Yia-Ping Liu

Cigarette smoking in outpatients with chronic schizophrenia in Taiwan: Relationships to socio-demographic and clinical characteristics

In individuals with schizophrenia, the prevalence of cigarette smoking is significantly higher than that of the general population; this appears to be associated with specific psychosocial and clinical characteristics. Indeed, some evidence suggests an increased risk of suicide among smokers with schizophrenia. The purpose of this study was to examine the characteristics of smokers with schizophrenia in Taiwan. In this cross-sectional study, 95 outpatients with DSM-IV diagnosis of schizophrenia were recruited and independently interviewed for nicotine dependency with tobacco use. The effects of cigarette smoking on the various measures, especially suicidality, were investigated. The results revealed that smokers with schizophrenia had higher rates of hospitalization, lifetime suicide attempts, antipsychotic treatment side effects, psychopathology, impulsivity, depression, anxiety, and suicidal risk than non-smokers with schizophrenia. When separate analyses were conducted in male and female patients, depressive symptoms were significant predictors of suicidality among males, whereas heavy smoking, anxious symptoms, and hopelessness were significant predictors among females. From this study, we may gain insights into the role of cigarette smoking in patients of schizophrenia in Taiwan. Furthermore, cigarette smoking may influence aspects of suicidality in schizophrenia.

Suicidal Behavior and Insight into Illness Among Patients with Schizophrenia Spectrum Disorders

The purpose of the present study was to explore the relationship between suicidal behavior and socio-demographic and clinical factors, including insight into illness, in patients with schizophrenia spectrum disorders. We evaluated 104 inpatients using the Self-Appraisal of Illness Questionnaire (SAIQ) for insight assessment, several Beck-related symptoms rating scales, and the Positive and Negative Syndrome Scale (PANSS) for psychopathology. These patients were also evaluated for suicidal behavior and risk using the critical items of the Scale for Suicide Ideation (SSI) and lifetime suicide attempts. Patients with suicidal behavior generally had greater insight into illness than those who were non-suicidal. After controlling for depressive symptoms, the association of insight into illness with current suicidal ideation remained significant, whereas the association between insight and lifetime suicide attempts was no longer significant. As predicted, the regression analyses revealed that those with greater suicide risk had significantly higher levels of depressive symptoms and hopelessness and more lifetime suicide attempts. Moreover, greater insight into illness appeared to have a close, independent connection to suicidal behavior. Our findings suggest that depression, hopelessness, and greater insight into illness are major risk factors for suicide in patients with schizophrenia. It is plausible that depression mediates the relationship between greater insight into illness and suicidal behavior. Aggressive improvement of insight without the risk of deteriorating depressive symptoms may be warranted to reduce the risk of suicide.

Critical period exists in the effects of isolation rearing on sensorimotor gating function but not locomotor activity in rat.

Isolation-reared (IR) rats exhibit various cognitive and behavioral abnormalities in adulthood of which locomotor hyperactivity and impaired prepulse inhibition (PPI) of an acoustic startle reflex are the two cardinal characteristics. Using an amended social deprivation-resocialization paradigm, the present study examined the role of the developmental specificity of the effects of IR and its interaction with the non-competitive NMDA receptor antagonist, MK-801. Locomotor activity and PPI were measured in three groups of adult rats: social control, IR throughout life, and IR for the first two weeks after weaning followed by social housing. MK-801 was injected intraperitoneally (i.p.) 30 min prior to testing at doses of 0, 0.02, 0.1, and 0.2 mg/kg. The results revealed that locomotor activity increased only in rats in the IR throughout life group but not in the other two groups. The impairment of PPI was seen in rats in the IR for the first two weeks and the IR throughout life groups. Furthermore, the effect of MK-801 on PPI was bidirectional in rats of the IR for the first two weeks and IR throughout life groups but not in the social control group. These results suggest that the IR-induced behavioral effects are developed distinctively in terms of the critical period hypothesis, which strengthens the developmental hypothesis of schizophrenic-like dysfunctions.

