Dose Of Antipsychotic Medication Research Articles

Eye movements as predictor of cognitive improvement after cognitive remediation therapy in patients with schizophrenia.

Baseline cognitive functions of patients predicted the efficacy of cognitive remediation therapy (CRT), but results are mixed. Eye movement is a more objective and advanced assessment of cognitive functions than neuropsychological testing. We aimed to investigate the applicability of eye movements in predicting cognitive improvement after patients with schizophrenia were treated with CRT. We recruited 79 patients with schizophrenia to complete 8 weeks of CRT and assessed their cognitive improvement outcomes. Eye movements were assessed by prosaccades, antisaccades, and free-viewing tasks at baseline, and neuropsychological tests in four cognitive domains were assessed before and after treatment to calculate treatment outcomes. Predictors of demographic information, clinical characteristics, and eye movement measures at baseline on cognitive improvement outcomes were analyzed using logistic regression analysis. We further compared the predictive performance between eye movement measurements and neuropsychological test regarding the effect of CRT on cognitive improvement, and explored factors that could be affect the treatment outcomes in different cognitive domains. As operationally defined, 33 patients showed improved in cognition (improved group) and 46 patients did not (non-improved group) after CRT. Patients with schizophrenia being employed, lower directional error rate in antisaccade task, and lower the gap effect (i.e., the difference in saccadic latency between the gap condition and overlap condition) in prosaccade task at baseline predicted cognitive improvement in CRT. However, performance in the free-viewing task not associated with cognitive improvement in patients in CRT. Our results show that eye-movement prediction model predicted the effect of CRT on cognitive improvement in patients with schizophrenia better than neuropsychological prediction model in CRT. In addition, baseline eye-movements, cognitive reserve, antipsychotic medication dose, anticholinergic cognitive burden change, and number of training sessions were associated with improvements in four cognitive domains. Eye movements as a non-invasiveness, objective, and sensitive method of evaluating cognitive function, and combined saccadic measurements in pro- and anti-saccades tasks could be more beneficial than free-viewing task in predicting the effect of CRT on cognitive improvement in patients with schizophrenia.

Clinical experiences of guided tapering of antipsychotics for patients with schizophrenia– a case series

Background80% of patients value information on treatment options as an important part of recovery, further patients with a history of psychotic episodes feel excluded from decision making about their antipsychotic treatment, and on top of that, mental health staff is prone to be reluctant to support shared decision making and medication tapering for patients with schizophrenia. This case series aims to demonstrate the tapering of antipsychotic medication and how guided tapering affects the patient’s feeling of autonomy and psychiatric rehabilitation.Case presentationWe present six patients diagnosed with schizophrenia (International Classification of Mental and Behavioral Disorders– 10th Edition codes F20.0–5, F20.7–9) who underwent professionally guided tapering in our clinic. The clinic aims to guide the patients to identify the lowest possible dose of antipsychotic medication in a safe setting to minimise the risk of severe relapse. Two patients completely discontinued their antipsychotic medication, two suffered a relapse during tapering, one chose to stop the tapering at a low dose, and one patient with treatment resistant schizophrenia, which is still tapering down.ConclusionsReducing the antipsychotic dose increased emotional awareness in some patients (n = 4) helping them to develop better strategies to handle stress and increased feelings of recovery. Patients felt a greater sense of autonomy and empowerment during the tapering process, even when discontinuation was not possible. Increased awareness in patients and early intervention during relapse may prevent severe relapse.Impact and implicationsSome patients with schizophrenia might be over medicated, leading to unwanted side effects and the wish to reduce their medication. The patients in our study illustrate how guided tapering of antipsychotic medication done jointly with the patient can lead to improved emotional awareness and the development of effective symptom management strategies. This may in turn lead to a greater sense of empowerment and identity and give life more meaning, supporting the experience of personal recovery.

Borderline personality disorder vs. schizophrenia spectrum disorders in young people recruited within an "Early Intervention in Psychosis" service: clinical and outcome comparisons.

