Shared and distinct alterations of white matter tracts in remitted and nonremitted patients with schizophrenia

Patients with schizophrenia do not usually achieve remission state even after adequate antipsychotics treatment. Previous studies found significant difference in white matter integrity between patients with good outcomes and those with poor outcomes, but difference is still unclear at individual tract level. This study aimed to use a systematic approach to identify the tracts that were associated with remission state in patients with schizophrenia. We evaluated 91 patients with schizophrenia (remitted, 50; nonremitted, 41) and 50 healthy controls through diffusion spectrum imaging. White matter tract integrity was assessed through an automatic tract‐specific analysis method to determine the mean generalized fractional anisotropy (GFA) values of the 76 white matter tract bundles in each participant. Analysis of covariance among the 3 groups revealed 12 tracts that were significantly different in GFA values. Post‐hoc analysis showed that compared with the healthy controls, the nonremission group had reduced integrity in all 12 tracts, whereas the remission group had reduced integrity in only 4 tracts. Comparison between the remission and nonremission groups revealed 4 tracts with significant difference (i.e., the right fornix, bilateral uncinate fasciculi, and callosal fibers connecting the temporal poles) even after adjusting age, sex, education year, illness duration, and medication dose. Furthermore, all the 4 tracts were correlated with negative symptoms scores of the positive and negative syndrome scale. In conclusion, our study identified the tracts that were associated with remission state of schizophrenia. These tracts might be a potential prognostic marker for the symptomatic remission in patients with schizophrenia.     

精神分裂症缓解期患者的心理防御机制研究

目的:探讨精神分裂症患者的心理防御机制。方法:采用防御机制问卷,对精神分裂症缓解期患者36例进行测试,并与34例正常人进行比较。结果:患者组不成熟防御机制因子分明显高于对照组。结论:精神分裂症患者在心理防御机制的使用上明显不同于正常人。     

Adjunctive imipramine maintenance treatment in schizophrenic patients with remitted postpsychotic depression

Ten patients with histories of postpsychotic depression responsive to adjunctive imipramine added to fluphenazine decanoate and benztropine underwent a double-blind trial of imipramine discontinuation 6 months after responding to the adjunctive imipramine. Discontinuation of imipramine was associated with depressive relapse.     

Cytokine profiles in drug-naive schizophrenic patients

A large body of evidence concerning immunological abnormalities in schizophrenic patients seems to suggest a role of the immune system in the multifactorial pathogenesis of schizophrenia.We investigated the production of various cytokines [interleukin (IL)-2, IL-4, IL-10, interferon (INF)-gamma] in drug-free (n=26) and drug-naive (n=7) schizophrenic patients and in healthy controls (n=33). Production of IL-2 and INF-gamma was significantly higher (respectively P=0.021 and P=0.001) in patients than in controls.These findings provide further evidence that immunological abnormalities are present in some schizophrenic patients.     

缓解期精神分裂症患者抑郁和自尊状况的调查及心理干预

目的了解缓解期精神分裂症患者抑郁/自尊状况及心理干预对其的影响。方法采用抑郁自评量表(self-ratting depression scale,SDS)及自尊量表(self-esteem scale,SES)对56例缓解期精神分裂症患者进行问卷调查,随机抽取其中20名患者进行深入访谈并进行逐步分析。根据调查分析存在的心理问题,有针对的实施为期6周的心理干预,然后再次测评SDS及SES,并与干预前进行比较。结果进行心理干预前后,缓解期精神分裂症患者SDS评分由(48.96±5.95)下降至(41.76±6.72);SES评分由(26.72±7.84)上升至(34.51±8.63);其差异有统计学意义(P<0.01)。结论缓解期精神分裂症患者存在多种内心体验而表现出抑郁或自卑,心理干预可改善缓解期精神分裂症患者的抑郁和自卑。     

The concordance between symptom information gathered from remitted schizophrenic patients and their relatives