Assessing cognitive insight in nonpsychiatric individuals and outpatients with schizophrenia in Taiwan: an investigation using the Beck Cognitive Insight Scale

BackgroundThe Beck Cognitive Insight Scale (BCIS) was designed for the assessment of the cognitive processes involved in self-reflection and the ability to modify erroneous beliefs and misinterpretations. Studies investigating the factor structure of the BCIS have indicated a two-factor model in the psychotic population. The factor structure of the BCIS, however, has not received much consideration in the nonpsychiatric population. The present study examined the factor structure and validity of the BCIS and compared its scores between nonpsychiatric individuals and outpatients with psychosis.MethodThe Taiwanese version of the BCIS was administered to 507 nonpsychiatric individuals and 118 outpatients with schizophrenia. The psychometric properties of the BCIS were examined through the following analyses: exploratory and confirmatory factor analyses, reliability, correlation analyses, and discriminative validity.ResultsThe BCIS showed adequate internal consistency and stability over time. Exploratory and confirmatory factor analyses on the 15-item measure indicated a two-factor solution that supported the two dimensions of the Taiwanese BCIS, which was also observed with the original BCIS. Following the construct validation, we obtained a composite index (self-reflectiveness minus self-certainty) of the Taiwanese BCIS that reflected cognitive insight. Consistent with previous studies, our results indicated that psychosis is associated with low self-reflectiveness and high self-certainty, which possibly reflect lower cognitive insight. Our results also showed that better cognitive insight is related to worse depression in patients with schizophrenia spectrum disorders, but not in nonpsychiatric individuals. The receiver operating characteristic (ROC) analyses revealed that the area under the curve (AUC) was 0.731. A composite index of 3 was a good limit, with a sensitivity of 87% and a specificity of 51%.ConclusionThe BCIS proved to be useful for measuring cognitive insight in Taiwanese nonpsychiatric and psychotic populations.

Subjective quality of life and suicidal behavior among Taiwanese schizophrenia patients

PurposeResearch of suicidal behavior in individuals with schizophrenia has often suggested that clinical characteristics and symptoms likely influence a patient’s suicidal risk. However, there is a lack of research describing the link between patients’ subjective quality of life (SQOL) and suicidal behavior in non-Western countries. Therefore, the current study attempts to explore how schizophrenia patients’ SQOL and their suicidal behavior are related in a Taiwanese sample.MethodsIn this study, 102 schizophrenia outpatients were investigated using the Taiwanese World Health Organization Quality of Life Schedule-Brief Version (WHO-QOL-BREF-TW), several Beck-Related symptom rating scales, and the Positive and Negative Syndrome Scale (PANSS) for psychopathology. These patients were also evaluated for suicidal risk using the critical items of the Scale for Suicide Ideation (SSI) and lifetime suicide attempts.ResultsStatistical analyses, including independent sample t tests, analysis of covariance (ANCOVA) and logistic stepwise regression models were completed. Compared with the non-suicidal group, suicidal patients had significantly lower scores in SQOL domains. The differences in social domain remained significant after adjusting for depressive symptoms. In multiple logistic regression analyses, level of depressive and psychotic symptoms increased and poor social and psychological SQOL were significant contributors to suicidal behavior. Having removed depressive symptoms from the model, only dissatisfaction with social SQOL was associated with heightened suicidal risk.ConclusionsSchizophrenia is associated with a high suicidal risk, of which depressive and psychotic symptoms are the major correlates. Again, the present study confirms and extends previous research showing that dissatisfied SQOL, particularly dissatisfaction with social relationships, should be considered in the assessment of suicidal risk in outpatients with schizophrenia, even when accounting other possible confounding factor such as depression.

