Tardive Dystonia due to D2 Antagonists and Other Agents

Tardive dystonia due to D2 antagonists or other agents is a potentially severe extrapyramidal side effect emerging after long-term drug treatment, prevalent but not limited to psychiatric populations. Its course is often deteriorating, and available treatments are frequently far from satisfying. It presents with sustained muscle contractions, abnormal postures, and repetitive twisting movements and leads to increased psychiatric morbidity, mortality, and decline of quality of life. Inadequate clinical skill and awareness of tardive dystonia can lead to neglect or misdiagnoses, considered as conversion symptoms or of psychogenic origin. Since the syndrome is persistent and often treatment resistant, prevention should be a mainstay of clinical care. Emerging evidence supports positive effects of atypical antipsychotics, particularly quetiapine and clozapine. Therapies such as tetrabenazine, valbenazine, deutetrabenazine, anticholinergics, baclofen, benzodiazepines, vitamin E, or non-pharmacologic interventions, namely botulinum toxin A, deep-brain stimulation, have been found to be helpful in some cases of tardive dystonia. This chapter comprehensively illustrates multiple aspects of this entity, including recent advances on etiology, pathophysiology, clinical presentation, epidemiology, pharmacogenomics, and treatment, aiming to enhance and deepen clinicians’ and researchers’ awareness of tardive dystonia, with the final goal of ameliorating patients’ prognosis and quality of life

Physiological Basis of the Couvade Syndrome and Peripartum Onset of Bipolar Disorder in a Man: A Case Report and a Brief Review of the Literature

Rapid hormonal changes during pregnancy as well as psycho-social stressors accompanying parenthood have often been associated with peripartum mood episodes in women with bipolar disorder or with not yet clinically expressed bipolar diathesis. Yet, little is known about the correlation of peripartum onset of bipolar disorder in men. We present the case of a man with bipolar disorder with peripartum onset and subsequent episodes following the peripartum initiation of the disease, as well as the association of the couvade syndrome, as a pathological response to a man due to hormonal shifts observed in males cohabiting with a pregnant female. The patient had his first depressive episode during the peripartum period of his spouse, followed by two mixed episodes with psychotic features that leaded to his compulsory psychiatric evaluation and subsequent hospitalization and the diagnosis of Bipolar Disorder I. There is a well-known correlation between the peripartum period and mood disturbances to the point of inducing full blown episodes, suggesting of a bipolar disorder initiation or mood episodes relapsing in female patients already diagnosed with bipolar disorder. Due to the patient's psychological disturbances and the phenomenology of his symptoms, mainly concerning the psychotic features accompanying his episodes, we discuss the possible underlying biological correlates as a triggering mechanism, that might overlap the manifestation of the Couvade Syndrome as well as the initiation or relapse of Bipolar Disorder in males. It seems that males are not less influenced by hormonal and psycho-social factors posed upon them during the peripartum period of their cohabiting female spouse

Comment on Keeler et al. Ketamine as a Treatment for Anorexia Nervosa: A Narrative Review. Nutrients 2021, 13, 4158

Anorexia Nervosa (AN) represents a difficult therapeutic challenge, with up to 4% prevalence among females and increasing incidence among youth [...

