Verification of successful maintenance by serum drug level during a guided antipsychotic reduction to reach minimum effective dose (GARMED) trial.

BACKGROUND: Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages. METHODS: A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC-MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups. RESULTS: A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL. CONCLUSIONS: The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

Patients with first-episode psychosis in northern Taiwan: neurocognitive performance and niacin response profile in comparison with schizophrenia patients of different familial loadings and relationship with clinical features.

BACKGROUND: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. METHODS: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients' impairment on the CPT, WCST, and NRA. RESULTS: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: -1.24 for NRA, - 1.06 for undegraded d', - 0.70 for degraded d', - 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. CONCLUSIONS: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation.

Guided antipsychotic reduction to reach minimum effective dose (GARMED) in patients with remitted psychosis: a 2-year randomized controlled trial with a naturalistic cohort.

BACKGROUND: Patients with remitted psychosis face a dilemma between the wish to discontinue antipsychotics and the risk of relapse. We test if an operationalized guided-dose-reduction algorithm can help reach a lower effective dose without increased risks of relapse. METHODS: A 2-year open-label randomized prospective comparative cohort trial from Aug 2017 to Sep 2022. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomized 2:1 into guided dose reduction group (GDR) v. maintenance treatment group (MT1), together with a group of naturalistic maintenance controls (MT2). We observed if the relapse rates would be different between 3 groups, to what extent the dose could be reduced, and if GDR patients could have improved functioning and quality of life. RESULTS: A total of 96 patients, comprised 51, 24, and 21 patients in GDR, MT1, and MT2 groups, respectively. During follow-up, 14 patients (14.6%) relapsed, including 6, 4, and 4 from GDR, MT1, and MT2, statistically no difference between groups. In total, 74.5% of GDR patients could stay well under a lower dose, including 18 patients (35.3%) conducting 4 consecutive dose-tapering and staying well after reducing 58.5% of their baseline dose. The GDR group exhibited improved clinical outcomes and endorsed better quality of life. CONCLUSIONS: GDR is a feasible approach as the majority of patients had a chance to taper antipsychotics to certain extents. Still, 25.5% of GDR patients could not successfully decrease any dose, including 11.8% experienced relapse, a risk comparable to their maintenance counterparts.

The changes of parental functioning of the patients with bipolar disorder and major depression since discharging from hospital: A longitudinal study.

AIMS AND OBJECTIVES: This study examined the changes in patients' parental functioning and the associated factors, including manic, depressive symptoms and social support from before discharge to 6 months post-discharge. BACKGROUND: For parents with bipolar disorder and major depression, parenting is a recovery factor for patients, but little research examines the dynamic parental functioning from acute hospitalisation to a remission stage. DESIGN: A longitudinal design was used. The STROBE Checklist were used in presenting this research. METHODS: Participants were inpatients with bipolar disorder or major depression (n = 33) recruited within one week before discharge from the acute psychiatric ward in Taiwan. Data on parental functioning was collected four times: before discharge (T1), the 1st (T2), the 3rd (T3) and the 6th (T4) months of post-discharge. Baseline parental functioning before admitting to the acute word was retrospectively assessed at T0. The questionnaires included positive and negative domains of parenting practice, hypomanic/manic symptoms, depressive symptoms and social support. Generalised estimating equations were applied for data analysis. RESULTS: The negative parenting domains (poor monitoring, inconsistent discipline) decreased during hospitalisation but increased at one month post-discharge, except corporal punishment at 3-months discharge. The positive parenting domains (parental involvement and nurturance/responsiveness) did not recovery to baseline. While clinical symptoms remained stable during 6 months post-discharge, social support decreased at 3 and 6 months post-discharge. Higher depressive symptoms and low social support were associated with positive parenting domains but not related to negative parenting domains. Manic symptoms were not associated with positive or negative parenting domains. CONCLUSIONS: Positive parenting domains did not fully return to the usual situation during 6 months post-discharge. RELEVANCE TO CLINICAL PRACTICE: Parenting functioning recovery program targeting at the impacts of depressive symptoms on the parenting functioning and insufficient social support is needed from hospitalisation to post-discharge.

