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

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

Effects of paliperidone extended release on the symptoms and functioning of schizophrenia.

BACKGROUND: We aimed to explore relations between symptomatic remission and functionality evaluation in schizophrenia patients treated with paliperidone extended-release (ER), as seen in a normal day-to-day practice, using flexible dosing regimens of paliperidone ER. We explored symptomatic remission rate in patients treated with flexibly dosed paliperidone ER by 8 items of Positive and Negative Syndrome Scale (PANSS) and change of Personal and Social Performance (PSP) scale. METHOD: This was a 12-week multicenter, open-label, prospective clinical study conducted in in-patient and out-patient populations. Flexible dosing in the range 3-12 mg/day was used throughout the study. All subjects attended clinic visits on weeks 0, 4, 8, and 12 as usual clinical practice for the 12-week observation period. Data were summarized with respect to demographic and baseline characteristics, efficacy measurement with PANSS scale, PSP, and social functioning score, and safety observations. Descriptive statistics were performed to identify the retention rate at each visit as well as the symptomatic remission rate. Summary statistics of average doses the subjects received were based on all subjects participating in the study. RESULTS: A total of 480 patients were enrolled. Among them, 426 patients (88.8%) had evaluation at week 4 and 350 (72.9%) completed the 12-week evaluation. Patients with at least moderate severity of schizophrenia were evaluated as "mild" or better on PANSS scale by all 8 items after 12 weeks of treatment with paliperidone ER. There was significant improvement in patients' functionality as measured by PSP improvement and score changes. Concerning the other efficacy parameters, PANSS total scale, PSP total scale, and social functioning total scale at the end of study all indicated statistically significant improvement by comparison with baseline. The safety profile also demonstrated that paliperidone ER was well-tolerated without clinically significant changes after treatment administration. CONCLUSIONS: Although the short-term nature of this study may limit the potential for assessing improvements in function, it is noteworthy that in the present short-term study significant improvements in patient personal and social functioning with paliperidone ER treatment were observed, as assessed by PSP scale. TRIAL REGISTRATION: Clinical Trials. PAL-TWN-MA3.

The long-term effects of psychotherapy added to pharmacotherapy on morning to evening diurnal cortisol patterns in outpatients with major depression.

BACKGROUND: Psychotherapy added to pharmacotherapy results in greater improvement in clinical outcomes than does pharmacotherapy alone. However, few studies examined how psychotherapy coupled with pharmacotherapy could produce a long-term protective effect by improving the psychobiological stress response. METHODS: The researchers recruited 63 subjects with major depressive disorder (MDD) in an outpatient department of psychiatry at a general hospital. The randomly assigned subjects formed 2 groups: 29 in combined therapy (COMB) and 34 in monotherapy (MT). The COMB included 8 weekly body-mind-spirit group psychotherapy sessions added to pharmacotherapy. MT consisted of pharmacotherapy only. The outcome measures, collected at the subjects' homes, included the Beck Depression Inventory II (BDI-II), the State Trait Anxiety Inventory (STAI) and salivary cortisol on awakening, 45 min after awakening, and at 12.00, 17.00 and 21.00 h. Evaluation of outcome measures was at baseline condition, and at months 2 (end of additional psychotherapy), 5 and 8. RESULTS: While the decreases in symptoms of depression were similar between COMB and MT (p > 0.05), the reductions in anxiety state were greater in COMB than in MT during the 8-month follow-up (p < 0.05). A steeper diurnal cortisol pattern more likely occurred in COMB than in MT in the 3 follow-up periods (p < 0.05, p <0.001 and p < 0.01). CONCLUSIONS: The superior outcomes of group psychotherapy added to pharmacotherapy for MDD outpatients could relate to decreasing the anxiety state and to producing long-term impacts on positive stress endocrine outcomes seen as a steeper diurnal cortisol pattern.

Psychometric validation of the S-QoL Chinese (Taiwan) version for patients with schizophrenia.

