Cumulative Antipsychotic Dose Research Articles

Striatum and globus pallidus structural abnormalities in schizophrenia: A retrospective study of the different stages of the disease

BackgroundThe basal ganglia are important structures for the release of dopamine in the limbic circuits of the midbrain, and the striatum and globus pallidus are the major nuclei of the basal ganglia, and the dysfunction of these regions has been the basis of many models that have attempted to explain the underlying mechanisms of schizophrenia symptoms. The purpose of this study was to investigate the changes in the volume of the striatum subregion and globus pallidus in three different stages of schizophrenia, and to analyze whether these volume changes were related to antipsychotic drugs and schizophrenia symptoms. MethodsIn this study, we investigated the volume of the striatum and globus pallidus in patients with schizophrenia at three different stages. The study included 57 patients with first-episode schizophrenia (FSZ), 51 patients with early-stage schizophrenia (ESZ), 86 patients with chronic schizophrenia (CSZ), and 191 healthy controls (HC), all of whom underwent structured magnetic resonance imaging (MRI) scans. Covariance analysis was performed using SPSS 26.0 was used for covariance analysis to determine whether there were significant differences in striatal subregion and globus pallidus volume between groups, and stratified analysis was used to further eliminate the effect of age on brain volume. Finally, the correlation analysis between the region of interest and the cumulative dose of antipsychotic drugs and psychotic symptoms was performed. ResultsThe comparison between the different stages of the illness showed significant volume differences in the left caudate nucleus (lCAU) (F = 2.665, adjusted p = 0.048), left putamen (lPUT) (F = 12.749, adjusted p < 0.001), left pallidum (lPAL) (F = 41.111, adjusted p < 0.001), and right pallidum (rPAL) (F = 14.479, adjusted p < 0.001). Post-hoc analysis with corrections showed that the volume differences in the lCAU subregion disappeared. Further stratified analysis controlling for age showed that compared with the HC, the lPAL (t = 4.347, p < 0.001) was initially significantly enlarged in the FSZ group, the lPUT (t = 4.493, p < 0.001), rPUT (t = 2.190, p = 0.031), lPAL (t = 7.894, p < 0.001), and rPAL (t = 4.983, p < 0.001) volumes were all significantly increased in the ESZ group, and the lPUT (t = 3.314, p = 0.002), lPAL (t = 6.334, p < 0.001), and rPAL (t = 3.604, p < 0.001) subregion volumes were also significantly increased in the CSZ group. Correlation analysis showed that lPUT and bilateral globus pallidus were associated with cumulative dose of antipsychotics, but were not associated with clinical symptoms in each subregion. ConclusionThe findings suggest that different subregions of the striatum and globus pallidus show significant volume differences at different stages of schizophrenia compared to HC. These volume differences may be strong radiographic evidence for schizophrenia. In addition, the lPAL was the only significantly different brain region observed in the FSZ group, suggesting that it may be a sensitive indicator of early brain structural changes in schizophrenia. Finally, our findings support the hypothesis that antipsychotic drugs have an effect on the volume of brain structures.

Longitudinal assessment of ventricular volume trajectories in early-stage schizophrenia: evidence of both enlargement and shrinkage

BackgroundLateral ventricular enlargement represents a canonical morphometric finding in chronic patients with schizophrenia; however, longitudinal studies elucidating complex dynamic trajectories of ventricular volume change during critical early disease stages are sparse.MethodsWe measured lateral ventricular volumes in 113 first-episode schizophrenia patients (FES) at baseline visit (11.7 months after illness onset, SD = 12.3) and 128 age- and sex-matched healthy controls (HC) using 3T MRI. MRI was then repeated in both FES and HC one year later.ResultsCompared to controls, ventricular enlargement was identified in 18.6% of patients with FES (14.1% annual ventricular volume (VV) increase; 95%CI: 5.4; 33.1). The ventricular expansion correlated with the severity of PANSS-negative symptoms at one-year follow-up (p = 0.0078). Nevertheless, 16.8% of FES showed an opposite pattern of statistically significant ventricular shrinkage during ≈ one-year follow-up (-9.5% annual VV decrease; 95%CI: -23.7; -2.4). There were no differences in sex, illness duration, age of onset, duration of untreated psychosis, body mass index, the incidence of Schneiderian symptoms, or cumulative antipsychotic dose among the patient groups exhibiting ventricular enlargement, shrinkage, or no change in VV.ConclusionBoth enlargement and ventricular shrinkage are equally present in the early stages of schizophrenia. The newly discovered early reduction of VV in a subgroup of patients emphasizes the need for further research to understand its mechanisms.

