Search

Aims: Schizophrenia, a debilitating mental disorder, is characterized by persistent negative symptoms such as avolition and anhedonia. Currently, there are no effective treatments available for these symptoms. Thus, our study aims to assess the efficacy of online high-definition transcranial direct current stimulation (online HD-tDCS) in addressing the negative symptoms of schizophrenia, utilizing a double-blind, randomized, sham-controlled trial design., Methods: Fifty-nine patients with schizophrenia were randomized to receive either active HD-tDCS or sham stimulation, targeting the left dorsolateral prefrontal cortex. Outcomes were measured by changes in the Positive and Negative Syndrome Scale Factor Score for Negative Symptom (PANSS-FSNS). Exact low-resolution electromagnetic tomography was used to assess the functional connectivity., Results: All 59 participants, including 50.84% females with an average age of 43.36 years, completed the trial. In the intention-to-treat analysis, patients receiving active HD-tDCS showed greater improvement in PANSS-FSNS scores compared to those receiving the sham procedure. The differences were 2.34 (95% confidence interval [CI], 1.28-3.40), 4.28 (95% CI, 2.93-5.62), and 4.91 (95% CI, 3.29-6.52) after the intervention, as well as at 1-week and 1-month follow-ups, respectively. A tingling sensation on the scalp was more common in the active group (63.3%) compared to the sham group (10.3%). Additionally, HD-tDCS was associated with a decrease in delta-band connectivity within the default mode network., Conclusions: High-definition transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia when combined with online functional targeting., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences © 2024 Japanese Society of Psychiatry and Neurology.)

Background and Objectives : Attentional dysfunction has long been viewed as one of the fundamental underlying cognitive deficits in schizophrenia. There is an urgent need to understand its neural underpinning and develop effective treatments. In the process of attention, neural oscillation has a central role in filtering information and allocating resources to either stimulus-driven or goal-relevant objects. Here, we asked if resting-state EEG connectivity correlated with attentional performance in schizophrenia patients. Materials and Methods : Resting-state EEG recordings were obtained from 72 stabilized patients with schizophrenia. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity between 84 intra-cortical current sources determined by eLORETA (exact low-resolution brain electromagnetic tomography) for five frequencies. The Conners' Continuous Performance Test-II (CPT-II) was administered for evaluating attentional performance. Linear regression with a non-parametric permutation randomization procedure was used to examine the correlations between the whole-brain functional connectivity and the CPT-II measures. Results : Greater beta-band right hemispheric fusiform gyrus (FG)-lingual gyrus (LG) functional connectivity predicted higher CPT-II variability scores (r = 0.44, p < 0.05, corrected), accounting for 19.5% of variance in the CPT-II VAR score. Greater gamma-band right hemispheric functional connectivity between the cuneus (Cu) and transverse temporal gyrus (TTG) and between Cu and the superior temporal gyrus (STG) predicted higher CPT-II hit reaction time (HRT) scores (both r = 0.50, p < 0.05, corrected), accounting for 24.6% and 25.1% of variance in the CPT-II HRT score, respectively. Greater gamma-band right hemispheric Cu-TTG functional connectivity predicted higher CPT-II HRT standard error (HRTSE) scores (r = 0.54, p < 0.05, corrected), accounting for 28.7% of variance in the CPT-II HRTSE score. Conclusions : Our study indicated that increased right hemispheric resting-state EEG functional connectivity at high frequencies was correlated with poorer focused attention in schizophrenia patients. If replicated, novel approaches to modulate these networks may yield selective, potent interventions for improving attention deficits in schizophrenia.

