Healthy Comparison Subjects Research Articles

Dissociable neural substrates of opioid and cocaine use identified via connectome-based modelling.

Opioid use disorder is a major public health crisis. While effective treatments are available, outcomes vary widely across individuals and relapse rates remain high. Understanding neural mechanisms of treatment response may facilitate the development of personalized and/or novel treatment approaches. Methadone-maintained, polysubstance-using individuals (n=53) participated in fMRI scanning before and after substance-use treatment. Connectome-based predictive modeling (CPM)—a recently developed, whole-brain approach—was used to identify pre-treatment connections associated with abstinence during the 3-month treatment. Follow-up analyses were conducted to determine the specificity of the identified opioid abstinence network across different brain states (cognitive vs. reward task vs. resting-state) and different substance use outcomes (opioid vs. cocaine abstinence). Post-treatment fMRI data were used to assess network changes over time and within-subject replication. To determine further clinical relevance, opioid abstinence network strength was compared to healthy subjects (n=38). CPM identified an opioid abstinence network (p=.018), characterized by stronger within-network motor/sensory connectivity, and reduced connectivity between the motor/sensory network and medial frontal, default mode and frontoparietal networks. This opioid abstinence network was anatomically distinct from a previously identified cocaine abstinence network. Relationships between abstinence and opioid and cocaine abstinence networks replicated across multiple brain states but did not generalize across substances. Network connectivity measured at post-treatment related to abstinence at 6-month follow-up (p<.009). Healthy comparison subjects displayed intermediate network strengths relative to treatment responders and non-responders. These data indicate dissociable anatomical substrates of opioid versus cocaine abstinence. Results may inform the development of novel opioid-specific treatment approaches to combat the opioid epidemic.

GPS mobility as a digital biomarker of negative symptoms in schizophrenia: a case control study

Mobility is an important correlate of physical, cognitive, and mental health in chronic illness, and can be measured passively with mobile phone global positional satellite (GPS) sensors. To date, GPS data have been reported in a few studies of schizophrenia, yet it is unclear whether these data correlate with concurrent momentary reports of location, vary by people with schizophrenia and healthy comparison subjects, or associate with symptom clusters in schizophrenia. A total of 142 participants with schizophrenia (n = 86) or healthy comparison subjects (n = 56) completed 7 days of ecological momentary assessment (EMA) reports of location and behavior, and simultaneous GPS locations were tracked every five minutes. We found that GPS-derived indicators of average distance travelled overall and distance from home, as well as percent of GPS samples at home were highly correlated with EMA reports of location at the day- and week-averaged level. GPS-based mobility indicators were lower in schizophrenia with medium to large effect sizes. Less GPS mobility was related to greater negative symptom severity, particularly diminished motivation, whereas greater GPS mobility was weakly associated with more community functioning. Neurocognition, depression, and positive symptoms were not associated with mobility indicators. Therefore, passive GPS sensing could provide a low-burden proxy measure of important outcomes in schizophrenia, including negative symptoms and possibly of functioning. As such, passive GPS sensing could be used for monitoring and timely interventions for negative symptoms in young persons at high risk for schizophrenia.

Serum Endocannabinoid Levels in Patients With End-Stage Renal Disease.

ContextPrevious studies have shown that the endocannabinoid system plays a major role in energy metabolism through the actions of its main mediators, 2-arachidonoyl-sn-glycerol (2-AG) and anandamide (AEA).ObjectiveWe examined serum levels of major endocannabinoid mediators and their association with clinical parameters in patients with end-stage renal disease (ESRD).Design and SettingSerum concentrations of 2-AG and AEA were measured in patients on maintenance hemodialysis (MHD) and controls, and correlations with various clinical and laboratory indices were examined. 2-AG was also measured in age and sex-matched healthy subjects for comparison of levels in patients undergoing MHD.Main Outcome MeasureSerum 2-AG.ResultsSerum 2-AG levels were significantly elevated in patients with ESRD compared with healthy controls. Higher levels of 2-AG were found in patients on MHD compared to healthy subjects, and similar findings were seen in a second set of subjects in independent analyses. Among 96 patients on MHD, 2-AG levels correlated significantly and positively with serum triglycerides (ρ = 0.43; P < 0.0001), body mass index (ρ = 0.40; P < 0.0001), and body anthropometric measures and negatively with serum high-density lipoprotein cholesterol (ρ = −0.33; P = 0.001) following adjustment for demographic and clinical variables.ConclusionsIn patients on MHD, levels of serum 2-AG, a major endocannabinoid mediator, were increased. In addition, increasing serum 2-AG levels correlated with increased serum triglycerides and markers of body mass. Future studies will need to evaluate the potential mechanisms responsible for these findings.

