scholarly journals Histamine H1 receptor deletion in cholinergic neurons induces sensorimotor gating ability deficit and social impairments in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Li Cheng ◽  
Cenglin Xu ◽  
Lu Wang ◽  
Dadao An ◽  
Lei Jiang ◽  
...  
Keyword(s):  
Functional Outcomes ◽  
Negative Symptoms ◽  
Cholinergic Neurons ◽  
Sensorimotor Gating ◽  
Social Impairment ◽  
H1 Receptor ◽  
Behavioral Deficits ◽  
Social Impairments ◽  
Cholinergic Projections ◽  
Functional Deficiency

AbstractNegative symptoms in schizophrenia strongly contribute to poor functional outcomes, however its pathogenesis is still unclear. Here, we found that histamine H1 receptor (H1R) expression in basal forebrain (BF) cholinergic neurons was decreased in patients with schizophrenia having negative symptoms. Deletion of H1R gene in cholinergic neurons in mice resulted in functional deficiency of cholinergic projections from the BF to the prefrontal cortex and in the formation of sensorimotor gating deficit, social impairment and anhedonia-like behavior. These behavioral deficits can be rescued by re-expressing H1R or by chemogenetic activation of cholinergic neurons in the BF. Direct chemogenetic inhibition of BF cholinergic neurons produced such behavioral deficits and also increased the susceptibility to hyperlocomotion. Our results suggest that the H1R deficiency in BF cholinergic neurons is critical for sensorimotor gating deficit, social impairments and anhedonia-like behavior. This finding may help to understand the genetic and biochemical bases of negative symptoms in schizophrenia.

A Group Intervention for Motivational Deficits: Preliminary Investigation of a Blended Care Approach Using Ambulatory Assessment

2021 ◽  
pp. 014544552110476
Author(s):  
Bénédicte Thonon ◽  
Marie-Noëlle Levaux ◽  
Evelyne van Aubel ◽  
Frank Larøi
Keyword(s):  
Group Intervention ◽  
Functional Outcomes ◽  
Negative Symptoms ◽  
Preliminary Investigation ◽  
Activity Level ◽  
Ambulatory Assessment ◽  
Specific Effects ◽  
Daily Step Count ◽  
Care Approach ◽  
Blended Care

Motivational deficits are an important predictor of functional outcomes in individuals with a serious mental illness such as schizophrenia and mood spectrum disorders. The aim of the present study was to explore the feasibility, acceptability, and preliminary efficacy of a group version of “Switch,” an intervention that targets motivational deficits, enriched with an ecological momentary intervention (EMI) approach (i.e., prompts on the participants’ smartphone to encourage the use of trained strategies in their daily life). Eight participants with schizophrenia, schizoaffective, or major depressive disorder entered the study. The intervention took place twice a week for 2 months. Assessment measures included traditional evaluations of motivational negative symptoms, apathy, quality of life and daily functioning, in addition to ambulatory assessment methods strategies, including the experience sampling method (ESM) to assess motivation and related processes, and actigraphy (daily step-count) to assess participants’ activity level. Four participants were considered as non-completers (followed less than 2/3 of the program) and four were considered as completers. Only completers presented a decrease in amotivation/apathy and an improvement in functional outcomes after the intervention and at follow-up. Furthermore, mixed-effects ESM models showed significant interaction effects on multiple processes related to motivation, indicating improvements only in completers: heightened motivation, increased engagement in meaningful and effortful activities, better mood, higher levels of confidence, increased frequency of projection into the future (pleasure anticipation), and of positive reminiscence. This preliminary investigation provides evidence that Switch may be an effective intervention, with specific effects on motivation and associated processes.

Social impairment in children with epilepsy assessed by the social responsiveness scale

2021 ◽  
pp. 135910452110331
Author(s):  
Samah K Aburahma ◽  
Hanan Hammouri ◽  
Ethar Hazaimeh ◽  
Omar Jbarah ◽  
Ahmad Nassar ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Social Responsiveness Scale ◽  
Social Impairment ◽  
Control Group ◽  
Social Responsiveness ◽  
Healthy Children ◽  
Normal Children ◽  
Social Impairments ◽  
Increased Risk ◽  
The Social

Children with epilepsy are at risk for impaired social cognition and autism. We aimed at evaluating the utility of the social responsiveness scale (SRS) for assessment of social impairment in these children. Prospective study; the SRS was applied to a group of children with epilepsy and a healthy control group. Intellectual disability in the epilepsy group was assessed utilizing adapted versions of the Wechsler Intelligence and adaptive behavior scales. One hundred and one children with epilepsy and 92 healthy children were included. The majority of children in both groups had normal SRS scores. Significant differences were identified in children with high total scores indicating significant deficiencies in reciprocal social behavior; high scores were found in 16% of children with epilepsy versus 7% of normal children, p < .05, particularly involving social communication, p < .05. Intellectual disability was identified in 42% of children with epilepsy, particularly processing speed index, p < .001. Intellectual disability had a significant effect on total scores, p = .016. Children with epilepsy have increased risk of social impairments. Social impairments are more likely in the presence of intellectual disability. The SRS is a quick identification tool that can be employed in the outpatient setting.