Background: Second-generation antipsychotics (SGAs) is thought responsible for the metabolic abnormalities of schizophrenic patients, however, some untreated schizophrenic patients had already developed problems with glucose metabolism. The present study examined the hypothesis that schizophrenia itself but not risperidone, an extensively employed SGA, is accountable for metabolic abnormalities., Methods: A 56-day risperidone regimen (1 mg/kg/day) was employed for rats of social isolation rearing (SIR) beginning at different developmental stage (28 or 56 days after weaning, i.e., adolescent and young adulthood, respectively). Metabolic parameters including body weight, systolic blood pressure (SBP), triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and plasma glucose were measured at baseline, 28, and 56 days of the regimen. Oral glucose tolerance test (OGTT) was performed at the end of the regimen. Insulin function was evaluated by area under the curve (AUC) of OGTT, homeostasis model assessment-insulin resistance (HOMA-ir), and Matsuda index., Results: Our results demonstrated that: (i) SIR rats presented higher body weight, plasma triglyceride, and HOMA-ir than social controls. (ii) Higher insulin resistance was specifically presented in young adult rather than adolescent SIR rats. (iii) Adolescent drugged rats showed a lower level of LDL in day 28 of the regimen than young adult. Risperidone led to a lower LDL level in only young adult IR rats in day 56 than undrugged rats. (iv) SIR-induced dysregulation of insulin can be reversed by chronic risperidone treatment beginning at adolescence but not young adulthood., Conclusions: Our findings support the primary role of schizophrenia in metabolic abnormalities and risperidone appear beneficial when administered earlier., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Background: We previously showed the efficacy of bi-anodal transcranial direct current stimulation (tDCS) over the prefrontal cortex (PFC) regions with extracephalic reference placement in improving negative symptoms in schizophrenia. In this ancillary investigation, the effects of this intervention on insight levels, other clinical outcomes, and cardio-respiratory and autonomic functions were examined and the potential of biomarkers for treatment response was explored., Methods: Schizophrenia patients were randomly allocated to receive 10 sessions of bi-anodal tDCS over the PFC regions with extracephalic reference placement (2 mA, 20 minutes, twice daily for 5 weeks) or sham stimulation. We examined, in 60 patients at baseline, immediately after stimulation and at follow-up visits, the insight levels, other clinical outcomes, blood pressure, respiratory rate, heart rate, and heart rate variability., Results: Insight levels as assessed by the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia awareness of the disease, positive and negative symptoms dimensions, and beliefs about medication compliance as assessed by Medication Adherence Rating Scale were significantly enhanced by active stimulation relative to sham. No effects were observed on cognitive insight, other clinical outcomes, or cardio-respiratory and autonomic functions. Heart rate variability indices as biomarkers were not associated with the clinical response to the intervention., Conclusions: Our results provide evidence for bi-anodal tDCS over the PFC regions with extracephalic reference placement in heightening the levels of insight into the disease and symptoms, as well as beliefs about medication compliance in schizophrenia, without impacting other clinical outcomes and cardio-respiratory/autonomic functions., (© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.)

High-frequency transcranial random noise stimulation (hf-tRNS) is a non-invasive neuromodulatory technique capable of increasing human cortex excitability. There were only published case reports on the use of hf-tRNS targeting the lateral prefrontal cortex in treating negative symptoms of schizophrenia, thus necessitating systematic investigation. We designed a randomized, double-blind, sham-controlled trial in a cohort of stabilized schizophrenia patients to examine the efficacy of add-on hf-tRNS (100-640 Hz; 2 mA; 20 min) using a high definition 4 × 1 electrode montage (anode AF3, cathodes AF4, F2, F6, and FC4) in treating negative symptoms (ClinicalTrials.gov ID: NCT04038788). Participants received either active hf-tRNS or sham twice daily for 5 consecutive weekdays. Primary outcome measure was the change over time in the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS), which was measured at baseline, after 10-session stimulation, and at one-week and one-month follow-ups. Among 36 randomized patients, 35 (97.2%) completed the trial. Intention-to-treat analysis showed a significantly greater decrease in PANSS-FSNS score after active (-17.11%) than after sham stimulation (-1.68%), with a large effect size (Cohen's d = 2.16, p < 0.001). The beneficial effect lasted for up to one month. In secondary-outcome analyses, the authors observed improvements with hf-tRNS of disorganization symptoms, unawareness of negative symptoms, subjective response to taking antipsychotics, and antipsychotic-induced extrapyramidal symptoms. No effects were observed on the neurocognitive performance and other outcome measures. Overall, hf-tRNS was safe and efficacious in improving negative symptoms. Our promising findings should be confirmed in a larger sample of patients with predominant negative symptoms., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Varying degrees of impaired clinical insight in schizophrenia differentially impact medication adherence and clinical outcomes, prompting in-depth investigations of the deficits. Research is scarce on the differences in peripheral physiological markers between varying degrees of impaired insight. The aims of this study were to examine the differences in (1) resting-state high-frequency heart rate variability (HF-HRV) and (2) crucial clinical outcomes between schizophrenia patients with varying degrees of insight impairment as measured by the Positive and Negative Syndrome Scale (PANSS) item G12 (lack of judgment and insight). The study recruited a sample of 95 stabilized schizophrenia patients with insight impairment. Patients were divided into 2 groups of either minimal insight impairment (n = 25, PANSS G12 = 2-3) or moderate-to-severe insight impairment (n = 70, PANSS G12 ≥ 4). Patients with moderate-to-severe insight impairment displayed lower HF-HRV, clinician-rated psychosocial function, medication adherence, and working memory capacity, and higher self-reported psychosocial function and life quality, but comparable cognitive insight compared to those with minimal insight impairment. A logistic regression model predicted moderate-to-severe insight impairment based on HF-HRV values at the optimal cut-off point of 3.655, with the sensitivity and specificity 84% and 72%, respectively. HF-HRV seems a peripheral marker sensitively reflecting central pathophysiology implicated in insight impairment of schizophrenia., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Little is known about the impact of fronto-temporal transcranial direct current stimulation (tDCS) on attitudes toward mental illness, psychosocial and autonomic functioning, life quality, and medication adherence among schizophrenia patients., Methods: Sixty schizophrenia patients were randomly allocated to receive 10 sessions of active (2 mA, 20 min, 2 sessions/day for five weekdays) or sham fronto-temporal tDCS. Self-Appraisal of Illness Questionnaire (SAIQ), Medication Adherence Rating Scale (MARS), World Health Organization Quality of Life-BREF (WHOQOL-BREF) and indices of heart rate variability (HRV) were measured at baseline, immediately after tDCS and at one-month follow-up visit., Results: There were significant group-by-time interactions for scores of SAIQ presence/outcome subscale, total MARS and its subscale of subjective response to taking medication, WHOQOL-BREF psychological domain. Relative to sham, tDCS significantly improved self-awareness of presence/outcome of schizophrenia (Cohen's d = 0.465, p = 0.0011), subjective response to taking medication (Cohen's d = 0.639, p < 0.001) and psychological domain of life quality (Cohen's d = 0.459, p = 0.00114). These effects lasted for less than one month. The group-by-time interactions were non-significant for clinician-rated psychosocial functioning, mean RR intervals, and all HRV indices., Conclusion: Fronto-temporal tDCS briefly optimizes self-reported insight levels, beliefs about treatment adherence, and psychological domain of life quality in patients with schizophrenia. Further studies are required to confirm whether patients treated with 5-day, 10-session tDCS in combination with multisession "maintenance" stimulation every month would attain favourable outcomes., Significance: We provide novel evidence for the potential utility of tDCS in schizophrenia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