Borderline Personality Disorder (BPD) is under-recognized in First-Episode Psychosis (FEP) and its psychotic manifestations are difficult to differentiate from Schizophrenia Spectrum Disorders (SSD). The aim of this investigation was to compare clinical, sociodemographic, and outcome characteristics between FEP patients with BPD vs. FEP subjects with SSD both at baseline and across a 2-year follow-up period. Participants completed the Health of the Nation Outcome Scale (HoNOS), the Positive And Negative Syndrome Scale (PANSS), and the Global Assessment of Functioning (GAF) scale both at entry and every 12months during the follow-up. A mixed-design ANOVA model was conducted to investigate the temporal stability of clinical scores within and between the two subgroups. Among 356 FEP participants, 49 had a BPD diagnosis. Compared to FEP/SSD (n = 307), FEP/BPD patients showed higher prevalence of employment, current substance use, and past attempted suicide. They had a lower equivalent dose of antipsychotic medication at entry and lower levels of negative symptoms. Finally, they had a higher 2-year drop-out rate and a significant improvement in psychopathological scores limited to the first year of treatment. BPD as categorical entity represents a FEP subgroup with specific clinical challenges. Appropriate treatment guidelines for this FEP subgroup are thus needed.

Sociodemographic and clinical characteristics of patients with borderline personality disorder enrolled for a first episode psychosis within a specialized “early intervention” service

Borderline Personality Disorder (BPD) is under-recognized in First Episode Psychosis (FEP). The aims of this investigation were: (a) to examine the prevalence of BPD in FEP patients enrolled within an Italian “Early Intervention in Psychosis” (EIP) service; (2) to compare sociodemographic, clinical and treatment characteristics at entry between FEP individuals with and without BPD; and (3) to compare their drop-out rates along a 2-year follow-up period. BPD was assessed using the Structured Clinical Interview for DSM-IV axis II personality disorders. All participants also completed the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Forty-nine (9.6%) FEP participants showed a BPD diagnosis. FEP individuals with BPD had a higher baseline prevalence of substance misuse, a lower baseline equivalent dose of antipsychotic medication, lower baseline levels of negative symptoms, and higher baseline levels of anxious-depressive features. They also had a higher 2-year drop-out rate. In conclusion, BPD is present in 10% of FEP patients. This FEP subgroup has peculiar clinical challenges (e.g. high substance misuse at entry, high drop-out rate) and additional comorbidities (e.g. high levels of depressive symptoms at entry), which would require appropriate treatment guidelines.

Concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer: A multicenter, retrospective, observational study.

There is concern that hydroxyzine exacerbates delirium, but a recent preliminary study suggested that the combination of haloperidol and hydroxyzine was effective against delirium. This study examined whether the concomitant use of hydroxyzine and haloperidol worsened delirium in patients with cancer. This retrospective, observational study was conducted at 2 general hospitals in Japan. The medical records of patients with cancer who received haloperidol for delirium from July to December 2020 were reviewed. The treatments for delirium included haloperidol alone or haloperidol combined with hydroxyzine. The primary outcome was the duration from the first day of haloperidol administration to the resolution of delirium, defined as its absence for 2 consecutive days. The time to delirium resolution was analyzed to compare the haloperidol group and hydroxyzine combination group using the log-rank test with the Kaplan-Meier method. Secondary outcomes were (1) the total dose of antipsychotic medications, including those other than haloperidol (measured in chlorpromazine-equivalent doses), and (2) the frequencies of detrimental incidents during delirium, specifically falls and self-removal of drip infusion lines. The unpaired t-test and Fisher's exact test were used to analyze secondary outcomes. Of 497 patients who received haloperidol, 118 (23.7%) also received hydroxyzine. No significant difference in time to delirium resolution was found between the haloperidol group and the hydroxyzine combination group (log-rank test, P = 0.631). No significant difference between groups was found in either chlorpromazine-equivalent doses or the frequency of detrimental incidents. This study showed that the concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer.

