Effectiveness of Switching to Long-acting Injectable Aripiprazole in Patients with Recent-onset and Chronic Schizophrenia

Objective@#This study investigated the effectiveness of switching to once-monthly long-acting injectable (LAI) aripiprazole from other second-generation antipsychotics including LAI paliperidone palmitate in both recent-onset and chronic schizophrenia patients. @*Methods@#This was a 24-week prospective, open-label, flexible dose-switching study in patients with schizophrenia. Scores on the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP) scale, Clinical Global Impression (CGI), Subjective Well-being Under Neuroleptics−Short Form (SWN-K), and a computerized emotional recognition test (ERT) were evaluated. Subjects were divided into two groups (recent onset and chronic) based on 5 years’ duration of the illness. @*Results@#Among the 82 patients participating, 67 (81.7%) completed the 24-week study. The discontinuation rate after switching to LAI aripiprazole did not differ according to clinical characteristics including type of previous antipsychotics. Scores on the PANSS, PSP, SWN-K, CGI, and ERT were significantly improved after a switch to LAI aripiprazole without exacerbation of metabolic parameters and bodyweight. The improvements in the PANSS, PSP, and CGI scores were significantly greater in patients with recent-onset than in those with chronic schizophrenia; the improvement in metabolic parameters was significantly greater in the latter group. @*Conclusion@#High rates of successful switching to LAI aripiprazole from other antipsychotics suggest its good tolerability and effectiveness. Improvements in psychopathology and social functioning were more evident in patients with recent-onset schizophrenia, and improvements in metabolic abnormalities were more prominent in patients with chronic schizophrenia.

Risperidone Induced DNA Methylation Changes in Dopamine Receptor and Stathmin Genes in Mice Exposed to Social Defeat Stress

Objective@#Understanding complex epigenetic mechanisms is necessary to fully elucidate the effects of antipsychotic drug. This study investigated DNA methylation and mRNA expression levels of dopamine D2 and D1 receptor (Drd2 and Drd1, respectively), nuclear receptor subfamily 3, group C, member 1 (Nr3c1) and stathmin 1 (Stmn1) in brain regions of mice exposed to social defeat stress (SDS) and effects of risperidone on altered methylation and mRNA expression levels induced by SDS. @*Methods@#Following SDS for 10 days, risperidone (0.2 mg/kg) or vehicle was administered to adult mice for 7 days. Brain tissues from the prefrontal cortex (PFC), hippocampus (HIP) and amygdala (AMY) were processed to measure methylation and mRNA levels of Drd2, Drd1, Nr3c1 and Stmn1 using pyrosequencing and real time-polymerase chain reaction. @*Results@#We found altered methylation status of Nr3c1 and Stmn1 in the HIP and AMY of mice exposed to SDS. These changes were reversed by risperidone treatment. In addition, different methylation patterns of Drd2 and Drd1 in the PFC and AMY between defeated and control mice were identified with risperidone treatment. @*Conclusion@#These findings suggest that risperidone can cause epigenetic changes in Drd2, Drd1, Nr3c1 and Stmn1 in defeated mice. These changes could be epigenetic mechanisms underlying antipsychotic efficacy.

Impact of Social Defeat Stress on DNA Methylation in Drd2, Nr3c1, and Stmn1 in Wild-type and Stmn1 Knock-out Mice

Objective@#Epigenetic profiles can be modified by stress. Dopamine receptor D2 (Drd2), glucocorticoid receptor gene (Nr3c1) and Stathmin 1 (Stmn1) genes are all implicated in adaptation to stress. The aim of study is to investigate impact of social defeat on DNA methylation in Drd2, Nr3c1, and Stmn1 in wild-type (WT) and Stmn1 knock-out (KO) mice. @*Methods@#The WT and Stmn1 KO mice were subjected to chronic social defeat. Brain tissues of the prefrontal cortex (PFC), amygdala (AMY) and hippocampus (HIP) were obtained. We measured DNA methylation levels of the Drd2, Nr3c1, and Stmn1 genes in the PFC, AMY, and HIP using pyrosequencing. @*Results@#In WT mice, social defeat stress did not induce any changes in Drd2 methylation, whereas significant hypermethylation occurred in Nr3c1 and Stmn1 in the susceptible and unsusceptible groups, respectively, compared to the control group. The methylation responses in the Stmn1 KO mice differed from those seen in the WT mice, such that hypermethylation was evident in all three genes in the susceptible and unsusceptible groups compared to control group. Comparison of the Stmn1 KO and WT mice revealed the same pattern of hypermethylation for all three genes. @*Conclusion@#Social defeat stress induced different epigenetic modifications in three genes among control, unsusceptible, and susceptible groups of WT and Stmn1 KO mice. In particular, hypermethylation of Nr3c1 in the HIP of the susceptible group, and of Stmn1 in the AMY of the unsusceptible group in WT mice, could serve as epigenetic biomarkers of stress susceptibility and stress resilience, respectively.