The experiences of family resilience from the view of the adult children of parents with bipolar disorder in Chinese society.

AIMS: This study explored how adult children perceived family resilience, barriers to develop family resilience and how cultural values influence their experience of parents with bipolar disorder in Chinese society. DESIGN: A qualitative design with an interpretive phenomenological analysis of data was employed. METHODS: Twenty adults who had lived with parents with bipolar disorder during childhood were recruited from the acute psychiatric ward when their parents were admitted to the hospital. They described their experiences of perceived family resilience and barriers to resilience (October 2013-September 2015). Semi-structured interviews were conducted in the hospital meeting room or at a convenient location. FINDINGS: Six themes were identified in family resilience: ill parents try to be good parents, parents' personal strengths, parents' positive attitudes towards mental illness, flexibility of family role, cohesive relationships between family members, and families' social connections. Three themes were identified in the barriers to develop family resilience: poor parenting/family function, conflict between parents and poor mental health literacy. CONCLUSION: Children's views of family resilience could transform their suffering from lived experiences with a mentally ill parent to a positive growth experience. Family resilience includes well and ill parents' efforts and social network's help to maintain family function. However, the conflicts between well and ill parents and poor family function result in a traumatic growth experience. IMPACT: To enhance a positive growth experience, family resilience programs for a parent with bipolar disorder aiming to cultivate both the ill and well parents' inner strength and their competence of parenting skills with connecting their social network to maintain family function is needed. Moreover, early stress-reduction intervention needs to be developed for children who did not experience family resilience.

Follow-up of subjects labelled with putative pre-psychotic states: Viewed from a transdiagnostic clinical high-at-risk mental state (CHARMS) paradigm.

BACKGROUND: Follow-up of subjects with putative pre-psychotic states is essential to clarify the transition process to psychosis, while "non-converters" also deserve clinical attention as many may evolve into other psychiatric disorders with diverse outcomes. This study aimed to examine help-seeking individuals who have been labelled at clinical high-risk state but not converting to full-blown psychosis during first two years of follow-up. METHODS: A retrospective observational cohort study of help-seeking subjects was conducted by reviewing medical records of participants in a previous early psychosis study at the study hospital between 2006 and 2020. We portrayed those who developed first episode psychosis after first 2-year follow-up in detail, and provided sketches of clinical macrophenotypes other than psychosis emerging from subjects among different risk groups. RESULTS: Among 132 eligible subjects, data of 98 (74.2%) were available for detailed evaluation. Of these, 15 transitioned to first-episode psychosis (11.4%) with time to psychosis from 2 to 11 years, 11 had anxiety spectrum (8.3%), 11 had depressive spectrum (8.3%), 10 had obsessive compulsive (7.6%), 5 had bipolar spectrum disorders (3.8%), 13 had predominantly schizotypal (9.8%) and 4 had other personality traits (3%), and 13 had problems attributable to adjustment or developmental issues (9.8%). CONCLUSION: Various diagnoses, either full- or sub-threshold, appropriately describe the diverse clinical phenomenology of a cohort presenting with non-specific and/or subthreshold psychotic symptoms. The clinical high-at-risk mental state (CHARMS) paradigm provides a reasonable transdiagnostic approach for orienting clinicians' attention toward young subjects seeking mental health help at an early stage of illness to potentially pluripotent trajectories.

Mismatch negativity and P3a in drug-naive adults with attention-deficit hyperactivity disorder.