The effects of cumulative antipsychotic dose on brain structures in patients with schizophrenia: Observational study of multiple CT scans over a long-term clinical course

Multiple lines of evidence indicate that antipsychotic agents could affect brain structures of schizophrenia patients. However, the effect of antipsychotic dosage or type on brain structure is uncertain. The present study retrospectively analyzed brain computed tomography (CT) images from a psychiatric hospital to examine the relationship between cumulative dose of antipsychotics and brain volume reduction in schizophrenia patients. A total of 43 patients with repeated relapse episode of psychosis were included and CT scans that were performed an average of 3.2 times per patient during nearly 13 years of follow-up were analyzed. The results revealed significant positive relationships of expansion of cerebrospinal fluid space with cumulative dosage of all antipsychotics and that of typical antipsychotics. Patients treated with antipsychotics including typical antipsychotics exhibited a greater volume reduction compared to patients treated with only atypical antipsychotics. The present study was one of the longest longitudinal studies examining the effects of antipsychotics on brain volume in schizophrenia patients. These results suggest a relation between cumulative lifetime antipsychotic dosage and progressive brain volume reduction in patients with schizophrenia. However, the effects of specific agent on brain structure are still uncertain, and more detailed analysis is needed.

Antipsychotic treatment effects and structural MRI brain changes in schizophrenia.

Progressive brain structural MRI changes are described in schizophrenia and have been ascribed to both illness progression and antipsychotic treatment. We investigated treatment effects, in terms of total cumulative antipsychotic dose, efficacy and tolerability, on brain structural changes over the first 24 months of treatment in schizophrenia. A prospective, 24-month, single-site cohort study in 99 minimally treated patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder, and 98 matched healthy controls. We treated the patients according to a fixed protocol with flupenthixol decanoate, a long-acting injectable antipsychotic. We assessed psychopathology, cognition, extrapyramidal symptoms and BMI, and acquired MRI scans at months 0, 12 and 24. We selected global cortical thickness, white matter volume and basal ganglia volume as the regions of interest. The only significant group × time interaction was for basal ganglia volumes. However, patients, but not controls, displayed cortical thickness reductions and increases in white matter and basal ganglia volumes. Cortical thickness reductions were unrelated to treatment. White matter volume increases were associated with lower cumulative antipsychotic dose, greater improvements in psychopathology and cognition, and more extrapyramidal symptoms. Basal ganglia volume increases were associated with greater improvements in psychopathology, greater increases in BMI and more extrapyramidal symptoms. We provide evidence for plasticity in white matter and basal ganglia associated with antipsychotic treatment in schizophrenia, most likely linked to the dopamine blocking actions of these agents. Cortical changes may be more closely related to the neurodevelopmental, non-dopaminergic aspects of the illness.

Dose-dependent effects of antipsychotics on efficacy and adverse effects in schizophrenia