No studies have examined the efficacy of bi-anodal transcranial direct current stimulation (tDCS) over bilateral dorsolateral prefrontal cortex (DLPFC) coupled with bilateral extracephalic references in treating negative symptoms of non-acute schizophrenia patients. This study aimed to investigate the therapeutic effects of the new approach of tDCS on negative symptoms, other schizophrenia symptoms, cognitive deficits and psychosocial functioning in a double-blind, randomized, sham-controlled trial. Patients with non-acute schizophrenia (N = 60) in randomized order received sham treatment or bilaterally provided tDCS (2 mA, twice-daily sessions for five consecutive days) with the anode over the DLPFC and the reference (cathode) over the ipsilateral forearm. The negative symptoms as measured by a dimensional approach of Positive and Negative Syndrome Scale (PANSS) were rapidly reduced by bimodal tDCS relative to sham stimulation (F = 24.86, Cohen's d = 0.661, p = 6.11 × 10 -6 ). The beneficial effect on negative symptoms lasted for up to 3 months. The authors also observed improvement with tDCS of psychosocial functioning as measured by the global score of Personal and Social Performance scale (PSP) and psychopathological symptoms especially for disorganization and cognitive symptoms as measured by the PANSS. No effects were observed on other schizophrenia symptom dimensions and the performance on a series of neurocognitive tests. Our results show promise for bi-anodal tDCS over bilateral DLPFC using bilateral extracephalic references in treating negative symptoms and other selected manifestations of schizophrenia. Further studies with electrophysiological or imaging evaluation help unravel the exact mechanism of action of this novel stimulation parameter of tDCS in schizophrenia patients. (ClinicalTrials.gov ID:NCT03701100)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The efficacy of fronto-temporal transcranial direct current stimulation in treating auditory verbal hallucinations and other psychopathological symptoms of schizophrenia patients has been examined in a small number of clinical trials with limited sample sizes, but the results are mixed. Fronto-temporal transcranial direct current stimulation has also been demonstrated to enhance patients' insight into their mental illness in an open-label pilot study. The current investigation aimed to investigate the therapeutic effects of fronto-temporal transcranial direct current stimulation on the severity of auditory verbal hallucinations, other schizophrenia symptoms, and insight in a large double blind, randomized, sham-controlled trial., Methods: Sixty patients with medication-refractory auditory verbal hallucinations were randomized over 2 conditions: transcranial direct current stimulation with 2-mA, twice-daily sessions for 5 consecutive days, with anodal stimulation to the left prefrontal cortex and cathodal stimulation to the left temporo-parietal junction, and sham treatment., Results: Fronto-temporal transcranial direct current stimulation failed to cause significant changes in the severity of auditory verbal hallucinations and other schizophrenia symptoms. The levels of insight into illness (effect size=0.511, P<.001) and positive symptoms (effect size=0.781, P<.001) were largely promoted by 5 days of transcranial direct current stimulation relative to sham treatment. The beneficial effects on the 2 insight dimensions remained 1 month after transcranial direct current stimulation., Conclusions: Fronto-temporal transcranial direct current stimulation is not more effective for auditory verbal hallucinations and other schizophrenia symptoms than sham treatment. But the results of transcranial direct current stimulation-associated improvement in awareness of illness and positive symptoms show promise and provide a new direction for future research into insight promotion interventions in schizophrenia.

