Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia: an international multicenter study.

BACKGROUND: The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. METHODS: Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. RESULTS: There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. DISCUSSION: Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

Internet-Delivered Cognitive Behavioral Therapy for Insomnia Comorbid With Chronic Pain: Randomized Controlled Trial.

BACKGROUND: Patients with chronic pain often experience insomnia symptoms. Pain initiates, maintains, and exacerbates insomnia symptoms, and vice versa, indicating a complex situation with an additional burden for these patients. Hence, the evaluation of insomnia-related interventions for patients with chronic pain is important. OBJECTIVE: This randomized controlled trial examined the effectiveness of internet-based cognitive behavioral therapy for insomnia (ICBT-i) for reducing insomnia severity and other sleep- and pain-related parameters in patients with chronic pain. Participants were recruited from the Swedish Quality Registry for Pain Rehabilitation. METHODS: We included 54 patients (mean age 49.3, SD 12.3 years) who were randomly assigned to the ICBT-i condition and 24 to an active control condition (applied relaxation). Both treatment conditions were delivered via the internet. The Insomnia Severity Index (ISI), a sleep diary, and a battery of anxiety, depression, and pain-related parameter measurements were assessed at baseline, after treatment, and at a 6-month follow-up (only ISI, anxiety, depression, and pain-related parameters). For the ISI and sleep diary, we also recorded weekly measurements during the 5-week treatment. Negative effects were also monitored and reported. RESULTS: Results showed a significant immediate interaction effect (time by treatment) on the ISI and other sleep parameters, namely, sleep efficiency, sleep onset latency, early morning awakenings, and wake time after sleep onset. Participants in the applied relaxation group reported no significant immediate improvements, but both groups exhibited a time effect for anxiety and depression at the 6-month follow-up. No significant improvements on pain-related parameters were found. At the 6-month follow-up, both the ICBT-i and applied relaxation groups had similar sleep parameters. For both treatment arms, increased stress was the most frequently reported negative effect. CONCLUSIONS: In patients with chronic pain, brief ICBT-i leads to a more rapid decline in insomnia symptoms than does applied relaxation. As these results are unique, further research is needed to investigate the effect of ICBT-i on a larger sample size of people with chronic pain. Using both treatments might lead to an even better outcome in patients with comorbid insomnia and chronic pain. TRIAL REGISTRATION: ClinicalTrials.gov NCT03425942; https://clinicaltrials.gov/ct2/show/NCT03425942.

Modeling psychological function in patients with schizophrenia with the PANSS: an international multi-center study.

BACKGROUND: The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model. METHODS: Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed. RESULTS: The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage. CONCLUSIONS: The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct "cores" of schizophrenia, the "Positive" and the "Negative," while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.

Is sleep disturbance in patients with chronic pain affected by physical exercise or ACT-based stress management? - A randomized controlled study.

BACKGROUND: Most people suffering chronic pain are plagued by sleeping difficulties. Cognitive behaviour therapy has produced promising results for insomnia comorbid with chronic pain, but the access to such treatment is often limited. Over the last ten years, interventions aiming to increase cognitive flexibility and physical activity have been assumed to be effective treatments for a variety of conditions, including insomnia and chronic pain. If proven effective, these treatments could constitute the first steps in a stepped care model for chronic pain and insomnia. METHODS: Two hundred ninety-nine chronic pain subjects were randomized to Exercise, ACT-based stress management (ACT-bsm), or an active control group. Two hundred thirty-two participants (78%) received their allocated intervention at least to some extent. These participants were evaluated using mixed model analyses for changes in sleep (Insomnia Severity Index, ISI), pain intensity, depression, and anxiety immediately after treatment, six months and twelve months after treatment. RESULTS: The mixed model analyses revealed that Exercise had a positive effect on insomnia compared with the control group and the effect remained after 12 months. No clear effect (i.e., both for completers and for completers together with treatment non-completers) upon ISI was found for the ACT-bsm. Pain intensity decreased significantly both in the exercise group and in the control group. For the two psychological variables (i.e., symptoms of anxiety and depression) were found significant improvements over time but no group differences. The treatment effects for ISI and pain intensity did not reach clinical significance per definitions presented in other relevant studies. CONCLUSIONS: Beneficial significant effects on insomnia was confirmed in the exercise condition. However, these changes were probably not clinically important. For pain intensity a general decrease was found in the Exercise condition and in the control condition, while no change occurred in ACT-bsm. No group differences were found for the two psychological variables. TRIAL REGISTRATION: The study was registered in Clinical Trials (Trial registration: ClinicalTrials.gov Id: NCT02399644 , 21 January 2015, retrospectively registered).

Insomnia is a risk factor for spreading of chronic pain: A Swedish longitudinal population study (SwePain).

