The event-related potential method has proven to be a useful tool for studying the effects of gender information in language. Studies have shown that mismatch between the antecedent and the following ...referent triggers two ERP components, N400 and P600. In the present study, we investigated how grammatical gender affects the mental representation of the grammatical subject. A match-mismatch paradigm was used to investigate how masculine grammatical gender and gender-balanced forms (the explicit mention of masculine and feminine forms as word pairs) as role nouns affect the processing of the referent in Slovenian. The morphological complexity of Slovenian language required the use of anaphoric verbs instead of nouns/pronouns, on which previous research was based. The results showed that following both the gender-balanced and the masculine generic forms, P600 (but not N400) was observed in response to the feminine verb but not to the masculine verb. The P600 amplitude was smaller in the case of the gender-balanced form than in the case of the masculine generic form only. We have concluded that gender-balanced forms are more open to feminine continuations than masculine generic forms. This is the first ERP study in Slovenian to address the effects of processing grammatical gender, thus contributing to existing research on languages with grammatical gender. The great strength of the study is that it is one of the first ERP studies to test the mental inclusivity of gender-balanced forms.
Background
Pharmacogenetic analyses can predict interpersonal differences in response to psychopharmacotherapy, which greatly facilitates the selection of the most effective medication at optimal ...doses. By personalizing therapy in this way, we can minimize adverse drug reactions (ADR) and prevent polypharmacy. Most psychotropic medications are metabolized by the cytochrome P450 enzymes CYP2D6, CYP2C19, and CYPA3A4, which influence drug metabolism and concentration, affecting both efficacy and the occurrence of ADR. The relationships between genetic variations and enzymatic activity allow pharmacogenetic analysis to provide important data for optimal drug selection. The following case report illustrates the impact of pharmacogenetic analysis on the course of pharmacologic treatment in an elderly patient with a major depressive episode.
Methods
We present a case of a 79-year-old patient treated for severe depression with psychotic symptoms. We collected data on treatment selection and response to treatment before and after pharmacogenetic analysis. For pharmacogenetic analysis, common functional variants in
CYP1A2
,
CYP3A4
,
CYP2B6
,
CYP2C19
, and
CYP2D6
were genotyped, and corresponding evidence-based treatment recommendations were prepared.
Results
The patient suffered from lack of efficacy and serious ADR of several medications, resulting in worsening depression and treatment resistance over the course of several months of treatment. Pharmacogenetic analysis provided important insights into the patient’s pharmacokinetic phenotype and allowed us to personalize treatment and achieve remission of the depressive episode.
Conclusion
In the case presented, we have shown how consideration of pharmacogenetic characteristics in an individual patient can improve treatment outcome and patient well-being. Knowledge of the patient’s pharmacogenetic characteristics helped us to personalize treatment, resulting in complete remission of psychopathology. Due to the complexity of psychiatric disorders, the efficacy of combinations of different medications, which are often required in individual patients, cannot be clearly explained. Therefore, it is of great importance to conduct further pharmacokinetic and pharmacogenetic studies to better assess gene-drug interactions in psychopharmacotherapy.
The standard approach to treatment in psychiatry is known as "treatment as usual" (TAU), in which the same types of treatment are administered to a group of patients. TAU often requires numerous dose ...adjustments and medication changes due to ineffectiveness and/or the occurrence of adverse drug reactions (ADRs). This process is not only time-consuming but also costly. Antipsychotic medications are commonly used to treat various psychiatric disorders such as schizophrenia and mood disorders. Some of the inter-individual differences in efficacy and ADRs observed in psychopharmacotherapy can be explained by genetic variability in the pharmacokinetics and pharmacodynamics of antipsychotics. A better understanding of (in)efficacy and possible ADRs can be achieved by pharmacogenetic analysis of genes involved in the metabolism of antipsychotics. Most psychotropic drugs are metabolized by genetically variable CYP2D6, CYP1A2, CYP3A4, and CYP2C19 enzymes. To demonstrate the utility of pharmacogenetic testing for tailoring antipsychotic treatment, in this paper, we present the case of a patient in whom a pharmacogenetic approach remarkably altered an otherwise intolerant or ineffective conventional TAU with antipsychotics.