Development of the Korea-Polyenvironmental Risk Score for Psychosis

Objective@#Comprehensive understanding of polyenvironmental risk factors for the development of psychosis is important. Based on a review of related evidence, we developed the Korea Polyenvironmental Risk Score (K-PERS) for psychosis. We investigated whether the K-PERS can differentiate patients with schizophrenia spectrum disorders (SSDs) from healthy controls (HCs). @*Methods@#We reviewed existing tools for measuring polyenvironmental risk factors for psychosis, including the Maudsley Environmental Risk Score (ERS), polyenviromic risk score (PERS), and Psychosis Polyrisk Score (PPS). Using odds ratios and relative risks for Western studies and the “population proportion” (PP) of risk factors for Korean data, we developed the K-PERS, and compared the scores thereon between patients with SSDs and HCs. In addition, correlation was performed between the K-PERS and Positive and Negative Syndrome Scale (PANSS). @*Results@#We first constructed the “K-PERS-I,” comprising five factors based on the PPS, and then the “K-PERS-II” comprising six factors based on the ERS. The instruments accurately predicted participants’ status (case vs. control). In addition, the K-PERS-I and -II scores exhibited significant negative correlations with the negative symptom factor score of the PANSS. @*Conclusion@#The K-PERS is the first comprehensive tool developed based on PP data obtained from Korean studies that measures polyenvironmental risk factors for psychosis. Using pilot data, the K-PERS predicted patient status (SSD vs. HC). Further research is warranted to examine the relationship of K-PERS scores with clinical outcomes of psychosis and schizophrenia.

A Comparison of Speech Features between Mild Cognitive Impairment and Healthy Aging Groups

Background@#and Purpose: Language dysfunction is a symptom common to patients with Alzheimer's disease (AD). Speech feature analysis may be a patient-friendly screening test for early-stage AD. We aimed to investigate the speech features of amnestic mild cognitive impairment (aMCI) compared to normal controls (NCs). @*Methods@#Spoken responses to test questions were recorded with a microphone placed 15 cm in front of each participant. Speech samples delivered in response to four spoken test prompts (free speech test, Mini-Mental State Examination [MMSE], picture description test, and sentence repetition test) were obtained from 98 patients with aMCI and 139 NCs.Each recording was transcribed, with speech features noted. The frequency of the ten speech features assessed was evaluated to compare speech abilities between the test groups. @*Results@#Among the ten speech features, the frequency of pauses (p=0.001) and mumbles (p=0.001) were significantly higher in patients with aMCI than in NCs. Moreover, MMSE score was found to negatively correlate with the frequency of pauses (r=−0.441, p<0.001) and mumbles (r=−0.341, p<0.001). @*Conclusions@#Frequent pauses and mumbles reflect cognitive decline in aMCI patients in episodic and semantic memory tests. Speech feature analysis may prove to be a speech-based biomarker for screening early-stage cognitive impairment.

Neuronal Signatures of Negative and Positive Schemas towards the Self and Others in Patients with Early Stage Schizophrenia

Objective@#The present study investigated the functional neuroanatomy underlying negative and positive schemas towards the self and others in patients with early stage schizophrenia spectrum disorders (SSDs) using a task-based fMRI procedure. @*Methods@#This study included 50 patients with SSDs and 52 controls. The schema-evoking task consisted of four active conditions and neutral condition. Differences in brain activation were compared between the two groups. Correlation analysis was performed between task-related activation and psychopathology. @*Results@#The SSD patients exhibited higher activity of the left middle and inferior frontal gyri under the negative-others minus neutral contrast as well as greater activation of the left superior and middle frontal gyri and right medial superior frontal gyrus under the positive- self minus neutral and positive-others minus neutral contrasts. Under the positive-others minus neutral contrast, negative correlation was observed between activity of the right inferior parietal gyrus and right angular and total score of the Positive and Negative Syndrome Scale (PANSS), whereas positive correlation between activity of the left middle cingulate gyrus and left/right precuneus and positive-others score of the Brief Core Schema Scales (BCSS). @*Conclusion@#The present findings suggest that the frontal brain regions of SSD patients are more sensitive to negative and positive schemas towards the self and/or others compared to those of controls.