BACKGROUND: Individuals with attention-deficit hyperactivity disorder (ADHD) often display over-response to stimuli that are irrelevant to the ongoing task, and their attentional abilities disproportionately worsen in the presence of competing stimuli. Auditory event-related potentials (ERPs) such as mismatch negativity (MMN) and P3a using the passive oddball paradigm have been studied in children and adolescents with ADHD. Still, there is no such data for adults with ADHD. This study aimed to compare the MMN and P3a and their clinical and neurocognitive correlations between drug-naive adults with ADHD and control adults. METHODS: We recruited 52 adults with ADHD (26.5 ± 6.2 years), and 62 age-matched controls (25.6 ± 5.6 years). They received the psychiatric interviews, auditory ERP, the Conners' continuous performance test (CCPT), and the Cambridge gambling test (CGT). They also completed the questionnaires about ADHD symptoms and real-world executive functions. MMN and P3a were assessed during a passive duration-deviant auditory oddball paradigm from the midline electrodes Cz. RESULTS: Adults with ADHD demonstrated smaller Cz MMN amplitude, more severe ADHD symptoms, poorer attention profiles (CCPT), and a wide range of executive dysfunctions than controls. As for the correlates, Cz peak amplitude of MMN correlated with inattention symptoms, executive dysfunctions, attentional vigilance (CCPT), and decision-making (CGT) in ADHD adults but only with decision-making in controls. CONCLUSIONS: Our findings that smaller amplitude of MMN and its differential associated pattern with inattention, real-world executive dysfunction, and decision-making, in drug-naive adults with ADHD from adult controls, provide evidence to support the potential electrophysiological biomarker for adult ADHD.

Abnormally low prolactin levels in schizophrenia patients after switching to aripiprazole in a randomized trial: a biomarker for rebound in psychotic symptoms?

BACKGROUND: Switching to aripiprazole from other antipsychotics can avoid antipsychotic-induced hyperprolactinemia but may result in an abnormally low prolactin level. This study aimed to assess whether the aripiprazole-induced abnormally low prolactin level was a biomarker for subsequent rebound of positive symptoms in schizophrenia patients. METHODS: Participants were 63 patients in an 8-week trial of switching to aripiprazole, in which preswitching antipsychotics were maintained for the first 2 weeks and aripiprazole was fixed at 15 mg orally throughout the trial. A prolactin level of < 3.7 ng/ml was defined as abnormally low, and an increase of two or more points in the positive subscore of the Positive and Negative Syndrome Scale at two adjacent ratings was defined as a psychotic rebound. RESULTS: Among 63 patients, 25 (39.7%) had an abnormally low prolactin level and 21 (33.3%) had a psychotic rebound after switching to aripiprazole. In patients with abnormally low prolactin levels, 48.0% of them had a rebound in psychotic symptoms, whereas in those without abnormally low prolactin levels 23.7% did so. Multivariable logistic regression analysis with adjustment for sex, early age at onset, and preswitching medications revealed that abnormally low prolactin levels were associated with psychotic rebound (adjusted odds ratio = 3.55, 95% confidence interval = 1.02, 12.5). Furthermore, there was concurrency between the trend of the cumulative proportion of patients having an abnormally low prolactin level and that of the cumulative proportion of patients having a rebound in psychotic symptoms. CONCLUSIONS: An abnormally low prolactin level after switching to aripiprazole in schizophrenia patients was a potential warning sign of a psychotic rebound. Hence, monitoring of prolactin levels after switching to aripiprazole may help avoid such rebound in schizophrenia. TRIAL REGISTRATION: NCT00545467 ; Date of registration: 17/10/2007.

Social cognition in schizophrenia: A network-based approach to a Taiwanese version of the Reading the Mind in the Eyes test.

BACKGROUND: This study aimed to examine social-cognitive impairments in patients with schizophrenia using the Eyes test. In contrast to previous methods using the correct answers, we developed the Taiwanese version of the Eyes test and constructed the response network to explore impairments in the emotional aspects of theory of mind in patients with schizophrenia. METHODS: Eighteen patients with schizophrenia and 18 healthy controls were recruited to examine their performance of the Eyes test. To explore the internal structures of mental states, we used network analysis to construct the networks of choice patterns (i.e. participants' answers) by using two network indicators, including density (an index of structure diversity of a network) and centrality (an index of the choice patterns within a network). Moreover, we divided all the choices into negative, positive, and neutral item groups based on emotion polarity. RESULTS: The patient group was slower and less accurate than the control group. Moreover, there was a negative correlation between accuracy and blunted affect, and there were positive correlations between reaction time and emotional withdrawal and apathetic social withdrawal. As compared to healthy controls, patients with schizophrenia showed larger density in the network structure and higher centrality than controls. Also, patients showed poorer performance on negative words than healthy controls. CONCLUSION: Our results demonstrated more diversity to recognize negative emotions from patients' choice patterns as compared to those in the control group. These findings suggest that deficits on recognizing negative emotions might be associated with the dysfunctions of mental states in schizophrenia.

