiting pathophysiological processes.

To assess the influence of whole-body cryostimulation on cognitive functions of patients with MCI.

RCT design is used to examine the influence of whole-body cryotherapy (WBC) on people with mild cognitive impairments (MCI) with the evaluation of psychometric, somatic and laboratory parameters. Participants undergo 10 sessions each day of 2–3 min of WBC in experimental group (−110 till −160 °C) and placebo (−20 °C). The CDR, MoCA, TYM, DemTect and SLUMS scales are used among others at baseline and follow-up. Preliminary data of 7 volunteers (n = 7, 49–79 years old) were presented. Results on Fig. 1.

Among obtained psychometric results show that all, except of one, patients significantly improved their scores after WBC. That is a very promising feedback for future evaluation of WBC effectiveness in prevention of dementia in patients with MCI.

The authors have not supplied their declaration of competing interest.

Patients with schizophrenia show impairments in social cognitive abilities, such as recognizing facial emotions. However, the relationships between specific deficits of emotion recognition and with clusters of psychotic remain unclear.

To explore whether facial emotion recognition was associated with severity of symptoms and to which presentation of psychotic symptoms.

Facial emotion recognition (FER) were evaluated in 58 patients with stable schizophrenia with a newly validated FER task constructed from photographs of the face of a famous Tunisian actress representing the Ekman's six basic emotions (happiness, anger, disgust, sadness, fear, and surprise). Symptomatology evaluation comprised the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Clinical Global Impressions Scale Improvement and severity (CGI).

Patients who failed to identify anger had significantly higher scores in hyperactivity item (P < 0.0001). The patients who had a difficulty to identify sadness had more grandiosity (P ≤ 0.002). The impairment in happiness recognition was correlated with hallucination (P = 0.007) and delusion (P = 0.024) items. Incapacity to identify fear was associated to lack of judgment and insight (P = 0.004).

Deficits in recognition of specific facial emotions may reflect severity of psychiatric symptoms. They may be related to specific clusters of psychotic symptoms, which need to be confirmed in further studies.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

The metabolic syndrome (MetS) and cognitive impairments, both related with poor outcomes in schizophrenia, are common in patients with this disorder. MetS has been associated with cognitive impairments in schizophrenia, but there is no general consensus regarding the description of various domains of neurocognition in patients with schizophrenia related to MetS.

The goal of this study was to assess cognitive functions in female patients with schizophrenia complicated by metabolic syndrome compared to those with schizophrenia without metabolic syndrome.

Fifty-four female patients diagnosed with schizophrenia were divided into two groups: MetS group (MetS+) and non-MetS group (MetS−). Cognitive functioning were investigated using the Brief Assessment of Cognition in Schizophrenia (BACS).

Twenty-seven (52%) patients with schizophrenia met criteria for the MetS diagnosis. Mean age of patients was 40.80. Patients from MetS+ group performed significantly worse on verbal memory (P = 0.005), executive functions (P = 0.028) and motor speed (P = 0.035) as compared to MetS− group. Patients with schizophrenia who were hypertensive showed cognitive impairments in 2 domains of cognition: attention and speed of information processing (P = 0.004) and verbal fluency (P = 0.001). Patients with hypertriglyceridemia performed significantly worse on verbal memory (P = 0.005). Motor speed was associated with waist circumference (P = 0.02).

At a mean age of 40 years old, female patients with schizophrenia and metabolic syndrome show difficulties in more domains of cognitive function compared to female patients with schizophrenia without metabolic syndrome. Our findings suggest a link between cognition and metabolic syndrome in female patients with schizophrenia.

The authors have not supplied their declaration of competing interest.

Medication non-adherence presents a considerable problem in patients with schizophrenia. Cognitive and executive functions can affect adherence. The association between medication non-adherence and cognitive impairment in schizophrenia is under investigated with limited and conflicting research data.

To prospectively assess the rate of drug adherence among a sample of patients with schizophrenia and to compare the cognitive and executive functions between adherent and non-adherent patients.

