Depressive Symptoms In Schizophrenia Research Articles

The Prevalence of Depressive Symptoms in Schizophrenia: A Cross-Sectional Study

The Prevalence of Depressive Symptoms in Schizophrenia: A Cross-Sectional Study

Development and Characterization of Nanofiber Strip Containing Sertraline for Buccal Application

Sertraline is one of the selective serotonin reuptake inhibitors indicated in major depressive disorder. Schizophrenia is a mental disorder with frequent depressive symptoms. Sertraline is thought to be useful for the treatment of depressive symptoms in schizophrenia. The objective of this study is to formulate sertraline-containing nanofiber strips produced by the electrospinning process, which can be easily dispersed by the buccal route, suitable for the use of schizophrenia patients. Here, various ratios (%5, %7.5 and %10) of polyvinyl pyrrolidone (PVP) polymer solutions were prepared, and electrical conductivity, viscosity and surface tension characterization studies were performed on polymer solutions. After characterization studies, a polymer solution containing 5% PVP was selected to prepare nanofibers. Nanofibers were obtained by using the electrospinning method, each strip containing 5 mg sertraline. It was observed that the optimum formulation selected nanofiber had an average particle diameter of 371-439 nm in the SEM image. Tensile strength and elongation at break percentage values of 5% PVP-sertraline nanofibers values were 0.449±0.284 (Mpa) and 22.6±3.66 (%), respectively. The loading capacity and encapsulation efficiency of the formulation are 4.53%±0.31 and 79.61±10.56 respectively. In vitro drug dissolution studies showed that sertraline-containing buccal nanofibers conformed to the Hixson-Crowell kinetic model.

The contribution of the cingulate cortex: treating depressive symptoms in first-episode drug naïve schizophrenia.

Our previous study has shown the cingulate cortex abnormalities in first-episode drug naïve (FEDN) schizophrenia patients with comorbid depressive symptoms. However, it remains largely unknown whether antipsychotics may induce morphometric change in cingulate cortex and its relationship with depressive symptoms. The purpose of this study was to further clarify the important role of cingulate cortex in the treatment on depressive symptoms in FEDN schizophrenia patients. In this study, 42 FEDN schizophrenia patients were assigned into depressed patients group (DP, n=24) and non-depressed patients group (NDP, n=18) measured by the 24-item Hamilton Depression Rating Scale (HAMD). Clinical assessments and anatomical images were obtained from all patients before and after 12-week treatment with risperidone. Although risperidone alleviated psychotic symptoms in all patients, depressive symptoms were decreased only in DP. Significant group by time interaction effects were found in the right rostral anterior cingulate cortex (rACC) and other subcortical regions in the left hemisphere. After risperidone treatment, the right rACC were increased in DP. Further, the increasing volume of right rACC was negatively associated with improvement in depressive symptoms. These findings suggested that the abnormality of the rACC is the typical characteristics in schizophrenia with depressive symptoms. It's likely key region contributing to the neural mechanisms underlying the effects of risperidone treatment on depressive symptoms in schizophrenia.

Cariprazine’s efficacy in treating depressive symptoms – pooled data from schizophrenia, bipolar depression and major depression trials