The concordance between symptom information gathered from remitted schizophrenic out-patients and the relatives with whom they live was assessed for different schizophrenic symptom clusters. It was hypothesized that the positive symptoms would show the greatest patient-relative concordance. Patients and relatives were also compared for levels of overall symptom reporting. It was hypothesized that long-term memory problems, anosognosia, and underreporting in order to appear healthy, would cause patients to report fewer symptoms than their relatives. An alternative hypothesis was that relatives would underreport symptoms to avoid “blame” for their relatives' illness, and because they did not have direct experience of the symptomatology. The 24-item version of the Brief Psychiatric Rating Scale (BPRS) was administered to 41 schizophrenic patients (chart diagnoses were validated by a DSM-III-R diagnostic checklist). Fourteen of the BPRS items were then used to glean information about patients' symptomatology from 41 relatives of the patients. Interviews with patients revealed significantly more symptomatology than interviews with patients' relatives for total and non-positive symptoms (both p-values < .01), but not positive symptoms. Intraclass correlations (ICC) between patients' and relatives' assessments were moderate for positive symptoms (ICC = .54, p < .01), low for total symptoms (ICC = .26, p = .05) and negligible for non-positive symptoms (.13, ns). Despite the potential for underreporting due to factors like anosognosia and long-term memory problems, patients are still the best source of information for schizophrenic symptomatology.     

Naloxone in chronic schizophrenic patients: neuroendocrine and behavioral effects

Naloxone produced improvement in abnormal thought content in medicated chronic schizophrenic patients, but not in drug-free patients. In contrast, drowsiness and increases in plasma prolactin concentrations were seen only in drug-free schizophrenic patients. Although growth hormone concentrations increased in drug-free and medicated schizophrenic patients, the time course was different in the two groups. Neuroleptics appear to alter naloxone's clinical and neuroendocrine effects in chronic schizophrenic patients.     

Diminished plasma oxytocin in schizophrenic patients with neuroendocrine dysfunction and emotional deficits

Polydipsic hyponatremic schizophrenic patients (PHS) exhibit enhanced plasma arginine vasopressin (pAVP) and hypothalamic pituitary adrenal (HPA) axis responses to stress that appear attributable to anterior hippocampal dysfunction. Neuroanatomic and electrophysiologic studies indicate oxytocin activity in PHS patients should also be affected. Furthermore, oxytocin normally diminishes HPA responses to stress and facilitates cognitive and behavioral functions impaired in schizophrenia, suggesting that diminished oxytocin activity could contribute to this subsets' neuropsychiatric disorder. In the present study, we measured plasma oxytocin levels at intervals before and after stress induction in six polydipsic hyponatremic (PHS), four polydipsic normonatremic (PNS), five nonpolydipsic normonatremic schizophrenic (NNS) patients and seven healthy controls. Most of these subjects also completed studies measuring their medial temporal lobe volumes, their hippocampal-mediated HPA feedback and their ability to discriminate different facial emotions (an oxytocin-sensitive measure which is markedly impaired in schizophrenia). Results demonstrated that 1) plasma oxytocin levels were lower (p=.006) in hyponatremic patients relative to the other three groups, whose levels were similar and did not change. Oxytocin levels across all subjects were 2) inversely correlated with anterior hippocampal (p=.004) (but not posterior hippocampal or amygdala volumes), and 3) directly correlated with the integrity of hippocampal-mediated HPA feedback (p=.039). Finally, 4) oxytocin levels predicted schizophrenic patients' ability to correctly identify facial emotions (p=.004). These preliminary data provide further evidence that neuroendocrine dysfunction in PHS reflects anterior hippocampal pathology and contributes to a characteristic neuropsychiatric syndrome.     

Mindfulness-based cognitive therapy for nonremitted patients with bipolar disorder

Introduction: Bipolar disorder is characterized by recurrent episodes of depression and/or mania along with interepisodic mood symptoms that interfere with psychosocial functioning. Despite periods of symptomatic recovery, many individuals with bipolar disorder continue to experience substantial residual mood symptoms that often lead to the recurrence of mood episodes. Aims: This study explored whether a new mindfulness‐based cognitive therapy (MBCT) for bipolar disorder would increase mindfulness, reduce residual mood symptoms, and increase emotion‐regulation abilities, psychological well‐being, positive affect, and psychosocial functioning. Following a baseline clinical assessment, 12 individuals with DSM‐IV bipolar disorder were treated with 12 group sessions of MBCT. Results: At the end of treatment, as well as at the 3 months follow‐up, participants showed increased mindfulness, lower residual depressive mood symptoms, less attentional difficulties, and increased emotion‐regulation abilities, psychological well‐being, positive affect, and psychosocial functioning. Conclusions: These findings suggest that treating residual mood symptoms with MBCT may be another avenue to improving mood, emotion regulation, well‐being, and functioning in individuals with bipolar disorder.     

