Positive association between increased homocysteine and deficit syndrome in Chinese patients with chronic schizophrenia: a large-scale cross-sectional study.

Emerging studies indicate that oxidative stress may contribute to deficit syndrome (DS) in patients with schizophrenia. Homocysteine (Hcy) is a well-known marker and mediator of oxidative stress that exhibits tight associations with schizophrenia. However, no previous studies have assessed the relationship of DS with Hcy. This study evaluated the prevalence, clinical characteristics, and association of DS with Hcy in 491 patients with schizophrenia. Plasma levels of Hcy and other metabolic parameters were measured. Positive and Negative Syndrome Scale and the proxy scale for deficit syndrome were employed to assess psychiatric symptoms and DS. The logistic regression model was conducted to assess independent factors associated with DS, and the Area Under the Curve (AUC) was used to assess the performance of our model. There was a high incidence of hyperhomocysteinemia (58.8%) and DS (24.4%). Plasma Hcy levels were significantly higher in patients with DS. Age, Hcy levels, and psychiatric symptoms were independently associated with DS. The combination of these variables perfectly differentiated DS and non-DS patients with an AUC value of 0.89. Our study suggests that elevated Hcy levels may be related to DS. Routine monitoring of Hcy is essential and may facilitate early detection of DS in patients with schizophrenia.

The Self-Evaluation of Negative Symptoms in Differentiating Deficit Schizophrenia: The Comparison of Sensitivity and Specificity with Other Tools.

INTRODUCTION: Psychometric properties of the Self-evaluation of Negative Symptoms (SNS) in subjects with the deficit subtype of schizophrenia (SCZ-D) have not been investigated so far. This study had the following aims: (1) to assess psychometric properties of SNS in subjects with SCZ-D and (2) to explore the usefulness of SNS, in comparison with other clinical characteristics, in screening for SCZ-D. METHODS: Participants were 82 stable outpatients with schizophrenia, including 40 individuals with SCZ-D and 42 individuals with the non-deficit subtype (SCZ-ND). RESULTS: Internal consistency was acceptable-to-good in both groups. Factor analysis revealed two dimensions (apathy and emotional). There were significant positive correlations of the SNS total score with the subscore of negative symptoms from the Positive and Negative Syndrome Scale (PANSS) and significant negative correlations with scores of the Social and Occupational Functioning Assessment Scale (SOFAS) in both groups, indicating good convergent validity. The following measures were found to be appropriate screening tools for differentiating SCZ-D and SCZ-ND (p < 0.001): the SNS total score (area under the curve [AUC]: 0.849, cut-off ≥16, sensitivity: 80.0%, specificity: 78.6%), the PANSS subscore of negative symptoms (AUC: 0.868, cut-off ≥11, sensitivity: 90.0%, specificity: 78.6%), and the SOFAS (AUC: 0.779, cut-off ≤59, sensitivity: 69.2%, specificity: 82.5%). Also, adding the SOFAS (cut-off ≤59) to the SNS (cut-off: ≥16) further improved sensitivity and specificity (AUC: 0.898, p < 0.001, sensitivity = 87.5%, specificity = 82.2%). Cognitive performance and age of psychosis onset were not found to be suitable measures for differentiating SCZ-D and SCZ-ND. CONCLUSION: The present findings indicate that the SNS has good psychometric properties in subjects with SCZ-D and those with SCZ-ND. Moreover, the SNS, the PANSS, and the SOFAS might be used as screening tools for SCZ-D.

Cerebral white matter changes in deficit and non-deficit subtypes of schizophrenia.