Implementation of a lifestyle and life‐skills intervention to prevent weight‐gain and cardiometabolic abnormalities in young people with first‐episode psychosis as part of routine care: The Keeping the Body in Mind program

AbstractObjectivesIn 2013, a cluster‐controlled pilot study found the 12‐week Keeping the Body in Mind (KBIM) lifestyle and life skills intervention was able to prevent weight gain in a small sample of youth experiencing first‐episode psychosis (FEP) with fewer than 4 weeks of antipsychotic exposure. This study aims to evaluate the effectiveness of KBIM as routine care on anthropometry and metabolic biochemistry in a larger sample of youth with FEP across three community mental health services.MethodThis retrospective chart audit was conducted on youth with FEP, prescribed a therapeutic dose of antipsychotic medication, and who engaged with KBIM between 2015 and 2019. Primary outcomes were weight and waist circumference. Secondary outcomes were blood pressure, blood glucose, and blood lipids. Outcomes were collected in at baseline and at 12 weeks. Data on program engagement were obtained from the participant's medical file.ResultsOne‐hundred and eighty‐two people met inclusion criteria, and up to 134 people had baseline and 12‐week data on one or more outcome. Mean number of sessions attended was 11.1 (SD = 7.3). Increases in weight and waist circumference were limited to 1.5 kg (SD = 5.3, t(133) = 3.2, p = .002) and 0.7 cm (SD = 5.8, t(109) = 1.2, p = .23) respectively. Eighty‐one percent of participants did not experience clinically significant weight gain (>7% of baseline weight). There were no significant changes in blood pressure or metabolic biochemistry.ConclusionThe prevention of substantial gains in weight and waist circumference observed in the initial pilot study was maintained with implementation of KBIM as part of routine clinical care for youth with FEP.

Time is the enemy: Negative symptoms are related to even slight differences in the duration of untreated psychosis

BackgroundNegative symptoms (NS) represent a detrimental symptomatic domain in schizophrenia affecting social and occupational outcomes. AimsWe aimed to identify factors from the baseline visit (V1) — with a mean illness duration of 0.47 years (SD = 0.45) — that predict the magnitude of NS at the follow-up visit (V3), occurring 4.4 years later (mean +/− 0.45). MethodUsing longitudinal data from 77 first-episode schizophrenia spectrum patients, we analysed eight predictors of NS severity at V3: (1) the age at disease onset, (2) age at V1, (3) sex, (4) diagnosis, (5) NS severity at V1, (6) the dose of antipsychotic medication at V3, (7) hospitalisation days before V1 and; (8) the duration of untreated psychosis /DUP/). Secondly, using a multiple linear regression model, we studied the longitudinal relationship between such identified predictors and NS severity at V3 using a multiple linear regression model. ResultsDUP (Pearson's r = 0.37, p = 0.001) and NS severity at V1 (Pearson's r = 0.49, p < 0.001) survived correction for multiple comparisons. The logarithmic-like relationship between DUP and NS was responsible for the initial stunning incremental contribution of DUP to the severity of NS. For DUP < 6 months, with the sharpest DUP/NS correlation, prolonging DUP by five days resulted in a measurable one-point increase in the 6-item negative symptoms PANSS domain assessed 4.9 (+/− 0.6) years after the illness onset. Prolongation of DUP to 14.7 days doubled this NS gain, whereas 39 days longer DUP tripled NS increase. ConclusionThe results suggest the petrification of NS during the early stages of the schizophrenia spectrum and a crucial dependence of this symptom domain on DUP. These findings are clinically significant and highlight the need for primary preventive actions.

Antipsychotics and Mortality in Adult and Geriatric Patients with Schizophrenia.

Patients with schizophrenia have a high mortality risk, and the role of antipsychotic medications remains inconclusive. In an aging society, older patients with schizophrenia warrant increased attention. This study investigated the association of antipsychotic medication dosages with mortality in patients with schizophrenia by using data from Taiwan's National Health Insurance Research Database from 2010 to 2014. This study included 102,964 patients with schizophrenia and a subgroup of 6433 older patients in addition to an age- and sex-matched control group. The findings revealed that among patients with schizophrenia, the no antipsychotic exposure group had the highest mortality risk (3.61- and 3.37-fold higher risk for overall and cardiovascular mortality, respectively) in the age- and sex-adjusted model, followed by the high, low, and moderate exposure groups. A similar pattern was observed in the older patients with schizophrenia. High exposure to antipsychotics was associated with the highest risks of overall and cardiovascular mortality (3.01- and 2.95-fold higher risk, respectively). In conclusion, the use of antipsychotics can be beneficial for patients with schizophrenia with recommended exposure levels being low to moderate. In older patients, high antipsychotic exposure was associated with the highest mortality risk, indicating that clinicians should be cautious when administering antipsychotic medications to such patients.