Neuronal Signatures of Negative and Positive Schemas towards the Self and Others in Patients with Early Stage Schizophrenia

Objective@#The present study investigated the functional neuroanatomy underlying negative and positive schemas towards the self and others in patients with early stage schizophrenia spectrum disorders (SSDs) using a task-based fMRI procedure. @*Methods@#This study included 50 patients with SSDs and 52 controls. The schema-evoking task consisted of four active conditions and neutral condition. Differences in brain activation were compared between the two groups. Correlation analysis was performed between task-related activation and psychopathology. @*Results@#The SSD patients exhibited higher activity of the left middle and inferior frontal gyri under the negative-others minus neutral contrast as well as greater activation of the left superior and middle frontal gyri and right medial superior frontal gyrus under the positive- self minus neutral and positive-others minus neutral contrasts. Under the positive-others minus neutral contrast, negative correlation was observed between activity of the right inferior parietal gyrus and right angular and total score of the Positive and Negative Syndrome Scale (PANSS), whereas positive correlation between activity of the left middle cingulate gyrus and left/right precuneus and positive-others score of the Brief Core Schema Scales (BCSS). @*Conclusion@#The present findings suggest that the frontal brain regions of SSD patients are more sensitive to negative and positive schemas towards the self and/or others compared to those of controls.

Differences in Symptoms, Functions, and Their Outcomes According to the Degree of Trauma in Patients with Early Psychosis / 신경정신의학

Methods@#The study involved 226 people who participated in the Korean Early Psychosis Cohort Study, and we divided the participants into two groups according to the degree of trauma.Positive and Negative Syndrome Scale (PANSS) and Social and Occupational Functioning Assessment Scale (SOFAS) were compared at the start of the study and at 12 months after the treatment using paired t-test and repeated measures analysis of variance. @*Results@#At the beginning of the study, there was no significant difference between the two groups. But after 12 months of treatment, the high trauma group showed less improvement in PANSS negative score, general psychopathological score, total score, and SOFAS than the low trauma group. @*Conclusion@#In patients with early psychosis and at least moderate severity of premorbid trauma, negative symptoms, general psychopathological, and social and occupational functional improvements after treatment are less.

Defining Treatment Response, Remission, Relapse, and Recovery in First-Episode Psychosis: A Survey among Korean Experts

Objective@#For the proper treatment of first-episode psychosis, assessment of treatment response, remission, relapse, and recovery is important. Therefore, the present study aimed to develop operational definitions of clinical outcomes in first-episode psychosis. @*Methods@#A questionnaire was developed by a panel of experts and underwent three revisions. The final survey was presented to 150 psychiatrists who were members of the Korean Society for Schizophrenia Research. Respondents selected factors that they believed were important to consider while defining treatment response, remission, relapse, and recovery using a 6-point Likert scale. Selected factors that constituted each definition were statistically extracted, and operational definitions were developed. @*Results@#A total of 91 experts responded to the survey. The extent of reduction in psychopathology, socio-occupational functioning, and duration of each state were the core factors of each definition. Outcomes obtained from discussions and consultations by experts have been summarized and proposed. @*Conclusion@#The criteria developed in this survey tended to be somewhat stricter than those used by other studies. The fundamental reason for this is that this survey focused on first-episode psychosis. A better understanding of each definition in first-episode psychosis is necessary to improve effective treatment outcomes.

Validation of the Korean Version of the 15-Item CommunityAssessment of Psychic Experiences in a College Population

Objective@#To investigate the reliability and validity of the Korean version of the Community Assessment of Psychic Experiences-15item positive scale (CAPE-15) in college students. @*Methods@#This study had two stages: initial screening with self-report questionnaires including the CAPE-15, and semi-structured interviewsto investigate the instrument’s diagnostic validity. The initial screening involved 1,749 college students. The modified Korean versionof Prodromal Questionnaire-16 item (mKPQ-16) was also administered. The criteria for ultra-high risk (UHR) of psychosis in theComprehensive Assessment of At-Risk Mental States (CAARMS) were the gold standard for diagnosis. @*Results@#Twelve of the interviewed subjects met the CAARMS criteria for UHR of psychosis. The area under the receiver operating characteristiccurve was highest (0.936) for the CAPE-15 distress score (p<0.001). The use of 6 as the cutoff for the CAPE-15 distress score resultedin the best balance of sensitivity (91.7%) and specificity (85.2%), with a favorable positive predictive value of 32.4%. The coefficientsof correlation between the CAPE-15 and mKPQ-16 were significant. @*Conclusion@#The Korean version of the CAPE-15 is a good instrument for screening for psychosis risk in collegiate settings. The validationof this scale could contribute to the early identification of psychosis in the Korean community. Psychiatry Investig 2020;17(4):306-311

