Search

Background Although remission is a priority target in psychosis, reported rates show a marked variation across studies and instability over time. Such variability, partly due to methodology, emphasizes the need to define the optimal assessment procedure, as well as to identify reliable predictors. This study aims to: 1. longitudinally compare remission status according to different criteria; 2. identify predictors of duration and stability. Methods 112 patients with schizophrenia or schizoaffective disorder underwent comprehensive clinical evaluations, with 24-month follow-up. Remission was assessed using three criteria: Remission in Schizophrenia Working Group (RSWG) vs Positive and Negative Syndrome Scale (PANSS) positive and negative scales (PANSS-PN) vs total score (PANSS-T). Kaplan-Meier survival analysis was used for longitudinal comparison, regression models to identify predictors of duration and stability. Results At enrolment 50% of patients were in remission according to RSWG, while only 23.2% reached the other criteria. PANSS-T cumulative remission rates showed the greatest stability. Stable remission according to RSWG criteria was predicted by negative symptoms, while no significant predictors emerged for PANSS-T. Remission duration was predicted by negative, positive and cognitive symptoms and treatment dosage for RSWG criteria, while for PANSS-T the predictors were cognitive symptoms and duration of illness. Conclusion Results are in line with previous literature on remission rates and further support the role of basal clinical predictors. In addition, this study shows that more stringent criteria are more stable over time, suggesting their predictive value and the relevance of their use to optimize evaluations also in clinical settings.

BACKGROUND Patients with bipolar disorder (BD) often have impairments in neurocognition, including affective processing and affective response inhibition. While studies suggest that cognitive control in general may decline with age in BD, less is known about age-related changes in response inhibition to emotionally salient information. METHODS 258 participants with BD and 54 healthy controls, ages 18-70, completed the Cambridge Neuropsychological Test Automated Battery (CANTAB) Affective Go/No-Go task to assess affective response inhibition to positive and negative valenced stimuli. We examined the relationship between BD and affective response inhibition (number of commission and omission errors and reaction time), as well as a potential moderating effect of age, using mixed effects linear regression models. RESULTS The BD group made more omission and commission errors overall than the control group (p

Background and purpose Multiple sclerosis (MS) is a chronic inflammatory disease causing a wide range of symptoms including motor and cognitive impairment, fatigue and pain. Over the last two decades, non-invasive brain stimulation, especially transcranial direct current stimulation (tDCS), has increasingly been used to modulate brain function in various physiological and pathological conditions. However, its experimental applications for people with MS were noted only as recently as 2010 and have been growing since then. The efficacy for use in people with MS remains questionable with the results of existing studies being largely conflicting. Hence, the aim of this review is to paint a picture of the current state of tDCS in MS research grounded on studies applying tDCS that have been done to date. Methods A keyword search was performed to retrieve articles from the earliest article identified until 14 February 2021 using a combination of the groups (1) ‘multiple sclerosis’, ‘MS’ and ‘encephalomyelitis’ and (2) ‘tDCS’ and ‘transcranial direct current stimulation’. Results The analysis of the 30 articles included in this review underlined inconsistent effects of tDCS on the motor symptoms of MS based on small sample sizes. However, tDCS showed promising benefits in ameliorating fatigue, pain and cognitive symptoms. Conclusion Transcranial direct current stimulation is attractive as a non-drug approach in ameliorating MS symptoms, where other treatment options remain limited. The development of protocols tailored to the individual's own neuroanatomy using high definition tDCS and the introduction of network mapping in the experimental designs might help to overcome the variability between studies.

Creutzfeld-Jakob Disease (CJD) is a rare disease but a common cause of rapidly progressive neurodegeneration. Although the "classic" presentation involves early dementia or behavioral changes, there are well-described atypical variants with less prominent cognitive symptoms at onset. One such variant is Corticobasal Syndrome (CBS), which may be seen with other underlying neurodegenerative processes, but when due to prion disease pathology involves much more rapid progression and certain characteristic imaging findings. This report presents a case presenting as CBS without cognitive or behavioral changes at onset, which rapidly progressed and was determined ultimately to be due to underlying CJD. This case illustrates the need for a high index of suspicion for CJD in order to drive appropriate diagnostic testing and careful review of imaging and EEG findings, which may be subtle in early disease.

Background: Smoking is a psychosocial problem regarding its causes mainly. In primary health care units, depression is the most common problem that affects the whole body and arises with physical, emotional, and cognitive symptoms. This study aimed to determine the prevalence rate of tobacco smoking and depressive symptoms among male medical students of Albaha university. Also, to investigate the association between tobacco smoking and depressive symptoms among male medical students of Albaha university. Method: A cross-sectional study was conducted on All the male medical students in the all-academic year levels of Al-Baha medical college using a self-administrated questionnaire. Results: Two hundred and eight medical students completed the study. About half of the participants (49.5%) weren't smokers. More than two-thirds (69.5%) started smoking in the first academic year. Our statistical analysis results reported; a significant correlation regarding the marital status (P-value = 0.000). The abnormality was significantly higher among current smokers (P-value = 0.013) and markedly lower among nonsmokers (P-value = 0.004). Regarding types of smoking, cigarette smokers were seriously depressed (P-value = 0.000). Conclusion: There is a relationship between smoking and depressive state among medical students. Researches must be conducted to explain this relation of depression symptoms with tobacco and not to increase the prevalence of smoking by helping students quit smoking.

OBJECTIVES To explore whether caregiver characteristics were associated with cognitive complaints reported by women with breast cancer undergoing chemotherapy. SAMPLE A SETTING 61 dyads of women with breast cancer and their caregivers were recruited at Duke Women's Cancer Care Raleigh in North Carolina. METHODS A VARIABLES An exploratory, cross-sectional design was used. Data were obtained on patients and caregivers. Patient cognitive complaints were represented by cognitive impairment (CI) and cognitive ability (CA). RESULTS Two significant associations were found. IMPLICATIONS FOR NURSING Healthcare providers should consider caregivers when assessing and managing patients' cognitive symptoms. This study suggests the value of including caregivers when establishing interventions for patients who have cognitive complaints.

Intrinsic brain tumors often occur within functional neural networks, leading to neurological impairment and disability of varying degrees. Advances in our understanding of tumor-network integration, human cognition and language processing, and multiparametric imaging, combined with refined intraoperative tumor resection techniques, have enhanced surgical management of intrinsic brain tumors within eloquent areas. However, cognitive symptoms impacting health-related quality of life, particularly processing speed, attention, concentration, working memory, and executive function, often persist after the postoperative recovery period and treatment. Multidisciplinary cognitive rehabilitation is the standard of care for addressing cognitive impairments in many neurological diseases. There is promising research to support the use of cognitive rehabilitation in adult brain tumor patients. In this review, we summarize the history and usefulness of postacute cognitive rehabilitation for adult brain tumor patients.