Genetic associations and expression of extra-short isoforms of disrupted-in-schizophrenia 1 in a neurocognitive subgroup of schizophrenia.

Disrupted-in-schizophrenia 1 (DISC1) was reported to be associated with schizophrenia. In a previous study, we found significant association with schizophrenia patients with deficient sustained attention assessed by continuous performance test (CPT). This study aimed to identify risk polymorphisms in this specific neurocognitive subgroup and investigate the expression of different isoforms of DISC1. A total of 83 genetic variants were identified through direct sequencing in 50 controls and 100 schizophrenia patients. Fourteen variants were genotyped in 600 controls and 912 patients. Patients were subgrouped by familial loading (multiplex or simplex) and performance on CPT. The frequency of AA genotype of rs11122324 at the 3'-UTR of Es and Esv1 isoforms and of rs2793091 at intron 4 were significantly higher in multiplex schizophrenia patients than those in controls (corrected p < 0.05). In further subgrouping, the frequency of AA genotype of the two SNPs were significantly higher in multiplex schizophrenia patients with deficient sustained attention than those in controls (corrected p < 0.005). The mRNA expression levels of two extra-short isoforms (Es and Esv1) in the EBV-transformed lymphocytes of schizophrenia were significantly higher than those of controls. Luciferase reporter assays demonstrated that the A-allele of rs11122324 significantly upregulated DISC1 extra-short isoforms transcription compared with the G-allele. We found two SNPs (rs11122324 and rs2793091) of DISC1 may be specifically associated with multiplex schizophrenia patients with deficient sustained attention. The SNP rs11122324 may be a risk polymorphism, which may have functional influence on the transcription of Es and Esv1 through increasing their expression.

Altered integrity of the right arcuate fasciculus as a trait marker of schizophrenia: a sibling study using tractography-based analysis of the whole brain.

Trait markers of schizophrenia aid the dissection of the heterogeneous phenotypes into distinct subtypes and facilitate the genetic underpinning of the disease. The microstructural integrity of the white matter tracts could serve as a trait marker of schizophrenia, and tractography-based analysis (TBA) is the current method of choice. Manual tractography is time-consuming and limits the analysis to preselected fiber tracts. Here, we sought to identify a trait marker of schizophrenia from among 74 fiber tracts across the whole brain using a novel automatic TBA method. Thirty-one patients with schizophrenia, 31 unaffected siblings and 31 healthy controls were recruited to undergo diffusion spectrum magnetic resonance imaging at 3T. Generalized fractional anisotropy (GFA), an index reflecting tract integrity, was computed for each tract and compared among the three groups. Ten tracts were found to exhibit significant differences between the groups with a linear, stepwise order from controls to siblings to patients; they included the right arcuate fasciculus, bilateral fornices, bilateral auditory tracts, left optic radiation, the genu of the corpus callosum, and the corpus callosum to the bilateral dorsolateral prefrontal cortices, bilateral temporal poles, and bilateral hippocampi. Posthoc between-group analyses revealed that the GFA of the right arcuate fasciculus was significantly decreased in both the patients and unaffected siblings compared to the controls. Furthermore, the GFA of the right arcuate fasciculus exhibited a trend toward positive symptom scores. In conclusion, the right arcuate fasciculus may be a candidate trait marker and deserves further study to verify any genetic association.

Automatic whole brain tract-based analysis using predefined tracts in a diffusion spectrum imaging template and an accurate registration strategy.

