Inflammation, hippocampal volume, and cognition in schizophrenia: results from the Northern Finland Birth Cohort 1966.

Increased blood interleukin-6 (IL-6) levels are a replicated abnormality in schizophrenia, and may be associated with smaller hippocampal volumes and greater cognitive impairment. These findings have not been investigated in a population-based birth cohort. The general population Northern Finland Birth Cohort 1966 was followed until age 43. Subjects with schizophrenia were identified through the national Finnish Care Register. Blood IL-6 levels were measured in n = 82 subjects with schizophrenia and n = 5373 controls at age 31. Additionally, 31 patients with schizophrenia and 63 healthy controls underwent brain structural MRI at age 34, and cognitive testing at ages 34 and 43. Patients with schizophrenia had significantly higher median (interquartile range) blood IL-6 levels than controls (5.31, 0.85-17.20, versus 2.42, 0.54-9.36, p = 0.02) after controlling for potential confounding factors. In both schizophrenia and controls, higher blood IL-6 levels were predictors of smaller hippocampal volumes, but not cognitive performance at age 34. We found evidence for increased IL-6 levels in patients with midlife schizophrenia from a population-based birth cohort, and replicated associations between IL-6 levels and hippocampal volumes. Our results complement and extend the previous findings, providing additional evidence that IL-6 may play a role in the pathophysiology of schizophrenia and associated brain alterations.

Could vitamin D reduce obesity-associated inflammation? Observational and Mendelian randomization study.

BACKGROUND: Obesity is associated with inflammation but the role of vitamin D in this process is not clear. OBJECTIVES: We aimed to assess the associations between serum 25-hydroxyvitamin D [25(OH)D], BMI, and 16 inflammatory biomarkers, and to assess the role of vitamin D as a potential mediator in the association between higher BMI and inflammation. METHODS: Northern Finland Birth Cohort 1966 (NFBC1966) 31-y data on 3586 individuals were analyzed to examine the observational associations between BMI, 25(OH)D, and 16 inflammatory biomarkers. Multivariable regression analyses and 2-sample regression-based Mendelian randomization (MR) mediation analysis were performed to assess any role of vitamin D in mediating a causal effect of BMI on inflammatory biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1), high sensitivity C-reactive protein (hs-CRP), and α1-acid glycoprotein (AGP)] for which observational associations were detected. For MR, genome-wide association study summary results ranging from 5163 to 806,834 individuals were used for biomarkers, 25(OH)D, and BMI. Findings were triangulated with a literature review of vitamin D supplementation trials. RESULTS: In NFBC1966, mean BMI (kg/m2) was 24.8 (95% CI: 24.7, 25.0) and mean 25(OH)D was 50.3 nmol/L (95% CI: 49.8, 50.7 nmol/L). Inflammatory biomarkers correlated as 4 independent clusters: interleukins, adhesion molecules, acute-phase proteins, and chemokines. BMI was positively associated with 9 inflammatory biomarkers and inversely with 25(OH)D (false discovery rate < 0.05). 25(OH)D was inversely associated with sICAM-1, hs-CRP, and AGP, which were positively associated with BMI. The MR analyses showed causal association of BMI on these 3 inflammatory biomarkers. There was no observational or MR evidence that circulating 25(OH)D concentrations mediated the association between BMI and these 3 inflammatory markers. Review of randomized controlled trials (RCTs) supported our findings showing no impact of vitamin D supplementation on inflammatory biomarkers. CONCLUSIONS: The findings from our observational study and causal MR analyses, together with data from RCTs, do not support a beneficial role of vitamin D supplementation on obesity-related inflammation.

Benzodiazepine Use Is Associated With Poorer Spinal Cord Stimulation Outcome in 373 Neuropathic Pain Patients.