In this case report, we present a 60-year-old patient with psychotic symptoms who suffered from severe extrapyramidal symptoms and a malignant neuroleptic syndrome during treatment with risperidone, fluphenazine, aripiprazole, brexpiprazole, and olanzapine. Therefore, we performed a pharmacogenetic analysis by genotyping common functional variants in genes involved in the pharmacokinetic pathways of prescribed antipsychotics, namely,
,
,
,
,
, and
. Treatment recommendations for drug-gene pairs were made according to available evidence-based pharmacogenetic recommendations from the Dutch Pharmacogenetics Working Group (DPWG) or Clinical Pharmacogenetics Implementation Consortium (CPIC).
Pharmacogenetic testing revealed a specific metabolic profile and pharmacokinetic phenotype of the patient, which in retrospect provided possible explanations for the observed ADRs. Based on the pharmacogenetic results, the choice of an effective and safe medication proved to be much easier. The psychotic symptoms disappeared after treatment, while the negative symptoms persisted to a lesser extent.
With the case presented, we have shown that taking into account the pharmacogenetic characteristics of the patient can explain the response to antipsychotic treatment and associated side effects. In addition, pharmacogenetic testing enabled an informed choice of the most appropriate drug and optimal dose adjustment. This approach makes it possible to avoid or minimize potentially serious dose-related ADRs and treatment ineffectiveness. However, due to the complexity of psychopathology and the polypharmacy used in this field, it is of great importance to conduct further pharmacokinetic and pharmacogenetic studies to better assess gene-drug and gene-gene-drug interactions.
Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder affecting women of reproductive age. Research has shown that epigenetic alterations such as DNA methylation may play a role in ...the development and progression of abnormal ovarian function and metabolic disorders in PCOS. Studies have identified specific genes (related with insulin signaling and steroid hormone metabolism) that are methylated in women with PCOS. DNA methylation appears to respond to various interventions aimed at altering health and lifestyle factors. We tested the efficacy of a mindfulness-based stress reduction program (MBSR) in PCOS patients. We examined its effects on anthropometric measurements, mental health and wellbeing, and alterations in DNA methylation in peripheral blood. MBSR was associated with a reduction in body mass index, waist circumference and blood glucose level, an improvement in subjectively perceived general health, emotional role limitation, and levels of pain, as well as mindfulness-like traits. MBSR reduced the expression of anxious symptomatology and subjectively perceived stress. Methylation changes were observed in four genes: COMT, FST, FKBP51, and MAOA. We conclude that MBSR may be a useful supplementary therapy to mitigate the deleterious effects of PCOS on mental health.
Depression and anxiety are common mental disorders that often occur together. Stress is an important risk factor for both disorders, affecting pathophysiological processes through epigenetic changes ...that mediate gene–environment interactions. In this study, we explored two proposed models about the dynamic nature of DNA methylation in anxiety and depression: a stable change, in which DNA methylation accumulates over time as a function of the duration of clinical symptoms of anxiety and depression, or a flexible change, in which DNA methylation correlates with the acute severity of clinical symptoms. Symptom severity was assessed using clinical questionnaires for anxiety and depression (BDI-II, IDS-C, and HAM-A), and the current episode and the total lifetime symptom duration was obtained from patients’ medical records. Peripheral blood DNA methylation levels were determined for the BDNF, COMT, and SLC6A4 genes. We found a significant negative correlation between COMT_1 amplicon methylation and acute symptom scores, with BDI-II (R(22) = 0.190, p = 0.033), IDS-C (R(22) = 0.199, p = 0.029), and HAM-A (R(22) = 0.231, p = 0.018) all showing a similar degree of correlation. Our results suggest that DNA methylation follows flexible dynamics, with methylation levels closely associated with acute clinical presentation rather than with the duration of anxiety and depression. These results provide important insights into the dynamic nature of DNA methylation in anxiety and affective disorders and contribute to our understanding of the complex interplay between stress, epigenetics, and individual phenotype.