BackgroundAntipsychotics are a cornerstone of pharmacological treatment of schizophrenia. Improved understanding of the dose-response relationship of antipsychotics in terms of efficacy, adverse effects, and mortality can help to optimize the pharmacological treatment of schizophrenia. MethodsThis narrative literature review summarizes current evidence on the relationship of antipsychotic dose with efficacy, adverse effects, and mortality in patients with schizophrenia. ResultsThe efficacy of antipsychotics generally appeared to be highly dose-dependent in the acute phase of schizophrenia, with each antipsychotic having a specific dose-response curve. The presence or absence of dose-dependency and its extent varied according to the type of adverse effect. Parkinsonism, hyperprolactinemia, weight gain, and neurocognitive impairment appeared to be dose-related. The following adverse effects might be at least somewhat dose-dependent: akathisia, tardive dyskinesia, osteoporosis, sexual dysfunction, diabetes mellitus, myocardial infarction, stroke, thromboembolism, QT interval prolongation, anticholinergic adverse effects, somnolence, pneumonia, hip fracture, and neuroleptic malignant syndrome. In contrast, the relationships of antipsychotic dose with dyslipidemia, hypotension, seizure, sialorrhea, and neutropenia and agranulocytosis remained unclear due to mixed findings and/or limited data. Although a higher lifetime cumulative antipsychotic dose might contribute to higher mortality, it is still difficult to conclude whether mortality increases in a dose-dependent manner. ConclusionThese findings could help clinicians to optimize antipsychotic treatment in patients with schizophrenia by balancing risks and benefits in clinical practice. However, further investigations with larger sample sizes and more robust study designs that focus on each antipsychotic agent are needed.

T138. ADOLESCENT ONSET OF PSYCHOSIS IMPACTS SEGREGATION OF CORTICO-SUBCORTICAL NETWORKS DURING DEVELOPMENT

BackgroundFunctional connectivity (FC) during the resting-state is reduced in schizophrenia, especially within the Default Mode Network (DMN) (Dong 2018), and between the hippocampus, striatum and ventral tegmental area (VTA), which together conform a Midbrain Network (Gangadin 2019). Cross-sectional studies in adult samples have reported altered FC between dopamine synthesizing centers in midbrain and cortical areas in schizophrenia (Martino 2018). Conceptualizing schizophrenia as a neurodevelopmental disorder, we hypothesize that these changes may take place in early ages, prior to the clinical onset of psychosis. Therefore, we aim to examine FC of the DMN and Midbrain networks longitudinally in adolescents at increased risk of developing psychosis compared with youth with early onset psychosis and healthy volunteers (HV).MethodsThis longitudinal case-control study encompassed adolescents (12.6–18.9 years old) with psychosis risk syndrome (PRS; n=47), first episode of psychosis (FEP; n=59), and age and sex-matched HV (n=34). Fourteen out of the 30 PRS with follow-up assessment developed psychosis (t-PRS). Resting-state fMRI data was available for 88 subjects at baseline and follow-up [no significant differences in relation to drop-outs]: 10 t-PRS re-scanned at 3–12 months (at transition), and 14 PRS who did not transited (nt-PRS), 35 FEP; and 29 HV re-scanned at 10–36 month follow-up. After exclusion due to poor acquisition or excess movement, the final sample encompassed: 27 FEP, 9 t-PRS, 12 nt-PRS and 28 HV. Individual time series were extracted from Regions of Interest (ROI): for the DMN, the medial Prefrontal Cortex (mPFC), precuneus (PC), and bilateral temporo-parietal junction (Schilbach 2016); and for the Midbrain Network, the associative and limbic striatum, VTA and subiculum (Gangadin 2019). The orthogonal parameters of movement, white matter and cerebrospinal fluid (and their derivatives) and head motion scrubbing regressors were regressed out before performing the correlations. Multivariate mixed-effect models were estimated, including group (4), time and group by time interaction as fixed effects; and time and individual variability as random effects.ResultsThere were no significant differences within-network FC. There was a significant group by time interaction in FC between the two networks (p = .02), driven by VTA-PC (pFDR = .02) and VTA-mPFC (pFDR = .04). Post-hoc analyses showed a significant reduction in FC in nt-PRS over time (psFDR ≤ .03), with FEP and t-PRS showing an opposite pattern (psFDR ≤ .01) in both networks. There was a trend-level reduction in FC over time in HV (ps ≤ .09), which showed significant differences relative to FEP (ps ≤ .04) in the VTA-PC and VTA-mPFC, and with t-PRS in the VTA-PC (p = .02). There was no significant difference between HV and nt-PRS. Cumulative dose of antipsychotics was negatively correlated with FC between mPFC-VTA in FEP at follow-up (r = -.41; p = .04); yet group by time effects survived when used as covariable. Sex, socio-economic status or global intelligence quotient did not exert significant effects.DiscussionOur findings suggest that the onset of psychosis during adolescence impacts on the age-normative reduction of FC between the DMN and Midbrain networks, characteristic of the network segregation which takes place during typical brain functional development (Satterthwaite 2013). Antipsychotic medication on cortico-subcortical FC appear to have a reversing effect on these findings, although longitudinal group differences in network connectivity persist despite controlling for this effect. Our data sheds light on the changes in the organization of brain function taking place in the early stages of psychosis, coinciding with a key developmental period.