OBJECTIVES: The aim of the study is to investigate whether benzodiazepine use differs between patients with favorable and unfavorable spinal cord stimulation (SCS) treatment outcome. We hypothesize that the patients with unfavorable SCS outcome would exhibit a higher level of benzodiazepine use. MATERIALS AND METHODS: Using a case-control study setting, we examined benzodiazepine use in SCS patients and in matched population controls as a potential risk factor poor SCS outcome. A total of 373 consecutive SCS patients treated in Kuopio University Hospital between 1997 and 2014 and their 1117 matched population controls were followed until patient death or the end of March 2016. RESULTS: Benzodiazepines were used during the 24-month period before or after SCS implantation by 42.3% of the SCS patients who had the device explanted, 39.5% who had an unsuccessful trial stimulation, 28.0% who still had the device at the end of the follow-up period, and 8.0% of the controls. Diazepam use before SCS increased the odds for explanting of SCS by 2.4-fold (95% Cl: 1.0-5.4). Starting clonazepam use after SCS was associated with a 5.2-fold (95% CI: 1.5-18.9) increase in the odds of unsuccessful trial stimulation. CONCLUSION: The benzodiazepine use in patients with poor SCS outcome illustrates the role of anxiety in SCS outcomes and the need for multidisciplinary treatment of pain.

Adverse childhood experiences and alexithymia in patients with major depressive disorder.

The purpose of the article: Adverse childhood experiences (ACEs) have been postulated to negatively affect the development of emotional regulation. However, little is known about specific associations between ACEs, depressive symptoms, and alexithymia or its components [i.e. difficulty in identifying feelings (DIF), difficulty in describing feelings to others (DDF) and externally-oriented thinking (EOT)] in patients with major depressive disorder (MDD). The aims of the present cross-sectional study were to (1) compare ACEs (emotional neglect, emotional abuse, physical neglect, physical abuse, sexual abuse) between alexithymic and non-alexithymic patients with MDD; (2) explore whether specific ACEs, depressive symptoms or the interaction between sex and depressive symptoms predicted TAS-20 or its components.Materials and Methods: The study sample consisted of 186 psychiatric outpatients with MDD (aged 21-61 years, mean 33.87 years, SD 10.88) recruited from the Department of Psychiatry, Kuopio University Hospital between 2016-2019. Alexithymia and its components were assessed using the 20-item Toronto Alexithymia Scale (TAS-20). ACEs were assessed with the Trauma and Distress Scale (TADS).Results: Almost all patients with alexithymia and 80% of non-alexithymic patients reported that they had experienced emotional abuse or neglect, at least sometimes. Approximately 60% of MDD patients reported having experienced physical neglect and 30% described physical abuse. Emotional and physical abuse and neglect predicted DDF score.Conclusions: These findings suggest that among MDD patients, early experiences of emotional and physical abuse and neglect is associated with difficulties in describing feelings in adulthood.

Antipsychotic Use Among 1144 Patients After Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose- At acute phase and neurointensive care, patients with aneurysmal subarachnoid hemorrhage (aSAH) may become agitated or delirious. We found no previous studies on psychotic disorders or antipsychotic drug (APD) use by long-term aSAH survivors. We defined the APD use and its risk factors among 12-month survivors of aSAH in an Eastern Finnish population-based cohort with long-term follow-up. Methods- We analyzed APD use in 1144 consecutive patients with aSAH alive at 12 months of the Kuopio intracranial aneurysm patient and family database and their age, sex, and birth municipality matched controls (3:1; n=3432) from 1995 to 2013 and median follow-up of 9 years. Using the Finish nationwide health registries, we obtained drug purchase and hospital discharge data. Results- In total, 140 (12%) of the 1144 patients started APD use first time after aSAH (index date), in contrast to 145 (4%) of the 3432 matched population controls. The cumulative rate of starting APD was 6% at 1 year and 9% at 5 years, in contrast to 1% and 2% in the controls, respectively. The rates at 1 and 5 years were only 1% and 2% in the 489 patients with a good condition (modified Rankin Scale score, 0 or 1 at 12 months; no shunt, intracerebral hemorrhage, or intraventricular hemorrhage). Instead, the highest rate of APD use, 23% at 5 years was among the 192 patients shunted for hydrocephalus after aSAH. Eighty-eight (63%) of the 140 aSAH patients with APD use had also concomitant antidepressant or antiepileptic drug use. Conclusions- The 12-month survivors of aSAH were significantly more likely to be started on APD after aSAH than their matched population controls. These patients often used antidepressant and antiepileptic drugs concomitantly. The use of APDs strongly correlated with signs of brain injury after aSAH, with low use if no signs of significant brain injury were present.

