Maintenance Therapy of Psychosis Spectrum Disorders in a Real-World Setting: Antipsychotics Prescription Patterns and Long-Term Benzodiazepine Use.

Background: Maintenance therapy of patients with primary psychosis spectrum disorders (PSD) in the Western Balkans has received limited interest so far. The present study aimed to investigate long-term prescription patterns among outpatients with PSD. Methods: Information about prescription of antipsychotics (AP), benzodiazepines (BZD) and other psychotropic medication over a 6-month period was collected from outpatients (n = 134; ICD-10 diagnosis F20-29) recruited by a larger multi-site study, to find mean daily number of psychotropic drugs, AP prescription patterns (including AP daily dose, route of administration, monotherapy vs. polypharmacy) and BZD utilization (long-term add-on BZD therapy). Additionally, sex-differences in the variables were explored. Results: Clinically stable outpatients (age 41.7 ± 11.0; male 62.7%; duration of untreated illness 12.7 ± 8.7 years; mean number of lifetime hospitalizations 2.6 ± 0.7) were prescribed 2.8 ± 1.1 psychotropic medications daily. The mean 6-month AP dose was 14.2 ± 7.8 mg olanzapine equivalents. Long-acting injectable AP was prescribed to 25.2% of the patients. Long-term AP monotherapy was found in 52.7% patients and most of them were prescribed second generation AP (65.2%). Long-term AP polypharmacy (42.7%) was more common in males (p = 0.015). The most frequent co-prescription patterns were first generation AP plus clozapine. The highest rate of long-term AP co-prescription was found for BZD (in 42.7% cases, average 6-months daily dose of 2.8 ± 2.7 mg lorazepam equivalents) and anticholinergics (33.6%). Conclusion: Existing appropriately designed interventions aiming to safely switch the inappropriate therapeutic regimens, i.e. very high prevalence of long-term AP polypharmacy and non-rational BZD co-prescription, should be implemented in the region of Western Balkans.

Psychometric Characteristics of the Macedonian Version of Clinical Assessment Interview for Negative Symptoms (CAINS).

BACKGROUND: Despite the importance of effective assessment and treatment of negative symptoms among patients with psychosis, no validated instruments are available in the Republic of North Macedonia. The aim of this paper was to explore psychometric properties, namely factorial structure, internal consistency, convergent and discriminant validity of the Clinical Assessment Interview for Negative Symptoms (CAINS). SUBJECTS AND METHODS: In this cross-sectional study 82 outpatients diagnosed with psychosis (64 with schizophrenia and 18 with bipolar disorder; female=34, mean age=41.05±10.09) were assessed. RESULTS: The exploratory factor analysis revealed two factorial structure of the negative symptoms as measured by the CAINS, i.e. 'expression and motivation' and 'pleasure'. Two items aimed to measure motivation for family relations and motivation for work/school activities loaded on the expression factor instead on motivation and pleasure factor which differs from the original version of the CAINS. Convergent validity was proven by positive relationship to negative symptoms as measured by the BPRS. Positive, but weak correlation with BPRS positive symptoms demonstrated its discriminant validity. Internal consistency of overall CAINS scale and its two subscales was very high. CONCLUSION: The CAINS can be used to assess negative symptoms in individuals with psychosis in the Macedonian clinical context. Consequently, this work can provide a foundation for further clinical advancement and research of negative symptoms in Macedonian healthcare.

Predictors and moderators of outcome of psychotherapeutic interventions for mental disorders in adolescents and young adults: protocol for systematic reviews.