A multivariate neuroimaging biomarker of individual outcome to transcranial magnetic stimulation in depression.

The neurobiology of major depressive disorder (MDD) remains incompletely understood, and many individuals fail to respond to standard treatments. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) has emerged as a promising antidepressant therapy. However, the heterogeneity of response underscores a pressing need for biomarkers of treatment outcome. We acquired resting state functional magnetic resonance imaging (rsfMRI) data in 47 MDD individuals prior to 5-8 weeks of rTMS treatment targeted using the F3 beam approach and in 29 healthy comparison subjects. The caudate, prefrontal cortex, and thalamus showed significantly lower blood oxygenation level-dependent (BOLD) signal power in MDD individuals at baseline. Critically, individuals who responded best to treatment were associated with lower pre-treatment BOLD power in these regions. Additionally, functional connectivity (FC) in the default mode and affective networks was associated with treatment response. We leveraged these findings to train support vector machines (SVMs) to predict individual treatment responses, based on learned patterns of baseline FC, BOLD signal power and clinical features. Treatment response (responder vs. nonresponder) was predicted with 85-95% accuracy. Reduction in symptoms was predicted to within a mean error of ±16% (r = .68, p < .001). These preliminary findings suggest that therapeutic outcome to DLPFC-rTMS could be predicted at a clinically meaningful level using only a small number of core neurobiological features of MDD, warranting prospective testing to ascertain generalizability. This provides a novel, transparent and physiologically plausible multivariate approach for classification of individual response to what has become the most commonly employed rTMS treatment worldwide. This study utilizes data from a larger clinical study (Australian New Zealand Clinical Trials Registry: Investigating Predictors of Response to Transcranial Magnetic Stimulation for the Treatment of Depression; ACTRN12610001071011; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=336262).

The Prevalence of Cavum Septum Pellucidum in Mental Disorders Revealed by MRI: A Meta-Analysis.

The prevalence of cavum septum pellucidum (CSP) in mental disorders, particularly schizophrenia spectrum disorders and mood disorders, remains uncertain. The authors used a meta-analytical approach to determine the prevalence of CSP in mental disorders and to compare these with the prevalence of CSP in psychiatrically healthy comparison subjects. PubMed and Embase were systematically searched for relevant articles published as of January 9, 2018. After a quality assessment of individual studies using the Newcastle-Ottawa Scale, a random-effects model within Stata statistical software was used to synthesize 25 eligible studies that included 2,392 patients with mental disorders and 1,445 psychiatrically healthy comparison subjects. The prevalence of CSP of any size and large CSP was found to be significantly higher in individuals with mental disorders compared with healthy comparison subjects, and the prevalence of CSP in schizophrenia spectrum and mood disorders did not differ between the groups. The meta-regression with predefined covariance indicated that imaging parameters were not associated with the heterogeneity among original studies; however, the mean age of enrolled subjects was identified as a possible source of heterogeneity. No publication bias was found.

Cognitive Change in Schizophrenia and Other Psychoses in the Decade Following the First Episode.

Schizophrenia is associated with a marked cognitive impairment that is widely believed to remain stable after illness onset. Yet, to date, 10-year prospective studies of cognitive functioning following the first episode with good methodology are rare. The authors examined whether schizophrenia patients experience cognitive decline after the first episode, whether this decline is generalized or confined to individual neuropsychological functions, and whether decline is specific to schizophrenia. Participants were from a population-based case-control study of patients with first-episode psychosis who were followed prospectively up to 10 years after first admission. A neuropsychological battery was administered at index presentation and at follow-up to patients with a diagnosis of schizophrenia (N=65) or other psychoses (N=41) as well as to healthy comparison subjects (N=103). The schizophrenia group exhibited declines in IQ and in measures of verbal knowledge and of memory, but not processing speed or executive functions. Processing speed and executive function impairments were already present at the first episode and remained stable thereafter. The magnitude of declines ranged between 0.28 and 0.66 standard deviations. Decline in measures of memory was not specific to schizophrenia and was also apparent in the group of patients with other psychoses. Healthy individuals with low IQ showed no evidence of decline, suggesting that a decline is specific to psychosis. Patients with schizophrenia and other psychoses experience cognitive decline after illness onset, but the magnitude of decline varies across cognitive functions. Distinct mechanisms consequent to the illness and/or psychosocial factors may underlie impairments across different cognitive functions.

