First Episode Research Articles

Common and distinct neural activities in frontoparietal network in first-episode bipolar disorder and major depressive disorder: Preliminary findings from a follow-up resting state fMRI study

BackgroundIt is difficult to distinguish bipolar disorder (BD) from major depressive disorder (MDD), especially with the initial depressive episode. In this study, we compared neural activities of BD and MDD patients during the first-episode (FE) to investigate common and distinct neural activities and further explore predictive indicators in the two diseases. MethodsFE-MDD patients were performed resting state functional magnetic resonance imaging and followed up after scanning. After follow-up, FE-MDD patients were regrouped into FE-BD and FE-MDD patients. The study included 24 FE-BD patients, 28 FE-MDD patients, and 30 age- and sex-matched healthy controls (HC) to investigate neural activities with regional homogeneity (ReHo) analysis among the 3 groups. ResultsCompared to HC, FE-BD patients displayed significantly higher ReHo values in the superior frontal gyrus, the medial superior frontal gyrus within right-side cerebral hemisphere than FE-MDD patients and HC. Compared to HC, FE-BD and FE-MDD patients displayed significant decreased ReHo values in the paracentral lobule, the precuneus and the median cingulate and paracingulate gyrus within bilateral cerebral hemisphere, and the postcentral gyrus and the precentral gyrus within the right-side. FE-BD displayed significant lower ReHo values than FE-MDD patients in these regions. LimitationsThe potential effects of medicine, age, course of disease and handedness on results could not be ignored. ConclusionsAbnormal neural activities of frontoparietal network may provide common and distinct markers to affective disorders and scientific basis for further prediction researches of affective disorders.

Cannabis consumption and non-alcoholic fatty liver disease. A three years longitudinal study in first episode non-affective psychosis patients

IntroductionIncreased incidence of obesity and excess weight lead to an increased incidence of non-alcoholic fatty liver disease (NAFLD). Recent evidence indicates a protective effect of cannabis consumption on weight gain and related metabolic alterations in psychosis patients. Overall, patients are at greater risk of presenting fatty diseases, such as NAFLD, partly due to lipid and glycemic metabolic disturbances. However, there are no previous studies on the likely effect of cannabis on liver steatosis. We aimed to explore if cannabis consumption had an effect on hepatic steatosis, in a sample of first-episode (FEP) non-affective psychosis. Material and methodsA total of 390 patients were evaluated at baseline and after 3 years of initiating the antipsychotic treatment. Anthropometric measurements and liver, lipid, and glycemic parameters were obtained at both time points. All but 6.7% of patients were drug-naïve at entry, and they self-reported their cannabis use at both time points. Liver steatosis and fibrosis were evaluated through validated clinical scores (Fatty Liver Index [FLI], Fibrosis-4 [FIB-4], and NAFLD). ResultsAt 3-year follow-up, cannabis users presented significantly lower FLI scores than non-users (F = 13.874; p < .001). Moreover, cannabis users less frequently met the criteria for liver steatosis than non-users (X2 = 7.97, p = .019). Longitudinally, patients maintaining cannabis consumption after 3 years presented the smallest increment in FLI over time, which was significantly smaller than the increment in FLI presented by discontinuers (p = .022) and never-users (p = .016). No differences were seen in fibrosis scores associated with cannabis. ConclusionsCannabis consumption may produce a protective effect against liver steatosis in psychosis, probably through the modulation of antipsychotic-induced weight gain.