Beck Hopelessness Scale: Exploring its Dimensionality in Patients with Schizophrenia

Hopelessness is a pre-eminent risk factor for suicide and non-fatal self-harm. Although the Beck Hopelessness Scale is often used for schizophrenia, its factor structure has been given relatively little consideration in this context. This study aimed to examine the reliability and validity of the Taiwanese version of the Beck Hopelessness Scale (BHS-T) in a chronic schizophrenia out-patient sample. One hundred and two (102) outpatients were evaluated using the translated Taiwanese version of the BHS (BHS-T), as well as several Beck-related symptom rating scales and the Positive and Negative Syndrome Scale (PANSS) for psycho-pathology. The patients were also evaluated for suicidal intent using the critical items of the Scale for Suicide Ideation (SSI) and suicide attempts. The psychometric properties of the BHS-T were also evaluated, including construct validity, internal consistency, test–retest reliability, convergence, and discriminative validity. The BHS-T showed good overall reliability and stability over time. This translated scale comprised a two-factor solution corresponding negative expectation and loss of motivation dimensions. Differences in mean hopelessness scores between participants with and without suicidal intent were significant. The results also indicated that, among individuals with schizophrenia, “negative expectation in the future” is more closely linked to suicide intent than “loss of motivation for the future”. The BHS-T is a reliable and valid instrument for measuring the multi-dimensionality of hopelessness and may complement clinical suicidal risk assessments in individuals with schizophrenia.

Traumatic stress causes distinctive effects on fear circuit catecholamines and the fear extinction profile in a rodent model of posttraumatic stress disorder

Central catecholamines regulate fear memory across the medial prefrontal cortex (mPFC), amygdala (AMYG), and hippocampus (HPC). However, inadequate evidence exists to address the relationships among these fear circuit areas in terms of the fear symptoms of posttraumatic stress disorder (PTSD). By examining the behavioral profile in a Pavlovian fear conditioning paradigm together with tissue/efflux levels of dopamine (DA) and norepinephrine (NE) and their reuptake abilities across the fear circuit areas in rats that experienced single prolonged stress (SPS, a rodent model of PTSD), we demonstrated that SPS-impaired extinction retrieval was concomitant with the changes of central DA/NE in a dissociable manner. For tissue levels, diminished DA and increased NE were both observed in the mPFC and AMYG. DA efflux and synaptosomal DA transporter were consistently reduced in the AMYG/vHPC, whereas SPS reduced NE efflux in the infralimbic cortex and synaptosomal NE transporter in the mPFC. Furthermore, a lower expression of synaptosomal VMAT2 was observed in the mPFC, AMYG, and vHPC after SPS. Finally, negative correlations were observed between retrieval freezing and DA in the mPFC/AMYG; nevertheless, the phenomena became invalid after SPS. Our results suggest that central catecholamines are crucially involved in the retrieval of fear extinction in which DA and NE play distinctive roles across the fear circuit areas.

Effects of SPAK knockout on sensorimotor gating, novelty exploration, and brain area-dependent expressions of NKCC1 and KCC2 in a mouse model of schizophrenia

SPAK (Sterile 20/SPS1-related proline/alanine-rich kinase) is a protein kinase belonging to the mitogen-activated protein kinase (MAPK) superfamily that has been found to be extensively distributed across the body. The SPAK downstream substrates NKCC1 and KCC2 in the central nervous system are important in the interpretation of developmental mental disorders. The present study aimed to clarify the role of SPAK-NKCC1/KCC2 using a rodent schizophrenia-like model. The mouse paradigm of isolation rearing (IR) was employed, as it simulates the sensorimotor gating abnormalities of schizophrenia. SPAK transgenic mice were used and were divided into four groups: social-wild type, social-SPAK(-/-), isolation-wild type, and isolation-SPAK(-/-). The prepulse inhibition (PPI) test and the novel object recognition test (NORT) were used to measure schizophrenia-associated dysfunctions in gating ability and the novelty recognition, respectively. Finally, the protein expressions of NKCC1/KCC2 in the prefrontal cortex and hippocampus were detected to determine correlations with the behavioral data. Our results demonstrated that SPAK-null mice had superior PPI and novelty recognition relative to wild type controls, with a concomitant increase in KCC2 in the prefrontal cortex. IR disrupted PPI and NORT performances with an associated increase in KCC2. Furthermore, rearing environment and gene manipulation had mutually interactive effects, as the IR-induced effects on PPI and NORT were reversed by SPAK knockout, and the increase in KCC2 and the decreased in the NKCC1/KCC2 ratio in the prefrontal cortex induced by SPAK knockout were reversed by IR. Our data supported the gene-environment hypothesis and demonstrated the potential value of SPAK manipulation in future schizophrenia studies.