A Quantitative Meta-analysis of Olfactory Dysfunction in Epilepsy.

Olfactory dysfunction in epilepsy is well-documented in several olfactory domains. However, the clinical specificity of these deficits remains unknown. The aim of this systematic meta-analysis was to determine which domains of olfactory ability were most impaired in individuals with epilepsy, and to assess moderating factors affecting olfactory ability. Extant peer-reviewed literature on olfaction in epilepsy were identified via a computerized literature search using PubMed, MEDLINE, PsycInfo, and Google Scholar databases. Twenty-one articles met inclusion criteria. These studies included a total of 912 patients with epilepsy and 794 healthy comparison subjects. Included studies measured olfaction using tests of odor identification, discrimination, memory, and detection threshold in patients with different types of epilepsy, including temporal lobe epilepsy (TLE), mixed frontal epilepsy (M-F), and mixed epilepsy (MIX). Olfactory deficits were robust in patients with epilepsy when compared to healthy individuals, with effect sizes in the moderate to large range for several olfactory domains, including odor identification (d = -1.59), memory (d = -1.10), discrimination (d = -1.04), and detection threshold (d = -0.58). Olfactory deficits were most prominent in patients with TLE and M-F epilepsy. Amongst patients with epilepsy, sex, age, smoking status, education, handedness, and age of illness onset were significantly related to olfactory performance. Overall, these meta-analytic findings indicate that the olfactory system is compromised in epilepsy and suggest that detailed neurobiological investigations of the olfactory system may provide further insight into this disorder.

Auditory steady-state EEG response across the schizo-bipolar spectrum

Deviant auditory steady-state responses (aSSRs) in the gamma range (30–90 Hz) may be translational biomarkers for schizophrenia (SZ). This study tests whether aSSR deviations are (i) specific to SZ across the psychosis dimension, (ii) specific to particular frequency bands, and (iii) present in bipolar I disorder without psychosis (BDNP). MethodsBeta (20-), low- (40-), and high-gamma (80-Hz) aSSRs were measured with EEG and compared across 113 SZ, 105 schizoaffective disorder (SAD), 99 bipolar disorder with psychosis (BDP), 68 BDNP, and 137 healthy comparison subjects (HC). Standard aSSR measures (single-trial power [STP] and inter-trial phase coherence [ITC]), as well as evoked responses to stimulus onsets/offsets and pre-stimulus power, were quantified. Multivariate canonical discriminant analysis was used to summarize variables that efficiently and maximally differentiated groups. Results(i) Psychosis groups showed reduced responses on ITC 20 Hz, STP/ITC 40 Hz, STP/ITC 80 Hz, indicating dimensional reductions in aSSR across the psychosis spectrum not specific to aSSR frequency. For the 40- and 80-Hz ITCs there was greater reduction in SZ compared to SAD, possibly indexing cortical disruptions linked to psychosis without mood symptoms. (ii) All probands had elevated pre-stimulus power, possibly compromising neural entrainment to the steady-state stimuli. (iii) Onset/Offset and 80 Hz ITC responses were most important for group discrimination and showed dimensional reduction across the schizo-bipolar spectrum. ConclusionsDeviant aSSRs were found across the schizo-bipolar spectrum at multiple frequencies with psychosis status and severity linked to greatest reductions at low and high gamma.

Objective diagnosis of post-stroke depression using NMR-based plasma metabonomics.