Automated tract-based analysis of diffusion MRI is an important tool for investigating tract integrity of the cerebral white matter. Current template-based automatic analyses still lack a comprehensive list of tract atlas and an accurate registration method. In this study, tract-based automatic analysis (TBAA) was developed to meet the demands. Seventy-six major white matter tracts were reconstructed on a high-quality diffusion spectrum imaging (DSI) template, and an advanced two-step registration strategy was proposed by incorporating anatomical information of the gray matter from T1-weighted images in addition to microstructural information of the white matter from diffusion-weighted images. The automatic analysis was achieved by establishing a transformation between the DSI template and DSI dataset of the subject derived from the registration strategy. The tract coordinates in the template were transformed to native space in the individual's DSI dataset, and the microstructural properties of major tract bundles were sampled stepwise along the tract coordinates of the subject's DSI dataset. In a validation study of eight well-known tracts, our results showed that TBAA had high geometric agreement with manual tracts in both deep and superficial parts but significantly smaller measurement variability than manual method in functional difference. Additionally, the feasibility of the method was demonstrated by showing tracts with altered microstructural properties in patients with schizophrenia. Fifteen major tract bundles were found to have significant differences after controlling the family-wise error rate. In conclusion, the proposed TBAA method is potentially useful in brain-wise investigations of white matter tracts, particularly for a large cohort study.

Fast Versus Slow Strategy of Switching Patients With Schizophrenia to Aripiprazole From Other Antipsychotics.

This study aimed to compare strategies differing in the speed of switching schizophrenic patients to aripiprazole from other antipsychotic agents, with dual administration for 2 weeks and then tapering off the current antipsychotic in fast (within 1 week) versus slow (within 4 weeks) strategies. This 8-week, open-label, randomized, parallel study assigned patients with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia or schizoaffective disorder to either the fast-switching (n = 38) or slow-switching (n = 41) group. Efficacy assessments at 5 time points included Positive and Negative Syndrome Scale and Clinical Global Impression scale. Safety assessments included extrapyramidal symptoms, metabolic profile, serum prolactin level, QTc interval, and adverse events. Drug concentrations and cytochrome P450 CYP2D6 and CYP3A4 genotypes were also measured. The fast- and slow-switching groups were comparable in demographical and clinical features at baseline and dropout rate. In the intention-to-treat analysis using mixed-effects models, there were significant within-group decreases over time in the Positive and Negative Syndrome Scale total scores (P = 0.03) and its subscores except for positive subscores, whereas no between-group differences were found. A reduction in body weight (P = 0.01) and lower levels of total cholesterol (P = 0.03), triglycerides (P = 0.03), and prolactin (P = 0.01) were noted in both groups but no increase in extrapyramidal symptoms or prolongation of QTc. The blood concentrations of aripiprazole in all patients were in a therapeutic range at day 56, with CYP2D6*10 polymorphisms being associated with aripiprazole concentrations. In conclusion, there is no significant difference between the fast- and slow-switching strategy in terms of improvements in clinical symptoms and metabolic profile in this 8-week study.

Initiating long-acting injectable antipsychotics during acute admission for patients with schizophrenia--A 3-year follow-up.

BACKGROUND/PURPOSE: The debate on whether long-acting injectable antipsychotic (LAIA) medication is superior to oral medication, in preventing rehospitalization of patients with schizophrenia, remains inconclusive. We compared rehospitalization rates over 3 years following discharge from an acute admission, in which patients either began using LAIAs regularly for the first time, or continued to use oral antipsychotics. METHODS: A retrospective observational study of 92 inpatients with schizophrenia from a university-based medical center during 2004-2008. The primary outcome measure is the rehospitalization rates between groups, as estimated by Kaplan-Meier survival analysis. RESULTS: Eighteen of 47 (38.3%) LAIA patients, and 16 of 45 (35.6%) oral medication patients were rehospitalized (average time to rehospitalization, 378 ± 262 vs. 378 ± 340 days; p = 0.997). The estimated cumulative rates of rehospitalization were similar between groups. The overall odds comparing the LAIA to the oral medication group were 1.085 ± 0.373 (95% confidence interval: 0.553-2.13, p = 0.813). Compared to the oral medication group, the LAIA group had fewer coded with sufficient previous treatment response (32% vs. 69%, p < 0.001), more poorly compliant (91% vs. 56%, p < 0.001), and a slightly longer length of stay at index admission (32.7 ± 11.3vs. 27.6 ± 12.1, p = 0.04). CONCLUSION: Initiating LAIAs during admission for an acute psychotic episode, to a group of patients with an inadequate previous treatment response and poorer compliance, might keep their rehospitalization rates to the level of their oral antipsychotic medication treated counterparts.

