Despite the rapid increase in disability and death due to Parkinson’s disease and associated psychiatric comorbidities (psychosis, depression, cognitive impairment, anxiety), the quest for a clear pathophysiological mechanism and treatment remains elusive. Numerous studies aim to identify a metabolomic fingerprint for PD and new, promising biomarkers are discovered with implications beyond neurodegenerative diseases, such as novel markers as predictors of bipolar type in depressed patients.Changes in neuronal microenvironment employ electrochemical techniques, such as cyclic voltammetry, used in both animal and human models of PD to monitor dopamine (DA) alterations in vivo, with high spatial and temporal resolution.

Our aim is to investigate the latest scientific literature on PD and associated neuropsychiatric disorders and review the applications cyclic voltammetry has in recent technological advances in the field.

To gain a broad understanding of the subject, we have consulted multiple scientific literature databases (PubMed, Google Academic, Science Direct) using the keywords “cyclic voltammetry, Parkinson’s disease, psychiatric disorders, dopamine” and included original research articles published in the last 10 years

The first in situ measurement of DA release in the human brain has been demonstrated in a sequential investment task, with implications for future research in decision-making behavior.

One study combines cyclic voltammetry and wireless telemetry for in vivo recording of changes in extracellular levels of DA, with high temporal and spatial resolution.

Disulfide nanorod-graphene-β-cyclodextrin nanocomposites biosensors have been succesfully used in detecting DA in rodent brain and human blood serum samples, with implications for minimally invasive measuring techniques.

Animal studies use cyclic voltammetry to monitor changes in DA levels in cerebrospinal fluid and plasma of mouse models of PD and investigate DA metabolism, release, uptake and receptor sensitivity in Knock-out mice, with implications for the diurnal variation of extracellular DA tone and release.Furthermore, a human alpha-synuclein-expressing mouse model of PD exhibited increased extracellular DA concentrations, decreased DA uptake and relieved paired-stimulus depression.

Cyclic voltammetry is a powerful tool in the expansion to humans of electrochemical recording techniques in PD. The final aim is to investigate DA neuron physiology before neurodegeneration onset and to measure neurotransmitter release in real time.

None Declared

The differential impact of depression across different periods in life on mortality remains inconclusive. We aimed to examine the association of depression that occurs at different age with all-cause mortality, and to explore the roles of dementia, as well as genetic and early-life environmental factors, in this association.

From the Swedish Twin Registry, 44,919 twin individuals were followed for up to 18 years. Depression was ascertained using the National Patient Registry and categorized as early-life (<45 years), midlife (45–64 years), and late-life (≥65 years) depression according to the age of the first diagnosis. Deaths were identified through the Cause of Death Register. Generalized estimating equation, generalized structural equation, and conditional logistic regression were used for unmatched, mediation, and co-twin matched analyses, respectively.

In unmatched analyses, the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of mortality were 1.71 (1.46–2.00) for depression at any age, 1.72 (1.36–2.17) for early-life, 1.51 (1.19–1.90) for midlife, and 4.10 (2.02–8.34) for late-life depression. Mortality was significantly higher in individuals with late-life depression than those with earlier-life depression (p < 0.05). The mediation analysis showed that 59.83% of the depression-mortality association was mediated by dementia. No significant difference in ORs between the unmatched and co-twin matched analyses was observed (p = 0.09).

Depression is associated with an increased risk of all-cause mortality, and dementia mediates approximately 60% of the impact of depression on mortality in late life. Genetic and early-life environmental factors may not play a significant role in the depression-mortality association.

Psychoneuroimmunology is a discipline that has emerged over the past decades as a broad interdisciplinary field that closely observes the relationship between the psychological state, the nervous system, the endocrine system, and the immune system. The natural aging process leads to alterations in the immune functions, involving lymphocyte dysregulation, and therefore leading to a higher risk of developing coronary artery diseases, infectious diseases or even cancer.

The aim of our inquiry is to evaluate the existing body of work with a focus on studies that observed the intricate connections between psychosocial factors and immunity.