Comparative study of young and late onset paranoid schizophrenia

The demographic features and symptomatology of young and late onset paranoid schizophrenia were studied in a sample of 88 patients who were consecutively hospitalized in the Psychiatric Department of the University Hospital of Patras, from 3-15-2005 to 5-7-2008. The sample consisted of 60 patients, 46 men and 14 women, with young onset paranoid schizophrenia, before the age of 30, and 21 late onset patients, 8 men and 13 women, with onset of the illness after the age of 35 years old. Demographic features, rates of smoking and alcohol and cannabis use, premorbid personality disorder features, the number and type of prodromal symptoms, the duration of the prodromal period and the symptomatologies of the active phase were compared between young and late onset groups, in the total sample and separately for the two sexes, and between the two sexes in each age group. SCID-I/P, PANSS, Calgary Depression Scale, SCID-II, and a clinical interview for the prodromal symptoms were applied. Statistical analysis was performed by applying the Wilcoxon rank-sum and chi-square tests. Young onset patients, particularly men, were more likely to have been born in urban regions, compared with late onset patients. Late onset women were most frequently married, compared with all other groups. There was not any significant difference regarding use of nicotine, alcohol or cannabis between young and late onset patients. In the young onset group, men more frequently used alcohol and cannabis than women. Similarly, late onset men smoked and tended to use cannabis more often than late onset women. In the premorbid period, young onset patients have significantly more traits of avoidant personality disorder compared with late onset patients. This finding tended to be significant in the female sample, as well. Late onset patients had significantly more traits of passive-aggressive personality disorder than young onset patients, in the total and male sample. In the young onset group, men had significantly more traits of paranoid and schizotypal personality disorder than women, whereas women had more traits of the depressive personality disorder. In the late onset group, men had more histrionic, narcissistic and antisocial traits than women. In the prodromal phase, young onset patients present with significantly more negative prodromal symptoms, in the total and the male sample. In the total sample, marked isolation and impairment of concentration are observed at a significantly higher rate in the young onset group, than in late onset patients. Also, in the young onset group, women had significantly shorter duration of prodromal period than men. During the active phase, young onset patients had significantly heavier total score of negative symptomatology, heavier lack of spontaneity and heavier disturbances of volition. On the other hand, late onset patients tended to suffer from heavier suspiciousness/ideas of persecution. In the male sample, young onset patients had heavier total negative symptomatology, blunted affect and lack of spontaneity. There were not any significant differences in the female sample. In the late onset group, men had heavier delusions than women. There was not any significant difference regarding depressive symptoms among the groups. Our findings indicate the modulatory effect of age of onset and sex on the clinical presentation of paranoid schizophrenia, in the premorbid period, prodromal and active phases, possibly following the developmental and maturational procedures that take place in the brain, throughout the life span, in the two sexes.