T24. CHANGES IN TELOMERE LENGTH IN YOUNG PEOPLE WITH FIRST EPISODE PSYCHOSIS: A 12-MONTHS FOLLOW-UP STUDY

BackgroundCellular aging is associated with the appearance of several chronic organic diseases, and many neuropsychiatric disorders such as schizophrenia spectrum disorders, which include psychotic disorders. Telomeres are one of the biomarkers of this cellular aging. Researches have shown that shorter telomere length is a biomarker of oxidation and cellular aging. Recent studies have concluded that patients with a first psychotic episode (FEP) have shorter telomere length than healthy controls (HC). However, there is no published data on the change in telomere length in the first years of illness.The purpose of this study is to evaluate the changes in telomere length measured in peripheral blood mononuclear cells (PBMCs) in a sample of patients with early-onset psychosis and healthy subjects.MethodsThis study included 10 young patients with FEP (50% female, mean age 18.4 years) and 10 young HC (60% female, mean age 16.4 years). PBMCs telomere length was determined using high-throughput quantitative fluorescence in situ hybridization (HT Q-FISH) at baseline and 12-month follow-up. We analysed in our sample of patients if there are significant differences according to the diagnosis and antipsychotic treatment.ResultsAt baseline, we did not find significant differences in telomere length between FEP patients and HC. After one-year follow-up, it was found that telomere length is shorter in patients with FEP than in HC (p=0.007).The diagnostics in the patients’ group were: 60% schizophrenia and 40% other diagnoses (20% psychosis not specified and 20% bipolar disorder). There was no significant difference between changes in telomeres length and diagnosis (p = 0.840).The antipsychotic treatment in the patients’ group after 12 months was: 20% risperidone, 50% aripiprazole, 10% clozapine, 10% paliperidone and 10% quetiapine. We didn′t find a strong association between the shortening of telomeres and the cumulative dose of antipsychotics.DiscussionThis is one of the first studies where it has been analysed a longitudinal data of telomere length. It is shown that patients with the first episode of psychosis have significantly shorter telomere length than healthy controls. Changes in telomere length during the first years of illness can represent an early marker of accelerated cellular aging. Further studies are needed with a larger sample to know mechanisms responsible for accelerating aging and the role of oxidative stress in the pathogenesis of psychosis.

Neuroleptic Malignant Syndrome, a Sequalae of Multiple Administration of Antipsychotics: A Case Report

Neuroleptic malignant syndrome (NMS) is a lethal adverse drug reaction (ADR) that is often attributed to the administration of dopamine blockers, antiemetic agents as well as anti-parkinsonism medication withdrawal. We describe a challenging case of NMS, with malignant catatonia as a differential diagnosis, who was difficult to respond to treatment. The patient developed severe complications following her exposure to rapid titration using high doses of olanzapine, which was abruptly converted to chlorpromazine due to lack of efficacy, in addition to administering multiple as needed (PRN) medications for agitation. Hyperthermia, muscle rigidity, dysautonomia, mental status changes, catatonia, and some laboratory derangement were reported in this case. It is possible that factors such as naïve patients, high doses of neuroleptics, a switch from one agent to another, rapid escalation, and the increased use of parenteral therapy for managing of agitation acted collectively or individually as risk factors for developing NMS. Health care professionals should be cautious about the cumulative dose of antipsychotics used per day, including PRN medications. The delay in recognizing the early symptoms of NMS could put patients at higher risk of mortality. Lastly, it is pivotal to exclude other infectious or autoimmune etiologies before treating as NMS case.