Genome-wide association study identifies seven novel loci associating with circulating cytokines and cell adhesion molecules in Finns.

BACKGROUND: Inflammatory processes contribute to the pathophysiology of multiple chronic conditions. Genetic factors play a crucial role in modulating the inflammatory load, but the exact mechanisms are incompletely understood. OBJECTIVE: To assess genetic determinants of 16 circulating cytokines and cell adhesion molecules (inflammatory phenotypes) in Finns. METHODS: Genome-wide associations of the inflammatory phenotypes were studied in Northern Finland Birth Cohort 1966 (N=5284). A subsequent meta-analysis was completed for 10 phenotypes available in a previous genome-wide association study, adding up to 13 577 individuals in the study. Complementary association tests were performed to study the effect of the ABO blood types on soluble adhesion molecule levels. RESULTS: We identified seven novel and six previously reported genetic associations (p<3.1×10-9). Three loci were associated with soluble vascular cell adhesion molecule-1 (sVCAM-1) level, one of which was the ABO locus that has been previously associated with soluble E-selectin (sE-selectin) and intercellular adhesion molecule-1 (sICAM-1) levels. Our findings suggest that the blood type B associates primarily with sVCAM-1 level, while the A1 subtype shows a robust effect on sE-selectin and sICAM-1 levels. The genotypes in the ABO locus associating with higher soluble adhesion molecule levels tend to associate with lower circulating cholesterol levels and lower cardiovascular disease risk. CONCLUSION: The present results extend the knowledge about genetic factors contributing to the inflammatory load. Our findings suggest that two distinct mechanisms contribute to the soluble adhesion molecule levels in the ABO locus and that elevated soluble adhesion molecule levels per se may not increase risk for cardiovascular disease.

High Level of Childhood Trauma Predicts a Poor Response to Spinal Cord Stimulation in Chronic Neuropathic Pain.

BACKGROUND: Spinal cord stimulation (SCS) relieves pain by delivering doses of electric current to the dorsal column of the spinal cord and has been found to be most effective in the treatment of neuropathic pain. Psychological distress is a significant risk factor for the development of chronic pain and has been found to affect the outcome of SCS. Childhood trauma is a risk factor for chronic pain, but has not previously been studied in SCS patients. OBJECTIVES: The objective of this prospective registry-based study was to investigate the prevalence of 5 domains of childhood trauma (emotional neglect, emotional abuse, physical neglect, physical abuse, and sexual abuse) and their relationship with the outcome of spinal cord stimulation on patients suffering from treatment-resistant chronic pain. METHODS: SCS patients treated at Kuopio University Hospital between 1/1/2015 and 12/31/2016 were sent a survey in the mail, the Trauma and Distress Scale, assessing childhood trauma (n = 43). Neuropathic pain, disability, anxiety, and depression were measured in the patients pre-surgery and at 6 and 12 months post-surgery. The patients who provided their name on the questionnaire (n = 22) and had suffered from 3 or more domains of trauma were grouped as the high-trauma group (n = 13) and the rest as the low-trauma group (n = 9). RESULTS: The questionnaire was completed by 40 patients (93%). At least 1 domain of trauma was experienced by 35 (88%) patients, and at least 2 by 24 (60%). The low-trauma group displayed a statistically significant decrease in the mean PainDETECT score from 21.5 before SCS to 16.5 at 12 months post-surgery (Wilk's lambda = 0.297, F(2,9) = 10.6, P = 0.004), contrary to the high- trauma group (Wilk's lambda = 0.904, F(2,6) = 0.3, P = 0.739). LIMITATIONS: Only 22 of the 40 patients provided their name on the questionnaire, which decreased the sample size on follow-up. CONCLUSION: This was the first study to investigate childhood trauma in SCS patients. Patients who had experienced high amounts of childhood trauma did not experience any relief from neuropathic pain 12 months' post-SCS, contrary to the low-trauma group. Childhood trauma might be a factor worth screening in the preoperative evaluation and aftercare of SCS candidates. KEY WORDS: Spinal cord stimulation, the Trauma and Distress Scale, chronic pain, childhood trauma, childhood abuse, childhood neglect, chronic back pain, back pain, psychological distress, neuropathic pain.

Decreased serum total cholesterol is associated with a history of childhood physical violence in depressed outpatients.