Complement component 4A protein levels are negatively related to frontal volumes in patients with schizophrenia spectrum disorders.

Excessive C4A-gene expression may result in increased microglia-mediated synaptic pruning. As C4A overexpression is observed in schizophrenia spectrum disorders (SSD), this mechanism may account for the altered brain morphology (i.e. reduced volume and cortical thickness) and cognitive symptoms that characterize SSD. Therefore, this study investigates the association of C4A serum protein levels with brain morphology and cognition, and in particular whether this association differs between recent-onset SSD (n=69) and HC (n=40). Serum C4A protein levels were compared between groups. Main outcomes included total gray matter volume, mean cortical thickness and cognitive performance. Regression analysis on these outcomes included C4A level, group (SSD vs. HC), and C4A*Group interactions. All statistical tests were corrected for age, sex, BMI, and antipsychotic medication dose. Follow-up analyses were performed on separate brain regions and scores on cognitive sub-tasks. The group difference in C4A levels was not statistically significant (p=0.86). The main outcomes did not show a significant interaction effect (p>0.13) or a C4A main effect (p>0.27). Follow-up analyses revealed significant interaction effects for the left medial orbitofrontal and left frontal pole volumes (p<0.001): C4A was negatively related to these volumes in SSD, but positively in HC. This study demonstrated that C4A was negatively related to - specifically - frontal brain volumes in SSD, but this relation was inverse for HC. The results support the hypothesis of complement-mediated brain volume reduction in SSD. The results also suggest that C4A has a differential association with brain morphology in SSD compared to HC.

Altered Temporal Dynamics of Resting-State Functional Magnetic Resonance Imaging in Adolescent-Onset First-Episode Psychosis.

Dynamic functional connectivity (dFC) alterations have been reported in patients with adult-onset and chronic psychosis. We sought to examine whether such abnormalities were also observed in patients with first episode, adolescent-onset psychosis (AOP), in order to rule out potential effects of chronicity and protracted antipsychotic treatment exposure. AOP has been suggested to have less diagnostic specificity compared to psychosis with onset in adulthood and occurs during a period of neurodevelopmental changes in brain functional connections. Seventy-nine patients with first episode, AOP (36 patients with schizophrenia-spectrum disorder, SSD; and 43 with affective psychotic disorder, AF) and 54 healthy controls (HC), aged 10 to 17 years were included. Participants underwent clinical and cognitive assessments and resting-state functional magnetic resonance imaging. Graph-based measures were used to analyze temporal trajectories of dFC, which were compared between patients with SSD, AF, and HC. Within patients, we also tested associations between dFC parameters and clinical variables. Patients with SSD temporally visited the different connectivity states in a less efficient way (reduced global efficiency), visiting fewer nodes (larger temporal modularity, and increased immobility), with a reduction in the metabolic expenditure (cost and leap size), relative to AF and HC (effect sizes: Cohen's D, ranging 0.54 to.91). In youth with AF, these parameters did not differ compared to HC. Connectivity measures were not associated with clinical severity, intelligence, cannabis use, or dose of antipsychotic medication. dFC measures hold potential towards the development of brain-based biomarkers characterizing adolescent-onset SSD.

Exploring negative symptoms heterogeneity in patients diagnosed with schizophrenia and schizoaffective disorder using cluster analysis