Structural connectivity in schizophrenia and bipolar disorder: Effects of chronicity and antipsychotic treatment

Previous studies based on graph theory parameters applied to diffusion tensor imaging support an alteration of the global properties of structural connectivity network in schizophrenia. However, the specificity of this alteration and its possible relation with chronicity and treatment have received small attention. We have assessed small-world (SW) and connectivity strength indexes of the structural network built using fractional anisotropy values of the white matter tracts connecting 84 cortical and subcortical regions in 25 chronic and 18 first episode (FE) schizophrenia and 24 bipolar patients and 28 healthy controls. Chronic schizophrenia and bipolar patients showed significantly smaller SW and connectivity strength indexes in comparison with controls and FE patients. SW reduction was driven by increased averaged path-length (PL) values. Illness duration but not treatment doses were negatively associated with connectivity strength, SW and PL in patients. Bipolar patients exposed to antipsychotics did not differ in SW or connectivity strength from bipolar patients without such an exposure. Executive functions and social cognition were related to SW index in the schizophrenia group. Our results support a role for chronicity but not treatment in structural network alterations in major psychoses, which may not differ between schizophrenia and bipolar disorder, and may hamper cognition.

Patterns of recovery course in early intervention for FIRST episode non-affective psychosis patients: The role of timing

BackgroundPrevention of symptom relapse and promotion of functional recovery are the two main goals of early intervention following a first episode of non-affective psychosis (FEP). The identification of patterns of recovery is important in developing and implementing recovery focused interventions at set time interval. MethodPatterns of recovery course, in terms of symptomatic and functional remission, were explored at 1 and 3-year follow-up in a sample of 373 consecutive FEP patients. Relapses during this period were considered. ResultsFour patterns of recovery course were defined: good stable (26%), good unstable (21%), poor unstable (10%), poor stable (43%). Those who met criteria for good stable recovery were more likely have less severe baseline negative symptoms (OR = 2.092; 95% CI = 0.99–4.419) and to not be diagnosed with schizophrenia (OR = 2.242; 95% CI = 1.015–4.954). Short DUP (OR = 2.152; 95% CI = 0.879–5.27) and low premorbid IQ (OR = 2.281; 95% CI = 0.954–5.457) increased the likelihood of good unstable recovery. Less severe baseline negative symptoms (OR = 3.851; 95% CI = 1.422–10.435) and single status (OR = 4.307; 95% CI = 1.014–18.293) increased the likelihood of a poor unstable recovery. Poor unstable pattern was significantly associated with a high relapse rate (73%). ConclusionsOur results shed light on identifying different recovery patterns in FEP. Despite evidence for early intervention effectiveness, we should explore ways to prevent relapse and improve long-term recovery, particularly in reference to the role of timing in the design of interventions.

Facing recovery: Emotional bias in working memory, rumination, relapse, and recurrence of major depression; an experimental paradigm conducted five years after first episode of major depression

Identifying vulnerability factors for relapse of depression is essential in planning preventive interventions. Emotional face processing in major depression (MDD) shows promise as a potential cognitive marker for depression. The current study investigates how working memory (WM) load in face processing relates to rumination and new episodes of MDD in a novel explorative paradigm. It was expected that history of MDD is associated with reduction of the ability to process sad stimuli in high WM load conditions and reduction of the ability to process happy stimuli in low WM conditions. It was further predicted that these relations are associated with rumination and risk for relapse. The experiment was included as a cross sectional part in a follow-up study of a population that previously experienced first episode (FE) depression. The FE (N = 23) and a healthy control group (N = 22) completed a WM face processing task. In the task, three happy or sad faces were presented, processed in either a high or low WM taxing manner, followed by a target stimulus consisting of one of the previous pictures. Response time and accuracy were dependent variables. Rumination and number of relapses or recurrences were measured. The FE group recalled the placement of significantly fewer happy faces in the low WM load condition, and significantly fewer sad faces in the high WM load condition compared to controls. Significantly different scores between groups predicted trait rumination. Poor accuracy in the sad high WM load condition correlated with high degree of rumination. Relapse or recurrence was predicted by rumination. The present study supports an emotional WM deficit in remitted MDD. This suggests that deficits in manipulation of sad faces could represent a trait bias related to rumination and depression.