We performed a systematic review on PubMed and a targeted literature search concentrating on all the factors involved in immunosenescence and their consequences.

The causality between emotional stressors (acute or chronic), lack of social support, adverse life events, coping mechanisms, personality traits, as well as endocrine changes and multiple age-related pathologies is often undeniable. Other relevant factors include nutrition, sleep, physical activity and substance use. As people grow older, they face a number of psychosocial stressors, such as retirement, social isolation, loss of independence, low income, a decrease in productivity and also somatic comorbidities. These factors, together with an age-related decline in immune function, can constitute not only a psychosocial disadvantage of the elderly, but also a risk factor able to trigger further deterioration of the immune system.

Age-associated alterations of the immune response represent a complex concept. Given that we are dealing with the phenomenon of aging in the general population, the field of psychoneuroimmunology can make a significant contribution in establishing the different mechanisms through which seniors can cushion the impact of stressors in regards to health and illness. Therefore, we can pave the way for an individualized approach and support for patients, as well as provide better therapeutic outcomes.

None Declared

The authors have not supplied their declaration of competing interest.

Case presentation of a middle aged lady Mrs. C.K., who developed tardive dyskinesia (TD) after a trial of an SSRI.

A 49-year-old Australian aboriginal lady, presented with involuntary movement of her face (bucco-linguo masticatory), movements after a 3 months trial of sertraline (maximum dose of 100 mg daily) for her depressive illness. There was no history of trials with anti-psychotics or any other medications, which may have caused the oral dyskinesias. Routine examinations including cognitive testing, EEG and MRI revealed no pathological findings. Her sertraline was ceased and she was commenced on mirtazapine 15 mg at night, which was hiked to 30 mg after 1 week and continued on this dose over the next 3 months. She exhibited good improvement in her depressive symptoms and a significant attenuation of her TD's. Involuntary movement scale rating: she was rated on the abnormal involuntary movement scale (AIMS) and showed gradual improvement in the severity of her orofacial dyskinetic movement. Her scores were–initial presentation (scored 22/36); at 4 weeks (9/36); 8 weeks (6/36) and at 16 weeks (4/36).

Although TD's are seen in approximately 1 to 5% of mental health patients treated with anti-psychotics (and some other medications like Levodopa, Metochlorpromide, etc.), research studies on SSRI's causing TD's are rare and few (Leo et al., 1996; Gerber et al., 1998).

To alert and educate clinicians about a relatively rare adverse-effect of SSRI producing an involuntary movement disorder.

The author has not supplied his/her declaration of competing interest.

The authors have not supplied their declaration of competing interest.

Over the past decades, immunotherapy treatments have been a revolution to many chronic diseases with encouraging results in clinical outcomes and quality of life. The use of monoclonal antibodies has yielded a great variability in terms of clinical efficacy and tolerability although it’s believed the incidence of psychotic symptoms is low (0,1-0,4%).

To review the effects of monoclonal antibodies on psychosis.

Review of literature using PubMed database. A total of 16 studies were included.

The targeted molecules by monoclonal antibodies may determine the risk of psychosis. While those who target TNF-alfa seem to have a reduced risk of psychosis (such as Infliximab, Adalimumab, Certolizumab and Golimumab), monoclonal antibodies who modulate lymphocytes may have a greater risk of psychosis namely Natalizumab, Belimumab, Basiliximab and Daclizumab, which seems to correlate to evidence of alterations in lymphocyte subsets in groups of patients with first psychotic episode and schizophrenia. Some seem to have positive correlation with psychosis namely monoclonal antibodies who have a supressing effect on the immune system, especially those who target adaptative immunity and those who are used in autoimmune diseases (vs oncologic conditions). It is unknown if delusions prevail over hallucinations or vice-versa. Despite the paucity of evidence, these findings corroborate the variability regarding the psychiatric effects of immunotherapy.

The available literature reports a low prevalence of psychotic symptoms associated with the use of monoclonal antibodies but it highlights the importance in knowing the immune mechanisms involved in psychotic disorders. Greater research is needed to correctly assess that risk.