Introduction
Patients with schizophrenia typically exhibit deficits in working memory (WM) associated with abnormalities in brain activity. Alterations in the encoding, maintenance and retrieval ...phases of sequential WM tasks are well established. However, due to the heterogeneity of symptoms and complexity of its neurophysiological underpinnings, differential diagnosis remains a challenge. We conducted an electroencephalographic (EEG) study during a visual WM task in fifteen schizophrenia patients and fifteen healthy controls. We hypothesized that EEG abnormalities during the task could be identified, and patients successfully classified by an interpretable machine learning algorithm.
Methods
We tested a custom dense attention network (DAN) machine learning model to discriminate patients from control subjects and compared its performance with simpler and more commonly used machine learning models. Additionally, we analyzed behavioral performance, event-related EEG potentials, and time-frequency representations of the evoked responses to further characterize abnormalities in patients during WM.
Results
The DAN model was significantly accurate in discriminating patients from healthy controls,
ACC
= 0.69, SD = 0.05. There were no significant differences between groups, conditions, or their interaction in behavioral performance or event-related potentials. However, patients showed significantly lower alpha suppression in the task preparation, memory encoding, maintenance, and retrieval phases
F
(1,28) = 5.93,
p
= 0.022, η
2
= 0.149. Further analysis revealed that the two highest peaks in the attention value vector of the DAN model overlapped in time with the preparation and memory retrieval phases, as well as with two of the four significant time-frequency ROIs.
Discussion
These results highlight the potential utility of interpretable machine learning algorithms as an aid in diagnosis of schizophrenia and other psychiatric disorders presenting oscillatory abnormalities.
Patients with Parkinson's disease (PD) often show early deficits in cognitive control, with primary difficulties in flexibility and relatively intact stable representations. The aim of our study was ...to assess executive function using an ecologically valid approach that combines measures of stability and flexibility. Fourteen patients without cognitive deficits and sixteen comparable control subjects completed a standardized neuropsychological test battery and a newly developed cognitive control challenge task (C3T). We found that the accuracy of C3T performance decreased with age in healthy participants and remained impaired in PD patients regardless of age. In addition, PD patients showed significantly lower overall performance for cognitive control tasks than healthy controls, even when they scored in the normal range on standardized neuropsychological tests. PD Patients responded significantly faster than healthy control subjects regarding flexible cognitive control tasks due to their impulsivity. Correlations showed that the C3T task targets multiple cognitive systems, including working memory, inhibition, and task switching, providing a reliable measure of complex cognitive control. C3T could be a valuable tool for characterizing cognitive deficits associated with PD and appears to be a more sensitive measure than standardized neuropsychological tests. A different assessment approach could potentially detect early signs of the disease and identify opportunities for early intervention with neuroprotective therapies.
The article is the second part of the survey on the use of the electroencephalographic (EEG) methods in the analysis of (literary) reading. Contrary to prevalent cognitive theories (the so-called ...modular model) alternative theories supported by emerging brain imaging data presuppose the existence and simultaneous interactions of a number of different representations, supported and maintained by distributed neuronal mechanisms (the so-called activated states model). This question can also be approached by using the time-frequency analysis of EEG data which allows an insight into parallel processing by dividing time course of oscillatory electrical activity of the brain into frequency bands. Individual frequency bands are considered to be important for various aspects of cognitive mechanisms, which are also the basis of language processing in reading.