抗精神病药对男性精神分裂症患者性功能与催乳素的影响

目的：探讨抗精神病药（APS）对恢复期精神分裂症患者性功能影响及其与催乳素相关性。方法：入组以氯丙嗪、氯氮平和利培酮单一治疗至少6个月各60例、具有稳定配偶的恢复期精神分裂症男性患者。以亚利桑那洲性经验量表（ASEX）进行总体性功能障碍（SD）评定,放免法检测血浆催乳素水平。结果：①氯丙嗪组ASEX总分以及5个分因子分均显著高于氯氮平组和利培酮组（P〈0.05或P〈0.001）,氯丙嗪组SD发生率也显著高于其他两组（P均〈0.05）。②利醅酮组血浆催乳素显著高于氯丙嗪组和氯氮平组（P均〈0.001）,血浆催乳素水平与全体患者（P=0.007）和利培酮组患者（P=0.006）ASEX总分呈显著正相关。结论：氯丙嗪较氯氮平和利培酮更易于发生SD,利培酮可能导致催乳素水平增高。     

Lactate vulnerability of remitted panic patients

Sodium lactate precipitates panic in 70-100% of clinically ill patients with panic disorders. The lactate vulnerability of remitted patients is unknown. In this study, 13 panic patients completed three sequential sodium lactate infusions: one before treatment, a second when panic free on tricyclic antidepressants (TCA), and a third when in remission and unmedicated for 1 to 6 months. Three out of 13 patients panicked at the third infusion as compared to 0/13 infused on TCA and 7/12 at pretreatment infusion. This result (1) indicates that lactate vulnerability can exist in clinically well, unmedicated patients, and (2) raises the possibility that lactate vulnerability may be a trait characteristic. Further studies are needed before definite conclusions can be drawn.     

Stability of self-esteem in bipolar disorder: comparisons among remitted bipolar patients, remitted unipolar patients and healthy controls

OBJECTIVES: Changes in beliefs about the self are a central feature of bipolar disorder, with grandiose self-belief common in mania and low self-esteem evident in periods of depression. We investigated whether unstable self-esteem is a characteristic of bipolar disorder in remission. METHODS: We compared 18 patients with DSM-IV bipolar disorder in remission, 16 patients with unipolar disorder in remission, and 19 healthy controls. The primary measure was a diary kept for one week and completed twice each day, measuring self-esteem and positive and negative affect. We also administered Winters and Neale's (J Abnorm Psychol 1985; 94: 282-290) implicit measure of attributional style. RESULTS: Whereas mean levels of self-esteem and affect were not abnormal in the remitted bipolar patients, the bipolar patients showed strong fluctuations in these processes. In common with the unipolar patients, they also showed a pessimistic attributional style on the Pragmatic Inference Task (PIT). CONCLUSIONS: Instability of self-esteem and affect is present in bipolar patients, even when their symptoms are in remission, and has previously been found in people at genetic risk of the disorder. It may be a marker of vulnerability to the disorder.     

Salivary cortisol profiles in patients remitted from recurrent depression: one-year follow-up of a mindfulness-based cognitive therapy trial

