Neuroanatomical differences between familial and sporadic schizophrenia and their parents: An optimized voxel-based morphometry study

Symptomatic differences have been reported between patients with familial and sporadic schizophrenia. The present study examined neuroanatomical differences between the two subgroups and their parents using voxel-based morphometry. High-resolution T1-weighted images were obtained using 3 Tesla magnetic resonance imaging from 20 patients with schizophrenia (familial subgroup, n = 10; sporadic subgroup, n = 10), 20 of their parents (familial subgroup, n = 10; sporadic subgroup, n = 10) and 20 healthy volunteers. Gray matter density (GMD) was compared between groups on a voxel-by-voxel basis. Compared with the sporadic patients, the familial patients had significantly reduced GMD in the thalamus bilaterally. Reduction of GMD in bilateral thalami was also found in familial parents in comparison with sporadic parents. Compared with controls, both familial and sporadic patients had lower GMD involving bilateral insula, right temporal lobe, right occipital lobe, left lenticular nucleus and right cerebellum. However, only familial patients showed lower GMD than controls in the right thalamus. Compared with controls, only familial parents showed lower GMD in the right insula extending to the right temporal lobe and the right parietal lobule. The present data suggest that familial schizophrenia is associated with more severe structural abnormalities than sporadic schizophrenia, especially in the thalamus.     

Direct and indirect costs in persons with chronic back pain and comorbid mental disorders--a systematic review

ObjectiveDirect inpatient and outpatient healthcare costs as well as indirect costs (e.g. productivity losses) are hypothesized to be increased in chronic back pain (CBP) patients with mental disorders. The aim of this systematic review is to examine this hypothesis by comparing costs in CBP patients with and without mental disorders.MethodsA comprehensive literature search (Medline, EMBASE, PsycINFO, Psyndex, EconLit, IBSS) was conducted. All studies were included which allowed for a comparison of direct and indirect costs between CBP patients with and without mental disorders.ResultsOf 2283 potentially relevant articles, 10 studies fulfilled the inclusion criteria. Total healthcare costs (SMD = 0.16 [SE = 0.06]; n = 1), CBP-related healthcare costs (SMD = 0.21 [0.06]; n = 1), CBP-related primary care visits (OR = 1.6 [95%-CI:1.2–2.3]; n = 1), CBP-related specialty care visits (OR = 1.4 [1.0–2.0];n = 1), CBP-related radiologic procedures (OR = 1.6 [1.0–2.5]; n = 1) and mental health visits (OR = 8.1 [7.3–9.1]; n = 2) were increased in CBP patients with depression. The incidence of new surgeries was increased in CBP patients with PTSD (OR = 4.2 [1.6–10.8]; n = 1). Pain-related healthcare use (n = 1) in CBP patients with both depression and anxiety and CBP-related hospital admissions (n = 1) in CBP patients with depression were not increased. Regarding indirect costs results were inconsistent for both return to work rates (n = 3) and work absence (n = 2).ConclusionThe results indicate increased direct but not indirect costs in CBP patients with mental disorders. However, the evidence is limited due to the low number of studies per outcome. This is all the more problematic, since the adequate allocation of healthcare resources will become a major topic of health care policy due to limited resources.     

Beta2-microglobulin abnormalities in antipsychotic-naïve schizophrenia: evidence for immune pathogenesis

Studies examining immune dysfunction in schizophrenia have reported decreased type-1 T-helper cell specific immunity (Th1) and increased type-2 T-helper cell specific immunity (Th2) and related abnormalities in inflammatory system. β2-Microglobulin (β2M) influences the development of dendritic cells, which play a significant role in regulating the differentiation of naive CD4⁺ T cells into Th1 or Th2 lineages. The present study examined serum β2M in antipsychotic-naïve schizophrenia patients (n = 43) in comparison with age, sex, handedness and socioeconomic status matched healthy controls (n = 43). Serum β2M was significantly higher in schizophrenia patients (1692.6 ± 354.4 ng/mL) than healthy controls (1409.6 ± 246.9 ng/mL) (t = 4.3; p < 0.0001). There was a significant positive correlation between β2M level and total psychopathology score (r = 0.32; p = 0.035). These novel observations suggest that β2M abnormalities might have a potential association with the pathogenesis of schizophrenia.     

Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: Results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR)

BackgroundThe electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice.MethodsParameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n = 1345) or a new oral antipsychotic (AP) (n = 277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review.ResultsAt 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p < 0.0001) and reduction in Clinical Global Impression Severity scores (?1.14 for RLAI versus ?0.94 for APs, p = 0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p < 0.05) and days (18.74 versus 13.02, p < 0.01) of hospitalizations at 24 months than oral AP patients.ConclusionsThis 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.     

Anterior cingulate morphology in people at genetic high-risk of schizophrenia

BackgroundMorphological abnormalities of the anterior cingulate (AC) occur in patients with schizophrenia and in symptomatic high-risk individuals, and may be predictive of subsequent psychosis. We investigated AC sulcal morphology in the Edinburgh High Risk Study cohort to see if such abnormalities are evident and predict psychosis in patients’ relatives. We also investigated the association of the cingulate sulcus (CS) and paracingulate sulcus (PCS) variants with intelligence quotient (IQ).Patients and methodsWe compared cingulate and paracingulate sulcal anatomy, using reliable standardised measurements, blind to group membership, in those at high genetic risk (n = 146), first episode patients (n = 34) and healthy controls (n = 36); and compared high-risk subjects who did (n = 17) or did not develop schizophrenia.ResultsInterruptions of the cingulate sulcus were more common in high-risk individuals and in those with schizophrenia, in both hemispheres, compared to controls. When separated by gender, these results were only present in males in the left hemisphere and only in females in the right hemisphere. A well-formed paracingulate sulcus was less common in high-risk participants and patients with schizophrenia, compared to controls; but this association was only present in males. These morphological variants of the paracingulate sulcus and the continuous cingulate sulcus were also associated with the higher IQ in male high-risk individuals.ConclusionsAn interrupted cingulate sulcus pattern in both males and females and paracingulate morphology in males are associated with increased genetic risk of schizophrenia. Associations between cingulate and paracingulate morphology and premorbid IQ scores provide evidence that intellectual ability could be related to particular cytoarchitectural brain regions. Given that these sulci develop in early fetal life, such findings presumably reflect early neurodevelopmental abnormalities of genetic origin, although environmental effects and interactions cannot be ruled out.     

CPAP with algorithm-based versus titrated pressure: A randomized study

BackgroundOur goal was to evaluate whether an algorithm-prescribed pressure is effective in sleep apnea–hypopnea syndrome (SAHS) patients requiring continuous positive airway pressure (CPAP).MethodsSAHS patients with an apnea–hypopnea index (AHI) >20/h were selected for a parallel group randomized study including an in-sleep laboratory acute phase and a domiciliary chronic phase. After baseline polysomnography, patients had a second night polysomnography either with CPAP at the algorithm-calculated pressure, followed by home treatment at this pressure without any correction or adjustment (calculation group), or with auto-CPAP titration, followed by home treatment at the pressure judged to be optimal from the auto-titration (titration group). The primary outcome was the change in Epworth sleepiness scale (ESS) at 6 months.ResultsThe calculated pressure (mean (SD)) was 7.0 (1.4) in the calculation group (n = 33), while the optimal pressure was 7.0 (2.2) cmH₂O in the titration group (n = 36). During the 6-month treatment at home, the ESS decreased from 8.3 (4.9) to 5.4 (4.0) in the calculation group (n = 20) and from 8.7 (5.4) to 6.4 (5.4) in the titration group (n = 20) (between-group difference not significant).ConclusionIn these SAHS patients with moderate sleepiness treated with CPAP, we found no difference in effectiveness between an algorithm-based pressure and an auto-titrated pressure.     

Prevalence and awareness of cardiovascular risk factors in patients with schizophrenia: A cross-sectional study in a low cardiovascular disease risk geographical area

ObjectivePrevalence of cardiovascular disease is high in schizophrenia. Our aim is to estimate the prevalence of cardiovascular risk factors (CVRF) among schizophrenia patients.MethodNational cross-sectional study in patients diagnosed with schizophrenia under treatment with second generation antipsychotics and admitted to short-stay hospitalisation units.ResultsA sample of 733 consecutively admitted patients was enrolled; the most prevalent CVRFs were smoking 71% (95% CI: 67–74%) and hypercholesterolemia 66% (61–70%) followed by hypertriglyceridemia 26% (26–32%), hypertension 18% (15–21%) and diabetes 5% (4–7%). Metabolic syndrome showed 19% (95% CI: 16–23%) prevalence or, according to updated definitions (Clin Cornerstone 7 [2005] 36–45), 24% (95% CI: 20–28%). The rate of patients within the high-risk range of a 10-year fatal cardiovascular event was 6.5%. CVRFs under routine management were diabetes (60%), hypertension (28%) and, to a lesser extent, dyslipemia (14%). Treatment for CVRFs was associated to gender, men for hypertension OR = 25.34, p < 0.03 and women for diabetes OR = 0.02, p < 0.03.ConclusionWe found that CVRFs in schizophrenia were prevalent and under-diagnosed, and thus with insufficient therapeutic management.     