We translated the S-QoL into the Chinese (Taiwan) language and evaluated the score distributions of the translated S-QoL in terms of ceiling/floor effect, internal consistency, test-retest reliability, and convergent and discriminant validity. To ensure conceptual and semantic equivalence of the S-QoL, the researchers performed both forward translation and back translation, consulted professionals, and completed a pilot trial on college students. Forty-one patients with schizophrenia were recruited. No significant ceiling/floor effects (<20%) were found in subscales of the translated S-QoL. The internal consistency reliabilities were acceptable to good for the whole scale and 7 of the subscales (Cronbach's alpha = 0.71-0.93), but not for the sentimental life subscale (Cronbach's alpha = 0.44). The test-retest reliabilities were moderate to high (ICC = 0.64-87, P < 0.001 to <0.0001). The convergent validities were supported by satisfactory correlations among subscales measuring related constructs of the translated S-QoL and those of the SQLS-R4, WHOQoL-BREF, and RESE (r = 0.36-0.82, P < 0.05 to <0.01). Discriminant validity was demonstrated between groups with different numbers of episodes and hospitalization. The S-QoL Chinese (Taiwan) version was found to have good psychometrics and is suggested as a feasible choice of disease-specific measure for capturing HRQoL in patients with schizophrenia.

The effects of gender and a co-occurring depressive disorder on neurocognitive functioning in patients with alcohol dependence.

AIMS: The present study aims to examine neuropsychological impairments by comorbidity and gender among patients with alcohol dependence. METHODS: The study sample is comprised of 123 subjects who fulfilled a Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-IV) diagnosis of alcohol dependence from January 2006 to December 2007. Subjects were asked to complete the following psychological tests: the Barratt Impulsivity Scale (BIS), Wechsler Adult Intelligence Scale, Wechsler Memory Scale and Color Trails Test. We compared the results of neuropsychological assessments based on two types of classifications: people with comorbid depression and people without comorbidity; females and males. RESULTS: The immediate visual memory and the BIS scores in patients with comorbid depression were significantly different from the scores in patients without comorbidity. In addition, females performed significantly poorer on the Working Memory Index than males and had a later age of regular drinking. CONCLUSIONS: Further investigation of the mechanism associated with the gender difference on cognition and exploration of the temporal relationship between alcohol dependence and depressive disorder on the cognitive aspect is needed.

Facilitation of glutamate release from rat cerebrocortical glutamatergic nerve terminals (synaptosomes) by phosphatidylserine and phosphatidylcholine.

Phosphatidylserine (PS) and phosphatidylcholine (PC) have been shown to enhance cognitive function. Considering that brain glutamatergic system is thought to participate in cognitive processing, our objective was to determine the effect of PS and PC on glutamate release from the nerve terminal (synaptosome) freshly isolated from rat cerebral cortex. Data showed that both PS and PC potently facilitate 4-aminopyridine (4-AP)-evoked Ca(2+)-dependent and Ca(2+)-independent glutamate release. Facilitation of glutamate release by PS or PC was associated with an increase of 4-AP-evoked depolarization and downstream elevation of cytoplasmic free calcium concentration ([Ca(2+)](c)). In addition, glutamate release elicited by direct Ca(2+)-entry with Ca(2+)-ionophore (ionomycin) was also facilitated by PS or PC. Furthermore, PS- or PC-mediated facilitation of 4-AP-evoked glutamate release was superseded or suppressed by protein kinase C (PKC) activator and inhibitor, respectively. Together, these results suggest that PS or PC effects a facilitation of glutamate exocytosis by increasing nerve terminal excitability and Ca(2+) influx into cerebrocortical nerve terminals through a signaling cascade involving PKC.

The effect of psychotherapy added to pharmacotherapy on cortisol responses in outpatients with major depressive disorder.

The present study examined the changes of depressive symptoms and salivary cortisol responses in 36 outpatients with major depression. These patients were randomly assigned to receive combination therapy (CT), consisting of antidepressants and body-mind-spirit group psychotherapy, or monotherapy (MT), consisting of antidepressants only. The results indicated that CT and MT had similar effects on reducing depressive symptoms. Nevertheless, the results revealed that cortisol levels at night appeared to have a greater reduction in CT than in MT, indicating a downward trend in CT but an upward trend in MT. Moreover, a steeper diurnal pattern of cortisol-a larger deviation in cortisol levels between 30 and 45 minutes postwaking and evening-was more likely associated with CT than MT. The findings suggest that CT produced a protective effect on outpatients with major depression, preventing the increased night salivary cortisol levels and the flatter diurnal cortisol pattern that tended to occur in MT.