Background: Post-stroke depression (PSD) is a frequent and serious complication of stroke. However, the underlying molecular basis of PSD remains largely unknown, and no empirical laboratory tests were available to diagnose this disorder.Materials and methods: A proton nuclear magnetic resonance (1H NMR)-based metabonomic approach was employed to profile plasma samples from 32 PSD, 35 stroke patients and 35 healthy comparison subjects (the training set) in order to identify metabolite biomarkers for PSD. Then, 10 PSD, 11 stroke patients and 11 healthy comparison subjects (test set) were used to validate the diagnostic performance of these biomarkers.Results: The multivariate statistical analysis demonstrated that PSD group was significantly distinguishable from non-PSD groups (non-depression stroke patients and healthy comparison group). Five plasma metabolites (phenylalanine, tyrosine, 1-methylhistidine, 3-methylhistidine and LDL CH3-(CH2)n-) were identified responsible for distinguishing PSD from non-PSD subjects. These metabolites were mainly involved in neurotransmitter metabolism and oxidative stress. The biomarker panel composing of these metabolites was capable of distinguishing test samples with a sensitivity of 100.0% and a specificity of 95.5%.Conclusion: Our findings suggest that plasma disturbances of neurotransmitter levels and oxidative stress were implicated in the onset of PSD; these disturbed metabolites biomarkers facilitate to the development of diagnostic tool for PSD.

Peripheral inflammation in mild cognitive impairment with possible and probable Lewy body disease and Alzheimer's disease.

Memory clinics and dementia services. Patients were classified based on clinical symptoms as probable MCI-LB (n = 38), possible MCI-LB (n = 18), and probable MCI-AD (n = 21). Healthy comparison subjects were recruited (n = 20). Ten cytokines were analyzed from plasma samples: interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor (TNF)-alpha. C-reactive protein levels were investigated. There was a higher level of IL-10, IL-1beta, IL-2, and IL-4 in MCI groups compared to the healthy comparison group (p &lt; 0.0085). In exploratory analyses to understand these findings, the MC-AD group lower IL-1beta (p = 0.04), IL-2 (p = 0.009), and IL-4 (p = 0.012) were associated with increasing duration of memory symptoms, and in the probable MCI-LB group, lower levels of IL-1beta were associated with worsening motor severity (p = 0.002). In the possible MCI-LB, longer duration of memory symptoms was associated with lower levels of IL-1beta (p = 0.003) and IL-4 (p = 0.026). There is increased peripheral inflammation in patients with MCI compared to healthy comparison subjects regardless of the MCI subtype. These possible associations with clinical features are consistent with other work showing that inflammation is increased in early disease but require replication. Such findings have importance for timing of putative therapeutic strategies aimed at lowering inflammation.

Lamotrigine Therapy and Biomarkers of Cerebral Energy Metabolism in Older Age Bipolar Depression

This study compared brain energy metabolism, as measured by cerebral concentrations of glutamate (Glu), glutamine (Gln), and N-acetyl aspartate (NAA), in older age bipolar depression (OABD) to that of psychiatrically healthy comparison subjects using proton (1H) magnetic resonance spectroscopy imaging at 4-Tesla. Metabolite levels were assessed in OABD subjects before and after 8 weeks of lamotrigine therapy with the goal of determining relationships between cerebral energy metabolism, depression symptom severity, and changes in depression symptom response. Individuals (n = 21, mean age: 62.0 ± 5.9 years) with bipolar disorder, current episode depressed, and a healthy comparison group (n = 14, mean age: 67.5 ± 8.8 years) were selected. Participants with bipolar disorder, current episode depressed, were treated in open label fashion with lamotrigine monotherapy for 8 weeks. All subjects were scanned with 1H magnetic resonance spectroscopy at 4T at baseline and again after 8 weeks to assess levels of cerebral metabolites in the anterior cingulate cortex and parieto-occipital cortex. Metabolite levels were examined as ratios relative to creatine (Cr). Response to 8 weeks of lamotrigine treatment in the bipolar disorder, current episode depressed group, was assessed as a continuous measure on the Montgomery-Asberg Depression Rating Scale. NAA/Cr ratio in OABD was significantly lower by 14% (95% confidence interval: [1%, 26%]) than in comparison subjects at baseline. However, there were no associations between NAA/Cr, Glu/Cr, or Gln/Cr and either depression severity or lamotrigine treatment. Group differences in NAA suggest evidence for a deficit in cerebral energy metabolism in OABD.