scholarly journals Time for a shift in focus in schizophrenia: From narrow phenotypes to broad endophenotypes

2005 ◽  
Vol 187 (3) ◽  
pp. 203-205 ◽  
Author(s):  
Mark Weiser ◽  
Jim van Os ◽  
Michael Davidson
Keyword(s):  
Risk Factors ◽  
Mental Illness ◽  
Genetic Factors ◽  
The Other ◽  
Social Impairment ◽  
Response To Treatment ◽  
Social Impairments ◽  
Biological Explanation ◽  
Biological Substrate ◽  
The One

SummaryMany manifestations of mental illness, risk factors, course and even response to treatment are shared by several diagnostic groups. For example, cognitive and social impairments are present to some degree in most DSM and ICD diagnostic groups. The idea that diagnostic boundaries of mental illness, including schizophrenia, have to be redefined is reinforced by recent findings indicating that on the one hand multiple genetic factors, each exerting a small effect, come together to manifest as schizophrenia, and on the other hand, depending on interaction with the environment, the same genetic variations can present as diverse clinical phenotypes. Rather than attempting to find a unitary biological explanation for a DSM construct of schizophrenia, it would be reasonable to deconstruct it into the most basic manifestations, some of which are common with other DSM constructs, such as cognitive or social impairment, and then investigate the biological substrate of these manifestations.

scholarly journals Involvement of Anti-Inflammatory, Antioxidant, and BDNF Up-Regulating Properties in the Antipsychotic-Like Effect of the Essential Oil of Alpinia Zerumbet in Mice: A Comparative Study With Olanzapine

2021 ◽  
Author(s):  
Fernanda Yvelize Ramos de Araújo ◽  
Adriano José Maia Chaves Filho ◽  
Adriana Mary Nunes ◽  
Gersilene Valente de Oliveira ◽  
Patrícia Xavier Lima Gomes ◽  
...  
Keyword(s):  
Weight Gain ◽  
Drug Therapy ◽  
Side Effects ◽  
Essential Oil ◽  
Negative Symptoms ◽  
Repeated Administration ◽  
Social Impairment ◽  
Standard Drug ◽  
Anti Inflammatory ◽  
Alpinia Zerumbet

Abstract The current drug therapy for schizophrenia effectively treats acute psychosis and its recurrence; however, this mental disorder’s cognitive and negative symptoms are still poorly controlled. Antipsychotics present important side effects, such as weight gain and extrapyramidal effects. The essential oil of Alpinia zerumbet (EOAZ) leaves presents potential antipsychotic properties that need further preclinical investigation. Here, we aimed to determine the effects of EAOZ in the prevention and reversal of schizophrenia-like symptoms (positive, negative, and cognitive) induced by ketamine (KET) repeated administration in mice and putative neurobiological mechanisms related to this effect. To this end, we evaluated antioxidant (GSH, nitrite levels), anti-inflammatory [interleukin (IL)-6], and neurotrophic [brain-derived neurotrophic factor (BDNF)] effects of this oil in hippocampal tissue. The atypical antipsychotic olanzapine (OLZ) was used as standard drug therapy. EOAZ, similarly to OLZ, prevented and reversed most KET-induced schizophrenia-like behavioral alterations, i.e., sensorimotor gating deficits and social impairment. EOAZ had a modest effect on the prevention of KET-associated working memory deficit. Compared to OLZ, EOAZ showed a more favorable side effects profile, inducing less cataleptic and weight gain changes. EOAZ efficiently protected the hippocampus against KET-induced oxidative imbalance, IL-6 increments, and BDNF impairment. In conclusion, our data add more mechanistic evidence for the anti-schizophrenia effects of EOAZ, based on its antioxidant, anti-inflammatory, and BDNF up-regulating actions. The absence of significant side effects observed in current antipsychotic drug therapy seems to be an essential benefit of the oil.

scholarly journals Disruption of VGLUT1 in cholinergic medial habenula projections increases nicotine self-administration