BACKGROUND: Adolescence and young adulthood is a risk period for the emergence of mental disorders. There is strong evidence that psychotherapeutic interventions are effective for most mental disorders. However, very little is known about which of the different psychotherapeutic treatment modalities are effective for whom. This large systematic review aims to address this critical gap within the literature on non-specific predictors and moderators of the outcomes of psychotherapeutic interventions among adolescents and young adults with mental disorders. METHODS: The protocol is being reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) Statement. PubMed and PsycINFO databases will be searched for randomized controlled and quasi-experimental/naturalistic clinical trials. Risk of bias of all included studies will be assessed by the Mixed Methods Appraisal Tool. The quality of predictor and moderator variables will be also assessed. A narrative synthesis will be conducted for all included studies. DISCUSSION: This systematic review will strengthen the evidence base on effective mental health interventions for young people, being the first to explore predictors and moderators of outcome of psychotherapeutic interventions for a wide range of mental disorders in young people. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020166756 .

Rare Pathogenic Copy Number Variation in the 16p11.2 (BP4-BP5) Region Associated with Neurodevelopmental and Neuropsychiatric Disorders: A Review of the Literature.

Copy number variants (CNVs) play an important role in the genetic underpinnings of neuropsychiatric/neurodevelopmental disorders. The chromosomal region 16p11.2 (BP4-BP5) harbours both deletions and duplications that are associated in carriers with neurodevelopmental and neuropsychiatric conditions as well as several rare disorders including congenital malformation syndromes. The aim of this article is to provide a review of the current knowledge of the diverse neurodevelopmental disorders (NDD) associated with 16p11.2 deletions and duplications reported in published cohorts. A literature review was conducted using the PubMed/MEDLINE electronic database limited to papers published in English between 1 January 2010 and 31 July 2020, describing 16p11.2 deletions and duplications carriers' cohorts. Twelve articles meeting inclusion criteria were reviewed from the 75 articles identified by the search. Of these twelve papers, eight described both deletions and duplications, three described deletions only and one described duplications only. This study highlights the heterogeneity of NDD descriptions of the selected cohorts and inconsistencies concerning accuracy of data reporting.

Analysis of EEG Characteristics and Coherence in Patients Diagnosed as Borderline Personality.

Borderline personality disorder is a clinically important psychiatric diagnosis that is distinct from major depressive, bipolar and posttraumatic stress disorders, despite the overlapping symptoms. The diagnosis is mainly clinical and must follow the DMS 5 (or ICD 10) characteristics. The most common age at first presentation is in late adolescence, but the disorder frequently can be stay as misdiagnosed. Our study is concerned to QEEG characteristics, as well as coherence in borderline patients compared with healthy group, matched by number, gender and age and selected randomly. Our obtained results showed that electrophysiological characteristics for borderlines are fairly without statistical differences, except in low bands (delta and theta), which showed significantly lower frequencies and coherence compared to a healthy group. Future research in this filed with more patients is highly recommended.

Inter- and Intra-Hemispheric EEG Coherence Study in Adults with Neuropsychiatric Disorders.

Functional connectivity between different regions of the brain in the resting state has been a recent topic of interest in neurophysiological research. EEG coherence happened to be an useful tool for measuring changes in neuro-psycho-physiological functioning which are not detectable by simply measuring amplitude or power spectra. The aim of our study was to investigate the changes in the EEG coherence in groups of different mental disorders such as: depression, general anxiety disorder, ADHD, Asperger syndrome and headaches, compared to control group. All measures were made in two conditions: eye opened (EO) and eyes closed (EC). The obtained results show that in EO condition there is a significantly lower coherence for delta waves between analyzed groups. For theta coherence only for Asperger syndrome we found lower coherence compared to control group, ADHD and headaches in parietal region (P3-P4). Obtained results for intrahemispheric coherence have shown that there was significantly lower coherence in both conditions for delta and theta bands in almost all sites for Asperger's syndrome, and opposite increased intrahemispheric coherence for patients with headaches (for delta band in the anterior regions and for theta band in the posterior regions). ADHD patients expressed lower delta inter-hemispheric coherence in frontal regions, and increased coherence of theta in central regions but increased delta coherence in posterior regions only in EO condition. For depressive and anxiety patients we found decreased intrahemispheric coherence for EO condition for delta brain waves all over the cortex. Concerning the coherence in anxiety patients in our current study we have obtained hypo coherence in centro-parieto-occipital region only for delta in inter-hemispheric coherence and also lower delta coherence through the cortex for intrahemispheric coherence. Our findings for interhemispheric hyper coherence in subjects with depression specifically for alpha and beta bands were confirmed in other studies. We suggest that EEG coherence analysis could be a sensitive parameter in the detection of electrophysiological abnormalities in patients with anxiety, depression, ADHD, Asperger syndrome and headaches. These results can confirm the development of QEEG state and trait biomarkers for psychiatric disorders.