The considerable clinical heterogeneity in schizophrenia makes elucidation of its neurobiology challenging. Subtyping the disorder is one way to reduce this heterogeneity and deficit status is one such categorization based on the prominence of negative symptoms. We aimed to utilize diffusion tensor imaging (DTI) to identify unique white matter cerebral changes in deficit schizophrenia (DS) compared with non-deficit schizophrenia (NDS) and healthy controls (HC) in an Asian sample. A total of 289 subjects (111 HC, 133 NDS and 45 DS) underwent DTI and completed rating scales which assessed the severity of psychopathology, psychosocial functioning and premorbid intelligence.We found that DS patients had fractional anisotropy (FA) reductions in the Body of the Corpus Callosum (BCC) and right Posterior Thalamic Radiation (PTR) regions relative to HCs, and FA reductions in the right PTR relative to NDS patients. NDS patients had FA reductions of the BCC and right PTR relative to HCs. Binomial logistic regression analyses revealed that FA reductions of the right PTR FA was an independent predictor of deficit status. The identified brain white matter changes especially in the PTR relate to deficits of cognitive control and emotional awareness, which may underlie psychopathology associated with deficit status like inattention and affective blunting. These potential biomarkers of DS warrant further examination to determine their utility for monitoring illness progression and intervention response in schizophrenia.

Association between DRD2 and ANKK1 polymorphisms with the deficit syndrome in schizophrenia.

BACKGROUND: The clinical course of schizophrenia varies among patients and is difficult to predict. Some patient populations present persistent negative symptoms, referred to as the deficit syndrome. Compared to relatives of non-deficit schizophrenia patients, family members of this patient population are at an increased risk of developing schizophrenia. Therefore, the aim of this study was to search for genetic underpinnings of the deficit syndrome in schizophrenia. METHODS: Three SNPs, i.e., rs1799732 and rs6276 located within DRD2, and rs1800497 within ANKK1, were identified in the DNA samples of 198 schizophrenia probands, including 103 patients with deficit (DS) and 95 patients with non-deficit schizophrenia (NDS). Results: No significant differences concerning any of the analyzed polymorphisms were found between DS and NDS patients. However, significant links were observed between family history of schizophrenia and the deficit syndrome, G/G genotype and rs6276 G allele. In a separate analysis, we identified significant differences in frequencies of rs6276 G allele between DS and NDS patients with family history of schizophrenia. No significant associations were found between DRD2 and ANKK1 SNPs and the age of onset or schizophrenia symptom severity. CONCLUSIONS: The results of our preliminary study fail to provide evidence of associations between DRD2 and ANKK1 polymorphisms with the deficit syndrome or schizophrenia symptom severity, but suggest potential links between rs6276 in DRD2 and the deficit syndrome in patients with hereditary susceptibility to schizophrenia. However, further studies are necessary to confirm this observation.

Characterization of deficit schizophrenia and reliability of the bidimensional model of its negative symptomatology.

Background: Cumulative evidence has demonstrated important differences between deficit (DS) and non-deficit (NDS) schizophrenia, suggesting that DS may be a separate disease. However, most data come from the same research groups and more replication is needed to validate this hypothesis.Aims: Our study aimed to examine the distribution of DS, to compare their characteristics with NDS patients and to analyze the reliability of the two-factor structure of its negative symptomatology in a Spanish clinical sample.Methods: Sixty clinically stabilized patients with schizophrenia were evaluated. The Schedule for the Deficit Syndrome was used for DS/NDS categorization. Patient characteristics included age, gender, education, age at onset of psychosis, duration of illness, family history of psychosis, type of antipsychotic regimen, schizophrenia subtype and severity of the disease.Results: DS prevalence was 28.3%. Bivariate analysis revealed statistical differences between DS and NDS in terms of years of education and schizophrenia subtype. Factor analysis replicated the two-factor solution consisting of the 'Expressive deficit' and 'Avolition-apathy' domains reported in previous studies.Conclusions: Our results were consistent with the published data and indicated that the DS profile in the Spanish population is similar to that in other populations, which would corroborate the homogeneity of DS within the schizophrenia spectrum and contribute to the hypothesis that DS constitutes a separate disease.

Antipsychotic drugs for patients with schizophrenia and predominant or prominent negative symptoms: a systematic review and meta-analysis.