IntroductionDepressive symptoms are a common feature of schizophrenia (SCH) and define bipolar disorder and major depressive disorder (MDD). Their emergence is related to altered neurotransmission at the serotonin receptors and potentially at dopamine D3 receptors.ObjectivesThe aim of this analysis was to examine the efficacy of cariprazine (CAR) in treating depressive symptoms in SCH, bipolar depression (BD) and MDD.MethodsClinical trials with randomised, double-blind, placebo (PLB)-controlled designs were included in these analyses. Data from 3 SCH [NCT00694707, NCT01104766, NCT01104779; 1.5-9 mg/d] and 3 BD [NCT01396447, NCT02670538, NCT02670551; 1.5-3 mg/d] studies were pooled. In MDD, add-on CAR to antidepressant treatment was evaluated against PLB in two studies [NCT03738215: 1.5 and 3 mg/d; NCT01469377: 1-2 mg/d and 2-4.5 mg/d).Least square (LS) mean changes were analysed using Mixed Model Repeated Measures: from baseline (BL) to Week 6 in the Positive and Negative Syndrome Scale (PANSS)-derived Marder anxiety/depression factor items (schizophrenia); from BL to Week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total scores (bipolar depression); and from BL to Week 6 [NCT03738215] and Week 8 [NCT01469377] in MADRS total score (major depressive disorder).ResultsAltogether, 1466 SCH (PLB=442, CAR=1024) patients were included in the pooled analysis. In the BD analysis, data from 1383 (PLB=460, CAR=923) patients were pooled. In the MDD trials, there were 502 CAR (1.5mg/d=250, 3 mg/d=252) and 249 PLB-treated patients [NCT03738215], and 544 CAR (1-2 mg/d=273, 2-4.5 mg/d=271) and 264 PLB patients in the other study [NCT01469377]. In SCH, CAR achieved significantly greater reductions than PLB on the Marder anxiety/depression factor domain (LS mean change: PLB= -2.66, CAR= -3.26, p<0.01): the effect was driven by 3 out of 4 items. In BD, CAR yielded significantly greater improvement on the MADRS compared to PLB (LS mean change: PLB= -12.05, CAR= -14.69, p<0.001), which was driven by 9 out of 10 items. In MDD [NCT03738215], CAR 1.5 mg/d add-on significantly alleviated depressive symptoms compared to PLB (LS mean change: PLB= -11.5, CAR 1.5mg/d= -14.1, p<0.01), while in the other MDD trial [NCT01469377], CAR 2-4.5 mg/d add-on produced significantly greater reductions than PLB (LS mean change: PLB= -12.5, CAR 2-4.5 mg/d= -14.6, p<0.01).ConclusionsThese findings indicate that CAR is an effective treatment option for the treatment of depressive symptoms independent of disease (in SCH, BD and MDD), being a transdiagnostic broad-spectrum treatment option.Disclosure of InterestR. McIntyre Grant / Research support from: CIHR/GACD/National Natural Science Foundation of China (NSFC), the Milken Institute, Consultant of: Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Gedeon Richter, Recordati, Atai Life Sciences, Speakers bureau of: Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Gedeon Richter, Recordati, Atai Life Sciences, R. Csehi Employee of: Gedeon Richter Plc., G. Németh Employee of: Gedeon Richter Plc.

Exploring the link between cognitive deficit, self-esteem, alexithymia, and depressive symptom of schizophrenia.

ObjectiveTo the best of our knowledge, studies have been rarely conducted to assess the correlation between cognitive deficit, self‐esteem, and alexithymia in the depressive symptoms of schizophrenia (SCZ). Therefore, this study aims to explore the risk factors associated with impairment of cognitive function, alexithymia, and self‐esteem among a representative sample of first‐episode schizophrenic patients.MethodWe recruited 107 first‐episode schizophrenic patients (48.6% male, 51.4% female, 36.94 ± 10.73 years) into the research group, according to the Diagnostic and Statistical Manual of Mental Disorders (5th edition). A total of 45 healthy people (51.1% male, 48.9% female, 32.47 ± 10.94 years) were enlisted in the healthy control group. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Cognitive functions were estimated using the Montreal Cognitive Assessment Scale (MoCA). The feelings of respect and self‐acceptance were tested using the Rosenberg Self‐Esteem Scale (RSES). Emotion of identifying and describing were measured by self‐report scale of Toronto Alexithymia Scale‐20 (TAS‐20).ResultsOverall cognitive impairment and alexithymia were found more serious in the patients of SCZ than the healthy group (p < .001, respectively). The patients of SCZ have higher self‐esteem than the healthy group (p = .013). Total score of MoCA, ability of visual space and executive function, and delayed recall were explored had negatively correlation with alexithymia (r = −.319, p = .001; r = −.248, p = .010; r = −0.263, p = .006). Total score of RSES and depressive symptoms of PANSS had a positive correlation with alexithymia (r = .394, p = .001; r = .208, p = .032). Stepwise regression analyses have shown a positive relationship between difficulty describing feelings and depression subscale of PANSS (β = .188, t = −2.007, p = .047) while a negative relationship between externally oriented thinking and depression subscale of PANSS (β = −.244, t = −2.603, p = .011). A positive link correlation also was found between the total scores of TAS and RSES (β = .372, t = 4.144, p = .001). A negative relevance was found between the total scores of TAS and scores of MoCA (β = −.305, t = −3.348, p = .001).ConclusionOverall impairment of cognitive function and alexithymia are commonly encountered in SCZ patients. Poor cognitive function, alexithymia, and high level self‐esteem may be specific detective risk factors for the depressive symptoms of SCZ.