BACKGROUND: Recent evidence suggests that insomnia negatively influences the occurrence of generalized pain. This study examined whether insomnia is a risk factor for the transition from local pain (LP) to generalized pain (i.e. spreading of pain). METHODS: This longitudinal study, with a follow-up of 24 months, included 959 participants (mean age: 55.8 years; SD: 13.9) with local or regional pain at baseline. Participants were grouped by insomnia symptoms as measured by the Insomnia Severity Index. Spreading of pain was measured by body manikins based on the spatial distribution of pain on the body. We defined two outcome categories; one with relatively localized pain (i.e. LP and moderate regional pain [MRP]), and one with relatively generalized pain (i.e. substantial regional pain and widespread pain [WSP]). Baseline age, sex, education, depressive symptoms, anxiety symptoms, catastrophizing, pain intensity and spread of pain were also included in the Generalized Linear Model analysis. RESULTS: The unadjusted model showed that the risk of spreading of pain increased with an increase in insomnia symptoms (no insomnia: 55.4%; subthreshold insomnia: 25.4% moderate insomnia: 16.5% and severe insomnia: 2.7%). The risk increased in a dose-dependent manner; moderate insomnia risk ratio (RR) 2.34 (95% confidence interval [CI]: 1.34-4.09) and severe insomnia RR 4.13 (95% CI: 1.56-10.92). The results were maintained in the fully adjusted model although MRP was the strongest predictor RR 6.95 (95% CI: 3.11-15.54). CONCLUSION: Our findings show a strong prospective relationship between insomnia symptoms and the transition from relatively localized to generalized pain. SIGNIFICANCE: This study shows that people with LP conditions are at much higher risk of developing WSP if they also have significant insomnia symptoms. The elevated risk is evident after 24 months and increases in a dose-dependent manner regarding the degree of exposure to insomnia symptoms. Local pain conditions are quite common in primary care, and an evaluation of the insomnia symptoms is highly recommended since the most common sleep problems can be treated effectively if detected.

Spreading of pain and insomnia in patients with chronic pain: results from a national quality registry (SQRP).

OBJECTIVE: To explore how demographics, pain, psychosocial factors and insomnia relate to the spread of chronic pain. METHODS: The study included 708 patients (68% women; median age 46 years; interquartile range 35-57 years) with chronic pain who were referred to a multidisciplinary pain centre. Spreading of pain was assessed using a questionnaire covering 36 anatomically predefined pain regions. Data were collected on demographics, pain symptoms, psychological distress, and insomnia (Insomnia Severity Index). Four sub-categories of chronic pain were established: chronic local pain, chronic regional pain medium, chronic regional pain heavy, and chronic widespread pain. RESULTS: The median number of pain regions was 10 (interquartile range 6-18). Prevalence of chronic pain was as follows: chronic local pain 9%, chronic regional pain medium 21%, chronic regional pain heavy 39%, and chronic widespread pain 31%. In the regression models, being a woman and persistent pain duration had the strongest associations with spreading of pain, but anxiety, pain interference, and insomnia were also important factors. CONCLUSION: Spreading of chronic pain can only partly be explained by the simultaneous levels of insomnia. Female sex, pain duration, pain interference and anxiety appear to have more significant relationships with the spread of pain. Targeting these factors may lead to improvements in treatment and prevention strategies.

Could PANSS be a useful tool in the determining of the stages of schizophrenia? A clinically operational approach.

Staging in schizophrenia might be an important approach for the better treatment and rehabilitation of patients. The purpose of this study was to empirically devise a staging approach in a sample of stabilized patients with schizophrenia. One hundred and seventy patients aged ≥18 years (mean = 40.7, SD = 11.6) diagnosed by DSM-5 criteria were evaluated with the Positive and Negative Syndrome Scale (PANSS). Principal components analysis (PCA) with varimax rotation was used. The model was examined in the total sample and separately across a hypothesized stage of illness based on three age groups and between the two sexes. The PCA revealed a six factor structure for the total sample: 1) Negative, 2) Positive, 3) Depression and anxiety, 4) Excitement and Hostility, 5) Neurocognition and 6) Disorganization. The separate PCAs by stage of illness and sex revealed different patterns and quality of symptomatology. The Negative and Positive factors were stable across all examined groups. The models corresponding to different stages differed mainly in terms of neurocognition and disorganization and their interplay. Catatonic features appear more prominent in males while in females neurocognition takes two forms; one with disorganization and one with stereotype thinking with delusions. This study suggests that the three arbitrary defined stages of illness (on the basis of age) seem to reflect a progress from a preserved insight and more coherent mental functioning to disorganization and eventually neurocognitive impairment. Sexes differ in terms of the relationship of psychotic features with neurocognition. These results might have significant research and clinical implications.

The Swedish version of the Insomnia Severity Index: Factor structure analysis and psychometric properties in chronic pain patients.