Altered functional connectivity and low-frequency signal fluctuations in early psychosis and genetic high risk

Studying individuals at increased genetic risk for schizophrenia may generate important theories regarding the emergence of the illness. In this investigation, genetic high-risk individuals (GHR, n = 37) were assessed with functional magnetic resonance imaging and compared to individuals in the first episode of schizophrenia (FESZ, n = 42) and healthy comparison subjects (HCS, n = 59). Measures of functional connectivity and the amplitude of low-frequency fluctuation (ALFF) were obtained in a global, data-driven analysis. The functional connectivity measure, termed degree centrality, assessed each voxel's connectivity with all the other voxels in the brain. GHR and FESZ displayed increased degree centrality globally and locally. On ALFF measures, GHR were indistinguishable from HCS in the majority of areas but resembled FESZ in insula, basal ganglia and hippocampus. FESZ evidenced reduced amplitude of the global neural signal as compared to HCS and GHR. Results support the hypothesis that schizophrenia diathesis involves functional connectivity and ALFF abnormalities. In addition, they further an emerging theory suggesting that increased connectivity and metabolism may be involved in schizophrenia vulnerability and early stages of the illness.

Microstructural white matter network-connectivity in individuals with psychotic disorder, unaffected siblings and controls.

BackgroundAltered structural network-connectivity has been reported in psychotic disorder but whether these alterations are associated with genetic vulnerability, and/or with phenotypic variation, has been less well examined. This study examined i) whether differences in network-connectivity exist between patients with psychotic disorder, siblings of patients with psychotic disorder and controls, and ii) whether network-connectivity alterations vary with (subclinical) symptomatology.MethodsNetwork-connectivity measures (global efficiency (GE), density, local efficiency (LE), clustering coefficient (CC)) were derived from diffusion weighted imaging (DWI) and were compared between 85 patients with psychotic disorder, 93 siblings without psychotic disorder and 80 healthy comparison subjects using multilevel regression models. In patients, associations between Positive and Negative Syndrome Scale (PANSS) symptoms and topological measures were examined. In addition, interactions between subclinical psychopathology and sibling/healthy comparison subject status were examined in models of topological measures.ResultsWhile there was no main effect of group with respect to GE, density, LE and CC, siblings had a significantly higher CC compared to patients (B = 0.0039, p = .002). In patients, none of the PANSS symptom domains were significantly associated with any of the four network-connectivity measures. The two-way interaction between group and SIR-r positive score in the model of LE was significant (χ2 = 6.24, p = .01, df = 1). In the model of CC, the interactions between group and respectively SIS-r positive (χ2 = 5.59, p = .02, df = 1) and negative symptom scores (χ2 = 4.71, p = .03, df = 1) were significant. Stratified analysis showed that, in siblings, decreased LE and CC was significantly associated with increased SIS-r positive scores (LE: B = −0.0049, p = .003, CC: B = −0.0066, p = .01) and that decreased CC was significantly associated with increased SIS-r negative scores (B = −0.012, p = .003). There were no significant interactions between group and SIS-r scores in the models of GE and density.ConclusionThe findings indicate absence of structural network-connectivity alterations in individuals with psychotic disorder and in individuals at higher than average genetic risk for psychotic disorder, in comparison with healthy subjects. The differential subclinical symptom-network connectivity associations in siblings with respect to controls may be a sign of psychosis vulnerability in the siblings.

Decomposing the constituent oscillatory dynamics underlying mismatch negativity generation in schizophrenia: Distinct relationships to clinical and cognitive functioning

Abnormalities in early auditory information processing (EAIP) contribute to higher-order deficits in cognition and psychosocial functioning in schizophrenia. A passive auditory oddball paradigm is commonly used to evoke event-related potential (ERP) measures of EAIP reflecting auditory sensory registration and deviance detection, including mismatch negativity (MMN) and P3a responses. MMN and P3a have been extensively studied in healthy subjects and neuropsychiatric patient populations and are increasingly used as translational biomarkers in the development of novel therapeutics. Despite widespread use, relatively few studies have examined the constituent oscillatory elements and the extent to which sensory registration and deviance detection represent distinct or intercorrelated processes. This study aimed to determine the factor structure and clinical correlates of these oscillatory measures in schizophrenia patients (n = 706) and healthy comparison subjects (n = 615) who underwent clinical, cognitive, and functional characterization and EEG testing via their participation in the Consortium of Genomics in Schizophrenia (COGS-2) study. Results revealed significant deficits in theta-band (4-7 Hz) evoked power and phase locking in patients. Exploratory factor analyses of both ERP and oscillatory measures revealed two dissociable factors reflecting sensory registration and deviance detection. While each factor shared a significant correlation with social cognition, the deviance detection factor had a unique relationship to multiple cognitive and clinical domains. Results support the continued advancement of functionally relevant oscillatory measures underlying EAIP in the development of precognitive therapeutics.