High-frequency rTMS in the treatment of depressive symptoms in schizophrenia: a neurophysiological profile of respondents and nonresponders

IntroductionDepressive symptoms in schizophrenia have a high prevalence – up to 20-60 %, at the different illness stages. Non-pharmacological treatment, namely rTMS, seems like a promising approach that lacks side-effects typical for antidepressants. RTMS is widely applied in the treatment of depression, however the studies within schizophrenia domain are still rather fewObjectivesThe aim was to examine a potential of neurophysiological data for prediction of the effects of rTMS in the treatment of patients with schizophrenia with depressive symptomsMethods20 male patients with schizophrenia (F20.004, F20.014, F20.414, ICD–10) were examined at the stage of incomplete remission with predominance of prolonged (more than 6 months) treatment resistant depressive symptoms. An examination (clinical and neurophysiological (oddball ERP and EEG) fragments)) was repeated twice - before and after a course of 10 Hz rTMS (left DLPC, 2000 pulses per session, 15 sessions).ResultsPoor outcome was associated with initially higher coherence in alpha and lower - in beta1 EEG bands. The amplitudes of non-target N100 and mismatch negativity didn’t differ the groups of responders and nonrespondersConclusionsThe disturbances within brain networks of beta1 and alpha generators merit attention as potential neurophysiological markers with predictive value in rTMS treatment of patients with schizophrenia with depressive symptoms.DisclosureNo significant relationships.

Family interventions for relapse prevention in schizophrenia: a systematic review and network meta-analysis

Family interventions are efficacious for relapse prevention in schizophrenia. Multiple different models have been developed. We aimed to compare the efficacy, acceptability, and tolerability of family interventions for relapse prevention in schizophrenia. In this systematic review and network meta-analysis, we searched for randomised controlled trials that investigated family intervention models aimed at preventing relapse in patients with schizophrenia. We searched EMBASE, MEDLINE, PsycINFO, BIOSIS, CENTRAL, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform up to Jan 20, 2020 and PubMed up to July 15, 2021. We included blinded and open-label randomised controlled trials in which at least 80% of patients had schizophrenia spectrum disorders. We excluded studies in which all patients were acutely ill, had a concurrent medical or psychiatric disorder, or were prodromal or "at risk of psychosis". Study selection and data extraction were done by two independent reviewers. Data were extracted about overall, positive, negative, and depressive symptoms of schizophrenia, quality of life, adherence, overall functioning, family burden, expressed emotion, and discontinuations due to inefficacy. The primary outcome was relapse, measured with operationalised criteria, psychiatric hospital admissions, or clinical judgement. We did a frequentist, random-effects, network meta-analysis to calculate odds ratios ([ORs]; dichotomous outcomes) or standardised mean differences (continuous outcomes) with 95% CIs. The study protocol was registered with PROSPERO, CRD42020169951. We identified 28 395 studies through the database search and 334 from references of previous studies. We compared 11 family intervention models tested on a total of 90 randomised controlled trials with 10 340 participants (3579 females and 5632 males with sex indicated; median age 31 years [range 14-65]) in the network meta-analysis. Ethnicity data were not available. All interventions, with the exception of crisis-oriented interventions and family psychoeducation with two sessions or fewer, reduced the relapse rate significantly when compared with treatment as usual at the primary timepoint of 12 months. ORs compared with treatment as usual ranged from 0·18 (95% CI 0·12-0·27) for family psychoeducation alone to 0·63 (0·42-0·94) for community-based interventions involving family members. The results were robust in various sensitivity and subgroup analyses. The confidence in the estimates ranged from moderate to very low for different comparisons. Almost all family intervention models were efficacious in preventing relapse in schizophrenia. Family psychoeducation alone, without behavioural or skills training, was superior to the more complex models. Our results suggest that in contexts where there are financial constraints, family psychoeducation alone should be implemented. German Ministry for Education and Research.

The Role of OXT, OXTR, AVP, and AVPR1a Gene Expression in the Course of Schizophrenia.