BackgroundDissecting the heterogeneity of schizophrenia may help foster progress in understanding its etiology and lay the groundwork for the development of new treatment options for primary or enduring negative symptoms (NS). In this regard, the present study aimed to: (1) to use cluster analysis to identify subgroups of Lebanese patients diagnosed with either schizophrenia or schizoaffective disorder based on NS clusters, and (2) to relate the statistically-derived subgroups to clinically relevant external validators (including measures if state and trait depression, stigma, insight, loneliness, social support).MethodA total of 202 adult long-stay, chronic, and clinically remitted patients (166 diagnosed with schizophrenia and 36 with schizoaffective disorder) were enrolled. A cluster analysis approach was adopted to classify patients based on the five NS domains social withdrawal, emotional withdrawal, alogia, avolition and anhedonia.ResultsA three-cluster solution was obtained based on unique NS profiles, and divided patients into (1) low NS (LNS; 42.6%) which characterized by the lowest mean scores in all NS domains, (2) moderate NS (MNS; 25.7%), and (3) high NS (HNS; 31.7%). Post-hoc comparisons showed that depression (state and trait), loneliness and social support could accurately distinguish the schizophrenia subgroups. Additionally, individuals in the HNS cluster had longer duration of illness, longer duration of hospitalization, and were given higher dosages of antipsychotic medication compared to those in the other clusters, but these differences did not achieve the statistical significance.ConclusionFindings provide additional support to the categorical model of schizophrenia by confirming the existence of three alternate subtypes based on NS. The determination of distinct NS subgroups within the broad heterogeneous population of people diagnosed with schizophrenia may imply that each subgroup possibly has unique underlying mechanisms and necessitates different treatment approaches.

Kynanthropic and vampirism delusions: a case report and review of the literature.

Zooanthropy (delusional beliefs of turning into an animal) is a rare but well recognised psychiatric phenomenon. This case describes the presence of kynanthropic delusions (delusional beliefs of turning into a dog). Multiple other psychotic symptoms were also evident including unusually the additional presence of delusions of vampirism. Delusional beliefs in this case were associated with behavioural changes including growling and barking, and less commonly an expressed craving for biting people's necks to suck human blood. Symptom intensity was associated with increased psychosocial stressors for this patient, with some benefit noted from very high doses of anti-psychotic medications. Brief admissions to the acute psychiatric inpatient unit and thus removal from environmental stressors has been associated with an amelioration in symptomatology.

Study Finds Higher-Dose Antipsychotic Polypharmacy Does Not Increase Hospitalization

Study Finds Higher-Dose Antipsychotic Polypharmacy Does Not Increase Hospitalization

Smoking and attention in schizophrenia spectrum disorders: What are we neglecting?

Individuals with schizophrenia spectrum disorders (SSDs) record elevated rates of smoking, which is often attributed to their effort to self-medicate cognitive and attentional symptoms of their illness. Empirical evidence for this hypothesis is conflicting, however. In this study, we aimed to test predictions derived from the cognitive self-medication hypothesis. We predicted that cigarette smoking status and extent would predict the attentional performance of participants with SSDs. Simultaneously, we wished to address methodological gaps in previous research. We measured distinct attentional components and made adjustments for the effects of other, attention-modulation variables. Sixty-one smokers (82.0% males, 26.73 ± 6.05 years) and 61 non-smokers (50.8% males, 27.10 ± 7.90 years) with recent-onset SSDs completed an X-type Continuous Performance Test, which was used to derive impulsivity and inattention component scores. Relationships between the two component scores and cigarette smoking status and extent were assessed using hierarchical regression. Effects of estimated premorbid intellectual functioning and antipsychotic medication dosage were held constant. Smokers had significantly higher inattention component scores than non-smokers when covariates were controlled (p = 0.026). Impulsivity remained unaffected by smoking status (p = 0.971). Cigarette smoking extent, i.e., the number of cigarettes smoked per day, was not associated with either inattention (p = 0.414) or impulsivity (p = 0.079). Models of smoking-related attentional changes can benefit from the inclusion of sample-specific component scores and attention-modulating covariates. Under these conditions, smokers with SSDs can show a partial attentional benefit. However, the limited scope of this benefit suggests that the cognitive self-medication hypothesis requires further testing or reconsidering.

Natural Oscillatory Frequency Slowing in the Premotor Cortex of Early-Course Schizophrenia Patients: A TMS-EEG Study.