PURPOSE OF REVIEW: Excessive synaptic pruning has first been suggested by Irwin Feinberg (1982) as an important pillar in the pathophysiology in schizophrenia (SCZ). This article reviews recent developments highlighting factors implicated in aberrant synaptic pruning and its contribution to disease onset and emergence of cognitive symptoms in SCZ. Unraveling these factors provides new insights for potential prevention and treatment strategies for psychotic disorders.RECENT FINDINGS: Increased pruning in SCZ was recently confirmed by a positron emission tomography-study employing the novel tracer [11C]UCB-J, demonstrating the consequential loss of synaptic density. Recent evidence supports the contributing role of astrocytes and increased complement-mediated microglial pruning in disease onset and cognitive symptoms in SCZ. Increased microglial pruning is mediated specifically by C4. Furthermore, environmental factors (e.g., infections and stress) can lead to dysbiosis which was recently linked to microglial activation and pruning in SCZ.SUMMARY: Recent findings render the pruning machinery a potential target for early treatment and prevention in individuals at high risk for SCZ. Minocycline can improve cognition in SCZ, probably by reducing excessive pruning. Probiotics might also have beneficial effects on cognition, although recent findings are not encouraging. N-acetyl-cysteine recovers functional connectivity in SCZ both in vitro and in vivo, making it an interesting candidate.

This article reports preliminary evidence for the effectiveness of eye movement desensitization and reprocessing psychotherapy (EMDR) therapy, applying bilateral alternating tactile stimulation in treating cognitive symptoms in patients with generalized anxiety disorder (GAD). A single-case experimental design was used in seven clinical cases. The Penn State Worry Questionnaire, Intolerance of Uncertainty, Cognitive Avoidance Questionnaire, and Negative Problem Orientation Questionnaire were administered at five points during pretreatment (which established the baseline phase serving as each participant's control), at three points during the treatment phase, at the end of it, and at the 3- and 6-month follow-ups. Each participant received 16 treatment sessions. Visual, statistical, and clinical significance analyses were conducted. The cognitive symptoms treated were: excessive worry, intolerance of uncertainty, cognitive avoidance, and negative orientation to problems. All four cognitive symptoms subsided, with large effect sizes in all cases, between pre- and posttreatment, which can be observed in the visual and statistical analysis of each case. Pre- and post-cognitions are specified in each case. According to the clinical significance analysis, all participants evidenced a change towards an improvement. Finally, evidence is given in favor of the usefulness of EMDR therapy for the treatment of cognitive symptoms in participants diagnosed with GAD. However, these results must be considered cautiously when generalizing data.

Purpose of review To provide an update of recent studies describing the effects of transcranial direct current stimulation (tDCS) on patients with schizophrenia, with particular focus on auditory verbal hallucinations (AVH), cognitive deficits, and negative symptoms. Recent findings As a low-cost, easy-to-use neuromodulation technique, tDCS may have clinical implications for those suffering from treatment-persistent AVH, negative symptoms, and cognitive symptoms in schizophrenia. Over the past decade, tDCS has shown no effects for negative symptoms, except when used at a high frequency of sessions, and inconclusive results for AVH and cognitive symptoms. The treatment has little to no adverse effects. Summary The studies reviewed here support the need for further investigation and empirical data regarding the use of tDCS. The underlying mechanisms of tDCS as well as the most effective stimulation parameters must be better understood. Findings support the need for increased duration and frequency of tDCS sessions. One of the next steps is the investigation of effects of concomitant nonpharmacological treatments with tDCS.

Reductions of baseline cerebral blood flow (CBF) of ∼10–20% are a common symptom of Alzheimer’s disease (AD) that appear early in disease progression and correlate with the severity of cognitive impairment. These CBF deficits are replicated in mouse models of AD and recent work shows that increasing baseline CBF can rapidly improve the performance of AD mice on short term memory tasks. Despite the potential role these data suggest for CBF reductions in causing cognitive symptoms and contributing to brain pathology in AD, there remains a poor understanding of the molecular and cellular mechanisms causing them. This review compiles data on CBF reductions and on the correlation of AD-related CBF deficits with disease comorbidities (e.g. cardiovascular and genetic risk factors) and outcomes (e.g. cognitive performance and brain pathology) from studies in both patients and mouse models, and discusses several potential mechanisms proposed to contribute to CBF reductions, based primarily on work in AD mouse models. Future research aimed at improving our understanding of the importance of and interplay between different mechanisms for CBF reduction, as well as at determining the role these mechanisms play in AD patients could guide the development of future therapies that target CBF reductions in AD.

INTRODUCTION[|]Patients with obesity have more restrictive eating behavior than those of normal weight, and are thought to cause depressive symptoms by leading to avoidant coping strategies. In this study, it was aimed to investigate the mediating role of eating, shape and weight concern the relationship between restricted eating and depression in individuals applying to bariatric surgery.[¤]METHODS[|]The study sample was composed of patients with morbid obesity who applied to Ondokuz Mayıs University Faculty of Medicine for bariatric surgery between 2016-2018. The sociodemographic data form, Beck Depression Scale and Eating Disorder Rating Scale were filled by the participants. The degree of representation of the observed variables to implicit variables was evaluated by the confirmatory measurement model. Then, the relationship pattern between variables was examined with the structural model test. Multiple fit indices were used in the confirmatory measurement model and the structural equation model.[¤]RESULTS[|]The study group consisted of 224 participants (mean age 37.6 +- 12.9). The average BMI of the participants is 45.5 +- 5.9. Three implicit variables were created, namely depression, anxiety, and limited eating. After confirming the measurement model, the mediating role of anxiety between depression and limited eating behavior was examined by path analysis. When the variance relations between the variables were examined, it was seen that restricted eating explained 76% of the variance in anxiety and 25% of the variance in depression.[¤]DISCUSSION AND CONCLUSION[|]Treating obesity from a psychiatric perspective, adopting an approach that takes into account the anxiety about eating, body weight and body image may increase the success of the treatment. A decrease in related anxiety can lead to reduced eating and depression levels.[¤]

Introduction Anxiety is characterized by psychological, physiological, and cognitive complaints. Current treatments have significant limitations, and often overlook any potential benefits to common cognitive symptoms, notably attention and executive function issues. The current study aimed to investigate the use of transcranial direct current stimulation (tDCS) on both common anxiety symptoms and executive function abilities in a college aged sample. Method As this is one of the first large scale anxiety studies utilizing tDCS, participants were given a single session of tDCS (anodal, cathodal, or sham) for 20 min at 2 mA over the left dorsolateral prefrontal cortex (lDLPFC). Participants also completed a series of self-reported anxiety measures and measures of executive functioning (Rey-O Copy and Wisconsin Card Sorting Task). Results While there were no differences in anxiety between tDCS groups, a trend was noted demonstrating better performance on Rey-O Copy for the cathodal group. Anxiety increased pre to post for all groups. Conclusion Overall, results suggest that while anodal stimulation of the lDLPFC may benefit cognitive abilities for this population, targeting psychological symptoms of anxiety likely requires stimulation over other cortex, possibly right DLPFC. Further, the use of tDCS, whether active or sham, may be distressing to patients.