Facilitatory effect of glutamate exocytosis from rat cerebrocortical nerve terminals by alpha-tocopherol, a major vitamin E component.

The effect of alpha-tocopherol, the major vitamin E component, on the release of endogenous glutamate has been investigated using rat cerebrocortical nerve terminals. Results showed that alpha-tocopherol facilitated the Ca2+-dependent but not the Ca2+-independent glutamate release evoked by 4-aminopyridine (4AP). This release facilitation was insensitive to glutamate transporter inhibitor L-trans-PDC or DL-TBOA, and blocked by the exocytotic neurotransmitter release inhibitor tetanus neurotoxin, indicating that alpha-tocopherol affects specifically the physiological exocytotic vesicular release without affecting the non-vesicular release. Facilitation of glutamate exocytosis by alpha-tocopherol was not due to its increasing synaptosomal excitability, because alpha-tocopherol did not alter the 4AP-evoked depolarization of the synaptosomal plasma membrane potential. Rather, examination of the effect of alpha-tocopherol on cytoplasmic free Ca2+ concentration revealed that the facilitation of glutamate release could be attributed to an increase in voltage-dependent Ca2+ influx. Consistent with this, the alpha-tocopherol-mediated facilitation of glutamate release was significantly reduced in synaptosomes pretreated with omega-CgTX MVIIC, a wide spectrum blocker of N- and P/Q-type Ca2+ channels. In addition, alpha-tocopherol modulation of glutamate release appeared to involve a protein kinase C (PKC) signalling cascade, insofar as pretreatment of synaptosomes with the PKC inhibitor GF109203X effectively suppressed the facilitatory effect of alpha-tocopherol on 4AP- or ionomycin-evoked glutamate release. Furthermore, alpha-tocopherol increased the phosphorylation of MARCKS, the major presynapic substrate for PKC, and this effect was also significantly attenuated by PKC inhibition. Together, these results suggest that alpha-tocopherol exerts an increase in PKC activation, which subsequently enhances voltage-dependent Ca2+ influx and vesicular release machinery to cause an increase in evoked glutamate release from rat cerebrocortical glutamatergic terminals. This finding might provide important information regarding to the action of vitamin E in the central nervous system.

Aripiprazole and its human metabolite OPC14857 reduce, through a presynaptic mechanism, glutamate release in rat prefrontal cortex: possible relevance to neuroprotective interventions in schizophrenia.

Aripiprazole is a novel atypical antipsychotic drug with neuroprotective properties. As excessive glutamate release is now considered to be part of the pathophysiology of schizophrenia, the objective of this study was to use an in vitro assay system to investigate the effect of aripiprazole and its human metabolite OPC14857 on the release of endogenous glutamate from isolated nerve terminals (synaptosomes), freshly prepared from rat prefrontal cortex. Both aripiprazole and OPC13857 potently inhibited 4-aminopyridine (4-AP)-evoked glutamate release in a concentration-dependent manner. Inhibition of glutamate release by aripiprazole and OPC13857 was associated with a reduction of 4AP-evoked Na+ influx and depolarization, as well as downstream elevation of cytoplasmic free calcium concentration mediated via N- and P/Q-type voltage-dependent Ca2+ channels (VDCCs). Release induced by direct Ca2+ entry with Ca2+ ionophore (ionomycin) was unaffected by aripiprazole or OPC13857, indicating that the inhibitory effect of aripiprazole or OPC13857 is not due to directly interfering with the release process at some point subsequent to Ca2+ influx. In addition, the dopamine D2 receptor antagonist haloperidol and the 5-HT 1A receptor antagonist WAY100635 all effectively blocked the aripiprazole or OPC13857-mediated inhibition of 4-AP-evoked glutamate release. Moreover, aripiprazole or OPC13857 modulation of 4-AP-evoked glutamate release appears to involve a protein kinase A (PKA) signaling cascade, insofar as pretreatment of synaptosomes with the PKA inhibitor H89 suppressed the inhibitory effect of aripiprazole or OPC13857. Together, these results suggest that aripiprazole and its human metabolite OPC14857 inhibit glutamate release from rat prefrontocortical nerve terminals, likely by the activation of dopamine D2 and 5-HT 1A receptors, which subsequently results in the reduction of nerve terminal excitability and downstream VDCC activation through a signaling cascade involving PKA. These actions of aripiprazole may contribute to its neuroprotective effect in excitotoxic injury.