Attitudes of the autism community to early autism research.

Investigation into the earliest signs of autism in infants has become a significant sub-field of autism research. This work invokes specific ethical concerns such as use of 'at-risk' language, communicating study findings to parents and the future perspective of enrolled infants when they reach adulthood. This study aimed to ground this research field in an understanding of the perspectives of members of the autism community. Following focus groups to identify topics, an online survey was distributed to autistic adults, parents of children with autism and practitioners in health and education settings across 11 European countries. Survey respondents (n = 2317) were positively disposed towards early autism research, and there was significant overlap in their priorities for the field and preferred language to describe infant research participants. However, there were also differences including overall less favourable endorsement of early autism research by autistic adults relative to other groups and a dislike of the phrase 'at-risk' to describe infant participants, in all groups except healthcare practitioners. The findings overall indicate that the autism community in Europe is supportive of early autism research. Researchers should endeavour to maintain this by continuing to take community perspectives into account.

Quantitative EEG in Children and Adults With Attention Deficit Hyperactivity Disorder: Comparison of Absolute and Relative Power Spectra and Theta/Beta Ratio.

In recent decades, resting state electroencephalographic (EEG) measures have been widely used to document underlying neurophysiological dysfunction in attention deficit hyperactivity disorder (ADHD). Although most EEG studies focus on children, there is a growing interest in adults with ADHD too. The aim of this study was to objectively assess and compare the absolute and relative EEG power as well as the theta/beta ratio in children and adults with ADHD. The evaluated sample comprised 30 male children and 30 male adults with ADHD diagnosed according to DSM-IV criteria. They were compared with 30 boys and 30 male adults matched by age. The mean age (±SD) of the children's group was 9 (±2.44) years and the adult group 35.8 (±8.65) years. EEG was recorded during an eyes-open condition. Spectral analysis of absolute (µV2) and relative power (%) was carried out for 4 frequency bands: delta (2-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-21 Hz). The findings obtained for ADHD children are increased absolute power of slow waves (theta and delta), whereas adults exhibited no differences compared with normal subjects. For the relative power spectra there were no differences between the ADHD and control groups. Across groups, the children showed greater relative power than the adults in the delta and theta bands, but for the higher frequency bands (alpha and beta) the adults showed more relative power than children. Only ADHD children showed greater theta/beta ratio compared to the normal group. Classification analysis showed that ADHD children could be differentiated from the control group by the absolute theta values and theta/beta ratio at Cz, but this was not the case with ADHD adults. The question that should be further explored is if these differences are mainly due to maturation processes or if there is a core difference in cortical arousal between ADHD children and adults.

Mental Health Legislation and Involuntary Hospitalization in the Republic of Macedonia.

As psychiatrists, we are often obliged to provide non-consensual treatment. This institute comprises the rights of the patients with mental health disorders. The aim of this paper is to explain the contemporary mental health legislation in our country the Republic of Macedonia and the problems with the implementation of involuntary hospitalisation. This could be overcome with close cooperation between the judicial and health care system.

Analysis of independent components of cognitive event related potentials in a group of ADHD adults.