Introduction: Patients with cholestatic diseases may develop fatigue and cognitive symptoms. The impact of symptom burden may be significant in some patients. To date, there are no effective pharmacological therapies to improve cognitive symptoms or fatigue in cholestasis and we are wholly reliant on supportive approaches. Area covered: This review provides an overview of cognitive symptoms and fatigue in the cholestatic liver disease primary biliary cholangitis (PBC), including pathophysiology and our approach to the management of these symptoms. Expert opinion: The impact of fatigue and cognitive symptoms on the perceived quality of life can be profound for patients with PBC. The pathophysiology of these symptoms is complex and poorly understood, making the development of therapeutic trials of symptom-directed therapies challenging. The current recommended management for fatigue and cognitive symptoms is mainly supportive.

Background Neuropsychiatric and cognitive symptoms account for substantial morbidity in Huntington's disease (HD), but their impact on functional status may not be captured using the Total Functional Capacity (TFC) scale. The objective of this study was to assess the impact of motor, cognitive, and neuropsychiatric symptoms on functional status in persons with HD, comparing two instruments. Methods Multiple regression analyses assessed the relationship between neuropsychiatric, cognitive, and motor symptoms and functional status as measured using TFC and Adult Functional Adaptive Behavior (AFAB) scales. Results Greater burden of neuropsychiatric (P = 0.017), cognitive (P = 0.001), and motor (P = 0.001) symptoms was associated with greater impairments to functional status as measured by the AFAB scale. Only motor symptoms were associated with TFC scores (P = 0.002). The 3 symptom domains explained more of the variance in AFAB than TFC scores (P = 0.016). Conclusions TFC may have limited applicability, particularly in early-stage HD patients, as a measure of functional status. The AFAB scale can be used in HD studies as a more holistic measure of functional status. © 2020 International Parkinson and Movement Disorder Society.

Schizophrenia is a complex psychiatric disease (or a conglomeration of disorders) manifesting with positive, negative and cognitive symptoms. The pathophysiology of schizophrenia is not completely known; however, it involves many neurotransmitters and their receptors. In order to treat schizophrenia, drugs need to be multi-target drugs. Indeed, the action of second and third generation antipsychotics involves interactions with many receptors, belonging mainly to aminergic GPCRs.In this review, the authors summarize current concepts of schizophrenia with the emphasis on the modern dopaminergic, serotoninergic, and glutamatergic hypotheses. Next, they discuss treatments of the disease, stressing multi-target antipsychotics. They cover different aspects of design of multi-target ligands, including the application of molecular modeling approaches for the design and benefits and limitations of multifunctional compounds. Finally, they present successful case studies of multi-target drug design against schizophrenia.Treatment of schizophrenia requires the application of multi-target drugs. While designing single target drugs is relatively easy, designing multifunctional compounds is a challenge due to the necessity to balance the affinity to many targets, while avoiding promiscuity and the problems with drug-likeness. Multi-target drugs bring many benefits: better efficiency, fewer adverse effects, and drug-drug interactions and better patient compliance to drug regime.

Purpose To investigate psychopathological reaction to traumatic stress, addressing in particular gender difference, in parental couples of children affected by epilepsy. Methods 50 mothers and 50 fathers, paired for one’s child, of children followed at the Pediatric Unit of a major Italian University Hospital with a diagnosis of epilepsy were enrolled, screened by means of the Semi-structured Clinical Interview for DSM-5 (SCID-5) and filled the Trauma and Loss Spectrum Self-Report (TALS-SR), an international instrument to evaluate post-traumatic stress symptomatology. Results 25 % of the total sample presented a diagnosis of PTSD with a statistically higher prevalence of mothers (36 % and 14 %, respectively; p = .021). Furthermore, 44 % (48 % mothers and 40 % fathers) presented a partial PTSD. Important gender differences emerged also for all cluster dimensions of the TALS-SR except for the Avoidance. Finally, the analysis of the single items of the TALS-SR evidenced that in mothers subgroup prevail cognitive symptoms of fear and sadness as well as somatic manifestations. Conclusions Our results point out the differences between mothers and fathers in trauma response and underline the need to develop gender targeted models of healthcare prevention and assistance.

Objective Cognitive symptoms of Parkinson's disease (PD) may be alleviated by moderate-to-vigorous physical activity (MVPA), but no published research has characterized the relationship between objectively measured sedentary behavior and cognitive symptoms of PD. Therefore, the objective of this study was to assess the cross-sectional relationship between sedentary time and cognitive performance in a small pilot sample of individuals with mild-to-moderate PD. Methods Objective measures of sedentary time were obtained using an armband accelerometer. Cognition was assessed with the Parkinson's Disease Cognitive Rating Scale and a computerized task-switching paradigm. Results The percentage of awake time spent in sedentary activities was negatively correlated with attention (β = -14.20, t(12) = -2.47, p = 0.03) but not other cognitive domains (p > 0.05) after controlling for MVPA and medication dosage. Conclusion Sedentary activity may have unique associations with cognition, particularly attention, over and above MVPA in individuals with PD.

Many patients referred to cognitive disorders clinics are not found to have evidence of any neurological disorder(s) to account for their symptoms. Many demonstrate incongruence between their subjective cognitive symptoms and preserved social and occupational functions. The term ‘functional cognitive disorders’ (FCD) has been used to denote this diagnostic category. This article aims to review the current state of knowledge regarding FCD. Studies of FCD are in their infancy, but available evidence suggests positive diagnosis may be made based on typical clinical profiles, including language discourse and simple clinical signs. Concurrent mood disorder and sleep disturbance are common, as well as other functional disorders. Pathogenesis is yet to be determined, but a disorder of metamemory has been suggested.