Cortisol awakening response in patients with psychosis: Systematic review and meta-analysis

The cortisol awakening response (CAR), defined as the increase in cortisol release in response to waking up, shows associations with social and environmental risk factors of schizophrenia and has been studied as a potential biomarker in schizophrenia. We report a systematic review and meta-analysis of 11 studies and 879 participants focusing on the CAR of patients with schizophrenia, first-episode psychosis, and at-risk mental states. Random-effects meta-analysis showed that CAR is attenuated in patients with psychosis compared to healthy controls (g = ⿿0.426, 95% CI ⿿0.585 to ⿿0.267, p < 0.001, 11 between-group comparisons, n = 879). Subgroup analysis showed flattened CAR in patients with schizophrenia (g = ⿿0.556, 95% CI ⿿1.069 to ⿿0.044, p < 0.05, 2 between-group comparisons, n = 114) and first-episode psychosis (g = ⿿0.544, 95% CI ⿿0.731 to ⿿0.358, p < 0.001, 6 between-group comparisons, n = 505), but not in individuals with at-risk mental states. These distinctive alterations of hypothalamic-pituitary-adrenal axis function may have important implications for CAR as a marker for transition risk. However, the lack of objective verification of sampling adherence in these studies may limit the interpretation of the results.     

Physician speciality and pain reduction in patients with depressive symptoms under treatment with venlafaxine

ObjectivesExcessive pain perception may lead to unnecessary diagnostic testing or invasive procedures resulting in iatrogenic complications and prolonged disability. Naturalistic studies on patients with chronic pain and depressive symptoms investigating the impact of medical speciality on treatment outcome in a primary care setting are lacking.MethodsIn this observational study, we examined whether the magnitude of pain reduction in 444 patients with depressive symptomatology under venlafaxine would relate differently to the medical speciality of the 122 treating physicians, namely psychiatrists (n = 110 patients), general practitioners (n = 236 patients), and internists (n = 98 patients).ResultsIndependent of age, gender, patient's region of origin, comorbidity, severity and duration of pain, and depressive symptoms at study entry, patients seemed to benefit significantly less in terms of pain reduction (p < 0.001) and of reduction in severity of depressive symptomatology by psychiatrists as compared to general practitioners (p < 0.019) and internists (p < 0.002).ConclusionsThe findings suggest that patients referred to psychiatrists are more difficult to treat than those referred to general practitioners and internists, and might not have been adequately prepared for psychiatric interventions. A supporting cooperation and networking between psychiatrists and primary care physicians may contribute to an integrated treatment concept and therefore, may lead to a better outcome in this challenging patient group.     

Optic neuritis in an ethnically diverse population: higher risk of atypical cases in patients of African or African-Caribbean heritage

PurposeTo investigate the presence of an ethnicity bias within patients presenting with optic neuritis in London.DesignObservational cross-sectional study.MethodsThe ethnicity profile of all patients attending a neuro-ophthalmology clinic in central London with acute optic neuritis over a 16 month period (n = 86) was studied. A comparison was made with the ethnicity profile of the population of London as well as patients with Multiple Sclerosis-associated optic neuritis (n = 41), Neuromyelitis Optica spectrum disorder-associated optic neuritis (n = 27) and patients with an atypical corticosteroid-dependent optic neuropathy (21).ResultsThe ethnicity profile of the patient cohort presenting to our clinic with acute optic neuritis over a 16 month period closely matched the ethnicity profile of London (P = 0.08). Within this cohort, patients of African or African-Caribbean heritage were found to be more likely to manifest either a pattern or aetiology of optic neuritis requiring immunosuppressive treatment in comparison with patients of a white Caucasian background (relative risk 3.47; 95% CI = 1.092 to 11.007). There was a disproportionately high representation of patients from an African or African-Caribbean background within the Neuromyelitis Optica spectrum-related optic neuritis diagnostic group (P < 0.00).ConclusionsPatients with acute isolated optic neuritis from African or African Caribbean backgrounds are over 3 times more likely than patients of white Caucasian backgrounds to have an ‘atypical’ pattern of optic neuritis where corticosteroid therapy may be required. Our results suggest that a patient's ethnic background is an important factor to be taken into consideration when deciding on the diagnosis and management of acute isolated optic neuritis.     