One hundred and nine patients with schizophrenia diagnosed according to the DSM-IV classification were initially assessed by the Wechsler Adult Intelligence Scale (WAIS), Wechsler Memory Scale-Revised (WMS-R) and Wisconsin Card Sorting Test (WCST) and six months later by the Brief Adherence Rating Scale (BARS).

Among the patients, 68.8% were non-adherent to their antipsychotic medication. Adherent patients (31.2%) had significantly higher mean scores for the total, verbal and performance IQ. Moreover, they had significantly higher mean scores in most of WMS subtests (orientation, information, verbal paired association, digit span, visual memory span), and higher mean scores for; total correct, conceptual level response, percentage and categories completed on the WSCT subscales (P < 0.0001). Whereas the non-adherent group had higher mean scores in; trials administered, total errors, perseverative responses, and perseverative errors (P < 0.0001). In a step regression analysis, digit span, conceptualization, total and percentage of errors were putative predictors of non-adherence to antipsychotic medications.

Cognitive deficits, especially verbal memory and executive functions were the strongest patients’ related factors associated with non-adherence to medication. Psychiatrists should consider possible cognitive factors influencing adherence to enable offering proper interventions.

The author has not supplied his declaration of competing interest.

The relation between C-reactive protein (CRP), depression and antidepressant consumption has been well explored in major depressive disorders but not in schizophrenia, which has a high rate of depression comorbidity. The objectives of this study were:

– to determine the prevalence of abnormal CRP levels, depression and antidepressant consumption in a multi-center community-dwelling sample of subjects with schizophrenia;

– to determine the association between abnormal CRP levels, depression and antidepressant consumption in schizophrenia.

Two hundred and nineteen stable patients with schizophrenia (mean age = 31.6 years, 75.3% male gender) were systematically included in the multicentre network of FondaMental Expert Center for schizophrenia (FACE-SZ) and assessed with Calgary Depression Scale for depression. High sensitivity CRP (hs-CRP) was measured with an assay using nephelometry (Dade Behring). Abnormal CRP level was defined by levels > 3 mg/L. Current medication was recorded.

Overall, 63 subjects (28.8%) were found to have abnormal CRP levels, 43 (20.1%) received a diagnosis of comorbid current depression, and 51 (31.9%) had ongoing antidepressant treatment. In univariate analysis, abnormal CRP levels were found to be significantly associated with metabolic syndrome (P = 0.0011) and with antidepressant consumption (P = 0.01), while depression, psychotic symptomatology, age of onset, illness duration, sociodemographic characteristics, current tobacco or cannabis status were not (all P > 0.05).

In a multivariate model, abnormal CRP was highly associated with antidepressant consumption independently of other confounding variables (adjusted odd ratio = 2.9, 95% confidence interval 1.2–6.8).

Abnormal CRP levels in schizophrenia were found to be associated with antidepressant consumption, but not with depression.

The authors have not supplied their declaration of competing interest.

Children born by cesarean section (“c-birth”) are known to have different microbiota and a natural history of different disorders including allergy, asthma and overweight compared to vaginally born (“v-birth”) children. C-birth is not known to increase the risk of schizophrenia (SZ), but to be associated with an earlier age at onset. To further explore possible links between c-birth and SZ, we compared clinical and biological characteristics of c-born SZ patients compared to v-born ones.

Four hundred and fifty-four stable community-dwelling SZ patients (mean age = 32.4 years, 75.8% male gender) were systematically included in the multicentre network of FondaMental Expert Center for schizophrenia (FACE-SZ).

Overall, 49 patients (10.8%) were c-born. These patients had a mean age at schizophrenia onset of 21.9 ± 6.7 years, a mean duration of illness of 10.5 ± 8.7 years and a mean PANSS total score of 70.9 ± 18.7. None of these variables was significantly associated with c-birth. Multivariate analysis showed that c-birth remained associated with lower peripheral inflammation (aOR = 0.07; 95% CI 0.009–0.555, P = 0.012) and lower premorbid ability (aOR = 0.945; 95% CI 0.898–0.994, P = 0.03) independently of age, age at illness onset, sex, education level, psychotic and mood symptomatology, antipsychotic treatment, tobacco consumption, birth weight and mothers suffering from schizophrenia or bipolar disorder.