Functional neurological disorder (FND) is a common cause of persistent and disabling neurological symptoms. These symptoms are varied and include abnormal control of movement, episodes of altered awareness resembling epileptic seizures and abnormal sensation and are often comorbid with chronic pain, fatigue and cognitive symptoms. There is increasing evidence for the role of neurologists in both the assessment and management of FND. The aim of this review is to discuss strategies for the management of FND by focusing on the diagnostic discussion and general principles, as well as specific treatment strategies for various FND symptoms, highlighting the role of the neurologist and proposing a structure for an interdisciplinary FND service.

Gang Wang,1 Kristin Hui Xian Tan,2 Hongye Ren,3 Lene Hammer-Helmich3 1Psychiatry Department, Beijing an Ding Hospital, Capital Medical University, China National Clinical Research Center for Mental Disorders, Beijing, People’s Republic of China; 2Health Economics & Epidemiology Statistics, Lundbeck Singapore Pte Ltd, Singapore; 3Medical Affairs Value Evidence, H. Lundbeck A/S, Valby, DenmarkCorrespondence: Lene Hammer-HelmichMedical Affairs Value Evidence, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, DenmarkTel +45 3083 2880Email leem@lundbeck.comPurpose: This post hoc analysis was undertaken to further explore the association of cognitive symptoms with health-related quality of life (HRQoL) and work productivity at the time of treatment initiation in Chinese patients with major depressive disorder (MDD) in the Prospective Research Observation to Assess Cognition in Treated patients with MDD (PROACT) study.Patients and Methods: This was an epidemiological, non-interventional, prospective cohort study in adult outpatients with moderate-to-severe MDD initiating antidepressant monotherapy (first or second line). Crude and adjusted analyses of covariance were performed to assess the association of perceived cognitive symptoms (20-item Perceived Deficits Questionnaire-Depression [PDQ-D] total score) or observed cognitive performance (Digit Symbol Substitution Test [DSST] score) with HRQoL (EuroQoL 5-Dimensions Questionnaire index) and work productivity (Work Productivity and Activity Impairment [WPAI] or Sheehan Disability Scale [SDS] absenteeism and presenteeism scores). Adjusted analyses included depression severity, age, sex, residential area (urban/rural), and educational level.Results: Of 1008 patients enrolled in the PROACT study, 986 were included in this analysis. Severity of perceived cognitive symptoms (ie, higher PDQ-D total score) was significantly associated with worse HRQoL (P< 0.001) and higher levels of absenteeism (P=0.020 for the WPAI and P=0.002 for the SDS) and presenteeism (P< 0.001 for both scales). The association of perceived cognitive symptoms with HRQoL and presenteeism was independent of depression severity. The association between observed cognitive performance (DSST score) and HRQoL was less robust. No association was seen between observed cognitive performance and levels of absenteeism or presenteeism assessed by either scale.Conclusion: Results of this real-world study illustrate the impact of cognitive symptoms on HRQoL and work productivity in Chinese patients with MDD, and highlight the importance of assessing and targeting cognitive symptoms in order to improve functional outcomes when treating patients with MDD.Keywords: major depressive disorder, cognitive symptoms, health-related quality of life, work productivity, presenteeism, absenteeism

Objective. Eating Disorders (EDs) are complex, heterogeneous, and severe psychiatric syndromes. They are highly comorbid with obsessive-compulsive disorder (OCD) which exacerbates the course of illness and impedes treatment. However, the direct functional relations between EDs and OCD symptoms remain largely unexplored. Hence, using network analysis, we investigated the relationship between ED and OCD at the level of symptoms in a heterogeneous clinical sample.Method. We used cross-sectional data of 303 treatment-seeking patients with clinically relevant ED and OCD pathology. We constructed a regularized partial correlation network that featured both ED and OCD symptoms as nodes. To determine each symptom’s influence, we calculated expected influence (EI) as an index of symptom centrality (i.e., “importance”). Bridge symptoms (i.e., symptoms from one syndromic cluster that have strong connections to symptoms of another syndromic cluster) were identified by computing bridge expected influence metrics.Results. Fear of weight gain and dietary restraint were especially important among the ED symptoms. Interference due to obsessions was the key feature of OCD. ED and OCD clustered distinctly with few potential bridges between clusters.Discussion. This study underscores the importance of cognitive symptoms for both ED and OCD although direct functional links between the two clusters are missing. Potentially, a network incorporating nodes capturing features of personality may account for diagnostic comorbidity better than specific symptoms of EDs or features of OCD do.

By 2026 an estimated 20.3 million cancer survivors will be living in the United States.1 Many of these survivors report cognitive symptoms that do not resolve after cancer treatment. These symptoms...

Schizophrenia (SZ) is a chronic psychiatric disorder characterized by positive (e.g., hallucinations and delusions), negative (e.g., apathy and impaired motivation), and cognitive symptoms (e.g., poor performance in executive functions and attention). Interleukin-2( IL-2) has been one of the most frequently studied cytokines in schizophrenia. Several studies have pointed to a potential role of IL-2 in SZ,with most studies reporting altered peripheral levels of IL-2 when compared with healthy controls. The aim of this work is to determine serum level of interlukin-2 in a sample of schizophrenic patients. Also to compare the serum levels of IL-2 in schizophrenic patients and healthy controls and to investigate a possible correlation with positive and negative symptoms of. This analytic (case control) study included thirty patients with schizophrenia and a similar number of normal healthy individuals as control group. Both groups were subjected to a semi structured interview, SCID, PANSS and serum level of IL-2.

The strong relationship between genetic determinants of Alzheimer's disease (AD) and the overproduction of beta-amyloid (Aβ) provides compelling support for the amyloid cascade hypothesis and has been central to AD drug development. It is hypothesized that disease-modifying treatments for AD should begin prior to the development of extensive neurodegeneration and onset of AD-related cognitive symptoms. Understanding of the molecular basis for the near universal presence of early onset AD in Down syndrome (DS) has grown exponentially in the past decade and recent studies have provided evidence that AD in DS is remarkably similar to other forms of AD. Individuals with DS therefore comprise the largest group in the world with genetically determined AD. In this chapter, therapeutic strategies that can be employed in clinical trials for AD in DS will be discussed as well as their underlying scientific rationale.

Rapid reconfigurations of brain activity support efficient neuronal communication and flexible behaviour. Suboptimal brain dynamics is associated to impaired adaptability, possibly leading to functional deficiencies. We hypothesize that impaired flexibility in brain activity can lead to motor and cognitive symptoms of Parkinson’s disease (PD). To test this hypothesis, we studied the ‘functional repertoire’—the number of distinct configurations of neural activity—using source-reconstructed magnetoencephalography in PD patients and controls. We found stereotyped brain dynamics and reduced flexibility in PD. The intensity of this reduction was proportional to symptoms severity, which can be explained by beta-band hyper-synchronization. Moreover, the basal ganglia were prominently involved in the abnormal patterns of brain activity. Our findings support the hypotheses that: symptoms in PD relate to impaired brain flexibility, this impairment preferentially involves the basal ganglia, and beta-band hypersynchronization is associated with reduced brain flexibility. These findings highlight the importance of extensive functional repertoires for correct behaviour.