Depression in the elderly is common and closely interrelated with the deterioration of the quality of life, especially in the institutionalized elderly.

In this work, we propose to determine the prevalence of depression in the elderly in institution, to assess their quality of life and to evaluate the correlations between depression and the quality of life.

Our study concerned 30 elderly subjects institutionalized at the retirement home(Sousse, Tunisia). Three validated Arabic version scales were used: The 30-item GDS (Geriatric Depression Scale), the MMSE (Mini Mental State Examination) and the SF36 (assessing the quality of life).

The mean age of our population was 75±7.3 years, the sex ratio was 1.73. The prevalence of depression was 37%. The elderly had a cognitive impairment in 16.7%. The mean global SF36 score were 11.2, attesting an altered quality of life in all our subjects: the mental component (9.43) were more altered than the physical one (13.03). No correlation between depression and quality of life was found. Depression was significantly correlated with the presence of a medical history (p=0.05). Depression had a negative and statistically significant correlation with the physical score of SF36 (r=-0.41, p=0.02) and tended towards significance for the “general health” dimension of SF36 (r=-0.32, p=0.08).

Our study shows a high frequency of depression in the institutionalized elderly as well as a deterioration in their quality of life. Depression is strongly linked to deterioration in physical condition.Our results underline the influence of somatic diseases as a major risk factor for depression in the elderly.

No significant relationships.

The concept of male depression is based on the hypothesis that typical symptoms of depression in men often seem to be masked by non-typical male distress symptoms not considered in common depression inventories. Despite clinical evidence, scientific evidence is still lacking. The study describes symptoms reported by males (on the Gotland Male Depression Scale (GMDS) in a community study and these were further validated against MDS criteria.

In a community study in Reykjanes Iceland, 534 males were rated by the GMDS. In the second phase a sub-sample of healthy and depressive males were examined by a trained psychiatrist in a semi-structured interview (N=137). Diagnosis was according to the DSM-IV for MDD. The symptoms on GMDS are self-rated from 0-3.

In the community sample the prevalence (>1 GMDS) of single symptoms was following: More stressed out than usual (16.8%), aggressiveness (11.8%), feeling of being burned out (14.5%), tiredness (18.2%), more irritable (15.3%), difficulty making decisions (10.8%), sleep problems (21%), anxiety/uneasiness (10.5%), increased use of alcohol/substances, hyperactivity ( 10.3%), behavioural changes (4.7%), feeling sad/hopeless (10.4%), self-pity (4.8%). All symptoms on GMDS correlated strongly with MDD. In a stepwiselogistic regression model, controlling for medication and age, three items contributed independently to MDD diagnoses. These were aggressiveness, being more irritable and anxiety/uneasiness.

Sleep problems and tiredness were most commonly reported symptoms. The best predicting symptoms for MDD were anxiety and acting out symptoms, aggression and irritability. This is of interest as these symptoms are not in the criteria for MDD.

The autonomic nervous system (ANS) plays a key role in maintenance of the homeostasis and adaptability of the body to different stimuli. The disturbances of ANS, especially sympathetic dysregulation in stress response, are associated with various disorders.

Thus, we aimed to study the sympathetic arousal in response to negative emotional stress and during recovery using heart rate variability (HRV) nonlinear analysis (symbolic dynamics parameter 0V%) and skin conductance level (SCL) as sympathetically-mediated indices in healthy students.

Seventy students (age: 23.1±0.2yr., 39 females) were examined during complex stress response: baseline – negative emotional stress – recovery. RR intervals (for HRV analysis) and electrodermal activity were continuously recorded during each period lasting six minutes. Evaluated parameters: HRV nonlinear analysis - symbolic dynamics index 0V% as cardiac sympathetic index, skin conductance level (SCL) as sympathetic cholinergic index.

Regarding electrodermal activity, the parameter SCL significantly increased in response to negative emotional stress (p<0.001) and remained higher after stress (recovery phase, p<0.001). Symbolic dynamics index 0V% was without significant changes.