Τα δημογραφικά χαρακτηριστικά και η συμπτωματολογία και της παρανοειδούς μορφής σχιζοφρένειας πρώιμης και όψιμης έναρξης μελετήθηκαν σε 88 ασθενείς, που νοσηλεύθηκαν στην Ψυχιατρική Κλινική του Πανεπιστημίου Πατρών, από 15-3-2005 έως 7-5-2008. Εξ’ αυτών, 60, 46 άνδρες και 14 γυναίκες, ενεφάνιζαν πρώιμη έναρξη της νόσου, πριν από την ηλικία των 30 ετών, ενώ 21, 8 άνδρες και 13 γυναίκες, ασθένησαν όψιμα, με έναρξη νόσου σε ηλικία ≥35 ετών. Συνεκρίθησαν τα δημογραφικά στοιχεία, η συχνότητα κατάχρησης ή εξάρτησης τον καπνό, οινόπνευμα και κάνναβη, τα στοιχεία προνοσηρών διαταραχών προσωπικότητας, ο αριθμός και ο τύπος των προδρόμων συμπτωμάτων, η διάρκεια της πρόδρομης φάσης και η συμπτωματολογία της ενεργού φάσης μεταξύ των ασθενών πρώιμης και όψιμης έναρξης, συνολικά και χωριστά για τα δύο φύλα, καθώς και μεταξύ ανδρών και γυναικών, στις δύο ηλικιακές ομάδες. Οι κλίμακες που εφαρμόσθηκαν ήταν οι SCID-I/P, PANSS, Calgary Depression Scale, SCID-II, καθώς και κλινική συνέντευξη για τα πρόδρομα συμπτώματα. Τα στοιχεία αναλύθηκαν με τις στατιστικές δοκιμασίες Wilcoxon rank-sum και χ2. Οι ασθενείς πρώιμης έναρξης, και ιδιαίτερα οι άνδρες, είχαν στατιστικώς σημαντικά μεγαλύτερη πιθανότητα να έχουν γεννηθεί σε αστική περιοχή σε σχέση με τους ασθενείς όψιμης έναρξης. Οι γυναίκες όψιμης έναρξης είχαν το μεγαλύτερο ποσοστό έγγαμης συμβίωσης από όλες τις άλλες ομάδες. Δεν παρατηρήθηκε στατιστικώς σημαντική διαφορά στη χρήση καπνού, οινοπνεύματος και κάνναβης μεταξύ των ομάδων πρώιμης και όψιμης έναρξης, συνολικά ή χωριστά στα δύο φύλα. Στην ομάδα πρώιμης έναρξης, οι άνδρες παρουσίαζαν σε μεγαλύτερη συχνότητα χρήση αλκοόλ και κάνναβης σε σχέση με τις γυναίκες. Παρομοίως, οι άνδρες όψιμης έναρξης κάπνιζαν και έτειναν να χρησιμοποιούν κάνναβη σε μεγαλύτερο ποσοστό από τις γυναίκες. Στην προνοσηρή περίοδο, οι πρώιμης έναρξης ασθενείς έχουν σημαντικά περισσότερα στοιχεία αποφευκτικής διαταραχής προσωπικότητας σε σχέση με τους όψιμης έναρξης. Αυτό το εύρημα πλησιάζει τη στατιστική σημαντικότητα και στο δείγμα των γυναικών. Οι ασθενείς όψιμης έναρξης, στο συνολικό δείγμα και στο δείγμα των ανδρών, εμφανίζουν στατιστικώς σημαντικά περισσότερα στοιχεία παθητικο-επιθετικής διαταραχής προσωπικότητας σε σχέση με τους ασθενείς πρώιμης έναρξης. Στην ομάδα με την πρώιμη έναρξη, οι άνδρες είχαν περισσότερα στοιχεία σχιζότυπης και παρανοειδούς διαταραχής προσωπικότητας από τις γυναίκες, ενώ οι τελευταίες είχαν περισσότερα στοιχεία καταθλιπτικής διαταραχής προσωπικότητας. Στους ασθενείς όψιμης έναρξης, οι άνδρες είχαν περισσότερα στοιχεία ιστριονικής, ναρκισσιστικής και αντικοινωνικής διαταραχής από τις γυναίκες. Στην πρόδρομη φάση, οι ασθενείς πρώιμης έναρξης παρουσιάζουν στατιστικώς σημαντικά μεγαλύτερο αριθμό αρνητικών συμπτωμάτων, στο συνολικό δείγμα και στο δείγμα των ανδρών. Στο συνολικό δείγμα, τα συμπτώματα της εκσεσημασμένης κοινωνικής απομόνωσης και της έκπτωσης της συγκέντρωσης παρατηρούνται σε στατιστικώς σημαντικά μεγαλύτερο ποσοστό στην ομάδα με την πρώιμη έναρξη σε σχέση με την ομάδα όψιμης έναρξης. Στους ασθενείς που νόσησαν πρώιμα, οι γυναίκες είχαν μικρότερη διάρκεια πρόδρομης περιόδου από τους άνδρες. Κατά την ενεργό φάση, η ομάδα πρώιμης έναρξης εμφάνιζε βαρύτερη συνολική αρνητική συμπτωματολογία, καθώς και βαρύτερα τα συμπτώματα της έλλειψης αυθορμητισμού και των διαταραχών της βούλησης. Αντίθετα, οι ασθενείς όψιμης έναρξης έτειναν νε έχουν βαρύτερο το σύμπτωμα της καχυποψίας/ιδεών δίωξης. Στο δείγμα των ανδρών, οι ασθενείς πρώιμης έναρξης είχαν στατιστικώς σημαντικά βαρύτερη συνολική αρνητική συμπτωματολογία, συναισθηματική αμβλύτητα και έλλειψη αυθορμητισμού. Στο δείγμα των γυναικών δεν ανευρέθησαν στατιστικώς σημαντικές διαφορές. Στους ασθενείς όψιμης έναρξης, οι άνδρες εμφάνιζαν σημαντικά βαρύτερες παραληρητικές ιδέες σε σχέση με τις γυναίκες. Ως προς την καταθλιπτική συμπτωματολογία, δεν παρατηρήθηκαν διαφορές μεταξύ των ομάδων. Συνολικά τα παραπάνω ευρήματα υποδεικνύουν την τροποποιητική επίδραση του φύλου και της ηλικίας έναρξης στην κλινική εμφάνιση της παρανοϊκής μορφής σχιζοφρένειας, κατά την προνοσηρή περίοδο, πρόδρομη και ενεργό φάση, πιθανόν ως αποτέλεσμα των διεργασιών ανάπτυξης και ωρίμανσης του εγκεφάλου με την πάροδο της ηλικίας, στα δύο φύλα