Polysomnographic findings, video-based sleep analysis and sleep perception in progressive supranuclear palsy

Objectives: To compare subjective sleep perception, sleep architecture, rapid eye movement (REM) sleep without atonia, and REM sleep behavior disorder (RBD) in patients with progressive supranuclear palsy (PSP) to patients with Parkinson’s disease (PD).Methods: A comparative sleep study using the Parkinson’s Disease Sleep Scale (PDSS), the Mini-Mental State Examination (MMSE), and cardiorespiratory polysomnography on two consecutive nights with synchronized video recording. The study was undertaken in a sleep laboratory in a movement disorder center. Forty patients matched for age and cognition with probable PSP (n = 20, aged 71 ± 8 years, MMSE ? 24 in n = 7) and PD (n = 20, aged 69 ± 5 years, MMSE ? 24 in n = 8).Results: PDSS sum scores showed no difference between PSP and PD. PSP patients had significantly lower sleep efficiency (43.0 ± 15.0%) compared to PD patients (62.8 ± 19.1%) (p < 0.0008). Seventeen PSP patients and 19 PD patients had REM without atonia (RWA). Seven PSP patients and 13 PD patients had clinical RBD. The amount of RWA was lower in PSP (14.5 ± 17.3%) than in PD (44.6 ± 31.3%) (p < 0.0007). Eleven PSP and 11 PD patients were newly identified with sleep-disordered breathing (SDB).Conclusions: Polysomnographically recorded sleep is more severely impaired in PSP than in PD. PDSS ratings do not reflect the poorer sleep quality in PSP, possibly pointing to a specific neuropsychological profile. RWA and RBD are present in both neurodegenerative diseases. So far undetected SDB affects more than half of all patients in this study.     

Working memory dysfunction in schizophrenia patients with obsessive-compulsive symptoms: An fMRI study

BackgroundA substantial proportion of schizophrenia patients also meets DSM-IV criteria for obsessive-compulsive disorder (OCD). Schizophrenia with OCD (“schizo-obsessive”) patients are characterized by distinct clinical characteristics, treatment response and prognosis. Whether schizo-obsessive patients exhibit a distinct pattern of brain activation is yet unknown. To address this question, the present functional magnetic resonance imaging (fMRI) study explicitly compared alterations in brain activation and functional connectivity (FC) underlying a working memory deficit in schizophrenia patients with and without OCD.MethodsfMRI was applied during the N-back working memory (WM) task in three groups: schizo-obsessive (n = 16), schizophrenia (n = 17) and matched healthy volunteers (n = 20). WM-related activation in the right dorsolateral prefrontal cortex (DLPFC) and the right caudate nucleus, brain areas relevant to schizophrenia and OCD, and FC analysis were used for the evaluation.ResultsThe two schizophrenia groups with and without OCD exhibited a similar reduction in activation in the right DLPFC and right caudate, as well as decreased FC compared to the healthy controls. Notably, reduced regional brain activation was not related to severity of schizophrenic or OCD symptoms.ConclusionsSchizo-obsessive patients do not differ from their non-OCD schizophrenia counterparts in brain activation patterns during the N-back WM task. Cognitive paradigms taping alternative neural networks (e.g., orbitofrontal cortex) particularly relevant to OCD, are warranted in the search for potential distinctive brain activation patterns of the schizo-obsessive subgroup.     