Our findings revealed increased sympathetically-mediated index SCL in response to negative emotional stress and in recovery phase indicating higher sympathetic arousal during complex stress response in young people. Surprisingly, cardiac sympathetic index 0V% was not sensitive to detect discrete changes in sympathetic arousal to negative emotion. We suggest that detailed knowledge about complex sympathetic regulatory mechanisms to emotional stress in healthy probands represents the first step for understanding of pathomechanisms leading to abnormal stress response in mental disorders.

This study was funded by the Slovak Scientific Grant Agency under grants VEGA 1/0044/18; VEGA 1/0190/20 and Ministry of Health of the Slovak Republic under the project registration number 2018/20-UKMT-16.

Le trouble bipolaire est une pathologie chronique qui nécessite la mise en place de stratégies non médicamenteuses éducatives [2]. Récemment, le concept de Serious game (jeu sérieux) [1] a fait son apparition dans les programmes d’éducation thérapeutique [4]. BIPOLIFE®[3], programme d’information ludoéducatif sur le trouble bipolaire accessible sur Internet, a été développé afin de s’intégrer dans la panoplie psychoéducative. BIPOLIFE® consiste à faire évoluer son avatar au quotidien. Ce jeu est basé sur 3 cibles : les règles hygiénodiététiques, l’observance médicamenteuse, le recours au médecin/psychiatre.

Mise en place d’une étude pilote évaluant l’acceptabilité de BIPOLIFE® et son effet sur la connaissance de la maladie auprès de 63 patients bipolaires sur 3 semaines. Les patients ont été évalués avec l’échelle de connaissance du trouble bipolaire et une échelle d’acceptabilité de BIPOLIFE®.

BIPOLIFE® semble être mieux accepté par des jeunes (p = 0,011) et plus efficace sur des hommes (p = 0,043) ayant une moins bonne connaissance de la maladie initiale (p ≤ 0,001). La majorité des patients a rapporté en avoir tiré bénéfice sur leur vie quotidienne, leur connaissance ou leur gestion de la maladie. Les patients ont déclaré que BIPOLIFE® est à conseiller à des personnes souffrant de TB (32 %), à leur proche entourage (32 %) ou au grand public (16 %).

Notre étude montre que BIPOLIFE® est déjà un outil pertinent dans la prise en charge des patients bipolaires. Des études complémentaires sont nécessaires pour évaluer précisément sa place dans les programmes de psychoéducation.

Although Positive (PS) and Negative Schizotypy (NS) are considered distinct entities, prefrontal dysfunction seems to be a common underlying mechanism. According to recent evidence, PS can be divided into Paranoid (ParS) and Cognitive-Perceptual (CPS).

To explore NS’, ParS’ and CPS’ profiles of prefrontal function/psychopathology/stressful childhood experiences.

To examine associations between NS, ParS and CPS with the above phenotype in a community sample.

140 healthy adults completed the Schizotypal-Personality Questionnaire (SPQ), Symptom-Checklist-90-Revised (SCL-90R), Wisconsin Card-Sorting Test (WCST), CANTAB Spatial Working Memory (SWM), Parental-Bonding Instrument (PBI) and Child Abuse/Trauma Scale (CAT). Associations between schizotypal dimensions and outcome variables were examined with separate forward regression-analyses (confounders: age, smoking).

High ParS and NS but not CPS were predicted by high CAT score and low parental-care respectively (Ps<0.001). High NS and high ParS predicted inefficient SWM strategy and increased WCST perseverative-errors (Ps<0.001; R2:0.155 and 0.243) while high ParS also predicted fewer WCST-completed categories and increased total errors (Ps<0.001; R2:0.138 and 0.174). All schizotypal dimensions along with reduced parental-care predicted high SCL-90 psychopathology in all dimensions (Ps<0.001); NS predicted mostly interpersonal sensitivity, depression and phobic anxiety (R2range:0.211-0.426), ParS predicted mostly obsessive-compulsive symptomatology, anxiety, paranoid ideation and psychoticism (R2range:0.257-0.373) and CPS predicted mostly somatization and anger/hostility (R2:0.240 and 0.213).