Elevated mirror neuron system activity in bipolar mania: Evidence from a transcranial magnetic stimulation study

The role of the "mirror neuron system" (MNS) in the pathophysiology of mood disorders is not well studied. Given its posited role in the often-impaired socio-emotional processes like intention detection, empathy, and imitation, we compared putative MNS-activity in patients with bipolar mania and healthy comparison subjects. We also examined the association between putative MNS-activity and hyper-imitative behaviors in patients. We studied 39 medication-free individuals diagnosed with mania and 45 healthy comparison subjects. TMS-evoked motor cortical reactivity was measured via single- and paired-pulse stimuli (assessing SICI-short and LICI-long interval intracortical inhibition) while subjects viewed a static image and goal-directed actions. Manic symptom severity and imitative behaviors were quantified using the Young's Mania Rating Scale and a modification of the Echolalia Questionnaire. Two-way repeated measures analysis of variance demonstrated a significant group ×time interaction effect indicating greater facilitation of cortical reactivity during action-observation (putative MNS-activity) in the patient group as compared to the healthy group. While LICI-mediated MNS-activity had a significant association with manic symptom severity (r=0.35, P=0.038), SICI-mediated MNS-activity was significantly associated with incidental echolalia scores in a subgroup of 17 patients with incidental echolalia (r=0.75, P<0.001). Our findings demonstrate that putative MNS-activity is heightened in mania, possibly because of disinhibition, and associated with behavioral consequences (incidental echolalia).

Alpha7 acetylcholine receptor autoantibodies are rare in sera of patients diagnosed with schizophrenia or bipolar disorder.

The α7 acetylcholine receptor (AChR) has been linked with the onset of psychotic symptoms and we hypothesized therefore that it might also be an autoimmune target. Here, we describe a new radioimmunoassay (RIA) using iodine 125-labelled α-bungarotoxin and membrane extract from transfected HEK293 cells expressing human α7 AChR. This RIA was used to analyze sera pertaining to a cohort of 711 subjects, comprising 368 patients diagnosed with schizophrenia spectrum disorders, 140 with bipolar disorder, 58 individuals diagnosed of other mental disorders, and 118 healthy comparison subjects. We identified one patient whose serum tested positive although with very low levels (0.2 nM) for α7 AChR-specific antibodies by RIA. Three out of 711 sera contained antibodies against iodine 125-labelled α-bungarotoxin, because they precipitated with it in the absence of α7 AChR. This first evidence suggests that autoantibodies against α7 AChR are absent or very rare in these clinical groups.

Increased prolidase activity and high blood monocyte counts in pediatric bipolar disorder

Various psychological, genetic, and biochemical factors are thought to be involved in the aetiology of pediatric bipolar disorder (PBD). However, few studies have evaluated the biochemical basis of PBD. The level of peripheral blood mononuclear cells and serum prolidase activity were determined in PBD and matched healthy comparison subjects.Blood from 38 (age range: 14–17) PBD-type I and 37 age- and gender-matched healthy comparison subjects was analyzed for numbers of neutrophils, lymphocytes, monocytes, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) and serum prolidase activity. The prolidase activity and monocyte count were significantly higher in PBD than the control group. There were no significant differences in numbers of neutrophils, lymphocytes, LMR and NLR between the patient and control groups. These results suggest that the immune system and prolidase activity may be activated in PBD. There is a clinical benefit from the early detection of PBD using serum prolidase activity levels and monocyte counts. Especially, prolidase activity may be a trait marker for diagnosing PBD. However, further studies are needed to verify these findings.

Impaired generalization of reward but not loss in obsessive-compulsive disorder.