BACKGROUND: Negative symptoms are the core of schizophrenia, but whether antipsychotics are efficacious for their treatment is unclear. Moreover, there is debate whether patients in relevant trials should have predominant negative symptoms or whether prominent negative symptoms are also acceptable. METHODS: We systematically reviewed randomised, blinded antipsychotic drug trials in patients with schizophrenia and either predominant or prominent negative symptoms (last search Dec 12, 2017). Separate pairwise meta-analyses were conducted in these two populations. The primary outcome was negative symptoms. Depressive, symptoms, positive symptoms, and extrapyramidal side-effects were analysed as causes of secondary negative symptoms. FINDINGS: We included 21 randomized-controlled trials with 3451 participants which revealed the following significant differences in the primary outcome: in patients with predominant negative symptoms amisulpride was superior to placebo (N = 4; n = 590, SMD 0.47, CI 0.23, 0.71), olanzapine was superior to haloperidol in a small trial (n = 35) and cariprazine outperformed risperidone (N = 1, n = 456, SMD - 0.29, CI - 0.48, - 0.11). In patients with prominent negative symptoms, olanzapine and quetiapine were superior to risperidone in single trials. Overall, studies in prominent negative symptoms were potentially more confounded by improvements of secondary negative symptoms. INTERPRETATION: Amisulpride is the only antipsychotic that outperformed placebo in the treatment of predominant negative symptoms, but there was a parallel reduction of depression. Cariprazine was better than risperidone in a large trial that was well-controlled for secondary negative symptoms, but the trial was sponsored by its manufacturer. Future trials should apply scientifically developed definitions such as the deficit syndrome and the persistent negative symptoms concept.

Neurocognitive impairment in deficit and non-deficit schizophrenia: a meta-analysis.

BACKGROUND: Most studies suggested that patients with deficit schizophrenia have more severe impairment compared with patients with non-deficit schizophrenia. However, it is not clear whether deficit and non-deficit schizophrenia are associated with differential neurocognitive profiles. METHODS: The aim of this meta-analytic review was to compare cognitive performances of deficit and non-deficit patients with each other and with healthy controls. In the current meta-analysis, differences in cognitive abilities between 897 deficit and 1636 non-deficit patients with schizophrenia were examined. Cognitive performances of 899 healthy controls were also compared with 350 patients with deficit and 592 non-deficit schizophrenia. RESULTS: Both deficit (d = 1.04-1.53) and non-deficit (d = 0.68-1.19) schizophrenia were associated with significant deficits in all cognitive domains. Deficit patients underperformed non-deficit patients in all cognitive domains (d = 0.24-0.84) and individual tasks (d = 0.39-0.93). The relationship between deficit syndrome and impairment in olfaction, social cognition, verbal fluency, and speed-based cognitive tasks were relatively stronger. CONCLUSIONS: Our findings suggest that there is consistent evidence for a significant relationship between deficit syndrome and more severe cognitive impairment in schizophrenia.

Neurocognitive impairment in the deficit subtype of schizophrenia.

Schizophrenia is a heterogeneous disorder characterized by numerous diverse signs and symptoms. Individuals with prominent, persistent, and idiopathic negative symptoms are thought to encompass a distinct subtype of schizophrenia. Previous work, including studies involving neuropsychological evaluations, has supported this position. The present study sought to further examine whether deficit patients are cognitively distinct from non-deficit patients with schizophrenia. A comprehensive neurocognitive battery including tests of verbal memory, vigilance, processing speed, reasoning, and working memory was administered to 657 patients with schizophrenia. Of these, 144 (22 %) patients were classified as deficit patients using a proxy identification method based on severity, persistence over time, and possible secondary sources (e.g., depression) of negative symptoms. Deficit patients with schizophrenia performed worse on all tests of cognition relative to non-deficit patients. These patients were characterized by a generalized cognitive impairment on the order of about 0.4 standard deviations below that of non-deficit patients. However, when comparing deficit patients to non-deficit patients who also present with negative symptoms, albeit not enduring or primary, no group differences in cognitive performance were found. Furthermore, a discriminant function analysis classifying patients into deficit/non-deficit groups based on cognitive scores demonstrated only 62.3 % accuracy, meaning over one-third of individuals were misclassified. The deficit subtype of schizophrenia is not markedly distinct from non-deficit schizophrenia in terms of neurocognitive performance. While deficit patients tend to have poorer performance on cognitive tests, the magnitude of this effect is relatively modest, translating to over 70 % overlap in scores between groups.

The Role of Two Factors of Negative Symptoms and Cognition on Social Functioning in Male Patients with Schizophrenia: A Mediator Model.

