Psychomotor Slowing Research Articles

Parkinsonism, Psychomotor Slowing, Negative and Depressive Symptoms in Schizophrenia Spectrum and Mood Disorders: Exploring Their Intricate Nexus Using a Network Analytic Approach.

Parkinsonism, psychomotor slowing, negative and depressive symptoms show evident phenomenological similarities across different mental disorders. However, the extent to which they interact with each other is currently unclear. Here, we hypothesized that parkinsonism is an independent motor abnormality showing limited associations with psychomotor slowing, negative and depressive symptoms in schizophrenia spectrum (SSD), and mood disorders (MOD). We applied network analysis and community detection methods to examine the interplay and centrality (expected influence [EI] and strength) between parkinsonism, psychomotor slowing, negative and depressive symptoms in 245 SSD and 99 MOD patients. Parkinsonism was assessed with the Simpson-Angus Scale (SAS). We used the Positive and Negative Syndrome Scale (PANSS) to examine psychomotor slowing (item #G7), negative symptoms (PANSS-N), and depressive symptoms (item #G6). In SSD and MOD, PANSS item #G7 and PANSS-N showed the largest EI and strength as measures of centrality. Parkinsonism had small or no influence on psychomotor slowing, negative and depressive symptoms in SSD and MOD. In SSD and MOD, exploratory graph analysis identified one community, but parkinsonism showed a small influence on its occurrence. Network Comparison Test yielded no significant differences between the SSD and MOD networks (global strength p value: .396 and omnibus tests p value: .574). The relationships between the individual domains followed a similar pattern in both SSD and MOD highlighting their transdiagnostic relevance. Despite evident phenomenological similarities, our results suggested that parkinsonism is more independent of negative and depressive symptoms than psychomotor slowing in both SSD and MOD.

Psychomotor Slowing in Psychosis and Inhibitory Repetitive Transcranial Magnetic Stimulation

Psychomotor slowing is a frequent symptom of psychosis, impairing gross and fine motor behavior. It is associated with poor outcomes and functioning, and no treatment is available. To investigate whether 15 sessions of inhibitory repetitive transcranial magnetic stimulation (rTMS) may reduce psychomotor slowing. This was a 4-arm, double-blind, randomized, sham-controlled trial at a university hospital in Switzerland. Enrollment took place from March 2019 to August 2022. Adults aged 18 to 60 years with schizophrenia spectrum disorders and severe psychomotor slowing were eligible. All patients continued existing medications, including antipsychotics and benzodiazepines. Those with substance misuse (other than nicotine), conditions associated with impaired or aberrant movement, convulsions, history of hearing problems, other conditions typically excluded from magnetic resonance imaging or TMS, any TMS treatment in the past 3 months, or those who were pregnant or breastfeeding were excluded. Of 615 patients screened for eligibility, 103 were randomized and 88 received at least 1 session of rTMS: 22 were assigned to 1-Hz rTMS, 22 to iTBS, 22 to sham, and 22 to the waiting group. Follow-up was conducted at 6 weeks and 24 weeks following the week 3 assessments including clinical, functional, and motor measures. Fifteen sessions of rTMS in 3 weeks over the supplementary motor area: 1-Hz rTMS, iTBS, sham, or no treatment (waiting). After 3 weeks, the waiting group received 15 sessions of 1-Hz rTMS over the supplementary motor area. The main outcome was the proportion of responders at week 3 in the Salpêtrière Retardation Rating Scale (SRRS) defined as a 30% or greater reduction from baseline (last-observation-carried-forward). The SRRS has 15 items and a maximum total score of 60. Of the 88 participants analyzed, 45 were men and 43 were women. The mean (SD) age was 36.3 (12.4) years and the mean (SD) SRRS score was 24.0 (5.9). A total of 69 participants completed the study. At week 3, response rates differed between groups: 15 of 22 (68%) in the 1-Hz rTMS group, 8 of 22 (36%) in the iTBS group, 7 of 22 (32%) in the sham group, and 4 of 22 (18%) in the waiting group (χ23 = 12.1; P = .007). The 1-Hz rTMS group had more responders than sham (odds ratio [OR], 0.13; 95% CI, 0.02-0.65; P = .03), iTBS (OR, 0.12; 95% CI, 0.02-0.61; P = .02), and waiting (OR, 0.04; 95% CI, 0.01-0.22; P = .003). In the waiting group, 10 of 16 participants (63%) responded after receiving 15 sessions of 1-Hz rTMS. No serious adverse events occurred. In this study, inhibitory add-on rTMS safely alleviated psychomotor slowing in psychosis compared with iTBS, sham, and no treatment. The treatment was also effective with delayed onset. Future studies need to explore the neural changes associated with supplementary motor area rTMS in psychosis. ClinicalTrials.gov Identifier: NCT03921450.