BackgroundHuntington’s disease (HD) is clinically characterized by progressing motor, cognitive and psychiatric symptoms presenting as varying phenotypes within these three major symptom domains. The disease is caused by an expanded CAG repeat tract in the huntingtin gene and the pathomechanism leading to these endophenotypes is assumed to be neurodegenerative. In 2012/2013 we recruited 107 HD gene expansion carriers (HDGECs) and examined the frequency of the three cardinal symptoms and in 2017/2018 we followed up 74 HDGECs from the same cohort to describe the symptom trajectories and individual drift between the endophenotypes as well as potential predictors of progression and remission.ResultsWe found higher age to reduce the probability of improving on psychiatric symptoms; increasing disease burden score ((CAG-35.5) * age) to increase the risk of developing cognitive impairment; increasing disease burden score and shorter education to increase the risk of motor onset while lower disease burden score and higher Mini Mental State Examination increased the probability of remaining asymptomatic. We found 23.5% (N = 8) to improve from their psychiatric symptoms.ConclusionsThere is no clear pattern in the development of or drift between endophenotypes. In contrast to motor and cognitive symptoms we find that psychiatric symptoms may resolve and thereby not entirely be caused by neurodegeneration. The probability of improving from psychiatric symptoms is higher in younger age and advocates for a potential importance of early treatment.

COVID-19 is an ongoing pandemic with a devastating impact on public health. Acute neurological symptoms have been reported after a COVID-19 diagnosis, however, the long-term neurological symptoms including pain is not well established. Using a prospective registry of hospitalized COVID-19 patients, we assessed pain and neurological function (including functional, cognitive and psychiatric assessments) of several hospitalized patients at 3 months. Our main finding is that 60% of the patients report pain symptoms. 71% of the patients still experienced neurological symptoms at 3 months and the most common symptoms being fatigue (42%) and PTSD (25%). Cognitive symptoms were found in 12%. Our preliminary findings suggests the importance of investigating long-term outcomes and rationalizes the need for further studies investigating the neurologic outcomes and symptoms of pain after COVID-19.

Introduction: The pre-supplementary motor area (Pre-SMA) plays a pivotal role in the control of voluntary motor control and freezing of gait (FOG) pathophysiological mechanism. Here, we aimed to modulate if the pre-SMA would have beneficial effects on motor and behavioural outcomes in freezing of gait. To test this hypothesis, we examined the left pre-SMA stimulating effect of repetitive Transcranial Magnetic Stimulation (rTMS) on motor, cognitive and behavioural parameters in Parkinson’s patients with FOG. Method: The study included 20 Parkinson’s patients with FOG (3 females, 17 males) who received the left Pre-SMA rTMS procedure. The clinical assessments were performed on all patients at the baseline and the patients were re-evaluated under the same clinical conditions one week after the end of the sessions. Results & Discussion: We found significant improvements in motor, cognitive and behavioural symptoms (p Conclusion: The high-frequency rTMS stimulation over the left preSMA has a restorative effect on the motor, cognitive and behavioural symptoms of Parkinson’s patients with FOG.

P139 Table 1Percentage of patients reporting various symptoms of Long COVIDSymptom Percentage of patients Fatigue 98% Worsening breathlessness 97% Cognitive symptoms 91% Myalgia 66% Chest pain 47% Ongoing cough 46% Anosmia 45% DiscussionPatients experience significant worsening breathlessness and fatigue. This significant symptom burden emphasises the need for dedicated Long COVID assessment hubs to support patients. Further research should investigate whether pulmonary rehabilitation and dedicated psychological input can improve patients’ symptoms.ReferenceNHS England and NHS Improvement (2021). Long COVID: the NHS plan for 2021/22.

Since its first emergence in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evolved into a global pandemic. Whilst often considered a respiratory disease, a large proportion of COVID-19 patients report neurological symptoms, and there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere. There are a number of mechanisms by which COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and it is reasonable to expect that many of these may translate into cognitive problems. Indeed, cognitive problems are one of the most commonly reported symptoms in those suffering from “Long COVID”—the chronic illness following COVID-19 infection that affects between 10–25% of sufferers. The COVID and Cognition Study is a part cross-sectional, part longitudinal, study documenting and aiming to understand the cognitive problems in Long COVID. In this first paper from the study, we document the characteristics of our sample of 181 individuals who had suffered COVID-19 infection, and 185 who had not. We explore which factors may be predictive of ongoing symptoms and their severity, as well as conducting an in-depth analysis of symptom profiles. Finally, we explore which factors predict the presence and severity of cognitive symptoms, both throughout the ongoing illness and at the time of testing. The main finding from this first analysis is that that severity of initial illness is a significant predictor of the presence and severity of ongoing symptoms, and that some symptoms during the acute illness—particularly limb weakness—may be more common in those that have more severe ongoing symptoms. Symptom profiles can be well described in terms of 5 or 6 factors, reflecting the variety of this highly heterogenous condition suffered by the individual. Specifically, we found that neurological and fatigue symptoms during the initial illness, and that neurological, gastro-intestinal, and cardiopulmonary symptoms during the ongoing illness, predicted experience of cognitive symptoms.

Background Many people are not recovering for months after being infected with COVID-19. Long Covid (LC) is a major public health problem that needs defining, quantifying and describing. We aimed to explore and develop understanding of LC symptoms following mild/moderate COVID-19 infection and describe its impact on daily life. Methods The survey was co-produced with people living with LC. Data was collected through an online social media survey mostly from online support groups using convenience non-probability sampling. The criteria for inclusion were adults with lab-confirmed or suspected COVID-19 infection managed in the community (non-hospitalised) in the first two weeks of illness. We used agglomerative hierarchical clustering to identify specific symptom clusters, and their demographic, and functional correlates. Results Data from 2550 participants with a median duration of illness of 7.7 months (interquartile range (IQR) 7.4–8.0) was analysed. The mean age was 46.5 years (standard deviation 11 years) with 82.8% females and 79.9% UK-based. 90% reported good, very good or excellent health prior to infection. Most participants described fluctuating (57.7%) or relapsing LC symptoms (17.6%). The most common initial symptoms that continued were exhaustion, headache, chest pressure/tightness and breathlessness. Cough, fever and chills were prevalent initial symptoms that became less so as the illness progressed. Cognitive dysfunction and palpitations became more common beyond the acute phase. 26.5% reported lab-confirmation of infection (NAAT or antibody). The biggest difference in symptoms between those who reported testing positive and those who did not was loss of smell/taste. Physical activity, stress and sleep disturbance were the most common symptom triggers. A third (32%) reported they were unable to live alone without any assistance at six weeks from start of illness. 66.4% reported taking time off sick, (median 60 days, IQR 20, 129). 37% reported loss of income due to illness. Eighty four percent of participants reported ongoing symptoms affecting at least three organ systems. There were two main ongoing symptoms clusters; the majority cluster (88.7%) exhibited mainly chest, cognitive symptoms and exhaustion, and the minority cluster (11.3%) exhibited multi-system symptoms which had persisted from the start. The multi-system cluster reported more severe functional impact. Conclusion This is an exploratory survey of LC characteristics. Whilst it is a non-representative sample, it highlights the heterogeneity of persistent symptoms, and the significant functional impact. To better characterise ongoing illness and prognosis, research is needed in a representative population-sample using standardised case definitions (to include those not lab-confirmed in the first pandemic wave).