OBJECTIVE: This study aims to compare the cognitive function and social functioning in male patients with deficit syndrome (DS) and non-DS, and to explore whether cognitive function serves as a mediator in the relationship between the two factors of negative symptoms (motivation and pleasure (MAP) and expressivity (EXP) deficits, and social functioning in schizophrenia patients. METHODS: One hundred and fifty-six male patients with schizophrenia and 109 age- and education-matched normal controls were enrolled in the current study. The Chinese version of a Schedule for Deficit Syndrome (SDS) was used for DS and non-DS categorization. The Brief Psychiatric Rating Scale (BPRS) and the Brief Negative Symptoms Scale (BNSS) were used to assess psychotic and negative symptoms in patients. The Social-Adaptive Functioning Evaluation (SAFE) was adopted to evaluate patients' social functioning, and a battery of classical neurocognitive tests was used to assess cognition, including sustained vigilance/attention, cognitive flexibility, ideation fluency, and visuospatial memory. RESULTS: We found that male patients with DS performed worse in all four cognitive domains and social functioning compared to non-DS patients. Both total negative symptoms and its two factors were significantly associated with all four domains of cognition and social functioning in male patients. Interestingly, our results indicate that only cognitive flexibility mediates the relationship between negative symptoms and social functioning in schizophrenia patients, but there were no differences between EXP and MAP negative factors in this model. CONCLUSION: Our findings suggest that DS patients may represent a unique clinical subgroup of schizophrenia, and the integrated interventions targeting both negative symptoms and cognition, especially cognitive flexibility, may optimally improve functional outcomes in schizophrenia patients.

ROI-based analysis of diffusion indices in healthy subjects and subjects with deficit or non-deficit syndrome schizophrenia.

We analyzed DTI data involving 22 healthy subjects (HC), 15 patients with deficit syndrome schizophrenia (DSZ), and 25 patients with non-deficit syndrome schizophrenia (NDSZ). We used a 1.5-T MRI scanner to collect diffusion-weighted images and T1 images, which were employed to correct distortions and deformations within the diffusion-weighted images. For 156 regions of interest (ROI), we calculated the average fractional anisotropy (FA), mean diffusion (MD), and radial diffusion (RD). Each ROI underwent a group-wise comparison using permutation F-test, followed by post hoc pairwise comparisons with Bonferroni correction. In general, we observed lower FA in both schizophrenia groups compared to HC (i.e., HC>(DSZ=NDSZ)), while MD and RD showed the opposite pattern. Notably, specific ROIs with reduced FA in schizophrenia patients included bilateral nucleus accumbens, left fusiform area, brain stem, anterior corpus callosum, left rostral and caudal anterior cingulate, right posterior cingulate, left thalamus, left hippocampus, left inferior temporal cortex, right superior temporal cortex, left pars triangularis and right lingual gyrus. Significantly, the right cuneus exhibited lower FA in the DSZ group compared to other groups ((HC=NDSZ)>DSZ), without affecting MD and RD. These results indicate that compromised neural integrity in the cuneus may contribute to the pathophysiological distinctions between DSZ and NDSZ.

Study the Effect of Relative Energy Deficiency on Physiological and Physical Variables in Professional Women Athletes: A Randomized Controlled Trial.

Energy deficits are often observed in athletes, especially in female athletes, due to the high expenditure of sport and strict diets. Low energy availability can cause serious health problems and affect sport performance. The aim of this study was to evaluate the effects of different personalized dietary plans on physiological and physical factors related to energy deficit syndrome in female professional handball players. Twenty-one professional female handball players, aged 22 ± 4 years, 172.0 ± 5.4 cm and 68.4 ± 6.7 kg, divided into three groups (FD: free diet; MD: Mediterranean diet; and AD: high antioxidant diet), participated in this 12-week randomized controlled trial. Energy expenditure through indirect calorimetry, energy availability, 7 day dietary intake analysis, blood pressure, cholesterol, menstrual function, body composition by both anthropometry and bioelectrical impedance, and strength performance were assessed. All participants showed low energy availability (<30 kcal/lean mass per day); despite this, all had eumenorrhea. Significant improvements were found after the intervention in all components of body composition (p < 0.05). In the remaining variables, despite slight improvements, none were significant neither over time nor between the different groups. Low energy availability has been observed in all professional female handball players, which may lead to serious consequences. A longer period of intervention is required to assess the differences between diets and improvements in other parameters.