ParS and NS were similar in terms of prefrontal dysfunction and childhood life experiences although they differed in their clinical psychopathology patterns. CPS seems to be a 'less severe” form of schizotypy in terms of prefrontal dysfunction and childhood experiences with minimal impact on current psychopathology.

The conceptualization of negative symptoms (NS) in schizophrenia is still controversial. Recent confirmatory factor-analytic studies suggested that the bi-dimensional model (motivational deficit [MAP] and expressive deficit [EXP]) may not capture the complexity of NS structure, which could be better defined by a five-factor (five NS domains) or a hierarchical model (five NS domains as first-order factors, and MAP and EXP, as second-order factors). A validation of these models is needed to define the structure of NS. To evaluate the validity and temporal stability of the five-factor or the hierarchical structure of the brief negative symptom scale (BNSS) in individuals with schizophrenia (SCZ), exploring associations between these models with cognition, social cognition, functional capacity, and functioning at baseline and at 4 years follow-up.

Clinical variables were assessed using state-of-the-art tools in 612 SCZ at two-time points. The validity of the five-factor and the hierarchical models was analyzed through structural equation models.

The two models had both a good fit and showed a similar pattern of associations with external validators at the two-time points, with minor variations. The five-factor solution had a slightly better fit. The associations with external validators favored the five-factor structure.

Our findings suggest that both five-factor and hierarchical models provide a valid conceptualization of NS in relation to external variables and that five-factor solution provides the best balance between parsimony and granularity to summarize the BNSS structure. This finding has important implications for the study of pathophysiological mechanisms and the development of new treatments.

Clozapine is widely known as the drug of choice in treating refractory schizophrenia. However, clozapine prescription requires close clinical and biological monitoring to prevent harmful side effects like agranulocytosis, neutropenia and myocarditis.

To show the benefits of lithium carbonate in the clozapine rechallenge of a patient with neutropenia under clozapine.

We present the clinical case of a patient who developed neutropenia under clozapine, we rechallenged with clozapine after lithium treatment to stimulate hematopoietic functions.

A 42-year-old man diagnosed with refractory schizophrenia, under clozapine for 11 years with a good clinical response at a dosage of 500mg per day (clozapine serum level 328ng/ml), developed a neutropenia (BCC at 840/mm3) within an interval of 2 months. Clozapine treatment was suspended and the patient presented a severe psychotic relapse requiring hospitalization. During hospitalization the patient remained symptomatic under haloperidol 15mg daily. At week 3 of clozapine cessation, neutrophil count reached 1510/mm3. After week 4 we introduced lithium carbonate and while reaching 500mg per day we observed an increase in the neutrophil count to 4850/mm3. We rechallenged with clozapine at week 12 after a poor clinical response, with incremental dosage to 150mg per day in 17 weeks. The blood cell count did not show any abnormalities and the patient had a good clinical response up to 11 months after the clozapine rechallenge.

Despite the lack of guidelines assessing clozapine rechallenge after neutropenia, the use of lithium carbonate may be considered to stimulate hematopoietic functions.

No significant relationships.

Belarus is undergoing legislative shifts towards community-based mental health care. Responding effectively to support this process requires an understanding of the experiences and challenges facing families caring for a relative affected by mental illness.

To identify how caring for a person with severe mental illness impacts on family carers, and what carers identify as their support needs.

Semi-structured interviews were undertaken with 17 caregivers of people affected by severe mental illness (diagnosis of F06.8, F20, F25, F7, and/or F 84) in Belarus between March - June 2019.

Care-giving for a family member was usually undertaken on a full time basis with no option for respite. Whilst caring did, in cases, strengthen family solidarity, it also resulted in intensive stress and burnout, financial pressures, and high levels of family tension, exacerbated when the person living with mental illness was perceived as a potential safety risk. High levels of societal stigma meant that care-givers commonly felt unable to discuss their circumstances, travel in public spaces, or participate in community activities. Stigma also deterred carers from seeking professional support. Priorities for support amongst carers included better information, public awareness raising and sensitization, advocacy to support patient integration into social and economic life, peer support and respite for family carers, and an increase in mental health specialists.