Psychomotor slowing in schizophrenia is associated with cortical thinning of primary motor cortex: A three cohort structural magnetic resonance imaging study

Psychomotor slowing (PS) is characterized by slowed movements and lower activity levels. PS is frequently observed in schizophrenia (SZ) and distressing because it impairs performance of everyday tasks and social activities. Studying brain topography contributing to PS in SZ can help to understand the underlying neurobiological mechanisms as well as help to develop more effective treatments that specifically target affected brain areas. Here, we conducted structural magnetic resonance imaging (sMRI) of three independent cohorts of right-handed SZ patients (SZ#1: n = 72, SZ#2: n = 37, SZ#3: n = 25) and age, gender and education matched healthy controls (HC) (HC#1: n = 40, HC#2: n = 37, HC#3: n = 38). PS severity in the three SZ cohorts was determined using the Positive and Negative Syndrome Scale (PANSS) item #G7 (motor retardation) and Trail-Making-Test B (TMT-B). FreeSurfer v7.2 was used for automated parcellation and segmentation of cortical and subcortical regions. SZ#1 patients showed reduced cortical thickness in right precentral gyrus (M1; p = 0.04; Benjamini-Hochberg [BH] corr.). In SZ#1, cortical thinning in right M1 was associated with PANSS item #G7 (p = 0.04; BH corr.) and TMT-B performance (p = 0.002; BH corr.). In SZ#1, we found a significant correlation between PANSS item #G7 and TMT-B (p = 0.005, ρ=0.326). In conclusion, PANSS G#7 and TMT-B might have a surrogate value for predicting PS in SZ. Cortical thinning of M1 rather than alterations of subcortical structures may point towards cortical pathomechanism underlying PS in SZ.

The Behavioral Mapping of Psychomotor Slowing in Psychosis Demonstrates Heterogeneity Among Patients Suggesting Distinct Pathobiology.

Psychomotor slowing (PS) occurs in up to half of schizophrenia patients and is linked to poorer outcomes. As standard treatment fails to improve PS, novel approaches are needed. Here, we applied the RDoC framework using 3 units of analysis, ie, behavior, self-report, and physiology to test, whether patients with PS are different from patients without PS and controls. Motor behavior was compared between 71 schizophrenia patients with PS, 25 without PS, and 42 healthy controls (HC) using 5 different measures: (1) for behavior, an expert rating scale: Motor score of the Salpêtrière Retardation Rating Scale, (2) for self-report, the International Physical Activity Questionnaire; and for physiology, (3) Actigraphy, which accounts for gross motor behavior, (4) Gait velocity, and (5) coin rotation task to assess manual dexterity. The ANCOVAs comparing the 3 groups revealed differences between patients with PS and HC in expert ratings, self-report, and instrumental measures (all P ≤ .001). Patients with PS also scored higher in expert ratings and had lower instrumental activity levels compared to patients without PS (all P ≤ .045). Instrumental activity levels correlated with an expert rating of PS (rho = -0.51, P-fdr corrected <.001) and classified similarly at 72% accuracy. PS is characterized by slower gait, lower activity levels, and slower finger movements compared to HC. However, only actigraphy and observer ratings enable to clearly disentangle PS from non-PS patients. Actigraphy may become the standard assessment of PS in neuroimaging studies and clinical trials.