Effects of atomoxetine on attention and impulsivity in the five-choice serial reaction time task in rats with lesions of dorsal noradrenergic ascending bundle.

Atomoxetine, a noradrenaline reuptake inhibitor (NRI), which is a non-stimulating medicine that is used for the treatment of patients with attention deficit hyperactivity disorder (ADHD), has been found to be effective in reducing behavioral impulsivity in rodents, but its efficacy in a dorsal noradrenergic ascending bundle (DNAB)-lesioned condition has not been examined. The present study aimed to investigate the effects of DNAB lesions on attention and impulsive control in the five-choice serial reaction time task (5-CSRTT) in rats treated with atomoxetine. The drug-induced changes in noradrenaline efflux in the medial prefrontal cortex were also measured. 5-CSRTT-trained rats were included in one of the following groups: N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)/Atomoxetine, Sham/Atomoxetine, DSP-4/Saline, or Sham/Saline. Acute atomoxetine (0.3 mg/kg) was administered 14 days after the DSP-4 regime. The behavioral testing included manipulations of the inter-trial interval (ITI), stimulation duration and food satiety. In vivo microdialysis of the noradrenaline efflux in the medial prefrontal cortex and the expression of the noradrenaline transporter (NAT) in the DNAB areas were examined. Atomoxetine reduced impulsivity and perseveration in the long-ITI condition with no effects on any other variables. This phenomenon was not influenced by DSP-4 pre-treatment. The DNAB-lesioned rats had lower noradrenaline efflux in the medial prefrontal cortex. DSP-4 caused no change in NAT expression in the DNAB areas. These findings suggested that noradrenaline reuptake may not be exclusively responsible for the atomoxetine effects in adjusting impulsivity. The role of DNAB should also be considered, particularly in conditions requiring greater behavioral inhibition.

Relationships of perceived public stigma of mental illness and psychosis-like experiences in a non-clinical population sample

PurposeStudies on the association between psychopathology, perceived public stigma, and labeling in mental illness have focused primarily on severe but rare mental disorders, especially schizophrenia, or other clinically defined psychotic disorders. Although evidence is mounting that psychosis-like experiences show high prevalence in the general population and lead to an increased risk of psychotic disorders, little is known about how psychosis-like experiences independently affect perceived public stigma in the non-clinical population. The aim of the present study was to examine the relationship between psychosis-like experiences and perceived public stigma in a non-clinical sample.MethodsFor this cross-sectional study, we recruited 524 individuals (239 male, 285 female) who had no lifetime history of psychiatric disorder. Participants completed questionnaires that asked for sociodemographic and clinical information, a measure of perceived public stigma (Perceived Psychiatric Stigma Scale [PPSS]), and two measures of psychosis-like experiences (Peters et al. Delusions Inventory [PDI]; Cardiff Anomalous Perceptions Scale [CAPS]).ResultsOf the sociodemographic characteristics analyzed in this study—gender, age, education level, marital status, and religion—only age simultaneously influenced PPSS, PDI, and CAPS scores. As hypothesized, perceived public stigma was positively correlated with measures of psychosis-like experiences, even after controlling for age. Furthermore, the perceived stigma was more strongly associated with delusion proneness than with anomalous perceptual experiences.ConclusionThe association between psychopathology and perceived public stigma appears to extend beyond clinically defined psychosis to more common psychosis-like experiences in a sample drawn from the general Han Chinese population.