Objective Insomnia is the most commonly diagnosed comorbidity disorder among patients with chronic pain. This circumstance requests brief and valid instruments for screening insomnia in epidemiological studies. The main object of this study was to assess the psychometric properties and factor structure of the Swedish version of the Insomnia Severity Index (ISI). The ISI is a short instrument designed to measure clinical insomnia and one of the most common used scales both in clinical and research practice. However there is no study in Sweden that guarantees neither its factor structure nor its feasibility in chronic pain patients. We further examined the measurement invariance property of the ISI across the two sexes. Methods The ISI was administered to 836 (269 men and 567 women) chronic pain patients from the Swedish Quality Registry for Pain Rehabilitation. This study used demographic data, the Hospital Anxiety and Depression Scale (HADS), the Mental Summary Component (MSC) of the Health Survey (SF-36) and the item 7 from Multidimensional Pain Inventory (MPI). The sample was divided into two random halves: exploratory factor analysis (EFA) was performed in the first sample (N1 = 334, 40%) and confirmatory factor analysis (CFA) in the second half of the sample (N2 = 502, 60%). The measurement and structural invariance of the proposed structure (4-item version) between the two sexes as well as reliability and validity indexes were further assessed. Results Exploratory factor analysis using the principal axis factoring method generated one global factor structure for the ISI, explaining 63.1% of the total variance. The one factor solution was stable between the two sexes. Principal component analysis was also applied and indicated almost identical results. The structure was further assessed by CFA, resulting in an adequate fit only after omitting three items. The difference on structural and measurement invariance in the loadings by participants' sex was not significant (Δχ2 = 10.6; df = 3; p = .69 and Δχ2 = 2.86; df = 3; p = 41 respectively). The shorter version four-item Insomnia Severity Index (ISI-4) was analysed further. The Chronbach's alpha for the global ISI-4 score was 0.88. The construct validity of the ISI-4 was also supported by the, Hospital Anxiety and Depression Scale, the Mental Summary Component of quality of life and quality of sleep data. Pain intensity was significantly associated with the ISI-4 score (beta = .29, p < 001) whereas no significant correlation between four-item Insomnia Severity Index score and age was observed (p > 05). Conclusions and implications Although short, the four-item Insomnia Severity Index (ISI-4) version seemed to effectively assess insomnia in chronic pain patients. An important clinical implication is that the four-item Swedish Insomnia Severity Index can be used in chronic pain cohorts when screening for insomnia problems. Its measurement and structural invariance property across the two sexes shows that the ISI-4 is a valid measure of the insomnia across groups of chronic patients. Our results also suggest its utility both in pain clinical practice and research purposes.

Internet-vs. group-delivered cognitive behavior therapy for insomnia: A randomized controlled non-inferiority trial.

UNLABELLED: The aim of this study was to compare guided Internet-delivered to group-delivered cognitive behavioral therapy (CBT) for insomnia. We conducted an 8-week randomized controlled non-inferiority trial with 6-months follow-up. Participants were forty-eight adults with insomnia, recruited via media. Interventions were guided Internet-delivered CBT (ICBT) and group-delivered CBT (GCBT) for insomnia. Primary outcome measure was the Insomnia Severity Index (ISI), secondary outcome measures were sleep diary data, depressive symptoms, response- and remission rates. Both treatment groups showed significant improvements and large effect sizes for ISI (Within Cohen's d: ICBT post = 1.8, 6-months follow-up = 2.1; GCBT post = 2.1, 6-months follow-up = 2.2). Confidence interval of the difference between groups post-treatment and at FU6 indicated non-inferiority of ICBT compared to GCBT. At post-treatment, two thirds of patients in both groups were considered responders (ISI-reduction > 7p). Using diagnostic criteria, 63% (ICBT) and 75% (GCBT) were in remission. Sleep diary data showed moderate to large effect sizes. We conclude that both guided Internet-CBT and group-CBT in this study were efficacious with regard to insomnia severity, sleep parameters and depressive symptoms. The results are in line with previous research, and strengthen the evidence for guided Internet-CBT for insomnia. TRIAL REGISTRATION: The study protocol was approved by, and registered with, the regional ethics review board in Linköping, Sweden, registration number 2010/385-31.

Comorbid insomnia in patients with chronic pain: a study based on the Swedish quality registry for pain rehabilitation (SQRP).

PURPOSE: This study investigates the prevalence of insomnia and its relationship to other symptoms and health aspects in patients with chronic pain. METHODS: Patients with chronic pain conditions (n = 845) referred to a multidisciplinary pain centre completed surveys provided by the Swedish quality registry for pain rehabilitation (SQRP). The SQRP collects data on socio-demographics, health status, symptoms of pain, mood and insomnia and life satisfaction. RESULTS: The majority of patients (65.3%) had clinical insomnia according to the insomnia severity index (ISI). Insomnia correlated significantly but weakly with pain, depression, anxiety and coping; the strongest multivariate correlations were found with depression and anxiety followed by pain interference and pain severity. Pain intensity, depression and anxiety correlated stronger than ISI with respect to the two investigated aspects of health. CONCLUSIONS: The prevalence of insomnia is high in patients with chronic pain conditions, but the level of importance in relation to other symptoms for health aspects is low, and the associations with other important symptoms are relatively weak. One way to increase the effects of multimodal rehabilitation programs may be to provide interventions directed specifically at insomnia rather than focusing only on interventions that address pain, depression and anxiety. Implications for Rehabilitation The prevalence of insomnia is high in patients with complex chronic pain conditions. Relatively low correlations existed between insomnia and pain intensity, depression, anxiety and other psychological aspects. Pain intensity, anxiety and depression were more important for perceived health aspects than insomnia. One way to increase the effects of multimodal rehabilitation programs may be to also include interventions directed directly to insomnia.