Associations between adverse childhood experiences (ACEs) and cholesterol in depressed patients are unclear. Therefore, we compared 78 adult outpatients with major depressive disorder (MDD) with (n = 24) or without (n = 54) experiences of physical violence in childhood. Background data were collected with questionnaires, and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured from fasting blood samples. Patients with a history of childhood physical violence had lower levels of TC than the control group. No differences were observed in HDL-C, LDL-C, or low-grade inflammation levels between the two groups. In multivariate models, decreased levels of TC were associated with childhood physical violence, and these associations remained significant after adjustments for age, gender, lifestyle, metabolic condition, socioeconomic situation, psychiatric status, suicidality, low-grade inflammation, the chronicity of depression, medications used and somatic diseases. At the 8-month follow-up, the results were essentially the same when the Trauma and Distress Scale (TADS) was used as the measure of ACEs. The specific mechanisms underlying cholesterol alterations associated with ACEs are a topic for future studies. Better understanding of these mechanisms might lead to possible new interventions in the prevention of adverse health effects resulting from ACEs.

Preoperative sense of coherence associated with the 10-year outcomes of lumbar spinal stenosis surgery.

A prospective 10-year follow-up study was conducted to determine the significance of the preoperative sense of coherence, with respect to the preoperative and 10-year clinical characteristics, among lumbar spinal stenosis patients ( N = 99). In addition, the predictive value of the preoperative sense of coherence regarding the 10-year surgery outcome was also evaluated. In a logistic regression analysis, a weak preoperative sense of coherence and low functional ability predicted the patients' functional ability 10 years after the surgery. Moreover, those patients with weak sense of coherence before surgery showed poorer functional ability 10 years after the surgery, but not preoperatively. A weak preoperative sense of coherence seems to associate with poorer long-term outcome after surgery; therefore, various rehabilitation strategies are discussed.

Prevalence of Schizophrenia in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive and potentially treatable neurodegenerative disease affecting elderly people, characterized by gait impairment and ventricular enlargement in brain imaging. Similar findings are seen in some patients with schizophrenia (SCZ). OBJECTIVE: To determine the prevalence of SCZ among patients suffering from probable or possible iNPH and the specific effects of comorbid SCZ on the outcome of the cerebrospinal fluid (CSF) shunting. METHODS: All medical records of the 521 iNPH patients in the NPH registry were retrospectively analyzed from 1991 until 2017. The prevalence of comorbidity of SCZ was determined and compared to that of general aged (≥65 yr) population in Finland. RESULTS: We identified a total of 16 (3.1%) iNPH patients suffering from comorbid SCZ. The prevalence of SCZ among the iNPH patients was significantly higher compared to the general population (3.1% vs 0.9%, P < .001). All iNPH patients with comorbid SCZ were CSF shunted and 12 (75%) had a clinically verified shunt response 3 to 12 mo after the procedure. The CSF shunt response rate did not differ between patients with and without comorbid SCZ. CONCLUSION: SCZ seems to occur 3 times more frequently among iNPH patients compared to the general aged population in Finland. The outcome of the treatment was not affected by comorbid SCZ and therefore iNPH patients suffering from comorbid SCZ should not be left untreated. These results merit validation in other populations. In addition, further research towards the potential connection between these chronic conditions is warranted.

Bifrontal active and sham rTMS in treatment-resistant unipolar major depression.

BACKGROUND AND AIM: Prevention of the recurrence of major depression and its residual symptoms requires effective treatment. Our aim was to study the effects of bifrontal active rTMS controlled by sham rTMS in treatment-resistant unipolar major depressive disorder (MDD). METHODS: Thirty-seven patients with treatment-resistant MDD were randomized into two groups. One group received a total of 30 sessions of active bifrontal rTMS (10 Hz rTMS on left dorsolateral prefrontal cortex (DLPFC) and 1 Hz rTMS on right DLPFC) and the other group received bilateral sham rTMS on five days a week for six weeks. RESULTS: Depressive symptoms significantly improved in both the groups, but without a significant group difference. Furthermore, patients with psychotic depression improved similarly to those with moderate or severe depression. CONCLUSIONS: The results of present study indicate a large sham effect of stimulation treatment. The intensive structured treatment protocol may explain the positive outcome in both the groups. It is important to recognize, appreciate, and utilize placebo effects as a significant means of rehabilitation in psychiatric care.