Heart rate variability and daytime functioning in insomniacs and normal sleepers: preliminary results.

OBJECTIVES: This study examined the differences in heart rate variability (HRV) and daytime functioning between insomniacs and normal sleepers. METHODS: All participants underwent an interview, a medical examination, and a sleep measurement protocol during which they wore an actigraph and logged a sleep diary for a 7-day period to verify their eligibility. Included in the study were 18 insomniacs and 21 normal sleepers. During a laboratory session, these participants completed four paper-pencil tests of sleepiness, anxiety, fatigue, and concentration difficulty and the Wisconsin Card Sorting Test. Resting HRV was recorded under paced breathing. RESULTS: Neither did insomniacs experience cognitive impairment nor did they experience excessive daytime sleepiness compared with normal sleepers. However, insomniacs experienced higher frequency of fatigue [effect size (ES)=1.14, P=.002] compared with normal sleepers. There was also a trend toward higher trait anxiety score (ES=0.62) and concentration difficulty (ES=0.59) in insomniacs than in normal sleepers. Although a tendency toward lower resting high- frequency (HF) HRV (ES=-0.57) in insomniacs than in normal sleepers was noted, neither the resting low-frequency (LF) HRV nor the LF/HF ratio were different between groups. Subjective sleep estimates correlated to self-reported daytime consequences such as fatigue and concentration difficulty but not cognitive function. On the contrary, objective sleep estimates correlated to problem-solving/conceptualization and learning but not self-reported daytime consequences. CONCLUSIONS: Insomniacs are not sleepier during the day than normal sleepers. However, they may experience such a daytime symptom as fatigue although cognitive function remains unimpaired.

Leptin and cholesterol levels are low in major depressive disorder, but high in schizophrenia.

BACKGROUND: Appetite, food intake and weight are frequently altered in psychiatric disorders such as major depression and schizophrenia. Leptin is an adipocyte hormone, as the product of the ob gene, regulating food intake and energy balance providing the hypothalamus with information on the amount of body fat. Leptin seems to be strongly associated with lipid metabolism. Moreover, leptin is involved in the control of other behaviors and in brain development. There are few studies about the amounts of plasma leptin in mood disorder and schizophrenia with inconsistent findings. The relationship between leptin and major depressive disorder is still unknown. We planned to investigate the relationship of the serum leptin concentration, cholesterol, and BMI between patients with major depressive disorder, schizophrenic patients and healthy control subjects. METHODS: In the present study, the BMI, plasma cholesterol and leptin levels, BDI, and BPRS were compared in 69 patients with major depressive disorder, 78 schizophrenic patients, and 51 healthy controls. RESULTS: The major findings of our study included (1) leptin and cholesterol levels were low in patients with major depressive disorder, but high in schizophrenic patients; (2) negative correlations between BDI scores and serum cholesterol or leptin levels in the patients with major depressive disorder; (3) an inconsistently positive correlation between mean leptin levels, cholesterol, and BMI among different groups; (4) positive correlations between serum cholesterol or leptin levels and the length of illness in the schizophrenic patients. CONCLUSIONS: In this study, our results indicate that that leptin and cholesterol might play differently important pathophysiological roles in these psychiatric disorders.

Role of central glutamatergic neurotransmission in the pathogenesis of psychiatric and behavioral disorders.

Glutamate is the most ubiquitous of the fast excitatory neurotransmitters in the central nervous system. In the process, glutamate fulfills numerous physiological functions, but also plays an important role in the pathophysiology of a variety of psychiatric and behavioral disorders such as schizophrenia. Recently, modulation of glutamatergic neurotransmission has been suggested to be involved in the mechanisms of action of antipsychotic drugs. Thus, pharmacological manipulation of glutamatergic transmission may be a feasible therapeutic strategy for treatment of schizophrenia. In this review article, we focus on the role of central glutamatergic neurotransmission in the pathogenesis and pharmacotherapy of schizophrenia and the development of new drugs targeting glutamate brain systems.