Motor abnormalities are associated with poor social and functional outcomes in schizophrenia

BackgroundUp to 50% of patients with schizophrenia are suffering from motor abnormalities, which may contribute to decreased quality of life, impaired work capacity, and a reduced life expectancy by 10–20 years. However, the effect of motor abnormalities on social and global functioning, as well as, functional capacity is not clear. We hypothesized, that the presence of motor abnormalities is associated with poorer functional outcomes in patients with schizophrenia. MethodsWe collected data on 5 different motor abnormalities in 156 patients suffering from schizophrenia spectrum disorders: parkinsonism, catatonia, dyskinesia, neurological soft signs and psychomotor slowing (PS). Additionally, we used three different scales to evaluate the functional outcomes in these patients: the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS) which use clinicians' judgment; and one using a performance-based measure of functional capacity, the brief version of the UCSD Performance-based Skills Assessment (UPSA-B). ResultsOur analysis demonstrated that patients with catatonia (all F > 4.5; p < 0.035) and parkinsonism (all F > 4.9; p < 0.027) scored lower on GAF and SOFAS compared to patients without catatonia and parkinsonism. In contrast, no significant difference on functional outcomes between patients with dyskinesia versus without dyskinesia exist in our study. Furthermore, there are statistically significant negative correlations for parkinsonism and PS with GAF, SOFAS and UPSA-B (all tau are at least −0.152, p-value <0.036). We also found significant negative correlations between catatonia and both GAF & SOFAS (all tau are at least −0.203, p-value<0.001) and between NES and SOFAS (tau = −0.137, p-value = 0.033). ConclusionHere, we showed that four of the most common motor abnormalities observed in schizophrenia were associated with at least one of the patients' functional outcomes. The stronger the motor impairment was the worse the global and social functioning. Future studies need to test, whether amelioration of motor abnormalities is linked to improved community functioning.

S38. EXPERT RATERS RELIABLY ASSESS PSYCHOMOTOR SLOWING IN PSYCHOSIS, BUT SELF-REPORT DOES NOT

BackgroundMotor abnormalities frequently occur in schizophrenia along with hallucinations, delusions, and negative symptoms. Psychomotor slowing (PS) is one of these motor abnormalities and is characterized by reduced levels of spontaneous gross motor activity as measured by actigraphy, slowed gait and slowing in fine motor tasks. Several reports indicated that 30–50% of schizophrenia patients are suffering from PS. Moreover, PS is associated with multiple disadvantages such as sedentary behavior, cardiometabolic risks and predicts poor treatment outcome and long-term cognition deficits. Therefore, there is a need to accurately and reliably evaluate PS in clinical settings.In the current study, we anaylized how the gold-standard actigraphy corresponds to either self-report or expert ratings.MethodsIn the present study, we evaluated the motor behavior of 23 patients suffering from schizophrenia spectrum disorders and 17 healthy controls using 3 distinct methods. (i) An observer rating scale: The Salpêtrière Retardation Rating Scale (SRRS), which is a 15 Items-scale ranging from 0 to 60 points measuring PS. A higher score indicates severe impairment. (ii) A self-report Questionnaire: the International Physical Activity Questionnaire (IPAQ), in which the participant report their physical activity. It is a 7 Items-scale, which estimates the weekly metabolic commitment to walk and to perform physical activities of moderate and vigorous intensities. The higher the score, the more active was the person during the last week. (iii) the gold-standard actigraphy, which measures the gross motor activity of the participants for 24h by wearing an actiwatch on the non-dominant arm. It integrates all movements of a subject whithin 24 hours into one parameter.ResultsBoth the physical activity measured with wrist activity (t(35) = 3.901, p < .005; controls: m = 349099, sd = 112853; patients: m = 228072, sd = 74639) and the observer rated SRRS-score (t(38) = -15.235, p < .001; controls: m = .41, sd = .62; patients: m = 26.30, sd = 6.96) differed between patients and controls. However, self-reported physical activity did not differ between both groups (t(38) = 1.452, p = .155; controls: m = 4502, sd = 6103; patients: m = 2241, sd = 3727).There is a trend for a negative correlation between the SRRS-score and the objective activity level, measured by actigraphy, in patients (r = -.378, p = .100). This suggests that patients with the highest SRRS scores indeed presented also the lowest level of global activity. There is also a positive correlation between the objective activity level and the self-reported activity in patients yet lacking statistical significance (r = .337, p = .147). However, there is no correlation between SRRS and IPAQ (r = .204, p = .349) in patients.DiscussionIn this study, we demonstrated that the expert ratings (SRRS) correspond well to the gold standard actigrahpy, even though this association is not significant yet. Thus, expert raters seem to rate PS correctly in patients. However, the self-report (IPAQ) neither corresponds well with the expert ratings nor the actigraphy. Thus, in evaluating PS in psychosis, researchers should not rely on self-report exclusively. Finally, this finding also suggests that patients may not perceive their physical inactivity correctly in case this was due to psychomotor slowing.