S179. PROGNOSTIC UTILITY OF MULTIVARIATE MORPHOMETRY IN SCHIZOPHRENIA

BackgroundGroups of spatially distributed regions show shared variance in morphometric properties (e.g. grey matter volume) among subjects, thus forming independent morphometric ‘sources’ or covariance-based networks. Source based morphometry is a multivariate approach that is based on independent component analysis, and accounts for the inter-relationahsip among different brain regions while filtering out noisy artefactual effects of mass univariate voxel-based approaches. We have previously demonstrated that with multivariate SBM, it is possible to identify the structural basis of subtle psychopathological features such as formal thought disorder, whose anatomical correlates have been hitherto elusive. In the current study, we use multivariate SBM to identify the morphometric sources in drug-naïve first episode subjects that show progressive changes that predict symptom change over 1 year.Methods63 first-episode, drug-naive patients with schizophrenia underwent brain magnetic resonance imaging scans at baseline (T0) and rescanned after 1 year follow-up (T1). Positive and Negative Syndrome Scale (PANSS) was used to assess their psychopathology. Source based morphometry (SBM) was performed to analyze the gray matter volume (GMV), paired T contrasts for loading coefficients of GMV were constructed to detect the components that showed a significant effect of time. The change in PANSS scores between baseline and 1 year was expressed as a ratio of the scores at baseline - adjusted change scores for positive symptoms (POS%), negative symptoms (NEG%) and disorganization symptoms (DISORG%), with each domain score derived using van der Gaag’s 5-factor approach. Multiple regression analysis was conducted to predict the percentage change scores in each domain using the T0 and T1 loading coefficients of components showing time effect with age, gender and cumulative antipsychotic dose as covariates.ResultsOf the 30 spatial components of gray matter identified by SBM, loading coefficients of anterior cingulate cortex (ACC), anterior insula (AI) & inferior frontal gyrus (IFG), superior temporal gyrus (STG), middle temporal gyrus (MTG) and dorsal lateral prefrontal cortex (DLPFC) reduced with time in patients. The lower volume of AI & IFG at baseline and at 1 year related to poor improvement in positive and disorganization symptoms; lower volume of STG & MTG at baseline and 1 year predicted poor improvement in negative symptoms.DiscussionThe baseline distribution of GM in AI & IFG, STG and MTG are predictive of the course of illness. The relationship between GM sources and symptom severity continues even after 1 year of naturalistic exposure to antipsychotic treatment. If judiciously combined with other available predictors of prognosis, source-based morphometric analysis can aid meaningful prognostication in schizophrenia.

Bipolar disorder and the risk of fracture: A nationwide population-based cohort study

BackgroundThe co-primary aims are: 1) to compare the risk of fracture between adults with bipolar disorder and those without bipolar disorder; and 2) to assess whether lithium, anticonvulsants and antipsychotics reduce risk of fracture among individuals with bipolar disorder. MethodsThe analysis herein is a population-based retrospective cohort study, utilizing the National Health Insurance (NHI) medical claims data collected between 1997 and 2013 in Taiwan. We identified 3705 cases with incident diagnoses of bipolar disorder during study period and 37,050 matched controls without bipolar diagnoses. Incident diagnosis of fracture was operationalized as any bone fracture after the diagnosis of bipolar disorder or after the matched index date for controls. ResultsBipolar patients had significantly higher risk of facture when compared to matched controls (17.6% versus 11.7%, respectively p<0.001). The hazard ratio (HR) was 1.33 (95% confidence interval [CI]＝1.23–1.48, p<0.001) after adjusting for covariates. Persons with bipolar disorder and a prior history of psychiatric hospitalization were had higher risk for bone fracture than those without prior history of psychiatric hospitalization when compared to match controls. Higher cumulative dose of antipsychotics or mood stabilizers did not increase the risk of fracture. LimitationsThe diagnoses of bipolar disorder were not confirmed with structured clinical interview. Drug adherence, exact exposure dosage, smoking, lifestyle, nutrition and exercise habits were unable to be assessed in our dataset. ConclusionsBipolar disorder is associated with increased risk of fracture, and higher cumulative dose of mood stabilizers and antipsychotics did not further increase the risk of fracture.