Psychometric validations and comparisons of schizophrenia-specific health-related quality of life measures.

To compare schizophrenia-specific quality of life measures, this study examined an 18-item Chinese version of 41-item Quality of Life Questionnaire in Schizophrenia (S-QoL; S-QoL-18-C) using 41 patients. The S-QoL-18-C was validated and compared with Schizophrenia Quality of Life Scale-Revision 4 (SQLS-R4). Index scores of S-QoL-18-C showed nearly identical psychometrics to S-QoL-C and S-QoL-18. No significant ceiling/floor effects were found, except with psychological and selfesteem subscales. Internal consistency was acceptable for whole scale and all subscales, except family relationships and sentimental life. Test-retest reliability was moderate to high (ICC=0.58-87). Score distributions and reliability of S-QoL-18-C were slightly lower than those of S-QoL-C. Convergent validity was supported by satisfactory correlations between subscales/index scores of S-QoL-18-C and similar scales (r=∣-0.35 ∣ to 0.80) and between corresponding subscales in S-QoL-18-C and S-QoL-C (r=0.85-0.97). S-QoL-18-C and SQLS-R4 demonstrated discriminant validity by differentiating among 30 patients with symptom remission, 30 patients without symptom remission, and 30 healthy individuals. Two patient groups were classified by criteria proposed by Remission in Schizophrenia Working Group. Three groups were controlled for five factors. Furthermore SQLS-R4, but not S-QoL-18-C, differentiated between patient groups with different hospitalization frequencies. Overall, S-QoL-18-C and SQLS-R4 show different advantages psychometrically.

Determinants of subjective health-related quality of life (HRQoL) for patients with schizophrenia.

PURPOSE: To identify the determinants of schizophrenia-specific HRQoL levels, five types of factors (i.e., sociodemographic, clinical, psychopathological, neurocognitive, and psychosocial factors) were simultaneously investigated in the same cross-sectional sample. METHODS: A total of 120 patients with a diagnosis of schizophrenia but not spectrum conditions were recruited by convenience sampling. Subjective HRQoL levels were measured using the disease-specific S-QoL-C. After sociodemographic and clinical data were collected, psychopathological data were self-rated with the Beck Depression Inventory-II (BDI-II) and were assessed with the Positive and Negative Syndrome Scale (PANSS) by professionally trained raters. Two neurocognitive assessments were conducted by licensed occupational therapists (OTs). Psychosocial factors were assessed using self-reports measures, including the, General Self-Efficacy Scale (GSES), Rosenberg Self-Esteem Scale (RSES), and Social Impact Scale (SIS). All measures were administered in random order. OTs, PANSS raters, and participants were blinded to score computation, and multiple hierarchical regression with the stepwise method was conducted. RESULTS: The S-QoL-C scores were most strongly affected by psychosocial factors and the psychopathological factors, followed by clinical and sociodemographic factors. Total scores on the BDI-II had the largest contributions to S-QoL-C index scores and seven of eight S-QoL-C subscales. In addition, the GSES, RSES, and SIS showed effects across the S-QoL-C subscales. The BDI-II, GSES, and RSES all influenced the S-QoL-C index scores, in addition to the number of hospitalizations. CONCLUSION: Psychosocial factors and psychopathological factors measured by the BDI-II had the greatest impact on schizophrenia-specific HRQoL levels. Psychiatric treatment programs focusing on psychosocial status and depressive symptoms can improve schizophrenia-specific HRQoL levels.

Efficacy of psychotherapy on diurnal cortisol patterns and suicidal ideation in adjustment disorder with depressed mood.

AIMS: The aims were to examine the effects of psychotherapy on depressive and anxiety symptoms, the occurrence of suicidal ideations and diurnal cortisol patterns in patients with adjustment disorder (AD) with depressed mood. METHODS: Participants recruited from an outpatient department of psychiatry at a general hospital were randomly assigned to one of two groups: 34 in psychotherapy group and 37 in control group. The control group consisted of one-session psychoeducation. Psychotherapy included the eight-weekly body-mind-spirit (BMS) group psychotherapy. Measures included Beck Depression Inventory-II and State Trait Anxiety Inventory. Salivary cortisol samples were collected from the patients at their homes on awakening; 30 and 45 min after awakening; and at 1200, 1700 and 2100 h. Measurements were taken at baseline and at months 2 (end of intervention), 5, 8 and 14. RESULTS: There was no differential change over time between the BMS and control groups in self-reported depression or anxiety symptoms. However, suicidal ideation appeared to be reduced in the psychotherapy group. Changes in diurnal cortisol patterns were also significantly different in group × time interactions, in favor of BMS group. CONCLUSIONS: Psychotherapy likely provides improvements in psychobiological stress responses and decreases the occurrence of suicidal ideation in patients with AD.