More dampened monocytic Toll-like receptor 4 response to lipopolysaccharide and its association with cognitive function in Chinese Han first-episode patients with schizophrenia

ObjectiveAccumulating evidence suggests alterations of the innate immune system are related to schizophrenia, although the precise mechanism remains to be elucidated. In this study, we aimed to detect the monocytic toll-like receptor 4 (TLR4) expression under basal and lipopolysaccharide (LPS)-stimulated conditions in first-episode (FE) Han Chinese patients with schizophrenia, as well as its association with cognitive function. MethodsWhole blood samples were taken in 42 FE schizophrenia patients and 36 healthy controls. Expressions of TLR4 on monocytes under basal and LPS-stimulated conditions were measured with flow cytometry. Psychopathological symptoms of schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS) and the MATRICS Consensus Cognitive Battery (MCCB) was administered to all of the participants. ResultsWe found no differences in percentage and mean fluorescence intensity (MFI) of TLR4 expression on monocytes between patients and controls at basal status. However, LPS challenge resulted in a lower cell-surface level of TLR4 on monocytes in FE schizophrenia patients as compared to healthy controls (TLR4+%: F = 4.092, p = 0.047; TLR4 + MFI: F = 4.820, p = 0.031). In addition, correlation analysis together with multivariate linear regression analysis identified basal percentage of TLR4 in monocytes as the beneficial factor for visual learning and working memory in FE patients with schizophrenia. ConclusionsOur findings suggested that TLR4 may be involved in the pathophysiology of schizophrenia, corroborating the role of innate immunity-related functional deficits in increased risk of schizophrenia.

Resting-state gamma-band power alterations in schizophrenia reveal E/I-balance abnormalities across illness-stages.

We examined alterations in E/I-balance in schizophrenia (ScZ) through measurements of resting-state gamma-band activity in participants meeting clinical high-risk (CHR) criteria (n = 88), 21 first episode (FEP) patients and 34 chronic ScZ-patients. Furthermore, MRS-data were obtained in CHR-participants and matched controls. Magnetoencephalographic (MEG) resting-state activity was examined at source level and MEG-data were correlated with neuropsychological scores and clinical symptoms. CHR-participants were characterized by increased 64-90 Hz power. In contrast, FEP- and ScZ-patients showed aberrant spectral power at both low- and high gamma-band frequencies. MRS-data showed a shift in E/I-balance toward increased excitation in CHR-participants, which correlated with increased occipital gamma-band power. Finally, neuropsychological deficits and clinical symptoms in FEP and ScZ-patients were correlated with reduced gamma band-activity, while elevated psychotic symptoms in the CHR group showed the opposite relationship. The current study suggests that resting-state gamma-band power and altered Glx/GABA ratio indicate changes in E/I-balance parameters across illness stages in ScZ.

Comparing cognitive clusters across first- and multiple-episode of psychosis

Cognitive impairments in psychotic disorders (PD) present heterogeneously across patients. Between 2 and 5 clusters have been identified in previous studies with first-episode (FEP) and multiple-episodes of psychosis (MEP) patients suggesting different profiles of impairment. Past findings suggest there are differences between FEP and MEP patients regarding severity and number of affected cognitive domains. Heterogeneity of cognitive deficits in PD has perhaps hindered our understanding of their course. The present study compared non-affective FEP and MEP patients to assess whether illness chronicity could influence cognitive impairment profiles. We analyzed cognitive data, collected with the Cogstate Schizophrenia Battery, of FEP and MEP patients using cluster analysis. We compared clustering methods to obtain a more robust solution. For FEP patients, data were collected at their entry to a specialized clinic; the MEP group consisted of in- and outpatients. Results suggested cognitive heterogeneity was similar in FEP and MEP samples, although in different proportions. Three clusters were identified as the most stable solution and comprised groups of patients with either 1- no cognitive impairment (over-representation of FEP), 2- generalized deficits (over-representation of MEP), or 3- intermediate impairments. These findings encourage early interventions adapted to the profile of impairment.

Early interventions in a US military FIRST episode psychosis program.