Impaired quality of life (QoL) is a common and clinically relevant feature of schizophrenia. In the present study, we attempted to formulate a model of QoL in the chronic stage of schizophrenia by including key variables-namely cognitive insight, self-stigma, insight into treatment, and medication compliance-that were proposed as its significant predictors in previous studies. We employed structural equation modeling (SEM) to simultaneously test the associations between these variables. A total of 170 community-dwelling patients with schizophrenia participated in this study. Cognitive insight, self-stigma, insight into treatment, medication compliance, and QoL were assessed through self-reporting. Symptoms were rated by interviewers. The influences of cognitive insight, stigma, insight into treatment, and medication compliance on QoL were supported using SEM. Our findings indicated that cognitive insight had a significant, positive, and direct effect on both self-stigma and insight into treatment; in contrast, it had a negative and direct effect on medication compliance. Notably, no evidence indicated a direct effect of cognitive insight on QoL. Thus, individuals with high cognitive insight reported low QoL because of stigma, low medication compliance, and their increased insight into treatment. In contrast, cognitive insight might indirectly ameliorate QoL mediated by the effect of insight into treatment on medication compliance. The findings provide additional support of the links between cognitive and clinical insight, self-stigma, medication compliance, and QoL in those with schizophrenia and suggest the need for screening and intervention services appropriate for this high-risk population.

Objective: Stigma resistance (SR) has recently emerged as a prominent aspect of research on recovery from schizophrenia, partly because studies have suggested that the development of stigma-resisting beliefs may help individuals lead a fulfilling life and recover from their mental illness. The present study assessed the relationship between personal SR ability and prediction variables such as self-stigma, self-esteem, self-reflection, coping styles, and psychotic symptomatology., Method: We performed an exploratory cross-sectional study of 170 community-dwelling patients with schizophrenia. Self-stigma, self-esteem, self-reflection, coping skills, and SR were assessed through self-report. Psychotic symptom severity was rated by the interviewers. Factors showing significant association in univariate analyses were included in a stepwise backward regression model., Results: Stepwise regressions revealed that acceptance of stereotypes of mental illness, self-esteem, self-reflection, and only 2 adaptive coping strategies (positive reinterpretation and religious coping) were significant predictors of SR. The prediction model accounted for 27.1% of the variance in the SR subscale score in our sample., Conclusions: Greater reflective capacity, greater self-esteem, greater preferences for positive reinterpretation and religious coping, and fewer endorsements of the stereotypes of mental illness may be key factors that relate to higher levels of SR. These factors are potentially modifiable in tailored interventions, and such modification may produce considerable improvements in the SR of the investigated population. This study has implications for psychosocial rehabilitation and emerging views of recovery from mental illness.