Sodium oxybate in the treatment of childhood narcolepsy-cataplexy: a retrospective study

ObjectiveTo evaluate the efficacy and side effect profile of sodium oxybate in the treatment for narcolepsy–cataplexy in the pediatric age group.MethodsA retrospective study was conducted on 15 children and adolescents with narcolepsy–cataplexy who had been treated with sodium oxybate. The mean age at diagnosis of narcolepsy was 11 years (range 3–17 years). Subjects were followed for 3–90 months (mean 33) after starting sodium oxybate. During this period of time they were also maintained on other medications for sleepiness (n = 14) and cataplexy (n = 6). The charts were reviewed for documentation of improvement in sleepiness or cataplexy, side effects, and functioning in daily life.ResultsSubsequent to the addition of sodium oxybate, sleepiness improved in 13/15 patients. In patients who had Epworth Sleepiness Scale (ESS) assessments, the score fell from a baseline median of 18 to 12 (n = 10, p = 0.01). The number of cataplexy episodes estimated by parents decreased from a median of 38/week pre-treatment to <1/week post treatment (n = 14, p < 0.001). Cataplexy severity, measured on an arbitrary scale, fell from a median of 3 (severe) to 1 (mild) in all 15 subjects (p < 0.001).Two of the 15 patients (13%) discontinued sodium oxybate, one for insurance reasons and the other due to constipation and dissociative feelings. A third patient stopped the medication temporarily due to body aches and dizziness, but then resumed treatment without recurrence of symptoms. Side effects in four others included tremor, blurring of vision, nocturnal awakenings, and increased nightmares. Overall, side effects occurred in 6/15 (40%) individuals. Improvement in social/academic spheres was noted in 11/15 (73%) subjects after starting sodium oxybate. The median BMI before and after treatment remained unchanged at 23 (n = 14, p = 0.99). Median values of height and weight before and after treatment also did not change significantly. The mean dose of sodium oxybate was 5 ± 2 g. Dose escalation owing to development of tolerance was not encountered.ConclusionsSodium oxybate is effective in alleviating sleepiness and cataplexy in childhood onset narcolepsy–cataplexy. The therapeutic response was sustained over time, and without development of tolerance. Forty percent of the subjects experienced adverse effects.     

At the boundary of the self: The insular cortex in patients with childhood-onset schizophrenia,their healthy siblings,and normal volunteers

The insular cortex (insula), whose normal function involves delineating the boundary between self and non-self stimuli, has been implicated in the pathophysiology of the positive symptoms of schizophrenia, including hallucinations and delusions. Childhood-onset schizophrenia (COS), that includes the onset of psychosis before age 13, is a severe and continuous form of the illness which shows profound and global progressive cortical brain abnormalities during adolescence which merge in the adult pattern with age. Using prospectively acquired anatomic brain magnetic resonance imaging (MRI) scans, a matched sample of COS patients, their nonpsychotic full siblings and healthy volunteers, we measured insular volume using the FreeSurfer automated software. COS patients (n = 98; 234 scans) had significantly lower right (p = 0.003), left (p < 0.001), and total (p < 0.001) insular volumes than healthy volunteers (n = 100; 248 scans). Right insular volume negatively correlated with positive symptoms as measured by the Scale for the Assessment of Positive Symptoms (SAPS) (p = 0.02), while both left (p = 0.01) and right (p = 0.006) insula volumes were positively correlated with overall functioning, as measured by the Children's Global Assessment Scale (CGAS) scores. COS siblings (n = 71; 153 scans), on the other hand, did not differ significantly from normal volunteers suggesting that the insular deficits are more related to the illness state than a familial endophenotype. These results also highlight the salience of the insula in positive symptoms of schizophrenia perhaps resulting from the inability to discriminate between self from the non-self in COS. Further work to connect insular deficits to other neurocircuitries is warranted.     

Q-ACP: a questionnaire for evaluating visual and gestural complaints in patients with posterior cortical atrophy

IntroductionPosterior cortical atrophy (PCA) is a clinical neurodegenerative syndrome associated with atrophy in parieto-occipital cortices, and characterized by prominent disorders of higher visual processing, affecting both dorsal and ventral streams.MethodsWe used a questionnaire (Q-ACP) specifically designed to assess visual and praxis dysfunctions in PCA. The Q-ACP contains 32 items (combined in 12 domains) aimed at describing everyday deficiencies that patients or caregivers notice about visual and gestural domains. It was administered to 34 patients with PCA (MMSE = 20.0 ± 5.1) which were compared with 17 patients with Alzheimer's disease (AD) (MMSE = 23.4 ± 1.9) and 31 normal controls (MMSE = 28.9 ± 1.1).ResultsQ-ACP of PCA patients (18.4 ± 5.3) was significantly greater than those of AD patients (2.7 ± 2.0) or normal controls (0.97 ± 1.6), and revealed disproportionate deficits on questions of visuospatial ability. Q-ACP was comparable in right (18.5 ± 4.3) and left (18.2 ± 6.8) PCA patients (p = 0.88). There was a negative correlation between MMSE and Q-ACP in PCA patients (r = –0.36; p = 0.045), but not in AD patients (r = –0.21; p = 0.42). When only the 22 PCA patients with MMSE equal or greater than 20 were considered, their Q-ACP score (17.2 ± 5.3) remained significantly greater than those of AD patients and normal controls (p = 0.0001). Controls had difficulties for only 12 of the 32 questions, and AD patients for 20 questions, whereas each of the 32 questions could be abnormal in the PCA group. The less often reported difficulties by PCA patients were for more easily reading small than big letters (14.7 %) whereas the most frequently impaired questions were for spatial and apractic agraphia (88.2 % for each question). Of the 12 domains of Q-ACP, all were impaired in PCA patients, 11 in AD patients and seven in controls.ConclusionQ-ACP is a useful tool for assessing visual and praxis everyday difficulties of patients with PCA. These difficulties are rarely observed in normal aged controls or patients with mild AD.     