Naval Medical Center San Diego's Psychiatric Transition Program is a specialized first episode psychosis treatment program that delivers coordinated specialty care to military service members with psychotic disorders. Due to the unique military environment, military service members with first episode psychosis are hypothesized to receive care very early after the emergence of first psychotic symptoms, resulting in significantly reduced duration of untreated psychosis. This study's aim is to calculate the duration of untreated psychosis for patients enrolled in Naval Medical Center San Diego's Psychiatric Transition Program (NMCSD PTP) from 01JUL2014-31DEC2016. Patients included in this study had a diagnosis of schizophreniform disorder (13.04%), schizophrenia (43.48%), schizoaffective disorder (8.70%), other specified schizophreniform disorder (30.43%), or brief psychotic disorder (4.35%) upon discharge from military service and NMCSD PTP. Duration of untreated psychosis was defined as the interval from emergence of positive psychotic symptoms to antipsychotic medication initiation. Duration of untreated psychosis was measured through retrospective review of the electronic medical record. A total of 69 subjects in the Naval Medical Center San Diego's Psychiatric Transition Program met inclusion criteria. Mean and median values as well as standard deviations were calculated for all included subjects. The mean duration to scheduled (non-PRN) neuroleptic medication was 37 days (median: 4 days). The mean duration to PRN neuroleptic medication was 21 days (median: 2 days). These data support our view that the structure of the military and military healthcare system markedly shortens the DUP for military service members who experience first episode psychosis.

Higher-order language dysfunctions as a possible neurolinguistic endophenotype for schizophrenia: Evidence from patients and their unaffected first degree relatives.

The purpose of the study was to examine the presence of pragmatic dysfunctions in first episode (FE) subjects and their healthy first degree relatives as a potential endophenotype for schizophrenia. Thirty-four FE patients, 34 parents of the patients (REL) and 32 healthy controls (HC) took part in the study. Pragmatic language functions were evaluated with the Right Hemisphere Language Battery, attention and executive functions were controlled, as well as age and education level. The parents differed from HC but not from their FE offspring with regard to overall level of language and communication and the general knowledge component of language processing. The FE participants differed from HC in comprehension of inferred meaning, emotional prosody, discourse dimensions, overall level of language and communication, language processing with regard to general knowledge and communication competences. The FE participants differed from REL regarding discourse dimensions. Our findings suggest that pragmatic dysfunctions may act as vulnerability markers of schizophrenia; their assessment may help in the diagnosis of early stages of the illness and in understanding its pathophysiology. In future research the adoptive and biological parents of schizophrenia patients should be compared to elucidate which language failures reflect genetic vulnerability and which ones environmental factors.

Reliability and validity of the self-report version of the apathy evaluation scale in first-episode Psychosis: Concordance with the clinical version at baseline and 12 months follow-up

Negative symptoms have traditionally been assessed based on clinicians’ observations. The subjective experience of negative symptoms in people with psychosis may bring new insight. The Apathy Evaluation Scale (AES) is commonly used to study apathy in psychosis and has corresponding self-rated (AES-S) and clinician-rated (AES-C) versions. The aim of the present study was to determine the validity and reliability of the AES-S by investigating its concordance with the AES-C. Eighty-four first-episode (FEP) patients completed the shortened 12-item AES-S and AES-C at baseline (T1) and 12 months (T2). Concordance was studied by degree of correlation, comparison of mean scores, and change and difference between diagnostic groups. The Positive and Negative Symptom Scale (PANSS) was used to study convergent and discriminative properties. High concordance was found between AES-S and AES-C at both T1 and T2 regarding mean values, change from T1 to T2, and the proportion with high levels of apathy. Both versions indicated high levels of apathy in FEP, while associations with PANSS negative symptoms were weaker for AES-S than AES-C. Controlling for depression did not significantly alter results. We concluded that self-rated apathy in FEP patients is in concordance with clinician ratings, but in need of further study.