Reduced resting heart rate variability (HRV) has been observed in patients with schizophrenia and their relatives, suggesting genetic predispositions. However, findings have not been consistent. We assessed cardiac autonomic response to deep breathing in first-degree relatives of patients with schizophrenia (n=45; 26 female; aged 39.69±14.82 years). Data were compared to healthy controls (n=45; 26 female; aged 38.27±9.79 years) matched for age, gender, body mass index and physical activity as well as to unmedicated patients with acute schizophrenia (n=45; 25 female; aged 37.31±12.65 years). Electrocardiograms were recorded under supine resting and deep-breathing conditions (10-12breaths/min). We measured HRV components including variance, low-frequency (LF) power, which may reflect baroreflex function, high-frequency (HF) power, which reflects cardiac parasympathetic activity, and LF/HF ratio, which may reflect sympatho-vagal balance. Patients rather than relatives exhibited lower resting-state HRV (variance, LF, and HF) than controls. As expected, deep breathing induced an increase in variance and HF-HRV in controls. However, such a response was significantly reduced in both patients and their relatives. In conclusion, the diminished cardiac autonomic reactivity to deep breathing seen in patients and their unaffected relatives indicates that this pattern of cardiac autonomic dysregulation may be regarded as a genetic trait marker for schizophrenia., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Increasing the evidence of inflammation's contribution to schizophrenia; using anti-inflammatory or neurotrophic therapeutic agents to see whether they improve schizophrenia treatment. Dextromethorphan (DM), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, might protect monoamine neurons. Whether treating schizophrenia with risperidone plus add-on DM is more effective than risperidone (RISP) alone, and the association between the ALDH2 polymorphism and treatment response were investigated., Methods: A double-blind study in which patients with schizophrenia were randomly assigned to the RISP + DM (60 mg/day; n = 74) or the RISP + Placebo (n = 75) group. The Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) scores were used to evaluate clinical response during weeks 0, 1, 2, 4, 6, 8, and 11. The genotypes of the ALDH2 polymorphism were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. A generalized estimating equation was used to analyze the effects of ALDH2 polymorphism on the clinical performance of DM., Results: PANSS and SANS scores were significantly lower in both groups after 11 weeks of treatment. SANS total scores were significantly lower in the RISP + DM group in patients with the ALDH2*2*2 genotype., Conclusions: RISP plus add-on DM treatment reduced negative schizophrenia symptoms in patients with the ALDH2 polymorphism., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: The impact of schizophrenia on vital diseases, such as chronic kidney disease (CKD), has not as yet been verified. This study aims to establish whether there is an association between schizophrenia and CKD., Design: A nationwide matched cohort study., Setting: Taiwan's National Health Insurance Research Database., Participants: A total of 2338 patients with schizophrenia, and 7014 controls without schizophrenia (1:3), matched cohort for sex, age group, geography, urbanisation and monthly income, between 1 January 2003 and 31 December 2007, based on the International Classifications of Disease Ninth Edition (ICD-9), Clinical Modification codes., Primary and Secondary Outcome Measures: After making adjustments for confounding risk factors, a Cox proportional hazards model was used to compare the risk of developing CKD during a 3-year follow-up period from the index date., Results: Of the 2338-subject case cohort, 163 (6.97%) developed a CKD, as did 365 (5.20%) of the 7014 control participants. Cox proportional hazards regression analysis revealed that patients with schizophrenia were more likely to develop CKD (HR=1.36, 95% CI 1.13 to 1.63; p<0.001). After adjusting for gender, age group, hypertension, diabetes mellitus, hyperlipidaemia, heart disease and non-steroid anti-inflammatory drugs (NSAIDs) usage, the HR for patients with schizophrenia was 1.25 (95% CI 1.04 to 1.50; p<0.05). Neither typical nor atypical antipsychotics was associated an increased risk of CKD in patients with schizophrenia., Conclusions: The findings from this population-based retrospective cohort study suggest that schizophrenia is associated with a 25% increase in the risk of developing CKD within only a 3-year follow-up period., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Unlabelled: Increasing evidence suggests that inflammation contributes to the etiology and progression of schizophrenia. Molecules that initiate inflammation, such as virus- and toxin-induced cytokines, are implicated in neuronal degeneration and schizophrenia-like behavior. Using therapeutic agents with anti-inflammatory or neurotrophic effects may be beneficial for treating schizophrenia. One hundred healthy controls and 95 Han Chinese patients with schizophrenia were tested in this double-blind study. Their PANSS scores, plasma interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and brain-derived neurotrophic factor (BDNF) levels were measured before and after pharmacological treatment. Pretreatment, plasma levels of IL-1β and TNF-α were significantly higher in patients with schizophrenia than in controls, but plasma BDNF levels were significantly lower. Patients were treated with the atypical antipsychotic risperidone (Risp) only or with Risp+ dextromethorphan (DM). PANSS scores and plasma IL-1β levels significantly decreased, but plasma TNF-α and BDNF levels significantly increased after 11 weeks of Risp treatment. Patients in the Risp+ DM group showed a greater and earlier reduction of symptoms than did those in the Risp-only group. Moreover, Risp+ DM treatment attenuated Risp-induced plasma increases in TNF-α. Patients with schizophrenia had a high level of peripheral inflammation and a low level of peripheral BDNF. Long-term Risp treatment attenuated inflammation and potentiated the neurotrophic function but also produced a certain degree of toxicity. Risp+ DM was more beneficial and less toxic than Risp-only treatment., Clinical Trial Registration: Protocol Record: HR-93-50;, Trial Registration Number: NCT01189006; URL: http://www.clinicaltrials.gov.