The neurodegenerative and neurodevelopmental hypotheses represent the basic etiological framework for the origin of schizophrenia. Additionally, the dopamine hypothesis, adopted more than two decades ago, has repeatedly asserted the position of dopamine as a pathobiochemical substrate through the action of psychostimulants and neuroleptics on the mesolimbic and mesocortical systems, giving insight into the origin of positive and negative schizophrenic symptoms. Meanwhile, cognitive impairments in schizophrenia remain incompletely understood but are thought to be present during all stages of the disease, as well as in the prodromal, interictal and residual phases. On the other hand, observations on the effects of NMDA antagonists, such as ketamine and phencyclidine, reveal that hypoglutamatergic neurotransmission causes not only positive and negative but also cognitive schizophrenic symptoms. This review aims to summarize the different hypotheses about the origin of psychoses and to identify the optimal neuroimaging method that can serve to unite them in an integral etiological framework. We systematically searched Google scholar (with no concern to the date published) to identify studies investigating the etiology of schizophrenia, with a focus on impaired central neurotransmission. The complex interaction between the dopamine and glutamate neurotransmitter systems provides the long-needed etiological concept, which combines the neurodegenerative hypothesis with the hypothesis of impaired neurodevelopment in schizophrenia. Pharmaco-magnetic resonance imaging is a neuroimaging method that can provide a translation of scientific knowledge about the neural networks and the disruptions in and between different brain regions, into clinically applicable and effective therapeutic results in the management of severe psychotic disorders.

Psychotic disorders occur as a result of pathobiochemical processes in the brain, which disrupt the central neurotransmission of molecules such as dopamine and glutamate. The dopamine hypothesis, adopted more than 2 decades ago, has repeatedly asserted its position as an etiopathogenetic substrate through the action of psychostimulants and neuroleptics on the mesolimbic and mesocortical systems, giving insight into the origin of positive and negative schizophrenic symptoms. On the other hand, cognitive impairments in schizophrenia remain not fully understood but are thought to be present during all stages of the disease, as well as in the prodromal the interictal and residual phases. Over the last decade, functional magnetic resonance imaging has focused on research of brain networks like the Default mode network, the Salience network and Central executive network, enabling a deeper understanding of cognitive deficits, as well as other phenomena such as disorganization of thought and behavior. The study of the nodes of these networks, such as the precuneus and insula, informs about their complex significant roles as structures responsible for important cognitive domains such as concentration, attention, ability to understand and reproduce information, as well as memory functions. It is suggested that the neurotransmission of dopamine and glutamate play a key role in these processes and their successful modulation in the correct brain regions through psychopharmacological and biomedical instrumental methods may lead to a significant reversal of conventional paradigms. Pharmaco-magnetic resonance imaging is a neuroimaging method that can provide the translation of scientific knowledge about the neural networks and the disruptions in and between different brain regions, into clinically applicable and effective therapeutic results in the management of severe psychotic disorders.

We evaluated the performance of CSF biomarkers for predicting risk of clinical decline and conversion to dementia in non-demented patients with cognitive symptoms. CSF samples from patients in two multicentre longitudinal studies (ADNI, n = 619; BioFINDER, n = 431) were analysed. Aβ(1–42), tTau and pTau CSF concentrations were measured using Elecsys CSF immunoassays, and tTau/Aβ(1–42) and pTau/Aβ(1–42) ratios calculated. Patients were classified as biomarker (BM)-positive or BM-negative at baseline. Ability of biomarkers to predict risk of clinical decline and conversion to AD/dementia was assessed using pre-established cut-offs for Aβ(1–42) and ratios; tTau and pTau cut-offs were determined. BM-positive patients showed greater clinical decline than BM-negative patients, demonstrated by greater decreases in MMSE scores (all biomarkers: –2.10 to –0.70). Risk of conversion to AD/dementia was higher in BM-positive patients (HR: 1.67 to 11.48). Performance of Tau/Aβ(1–42) ratios was superior to single biomarkers, and consistent even when using cut-offs derived in a different cohort. Optimal pTau and tTau cut-offs were approximately 27 pg/mL and 300 pg/mL in both BioFINDER and ADNI. Elecsys pTau/Aβ(1–42) and tTau/Aβ(1–42) are robust biomarkers for predicting risk of clinical decline and conversion to dementia in non-demented patients, and may support AD diagnosis in clinical practice.

Pain has well-established effects on attention. At present, parallel literatures exist that have examined the effects of experimentally induced pain and consider cognitive performance in patients with chronic pain states. However, no study to date as attempted to examine the combined or differing effects of these 2 manifestations of pain in a single study. Twenty-four participants with fibromyalgia (aged 43.00 ± 28.28 years) and 26 healthy controls (aged 36.07 ± 11.93 years) completed an n-back task, an attentional switching task, and a divided attention task, once during induced, moderately intense pressure pain, and once without induced pain. Pain induction had selective effects on the n-back task and an overall decrease in accuracy on the attentional switching task. Conversely, patients with fibromyalgia were selectively impaired in performance on the divided attention task. These data therefore suggest that the effects of pain are not summative and rather that the mechanisms that underlie the negative effects of pain on performance in acute and chronic states may differ. More research is needed to examine these mechanisms and how these negative effects can be ameliorated to treat cognitive symptoms in pain. PERSPECTIVE: This article presents a study to examine the effects of an acute, induced pain model on cognitive performance in both patients with fibromyalgia and healthy control populations. We established that the effects of acute and chronic pain on attention are different, suggesting that different models need to be developed to understand these phenomena.