Schizophrenia is a serious and chronic mental illness, the symptoms of which usually appear for the first time in late adolescence or early adulthood. To date, much research has been conducted on the etiology of schizophrenia; however, it is still not fully understood. Oxytocin and vasopressin as neuromodulators that regulate social and emotional behavior are promising candidates for determining the vulnerability to schizophrenia. The aim of this study was to evaluate the expression of OXT, OXTR, AVP, and AVPR1a genes at the mRNA and protein levels in patients with schizophrenia. Due to the neurodegenerative nature of schizophrenia, the study group was divided into two subgroups, namely, G1 with a diagnosis that was made between 10 and 15 years after the onset of the illness, and G2 with a diagnosis made up to two years after the onset of the illness. Moreover, the relationship between the examined genes and the severity of schizophrenia symptoms, assessed using PANSS (Positive and Negative Syndrome Scale) and CDSS scales (Clinical Depression Scale for Schizophrenia) was evaluated. The analysis of the expression of the studied genes at the mRNA and protein levels showed statistically significant differences in the expression of all the investigated genes. OXT and AVPR1a gene expression at both the mRNA and protein levels were significantly lower in the schizophrenia group, and OXTR and AVP gene expression at both the mRNA and protein levels was higher in the schizophrenia subjects than in the controls. Furthermore, a significant correlation of OXT gene expression at the mRNA and protein levels with the severity of depressive symptoms in schizophrenia as assessed by CDSS was found.

ДИНАМИКА КЛИНИЧЕСКОГО СОСТОЯНИЯ ПАЦИЕНТОВ С ШИЗОФРЕНИЕЙ С ПОСТПСИХОТИЧЕСКОЙ ДЕПРЕССИЕЙ, С ДУШЕВНОЙ БОЛЬЮ ПОД ВЛИЯНИЕМ БИНАУРАЛЬНОЙ СТИМУЛЯЦИИ ГОЛОВНОГО МОЗГА

In some cases, in the depressive symptoms of schizophrenia, the phenomenon of mental pain or «vital melancholy» is traced, which often has an obsessive nature and proceeds with suicidal intentions. The low effect of existing methods of therapy of this condition with the help of psychopharmacotherapy is noted. In this study, the authors attempted to additionally influence this symptom complex using binaural stimulation of the brain, along with psychopharmacotherapy. The authors used Th e Psychach e Scal e t o asses s mental pain and measure it numerically, and the PANSS scale to diagnose the clinical symptoms of schizophrenia. In the main group of patients receiving binaural brain stimulation, it was possible to achieve better treatment results for a number of symptoms related to the negative cluster, the cluster of general symptoms and one more additional symptom: emotional lability than in the control group that did not receive this specific additional treatment. The use of binaural brain stimulation in combination with drug therapy has significantly reduced the severity of mental pain in patients with schizophrenia.

Lipid and Energy Metabolism of the Gut Microbiota Is Associated with the Response to Probiotic Bifidobacterium breve Strain for Anxiety and Depressive Symptoms in Schizophrenia.

A recent meta-analysis found that probiotics have moderate-to-large beneficial effects on depressive symptoms in patients with psychiatric disorders. However, it remains unclear how the baseline gut microbiota before probiotic administration influences the host’s response to probiotics. Therefore, we aimed to determine whether the predicted functional profile of the gut microbiota influences the effectiveness of probiotic treatment in patients with schizophrenia. A total of 29 patients with schizophrenia consumed Bifidobacterium breve A-1 (synonym B. breve MCC1274) for 4 weeks. We considered patients who showed a 25% or more reduction in the Hospital Anxiety and Depression Scale total score at 4 weeks from baseline to be “responders” and those who did not to be “non-responders”. We predicted the gut microbial functional genes based on 16S rRNA gene sequences and applied the linear discriminant analysis effect size method to determine the gut microbial functional genes most likely to explain the differences between responders and non-responders at baseline. The results showed that lipid and energy metabolism was elevated at baseline in responders (n = 12) compared to non-responders (n = 17). These findings highlight the importance of assessing the gut microbial functional genes at baseline before probiotic therapy initiation in patients with psychiatric disorders.

Abnormal regional homogeneity (ReHo) and fractional amplitude of low frequency fluctuations (fALFF) in first-episode drug-naïve schizophrenia patients comorbid with depression.