Comparison of early maladaptive schemas between borderline personality disorder and chronic depression.

Borderline personality disorder (BPD) and chronic depression (CD) are common and challenging mental disorders. Maladaptive cognitive schemas have been proposed to increase vulnerability to both disorders. In order to elucidate the role of maladaptive cognitive schemas in BPD and CD, this study compared psychiatric outpatients with BPD (N = 30) and CD (N = 30) in terms of early maladaptive schemas (EMSs). The groups were compared using the Young Schema Questionnaire short form-extended (YSQ-S2-extended) and the 15D health status questionnaire. BPD patients showed higher endorsement on the majority of EMSs, poorer social functioning, and greater concurrent distress than CD patients. However, after controlling for concurrent effects of psychological distress, the groups did not differ in 14 out of the 18 EMSs. These findings point to significant similarities in maladaptive beliefs between the 2 disorders and do not support broad, specific patterns of EMSs associated with either disorder. The results highlight the need for further study of the role of maladaptive schemas in the development and treatment of chronic mental disorders.

Global arginine bioavailability ratio is decreased in patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is characterized by increased oxidative and nitrosative stress. We compared nitric oxide metabolism, i.e., the global arginine bioavailability ratio (GABR) and related serum amino acids, between MDD patients and non-depressed controls, and between remitted and non-remitted MDD patients. METHODS: Ninety-nine MDD patients and 253 non-depressed controls, aged 20-71 years, provided background data via questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of ornithine, arginine, citrulline, and symmetric and asymmetric dimethylarginine. GABR was calculated as arginine divided by the sum of ornithine plus citrulline. We compared the above measures between: 1) MDD patients and controls, 2) remitted (n=33) and non-remitted (n = 45) MDD patients, and 3) baseline and follow-up within the remitted and non-remitted groups. RESULTS: Lower arginine levels (OR 0.98, 95% CI 0.97-0.99) and lower GABR (OR 0.13, 95% CI 0.03-0.50) were associated with the MDD vs. the non-depressed group after adjustments for potential confounders. The remitted group showed a decrease in GABR, arginine, and symmetric dimethylarginine, and an increase in ornithine after the follow-up compared with within-group baseline values. The non-remitted group displayed an increase in arginine and ornithine levels and a decrease in GABR. No significant differences were recorded between the remitted and non-remitted groups. LIMITATIONS: The MDD group was not medication-free. CONCLUSIONS: Arginine bioavailability may be decreased in MDD. This could impair the production of nitric oxide, and thus add to oxidative stress in the central nervous system.

Depression is associated with the long-term outcome of lumbar spinal stenosis surgery: a 10-year follow-up study.

BACKGROUND CONTEXT: Depression is associated with greater postoperative disability in patients with lumbar spinal stenosis (LSS). No previous studies have reported the association in a 10-year follow-up. PURPOSE: To evaluate the association between preoperative and postoperative depressive symptoms and the surgical outcome among patients with LSS in a 10-year follow-up. In addition, we examined the effects of the depressive burden on the surgical outcome. DESIGN: A prospective observational follow-up study. PATIENT SAMPLE: A total of 102 patients with LSS underwent decompressive surgery, and 72 of the original sample participated in the 10-year follow-up study. OUTCOME MEASURES: Self-report measures: the Oswestry Disability Index (ODI) and visual analog scale (VAS). METHODS: Data were collected using a questionnaire that was administered seven times during the study period. Depressive symptoms were measured with the Beck Depressive Inventory (BDI). The depressive burden was calculated by summing the preoperative and all follow-up BDI scores. Statistical analysis included cross-sectional group comparisons and linear mixed models. The authors report no conflicts of interest related to this work. RESULTS: The high depressive burden group had a poorer outcome for pain, disability, and the walking distance at the 10-year follow-up. In linear mixed models, a higher preoperative BDI score associated with higher disability. Furthermore, higher postoperative BDI scores and the depressive burden were associated with higher disability and pain in the 10-year follow-up. CONCLUSIONS: Patients with LSS with even slightly elevated depressive symptoms have an increased risk of postoperative pain and disability in a 10-year follow-up. To improve the surgical outcome among these patients, screening for depression both preoperatively and during the rehabilitation following surgery is important.