Poster #T218 THE THIRD NATIONAL SURVEY ABOUT PRESCRIPTION PATTERNS OF PSYCHOTROPIC DRUG FOR THREE MENTAL DISORDERS IN CHINA

Tardive dyskinesia (TD) is one of the most distressing side effects of antipsychotic treatment. As prevalence studies of TD in Asian population are scarce, a cross-sectional study was performed to assess the frequency of TD in Indian patients with schizophrenia and risk factors of TD.Cross-sectional study of 160 Indian patients fulfilling the DSM-IV TR criteria for schizophrenia and who received antipsychotics for at least one year, were examined with two validated scales for TD. Logistic regression analyses were used to examine the relationship between TD and clinical risk factors.The frequency of probable TD in the total sample was 26.4%. The logistic regression yielded significant odds ratios between TD and age, intermittent treatment, and total cumulative antipsychotic dose. The difference of TD between SGA and FGA disappeared after adjusting for important co-variables in regression analysis.Indian patients with schizophrenia and long-term antipsychotic treatment have a high risk of TD, and TD is associated with older age, intermittent antipsychotic treatment, and a high total cumulative antipsychotic dose. Our study findings suggest that there is no significant difference between SGAs with regards to the risk of causing TD as compared to FGAs.

Prevalence and risk factors associated with tardive dyskinesia among Indian patients with schizophrenia

BackgroundTardive dyskinesia (TD) is one of the most distressing side effects of antipsychotic treatment. As prevalence studies of TD in Asian population are scarce, a cross-sectional study was performed to assess the frequency of TD in Indian patients with schizophrenia and risk factors of TD. MethodCross-sectional study of 160 Indian patients fulfilling the DSM-IV TR criteria for schizophrenia and who received antipsychotics for at least one year, were examined with two validated scales for TD. Logistic regression analyses were used to examine the relationship between TD and clinical risk factors. ResultsThe frequency of probable TD in the total sample was 26.4%. The logistic regression yielded significant odds ratios between TD and age, intermittent treatment, and total cumulative antipsychotic dose. The difference of TD between SGA and FGA disappeared after adjusting for important co-variables in regression analysis. ConclusionIndian patients with schizophrenia and long-term antipsychotic treatment have a high risk of TD, and TD is associated with older age, intermittent antipsychotic treatment, and a high total cumulative antipsychotic dose. Our study findings suggest that there is no significant difference between SGAs with regards to the risk of causing TD as compared to FGAs.

Tardive dyskinesia in a pregnant woman with low dose, short-duration risperidone: possible role of estrogen-induced dopaminergic hypersensitivity

Tardive dyskinesia in a pregnant woman with low dose, short-duration risperidone: possible role of estrogen-induced dopaminergic hypersensitivity

Psychiatric Morbidity, Phenomenology and Management in Hospitalized Female Foreign Domestic Workers in Lebanon