M164. RESTING-STATE CEREBRAL BLOOD FLOW IN SCHIZOPHRENIA PATIENTS WITH PSYCHOMOTOR SLOWING

BackgroundSchizophrenia patients who are suffering from psychomotor slowing (PS) present reduced levels of spontaneous motor activity, as well as slowing of gait and of fine motor dexterity. These motor abnormalities predict poor clinical outcomes for the patients. Recently, MRI studies have shown both aberrant functional and structural connectivity in schizophrenia patients with PS especially in the basal ganglia and the motor/premotor cortex. Arterial spin labeling imaging (ASL) perfusion MRI allows for quantitative measurement of cerebral blood flow (CBF). We used this approach to assess the difference in resting-state CBF between schizophrenia patients with psychomotor slowing and healthy controls as well as the relationships between CBF and motor symptoms in patients. In the current study, we included patients with moderate to severe PS. We hypothesized the intensity of the motor impairment in the patients would be linked to an abnormal increase of the CBF in several areas of the motor system, including basal ganglia, parietal cortex, and motor/premotor cortex.Methods30 participants (13 healthy controls and 17 schizophrenia patients with PS) took part in an MRI session during which we acquired ASL perfusion MRI. We also evaluated psychomotor slowing in patients using 3 distinct measures (a self-report of motor activity using the International Physical Activity Questionnaire (IPAQ), an observer rating using the Salpêtrière Retardation Rating Scale (SRRS), and an objective measure of the global level of activity using wrist actigraphy). First, we assessed differences between groups in quantitative resting CBF. Then, in patients, we explored the association between the 3 different motor disorder measures and the whole-brain resting CBF.ResultsA group comparison showed significantly increased CBF in the right inferior temporal gyrus in patients compared to healthy controls (two samples t-test: t=3.44, p<0.001 (uncorrected), cluster-level correction (kE=75): p(FWE-corr)=0.028, q(FDR-corr)=0.005). Increased severity of psychomotor slowing as measured by SRRS was associated with higher CBF in a widespread network (Multiple regression Z>4, p<0.001 (uncorrected), cluster-level correction (kE=75) p(FWE-corr)<0.001, q(FDR-corr)<0.001)) including the basal ganglia (i.e. striatum and putamen), the right lateral premotor cortex, bilateral Insulas, anterior cingulate cortices, inferior temporal gyri, parietal cortices, and the right parahippocampus. Both IPAQ and actigraphy failed to correlate with the resting CBF.DiscussionThese findings suggest that schizophrenia patients with PS presented an alteration of the resting cerebral blood flow compared to healthy controls. Moreover, in line with our hypothesis, the severity of the psychomotor slowing seems to be associated with increased blood flow in schizophrenia patients in a large network including basal ganglia, parietal cortex, and lateral premotor cortex. Finally among the 3 distinct measures used in the current study, only the SRRS seems to be associated with an abnormal increase of the cerebral blood flow. These findings confirm that psychomotor slowing is associated with an alteration of the cerebral blood flow in the motor/premotor network. We expect refined results as we include more subjects in the running study.