Association of empathy with clinical symptoms and cognitive function in Chinese chronic schizophrenia patients with and without deficit syndrome.

BACKGROUND: Patients with deficit syndrome (DS) are known to experience cognitive impairment. However, there is no consistent conclusion on the impairment of neurocognitive features in DS patients, and no studies have examined their empathy. The purpose of this study was to compare neurocognition and empathy in patients with DS and non-DS schizophrenia. METHODS: Totally, 665 patients with chronic schizophrenia were enrolled. DS patients were identified by the Proxy Scale for Deficit Syndrome (PDS). Neurocognition and social cognition were assessed by Repeatable Battery for the measurement of Neuropsychological Status (RBANS) and the Interpersonal Reactivity Index (IRI), respectively. In addition, psychopathological symptom severity was assessed by the Positive and Negative Syndrome Scale (PANSS). RESULTS: Participants included 150 patients with DS and 140 patients with non-DS. DS patients performed significantly worse on the all RBANS domain (except for visuospatial) and total scores as well as IRI scores. Regression analysis showed that PANSS general psychopathology and education were associated with RBANS total score in the DS group (adjusted R2 = 0.29), while education and PANSS negative symptoms were correlated with RBANS total score in non-DS patients (adjusted R2 = 0.33). In the non-DS group, suicide attempts and PANSS negative symptom score were independently associated with IRI total score (adjusted R2 = 0.06), whereas in the DS group, no variable was associated with IRI total score. CONCLUSIONS: Our findings suggest that patients with DS may have poor neurocognitive and empathy performance. In chronic schizophrenia patients, negative symptoms may play a different role in cognition between DS and non-DS groups.

Contrasting Frontoparietal Network Connectivity in Antipsychotic Medication-Naive First-Episode Psychosis Patients Who Do and Do Not Display Features of the Deficit Syndrome.

BACKGROUND: The deficit syndrome is a clinical subtype of schizophrenia that is characterized by enduring negative symptoms. Several lines of evidence point to frontoparietal involvement, but the frontoparietal control network (FPCN) and its subsystems (FPCNA and FPCNB) proposed by Yeo et al. have not been systematically characterized at rest in patients with the deficit syndrome. METHODS: We used resting-state fMRI to investigate the FPCN and its subnetworks in 72 healthy controls and 65 antipsychotic medication-naive, first-episode psychosis patients (22 displayed deficit syndrome features, 43 did not). To assess whole-brain FPCN connectivity, we used the right posterior parietal cortex as the seed region. We then performed region of interest analyses in FPCN subsystems. RESULTS: We found that patterns of FPCN dysconnectivity to the whole brain differed in patients who displayed deficit syndrome features compared with those who did not. Examining the FPCN on a more granular level revealed reduced within-FPCN(A) connectivity only in patients displaying deficit features. FPCNB connectivity did not differ between patient groups. DISCUSSION: Here, we describe a neurobiological signature of aberrant FPCN connectivity in antipsychotic-naive, first-episode patients who display clinical features of the deficit syndrome. Importantly, frontoparietal subnetwork connectivity differentiated subgroups, where the FPCNA is selectively involved in patients with deficit features. Our findings add to the growing body of literature supporting a neurobiological distinction between two clinical subtypes of schizophrenia, which has the potential to be leveraged for patient stratification in clinical trials and the development of novel treatments.

From Memories of Past Experiences to Present Motivation? A Meta-analysis on the Association Between Episodic Memory and Negative Symptoms in People With Psychosis.