Few studies have examined changes of diurnal cortisol profiles prospectively, in relation to non-pharmacological interventions such as mindfulness-based cognitive therapy (MBCT). Fifty-six patients remitted from recurrent depression (≥3 episodes) were included in an 8-week randomized controlled trial comparing MBCT plus treatment as usual (TAU) with TAU for depression relapse prophylaxis. Saliva samples (0, 15, 30, 45, 60 min post-awakening, 3 PM, 8 PM) were collected on six occasions (pre- and post-intervention, 3-, 6-, 9-, 12-month follow-up). Cortisol awakening response (CAR), average day exposure (AUCday) and diurnal slope were analyzed with mixed effects models (248 profiles, 1-6 per patient). MBCT (n = 28) and TAU groups (n = 28) did not significantly differ with respect to baseline variables. Intra-individual variability exceeded inter-individual variability for the CAR (62.2% vs. 32.5%), AUC(day) (30.9% vs. 23.6%) and diurnal slope (51.0% vs. 34.2%). No time, group and time by group effect was observed for the CAR and diurnal slope. A significant time effect (p = 0.003) was detected for AUCday, which was explained by seasonal variations (p = 0.012). Later wake-up was associated with lower CAR (-11.7% per 1-hour later awakening, p < 0.001) and lower AUCday (-4.5%, p = 0.014). Longer depression history was associated with dampened CAR (-15.2% per 10-year longer illness, p = 0.003) and lower AUCday (-8.8%, p = 0.011). Unchanged cortisol secretion patterns following participation in MBCT should be interpreted with regard to large unexplained variability, similar relapse rates in both groups and study limitations. Further research is needed to address the scar hypothesis of diminished HPA activity with a longer, chronic course of depression.     

The DEX/CRH neuroendocrine test and the prediction of depressive relapse in remitted depressed outpatients

Hypothalamo-pituitary-adrenal (HPA) system dysfunction is the most characteristic biological alteration found in a majority of depressed patients. Accumulating evidence suggests that the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test is highly sensitive to detect HPA system abnormalities. The aim of this study was to evaluate whether the DEX/CRH test has a predictive value for the risk of depressive relapse in outpatients who are in clinical remission from a major depressive episode. Thirty-eight depressed outpatients (23 women, 15 men) in remission (MADRS score < or =8) underwent the DEX/CRH test and were followed up for 12 months regarding the occurrence of a new depressive episode. In parallel we recruited 24 controls (13 men and 11 women). The main result is a statistically significant difference concerning the delta and AUC numbers for cortisol plasmatic values between the group of patients who relapsed during the 1-year follow-up and control subjects, but not between the group of patients with prolonged remission and controls. These results suggest that in outpatients who are in clinical remission from a major depressive episode, high delta and AUC values in the DEX/CRH test compared to controls subjects can be associated with a higher risk of relapse.     

Residual cognitive impairments in remitted depressed patients

Depressive disorders are associated with various cognitive impairments. Studies on whether or not these impairments persist into the euthymic phase have shown conflicting results, due to differences in test versions and in study samples. In this paper, we aimed to compare the cognitive performance of remitted depressed patients with that of age- and gender-matched healthy volunteers across a wide range of cognitive domains. In two studies, we found few differences on neutral as well as emotional information processing tests. The findings indicate that remitted depressed patients who use antidepressant medication still show an increased recognition of facial expression of fear compared to healthy controls. Patients also performed worse on a test of recognition of abstract visual information from long-term memory. No other residual cognitive impairments were found. These results indicate that most of the cognitive impairments associated with depression resolve with recovery through medication, even when recovery is incomplete. Considering the finding that remitted depressed patients have higher levels of cognitive reactivity, future studies may investigate the possibility that these cognitive impairments have not resolved but have become latent, and may therefore easily be triggered by small changes in mood state.     

Cytokine profiles in schizophrenic patients treated with risperidone: a 3-month follow-up study

An increasing body of evidence suggests a role for the immune system in the pathogenesis of schizophrenia. The information concerning the effects of antipsychotics on cytokine profiles are limited and often controversial in particular regarding novel antipsychotics. The authors first investigated the production of various cytokines [interleukin (IL)-2, IL-4, IL-10, interferon (INF)-gamma] in drug-free (n = 12) and drug-naive (n = 3) schizophrenic patients and in healthy controls (n = 33) and then the modifications of cytokines values during a 3-month period of treatment with risperidone. In the baseline condition, the production of IL-2 and INF-gamma was significantly higher (P = .023 and .026, respectively) in patients than in controls. In the same patients, the use of risperidone was associated with augmented IL-10 (a suppressor of Type I cytokines) and decreased INF-gamma production. This modification suggests that clinical improvement is associated with a reduction in the inflammatory-like situation present in not currently treated schizophrenic patients.