Ko merimo spremembe napetosti na povrsini glave pri branju, j e samoumevno, da gre za tihi nacin branja.8 Ce bi namrec brali naglas, bi se v elektroencefalografskem zapisu pojavljale dodatne motnje ...zaradi aktivnosti in naprezanja misic na obrazu in vratu pri govoru. Osnovna predpostavka EEG snemanja je, da imajo kognitivni (in custveni) procesi v poteku jezikovne obdelave in bralnega razumevanja vpliv na spreminjanje EEG signala, kar pomeni, da je iz teh sprememb mogoce sklepati na razlike v kognitivnem procesiranju jezikovnih podatkov (npr. na semanticno obdelavo, obdelavo sintakticnih Struktur). Kognitivne nevroznanstvene raziskave, ki se (tihega) branja lotevajo s pomocjo ERP metode, je mogoce v grobem razdeliti na tiste, ki se ukvarjajo z merjenjem in analizo elektricne aktivnosti celic mozganske skorje pri branju (samo) posameznih besed (ang. Word-by-Word-Processing), in raziskave, ki jih zanima elektricni potencial mozganov pri branju in razumevanju stavkov (ang. Sentence Reading/Sentence Comprehension). V nevrolingvisticnih ERP raziskavah se povprecni elektricni odziv mozganov na posamezne besede ugotavlja z ozirom na psiholingvisticne dejavnike, kakor so pogostnost pojavljanja besede, njena besednovrstna pripadnost ipd.; besede so za namene eksperimenta bodisi razvrscene v naborne nize oz. sezname bodisi tvorijo besedne pare, tako da je mogoce primerjati odziv mozganov na besednovrstno razlicne besede, na razlicno frekventne besede itd. Besede so lahko vpete v stavke. Pri procesiranju stavkov se uporabljata dve vrsti jezikovnega oz. stavcnega gradiva. Ena vrsta stavkov vsebuje razlicne nepravilnosti oz. odklone, ki jih je mogoce vecinoma umestiti na leksikalnosemanticno in morfo-sintakticno raven, druga vrsta gradiva je ustrezno tvorjena na vseh jezikovnih ravneh. Obe vrsti gradiva se v nevrolingvisticnih eksperimentih uporabljata vzporedno, ker pri funkcijskih slikovnih raziskavah mozganov prideta v postev ponavljanje podobnih dogodkov in primerjava med deloma razlicnimi dogodki (eksperimentalni pogoji), da lahko z analizo signalov izluscimo relativne razlike mozganov med pogoji in zmanjsamo vpliv nakljucnega elektricnega suma. Nevrolingvisticna raziskava torej preverja, v cem je elektricna aktivnost mozganov, ki jo izzovejo pravilno/ustrezno tvorjene besede ali stavki, kakovostno drugacna od tiste, kijo izzovejo oblikoslovno-skladenjski in besednopomenski odkloni. Zaradi tega je elektricni odziv mozganov na razlicno smiselne besede problematicno meriti zgolj s primerjavo posameznih besed in loceno od stavcne strukture oz. sirsega (stavcnega) konteksta. Za povprecenje elektricnega potencíala mozganov na besede v stavcnem kontekstu (naj)pogosteje vzamejo tip jezikovne naloge zapolnjevanja praznih mest v stavku (ang. Cloze Probability Test, nem. Lückentexttest)\ praznina je obicajno na koncu stavka. Tip naloge sta uporabila ze Kutasova in S. A. Hillyard. Pokazala sta, daje komponenta N400 obcutljiva na kontekstualno ne/ ustreznost besede na koncu stavka (nepricakovana besedaje izzvala negativnejsi val N400). Vendar ni mogoce spregledati vpliva, ki ga ima na komponento preostanek stavka oz. predhodni stavcni kontekst, saj v bistvu tlakuje pot besedi, s katero bralee nato zapolni prazno mesto na koncu stavka. Amplituda N400 je torej