Network Structures of Social Functioning Domains in Schizophrenia and Bipolar Disorder: A Preliminary Study

Objective@#This study used network analyses to examine network structures reflecting interactions between specific domains of social functioning in schizophrenia (SZ) and bipolar disorder (BD). @*Methods@#We used the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) to assess six domains of social functioning (‘cognition’, ‘mobility’, ‘self-care’, ‘getting along’, ‘life activities’, and ‘participation’) in 143 patients with SZ, 81 patients with BD, and 106 healthy subjects. We constructed regularized partial correlation networks, estimated network centrality and edge strength, tested network stability, and compared SZ and BD network structures. @*Results@#Patients with SZ showed a significantly higher level of functional disability than patients with BD. In the networks we constructed, ‘cognition’ was the most central domain of social functioning in both SZ and BD. The ‘cognition’ domain was primarily associated with the ‘getting along’ domain in the SZ network and the ‘life activities’ domain in the BD network. We found no significant group-level differences in network structures for SZ vs. BD. @*Conclusion@#Our results suggest that cognition may play a pivotal role in social functioning in both SZ and BD. In addition, domains of social functioning in SZ and BD have similar network structures despite the higher level of disability in SZ compared to BD.

Korean Medication Algorithm for Schizophrenia 2019, Second Revision: Treatment of Psychotic Symptoms

Objective@#In 2001, the Korean College of Neuropsychopharmacology and the Korean Society for Schizophrenia Research developed the Korean Medication Algorithm Project for Schizophrenia (KMAP-SPR 2001, revised 2006) through a consensus of expert opinion. The present study was carried out to support the second revision of the KMAP-SPR. @*Methods@#Based on clinical guidelines and studies on the treatment of psychotic symptoms in schizophrenia, the Executive committee completed a draft of KMAP-SPR 2019. To obtain an expert consensus, a Review committee of 100 Korean psychiatrists was formed and 69 responded to a 30-item questionnaire. Based on their responses, the KMAP-SPR 2019 was finalized. @*Results@#The revised schizophrenia algorithm now consists of 5 stages. At Stage 1, monotherapy with atypical antipsychotics was recommended by expert reviewers as the first-line strategy. At Stage 2, most reviewers recommended the use of typical or atypical antipsychotic drugs not used at Stage 1. At Stage 3, many reviewers agreed with the administration of clozapine. At Stage 4, a combination of clozapine and other agents such as antipsychotics, mood stabilizers, antidepressants, or electroconvulsive therapy was recommended. At Stage 5, most reviewers recommended combined treatment with an antipsychotic other than clozapine; and a mood stabilizer, antidepressant, or electroconvulsive therapy. At any stage, prescribing long-acting injectable antipsychotics at the discretion of the clinician was recommended. @*Conclusion@#Compared with previous versions, the KMAP-SPR 2019 now recommends using clozapine earlier in treatment-refractory schizophrenia. In addition, the use of long-acting injectable antipsychotics is now considered to be available at any stage.

Korean Treatment Guideline on Pharmacotherapy of Co-existing Symptoms and Antipsychotics-related Side Effects in Patients with Schizophrenia / 대한정신분열병학회지

