RESUMO
There is a longstanding ambiguity regarding the clinical diagnosis of dementia syndromes predominantly targeting executive functions versus behaviour and personality. This is due to an incomplete understanding of the macro-scale anatomy underlying these symptomatologies, a partial overlap in clinical features and the fact that both phenotypes can emerge from the same pathology and vice versa. We collected data from a patient cohort of which 52 had dysexecutive Alzheimer's disease, 30 had behavioural variant frontotemporal dementia (bvFTD), seven met clinical criteria for bvFTD but had Alzheimer's disease pathology (behavioural Alzheimer's disease) and 28 had amnestic Alzheimer's disease. We first assessed group-wise differences in clinical and cognitive features and patterns of fluorodeoxyglucose (FDG) PET hypometabolism. We then performed a spectral decomposition of covariance between FDG-PET images to yield latent patterns of relative hypometabolism unbiased by diagnostic classification, which are referred to as 'eigenbrains'. These eigenbrains were subsequently linked to clinical and cognitive data and meta-analytic topics from a large external database of neuroimaging studies reflecting a wide range of mental functions. Finally, we performed a data-driven exploratory linear discriminant analysis to perform eigenbrain-based multiclass diagnostic predictions. Dysexecutive Alzheimer's disease and bvFTD patients were the youngest at symptom onset, followed by behavioural Alzheimer's disease, then amnestic Alzheimer's disease. Dysexecutive Alzheimer's disease patients had worse cognitive performance on nearly all cognitive domains compared with other groups, except verbal fluency which was equally impaired in dysexecutive Alzheimer's disease and bvFTD. Hypometabolism was observed in heteromodal cortices in dysexecutive Alzheimer's disease, temporo-parietal areas in amnestic Alzheimer's disease and frontotemporal areas in bvFTD and behavioural Alzheimer's disease. The unbiased spectral decomposition analysis revealed that relative hypometabolism in heteromodal cortices was associated with worse dysexecutive symptomatology and a lower likelihood of presenting with behaviour/personality problems, whereas relative hypometabolism in frontotemporal areas was associated with a higher likelihood of presenting with behaviour/personality problems but did not correlate with most cognitive measures. The linear discriminant analysis yielded an accuracy of 82.1% in predicting diagnostic category and did not misclassify any dysexecutive Alzheimer's disease patient for behavioural Alzheimer's disease and vice versa. Our results strongly suggest a double dissociation in that distinct macro-scale underpinnings underlie predominant dysexecutive versus personality/behavioural symptomatology in dementia syndromes. This has important implications for the implementation of criteria to diagnose and distinguish these diseases and supports the use of data-driven techniques to inform the classification of neurodegenerative diseases.
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Doença de Alzheimer , Demência Frontotemporal , Humanos , Doença de Alzheimer/patologia , Fluordesoxiglucose F18 , Demência Frontotemporal/patologia , Função Executiva , Córtex Cerebral/patologia , Testes NeuropsicológicosRESUMO
Dravet syndrome is a severe epileptic encephalopathy, characterized by drug-resistant epilepsy, severe cognitive and behavioural deficits, with increased risk of sudden unexpected death (SUDEP). It is caused by haploinsufficiency of SCN1A gene encoding for the α-subunit of the voltage-gated sodium channel Nav1.1. Therapeutic approaches aiming to upregulate the healthy copy of SCN1A gene to restore its normal expression levels are being developed. However, whether Scn1a gene function is required only during a specific developmental time-window or, alternatively, if its physiological expression is necessary in adulthood is untested up to now. We induced Scn1a gene haploinsufficiency at two ages spanning postnatal brain development (P30 and P60) and compared the phenotypes of those mice to Scn1a perinatally induced mice (P2), recapitulating all deficits of Dravet mice. Induction of heterozygous Nav1.1 mutation at P30 and P60 elicited susceptibility to the development of both spontaneous and hyperthermia-induced seizures and SUDEP rates comparable to P2-induced mice, with symptom onset accompanied by the characteristic GABAergic interneuron dysfunction. Finally, delayed Scn1a haploinsufficiency induction provoked hyperactivity, anxiety and social attitude impairment at levels comparable to age matched P2-induced mice, while it was associated with a better cognitive performance, with P60-induced mice behaving like the control group. Our data show that maintenance of physiological levels of Nav1.1 during brain development is not sufficient to prevent Dravet symptoms and that long-lasting restoration of Scn1a gene expression would be required to grant optimal clinical benefit in patients with Dravet syndrome.
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Epilepsias Mioclônicas , Morte Súbita Inesperada na Epilepsia , Humanos , Camundongos , Animais , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Epilepsias Mioclônicas/genética , Interneurônios/fisiologia , Encéfalo , Mutação , Modelos Animais de DoençasRESUMO
Behavioural flexibility might help animals cope with costs of genetic variants under selection, promoting genetic adaptation. However, it has proven challenging to experimentally link behavioural flexibility to the predicted compensation of population-level fitness. We tested this prediction using the field cricket Teleogryllus oceanicus. In Hawaiian populations, a mutation silences males and protects against eavesdropping parasitoids. To examine how the loss of this critical acoustic communication signal impacts offspring production and mate location, we developed a high-resolution, individual-based tracking system for low-light, naturalistic conditions. Offspring production did not differ significantly in replicate silent versus singing populations, and fitness compensation in silent conditions was associated with significantly increased locomotion in both sexes. Our results provide evidence that flexible behaviour can promote genetic adaptation via compensation in reproductive output and suggest that rapid evolution of animal communication systems may be less constrained than previously appreciated.