Despite the heavy burden of schizophrenia, research on biomarkers associated with its early course is still ongoing. Single-pulse Transcranial Magnetic Stimulation coupled with electroencephalography (TMS-EEG) has revealed that the main oscillatory frequency (or "natural frequency") is reduced in several frontal brain areas, including the premotor cortex, of chronic patients with schizophrenia. However, no study has explored the natural frequency at the beginning of illness. Here, we used TMS-EEG to probe the intrinsic oscillatory properties of the left premotor cortex in early-course schizophrenia patients (<2 years from onset) and age/gender-matched healthy comparison subjects (HCs). State-of-the-art real-time monitoring of EEG responses to TMS and noise-masking procedures were employed to ensure data quality. We found that the natural frequency of the premotor cortex was significantly reduced in early-course schizophrenia compared to HCs. No correlation was found between the natural frequency and age, clinical symptom severity, or dose of antipsychotic medications at the time of TMS-EEG. This finding extends to early-course schizophrenia previous evidence in chronic patients and supports the hypothesis of a deficit in frontal cortical synchronization as a core mechanism underlying this disorder. Future work should further explore the putative role of frontal natural frequencies as early pathophysiological biomarkers for schizophrenia.

Connectivity alterations of mesostriatal pathways in first episode psychosis

Background and hypothesisPathogenic understanding of the psychotic disorders converges on regulation of dopaminergic signaling in mesostriatocortical pathways. Functional connectivity of the mesostriatal pathways may inform us of the neuronal networks involved.Study designThis longitudinal study of first episode psychosis (FEP) (49 patients, 43 controls) employed seed-based functional connectivity analyses of fMRI data collected during a naturalistic movie stimulus.Study resultsWe identified hypoconnectivity of the dorsal striatum with the midbrain, associated with antipsychotic medication dose in FEP, in comparison with the healthy control group. The midbrain regions that showed hypoconnectivity with the dorsal striatum also showed hypoconnectivity with cerebellar regions suggested to be involved in regulation of the mesostriatocortical dopaminergic pathways. None of the baseline hypoconnectivity detected was seen at follow-up.ConclusionsThese findings extend earlier resting state findings on mesostriatal connectivity in psychotic disorders and highlight the potential for cerebellar regulation of the mesostriatocortical pathways as a target of treatment trials.

Smartwatch digital phenotypes predict positive and negative symptom variation in a longitudinal monitoring study of patients with psychotic disorders.

Monitoring biometric data using smartwatches (digital phenotypes) provides a novel approach for quantifying behavior in patients with psychiatric disorders. We tested whether such digital phenotypes predict changes in psychopathology of patients with psychotic disorders. We continuously monitored digital phenotypes from 35 patients (20 with schizophrenia and 15 with bipolar spectrum disorders) using a commercial smartwatch for a period of up to 14 months. These included 5-min measures of total motor activity from an accelerometer (TMA), average Heart Rate (HRA) and heart rate variability (HRV) from a plethysmography-based sensor, walking activity (WA) measured as number of total steps per day and sleep/wake ratio (SWR). A self-reporting questionnaire (IPAQ) assessed weekly physical activity. After pooling phenotype data, their monthly mean and variance was correlated within each patient with psychopathology scores (PANSS) assessed monthly. Our results indicate that increased HRA during wakefulness and sleep correlated with increases in positive psychopathology. Besides, decreased HRV and increase in its monthly variance correlated with increases in negative psychopathology. Self-reported physical activity did not correlate with changes in psychopathology. These effects were independent from demographic and clinical variables as well as changes in antipsychotic medication dose. Our findings suggest that distinct digital phenotypes derived passively from a smartwatch can predict variations in positive and negative dimensions of psychopathology of patients with psychotic disorders, over time, providing ground evidence for their potential clinical use.