Psychomotor Slowing in Schizophrenia: Implications for Endophenotype and Biomarker Development.

Motor abnormalities (e.g., dyskinesia, psychomotor slowing, neurological soft signs) are core features of schizophrenia that occur independent of drug treatment and are associated with the genetic vulnerability and pathophysiology for the illness. Among this list, psychomotor slowing in particular is one of the most consistently observed and robust findings in the field. Critically, psychomotor slowing may serve as a uniquely promising endophenotype and/or biomarker for schizophrenia considering it is frequently observed in those with genetic vulnerability for the illness, predicts transition in subjects at high-risk for the disorder, and is associated with symptoms and recovery in patients. The purpose of the present review is to provide an overview of the history of psychomotor slowing in psychosis, discuss its possible neural underpinnings, and review the current literature supporting slowing as a putative endophenotype and/or biomarker for the illness. This review summarizes substantial evidence from a diverse array of methodologies and research designs that supports the notion that psychomotor slowing not only reflects genetic vulnerability, but is also sensitive to disease processes and the pathophysiology of the illness. Furthermore, there are unique deficits across the cognitive (prefix "psycho") and motor execution (root word "motor") aspects of slowing, with cognitive processes such as planning and response selection being particularly affected. These findings suggest that psychomotor slowing may serve as a promising endophenotype and biomarker for schizophrenia that may prove useful for identifying individuals at greatest risk and tracking the course of the illness and recovery.

Inflammation Mediates Body Weight and Ageing Effects on Psychomotor Slowing

Inflammation (immune system activation) affects neuronal function and may have consequences for the efficiency and speed of functional brain processes. Indeed, unusually slow psychomotor speed, a measure predictive of behavioural performance and health outcomes, is found with obesity and ageing, two conditions also associated with chronic inflammation. Yet whether inflammation is the mediating factor remains unclear. Here, we assessed inflammation by indexing interleukin-6 level in blood and measured psychomotor speed as well as indices of selective visual attention in young (mean = 26 years) or old (mean = 71 years) adults (N = 83) who were either lean or currently significantly overweight (mean body mass index = 22.4 and 33.8, respectively). Inflammation was positively and significantly correlated with psychomotor speed, age, and body mass index but not with attention measures. Using mediation analyses we show for the first time that inflammation fully accounts for the significant psychomotor slowing found in those with high BMI. Moreover, we further show that age-related psychomotor slowing is partially mediated by inflammation. These findings support the proposal that reducing inflammation may mitigate weight- and age-related cognitive decline and thereby improve performance on daily tasks and health outcomes more generally.

103. Dopaminergic Decline, Psychomotor Slowing, and Late Life Depression

Decreased processing and gait speed are common in late life depression (LLD), explain much of the disability associated with LLD, and predict antidepressant non-response. Since progressive age-related reductions in dopamine levels may contribute to slowing, our goal was to evaluate dopamine augmentation as a novel therapeutic strategy for LLD.

Overcoming Psychomotor Slowing in Psychosis (OCoPS-P)

Overcoming Psychomotor Slowing in Psychosis (OCoPS-P)

Antibodies to Signaling Molecules and Receptors in Alzheimer's Disease are Associated with Psychomotor Slowing, Depression, and Poor Visuospatial Function.