Inflammation and mitochondrial dysfunction in affective disorders-novel understandings, novel treatments?

Background: Mitochondria are involved in energy production, oxidative balance, cell survival/apoptosis, immune response, and inflammation. A possible role in affective disorders has fueled research on mitochondrial targets for novel treatments. Methods: A systematic review of the literature was conducted, in Science Direct, Scopus and PubMed databases, from inception to 12th September 2022. Key words used were mitochondria AND/OR inflammation AND affective OR bipolar OR depression AND therapy OR treatment OR intervention. Results: Twenty-one studies were included in the analysis. Animal studies (n=16) have shown positive results for Nucleus Accumbens Deep Brain Stimulation (NAc DBS), Near-Infrared Photobiomodulation (NIR-PBM), exercise, 48-hour fasting, and fluoxetine, Li, valproate, BI-11A7 Bid inhibitor, methylene blue (MB), AC-5216, atractylenolide-III (ALT-III), ONO-2952, oxytocin (OT), tocopherol-a, Coenzyme Q10 (CoQ10). Human studies (n=5) have tested adjunctive therapies, with NAC plus antioxidant combination therapy, triacetyl-uridine (TAU), cytidine add-on, and andacetyl-l-carnitine and a-lipoic acid combination, with positive (TAU), negative, or difficult-to-interpret results. Limitations: The search was conducted on three databases only, and only articles written in English were included. Unpublished articles or research with negative results may have been missed. Conclusion: Mitochondria-targeting interventions are promising novel treatments for depression and bipolar disorder

Clinical implementation of preemptive pharmacogenomics in psychiatry

Background:Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology, demonstrating a beneficial effect of PGx-guided treatment in reducing adverse drug reactions, there are very few such studies in psychiatry, none of which spans across all main psychiatric indications, namely schizophrenia, major depressive disorder and bipolar disorder. In this study we aim to investigate the clinical effectiveness of PGx-guided treatment (occurrence of adverse drug reactions, hospitalisations and re-admissions, polypharmacy) and perform a cost analysis of the intervention. Methods: We report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder. Findings: We show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm), less duration of initial hospitalisations (n = 3305 total days of hospitalisation in the PGx-guided arm from 110 patients, versus n = 6517 in the control arm from 187 patients) and duration of hospitalisation upon readmission (n = 579 total days of hospitalisation upon readmission in the PGx-guided arm, derived from 19 patients, versus n = 928 in the control arm, from 32 patients respectively). It was also shown that in the vast majority of the cases, there was less drug dose administrated per drug in the PGx-guided arm compared to the control arm and less polypharmacy (n = 124 patients prescribed with at least 4 psychiatric drugs in the PGx-guided arm versus n = 143 in the control arm) and smaller average number of co-administered psychiatric drugs (2.19 in the PGx-guided arm versus 2.48 in the control arm. Furthermore, less deaths were reported in the PGx-guided arm (n = 1) compared with the control arm (n = 9). Most importantly, we observed a 48.5% reduction of treatment costs in the PGx-guided arm with a reciprocal slight increase of the quality of life of patients suffering from major depressive disorder (0.935 versus 0.925 QALYs in the PGx-guided and control arm, respectively).Interpretation: While only a small proportion (∼25%) of the entire study sample had an actionable genotype, PGx-guided treatment can have a beneficial effect in psychiatric patients with a reciprocal reduction of treatment costs. Although some of these findings did not remain significant when all patients were considered, our data indicate that genome-guided psychiatric treatment may be successfully integrated in mainstream healthcare. </p