Intramuscular olanzapine versus intramuscular haloperidol plus lorazepam for the treatment of acute schizophrenia with agitation: An open-label, randomized controlled trial.

BACKGROUND/PURPOSE: To compare the efficacy and safety profile between intramuscular (IM) olanzapine and IM haloperidol plus IM lorazepam in acute schizophrenic patients with moderate to severe agitation. METHODS: This was a prospective, randomized, open-label study. Acutely agitated patients with schizophrenia or schizoaffective disorder (n = 67) were randomized to receive 10 mg IM olanzapine (n = 37) or 5 mg IM haloperidol plus 2 mg IM lorazepam (n = 30). Agitation was measured with Positive and Negative Syndrome Scale Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES) during the first 2 hours and at 24 hours after the first injection. Safety was assessed using the Simpson-Angus Scale and Barnes Akathisia Rating Scale and by recording adverse events at 24 hours following the first injection. The Clinical Global Impression-Severity scale was also rated. RESULTS: The PANSS-EC scores decreased significantly at 2 hours after the first injection in both groups (olanzapine: -10.2, p < 0.001; haloperidol + lorazepam: -9.9, p < 0.001). Haloperidol plus lorazepam was not inferior to olanzapine in reducing agitation at 2 hours. There were no significant differences in PANSS-EC or ACES scores between the two groups within 2 hours following the first injection. The frequencies of adverse events and changes in Clinical Global Impression-Severity, Simpson-Angus Scale, and Barnes Akathisia Rating Scale scores from baseline to 24 hours showed no significant differences between the groups. CONCLUSION: The findings suggest that IM haloperidol (5 mg) plus lorazepam (2 mg) is not inferior to IM olanzapine (10 mg) in the treatment of acute schizophrenic patients with moderate to severe agitation (ClinialTrials.gov identifier number NCT00797277).

Frequency-specific alternations in the amplitude of low-frequency fluctuations in schizophrenia.

Schizophrenia has been associated with abnormal task-related brain activation in sensory and motor regions as well as social cognition network. Recently, two studies investigated temporal correlation between resting-state functional magnetic resonance imaging (R-fMRI) low-frequency oscillations (LFOs) in schizophrenia but reported mixed results. This may be due to the different frequency bands used in these studies. Here we utilized R-fMRI to measure the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) in three different frequency bands (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.08 Hz; and typical band: 0.01-0.08 Hz) in 69 patients with schizophrenia and 62 healthy controls. We showed that there were significant differences in ALFF/fALFF between the two bands (slow-5 and slow-4) in regions including basal ganglia, midbrain, and ventromedial prefrontal cortex. Importantly, we also identified significant interaction between frequency bands and groups in inferior occipital gyrus, precuneus, and thalamus. The results suggest that the abnormalities of LFOs in schizophrenia is dependent on the frequency band and suggest that future studies should take the different frequency bands into account when measure intrinsic brain activity.

The tridimensional personality of male heroin users treated with methadone in Taiwan.

It was our assumption that male heroin users have the personality traits of high impulsivity and low social interaction. Compliance regarding methadone maintenance therapy (MMT) is hypothesized to be related to personality features. We recruited 43 patients that had been receiving MMT and 43 healthy volunteers. All participants completed a Tridimensional Personality Questionnaire (TPQ). Information related to the Opiate Treatment Index (OTI) was gathered from the heroin group. The personality dimensions in the heroin user group and the control group were compared. We further investigated the association between TPQ and OTI. The heroin group presented with lower reward dependence than the control group. Regarding sub-dimensions, heroin users showed higher impulsivity and fatigability, and lower exploratory excitability and social dependence. The explosive (borderline) pattern was more common among the heroin users. The odds ratio of explosive pattern developing to heroin dependence was 4.19. Q scores of heroin use and the maximal methadone dose were associated with persistence.

Mismatch Negativity and P3a in Unaffected Siblings of Individuals with Autism Spectrum Disorder and the Exploration on the Neurocognitive Implications.