40 million female domestic workers worldwide experience the inhumane conditions associated with this unregulated occupation, a situation that induces psychiatric morbidities in many. The case in Lebanon is not any better where it is estimated that one foreign domestic worker (FDW) commits suicide weekly. 33 female FDW and 14 female Lebanese (control group, CG) were enrolled. Brief Psychotic Rating Scale (BPRS) and Clinical Global Impression (CGI) scales were administered on admission and discharge and socio-demographic, living conditions, mental health care data and phenomenological observations were collected. Sexual, physical, and verbal abuses were detected in FDW (12.5, 37.5, and 50.0 %. respectively). 66.7 % of them were diagnosed with brief psychotic episode. The mean duration of hospital stay (13.1 days) was significantly lower in the FDW group. The mean cumulative antipsychotic dose of the FDW was 337.1 mg of chlorpromazine equivalent and the mean BPRS total pre-score of FDW was 66.4 with a much improved state on the CGI global improvement scale, all of which were nonsignificantly different from the CG. Striking phenomenological findings among FDW were acute anorexia (39.4 %), nudity (30.3 %), catatonic features (21.2 %), and delusion of pregnancy (12.1 %). Inpatient FDW are more diagnosed with psychotic than affective disorders and receive approximately similar treatment as controls in spite of the trend to rapidly discharge and deport the worker to limit the costs. Both groups presented with similar severity, although the FDW had peculiar phenomenological observations.

A follow-up MRI study of the fusiform gyrus and middle and inferior temporal gyri in schizophrenia spectrum

While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the superior temporal gyrus (STG) during the early phases of schizophrenia, it remains largely unknown whether other temporal lobe structures also exhibit similar progressive changes and whether these changes, if present, are specific to schizophrenia among the spectrum disorders. In this longitudinal MRI study, the gray matter volumes of the fusiform, middle temporal, and inferior temporal gyri were measured at baseline and follow-up scans (mean inter-scan interval=2.7 years) in 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. Both schizophrenia and schizotypal patients had a smaller fusiform gyrus than controls bilaterally at both time points, whereas no group difference was found in the middle and inferior temporal gyri. In the longitudinal comparison, the schizophrenia patients showed significant fusiform gyrus reduction (left, -2.6%/year; right, -2.3%/year) compared with schizotypal patients (left: -0.4%/year; right: -0.2%/year) and controls (left: 0.1%/year; right: 0.0%/year). However, the middle and inferior temporal gyri did not exhibit significant progressive gray matter change in all diagnostic groups. In the schizophrenia patients, a higher cumulative dose of antipsychotics during follow-up was significantly correlated with less severe gray matter reduction in the left fusiform gyrus. The annual gray matter loss of the fusiform gyrus did not correlate with that of the STG previously reported in the same subjects. Our findings suggest regional specificity of the progressive gray matter reduction in the temporal lobe structures, which might be specific to overt schizophrenia within the schizophrenia spectrum.

A follow-up MRI study of the superior temporal subregions in schizotypal disorder and first-episode schizophrenia

While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the superior temporal gyrus (STG) during the early phases of schizophrenia, it remains unknown whether patients with schizotypal features exhibit similar STG changes. In this study, longitudinal MRI data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The volumes of the STG and its subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT), rostral STG, and caudal STG] were measured on baseline and follow-up (mean: 2.7 years) scans and were compared across groups. At the baseline, both the schizophrenia and schizotypal patients had smaller left PT and left caudal STG than the controls. In a longitudinal comparison, the schizophrenia patients showed significant gray matter reduction of the STG over time (left: − 2.8%/year; right: − 1.5%/year) compared with the schizotypal patients (left: − 0.6%/year; right: − 0.3%/year) and controls (left: 0.0%/year; right: − 0.1%/year) without a prominent effect of subregion or type of antipsychotic (typical/atypical). In the schizophrenia patients, greater annual volume reductions of the left PP and right PT were correlated with less improvement of positive psychotic symptoms. A higher cumulative dose of antipsychotics during follow-up in schizophrenia was significantly correlated with less severe gray matter reductions in the left PT and bilateral caudal STG. Our findings suggest that the left posterior STG subregions are commonly reduced in diseases of the schizophrenia spectrum; whereas, schizophrenia patients exhibit further progressive STG changes associated with overt psychosis in the early years of the illness.