The current study aimed to characterize the regional homogeneity (ReHo) or fractional amplitude of low frequency fluctuations (fALFF) alterations in first-episode drug-naïve schizophrenia comorbid with depression. Sixty-nine first-episode drug-naïve schizophrenia patients and 34 healthy controls (HC) were included in the final analysis. Schizophrenia patients were divided into depressive patients (DP) and non-depressive patients (NDP), with 35 and 34 patients respectively, using the Hamilton Rating Scale for Depression -17(HRSD-17). All participants underwent resting-state fMRI (rs-fMRI), the fALFF (slow-4 and slow-5 bands) and ReHo were used to process the data. The results revealed eleven brain regions with altered slow-5 fALFF, eleven brain regions with altered slow-4 fALFF and ten brain regions with altered ReHo among DP, NDP and HC groups. Compared to NDP, the DP group had increased slow-5 fALFF in the Right Inferior Temporal Gyrus, increased ReHo in the Right Superior and Inferior Frontal Gyrus. The altered slow-5 fALFF in the Right Inferior Temporal Gyrus, altered ReHo in the Right Inferior Frontal Gyrus and Superior Frontal Gyrus were all positively correlated with the depressive symptoms in patients. However, there were no significant differences in slow-4 fALFF between DP and NDP groups. Our results indicate that the increased slow-5 fALFF in the Right Inferior Temporal Gyrus, increased ReHo in the Right Superior and Inferior Frontal Gyrus were associated with depressive symptoms in schizophrenia, which may provide preliminary evidence in better understanding the neural mechanisms underlying depressive symptoms in schizophrenia.

Rhythmic transcranial magnetic stimulation in the treatment of resistant depression in schizophrenia

Rhythmic transcranial magnetic stimulation (rTMS) has long been actively used in the treatment of depressive disorders in various mental illnesses. At the same time, the question of the predictability of the results of this method for an individual patient remains open. Based on the existing ideas about the relationship of rTMS mechanisms with changes in the state of neural networks, one of the most perspective line is the search for prognostically significant neurophysiological markers. The study analyzed a wide range of EEG characteristics and evoked potentials recorded before treatment in the groups of responders and nonresponders in patients with depressive symptoms in schizophrenia, who have completed a course of rhythmic transcranial magnetic stimulation. The study revealed associations between an unfavorable treatment outcome and greater coherence in the alpha range (mainly in the caudal regions bilaterally) and less coherence in the beta1 range (involving temporal leads and left-hemisphere asymmetry). At the same time, such indicators as the amplitude of the N100 wave and the negativity of the mismatch were uninformative in terms of predicting the effectiveness of therapy.

Serum levels of neuropeptide Y in patients with chronic schizophrenia during treatment augmentation with sarcosine (results of the double-blind randomized controlled PULSAR study).

Modulation of glutamatergic neurotransmission in schizophrenia by sarcosine leads to a reduction in primary negative symptoms, while its metabolic profile is safe. In order to extend research in the area, we assessed serum levels of neuropeptide Y (NPY), a hypothalamic hormone related to anxiety and depression, also involved in mechanisms inducing weight gain. Additionally, we analyzed associations between NPY concentrations and its changes with severity of symptoms and metabolic parameters. A prospective 6-month, randomized, double-blind placebo-controlled trial was completed by 57 subjects with chronic schizophrenia with predominant negative symptoms and stable antipsychotic treatment. The participants received 2 g of sarcosine (n = 28) or placebo (n = 29) daily. We assessed serum NPY concentrations and severity of symptoms (with the Positive and Negative Syndrome Scale [PANSS] and Calgary Depression Scale for Schizophrenia) at the beginning of the study, after 6 weeks and 6 months. Sarcosine did not affect NPY levels in all time points. The highest decrease in NPY concentrations was observed in the subjects who were initially depressed, who became euthymic at the last visit. We noticed an improvement in the total PANSS score, and negative symptom and general psychopathology subscales in the sarcosine group, however, without any correlation with NPY levels. The use of sarcosine does not change NPY levels. Peripheral NPY concentrations may be related to depressive symptoms in schizophrenia.

A Comprehensive Analysis of the Effect of SIRT1 Variation on the Risk of Schizophrenia and Depressive Symptoms.