2021 ◽  
Author(s):  
Elizabeth A Souter ◽  
Yen-Chu Chen ◽  
Vivien Zell ◽  
Valeria Lallai ◽  
Thomas Steinkellner ◽  
...  
Keyword(s):  
Cholinergic Neurons ◽  
Nicotine Addiction ◽  
Conditional Knockout ◽  
Self Administration ◽  
Interpeduncular Nucleus ◽  
Medial Habenula ◽  
Field Assay ◽  
Nicotine Consumption ◽  
Additional Support ◽  
Cholinergic Projections

Cholinergic projections from the medial habenula (MHb) to the interpeduncular nucleus (IPN) have been studied for their complex contributions to nicotine addiction and have been implicated in nicotine reinforcement, aversion, and withdrawal. While it has been established that MHb cholinergic projections co-release glutamate, no direct evidence has demonstrated a role for this specific glutamate projection in nicotine consumption. In the present study, a novel floxed Slc17a7 (VGLUT1) mouse was generated and used to create conditional knockout (cKO) mice that lack VGLUT1 in MHb cholinergic neurons. Histochemical approaches and optogenetics-assisted electrophysiology were used to validate the disruption of VGLUT1 from cholinergic MHb to IPN projections. The mice displayed no gross phenotypic abnormalities and exhibited normal exploratory and locomotor behavior in the open-field assay. However, the loss of VGLUT1-mediated glutamate co-release led to increased nicotine self-administration. These findings indicate that glutamate co-release from ventral MHb cholinergic neurons opposes nicotine consumption and provide additional support for targeting this synapse to develop potential treatments to nicotine addiction.

scholarly journals The Clinical Course and Prognostic Problems of Youth Depressions with Attenuated Schizophrenic Symptoms

2021 ◽  
pp. 42-52
Author(s):  
V. G. Kaleda ◽  
M. A. Omelchenko
Keyword(s):  
Depressive Episode ◽  
Functional Outcomes ◽  
Negative Symptoms ◽  
Clinical Course ◽  
Control Group ◽  
Youth Depression ◽  
Early Markers ◽  
Spectrum Disorders

Objective Clinical and follow-up verification of Attenuated Schizophrenic Symptoms (ASS) in the first youth depressive episode as early markers of the schizophrenic process, establishing further variants of the course of the disorder and its outcomes.Materials and methods. 124 young inpatients (averaged age 19,6±2,3 years) with the first depressive episode with ASS were examined. The control group consisted of 27 patients with youth depression without ASS. All patients have been tracked for at least five years. The average follow-up period was 7,1±1,6 years. The HDRS, SOPS, SANS and PSP scales were used to assess the symptomatic and functional outcomes. Statistical analysis was carried out using STATISTICA 12.Results. The typological classification of youth depressions (ASD) with ASS has been developed with the identification of three main types: (1) with attenuated positive symptoms (APS), (2) with attenuated negative symptoms (ANS), and (3) with attenuated symptoms of disorganization. Youth depression with ASS, compared to the control group, is more likely to move into chronic forms, has reliably worse functional and symptomatic outcomes, and is more associated with the diagnosis of schizophrenic spectrum disorders at five years follow-up.Conclusion. Attenuated schizophrenic symptoms in the structure of youth depressions have high affinity to each other, indicating a common pathogenic mechanism of their formation, and also have predicate value as risk factors for schizophrenia.

scholarly journals Developmental precursors of child- and adolescent-onset schizophrenia and affective psychoses: diagnostic specificity and continuity with symptom dimensions

2003 ◽  
Vol 182 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Chris Hollis
Keyword(s):  
Psychotic Symptom ◽  
Early Onset ◽  
Negative Symptoms ◽  
Child And Adolescent ◽  
Social Impairment ◽  
First Episode ◽  
Retrospective Case ◽  
Symptom Dimensions ◽  
Affective Psychoses ◽  
Developmental Continuity

BackgroundAn increased rate of premorbid impairment has been reported in both child- and adolescent-onset schizophrenic and affective psychoses.AimsTo examine the evidence for a specific association between premorbid impairment and child- and adolescent-onset schizophrenia, and whether specific continuities exist between premorbid impairments and psychotic symptom dimensions.MethodRetrospective case note study of 110 first-episode child- and adolescent-onset psychoses (age 10–17 years). DSM–III–R diagnoses derived from the OPCRIT algorithm showed 61 with schizophrenia (mean age 14.1 years) and 49 with other non-schizophrenic psychoses (mean age 14.7 years).ResultsPremorbid social impairment was more common in early-onset schizophrenia than in other early-onset psychoses (OR 1.9, P=0.03). Overall, impaired premorbid development, enuresis and incontinence during psychosis were specifically associated with the negative psychotic symptom dimension.ConclusionsPremorbid social impairments are more marked in child- and adolescent-onset schizophrenia than in other psychoses. There appears to be developmental continuity from premorbid impairment to negative symptoms.

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