Alzheimer's disease (AD) is associated with several antibodies as well as signaling molecules and receptors. These may be detrimental in the presence of a disrupted blood-brain barrier (BBB). To investigate whether the levels of antibodies toward 33 signaling molecules involved in neurotransmitter, vascular, and immune functions were associated with AD and, within the AD group; cognitive function and mood. Antibodies in sera from patients with mild AD [(n = 91) defined as a Mini-Mental State Examination ≥ 20 or a Clinical Dementia Rating Scale≤1] and healthy controls (n = 102) were measured with enzyme-linked immunosorbent assays. Levels in AD and controls were compared by Mann-Whitney test. In the AD group, associations between antibodies and psychometric test scores were analyzed by robust regression. The false discovery threshold was set to 0.05. Antibodies to serotonin receptors [5-HT2AR (effect size (r) = 0.21, p = 0.004), 5-HT2CR (r = 0.25, p = 0.0005) and 5-HT7R (r = 0.21, p = 0.003)], vascular endothelial growth factor receptor 1 [VEGFR1 (r = 0.29, p < 0.001)] and immune-receptors (Stabilin-1 (r = 0.23, p = 0.001) and C5aR1 (r = 0.21, p = 0.004) were higher in AD. Psychomotor speed was associated with D1R-abs (β 0.49, p < 0.001), depression with ETAR-abs (β 0.31, p < 0.001), and visuospatial function with 5-HT1AR-abs (β 0.27, p = 0.004) despite similar antibody levels compared to controls. Antibody levels to VEGFR1, serotonergic receptors, and receptors in the immune system were increased in AD. Antibodies at similar levels as in controls were associated cognitive dysfunction and depression in AD.

Regional Gray Matter Volumes as Related to Psychomotor Slowing in Adults with Type 1 Diabetes.

Psychomotor slowing is a common cognitive complication in type 1 diabetes (T1D), but its neuroanatomical correlates and risk factors are unclear. In nondiabetic adults, smaller gray matter volume (GMV) and presence of white matter hyperintensities are associated with psychomotor slowing. We hypothesize that smaller GMV in prefronto-parietal regions explains T1D-related psychomotor slowing. We also inspect the contribution of microvascular disease and hyperglycemia. GMV, white matter hyperintensities (WMH), and glucose levels were measured concurrently with a test of psychomotor speed (Digit Symbol Substitution Test [DSST]) in 95 adults with childhood-onset T1D (mean age/duration = 49/41 years) and 135 similarly aged non-T1D adults. Linear regression models tested associations between DSST and regional GMV, controlling for T1D, sex, and education; a bootstrapping method tested whether regional GMV explained between-group differences in DSST. For the T1D cohort, voxel-based and a priori regions-of-interest methods further tested associations between GMV and DSST, adjusting for WMH, hyperglycemia, and age. Bilateral putamen, but no other regions examined, significantly attenuated DSST differences between the cohorts (bootstrapped unstandardized indirect effects: -3.49, -3.26; 95% confidence interval = -5.49 to -1.80, -5.29 to -1.44, left and right putamen, respectively). Among T1D, DSST was positively associated with GMV of bilateral putamen and left thalamus. Neither WMH, hyperglycemia, age, nor other factors substantially modified these relationships. For middle-aged adults with T1D and cerebral microvascular disease, GMV of basal ganglia may play a critical role in regulating psychomotor speed, as measured via DSST. Studies to quantify the impact of basal ganglia atrophy concurrent with WMH progression on psychomotor slowing are warranted.

Preserved Emotional Modulation of Motor Response Time Despite Psychomotor Slowing in Young-Old Adults

ABSTRACTWhereas aging affects cognitive and psychomotor processes negatively, the impact of aging on emotional processing is less clear. Using an “old–new” binary decision task, we ascertained the modulation of response latencies after presentation of neutral and emotional pictures in “young” (M = 27.1 years) and “young-old” adults with a mean age below 60 (M = 57.7 years). Stimuli varied on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Young-old adults had significantly longer reaction times. However, young and young-old adults showed the exact same pattern of response time modulation by emotional stimuli: Response latencies were longer for high-arousal than for low-arousal pictures and longer for negative than for positive or neutral stimuli. This result suggests that the specific effects of implicitly processed emotional valence and arousal information on behavioral response time are preserved in young-old adults despite significant age-related psychomotor decline.