Altogether, literature data as well as our results suggest that c-birth is associated with lower weight gain and lower inflammation in schizophrenia, which could be explained by microbiota differences. Further studies should take into account c-birth when exploring the role of microbiota in SZ patients.

The authors have not supplied their declaration of competing interest.

The aim of this study is to explore connectivity of the left dorsolateral prefrontal cortex (LDLPC) by functional magnetic resonance imaging during resting state, in subjects affected by schizophrenia and unaffected relatives.

We recruited a group of 29 patients diagnosed with schizophrenia, who were treated with atypical antipsychotics, who are and were clinically stable in the last 6 months and had an illness duration range from 5 up to 15 years. We also recruited a group of 23 unaffected relatives, without history of other mental, neurological or somatic disease and a group of 37 healthy volunteers. No subject in any of the three groups met criteria for substance use disorders.

All three groups were clinically evaluated, and a functional magnetic resonance during Resting State was performed.

Functional images were reoriented to the first scan, normalized to the MNI EPI template and smoothed with an 8 mm Gaussian kernel, with SPM. The CONN-FMRI Toolbox v1.2 was used to create individual subject seed-to-voxel connectivity maps, to the corresponding seeds of the default mode network.

Fig. 1.

Our results show a significant increase in connectivity between LDLPC and anterior prefrontal cortex, dorsolateral prefrontal cortex and somatosensory association areas, especially between patients and controls. It is noteworthy to mention that we found a significant decrease in connectivity between LDLPC and supramarginal gyrus, superior temporal gyrus and somatosensory association areas between unaffected relatives and controls.

The authors have not supplied their declaration of competing interest.

Brexpiprazole is a serotonin-dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors.

Evaluating the efficacy, safety, and tolerability of flexible doses of brexpiprazole compared with placebo in patients with acute schizophrenia.

Primary endpoint was change from baseline to week 6 in PANSS total score and key secondary endpoint was change from baseline to week 6 in CGI-S score.

Phase 3, multi-center, randomized, double-blind, placebo-controlled, active reference, trial (NCT01810380). Hospitalized patients were randomized to brexpiprazole (2 to 4 mg/day), placebo, or quetiapine extended release (400 to 800 mg/day) for 6 weeks. Quetiapine was included as an active reference. Changes from baseline were analyzed using an MMRM approach.

Mean change in PANSS total score was −20.0 and −15.9 in the brexpiprazole (n = 150) and placebo (n = 159) groups, respectively (P = 0.056). Sensitivity analyses suggested treatment effect (e.g., ANCOVA, LOCF: P = 0.025; ANCOVA, OC: P = 0.026). Mean change in PANSS total score (−24.0) with quetiapine (n = 150) was significantly greater than that with placebo (P < 0.001), demonstrating sensitivity of the assay. Brexpiprazole separated from placebo on the mean change in CGI-S score (−1.2 vs. −0.9, P = 0.014). The proportion of patients reporting TEAEs were similar between the brexpiprazole and placebo treatment groups (54% versus 54.7%).

Treatment with brexpiprazole showed a clinically meaningful improvement in patients with acute schizophrenia. While the difference between brexpiprazole and placebo only approached statistical significance, sensitivity analyses and secondary endpoints supported a treatment effect of brexpiprazole.

The authors have not supplied their declaration of competing interest.

Self-stigma is the maladaptive psychosocial phenomenon that can affect the patient's self-image, may lead to dysphoria, social isolation, reduced adherence and quality of life. Maladaptive coping strategies may adversely disturb the overall functioning of psychiatric patients.

Thinking about coping strategies and self-stigma in practice may play a significant role in understanding patients with schizophrenia spectrum disorders, especially for mental health professionals. Focus on coping strategies could be a useful concept in supportive and educational therapy to help patients in using more adaptive coping strategies and decrease their self-stigma.

The aim of this study was to determine the relation between coping strategies and the self-stigma among outpatients with schizophrenia and related disorders.