In the last decade, many studies have tried to define the neural correlates of attention deficit hyperactivity disorder (ADHD). The main aim of this study is the comparison of the ERPs independent components in the four QEEG subtypes in a group of ADHD adults as a basis for defining the corresponding endophenotypes among ADHD population. Sixty-seven adults diagnosed as ADHD according to the DSM-IV criteria and 50 age-matched control subjects participated in the study. The brain activity of the subjects was recorded by 19 channel quantitative electroencephalography (QEEG) system in two neuropsychological tasks (visual and emotional continuous performance tests). The ICA method was applied for separation of the independent ERPs components. The components were associated with distinct psychological operations, such as engagement operations (P3bP component), comparison (vcomTL and vcom TR), motor inhibition (P3supF) and monitoring (P4monCC) operations. The ERPs results point out that there is disturbance in executive functioning in investigated ADHD group obtained by the significantly lower amplitude and longer latency for the engagement (P3bP), motor inhibition (P3supF) and monitoring (P4monCC) components. Particularly, the QEEG subtype IV was with the most significant ERPs differences comparing to the other subtypes. In particular, the most prominent difference in the ERPs independent components for the QEEG subtype IV in comparison to other three subtypes, rise many questions and becomes the subject for future research. This study aims to advance and facilitate the use of neurophysiological procedures (QEEG and ERPs) in clinical practice as objective measures of ADHD for better assessment, subtyping and treatment of ADHD.

Use of early intervention for young children with autism spectrum disorder across Europe.

Little is known about use of early interventions for autism spectrum disorder in Europe. Parents of children with autism spectrum disorder aged 7 years or younger (N = 1680) were recruited through parent organisations in 18 European countries and completed an online survey about the interventions their child received. There was considerable variation in use of interventions, and in some countries more than 20% of children received no intervention at all. The most frequently reported interventions were speech and language therapy (64%) and behavioural, developmental and relationship-based interventions (55%). In some parts of Europe, use of behavioural, developmental and relationship-based interventions was associated with higher parental educational level and time passed since diagnosis, rather than with child characteristics. These findings highlight the need to monitor use of intervention for children with autism spectrum disorder in Europe in order to contrast inequalities.

Machine learning approach for classification of ADHD adults.

Machine learning techniques that combine multiple classifiers are introduced for classifying adult attention deficit hyperactivity disorder (ADHD) subtypes based on power spectra of EEG measurements. The analyzed sample includes 117 adults (67 ADHD, 50 controls). The measurements are taken for four different conditions: two resting conditions (eyes open and eyes closed) and two neuropsychological tasks (visual continuous performance test and emotional continuous performance test). We divide the sample into four data sets, one for each condition. Each data set is used for training of four different support vector machine classifiers, while the output of classifiers is combined using logical expression derived from the Karnaugh map. The results show that this approach improves the discrimination between ADHD and control groups, as well as between ADHD subtypes.

Perceived stress in dental practice.

Stress is a normal physiological response to events that make us feel threatened, or upset our balance in some way. In medicine, it is known that stress, as an emotional state, can be a trigger for many psychosomatic disorders. Work stress and burnout are considered to be serious professional risks in dentistry. The dentist should be aware of these stressors and attempt to manage them in order to avoid becoming occupationally dissatisfied. On the other hand, the other common characteristic of modern life is a growing burden of different chronic diseases. Periodontal disease is one of the two most important oral diseases contributing to the global burden of chronic disease. The aim of this study was to assess the perceived stress in patients with periodontal pathologies, and to compare it with the stress in doctors-dentists and students of dentistry as future professionals. Our study confirmed the presence of significant stress in all three groups of examinees (patients, doctors, and students). Surprisingly, the obtained PSQ scores are similar in the examined groups. In addition, no differences between perceived stress in males and females have been found. There is a minimal positive correlation between age and obtained scores. However, stress must be evaluated as a risk factor both for professionals or for chronic dental patients and some response measures must be undertaken.

Anxiety and personality characteristics in children undergoing dental interventions.