Although cobalamin deficiency is widely known and usually presents with hematologic and neuropsychiatric manifestations, the psychiatric symptoms are not usually the predominant manifestation. We describe a young single male vegetarian who developed a cobalamin-induced psychotic episode without preceding neurologic manifestations and without any hematologic symptoms. He recovered after a short course of antipsychotics and oral cobalamin supplementation and remained asymptomatic and functionally independent at 1 year of follow-up.

EEG studies indicated that schizophrenia patients had increased resting-state theta-band functional connectivity, which was associated with negative symptoms. We recently published the first study showing that theta (6 Hz) transcranial alternating current stimulation (tACS) over left prefrontal and parietal cortices during a working memory task for accentuating frontoparietal theta-band synchronization (in-phase theta-tACS) reduced negative symptoms in schizophrenia patients. Here, we hypothesized that in-phase theta-tACS can modulate theta-band large-scale networks connectivity in schizophrenia patients. In this randomized, double-blind, sham-controlled trial, patients received twice-daily, 2 mA, 20-min sessions of in-phase theta-tACS for 5 consecutive weekdays (n = 18) or a sham stimulation (n = 18). Resting-state electroencephalography data were collected at baseline, end of stimulation, and at one-week follow-up. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity across 84 cortical regions at theta frequency (5–7 Hz). EEG data from 35 patients were analyzed. We found that in-phase theta-tACS significantly reduced the LPS between the posterior cingulate (PC) and the parahippocampal gyrus (PHG) in the right hemisphere only at the end of stimulation relative to sham (p = 0.0009, corrected). The reduction in right hemispheric PC-PHG LPS was significantly correlated with negative symptom improvement at the end of the stimulation (r = 0.503, p = 0.039). Our findings suggest that in-phase theta-tACS can modulate theta-band large-scale functional connectivity pertaining to negative symptoms. Considering the failure of right hemispheric PC-PHG functional connectivity to predict improvement in negative symptoms at one-week follow-up, future studies should investigate whether it can serve as a surrogate of treatment response to theta-tACS. [ABSTRACT FROM AUTHOR]

Background: Homicidal offenders with schizophrenia who went through psychiatric evaluations are a small but significant group during a criminal appeal. Aim: Our aims are to explore whether the types of crime, such as homicide or not, would be related to the verdicts for the alleged offenders with schizophrenia in Taiwan. Our hypothesis was that homicide cases, rather than other alleged offenses, would be more likely to be regarded as no responsibility (legal insanity) or diminished responsibility for those defendants in the forensic psychiatric evaluation opinions or the court verdicts. Methods: A retrospective comparison of the homicide offenders with the nonhomicide offenders with schizophrenia, registered between December 2000 and November 2009, was conducted in the web-based, national, open-access court verdict databank. Results: There were 33 (3.4%) in 9691 criminal homicide offenders that had a diagnosis of schizophrenia. There were 33 in the homicide group and 22 in the nonhomicide group. Among these defendants in the homicide group, 3 (9.1%) were regarded as legal insanity, and 21 (63.6%) were regarded as diminished responsibility in comparison to the zero (0%) as legal insanity and nine (40.9%) as diminished responsibility in the nonhomicide group (P = 0.029). In addition, the group with multiple evaluations tended to receive forensic psychiatric opinions as legal insanity (N = 3; 33.3%), and the group with single evaluation tended to receive forensic psychiatric opinions as diminished responsibility (N = 16; 66.67%) (P = 0.017). The group with multiple evaluations tended to be ruled as legal insanity in the court (P = 0.001). Conclusion: Homicide cases would be more likely to be regarded as legal insanity or diminished responsibility for the defendants with schizophrenia in the forensic psychiatric evaluation opinions or the court verdicts. [ABSTRACT FROM AUTHOR]