Antipsychotic treatment and cognitive function in patients with schizophrenia

IntroductionIt is known that cognitive impairment is one of the main symptoms of schizophrenia, which determines the functional outcome. The question of the effect of antipsychotics on the cognitive functions of these patients is still unresolved. Cognitive impairment while taking antipsychotics is thought to be mostly related to extrapyramidal abnormalities. In practice, it is difficult to distinguish what causes a patient’s complaints of cognitive decline. Is it related to taking the medication? Or a worsening mental state? Age, lifestyle, etc.?ObjectivesWe analyzed the relationship of cognitive impairment with the severity of extrapyramidal symptoms, mental status gravity, age, and dose of antipsychotic and cholinergic medication at weeks 2 and 8 of treatment.MethodsWe examined 37 patients with schizophrenia on stable antipsychotic treatment at weeks 2 and 8 of therapy. Thirty patients received a 2nd-generation antipsychotic, and seven patients received a 1st-generation antipsychotic. The anticholinergic drug was trihexyphenidyl. The antipsychotic dose was estimated in olanzapine equivalent. Extrapyramidal symptoms were assessed by The Scale for Extrapyramidal Symptoms (SAS), severity of mental condition was rated by The Positive and Negative Syndrome Scale (PANSS), cognitive function was measured by The Brief Assessment of Cognition in Schizophrenia (BACS).ResultsAs previously described, patients with more severe extrapyramidal symptoms tended to have lower BACS composite scores (rxy = -0.318, p-value = 0.055) at week 8 of therapy. The total score on the SAS scale, as expected, only negatively correlated with scores on the Token Motor Task test (rxy = -0.412, p-value = 0.011) at the 8th week of therapy. There were also negative correlations between Token Motor Task scores and trihexyphenidyl dose (rxy = -0.496, p-value = 0.002). At both weeks 2 and 8, there was a negative relationship between age and Symbol Coding scores (rxy = -0.387, p-value = 0.018; rxy = -0.35, p-value = 0.034, respectively). Verbal Fluency scores were lower in patients with high scores on the PANSS excitement component and at week 2 (rxy = -0.42, p-value = 0.01), this trend continued at week 8 (rxy = -0.31, p-value=0.063) . Tower of London scores were negatively associated at week 8 with cognitive and positive PANSS scores (rxy = -0.46, p-value = 0.004; rxy = -0.336, p-value = 0.042, respectively).ConclusionsThus, we have demonstrated that cognitive impairment in patients with schizophrenia is associated with various factors, and not only antipsychotic treatment.Disclosure of InterestNone Declared

Perturbed iron biology in the prefrontal cortex of people with schizophrenia

Despite loss of grey matter volume and emergence of distinct cognitive deficits in young adults diagnosed with schizophrenia, current treatments for schizophrenia do not target disruptions in late maturational reshaping of the prefrontal cortex. Iron, the most abundant transition metal in the brain, is essential to brain development and function, but in excess, it can impair major neurotransmission systems and lead to lipid peroxidation, neuroinflammation and accelerated aging. However, analysis of cortical iron biology in schizophrenia has not been reported in modern literature. Using a combination of inductively coupled plasma-mass spectrometry and western blots, we quantified iron and its major-storage protein, ferritin, in post-mortem prefrontal cortex specimens obtained from three independent, well-characterised brain tissue resources. Compared to matched controls (n = 85), among schizophrenia cases (n = 86) we found elevated tissue iron, unlikely to be confounded by demographic and lifestyle variables, by duration, dose and type of antipsychotic medications used or by copper and zinc levels. We further observed a loss of physiologic age-dependent iron accumulation among people with schizophrenia, in that the iron level among cases was already high in young adulthood. Ferritin, which stores iron in a redox-inactive form, was paradoxically decreased in individuals with the disorder. Such iron-ferritin uncoupling could alter free, chemically reactive, tissue iron in key reasoning and planning areas of the young-adult schizophrenia cortex. Using a prediction model based on iron and ferritin, our data provide a pathophysiologic link between perturbed cortical iron biology and schizophrenia and indicate that achievement of optimal cortical iron homeostasis could offer a new therapeutic target.

NEUROLEPTIC MALIGNANT SYNDROME: AN UNUSUAL CASE TO INCREASE CLINICAL ATTENTION

A 26-year-young man was taken to the hospital with symptoms of schizophrenia, and treatment began with a high dose of antipsychotic medication. After receiving medication for 3–4 days, the patient experienced persistently high body temperatures, tight muscles, and raised blood levels of CK-MB and CK-NAC. The results of all other investigations were normal. A rare Neuroleptic Malignant Syndrome (NMS) was made and treatment started with immediate withdrawal of the causative drug, and timely supportive therapy led to a successful recovery. This case illustrates the importance of adopting a broad differential diagnosis for fever, carefully reviewing the prescription lists of all patients, and taking NMS into account in patients who have both fever and stiffness.