Generalizing from past experiences can be adaptive by allowing those experiences to guide behavior in new situations. Generalizing too much, however, can be maladaptive. For example, individuals with pathological anxiety are believed to overgeneralize emotional responses from past threats, broadening their scope of fears. Whether individuals with pathological anxiety overgeneralize in other situations remains unclear. The present study (N=57) used a monetary sensory preconditioning paradigm with rewards and losses to address this question in individuals with obsessive-compulsive disorder (OCD) and social anxiety disorder (SAD), comparing them to healthy comparison subjects (HC). In all groups, we tested direct learning of associations between cues and reward vs. loss outcomes, as well as generalization of learning to novel choice options. We found no differences between the three groups in the direct learning of stimuli with their outcomes: all subjects demonstrated intact stimulus-response learning by choosing rewarding options and avoiding negative ones. However, OCD subjects were less likely to generalize from rewards than either the SAD or HC groups, and this impairment was not found for losses. Additionally, greater deficits in reward generalization were correlated with severity of threat estimation, as measured by a subscale of the Obsessive Beliefs Questionnaire, both within OCD and across all groups. These findings suggest that a compromised ability to generalize from rewarding events may impede adaptive behavior in OCD and in those susceptible to high estimation of threat.

Neurocognition in Post-Treatment Lyme Disease and Major Depressive Disorder

Neurocognitive dysfunction in patients with residual or emergent symptoms after treatment for Lyme Disease is often attributed to comorbid depression. In this study, patients with Post-Treatment Lyme Disease Syndrome (PTLDS) were compared to patients with Major Depressive Disorder (MDD), as well as healthy comparison subjects (HC), on neurocognitive measures administered through the same laboratory, to determine if patterns of performance were similar. Two analyses were conducted. First, performance on the Wechsler Adult Intelligence Scale (WAIS-III) and on subtests from the Wechsler Memory Scale (WMS-III) was compared among the groups. Second, comparable subgroups of PTLDS and MDD patients with at least one low WMS-III score were compared on an additional set of measures assessing motor function, psychomotor performance, attention, memory, working memory, and language fluency, to determine if the overall profile of performance was similar in the two subgroups. In the first analysis, PTLDS patients performed more poorly than both MDD and HC on tasks assessing verbal abilities, working memory, and paragraph learning. Processing speed in the two patient groups, however, was equally reduced. In the second analysis, MDD patients with low WMS-III exhibited concomitantly greater difficulties in psychomotor speed and attention, while low-WMS-III PTLDS patients exhibited greater difficulties in language fluency. MDD and PTLDS can be confused neuropsychologically because both exhibit similar levels of psychomotor slowing. However, problems on memory-related tasks, though mild, are more pronounced in PTLDS. PTLDS patients with poorer memory also exhibit poorer language fluency, and less deficit in processing speed and attention compared to MDD.

Variation of nicotinic subtype α7 and muscarinic subtype M3 acetylcholine receptor expression in three main types of leukemia.

Cholinergic receptors, such as α7-nicotinic acetylcholine receptor (α7-nAChR) and M3-muscarinic acetylcholine receptor (M3-mAChR), have been demonstrated to serve a significant role in the proliferation, differentiation and apoptosis of leukemic cells. However, the expression of these receptors in samples from patients with leukemia remains unclear. The present study aimed to determine the expression of M3-mAChR and α7-nAChR in the bone marrow or peripheral blood of 51 patients with leukemia, including acute myeloid leukemia (AML; n=33), acute lymphoblastic leukemia (ALL; n=13), and chronic myeloid leukemia (CML; n=5). Peripheral blood mononuclear cells (PBMCs) were also isolated from healthy subjects (n=5) for comparison. Western blot analysis was performed to determine the protein expression profiles, and a pattern of decreased α7-nAChR levels in patients with leukemia was observed. Among the leukemia types, the lowest expression of α7-nAChR and M3-mAChR were identified in patients with T-cell ALL/lymphoma (T-ALL). CML exhibited the highest level of M3-mAChR, which was significantly different from APL and AML-M4, yet not from healthy subjects (P<0.05). Therefore, different expression profiles of α7-nACR and M3-mAChR were detected amongst the leukemia types. Collectively, the present study supports the potential role of cholinergic signaling in mediating leukemogenesis. However, further studies in larger cohorts are required to validate these findings.