OBJECTIVES: The current study covers a secondary revision of the guidelines for the pharmacotherapy of schizophrenia issued by the Korean Medication Algorithm for Schizophrenia (KMAP-SCZ) 2001, specifically for co-existing symptoms and antipsychotics-related side-effects in schizophrenia patients. METHODS: An expert consensus regarding the strategies of pharmacotherapy for positive symptoms of schizophrenia, co-existing symptoms of schizophrenia, and side-effect of antipsychotics in patients with schizophrenia was retrieved by responses obtained using a 30-item questionnaire. RESULTS: For the co-existing symptoms, agitation could be treated with oral or intramuscular injection of benzodiazepine or antipsychotics; depressive symptoms with atypical antipsychotics and adjunctive use of antidepressant; obsessive-compulsive symptoms with selective serotonin reuptake inhibitors and antipsychotics other than clozapine and olanzapine; negative symptoms with atypical antipsychotics or antidepressants; higher risk of suicide with clozapine; comorbid substance abuse with use of naltrexone or bupropion/ varenicline, respectively. For the antipsychotics-related side effects, anticholinergics (extrapyramidal symptom), propranolol and benzodiazepine (akathisia), topiramate or metformin (weight gain), change of antipsychotics to aripiprazole (hyperprolactinemia and prolonged QTc) or clozapine (tardive dyskinesia) could be used. CONCLUSION: Updated pharmacotherapy strategies for co-existing symptoms and antipsychotics-related side effects in schizophrenia patients as presented in KMAP-SCZ 2019 could help effective clinical decision making of psychiatrists as a preferable option.

The Development of the Brooding Scale

OBJECTIVE: The purpose of this study was to develop a Brooding Scale (BS) and to confirm its psychometric properties. METHODS: A preliminary questionnaire was developed based on a literature review and face-to-face interviews with healthy subjects. To evaluate reliability and construct validity, a 15-item BS was administered to 124 healthy subjects. Convergent validity was tested by assessing the relationship between the BS and the Ruminative Response Scale (RRS). Discriminant validity was confirmed in 58 patients with schizophrenia. RESULTS: The internal consistency for the BS was excellent. An exploratory factor analysis yielded two factors: the emotional (six items) and cognitive (five items) domains, which explained 33.83% and 23.69% of the variance, respectively. The BS total score and scores for factors 1 and 2 showed significant positive correlations with the RRS. The total score and sub-factor scores of the BS were significantly higher in patients with schizophrenia than in healthy subjects. CONCLUSION: The BS can be used as a reliable and valid tool to assess brooding in healthy adults. In addition, it had good discriminant validity for patients with schizophrenia.

Neural Signature for Auditory Hallucinations in Schizophrenia: A High-Resolution Positron Emission Tomography Study with Fludeoxyglucose (¹⁸F)

OBJECTIVE: Auditory hallucinations (AHs) are a core symptom of schizophrenia. We investigated the neural signature of AHs by comparing hallucinating patients with schizophrenia with non-hallucinating patients with schizophrenia. METHODS: We recruited hallucinating patients with schizophrenia meeting the criteria for persistent, prominent, and predominant AHs (n=10) and non-hallucinating patients with schizophrenia (n=12). Various clinical assessments were performed incluing Psychotic Symptom Rating Scale for Auditory Hallucinations. Using fludeoxyglucose (¹⁸F) positron emission tomography, regional differences in neural activity between the groups were analyzed. RESULTS: The regions of interest analysis showed significantly lower standardized uptake value ratio (SUVR) in the superior, middle, and inferior frontal gyri, and higher SUVR in the putamen in patients with AHs versus patients without AHs. These findings were confirmed in the voxel-wise analysis. CONCLUSION: Our findings indicate that hypoactivity in the frontal and cingulate gyri, coupled with hyperactivity in the temporal gyrus and putamen, may contribute to the pathophysiology of AHs.

Pharmacotherapeutic Strategies to Prevent Relapse in Schizophrenia / 신경정신의학

Successful treatment is very high in patients with first episode schizophrenia (FES). On the other hand, the problem is a frequent relapse often caused by non-compliance. The non-compliance rate in patients with FES is 40–60% within 1 year. The causes of non-compliance are diverse, such as poor insight, drug side effects, attitude of caregiver, social stigma, etc. Clinicians should be able to provide appropriate psychosocial intervention and long acting injectable antipsychotics (LAI) to overcome non-compliance. Recently, there is solid and accumulating evidence demonstrating superiority of LAI over oral medication in terms of reducing relapse or rehospitalization. In particular, a substantial portion (approximately 30–50%) of patients and caregivers prefer LAI to oral medication. Shared decision-making is the process that clinicians and patients/caregiver should go through in order to obtain the full benefits from LAI.