Ethyl-Eicosapentaenoic Acid in First-Episode Psychosis

To investigate if ethyl-eicosapentaenoic acid (E-EPA) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis (FEP). We performed a 12-week, randomized, double-blind, placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients. Sixty-nine patients were eligible for analysis; a post hoc analysis was computed for a subgroup of nonaffective FEP patients (N = 53). The first participant was included in November 2000 and the last participant completed the trial in August 2003. Primary outcome measures were symptom change scores and time to first response, while tolerability measures and cumulative antipsychotic dose were secondary outcome measures. Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores. Cox regression analysis revealed a significant treatment by diagnosis interaction (p = .024) for time to first response favoring E-EPA in nonaffective psychosis. Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 (42.9% [15/35] vs. 17.6% [6/34] for all participants, p = .036; 54.2% [13/24] vs. 17.2% [5/29] for the nonaffective psychosis subset, p = .008); however, the difference at week 12 was no longer significant. Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20% less antipsychotic medication between weeks 4 through 6 (p = .03), had less extrapyramidal side effects in the initial 9 weeks (p < .05 for all participants and for all timepoints), and reported less constipation (p = .011) and fewer sexual side effects (p = .016) than those treated with antipsychotic medication alone. The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications. However, it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis, possibly due to a ceiling effect, since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone. Further controlled trials in nonaffective early psychosis seem warranted. Australian Clinical Trials Registry identifier 12605000267651 (http://actr.org.au).

Antipsychotics and risk of first‐time hospitalization for myocardial infarction: a population‐based case–control study

Use of antipsychotics has been linked with an adverse cardiovascular risk factor profile and an increased risk of dysrhythmia and sudden cardiac death. However, detailed data on the association between use of antipsychotics and development of atherosclerotic disease are limited. To examine risk of hospitalization for myocardial infarction (MI) amongst users of antipsychotics compared with non-users. A population-based case-control study using data from hospital discharge registries in the counties of North Jutland, Viborg and Aarhus, Denmark, and the Danish Civil Registration System. We identified 21,377 cases of first-time hospitalization for MI and 106,885 sex- and age-matched non-MI population controls in the period 1992-2004. All prescriptions for antipsychotics filled prior to the date of admission for MI were retrieved from population-based prescription databases. We used conditional logistic regression to adjust for a wide range of covariates. Current users of atypical [adjusted relative risk: 0.98, 95% confidence interval (CI): 0.88-1.09] and typical antipsychotics (adjusted relative risk: 0.99, 95% CI: 0.96-1.03) had no increased overall risk of being admitted to hospital for MI when compared with non-users of antipsychotics. These findings were consistent in all examined subgroups. Further, we found no association between the cumulative dose of antipsychotics and the risk of hospitalization for MI. These findings do not support the hypothesis that use of antipsychotics and in particular atypical antipsychotics is associated with increased risk of MI.

Prevalence of and risk factors for tardive dyskinesia in a Xhosa population in the Eastern Cape of South Africa

Objective Despite prolonged use of antipsychotic drug treatment, the prevalence of tardive dyskinesia (TD) in a Xhosa population has not been evaluated. This study was undertaken to assess the prevalence and identify possible factors, including antioxidant intake and smoking history, which may increase or reduce the risk of TD. Method One hundred two subjects who had been exposed to typical antipsychotic drugs for at least 6 months and were currently on an antipsychotic were screened for abnormal movements using the Abnormal Involuntary Movement Scale (AIMS) rating scale. Data about current and past antipsychotic therapy, diagnoses, smoking history, and dietary factors were gathered from the patient and from chart view. Result Twenty-eight and four-tenths percent of subjects met criteria for tardive dyskinesia. Years of treatment and total cumulative antipsychotic dose were significant predictors of TD. Subjects with higher total consumption of foods containing antioxidants had lower rates of TD, but only consumption of onions was significantly associated with reduced prevalence. TD was less prevalent in smokers, but this difference did not reach statistical significance. Age, sex, and psychiatric diagnosis did not predict presence of TD. Conclusion The result of this study indicate that TD in this population is more prevalent than previously believed within this local clinical context. Prolonged treatment and total antipsychotic drug exposure are important risk factors for TD in this population. Further study of the role of concurrent medications and dietary factors is indicated.