Depressive symptoms could be considered a mutual manifestation of major depressive disorder and schizophrenia. Rs3758391 is a functional locus of Sirtuin (SIRT1) involving depression etiology. In this study, we hypothesized that the SIRT1 SNP rs3758391 might be a hazard for schizophrenia pathogenesis, especially related to the appearance of depressive symptoms. We recruited 723 healthy controls and 715 schizophrenia patients, the occurrence of psychotic and depressive symptoms was evaluated by Calgary Depression Scale (CDSS) and PANSS. Meanwhile, qt-PCR was used to detect the mRNA levels of SIRT1 in peripheral blood of 197 olanzapine monotherapy schizophrenia patients. 45.6% of schizophrenia patients had depressive symptoms. In the patient group, mRNA levels of patients with depressive symptoms were significantly lower than those without depressive symptoms (P < 0.01). CDSS scores of schizophrenia patients with different rs3758391 genotypes were significantly different (P < 0.01). Post hoc comparisons indicated that the CDSS scores of rs3758391 C/C and C/T carriers were higher than those of T/T carriers (Ps < 0.01). In the occipital cortex, our eQTL analysis showed that there was a clear correlation between rs3758391 and the SIRT1 mRNA levels. Our preliminary findings provide suggestive evidence that SIRT1 makes schizophrenia patients more prone to depressive symptoms. This SNP might be a biomarker of depression in schizophrenia.

Homocysteine, but not MTHFR gene polymorphism, influences depressive symptoms in patients with schizophrenia

BackgroundMethylenetetrahydrofolate reductase (MTHFR) is the key enzyme of folate metabolism in the process of one-carbon cycle and its deficiency results in elevated homocysteine concentration. In this study, we hypothesized that MTHFR C677T polymorphism and homocysteine concentration may play important roles in the development of depressive symptoms in schizophrenia. MethodsWe recruited 715 patients with stable schizophrenia, and among them, 197 schizophrenia patients under olanzapine monotherapy were enrolled for homocysteine concentration analysis. The Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) were employed to evaluate psychiatric and depressive symptoms. ResultsWhen the 715 schizophrenia patients were evaluated by CDSS, 326 individuals (45.6%) had depressive symptoms. No significant differences were observed in C677T genotype and allele distributions between the schizophrenia with or without depression groups. Schizophrenia patients with depression have higher levels of homocysteine than those without depression (P = 0.019). There was a positive correlation between the homocysteine levels and CDSS score (r = 0.22, P = 0.002). ConclusionOur findings suggested that higher levels of homocysteine may be a risk factor for the development of depressive symptoms in schizophrenia patients.

Reward processing electrophysiology in schizophrenia: Effects of age and illness phase

BackgroundReward processing abnormalities may underlie characteristic pleasure and motivational impairments in schizophrenia. Some neural measures of reward processing show age-related modulation, highlighting the importance of considering age effects on reward sensitivity. We compared event-related potentials (ERPs) reflecting reward anticipation (stimulus-preceding negativity, SPN) and evaluation (reward positivity, RewP; late positive potential, LPP) across individuals with schizophrenia (SZ) and healthy controls (HC), with an emphasis on examining the effects of chronological age, brain age (i.e., predicted age based on neurobiological measures), and illness phase. MethodsSubjects underwent EEG while completing a slot-machine task for which rewards were not dependent on performance accuracy, speed, or response preparation. Slot-machine task EEG responses were compared between 54 SZ and 54 HC individuals, ages 19 to 65. Reward-related ERPs were analyzed with respect to chronological age, categorically-defined illness phase (early; ESZ versus chronic schizophrenia; CSZ), and were used to model brain age relative to chronological age. ResultsIllness phase-focused analyses indicated there were no group differences in average SPN or RewP amplitudes. However, a group × reward outcome interaction revealed that ESZ differed from HC in later outcome processing, reflected by greater LPP responses following loss versus reward (a reversal of the HC pattern). While brain age estimates did not differ among groups, depressive symptoms in SZ were associated with older brain age estimates while controlling for negative symptoms. ConclusionsESZ and CSZ did not differ from HC in reward anticipation or early outcome processing during a cognitively undemanding reward task, highlighting areas of preserved functioning. However, ESZ showed altered later reward outcome evaluation, pointing to selective reward deficits during the early illness phase of schizophrenia. Further, an association between ERP-derived brain age and depressive symptoms in SZ extends prior findings linking depression with reward-related ERP blunting. Taken together, both illness phase and age may impact reward processing among SZ, and brain aging may offer a promising, novel marker of reward dysfunction that warrants further study.

The association between insight and depressive symptoms in schizophrenia: Undirected and Bayesian network analyses.

Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions. Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression. After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms. In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem.