Memory Dysfunction, Psychomotor Slowing, and Decreased Executive Function Predict Mortality in Patients With Heart Failure and Low Ejection Fraction

Background The purpose of this study was to evaluate whether dysfunction of specific cognitive abilities is a predictor of impending mortality in adults with systolic heart failure (HF). Methods A total of 166 stable outpatients with HF completed cognitive function evaluation in language, working memory, memory, visuospatial ability, psychomotor speed, and executive function using a neuropsychological test battery. Demographic and clinical variables, comorbidity, depressive symptoms, and health-related quality of life were also measured. Patients were followed for 12 months to determine all-cause mortality. Results There were 145 survivors and 21 deaths. In logistic regression analyses, significant predictors of mortality were lower left ventricular ejection fraction (LVEF) and poorer scores on measures of global congnitive function Mini-Mental State Examination [MMSE], working memory, memory, psychomotor speed, and executive function. Memory loss was the most predictive cognitive function variable (overall χ 2 = 17.97, df = 2, P < .001; Nagelkerke R 2 = 0.20). Gender was a significant covariate in 2 models, with men more likely to die. Age, comorbidity, depressive symptoms, and health-related quality of life were not significant predictors. In further analyses, significant predictors of mortality were lower systolic blood pressure and poorer global cognitive function, working memory, memory, psychomotor speed, and executive function, with memory being the most predictive. Conclusions As hypothesized, lower LVEF and memory dysfunction predicted mortality. Poorer global cognitive score as determined by the MMSE, working memory, psychomotor speed, and executive function were also significant predictors. LVEF or systolic blood pressure had similar predictive values. Interventions are urgently needed to prevent and manage memory loss in HF.

Peripheral Inflammation is Associated with Altered Substantia Nigra Activity and Psychomotor Slowing in Humans

BackgroundSystemic infections commonly cause sickness symptoms including psychomotor retardation. Inflammatory cytokines released during the innate immune response are implicated in the communication of peripheral inflammatory signals to the brain.MethodsWe used functional magnetic resonance brain imaging (fMRI) to investigate neural effects of peripheral inflammation following typhoid vaccination in 16 healthy men, using a double-blind, randomized, crossover-controlled design.ResultsVaccination had no global effect on neurovascular coupling but markedly perturbed neural reactivity within substantia nigra during low-level visual stimulation. During a cognitive task, individuals in whom typhoid vaccination engendered higher levels of circulating interleukin-6 had significantly slower reaction time responses. Prolonged reaction times and larger interleukin-6 responses were associated with evoked neural activity within substantia nigra.ConclusionsOur findings provide mechanistic insights into the interaction between inflammation and neurocognitive performance, specifically implicating circulating cytokines and midbrain dopaminergic nuclei in mediating the psychomotor consequences of systemic infection.

Psychomotor Slowing in Schizophrenia

Psychomotor slowing (PS) is a cluster of symptoms that was already recognized in schizophrenia by its earliest investigators. Nevertheless, few studies have been dedicated to the clarification of the nature and the role of the phenomenon in this illness. Moreover, slowed psychomotor functioning is often not clearly delineated from reduced processing speed. The current, first review of all existing literature on the subject discusses the key findings. Firstly, PS is a clinically observable feature that is most frequently established by neuropsychological measures assessing speed of fine movements such as writing or tasks that require rapid fingertip manipulations or the maintenance of maximal speed over brief periods of time in manual activities. Moreover, the slowed performance on the various psychomotor measures has been demonstrated independent of medication and has also been found to be associated with negative symptoms and, to a lesser extent, with positive and depressive symptoms. Importantly, performance on the psychomotor tasks proved related to the patients' social, clinical, and functional outcomes. Several imaging studies showed slowed performance to coincide with dopaminergic striatal activity. Finally, conventional neuroleptics do not improve the patients' PS symptoms, in contrast to the atypical agents that do seem to produce modestly improving effects.