odvisna od povezanosti s prejsnjimi besedami v stavku, bralcevimi pricakovanji, kakor se oblikujejo v poteku branja, kar pomeni, da ucínek N400 odraza tudi vpliv predhodnega besednega oz. stavcnega konteksta.21 (Kutas/Hillyard 1984; van Petten/ M. Kutas 1987; Osterhaut/Holcomb 1992: 786-87; Kutas/van Petten 1994: 120)22 Podoben tip jezikovne naloge vkljucuje stavcne pare, samo da ti vsebujejo vse besede, eden od stavkov pa se zakljuci s pomensko oz. kontekstualno neustrezno besedo. Ilustrativen primerje ERP raziskava nizozemskih raziskovalcev23 (Haid idr. 2006). Pri stavkíh, kí so vsebovalí semanticne anomalije, je bila ugotovljena negativnejsa amplituda vala N400.24 Elektroencefalografija, na kratko EEG, je ena izmed neinvazivnih metod slikanja mozganov,1 s katero merimo kontinuirano elektricno aktivnost mozganov. Zajeti elektricni signal je »sestevek elektricne aktivnosti vecjega stevila zivcnih celic mozganske skorje«, na njegove lastnosti pa vplivajo tako lastnosti nevronov kakor medsebojni odnosi med nevronskimi omrezji v mozganih. Spremembe v EEG signalu so posledica bolj ali manj usklajenega (sojdelovanja nevronskih omrezij, ki se v EEG zapisu odraza v spreminjajocih se amplitudah zivcne aktivnosti mozganske skorje v razlicnih frekvencnih spektrih. (Silva 1991; Coenen 1995; Whittington idr. 2000; S. Brezan idr. 2004: 63) Signal se zajema s pomocjo elektrod, ki se namestijo napovrsini glave (skalpu). Elektroencefalografija se na podrocju medicine uporablja predvsem preko kvalitativne ocene neposredno vidnih znacilnosti signala - v nevrologiji in psihiatriji npr. za diagnosticiranje epilepsije, ugotavljanje mozganskih disfunkcij, motenj pozornosti. Kvantitativni nacini obdelave signala pa obsegajo razlicne in bolj ali manj kompleksne transformacije po principih teorije obdelave signalov, ki dovoljujejo dolocanje specificnih komponent v signalu, ki so v kontinuiranem posnetku sicer prekrite z elektricnim surnom okolice. Kvantitativno analizo prakticirajo predvsem na podrocjih kognitivne psihologije in kognitivne nevroznanosti, ker omogoca najbolj natancno mero casovnega poteka zaznavnih in kognitivnih procesov v mozganih, z milisekundno locljivostjo, pri cerner pa seje potrebno zavedati, da je prostorska locljivost metode v primerjavi z drugimi metodami funkcijskega slikanja mozganov slaba. Z drugimi besedami lahko z EEG metodami casovno natancno merimo odziv mozganov kot celóte, medtem ko tezje sklepamo na doprinos razlicnih delov mozganov, za kar so uporabnejse druge omenjene neinvazivne metode slikanja. EEG se vse pogosteje uporablja tudi na sorazmerno novih, komercialnih podrocjih, kakor je nevromarketing, kjer je lahko ucinkovit pri odkrivanju vzorcev ravnanj potrosnikov. V empiricni literarni znanosti (ELZ) za to método nimamo relevantnejsih zgledov.2 Zato je zanjo metodolosko in vsebinsko najzanimivejse siroko in v zadnjih petindvajsetih letih hitro rastoce podrocje eksperimentalnih nevrolingvisticnih raziskav. Med njimi pozornost vzbuja skupina raziskav, ki jih zanimajo elektrofizioloske podlage jezikovne obdelave. Ukvarjajo se z merjenjem in analizo sprememb v elektricnih potencialih mozganov in njihovih ritmih, kakor jih izzove kognitivno procesiranje razlicnih vrstjezikovnih podatkov pri branju in pri bralnem razumevanju.