S130. INCIDENCE OF FIRST EPISODE OF PSYCHOSIS IN AN AUSTRALIAN COHORT AND ASSOCIATIONS WITH NEIGHBOURHOOD CHARACTERISTICS

BackgroundThe incidence of psychotic disorders varies between geographical areas and is associated with neighbourhood characteristics. However, the research to date has been mainly confined to Northern European and North American populations. This study will determine whether the incidence of first episode psychosis (FEP) is associated with neighbourhood characteristics, specifically social deprivation, unemployment, social fragmentation and social capital.MethodsThis study was conducted at the Early Psychosis Prevention and Intervention Centre (EPPIC) which provides specialist treatment to all young people aged 15–24 diagnosed with a FEP residing in a defined geographical catchment area within western and northwestern Melbourne. Census data was used to code postcodes for neighbourhood characteristics and determine the at-risk population of people aged 15–24 living within the catchment area. Incidence rate ratios were calculated.Results527 young people treated for a FEP over a three-year period met inclusion criteria. This represents an annual incidence rate of 105.34 per 100,000 persons aged 15–24 per year. There was an increased incidence of FEP in neighbourhoods of greatest social deprivation (IRR=1.60, p=0.003), highest unemployment (IRR=1.67, p=0.001), least social capital (IRR=1.32, p=0.06) and above average social fragmentation (IRR=1.57, p=0.005). All these associations were stronger for non-affective psychoses and absent for affective psychoses. There was variation between sexes, with association only present for social fragmentation in women and social deprivation in men.DiscussionThis study demonstrates that the incidence of psychotic disorders varies according to neighbourhood characteristics, with higher rates in neighbourhoods with higher inequality. Services in each area should be resourced appropriately to ensure that the expected incidence can be effectively managed.

PROLACTIN LEVEL IN PATIENTS WITH FIRST EPISODE SCHIZOPHRENIA TREATED FOR ONE YEAR WITH ATYPICAL ANTIPSYCHOTICS.

Atypical antipsychotics (AAs) are the first-line treatments for schizophrenia, schizoaffective disorder and bipolar disorder. However, they are now extensively utilized as off label in a myriad of diseases despite their frequently serious metabolic side-effects and hyperprolactinemia. The purpose of our study was to observe long-term (one year) prolactin level change in first episode schizophrenia patients treated with one of the four AAs: olanzapine, quetiapine, amisulpride, ziprasidone. This study is an analysis of the prolactin level associated with the atypical antipsychotics used in European First Episode Schizophrenia Trial (EUFEST) study. Seventy-three first episode schizophrenia patients from the 113 patients, randomized to one of the four AAs treatment arms. Prolactin level was obtained at baseline, 6 and 12 months for all the four AAs. Analyses have been done for each antipsychotic separately for each sex. For the male patients neither of the four antipsychotics have been associated with a statistically significant increase of prolactin level in the entire study (p>0.05). In case of the female patients, treatment with olanzapine (p=.021) and ziprasidone (p=.005) has been associated with a decrease of prolactin level in one year compared with baseline. In both men and women, the administration of these four AAs is not associated with the increase of prolactin levels, moreover, in women's case, there is a reduction of prolactin values at administration of Olanzapine and Ziprasidone. These results are optimistic, suggesting that long term administration of these antipsychotics is safe regarding prolactin level.

Clostridium diffi cile infection in children: characteristics and treatment – a single-center study from Romania

The incidence of Clostridium diffi cile infection (CDI) in children is progressively increasing. The study evaluated the characteristicsand antibacterial treatment of CDI at a Romanian pediatric gastroenterology department. We performed a retrospective study toanalyze cases diagnosed with CDI, identifi ed through immunoassays for Clostridium diffi cile toxins in stools, between January 1,2005 and December 31, 2015. Eighty-nine episodes of CDI were diagnosed in 73 patients. We noticed an increasing incidence reachingmaximum in 2014 with 6.9 cases/1000 patients. Almost 40% of patients had community-acquired CDI. The most frequentlyassociated comorbidities were infl ammatory bowel disease and cow’s milk allergy. There was a small percentage of recurrent episodes(24.2%). Metronidazole was administered as fi rst-line treatment in 49.2% of mild/moderate cases and proved eff ective in 79.4%of these. More than 70% of all patients in which metronidazole was not effi cient had comorbidities, compared to 22.2% of patientswhere metronidazole was effi cacious. The alternative was vancomycin which cured the disease in all cases. In severe forms, a combinationof intravenous metronidazole and oral vancomycin was the effi cient solution. Oral vancomycin was the effi cacious treatmentfor the fi rst recurrence. We report an increasing incidence of CDI in Romanian children. The failure rate for metronidazoletreatment was low, thus metronidazole may be safely recommended for the fi rst episode of mild/moderate CDI. Vancomycin provedeff ective in all cases, regardless of the fi rst episode or recurrence, and may be used effi ciently as fi rst-line treatment.Key words: Clostridium diffi cile; antibacterial treatment; children