Evidence suggests different mismatch negativity (MMN) and P3a responses in individuals with autism spectrum disorder (ASD). Since unaffected siblings shared aberrant neurocognition and brain connectivity with ASD probands, this study investigated MMN and P3a responses in unaffected siblings and explored its neurocognitive implications and effects modifiers. We assessed 43 unaffected siblings of ASD probands and 64 non-autistic comparisons (NTC) using MMN and P3a on both frequency and duration oddball paradigms. The amplitude and latency of MMN and P3a were compared between unaffected siblings and NTC, and validated in 67 ASD probands. In addition, the neurocognitive correlates of MMN and P3a parameters were explored in attention performance, spatial working memory (SWM), and visual research via the tasks of the Conners' Continuous Performance Test and the Cambridge Neuropsychological Test Automated Battery. Compared to NTC, unaffected siblings and ASD probands presented a shorter MMN latency. The P3a amplitude of the duration paradigm (dP3a) was correlated with fewer commission errors, fewer SWM total errors, higher detectability, and more correct responses on visual search tasks. In addition, the dP3a amplitude significantly interacted with sibship, age, and full-scale IQ to predict attention performance, SWM total errors, and total correct response on visual search. Findings suggest that unaffected siblings of ASD may have earlier brain responses upon novelty discrimination. P3a amplitude may correlate with better neurocognitive performance, but the effect was moderated by sibship, age, and intelligence.

Aripiprazole for drug-naive or antipsychotic-short-exposure subjects with ultra-high risk state and first-episode psychosis: an open-label study.

INTRODUCTION: This study aimed to observe treatment response using aripiprazole for subjects with ultra-high risk (UHR) state of psychosis or at their first-episode psychosis (FEP) who were drug-naive or only have received antipsychotic therapy temporarily. METHODS: All patients received aripiprazole 3.75 mg/d initially to test tolerability and increased to 7.5 mg during the first 2 weeks. A flexible dosing strategy based on clinical improvement and tolerability with a target dose 15 mg/d by the end of the fourth week. Clinical severity was assessed by a Mandarin version of the positive and negative syndrome scale for schizophrenia at baseline, the end of the second and the fourth week. Adverse reactions were recorded by a log, and concomitant medications were allowed. RESULTS: A total of 20 FEP and 11 UHR patients, including 18 drug-naive (11 FEP and 7 UHR) and 13 antipsychotic-short-exposure patients (9 FEP and 4 UHR), participated in and 29 completed the study. Most of them received aripiprazole no more than 7.5 mg/d at end point with favorable response, although many of them reported adverse events. Both UHR and FEP patients got significant decrease of positive symptom scores in a similar pattern. Both groups did not show significant changes in negative symptom scores. CONCLUSION: The treatment response of UHR patients is likely a continuum from that of the FEP patients. Low-dose aripiprazole revealed potential efficacy for patients with less severe psychopathology, at putative prodromal or early state of psychosis, yet still was accompanied by adverse events while treating this mostly drug-naive population.

Electroconvulsive therapy for treatment-resistant depression.

Electroconvulsive therapy (ECT), the oldest brain stimulation procedure in psychiatry, is associated with rapid response and remission in majority of patients with resistant, severe, and sometimes life-threatening depression. ECT has been included as an essential component in the definition of treatment-resistant depression (TRD) to display the course and diversification of TRD. On the other hand, ECT remains the treatment of choice for the most severe incapacitating forms of TRD and is a cost-effective treatment. In this chapter, we reviewed some essential studies, meta-analysis, and expert guidelines regarding ECT in TRD. ECT should not be considered as a treatment of last resort, and its administration should be considered on the basis of individual patient and illness factors. The clinical role of ECT vs other neurostimulation treatments for TRD, that is, repetitive transcranial magnetic stimulation, were also explored. Much effort has been directed toward the clinical and basic research about mechanisms of action of ECT in depression. A thorough understanding of the neurobiological effects of ECT may increase our understanding of its therapeutic effects, ultimately leading to improved patient care. We also showed that the distinct mechanisms of ECT in biological treatments of major depressive disorder (MDD) and some recent approaches to understand this most common psychiatric disorder. ECT should remain a standard part of modern psychiatric medicine. We recommend a more careful and thoughtful application of this traditional but effective technology.