Metabolic profiling identifies TC and LDL as potential serum biomarkers for depressive symptoms in schizophrenia

This study aimed to explore the relationship between serum levels of cardiometabolic biomarkers and depressive symptoms in schizophrenia patients treated with atypical antipsychotics. A total of 210 patients with schizophrenia and 70 healthy controls were recruited in our present study. All patients were rated on the 17-item Hamilton Depression Rating Scale (HAMD-17) to measure depressive symptoms and the Positive and Negative Syndrome Scale (PANSS) for psychopathology. Serum cardiometabolic biomarkers (HDL, LDL, TC, TG, GLU) in all participants were measured. Our results showed that schizophrenia patients had higher levels of serum GLU, TG, TC, LDL and BMI, but lower levels of HDL than controls (all P < 0.05). Compared to patients without depressive symptoms, those with depressive symptoms showed higher PANSS total, general psychopathology, positive and negative symptom scores (all p < 0.05), as well as higher serum levels of LDL (p < 0.001) and TC (p = 0.011). In addition, our correlation analysis showed that serum LDL (P < 0.001) and TC (P = 0.045) levels were positively associated with HAMD total scores in schizophrenia patients after age, sex and education levels were controlled. Our results suggest the appearance of depression in schizophrenia patients may be associated with high levels of metabolic parameters, especially TC and LDL.

Depressive symptoms in schizophrenia patients: A possible relationship between SIRT1 and BDNF

ObjectivesDepressive symptoms are commonly seen in schizophrenia. Increasing evidence implicates that both SIRT1 and BDNF closely related to the development of depression. So we here aimed to explore the effect of BDNF and SIRT1 on the depressive symptoms, and also explore the risk factors for the depressive symptoms in schizophrenia patients. MethodsA group of 203 participants (case/controls, 174/29) was recruited in the present work. Significant depression was classified by the CDSS score 7 or above. The psychotic symptoms and cognitive functions in schizophrenia patients were evaluated by PANSS and RBANS respectively. And the plasma concentration of SIRT1 and BDNF were measured in 167 participants (case/controls, 138/29). ResultsCompared to healthy subjects, schizophrenia patients exhibited notably lower levels of BDNF (P < 0.05). And we observed that patients with depression displayed a worse psychotic symptom (P < 0.01), a poorer cognitive function(P < 0.05), as well as lower plasma BDNF and SIRT1 levels (Bonferroni corrected P < 0.05) compared to those no depressive patients. And the SIRT1 levels were positively correlated with BDNF levels in the case group (P < 0.001). And the regression analysis showed that negative symptoms and general psychopathology in PANSS, attention and delayed memory in RBANS, BDNF and SIRT1 were independent risk factors for depressive symptoms in schizophrenia. ConclusionAside from the association with psychotic symptoms, we provided evidence suggesting that low BDNF and SIRT1 concentration value may be responsible for the occurrence of depression in schizophrenic patients.

Effect of bifidobacterium breve A-1 on anxiety and depressive symptoms in schizophrenia: A proof-of-concept study

BackgroundStudies of probiotics have suggested they have a positive effect on anxiety and depressive symptoms in humans. This study investigated the effect of consuming the probiotic Bifidobacterium breve A-1 on anxiety and depressive symptoms in patients with schizophrenia and explored its effect on immune products such as cytokines and chemokines. MethodsIn this open-label single-arm study, all participants received B. breve strain A-1 (1011 cfu/day) for 4 weeks followed by 4 weeks of observation. The primary outcome was the Hospital Anxiety and Depression Scale (HADS) score. Secondary outcomes were anxiety and depressive symptoms on the Positive and Negative Syndrome Scale (PANSS), blood test findings, and fecal microbiome composition. ResultsTwenty-nine outpatients completed the study. HADS total score and PANSS anxiety/depression score were significantly improved at 4 weeks. Based on the criterion of a greater than 25% reduction in HADS total score at 4 weeks from baseline, there were 12 responders and 17 non-responders. Responders were found to have fewer negative symptoms, reduced intake of dairy products, and higher relative abundance of Parabacteroides in the gut microbiome than non-responders. Moreover, IL-22 and TRANCE expression was significantly increased at 4 weeks from baseline in responders but not in non-responders. LimitationsThis open-label, single-arm study cannot exclude a placebo effect. ConclusionsThe results suggest the potential effect of B. breve A-1 in improving anxiety and depressive symptoms in patients with schizophrenia. Further studies should investigate this effect in patients with other psychiatric conditions and assess dietary habits and the gut microbiome.