Anxiety about and fear of dental treatment have been recognized as sources of problems in the management of child dental patients. It has been suggested that some individuals who are fearful of or anxious about dental treatment have a constitutional vulnerability to anxiety disorders as is evidenced by the presence of multiple fears, generalized anxiety or panic disorders. Concerning the child population, maternal anxiety is considered to be a major factor affecting the behaviour of young children expecting dental intervention. The aim of the study was to the measure general anxiety of children undergoing dental intervention and to compare it with some personality characteristics, such as psychopathology, extroversion and neuroticism. The evaluated sample comprises 50 children (31 girls and 19 boys), randomly selected at the University Dental Hospital, Skopje. The mean age for girls was 11.4 (± 2.4) years, and for boys 10.7 (± 2.6) years. Two psychometric instruments were used: the General Anxiety Scale for Children (GASC) and the Eysenck Personality Questionnaire (EPQ). The study confirms the presence of a high anxiety level (evaluated with GASC) among all children undergoing dental intervention. It also confirmed differences in anxiety scores between girls and boys, girls having higher scores for anxiety. Personality characteristics (evaluated with EPQ) showed low psychopathological traits, moderate extroversion and neuroticism, but accentuated insincerity (evaluated with L scale). L scales are lower with increasing age, but P scores rise with age, which could be related to puberty. No correlation was found between personality traits (obtained scores for EPQ) and anxiety except for neuroticism, which is positively correlated with the level of anxiety. In the management of dental anxiety some response measures (psychological support, biofeedback, and relaxation techniques) are recommended.

Quantitative EEG Spectrum-weighted Frequency (Brain Rate) Distribution in Adults with ADHD.

OBJECTIVE: The aim of this study is to explore the applicability of brain rate (fb) for the diagnosis of attention-deficit/hyperactivity disorder (ADHD), analyzing the spatial distribution of fb through analysis of its values in sagittal and lateral electrodes' positions, recorded in four conditions (eyes closed, eyes opened, visual continuous performance task and emotional continuous performance task). METHODS: Sixty-seven adults diagnosed with ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and 50 age-matched control subjects participated in the study. The brain activity of the subjects was recorded by 19 channel quantitative electroencephalography (QEEG) system and fb was calculated with the fb software. RESULTS: Maximum values of fb for sagittal topography are obtained in central region and the minimum in frontal region, while lateral topography maximum values are found in the left and right sides and the minimum in midline region. A positive correlation between the fb values and the QEEG spectra subtypes was obtained, with lower values for normals, first and second subtype, and higher values for the third and fourth subtype. On the other hand, there was no correlation between behavioral symptoms and fb values. CONCLUSION: The applicability of an fb indicator in the diagnosis of ADHD is especially pronounced for the higher subtypes (ADHD III and IV), corresponding to heterogeneous and multifactorial character of this disorder.

Simultaneous EEG and EMG biofeedback for peak performance in musicians.

The aim of this study was to determine the effects of alpha neurofeedback and EMG biofeedback protocols for improvement of musical performance in violinists. The sample consisted of 12 music students (10 violinists and 2 viola players) from the Faculty of Music, Skopje (3 males, mean age of 20 +/- 0 and 9 females, mean age = 20.89 +/- 2.98). Six of them had a low alpha peak frequency (APF) (< 10 Hz), and six a high APF (> 10 Hz). The sample was randomized in two groups. The students from the experimental group participated in 20 sessions of biofeedback (alpha/EMG), combined with music practice, while the students from the control group did only music practice. Average absolute power, interhemispheric coherence in the alpha band, alpha peak frequency (APF), individual alpha band width (IABW), amount of alpha suppression (AAS) and surface forehead integrated EMG power (IEMG), as well as a score on musical performance and inventories measuring anxiety, were assessed. Alpha-EEG/EMG-biofeedback was associated with a significant increase in average alpha power, APF and IABW in all the participants and with decreases in IEMG only in high-APF musicians. The biofeedback training success was positively correlated with the alpha power, IcoH, APF, IABW and baseline level of APF and IABW. Alpha-EEG/EMG biofeedback is capable of increasing voluntary self-regulation and the quality of musical performance. The efficiency of biofeedback training depends on the baseline EEG alpha activity status, in particular the APF.