An early improvement in depressive symptoms predicts symptomatic remission of schizophrenia treated with quetiapine: a multicenter, 4-week case-control study.

The aim of this study was to determine whether an early improvement in depressive symptoms is a predictor of symptomatic remission in schizophrenia. Patients with DSM-IV schizophrenia diagnosis who received antipsychotic treatment but did not fulfill Andreasen's symptomatic remission criteria were recruited. Each patient received quetiapine with a flexible dose strategy of 300-800 mg daily for 4 weeks after a 1-week washout period of previous antipsychotics. Remission was defined by Andreasen's criteria, which includes eight items of the Positive and Negative Symptom Scale with scores of less than three in each item. Seventy-five patients completed the study. Of these, 27 (36%) achieved symptomatic remission after treatment with quetiapine. A significant improvement in depressive symptoms was found in both the remission and the nonremission groups, although the improvement was less pronounced in the nonremission group at the endpoint. Binary logistic regression analysis showed that age (ß=-0.07, P=0.02) and early improvement in depressive symptoms within the first 3 days were predictive of symptomatic remission (ß=-0.27, P=0.01) for the treatment of schizophrenia. Our data suggest that an early improvement in depressive symptoms in the treatment of schizophrenia is crucial for symptomatic remission.

The interaction effect between low income and severe illness on the risk of death by suicide after self-harm.

BACKGROUND: Previous Western studies have reported that the prevalence of death by suicide within 1 year after self-harm was 0.5-2%; however, no studies have focused on the Far East. AIMS: To calculate the prevalence of death by suicide after self-harm over different lengths of follow-up time and to determine the predictors of death by suicide after self-harm. METHOD: Our study was based on 3,388 inpatients hospitalized between 2000 and 2007 in any of the 1,230 hospitals in Taiwan. Death by suicide after self-harm among the members of this cohort was tracked after 3 months, 6 months, and 1-8 years. The tracking continued until December 31, 2008. We analyzed the prevalence and risk factors of death by suicide after self-harm using Cox's regression model. RESULTS: Of the 3,388 individuals with a history of self-harm included in the study, 48 (1.4%) died by suicide after self-harm within 3 months and 97 (2.9%) within 1 year. In all, 144 (4.3%) died by suicide after self-harm within 8 years. The predictors of death by suicide were violent methods (such as hanging, drowning, firearms, and jumping), low income, and severe illness. Moreover, an interaction effect was noted between low income and severe illness on the outcome (death by suicide). CONCLUSION: It seems that effective healthcare for individuals who engage in self-harming behavior would benefit from supplementing medical care with social assistance, such as the support of a social worker.

The self-perceived symptom distress and health-related conditions associated with morning to evening diurnal cortisol patterns in outpatients with major depressive disorder.

OBJECTIVE: This study was an examination of 126 major depressive disorder (MDD) outpatients' morning to evening diurnal cortisol patterns to determine their association with family histories of mental illness, self-perceived depressive and anxiety distress, self-perceived health-related conditions, and healthy behaviors. METHODS: 126 MDD outpatients and 106 healthy subjects were recruited. Self-reports of symptom distress, health-related conditions, and healthy behaviors and objective measures of salivary cortisol upon awakening, 45min after awakening, and at 1200, 1700, and 2100h were collected at subjects' homes. The individual growth curve model was used to manage data and to analyze repeated observations of self-report data associated with diurnal cortisol patterns. RESULTS: For MDD outpatients, flatter diurnal cortisol patterns were more likely found in subjects with family histories of mental illness than in those without. Patient-reported shorter total sleep hours, more severe levels of depression and higher suffering levels were positively associated with flatter diurnal cortisol patterns. Less than 5 sleep hours was more likely associated with flatter diurnal cortisol patterns than above 7 sleep hours. Severe levels of depression were more likely related to flatter diurnal cortisol patterns than moderate and mild levels of depression. Higher anxiety levels, better sleep quality and higher levels of physical activity reported by patients were positively associated with steeper diurnal cortisol patterns. Unlike the MDD outpatients, the only trait associated with diurnal cortisol patterns in healthy subjects was total sleep hours. CONCLUSIONS: These results suggested that self-perceived good sleep quality, total hours slept of 7 or greater, and self-perceived higher levels of physical activity in the home environment could be positively related to positive stress endocrine outcomes seen as steep diurnal cortisol patterns in outpatients with major depressive disorder.