Objective The growing prevalence of chronic conditions requiring changes in lifestyle and at-home self-management has increased interest in and need for supplementing clinic visits with data generated by patients outside the clinic. Patient-generated health data (PGHD) support the ability to diagnose and manage chronic conditions, to improve health outcomes, and have the potential to facilitate more “connected health” between patients and their care teams; however, health systems have been slow to adopt PGHD use in clinical care. Materials and Methods We surveyed current and potential users of PGHD to catalog how PGHD is integrated into clinical care at an academic health center. The survey included questions about data type, method of collection, and clinical uses of PGHD. Current users were asked to provide detailed case studies of PGHD use in research and care delivery. Results Thirty-one respondents completed the survey. Seventeen individuals contributed detailed case studies of PGHD use across diverse areas of care, including behavioral health, metabolic and gastrointestinal conditions, musculoskeletal/progressive functional conditions, cognitive symptoms, and pain management. Sensor devices and mobile technologies were the most commonly reported platforms for collection. Clinicians and researchers involved in PGHD use cited the potential for PGHD to enhance care delivery and outcomes, but also indicated substantial barriers to more widespread PGHD adoption across healthcare systems. Conclusion The results of our survey illustrate how PGHD is used in targeted areas of one healthcare system and provide meaningful insights that can guide health systems in supporting the widespread use of PGHD in care delivery.

Background People with mild hearing loss at age 50 are twice as likely to develop dementia increasing to a five times greater risk for those with severe hearing loss. The prevalence of dementia and hearing impairment increase with age. Intact hearing enables cognition, facilitates social interaction and enhances communication. Hearing loss, social isolation and dementia are commonly interwoven. We recently commenced routine audiology screening in our memory service. Methods Consecutive patients with mild cognitive impairment attending a tertiary memory assessment and support service were referred for full audiology screening. People were routinely referred on basis of cognitive diagnosis, and not on the basis of perceived hearing loss. Assessment included ENT history, otoscopy, tympanometry, pure tone audiometry and speech audiometry to determine the presence, type and amount of any hearing loss present. This included speech discrimination testing – a functional test to determine processing of 10 phonetically balanced words with 100% being an optimal response. Results 20 people (12 women), mean age 72.3 (range 57-87) were assessed. The majority had amnestic MCI 18/20 (90%). 9/20 (45%) patients subjectively complained of hearing loss. 7/20 (35%) had history of occupational noise exposure. 12/20 (60%) had occlusion due to ear wax. Hearing loss identified: Mild 8/20 (40%); Moderate to severe 7/20 (35%); with Normal hearing in 5/20 (25%). High frequency hearing loss was noted in 19/20 (95%). Speech discrimination score was impaired in those with hearing loss: mean 89.4% (range 66-100). 6/20 (30%) received referral for hearing aids. Conclusion This study highlights the importance of incorporating an assessment of auditory acuity as part of memory assessment and post-diagnostic care-pathway for people with mild cognitive complaints given the established impact hearing loss has on the future risk for cognitive decline. Hearing loss is frequently unidentified and is a clear modifiable risk factor to promote brain health.

Background Current evidence strongly implicates the burden of vascular risk factors (VRF) in the development of stroke, cognitive decline and dementia. This effect is mediated through several mechanisms, including amyloidogenesis, chronic neuroinflamation, cerebral perfusion and white-matter changes. Vascular risk profiling is well-embedded in stroke and cardiac services, but less so in memory services. Methods A review of established modifiable VRF (hypercholesterolemia, Body Mass Index (BMI), hypertension, HbA1c, smoking and alcohol habits) of people with mild cognitive complaints (mild cognitive impairment and subjective memory decline) in a memory service was performed. Risk factors measured in clinic were classified as: systolic ≥140mmHg / diastolic ≥90mmHg hypertension; LDL cholesterol >3mmol/l; HbA1c >39mmol/mol; weekly alcohol >21units; smoking and BMI >24.9kg/m2. Data was recorded and analysed using Microsoft Excel. Results Thirty-seven people, including 16 females (mean age 71.4, range of 49-83 years), were reviewed. 13/37 (35%) were aged ≤69 years. A total of 91 VRFs were identified in the study population. 29/37 (78%) had ≥2 VRF present. 3/37 (8%) had five VRF. 18/37 (49%) had prior history of either stroke, vascular or heart disease. Five of thirty-seven, (13.5%) and 13/37 (35%) were current and ex-smokers respectively, 2/37 (5%) consumed excess alcohol, 24/37 (65%) had elevated BMI and 11/37 (30%) had elevated LDL cholesterol. 21/37 (57%) had hypertension. Of these, 11/21 were known but poorly-controlled and 10/21 were identified de novo. All of the 32% (12/37) who had hyperglycaemia were de novo. Conclusion This study highlights the high prevalence of unidentified or poorly controlled VRF in people with mild cognitive symptoms attending a memory service. Given its importance to brain health and mitigation of future cognitive decline, a structured focus on identifying and managing these VRF in this setting is necessary. Exercise-based lifestyle programs should be embedded in post-diagnostic services for this population.

Background Dementia poses a serious threat to the wellbeing of the elderly. In the context of the rapidly ageing population of Vietnam however, little is known about the prevalence of symptoms and other related factors. This study aims to detect the prevalence of cognitive symptoms of dementia in the elderly in Vietnam as well as other associated factors. Methods A cross-sectional study was conducted over a period of six communes at the Northern, Central and Southern region of Vietnam. Prevalence of cognitive symptoms of dementia was the outcome of interest and assessed by Mini Mental State Evaluation (MMSE) questionnaire and was standardized according to the age structure of Vietnam. A total of 3308 adults aged 60 and above were included. Association between having cognitive symptoms of dementia and other factors was assessed with logistic regression. Findings Cognitive symptoms of dementia were perceived in 46.4% of the sample group. The symptoms were more common among participants who were older, female, had a lower educational level, were not physically active or have previously had stroke. Conclusions Prevalence of cognitive symptoms of dementia in adults aged 60 and above was relatively high in Vietnam. Other modifiable associated factors including physical inactivity and social connectedness should also be considered in designing intervention program to prevent dementia in the future.

Many studies have been conducted to investigate the effect of cultural influences on menopausal symptoms; however, associations between immigration transition and cognitive symptoms have rarely been uncovered. This secondary analysis aimed to determine these associations among 1,054 midlife women in the United States using the data from two national Internet surveys. The surveys included multiple questions on immigration transition, health and menopausal status, and the Cognitive Symptom Index for Midlife Women. The data analysis was performed using descriptive and inferential statistics including hierarchical multiple regression analyses. Nonimmigrants had larger numbers and higher severity scores of total cognitive symptoms than immigrants ( p < .001). Immigration status explained 1.28% of the total variances in the total numbers and 1.46% of the total variances in the total severity scores of total cognitive symptoms ( p < .001). The study supported significant associations between immigration transition and cognitive symptoms of women at midlife.