IgM-monoclonal gammopathy neuropathy and tremor: a first epidemiologic case control study

IntroductionSmall case series suggest tremor occurs frequently in IgM-monoclonal gammopathy of undetermined significance (IgM-MGUS) neuropathy. Epidemiologic study to confirm this association is lacking. Whether the neuropathy or another remote IgM-effect is causal remains unsettled.Materials and methodsAn IgM-MGUS neuropathy case cohort (n = 207) was compared to age, gender, and neuropathy impairment score (NIS) matched, other-cause neuropathy controls (n = 414). Tremor details were extracted from structured neurologic evaluation. All patients underwent nerve conductions.ResultsTremor occurrence was significantly higher in IgM-MGUS case cohort (29%) than in control cohort (9.2%) (p = 0.001). In IgM-MGUS cases, tremor was associated with worse NIS (p = 0.025) and demyelinating nerve conductions (p = 0.020), but 11 of 60 (18%) IgM-MGUS cases with tremor had axonal neuropathy. In other-cause neuropathy controls, tremor was associated with axonal nerve conductions (p = 0.03) but not with NIS severity (p = 0.57). Tremor occurrence associated with older age in controls, (p = 0.004) but not in IgM-MGUS cases (p = 0.272). Most IgM-MGUS tremor cases (49/60) had a postural-kinetic tremor, 8 had rest tremor, 3 had mixed rest-action. Alternative causes of tremor was identified in 42% of IgM-MGUS cases, the most common type is inherited essential tremor 6/60 (p = 0.04).ConclusionsThis first epidemiologic case-control study validates association between IgM-MGUS neuropathy and tremor. Among IgM-MGUS neuropathy cases, severity as well as type of neuropathy (demyelinating over axonal) correlated with tremor occurrence. IgM-MGUS paraproteinemia may increase tremor expression in persons recognized with common other risk factors for tremor.     

Psychiatric and behavioral side effects of the newer antiepileptic drugs in adults with epilepsy

ObjectivePsychiatric/behavioral side effects (PSEs) are common in patients taking antiepileptic drugs (AEDs). The objective of the study described here was to compare the PSE profiles of the newer AEDs.MethodsWe examined the charts of 1394 adult outpatients seen at the Columbia Comprehensive Epilepsy Center who had taken one of the newer AEDs. We compared the rate of AED-related PSEs in patients newly started on the newer AEDs both before and after controlling for non-AED predictors of PSEs.ResultsOverall, 221 of 1394 (16%) patients experienced PSEs. The average rate of AED-related PSEs for a single AED was 8.4%, with 6.1% resulting in dosage change and 4.3% resulting in AED discontinuation. Significantly fewer PSEs were attributed to gabapentin (n = 160, 0.6% incidence, P < 0.001) and lamotrigine (n = 547, 4.8% incidence, P < 0.001), and significantly more PSEs were attributed to levetiracetam (n = 521, 15.7% incidence, P < 0.001; 8.8% discontinued LEV because of PSEs). Vigabatrin, felbamate, and oxcarbazepine were associated with similarly low rates of PSEs in many analyses but with fewer of patients. Tiagabine was associated with high PSE rates (similar to those for levetiracetam), but was used much less commonly at our center. Intermediate rates of PSEs were attributed to topiramate and zonisamide (both nonsignificant). Psychiatric history was the most significant nondrug predictor of AED-related PSEs (PSEs occurred in 23% of patients with a psychiatric history vs 12% of patients without such a history, P < 0.001). The relative rates of AED-related PSEs were similar when controlling for non-AED predictors and when analyzing only patients on monotherapy.ConclusionsThere are significant differences between the newer AEDs in terms of their PSE profiles. Patients taking levetiracetan experience significantly more PSEs than average, and patients taking gabapentin and lamotrigine experience significantly fewer PSEs. Even with the medication with the highest rate of PSEs (levetiracetam), less than 10% of patients discontinued it because of PSEs. A past psychiatric condition is the most significant nondrug predictor of AED-related PSEs.     