Reduced left-lateralized electroencephalographic (EEG) frontal alpha asymmetry (FAA), a biomarker for the imbalance of interhemispheric frontal activity and motivational disturbances, represents a neuropathological attribute of negative symptoms of schizophrenia. Unidirectional high-frequency transcranial random noise stimulation (hf-tRNS) can increase the excitability of the cortex beneath the stimulating electrode. Yet, it is unclear if hf-tRNS can modulate electroencephalographic FAA in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast hf-tRNS and sham stimulation for treating negative symptoms in 35 schizophrenia patients. We used electroencephalography to investigate if 10 sessions of hf-tRNS delivered twice-a-day for five consecutive weekdays would modulate electroencephalographic FAA in schizophrenia. EEG data were collected and FAA was expressed as the differences between common-log-transformed absolute power values of frontal right and left hemisphere electrodes in the alpha frequency range (8–12.5 Hz). We found that hf-tRNS significantly increased FAA during the first session of stimulation (p = 0.009) and at the 1-week follow-up (p = 0.004) relative to sham stimulation. However, FAA failed to predict and surrogate the improvement in the severity of negative symptoms with hf-tRNS intervention. Together, our findings suggest that modulating electroencephalographic frontal alpha asymmetry by using unidirectional hf-tRNS may play a key role in reducing negative symptoms in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Schizophrenia is associated with increased resting-state large-scale functional network connectivity in the gamma frequency. High-frequency transcranial random noise stimulation (hf-tRNS) modulates gamma-band endogenous neural oscillations in healthy individuals through the application of low-amplitude electrical noises. Yet, it is unclear if hf-tRNS can modulate gamma-band functional connectivity in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast hf-tRNS (N = 17) and sham stimulation (N = 18) for treating negative symptoms in 35 schizophrenia patients. Short continuous currents without neuromodulatory effects were applied in the sham group to mimic real-stimulation sensations. We used electroencephalography to investigate if a five-day, twice-daily hf-tRNS protocol modulates gamma-band (33–45 Hz) functional network connectivity in schizophrenia. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity from regions within the default mode network (DMN) and fronto-parietal network (FPN), and functional connectivity was computed using lagged phase synchronization. We found that hf-tRNS reduced gamma-band within-DMN and within-FPN connectivity at the end of stimulation relative to sham stimulation. A trend was obtained between the change in within-FPN functional connectivity from baseline to the end of stimulation and the improvement of negative symptoms at the one-month follow-up (r = −0.49, p = 0.055). Together, our findings suggest that hf-tRNS has potential as a network-level approach to modulate large-scale functional network connectivity pertaining to negative symptoms of schizophrenia. [ABSTRACT FROM AUTHOR]

Research suggests that accurate measurement is essential in evaluating internalized stigma and abilities to combat with stigma for treatment compliances and outcomes in individuals with mental illness. The purpose of this study was to assess the reliability and validity of the Chinese version of the Internalized Stigma of Mental Illness Scale (ISMIS-C), which is one of the few tools available to measure internalized stigma and stigma resistance (SR) simultaneously. A total of 160 outpatients with ( n = 103) and without ( n = 57) psychotic disorders were administrated with the ISMIS-C, and measures of self-esteem, self-efficacy, depression, and hopelessness. Overall, the 29-item ISMIS-C was presented to be internal reliable (Cronbach's alpha = 0.90), and reliable over time (intraclass correlation coefficients = 0.36-0.73). The construct validity of the ISMIS-C derived from the factor analysis was nearly identical to the original version. ISMIS-C dimension scores were well correlated with each other and measures of self-esteem, self-efficacy, depression, and hopelessness. Our data also demonstrated that psychotic patients experienced higher internalized stigma scores than those without psychotic diagnoses, but endorsed indifferently on SR scores. This scale can be used as an informative device when investigating 'internalized stigma' and 'SR' among individuals with or without psychotic disorders. [ABSTRACT FROM AUTHOR]

Objective: Altered cardiac autonomic function has been proposed in schizophrenia, but the results are mixed. Therefore, analyses with larger sample sizes and better methodology are needed. Methods: To examine whether acute schizophrenia is associated with cardiac autonomic dysfunction, 314 unmedicated patients with acute schizophrenia and 409 healthy volunteers, aged 18–65 years, were recruited for a case–control analysis. The severity of schizophrenia symptoms was assessed with the Positive and Negative Syndrome Scale. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV) parameters during the supine–standing–supine test. Frequency-domain indices of HRV were obtained. Results: Unmedicated patients with acute schizophrenia consistently exhibited reduced mean RR interval and HRV levels in a supine rest and standing position compared with healthy volunteers. The severity of psychopathology, in particular positive symptoms, was negatively correlated with cardiac vagal control. Conclusion: These data suggest that acute schizophrenia is accompanied by cardiac autonomic dysregulation. In view of the higher risk for cardiac complications in these patients, one might also consider the antipsychotic treatment in favour of improving cardiac autonomic modulation. Further studies using larger patient groups and controlled therapeutics may better understand the influence of antipsychotic treatment on cardiac autonomic regulation in schizophrenia. [ABSTRACT FROM AUTHOR]