The structural connectivity pathology of first-episode schizophrenia based on the cardinal symptom of auditory verbal hallucinations

Heterogeneous findings across studies of structural abnormality in schizophrenia (SZ) have impeded the development a unified theory of white matter pathology. As a cardinal symptom of SZ, auditory verbal hallucination (AVH) has been suspected to be associated with improper communication among several brain regions, which might indicated white matter pathology. Participants comprised 25 first-episode (FE) patients with AVH, 25 patients without AVH and 25 healthy subjects. Diffusion tensor imaging (DTI) measures were calculated using the TBSS of FSL. Voxel-based ANOVA tests were performed among the three groups and threshold-free cluster enhancement (TFCE) method correction was used for multiple comparisons. Voxel-based one-way ANOVA showed significant group effects for fractional anisotropy (FA) and radial diffusivity (RD) values. Post-hoc t-tests indicated that schizophrenia patients had lower FA and higher RD values in the internal capsule and anterior corona radiata than control subjects. Post-hoc analyses exhibited more widespread fiber disruptions in AVH patients than non-AVH patients. These results hinted on the important role of projection fiber disruption in schizophrenia patients. In addition, the current study also suggested that direct comparison between studies using patients with different symptom profiles should be interpreted with caution.

Redox Dysregulation in Schizophrenia Revealed by in vivo NAD+/NADH Measurement.

Balance between the redox pair of nicotinamide adenine dinucleotides (oxidized NAD+ and reduced NADH), reflects the oxidative state of cells and the ability of biological systems to carry out energy production. A growing body of evidence suggests that an "immuno-oxidative" pathway including oxidative stress, mitochondrial dysfunction, neuroinflammation, and cell-mediated immune response may contribute to disruptions in brain activity in schizophrenia (SZ). The aim of this study is to assess possible redox imbalance in SZ patients by using a novel in vivo 31P MRS technique. The participants included 40 healthy controls, 21 chronic SZ, 13 first-episode (FE) SZ, and 18 FE bipolar disorder (BD) patients (as a psychiatric control group). All participants initially underwent structural imaging at a 3 Tesla (3 T) and 31P MRS measurements were performed on a 4 T MR scanner. NAD+ and NADH components were determined by nonlinear least-square fitting of the model simulated spectra; these incorporated prior chemical shift and coupling constant information to in vivo resonances obtained from 31P MRS experiments. We found a significant reduction in the NAD+/NADH ratio in chronically ill SZ patients compared to a matched healthy control group, and in FE SZ patients compared to both a matched FE BD patient group and a matched healthy control group. These findings provide evidence for redox imbalance in the brain in all phases of SZ, potentially reflecting oxidative stress.

Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia.

Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis.