Comparative Efficacy and Safety of Long-acting Injectable and Oral Second-generation Antipsychotics for the Treatment of Schizophrenia: A Systematic Review and Meta-analysis

We aimed to compare the efficacy and safety of long-acting injectable (LAI) and oral second-generation antipsychotics (SGAs) in treating schizophrenia by performing a systematic review and meta-analysis. MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library, as well as five Korean databases, were systemically searched to identify studies published from 2000 to 16 April 2015, which compared the efficacy and safety of LAI and oral SGAs. Using data from randomized controlled trials (RCTs), meta-analyses were conducted. In addition, the GRADE (the Grading of Recommendations, Assessment, Development and Evaluation) approach was applied to explicitly assess the quality of the evidence. A total of 30 studies including 17 RCTs and 13 observational studies were selected. The group treated with LAI SGAs was characterized by significantly lower relapse rates, longer times to relapse and fewer hospital days, but also by a higher occurrence of extrapyramidal syndrome and prolactin-related symptoms than that in the group treated with oral SGAs. Our findings demonstrate that there is moderate to high level of evidence suggesting that in the treatment of schizophrenia, LAI SGAs have higher efficacy and are associated with higher rates of extrapyramidal syndrome and prolactin-related symptoms. Additionally, the use of LAI SGAs should be combined with appropriate measures to reduce dopamine D2 antagonism-related symptoms.

School Counselors' Recognition of the Ultra-High Risk for Psychosis

The ability to identify students at ultra-high risk (UHR) for psychosis in school settings is crucial for enabling appropriate referral to a clinician and positive therapeutic results. The aim of this study was to examine school counselors' recognition of the diagnosis and appropriate treatment recommendations for students at UHR for psychosis. In total, 132 school counselors completed surveys, including questions relating to a vignette about a student at UHR for psychosis. In total, 12.4% of the sample provided the correct diagnosis, much lower than that for other schizophrenia spectrum disorders and non-psychotic disorders, including depressive disorder. Although most school counselors preferred psychiatrists as the first-line treatment for students at UHR for psychosis, counseling centers were also mentioned as potential treatment options. In terms of medication, antipsychotics were preferred over other medication classes. It is necessary to design appropriate educational and training programs for school counselors to promote identification and effective referral of those at UHR for psychosis.

Validation of the Korean version of the 16-Item Prodromal Questionnaire in a Non-Help-Seeking College Population

OBJECTIVE: To examine the reliability and validity of the Korean version of the 16-item Prodromal Questionnaire (KPQ-16) in non-help-seeking university students. METHODS: Among 2,246 university students participated in the initial screening, 257 subjects with KPQ-16 scores ≥4 were interviewed. The criteria for ultra-high risk (UHR) of psychosis of the Comprehensive Assessment of At-Risk Mental States (CAARMS) were the gold standard for diagnosis. An exploratory modified version of the questionnaire (mKPQ-16), to which three items from the Eppendorf Schizophrenia Inventory were added, was also used to compensate for items on thought and cognitive problems. RESULTS: Seventeen subjects met the CAARMS criteria for UHR of psychosis. The area under the receiver operating characteristic curve (AUROC) was highest for the mKPQ-16 total score (AUROC=0.831, p < 0.001). The use of cutoff total scores of 7 for the mKPQ-16 and 6 for the KPQ-16 resulted in the best balance of sensitivity (76.5% and 64.7%, respectively) and specificity (75.4% and 71.2%, respectively). CONCLUSION: The Korean versions of the PQ-16 are good instruments for screening for psychosis risk in university students. This validation of a questionnaire version with a small number of items may make it feasible to screen large numbers of young adults in the community.

Longer Telomere Length of T lymphocytes in Patients with Early and Chronic Psychosis

OBJECTIVE: To investigate pathological conditions that act as sources of pro-inflammatory cytokines and cytotoxic substances to examine telomere length (TL) in patients with either early (duration of illness [DI] ≤5 years) or chronic (DI >5 years) psychosis using T lymphocytes. METHODS: Based on these factors and the important role that T lymphocytes play in inflammation, the present study measured the TL of T lymphocytes in patients with either early or chronic psychosis. Additionally, smoking, metabolic syndrome, depression, and cognitive functioning were assessed to control for confounding effects. RESULTS: TL was significantly longer in patients with early and chronic psychosis than in healthy control subjects and, moreover, the significance of these findings remained after controlling for age, smoking, metabolic syndrome, DI, chlorpromazine-equivalent dose, and cognitive functioning (F=9.57, degree of freedom=2, p<0.001). Additionally, the DI, chlorpromazine-equivalent doses, and the five-factor scores of the Positive and Negative Syndrome Scale were not significantly correlated with the TL of T lymphocytes in either all patients or each psychosis group. CONCLUSION: Possible mechanisms underlying the effects of antipsychotic medications on telomerase are discussed in the present study, but further studies measuring both telomerase activity and TL using a prospective design will be required.