The comparison of effectiveness of two modalities of mental health nurse follow-up programmes for female outpatients with depression in Taipei, Taiwan.

AIMS AND OBJECTIVES: This study compares the effectiveness of two modalities of mental health nurse three-month follow-up programmes: telephone counselling programme and group therapy programme for female outpatients with depression. BACKGROUND: The lifetime prevalence of major depression is 15% and is about twice as common in women as in men. Outpatients with depression often discontinue their treatment after the initial visits to their physicians. METHODS: This study used a quasi-experimental, pre-post-test comparison group design. Twenty-six female outpatients with depression were assigned to one of follow-up programmes: telephone counselling programme or group therapy programme. To qualify for group therapy programme, potential participants were required to come to group sessions weekly. To be accepted into telephone counselling programme, potential participants had to be able to be contacted by phone regularly. Mental health nurse three-month follow-up programmes included care management and structured psychotherapy. Patients in telephone counselling programme received 10 regular telephone calls of 30-60 minutes each. Patients in group therapy programme received 12 sessions of weekly group meetings of 90-120 minutes each. RESULTS: Wilcoxon signed ranks tests provided evidence that the group therapy programme (S = -52.5, p < 0.001; S = 31.5, p = 0.046) and telephone counselling programme (S = -36, p = 0.002; S = 25, p = 0.050) follow-up programmes were effective in terms of relieving depressed symptoms and improving quality of life. According to Quade's analysis of covariance, telephone counselling programme and group therapy programme appeared to have similar effects of relieving depressed symptoms (F(1,24) = 0.06, p = 0.813) and increasing quality of life (F(1,24) = 0.07, p = 0.792). While there was no significant difference in using emergency services ( chi(2)(1)= 0.89, p = 0.539) between telephone counselling programme and group therapy programme, the rate of adherence to scheduled outpatient appointments with psychiatrists was higher among patients in group therapy programme than patients in telephone counselling programme (chi(2)(3) = 8.67, p = 0.034). CONCLUSIONS: Establishing two modalities of mental health nurse follow-up programmes in Taiwan could benefit patients with different needs. RELEVANCE TO CLINICAL PRACTICE: Mental health nurses specialized in management of depression could provide not only care management but also structured psychotherapy.

Effects of haloperidol and clozapine on glutamate release from nerve terminals isolated from rat prefrontal cortex.

The present study was conducted to understand the effect of haloperidol, a typical antipsychotic, and clozapine, an atypical one, on the release of endogenous glutamate in nerve terminals isolated from rat prefrontal cortex using an on-line enzyme-linked fluorometric assay. We found that both haloperidol and clozapine significantly inhibited 4-aminopyridine (4AP)-evoked and veratridine-evoked but not KCl-evoked glutamate release from prefrontocortical synaptosomes. This inhibition produced by these two drugs was concentration-dependent with different potency, and associated with a reduction both in the depolarization-evoked increase in the intrasynaptosomal free Na(+) concentration ([Na(+)](i)) and in 4AP or KCl-evoked depolarization of the synaptosomal plasma membrane potential. Additionally, in the presence of calcium-free medium containing 0.2 mM EGTA, the Ca(2+)-independent component of 4AP-evoked glutamate release was also inhibited by haloperidol or clozapine. Based on these results, we suggest that haloperidol and clozapine inhibit glutamate release from rat prefrontocortical nerve terminals by affecting ion-channel activities determining nerve terminal excitability, probably as a result of Na(+) channel blockage or K(+) channel activation.