Caregiving affected family carers on multiple levels with predominantly negative consequences. Priorities identified by carers need to be considered and acted upon if community-based care is to become an effective option.

Dementia with Lewy Bodies (DLB) is a primary degenerative dementing syndrome characterized by visual hallucinations, fluctuation in cognition, depressive symptoms and parkinsonism. Literature has shown the utility of electroconvulsive therapy (ECT) in demented patients regarding depressive symptoms and agitation. Nevertheless, the majority of cases described include patients with vascular dementia and Alzheimer’s disease. There are no cases informed concerning ECT in DLB patients with agitation and aggressive behaviors.

Evaluate the impact of electroconvulsive therapy (ECT) for agitation in a patient with diagnosis of Lewy Bodies Dementia (DLB).

Case report. 68-year-old male, with no prior neuropsychiatric history, was present for psychiatric evaluation for 5 year history of progressive dementia with fluctuations in cognition, complex visual hallucinations, delusional beliefs, depressive mood, anhedonia, irritability, associated to parkinsonism and increasing autoaggressive behaviors and agitation.

An extensive neurologic workup including neuroimaging, EEG and laboratory studies failed to reveal a specific etiology. Neuropsychological testing reveals frontal, attentional, and visuospatial dysfunction. A presumptive diagnosis of DLB was made.

Medication trials including donepezil, memantine, lamotrigine, sertraline, quetiapine, risperidone and melatonin failed to manage his depressive, psychotic and behavioral disturbances.

Considering past medication failures and prominent behavioral disturbances family consented for an acute course of ECT.

Initial acute phase consisted of 6 sessions of right unilateral, brief pulse width (0.3 ms) ECT tri-weekly utilizing Mecta Spectrum. Anesthesia was induced with propofol, and received succinylcholine for muscle relaxation. Initial charge was 115 mC (6x seizure threshold), then raised to 192 mC. Seizure duration averaged in 22 seconds. No adverse reactions reported.

Clinical outcomes were measured with the CGI-Efficacy Index. Pre-ECT CGI-SI score was 6 (severely ill) and post-ECT CGI-I was 3 (minimally improved).

Mood and behavioral disturbances are a frequent primary motive consultations in DLB patients. The treatment is challenging due to the sensitivity to antidopaminergic medications evidenced in this type of patients. This case suggests that ECT has an impact in the treatment of agitation and aggression in DLB patients, although further investigation is needed.

None Declared

A variety of psychological determinants, such as vulnerability to stress, low levels of psychological well-being and several comorbidities, have been hypothesized to play a role in the development, and maintenance of Internet Gaming Disorder (IGD). However, evidence has been insufficient to sustain an overarching model of the causal pathways leading to IGD.

. This study aimed to depict a model of the causal links between vulnerability to stress, psychological well-being, and symptoms of common mental disorders (e.g., depression, generalized anxiety, phobic anxiety, obsessive-compulsive disorder, somatization, and hostility).

. A community-based sample of Portuguese gamers (N = 153; Mage = 21.92; 15.29% female) completed measures of IGD (IGDS9-SF), mental health (SCL-90-R), psychological well-being (EBEP), and vulnerability to stress (23QVS). A machine learning algorithm – Greedy Fast Causal Inference – was used to infer a model of the causal pathways linking those psychological determinants to IGD.

. Hostility and psychological well-being were directly involved with a subgroup of IGD symptoms (i.e., gaming used as escape, tolerance, withdrawal, and loss of control). Stress vulnerability and symptoms of mental disorders were only indirectly implicated in the causal pathways leading to IGD.

. It is likely that several psychological factors implicated in the causal pathways leading to IGD, have not been yet identified. Future research should directly test specific models of the causal pathways involved in the development and maintenance of IGD symptoms.

No significant relationships.