BackgroundFibromyalgia (FM) is a chronic pain syndrome with a controversial etiopathogenesis. Patients with FM usually complain of cognitive symptoms, which are described as “fibrofog.” These cognitive complaints might be caused partially by dissociative disorders (DD). The aim of this research is to determine the association between FM and DD.MethodsThe authors conducted a case-control study for this purpose, integrated by 3 groups: control (C), patients with rheumatic disorders (R), and patients with FM (FM), who were compared through the Dissociative Experiences Scale (DES).The findings are as follows: 42% were taking medications in the FM group, and their differences in scores with those who were not under medications were then considered. In terms of the results, the FM group showed higher scores than both C and R groups (p < 0.05). Patients with FM who were taking antidepressants had lower scores than those who were not (Z-score –8.03; p < 0.05); and finally, 5.71% had a score over 30 (χ2 = 3.73, p = 0.15).ConclusionPatients with FM had higher scores, which might be related to the association of dissociative experiences, lifetime trauma, and victimization. Antidepressants might have some role on dissociative symptoms as well.

Introduction: Myotonic dystrophy (DM) is a chronic, multisystemic, neurological condition. Patients and caregivers are uniquely suited to identify what symptoms are most important and highlight the unmet needs that are most relevant to DM. Methods: We conducted a North American, cross‐sectional study of people with DM type‐1, congenital DM, and DM type‐2 and their family members. We sent patients and caregivers separate surveys to identify and quantitate the issues of greatest importance, examine the differences between groups, and identify the most important challenges experienced by this population. Results: 1,180 people with DM and 402 family members/caregivers responded to the surveys. They reported considerable physical and cognitive symptoms, extensive diagnostic delays, and varying clinical phenotypes on the basis of DM type. Discussion: Marked disease burden and numerous unmet needs exist in DM. These needs vary based on DM type and highlight the complex clinical phenotypes of these neurological disorders. Muscle Nerve 59:457–464, 2019

Background: In this study, we investigated the fusion of texture and morphometric features as a possible diagnostic biomarker for Alzheimer’s Disease (AD). Methods: In particular, we classified subjects with Alzheimer’s disease, Mild Cognitive Impairment (MCI) and Normal Control (NC) based on texture and morphometric features. Currently, neuropsychiatric categorization provides the ground truth for AD and MCI diagnosis. This can then be supported by biological data such as the results of imaging studies. Cerebral atrophy has been shown to correlate strongly with cognitive symptoms. Hence, Magnetic Resonance (MR) images of the brain are important resources for AD diagnosis. In the proposed method, we used three different types of features identified from structural MR images: Gabor, hippocampus morphometric, and Two Dimensional (2D) and Three Dimensional (3D) Gray Level Co-occurrence Matrix (GLCM). The experimental results, obtained using a 5-fold cross-validated Support Vector Machine (SVM) with 2DGLCM and 3DGLCM multi-feature fusion approaches, indicate that we achieved 81.05% ±1.34, 86.61% ±1.25 correct classification rate with 95% Confidence Interval (CI) falls between (80.75-81.35) and (86.33-86.89) respectively, 83.33%±2.15, 84.21%±1.42 sensitivity and 80.95%±1.52, 85.00%±1.24 specificity in our classification of AD against NC subjects, thus outperforming recent works found in the literature. For the classification of MCI against AD, the SVM achieved a 76.31% ± 2.18, 78.95% ±2.26 correct classification rate, 75.00% ±1.34, 76.19%±1.84 sensitivity and 77.78% ±1.14, 82.35% ±1.34 specificity. Results and Conclusion: The results of the third experiment, with MCI against NC, also showed that the multiclass SVM provided highly accurate classification results. These findings suggest that this approach is efficient and may be a promising strategy for obtaining better AD, MCI and NC classification performance.

Background: The prevalence of hypothyroidism in the developed world is about 4-5% and in India is 10.9%. The goal of treating hypothyroidism is to maintain thyrotropin (TSH) levels within the normal reference range. Studies have shown that even within the normal range of TSH, patients with low normal TSH (LNT) have better outcomes when compared to patients with high normal TSH (HNT). Aims and Objectives: Our study aimed to find whether patients treated at a dose of levothyroxine resulting in an LNT had improved clinical outcomes and biochemical parameters, when compared to those on a levothyroxine dose resulting in an HNT. Materials and Methods: 180 patients with hypothyroidism on treatment, who had a TSH of 0.27-4.2mIU/L and had been on treatment with a stable dose of at least 50 micrograms of levothyroxine for at least 6 months were administered the Thyroid Symptom Questionnaire. TSH was assayed. Blood pressure and BMI were measured. Serum lipids were measured by spectrophotometry. Results: We found that patients with LNT and HNT did not differ with respect to cognitive symptoms , feelings of coldness, lethargy and fatigue. However, patients with LNT had a better lipid profile (mean LDL 132.24 in HNT and 115.39 in LNT p= 0.08) and lower BMI (1.045kg/m 2 lower in LNT compared to HNT) compared to HNT. Conclusion: Treating patients with a dose of thyroxine titrated to achieve LNT might decrease the cardiovascular risk by improving the lipid profile and BMI.

Maternal immune activation induced by Poly(I:C) administration is one of the most commonly used animal models of schizophrenia at present. Previous work from our team has demonstrated that some, but not all of the features often reported for maternal immune activation exposure in rodents can be observed in rats exposed to maternal immune activation at mid or late gestation. To determine whether previous findings in our laboratory were due to these time points simply being less sensitive neurodevelopmental periods for rats with regard to maternal immune activation effects, we aimed to investigate whether maternal immune activation at an often-reported sensitive period (mid-late gestation, day 14) resulted in more behavioural features reflective of face validity for schizophrenia. We examined the behavioural outcomes of mid-late maternal immune activation on a battery of behavioural tests aimed at assessing validity for positive, negative and cognitive symptoms of schizophrenia. We found that rats exposed to maternal immune activation, compared to controls, exhibited enhanced sensitivity to the locomotor-stimulating effects of amphetamine and reduced exploration of novel objects. These findings present a unique profile of effects, different to what has already been established for the same time point in rats, and different to what we had found at earlier and later time points. This work, among others in the literature, highlights the varying nature of models of maternal immune activation and we submit that it is essential for laboratories to characterise their models of maternal immune activation on behaviour rather than assuming that the effects from one laboratory apply in their own.