Genetic Variations Associated with Sleep Disorders in Patients with Schizophrenia: A Systematic Review

Background: Schizophrenic patients commonly suffer from sleep disorders which are associated with acute disease severity, worsening prognoses and a poorer quality of life. Research is attempting to disentangle the complex interplay between schizophrenia and sleep disturbances by focusing not only on demographic and clinical characteristics, but also on the identification of genetic factors. Methods: Here, we performed a systematic literature review on the topic of genetic variations in sleep-disordered schizophrenic patients in an attempt to identify high quality investigations reporting scientifically sound and clinically useful data. For this purpose, we conducted a thorough search of PubMed, ScienceDirect and GoogleScholar databases, according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. Results: Our search yielded 11 eligible studies. Certain genetic variations were reported to be associated with schizophrenia-related sleep disorders. Antipsychotic-induced restless legs syndrome was linked to polymorphisms located on CLOCK, BTBD9, GNB3, and TH genes, clozapine-induced somnolence was correlated with polymorphisms of HNMT gene, while insomnia was associated with variants of the MTNR1 gene. Conclusions: There are significant genetic associations between schizophrenia and co-morbid sleep disorders, implicating the circadian system, dopamine and histamine metabolism and signal transduction pathways

Clinical implementation of preemptive pharmacogenomics in psychiatryResearch in context

Summary: Background: Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology, demonstrating a beneficial effect of PGx-guided treatment in reducing adverse drug reactions, there are very few such studies in psychiatry, none of which spans across all main psychiatric indications, namely schizophrenia, major depressive disorder and bipolar disorder. In this study we aim to investigate the clinical effectiveness of PGx-guided treatment (occurrence of adverse drug reactions, hospitalisations and re-admissions, polypharmacy) and perform a cost analysis of the intervention. Methods: We report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder. Findings: We show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm), less duration of initial hospitalisations (n = 3305 total days of hospitalisation in the PGx-guided arm from 110 patients, versus n = 6517 in the control arm from 187 patients) and duration of hospitalisation upon readmission (n = 579 total days of hospitalisation upon readmission in the PGx-guided arm, derived from 19 patients, versus n = 928 in the control arm, from 32 patients respectively). It was also shown that in the vast majority of the cases, there was less drug dose administrated per drug in the PGx-guided arm compared to the control arm and less polypharmacy (n = 124 patients prescribed with at least 4 psychiatric drugs in the PGx-guided arm versus n = 143 in the control arm) and smaller average number of co-administered psychiatric drugs (2.19 in the PGx-guided arm versus 2.48 in the control arm. Furthermore, less deaths were reported in the PGx-guided arm (n = 1) compared with the control arm (n = 9). Most importantly, we observed a 48.5% reduction of treatment costs in the PGx-guided arm with a reciprocal slight increase of the quality of life of patients suffering from major depressive disorder (0.935 versus 0.925 QALYs in the PGx-guided and control arm, respectively). Interpretation: While only a small proportion (∼25%) of the entire study sample had an actionable genotype, PGx-guided treatment can have a beneficial effect in psychiatric patients with a reciprocal reduction of treatment costs. Although some of these findings did not remain significant when all patients were considered, our data indicate that genome-guided psychiatric treatment may be successfully integrated in mainstream healthcare. Funding: European Union Horizon 2020