Why Does the Health-Related Quality of Life in Idiopathic Normal-Pressure Hydrocephalus Fail to Improve Despite the Favorable Clinical Outcome?

OBJECTIVE: Occasionally, a favorable clinical disease-specific outcome does not reflect into improved generic health-related quality of life (HRQoL) in patients with idiopathic normal-pressure hydrocephalus (iNPH) at 1 year after the installation of a cerebrospinal fluid shunt. Our aim was to identify factors causing this discrepancy. METHODS: The 1-year HRQoL outcomes of 141 patients with iNPH were evaluated with the generic 15D instrument, in which the minimum clinically important change/difference on the 0-1 scale has been estimated to be ±0.015. A 12-point iNPH grading scale (iNPHGS) was used as a clinical disease-specific outcome measure, in which a 1-point decrease is considered to be clinically important. We identified 29 (21%) patients with iNPH from our prospective study whose HRQoL deteriorated or remained the same despite of a favorable iNPHGS outcome. We analyzed this discrepancy using patients' clinical variables and characteristics. RESULTS: Multivariate binary logistic regression analysis indicated that a greater (worse) iNPHGS score at baseline (adjusted odds ratio [OR], 1.7; 95% confidence interval [CI] 1.3-2.3; P < 0.001), comorbid chronic pulmonary disease (40% vs. 20%; adjusted OR 17.8; 95% CI 3.6-89.9; P < 0.001), and any comorbid nonmetastatic tumor (62% vs. 17%; adjusted OR 11.5; 95% CI 1.5-85.3; P = 0.017) predicted discrepancy between iNPHGS and 15D outcomes. CONCLUSIONS: Frail patients suffering from certain pre-existing comorbidities may not experience improvement in generic HRQoL despite of a favorable clinical disease-specific response. Acknowledging the comorbidity burden of the patient may help clinicians and the patients to understand the conflict between patient-reported and clinical outcomes.

Dietary patterns are associated with the prevalence of alexithymia.

Recent evidence supports the association between healthy dietary patterns and a reduced risk of depression. The objective was: (1) to examine the associations between dietary patterns and alexithymic features; and (2) investigate whether these possible associations are explained by depressive symptoms in a cross-sectional study among the Finnish general population aged 25-65 years. The study population was a part of the population-based Kuopio Depression Study (KUDEP) conducted in central-eastern Finland (n = 1747). Dietary data were collected using a food frequency questionnaire and dietary patterns from 22 predefined food groups, which were extracted by factor analysis. Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20) and depression using the 21-item Beck Depression Inventory (BDI-21). Altogether, 173 of the study subjects (9.9%) were alexithymic. Three dietary patterns were identified: "prudent," "Western" and "traditional." Lower scores for a healthy prudent dietary pattern and higher scores for an unhealthy Western dietary pattern were associated with an increased likelihood of belonging to the alexithymic group among subjects with elevated depressive symptoms. Among subjects without depressive symptoms, alexithymia was associated with lower scores in the prudent dietary pattern, but also with higher scores in the traditional dietary pattern. General population subjects with alexithymic features may have unhealthier dietary patterns than non-alexithymic subjects.

Low sense of coherence during postoperative recovery is associated with a poorer lumbar spinal stenosis - surgical outcome: A 5-year follow-up study.

This study investigated the association between the 3-month postoperative sense of coherence and the 5-year postoperative outcome of decompressive surgery for lumbar spinal stenosis. The participants with a lower sense of coherence at the 3-month follow-up had a poorer functional ability and lower satisfaction with surgery, higher pain ratings, lower life satisfaction and more depressive symptoms 5 years postoperatively. A low 3-month sense of coherence associated with greater pain and a poorer functional ability 5 years postoperatively. Evaluating sense of coherence and depressive symptoms in patients who have had lumbar spinal stenosis surgery may help in identifying those in need of enhanced support for postoperative recovery.

The Association Between Musculoskeletal Pain and Circulating Ornithine: A Population-Based Study.