The effect of continuous positive airway pressure treatment on physical activity in patients with obstructive sleep apnoea: A randomised controlled trial

BackgroundContinuous positive airway pressure (CPAP) improves daytime sleepiness in patients with obstructive sleep apnoea (OSA). The effect of CPAP on physical activity is unclear. We hypothesized that activity would increase after CPAP treatment.MethodsA double blind, parallel, randomised, controlled trial using therapeutic and placebo CPAP was performed in men with newly diagnosed OSA (more than 10 > 4% SaO₂ dips/hour and Epworth Sleepiness Score [ESS] ?9). Activity was measured by wrist actigraphy before and after three months of CPAP therapy.ResultsThirty-six men completed 1 week of continuous actigraphy before and after therapeutic CPAP (n = 16) or placebo CPAP (n = 20). The two groups were well-matched at baseline, with no significant differences in mean age, body mass index, ESS and SaO₂ dips/hour. Mean (SD) ESS and modified maintenance of wakefulness test (OSLER) improved significantly after CPAP. ESS change in the therapeutic group was ?6.1 (4.4), compared to placebo, ?2.8 (5.0); difference between groups p = 0.04; OSLER (minutes), therapeutic +10.4 (14.4), placebo ?5.0 (12.0), p = 0.003. There was no significant difference between groups in mean hourly activity levels for the seven days at baseline; activity levels did not significantly change in either group after CPAP [daytime activity (arbitrary units): therapeutic ?13.9 (93.1) vs. placebo +8.3 (62.9), p = 0.4]. There was no correlation between change in activity and CPAP use.ConclusionActivity does not increase after CPAP in men with OSA, despite improvements in daytime sleepiness. The reasons for this are not clear, but may be due to longstanding, habitual patterns of activity.     

Serum BDNF levels and weight gain in schizophrenic patients on long-term treatment with antipsychotics

Several lines of evidence suggest that central brain-derived neurotrophic factor (BDNF) modulates food intake, metabolism, and increases in body weight. Reports have also shown that serum BDNF is altered in schizophrenic patients treated with antipsychotics. This study aimed to determine if there was a relationship between BDNF and antipsychotic-induced weight gain in patients with chronic schizophrenia. Serum BDNF was measured in 124 schizophrenia patients chronically treated with clozapine (n = 57), risperidone (n = 23) or typical antipsychotics (n = 44) and 50 healthy control subjects. To further assess group differences in serum BDNF, additional analyses were performed in a subset of patients and controls individually matched for body mass index (BMI). BDNF levels were lower in patients with schizophrenia than normal controls. However, this difference was not present when controlling for current BMI. In the individually BMI-matched sample, no differences in serum BDNF levels were observed in schizophrenic patients compared to BMI-matched healthy controls. BDNF levels negatively correlated with BMI gain in female but not in male patients when gender was considered. Antipsychotic class exerted differential effects over BDNF levels and BMI gain. Our findings suggest that decreased BDNF levels may be associated with weight gain in female schizophrenic patients on long-term antipsychotic treatment.     

Auditory P300 latency prolongation with age in schizophrenia: Gender and subcomponent effects

Previous studies showing prolongation of auditory P300b latency with increasing age provided support for post-onset progressive change in schizophrenia. We sought to extend the findings by evaluating the effects of gender and the subcomponents (P3b versus P3a) in schizophrenia (N = 108) and controls (N = 70). P3b latency significantly correlated with age in schizophrenia (Spearman's rho = 0.214, P = 0.026) and in male patients with schizophrenia (rho = 0.260, P = 0.049) whereas, it did not reach significance in female patients with schizophrenia (rho = 0.174, P = 0.23). P3a latency showed no correlation. Our findings may provide evidence for progressive change in the brain function in schizophrenia, and this change may be slower in female than male patients. P3b may serve as a more sensitive index for cognitive decline than P3a.