Social robots as psychometric tools for cognitive assessment: a pilot test

Recent research demonstrated the benefits of employing robots as therapeutic assistants and caregivers, but very little is known on the use of robots as a tool for psychological assessment. Socially capable robots can provide many advantages to diagnostic practice: engage people, guarantee standardized administration and assessor neutrality, perform automatic recording of subject behaviors for further analysis by practitioners. In this paper, we present a pilot study on testing people’s cognitive functioning via social interaction with a humanoid robot. To this end, we programmed a social robot to administer a psychometric tool for detecting Mild Cognitive Impairment, a risk factor for dementia, implementing the first prototype of robotic assistant for mass screening of elderly population. Finally, we present a pilot test of the robotic procedure with healthy adults that show promising results of the robotic test, also compared to its traditional paper version

The many faces of mitochondrial dysfunction in depression: From pathology to treatment

Introduction The last years of neurobiological research have transformed the way we consider mental illnesses. We have gone from a deterministic genetic view to a broader vision that includes the involvement of non-cerebral systems. This is especially true for major depression (MD). Historically, MD has been perceived as a multifactorial disorder correlated to various neurobiological changes like neurotransmitter deficits, endocrine disturbances, impaired plasticity, and neural adaptation (Benatti et al., 2016). Indeed, the development and progression of depressive disorders has been conceived as the disruption of body allostasis, defined as the process of achieving stability of physiological and mental processes through dynamic change (Wang et al., 2019). The main player in the “allostatic game” is the brain, an organ designed to integrate signals from the periphery that anticipate fluctuations, changes, and needs and coordinates allostatic mediators in order to develop successful coping mechanisms that ultimately lead to an adaptative strategy and resilience (de Kloet et al., 2005). The establishment and maintenance of these mechanisms requires large amounts of energy from the organism. Without energy, or in a partial lack of energy, the biological mechanisms necessary to respond appropriately to stimuli may not occur or be established incorrectly or abnormally. Human and animal studies suggest an intriguing link between our body’s ability to produce energy and the brain’s ability to correctly perform the complex cellular and molecular processes involved in allostatic processes. In eukaryotic cells, mitochondria are the powerhouse that produces and distributes energy to all other components. Functional or quantitative alterations of the ability of mitochondria to adequately supply energy can have important repercussions primarily on cellular processes and cascades of serial events (Herst et al., 2017) as well as on the correct functioning of the organism including mechanisms of brain plasticity, mood, and behavior in general (Allen et al., 2018). In this framework, it is particularly intriguing to think of the mitochondria as an active regulator of many of the biological phenomena involved in depression and in the efficacy of or resistance to the most widely used pharmacological treatments. Once the energetic equilibrium is compromised, the body becomes more “vulnerable.” This is especially true for stress-related disorders, such as depression. In fact, depression is often associated with energetic imbalance leading to profound effects on the disease (Zuccoli et al., 2017). The driving questions then are as follows: What happens to the brain in the presence of an energetic imbalance? Does depression or depression-related symptoms impact mitochondrial energetic efficiency? Is antidepressant efficacy mediated by mitochondrial functionality

Impairment of quality of life associated with lifetime diagnosis of posttraumatic stress disorder in women-a national survey in italy

Introduction: The aim of the study was to measure the lifetime prevalence of Post-Traumatic Stress Disorder (PTSD) among women of an Italian community sample, the comorbidity of PTSD with mood and anxiety disorders and the burden attributable to PTSD in worsening the Quality of Life (QoL). Methods: Community survey on a sample of 1961 adult women randomly selected. Tools: psychiatric clinical interview ANTAS partially derived from the SCID-DSM-IV, administered by psychologists or medical doctors; Short Form Health Survey (SF-12); Mood Disorder Questionnaire (MDQ). Results: Lifetime prevalence of PTSD in women was 1.3%, (1.4% in<45 years aged, 1.3% in >44 years aged; p=0.8). In order of risk of comorbidity, PTSD was associated with: Bipolar Spectrum Disorders (MDQ+), Panic Disorders (PD) and Major Depressive Disorder (MDD). People with PTSD showed an SF-12 mean score lower than women of the same sample without PTSD (standardized by gender and age), with a mean difference (attributable burden) of 3.9±0.9 similarly to MDD and Eating Disorders and higher than PD. Among the analyzed nonpsychiatric diseases, Multiple Sclerosis and Carotid Atherosclerosis showed a higher burden in impairing QoL than PTSD; Wilson’s Disease showed a similar burden and Celiac Disease was found less impairing on QoL than PTSD. Conclusion: The attributable burden in worsening women’ perceived QoL due to a lifetime diagnosis of PTSD was found comparable to those caused by MDD, Eating Disorders or by neurological condition such as Wilson’s Disease. The comorbidity of PTSD with Bipolar Spectrum Disorders was remarkable, even further studies are needed to clarify the direction of causality

Fluoxetine and vortioxetine reverse depressive-like phenotype and memory deficits induced by Aβ1-42 oligomers in mice: A key role of transforming growth factor-β1