Based on findings from cognitive science, it has been theorized that the reductions in motivation and goal-directed behavior in people with psychosis could stem from impaired episodic memory. In the current meta-analysis, we investigated this putative functional link between episodic memory deficits and negative symptoms. We hypothesized that episodic memory deficits in psychosis would be related to negative symptoms in general but would be more strongly related to amotivation than to reduced expressivity. We included 103 eligible studies (13,622 participants) in the analyses. Results revealed significant, moderate negative associations of episodic memory with negative symptoms in general (k = 103; r = -.23; z = -13.40; P ≤ .001; 95% CI [-.26; -.20]), with amotivation (k = 16; r = -.18; z = -6.6; P ≤ .001; 95% CI [-.23; -.13]) and with reduced expressivity (k = 15; r = -.18; z = -3.30; P ≤.001; 95% CI[-.29; -.07]). These associations were not moderated by sociodemographic characteristics, positive symptoms, depression, antipsychotic medication or type of negative symptom scale. Although these findings provide sound evidence for the association between episodic memory deficits and amotivation, the rather small magnitude and the unspecific pattern of this relationship also indicate that episodic memory deficits are unlikely to be the only factor relevant to amotivation. This implicates that future research should investigate episodic memory in conjunction with other factors that could account for the association of episodic memory deficits and amotivation in psychosis.

Differences in inflammatory marker profiles and cognitive functioning between deficit and nondeficit schizophrenia.

Deficit schizophrenia (DS) patient is a homogenous subtype of schizophrenia that includes primary and enduring negative symptoms. This study aimed to compare the differences in cognitive functioning and plasma levels of C-reactive protein (CRP) and inflammatory cytokines among DS patients, nondeficit schizophrenia (NDS) patients, and healthy controls (HCs). A total of 141 schizophrenia patients and 67 HCs were included in this study. The schizophrenia patients were divided into DS (N= 51) and NDS (N=90) groups based on the Proxy for the Deficit Syndrome Scale (PDS). The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to evaluate the clinical symptoms and cognitive performances, respectively. The plasma level of CRP, IL-1ß, Il-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ were measured using enzyme-linked immunosorbent assays (ELISAs). Our results showed that DS patients had the worst cognitive performance, especially in the immediate memory, attention, and language dimensions, compared to the NDS and HC groups. Compared to the HCs group, DS patients had higher levels of CRP, IL-1ß, IL-6, IL-8, IFN-γ, and total proinflammatory cytokines, and NDS patients had higher levels of IL-1ß, IFN-γ, and proinflammatory cytokines. We also found that CRP levels were significantly increased in DS patients compared to NDS patients. Moreover, stepwise logistic regression analysis revealed that CRP is an independent risk factor for DS. Sex stratification analysis showed significant differences in almost all cytokines in female samples but not in male samples. The significant differences in cognitive performance and inflammatory components among groups suggest that deficit syndrome is an independent endophenotype of schizophrenia patients with unique immune-inflammatory features, but may have sex characteristics.

Deficit syndrome in Chinese patients with first-episode drug naïve schizophrenia: Prevalence, demographic and clinical characteristics.

BACKGROUND: Deficit syndrome (DS) is a common subgroup of schizophrenia. However, few studies have examined the prevalence and risk factors for DS in Chinese Han patients with schizophrenia. The aim of this study was to assess prevalence, demographic and clinical characteristics of DS in Chinese Han patients with first-episode drug naïve (FEDN) schizophrenia. METHODS: In total, 235 patients with schizophrenia were recruited, and clinical and demographic data were collected. The Positive and Negative Syndrome Scale (PANSS) was utilized for the psychopathological symptoms, and the 17-item Hamilton Depression Rating Scale (HDRS-17) for depressive symptoms. The Proxy for the Deficit Syndrome (PDS) was adopted to identify DS. RESULTS: The prevalence of DS in the cohort of first-episode schizophrenia patients was 23.0%. Compared to those patients without DS, patients with DS had younger age, lower education level, and were more likely to be single. Further, DS patients had significantly lower scores of positive symptoms, general psychopathology, and depression than non-DS patients. Patients with DS had fewer suicide attempts, but they had more severe negative symptoms and cognitive impairment (all p < 0.05). Multiple regression showed that poor cognitive functioning, lower levels of depression and younger age at onset were predictors of DS. CONCLUSIONS: Chinese Han patients with FEDN schizophrenia have high prevalence of DS. Some demographic and clinical parameters may be associated with DS.

Investigating the Relationship between White Matter Connectivity and Motivational Circuits in Subjects with Deficit Schizophrenia: A Diffusion Tensor Imaging (DTI) Study.