Cognitive functioning in individuals at ultra-high risk for psychosis, first-degree relatives of patients with psychosis and patients with first-episode schizophrenia

ObjectiveThe aim of the present study was to investigate and compare cognitive functioning of first-degree relatives of people with schizophrenia who were also at ultra-high risk (UHR) for psychosis with patients with first-episode (FE) schizophrenia, first degree relatives of patients not fulfilling UHR criteria (FDR), and healthy control (HC) subjects. MethodForty subjects in each group were included, underwent a face-to-face interview and completed a neurocognitive test battery, including the Trail Making Test-A (TMT-A, psychomotor functions), Stroop Color Word Test (attention), Digit Symbol Coding Test (DST, processing speed and working memory) and Hopkins Verbal Leaning Test-Revised (HVLT-R, verbal memory). ResultsFunctioning in all the cognitive test domains displayed a gradual decrease from the HC, FDR, UHR to FE groups. After controlling for covariates, there were still significant differences in TMT-A (F(7160)=35.4, P<0.001), DST (F(7160)=38.9, P<0.001), Stroop Color Word Test (F(7160)=35.0, P<0.001), Stroop Word Test (F(7160)=36.2, P<0.001), Stroop Color Test (F(7160)=40.9, P<0.001) and HVLT-R (F(7160)=62.5, P<0.001) between the four groups, indicating that the cognitive functioning in the UHR group was intermediate between the FE and FDR groups, while the FDR group had poorer performance than the HC group, and the FE group had the poorest cognitive functioning across all four examined domains. ConclusionThe results indicate that impairments in processing speed, attention, working memory and verbal memory exist in both UHR and FDR subjects. In order to clarify the associations between cognitive functioning and UHR and schizophrenia, longitudinal studies are warranted.

Essential brain structural alterations in major depressive disorder: A voxel-wise meta-analysis on first episode, medication-naive patients

BackgroundBecause brain morphological abnormalities in major depressive disorder (MDD) may be modulated by medication and episodes, previous meta-analyses of voxel-based morphometry (VBM) studies therefore have been biased for including medicated patients or medication-free patients who had ever received drugs, as well as patients with different episodes. We sought to identify the essential morphological features without the interference of medication and episodes in MDD. MethodsSeed-based d Mapping was applied to analyze the gray matter differences between all first episode (FE), medication-naive MDD patients and healthy controls. Subgroup meta-analyses and meta-regression were used to explore the effects of methodology, demographics and clinical characteristics. ResultsWe identified 10 studies comprising 329 FE, medication-naive MDD patients and 340 healthy controls. Gray matter volumes were increased in the bilateral thalamus, cuneus, left paracentral lobule and medial superior frontal gyrus, and decreased in the right dorsolateral superior frontal gyrus, left insula and middle frontal gyrus in patients. Decreased volume in the right inferior temporal gyrus was only observed in patients with short illness duration and studies with threshold corrections. Moreover, there were different results between 3.0T MRI and 1.5T MRI studies. Meta-regression analyses revealed that mean age and the percentage of female patients were not significantly correlated with gray matter changes. LimitationsThere are heterogeneities in demographics, clinical features and analyzing methods of selected studies. ConclusionsThe present meta-analysis revealed that structural abnormalities in the fronto-limbic networks are the essential characteristics in MDD and could contribute to the high risk of suicide in patients.

Driving skills in unmedicated first- and recurrent-episode schizophrenic patients.

The present study was designed to examine driving skills according to regulations of the German guidelines for road and traffic safety in unmedicated schizophrenic inpatients. A total of 13 first-episode (FES) and 13 recurrent-episode (RES) schizophrenic inpatients were included in the analysis and compared with a group of 20 healthy controls (HC). Data were collected with the computerised Wiener Testsystem measuring visual perception, reactivity and stress tolerance, concentration and vigilance. Analysis of data indicates that a great proportion (58%) of schizophrenic patients were impaired in psychomotor functions related to driving skills. FES and RES significantly differed with respect to driving ability with a greater proportion in the FES (38%) showing severe impairments when compared with RES (25%). Differences with respect to HC performance were most pronounced in concentration and for the FES additionally in visual perception. Analysis of our data indicates that a great proportion of schizophrenic patients are impaired in psychomotor functions related to driving skills that cannot be attributed to adverse side effects of psychopharmacological treatment. Besides, we cannot confirm a chronical decline of psychomotor functions related to driving skills at least in the early course of schizophrenic illness.