Depression is a risk factor for the development of Alzheimer's disease (AD), and the presence of depressive symptoms significantly increases the conversion of mild cognitive impairment (MCI) into AD. A long-term treatment with antidepressants reduces the risk to develop AD, and different second-generation antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are currently being studied for their neuroprotective properties in AD. In the present work, the SSRI fluoxetine and the new multimodal antidepressant vortioxetine were tested for their ability to prevent memory deficits and depressive-like phenotype induced by intracerebroventricular injection of amyloid-beta (1-42) (A beta(1-42)) oligomers in 2-month-old C57BL/6 mice. Starting from 7 days before A beta injection, fluoxetine (10 mg/kg) and vortioxetine (5 and 10 mg/kg) were intraperitoneally injected daily for 24 days. Chronic treatment with fluoxetine and vortioxetine (both at the dose of 10 mg/kg) was able to rescue the loss of memory assessed 14 days after A beta injection by the passive avoidance task and the object recognition test. Both antidepressants reversed the increase in immobility time detected 19 days after A beta injection by forced swim test. Vortioxetine exerted significant antidepressant effects also at the dose of 5 mg/kg. A significant deficit of transforming growth factor-beta 1 (TGF-beta 1), paralleling memory deficits and depressive-like phenotype, was found in the hippocampus of A beta -injected mice in combination with a significant reduction of the synaptic proteins synaptophysin and PSD-95. Fluoxetine and vortioxetine completely rescued hippocampal TGF-beta 1 levels in A beta -injected mice as well as synaptophysin and PSD-95 levels. This is the first evidence that a chronic treatment with fluoxetine or vortioxetine can prevent both cognitive deficits and depressive-like phenotype in a non-transgenic animal model of AD with a key contribution of TGF-beta 1

Prenatal stress induces a depressive-like phenotype in adolescent rats: The key role of TGF-β1 pathway

Stressful experiences early in life, especially in the prenatal period, can increase the risk to develop depression during adolescence. However, there may be important qualitative and quantitative differences in outcome of prenatal stress (PNS), where some individuals exposed to PNS are vulnerable and develop a depressive-like phenotype, while others appear to be resilient. PNS exposure, a well-established rat model of early life stress, is known to increase vulnerability to depression and a recent study demonstrated a strong interaction between transforming growth factor-β1 (TGF-β1) gene and PNS in the pathogenesis of depression. Moreover, it is well-known that the exposure to early life stress experiences induces brain oxidative damage by increasing nitric oxide levels and decreasing antioxidant factors. In the present work, we examined the role of TGF-β1 pathway in an animal model of adolescent depression induced by PNS obtained by exposing pregnant females to a stressful condition during the last week of gestation. We performed behavioral tests to identify vulnerable or resilient subjects in the obtained litters (postnatal day, PND > 35) and we carried out molecular analyses on hippocampus, a brain area with a key role in the pathogenesis of depression. We found that female, but not male, PNS adolescent rats exhibited a depressive-like behavior in forced swim test (FST), whereas both male and female PNS rats showed a deficit of recognition memory as assessed by novel object recognition test (NOR). Interestingly, we found an increased expression of type 2 TGF-β1 receptor (TGFβ-R2) in the hippocampus of both male and female resilient PNS rats, with higher plasma TGF-β1 levels in male, but not in female, PNS rats. Furthermore, PNS induced the activation of oxidative stress pathways by increasing inducible nitric oxide synthase (iNOS), NADPH oxidase 1 (NOX1) and NOX2 levels in the hippocampus of both male and female PNS adolescent rats. Our data suggest that high levels of TGF-β1 and its receptor TGFβ-R2 can significantly increase the resiliency of adolescent rats to PNS, suggesting that TGF-β1 pathway might represent a novel pharmacological target to prevent adolescent depression in rats

A network study to differentiate suicide attempt risk profiles in male and female patients with major depressive disorder

Suicide attempts are a possible consequence of Major Depressive Disorder (MDD), although their prevalence varies across different epidemiological studies. Suicide attempt is a significant predictor of death by suicide, highlighting its importance in understanding and preventing tragic outcomes. Researchers are increasingly recognizing the need to study the differences between males and females, as several distinctions emerge in terms of the characteristics, types and motivations of suicide attempts. These differences emphasize the importance of considering gender-specific factors in the study of suicide attempts and developing tailored prevention strategies. We conducted a network analysis to represent and investigate which among multiple neurocognitive, psychosocial, demographic and affective variables may prove to be a reliable predictor for identifying the 'suicide attempt risk' (SAR) in a sample of 81 adults who met DSM-5 criteria for MDD. Network analysis resulted in differences between males and females regarding the variables that were going to interact and predict the SAR; in particular, for males, there is a stronger link toward psychosocial aspects, while for females, the neurocognitive domain is more relevant in its mnestic subcomponents. Network analysis allowed us to describe otherwise less obvious differences in the risk profiles of males and females that attempted to take their own lives. Different neurocognitive and psychosocial variables and different interactions between them predict the probability of suicide attempt unique to male and female patients

Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease

Keratin 9 was recently identified as an important component of a biomarker panel which demonstrated a high diagnostic accuracy (87%) for Alzheimer’s disease (AD). Understanding how a protein which is predominantly expressed in palmoplantar epidermis is implicated in AD may shed new light on the mechanisms underlying the disease. Here we use immunoassays to examine blood plasma expression patterns of Keratin 9 and its relationship to other AD-associated proteins. We correlate this with the use of an in silico analysis tool VisANT to elucidate possible pathways through which the involvement of Keratin 9 may take place. We identify possible links with Dickkopf-1, a negative regulator of the wnt pathway, and propose that the abnormal expression of Keratin 9 in AD blood and cerebrospinal fluid may be a result of blood brain barrier dysregulation and disruption of the ubiquitin proteasome system. Our findings suggest that dysregulated Keratin 9 expression is a consequence of AD pathology but, as it interacts with a broad range of proteins, it may have other, as yet uncharacterized, downstream effects which could contribute to AD onset and progression