Deficit schizophrenia is a subtype of schizophrenia presenting primary and enduring negative symptoms (NS). Although one of the most updated hypotheses indicates a relationship between NS and impaired motivation, only a few studies have investigated abnormalities of motivational circuits in subjects with deficit schizophrenia (DS). Our aim was to investigate structural connectivity within motivational circuits in DS. We analyzed diffusion tensor imaging (DTI) data from 46 subjects with schizophrenia (SCZ) and 35 healthy controls (HCs). SCZ were classified as DS (n = 9) and non-deficit (NDS) (n = 37) using the Schedule for Deficit Syndrome. The connectivity index (CI) and the Fractional Anisotropy (FA) of the connections between selected brain areas involved in motivational circuits were examined. DS, as compared with NDS and HCs, showed increased CI between the right amygdala and dorsal anterior insular cortex and increased FA of the pathway connecting the left nucleus accumbens with the posterior insular cortex. Our results support previous evidence of distinct neurobiological alterations underlying different clinical subtypes of schizophrenia. DS, as compared with NDS and HCs, may present an altered pruning process (consistent with the hyperconnectivity) in cerebral regions involved in updating the stimulus value to guide goal-directed behavior.

Current perspectives in treating negative symptoms of schizophrenia: A narrative review (Review).

The negative symptoms of schizophrenia are an unmet treatment target as currently approved treatments mostly control positive symptoms. The persistence of these symptoms holds back the patient's reinstatement in society, making them incapable of fulfilling their social, professional, or family roles. There is overwhelming research evidence suggesting that the negative symptoms of schizophrenia are associated with poorer functioning and lower quality of life than positive symptoms, confirming the need for developing new treatments for this particular category of symptoms. This present review aims to review clinical trials addressing novel pharmacological approaches addressing primary negative symptoms of schizophrenia. We overview both monotherapies, first-generation and second-generation antipsychotics, and add-on therapies, including psychostimulants, anti-inflammatory drugs, antidepressants, molecules targeting glutamatergic, cholinergic or serotonergic systems and hormones. Our findings suggest that the primary negative symptoms of schizophrenia may be mitigated by adjunctive therapies, and we highlight the pharmacological agents that have proven superior efficacy. Novel compounds such as cariprazine and MIN-101, to date, show promising results, but large clinical trials are needed to test their efficacy and safety.

White Matter Neurometabolic Signatures Support the Deficit and Nondeficit Distinction in Antipsychotic-Naïve First-Episode Psychosis Patients.

The deficit syndrome is thought to be a more homogenous clinical subgroup within the syndrome of schizophrenia that is characterized by enduring negative symptoms. It is hypothesized that distinct pathophysiological processes underlie the subtypes, where the deficit syndrome reflects an early onset nonprogressive developmental process, and the nondeficit form of the illness is characterized by attenuated neuroplasticity secondary to elevated glutamate levels. We used single-voxel magnetic resonance spectroscopy (PRESS; TE: 30 ms) to measure left frontal white matter neurometabolite levels in 61 antipsychotic-naïve first-episode psychosis patients (39 who did not display deficit features, 22 who did display deficit features, assessed with the Schedule for the Deficit Syndrome) and 59 healthy controls. Metabolite levels were quantified with the LCModel. We used a MANCOVA to determine neurometabolite differences between healthy controls, deficit syndrome patients, and nondeficit patients. We report a significant group difference when all metabolites were considered jointly (F[10,208] = 2.16; P = .02). Post hoc analyses showed that patients presenting without deficit features had higher glutamate levels than patients with deficit features and controls. Patients presenting without deficit features also had significantly higher myoinositol levels than controls; myoinositol levels were trend-level higher in patients presenting with deficit features compared to controls. Our data support the idea that the pathophysiology of patients presenting without deficit features may differ from those presenting with deficit features.

[Typology of impaired attention in children and related behavioral disorders]. / Tipy narushenii vnimaniia u detei i sviazannye s nimi rasstroistva povedeniia.

A review of publications devoted to the study of impaired attention in children is presented. The authors identified the main types of impaired attention, examined the main psycho-neurological diseases, in which impaired attention is the leading symptom, and approaches to treatment of these disorders.