Negative symptoms represent an unmet need for schizophrenia treatment. The effect of theta frequency transcranial alternating current stimulation (theta-tACS) applied during working memory (WM) tasks on negative symptoms has not been demonstrated as of yet. We conducted a randomized, double-blind, sham-controlled trial of 36 stabilized schizophrenia patients, randomized to receive either twice daily, 6 Hz 2 mA, 20 min sessions of in-phase frontoparietal tACS or sham for five consecutive weekdays. Participants were concurrently engaged in WM tasks during stimulation. The primary outcome measure was the change over time in the Positive and Negative Syndrome Scale (PANSS) negative subscale score measured from baseline through to the 1-month follow-up. Secondary outcome measures were other symptom clusters, neurocognitive performance, and relevant outcomes. The intention-to-treat analysis demonstrated greater reductions in PANSS negative subscale scores at the end of stimulation in the active (−13.84%) than the sham (−3.78%) condition, with a large effect size (Cohen's d = 0.96, p = 0.006). The positive effect endured for at least one month. Theta-tACS also showed efficacies for cognitive symptoms, WM capacity, and psychosocial functions. Online theta-tACS offers a novel approach to modulate frontoparietal networks to treat negative symptoms of schizophrenia. The promising results require large-scale replication studies in patients with predominantly negative symptoms. [ABSTRACT FROM AUTHOR]

Highlights: [•] REM sleep was necessary to change the IR-associated sensorimotor gating parameters. [•] Only the enduring social deprivation impaired the startle habituation under REMSD. [•] Timing and persistence of sociality are differently involved in gating function. [Copyright &y& Elsevier]

Abstract: Objective: Clarifying the similarities and differences between the two most common subtypes of bipolar disorder, bipolar-I and bipolar-II, is essential for improving our understanding of them. Because the serotonergic system has been implicated in the pathogenesis of bipolar disorder, it may be important to investigate genes such as the aldehyde dehydrogenase 2 (ALDH2) and serotonin 2A receptor genes, which are involved in metabolizing serotonin and encoding serotonin receptors. We examined the association of the ALDH2 and 5-HT2A-A1438G polymorphisms with bipolar I and II and possible interactions between these genes. Methods: One thousand forty-nine participants were recruited: 249 with bipolar-I, 456 with bipolar-II, and 344 healthy controls. The genotypes of the ALDH2 and 5HT2A-A1438G polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Results: Logistic regression analysis showed a significant effect of the ALDH2 and the 5-HT2A-A1438G polymorphisms, and a significant interaction effect for the A/G genotypes of the 5-HT2A-A1438G polymorphism and the ALDH2*1*1 genotypes (p =0.004) discriminated between bipolar-I patients and controls without bipolar disorder. These polymorphisms, however, were not associated with bipolar-II disorder. Limitations: The significant differences of age and gender between patients and controls limit the comparison, although statistical adjustments were made for them. Conclusion: Our findings provide initial evidence that the ALDH2 and 5-HT2A genes interact in bipolar-I but not in bipolar-II disorder. Our findings suggest a unique genetic distinction between bipolar-I and bipolar-II. [Copyright &y& Elsevier]

Abstract: Objectives: Studies report high comorbidity of lifetime anxiety disorders with bipolar disorders in Western patients, but it is unclear in Taiwan. The authors explored the comorbidity of anxiety disorders in different bipolar disorder subtypes in Han Chinese in Taiwan. Methods: Three hundred twenty-five patients with bipolar disorder (bipolar I: 120; bipolar II: 205) disorder were recruited from two general medical outpatient services. They were evaluated and their diagnoses confirmed by a psychiatrist using the Chinese version of the Modified Schedule of Affective Disorder and Schizophrenia-Lifetime. The exclusion criteria were: any DSM-IV-TR Axis I diagnosis, other than bipolar disorder, being outside the 18–65-year-old age range, any other major and minor mental illnesses except anxiety disorder, any neurological disorders or organic mental disorders. Results: Thirty-two (26.7%) of patients were comorbid with lifetime anxiety disorder and bipolar I, 80 (39.0%) with lifetime anxiety disorder and bipolar II, 7 (5.8%) were comorbid with two or more anxiety disorders and bipolar I, and 27 (13.2%) with two or more anxiety disorders and bipolar II. Conclusion: That more than twice as many bipolar II than bipolar I patients reported two or more anxiety disorders implies that the complication is more prevalent in bipolar II patients. [Copyright &y& Elsevier]