Objective: Based on several previous clinical studies, we hypothesized that ornithine levels are different among subjects with persistent musculoskeletal pain compared with other subjects in the population. Design: The study sample consisted of 221 adults with nonpersistent pain, 76 with persistent pain, and 61 with no pain. Concentrations of glutamic acid, ornithine, citrulline, arginine, proline, and spermidine were analyzed using a mass spectrometer. Setting: Lapinlahti municipality in Finland. Results: For the subjects with no pain, nonpersistent pain, and persistent pain, the ornithine concentrations for men were 85.3 µmol/L (SD = 28.9 µmol/L), 98.9 µmol/L (SD = 37.8 µmol/L), and 102.1 µmol/L (SD = 37.1 µmol/L; P = 0.033), respectively. The corresponding concentrations for women were 82.8 µmol/L (SD = 25.2 µmol/L), 83.7 µmol/L (SD = 27.8 µmol/L), and 103.2 µmol/L (SD = 34.9 µmol/L; P = 0.0031). There were no significant differences between the pain groups for any of the other investigated amino acids. Relative sex-specific ornithine concentration adjusted for age, glomerular filtration rate, smoking, body mass index, physical activity, and depressive symptoms was associated with pain ( P = 0.025), the ornithine level being higher in the persistent pain group than in the no pain ( P = 0.006) and nonpersistent pain ( P = 0.032) groups. Conclusion: Ornithine levels are elevated in general population subjects with persistent pain.

Treatment-resistant Major Depressive Disorder with Psychotic Features is Associated with Impaired Processing Speed.

OBJECTIVE: A proportion of patients with major depressive disorder (MDD) show cognitive impairment that is associated with treatment nonresponse and poorer functional recovery. A broader range of cognitive dysfunction has been found to be associated with treatment-resistant depression (TRD) and with the presence of psychotic symptoms. Thus far, the effects of psychotic symptoms on the neuropsychological profile of patients with treatment-resistant MDD have not been investigated. METHOD: In the present study, 44 treatment-resistant MDD patients with (n = 12) or without (n = 32) psychotic symptoms-based on the Structured Clinical Interview (SCID I)-were compared with regard to their clinical status and performance in a neuropsychological test battery. The neuropsychological test battery assessed verbal skills, processing speed, executive functions and memory functions. RESULTS: Patients with psychotic TRD displayed lower performance in processing speed than non-psychotic patients. The group differences were not associated with the severity or pervasiveness of depressive symptoms. The duration of depression (from the onset of depressive symptoms) was longer in the group of non-psychotic TRD patients, but no other group differences with respect to sociodemographic characteristics, age at the onset of symptoms or symptom severity were found. CONCLUSIONS: The results imply that among individuals suffering from MDD, patients with the psychotic subtype who are unresponsive to standard pharmacological and psychosocial treatments have an increased vulnerability to cognitive dysfunction in the area of processing speed. Further research with larger sample size is warranted to determine whether these group differences persist after remission.

Life dissatisfaction is associated with depression and poorer surgical outcomes among lumbar spinal stenosis patients: a 10-year follow-up study.

Life satisfaction is associated with overall somatic health and the short-term surgical outcome in lumbar spinal stenosis (LSS) patients. In this study, the long-term relationship between life satisfaction and the surgical outcome in LSS patients was investigated in a 10-year follow-up. This prospective clinical study included 102 LSS patients who underwent decompressive surgery. They completed a set of questionnaires first preoperatively and then 6 times postoperatively (at 3 and 6 months, and at 1, 2, 5 and 10 years). The final study population at the 10-year follow-up comprised 72 patients. A four-item life satisfaction scale was used to measure global life satisfaction. The sum of all seven life satisfaction scores provided a measure of the life dissatisfaction burden over the entire 10-year follow-up. Depression was measured using the Beck Depression Inventory. The surgical outcome was evaluated using the Oswestry Disability Index, pain evaluation (visual analogue scale), self-reported walking capacity and overall satisfaction with the surgery. Both preoperative life dissatisfaction and the long-term life dissatisfaction burden were associated with poorer 10-year surgical outcomes (i.e. Oswestry Disability Index and visual analogue scale) in logistic regression analyses. Life dissatisfaction was also associated with symptoms of depression. Monitoring subjective well-being, especially life satisfaction and mood, in LSS patients before and after surgery may help in detecting those at risk of a poorer long-term surgical outcome.