Nucleus Accumbens Dopamine and the Forebrain Circuitry Involved in Behavioral Activation and Effort-Related Decision Making: Implications for Understanding Anergia and Psychomotor Slowing in Depression

The notion that motivated behaviors having an energetic or activational component is an old one, and there are numerous examples of this idea from the literatures of psychology and ethology. Behavioral researchers have demonstrated that vigor or persistence of work output in stimulus-seeking behavior is a fundamental aspect of motivation. In addition, psychiatrists and clinical psychologists have come to emphasize the importance of energy-related dysfunctions, such as psychomotor slowing and apathy, in various clinical syndromes. Because of the potential scientific importance and clinical relevance of behavioral activation processes, it is critical to determine the brain mechanisms that are involved. Considerable evidence indicates that DA in nucleus accumbens is involved in activational aspects of motivation. Accumbens DA depletions decrease spontaneous, stimulant-induced, and food-induced motor activity. In addition, the effects of accumbens DA depletions on food-seeking behavior depend greatly upon the response requirements of the task. Research involving concurrent choice tasks has shown that rats with accumbens DA depletions reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead select a less-effortful type of food-seeking behavior. Rats with accumbens DA depletions are particularly sensitive to lever pressing schedules with high ratio requirements (i.e., a large number of lever presses must be emitted for reinforcement to occur). Together with studies of frontal cortex function in animals, and clinical studies on neurochemical and other functional changes in the human brain, this line of research could have implications for understanding the brain circuitry involved in energy-related psychiatric disorders such as psychomotor slowing in depression, anergia, fatigue and apathy.

Psychomotor Slowing as a Predictor of Fluoxetine Nonresponse in Depressed Outpatients

This study examined the utility of baseline psychomotor speed, measured with neuropsychological tests, to predict fluoxetine response in moderately depressed outpatients. The authors hypothesized that since psychomotor slowing in depressed patients has been linked to reduced dopaminergic neurotransmission, patients with slowing would be unresponsive to fluoxetine, a selective serotonin reuptake inhibitor. After baseline neuropsychological testing, patients were treated openly with fluoxetine for 12 weeks. Thirty-seven patients completed the trial. Compared to the 25 patients who responded, the 12 patients who did not respond to fluoxetine exhibited significantly poorer performance in verbal fluency on the Controlled Oral Word Association Test FAS and in color naming on the Stroop Color and Word Test. In addition, the nonresponders tended to perform worse than the responders on the Stroop Color and Word Test reading subtest and the WAIS-III digit symbol subtest. Differential treatment response was specific to psychomotor speed because responders and nonresponders did not perform differently on tasks of executive functioning, attention, visuospatial functioning, or verbal intelligence. Psychomotor slowing may identify a subgroup of depressed patients who have a dopaminergic deficit that is unresponsive to fluoxetine monotherapy and who should therefore receive an alternative treatment.

HIV Dementia Scale and Psychomotor Slowing—The Best Methods in Screening for Neuro-AIDS

The authors examined the correlation between Human Immunodeficiency Virus (HIV) Dementia Scale (HDS) and psychomotor tests, evaluating basal ganglia function in 266 HIV-seropositive, Caucasian, homosexual men. Fifty-five HIV-positive, patients with mild dementia (HDS score < or =10) showed significant slowing of most rapid alternating movements (MRAM) and significantly prolonged contraction times compared to 211 HIV-positive nondemented patients (HDS score >10). Motor performance correlated significantly with the time-dependent HDS subscores for psychomotor speed and construction and HDS sum score. In contrast to contraction times and MRAM, HDS scores also showed significant correlations to age, premorbid and actual intelligence, and duration of HIV seropositivity.