Stress Coping Style Questionnaire (SVF-78), Internalized Stigma of Mental Illness (ISMI) and severity of the disorder (measured by Clinical Global Impression objective and subjective form) were assessed.

One hundred and four patients suffering from schizophrenia (n = 67), schizoaffective disorder (n = 30), polymorphic psychotic disorder (n = 3), schizotypal disorder (n = 2) and delusional disorder (n = 2) were included in the study. The results showed that there was a high positive correlation between negative coping and self-stigma, and the negative correlation between positive strategies and the overall score of self-stigma. Stepwise regression analysis showed that negative coping (especially resignation), subjective severity SubjCGI and positive coping strategies (especially positive self-instruction) explains 52.8% of the overall score variance of self-stigma (Tables 1–3).

This study revealed that there is a connection between self-stigma and coping strategies in patients suffering from schizophrenia spectrum disorders.

The authors have not supplied their declaration of competing interest.

The effects of long-term antipsychotic medication use on structural brain changes in psychoses are still unknown. Severity and duration of illness are key confounders when evaluating antipsychotic effects on brain morphology.

Understanding the role of antipsychotic medication on brain morphology in psychoses.

To analyze whether cumulative lifetime or current antipsychotic medication dose relates to brain morphology in schizophrenia and other psychoses at age of 43 years.

Forty-four schizophrenia cases and 35 with other psychoses from the Northern Finland Birth Cohort 1966 were scanned on a 1.5T GE Signa scanner and brain structures were extracted using volBrain automated volumetry system (http://volbrain.upv.es). Data of antipsychotic medication were collected from medical records and interviews. We used linear regression model to analyze the effect of antipsychotic medication on brain volumes and used intracranial volume and onset age as covariates. We also performed additional analyses adding psychotic symptoms (PANSS Total score) as a covariate.

Higher lifetime and current dose associated to left lateral ventricle increase (b = 0.33, P = 0.033; b = 0.307, P = 0.042, respectively) and right and left accumbens decrease (b = −0.405, P = 0.013, b = −0.404, P = 0.010; b = −0.302, P = 0.027, b = −0.282, P = 0.036, respectively) in schizophrenia but not in other psychoses. When PANSS was added to the model, the findings remained regarding right and left accumbens, but not regarding left lateral ventricle.

It seems that antipsychotic medication affects the brain in schizophrenia, but not in the heterogeneous group of other psychoses. In schizophrenia, brain changes associated to antipsychotic medication cannot be explained by illness duration or symptom severity.

The authors have not supplied their declaration of competing interest.

To observe the association between adverse effects of long-term use of antipsychotic drugs in female schizophrenic patients and dopamine D2 receptor (DRD2), cytochrome P450 (CYP) 2D6, estrogen receptor-α gene (ESR1).

The subjects were 89 female schizophrenic patients (age range from 18 to 40) who had been taking the same medication for more than 3 months. The adverse effects with regard to hyperprolactinemia were studied through the blood collection at one point of the subjects. Furthermore, the effect of DRD2, CYP2D6, ESR1 on serum prolactin level and amenorrhea was analyzed.

There was a lower concentration of E2 in patients with amenorrhea. In addition, an inverse correlation was found between prolactin level and E2 level. Hyperprolactinemia (HPRL) was commonly found in patients who had been using risperidone, amisulpride and paliperidone; in contrast, HPRL was found less in those who had been taking aripiprazole, olanzapine, ziprasidone, clozapine and quetiapine. Moreover, female schizophrenic patients who had DRD2 Taq1 A1 allele had twice the chance of developing amenorrhea than those who did not have A1 allele. Female schizophrenic patients who had Taq1 A1 allele also had 48% higher concentration level of prolactin than those who did not have A1 allele. There was no association found between prolactin and CYP2D6 or ESR1.

Female schizophrenic patients who had DRD2 Taq1 A1 allele showed high prolactin level and high-frequency of HPRL. Therefore, reducing the use of prolactin-elevating antipsychotics for female schizophrenic patients with DRD2 Taq1 A1 allele would be one method minimizing the adverse effects of drug-induced hyperprolactinemia.

The authors have not supplied their declaration of competing interest.