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Críquete , Gryllidae , Masculino , Feminino , Animais , Comportamento Sexual Animal , Vocalização Animal , Havaí , Mutação , Gryllidae/genética , Evolução BiológicaRESUMO
Human-induced rapid environmental change (HIREC) is creating environments deviating considerably from natural habitats in which species evolved. Concurrently, climate warming is pushing species' climatic envelopes to geographic regions that offer novel ecological conditions. The persistence of species is likely affected by the interplay between the degree of ecological novelty and phenotypic plasticity, which in turn may shape an organism's range-shifting ability. Current modelling approaches that forecast animal ranges are characterized by a static representation of the relationship between habitat use and fitness, which may bias predictions under conditions imposed by HIREC. We argue that accounting for dynamic species-resource relationships can increase the ecological realism of range shift predictions. Our rationale builds on the concepts of ecological fitting, the process whereby individuals form successful novel biotic associations based on the suite of traits they carry at the time of encountering the novel condition, and behavioural plasticity, in particular learning. These concepts have revolutionized our view on fitness in novel ecological settings, and the way these processes may influence species ranges under HIREC. We have integrated them into a model of range expansion as a conceptual proof of principle highlighting the potentially substantial role of learning ability in range shifts under HIREC.
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Mudança Climática , Ecossistema , Animais , Humanos , Evolução BiológicaRESUMO
Understanding species distributions and predicting future range shifts requires considering all relevant abiotic factors and biotic interactions. Resource competition has received the most attention, but reproductive interference is another widespread biotic interaction that could influence species ranges. Rubyspot damselflies (Hetaerina spp.) exhibit a biogeographic pattern consistent with the hypothesis that reproductive interference has limited range expansion. Here, we use ecological niche models to evaluate whether this pattern could have instead been caused by niche differentiation. We found evidence for climatic niche differentiation, but the species that encounters the least reproductive interference has one of the narrowest and most peripheral niches. These findings strengthen the case that reproductive interference has limited range expansion and also provide a counterexample to the idea that release from negative species interactions triggers niche expansion. We propose that release from reproductive interference enables species to expand in range while specializing on the habitats most suitable for breeding.
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Modelos Teóricos , Odonatos , Animais , Reprodução , EcossistemaRESUMO
Social play behaviour is a rewarding activity that can entail risks, thus allowing young individuals to test the limits of their capacities and to train their cognitive and emotional adaptability to challenges. Here, we tested in rats how opportunities for risk-taking during play affect the development of cognitive and emotional capacities and medial prefrontal cortex (mPFC) function, a brain structure important for risk-based decision making. Male and female rats were housed socially or social play-deprived (SPD) between postnatal day (P)21 and P42. During this period, half of both groups were daily exposed to a high-risk play environment. Around P85, all rats were tested for cognitive performance and emotional behaviour after which inhibitory currents were recorded in layer 5 pyramidal neurons in mPFC slices. We show that playing in a high-risk environment altered cognitive flexibility in both sexes and improved behavioural inhibition in males. High-risk play altered anxiety-like behaviour in the elevated plus maze in males and in the open field in females, respectively. SPD affected cognitive flexibility in both sexes and decreased anxiety-like behaviour in the elevated plus maze in females. We found that synaptic inhibitory currents in the mPFC were increased in male, but not female, rats after high-risk play, while SPD lowered prefrontal cortex (PFC) synaptic inhibition in both sexes. Together, our data show that exposure to risks during play affects the development of cognition, emotional behaviour and inhibition in the mPFC. Furthermore, our study suggests that the opportunity to take risks during play cannot substitute for social play behaviour.
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Cognição , Córtex Pré-Frontal , Assunção de Riscos , Animais , Córtex Pré-Frontal/fisiologia , Masculino , Feminino , Ratos , Cognição/fisiologia , Jogos e Brinquedos , Comportamento Social , Ansiedade/fisiopatologia , Células Piramidais/fisiologia , Emoções/fisiologia , Comportamento Animal/fisiologiaRESUMO
Recent electroencephalography (EEG) studies have shown that patterns of brain activity can be used to differentiate amyotrophic lateral sclerosis (ALS) and control groups. These differences can be interrogated by examining EEG microstates, which are distinct, reoccurring topographies of the scalp's electrical potentials. Quantifying the temporal properties of the four canonical microstates can elucidate how the dynamics of functional brain networks are altered in neurological conditions. Here we have analysed the properties of microstates to detect and quantify signal-based abnormality in ALS. High-density resting-state EEG data from 129 people with ALS and 78 HC were recorded longitudinally over a 24-month period. EEG topographies were extracted at instances of peak global field power to identify four microstate classes (labelled A-D) using K-means clustering. Each EEG topography was retrospectively associated with a microstate class based on global map dissimilarity. Changes in microstate properties over the course of the disease were assessed in people with ALS and compared with changes in clinical scores. The topographies of microstate classes remained consistent across participants and conditions. Differences were observed in coverage, occurrence, duration, and transition probabilities between ALS and control groups. The duration of microstate class B and coverage of microstate class C correlated with lower limb functional decline. The transition probabilities A to D, C to B and C to B also correlated with cognitive decline (total ECAS) in those with cognitive and behavioural impairments. Microstate characteristics also significantly changed over the course of the disease. Examining the temporal dependencies in the sequences of microstates revealed that the symmetry and stationarity of transition matrices were increased in people with late-stage ALS. These alterations in the properties of EEG microstates in ALS may reflect abnormalities within the sensory network and higher-order networks. Microstate properties could also prospectively predict symptom progression in those with cognitive impairments.
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Esclerose Lateral Amiotrófica , Disfunção Cognitiva , Humanos , Eletroencefalografia , Estudos Retrospectivos , Encéfalo , Mapeamento Encefálico , Disfunção Cognitiva/etiologiaRESUMO
Behavioural plasticity allows organisms to respond to environmental challenges on short time scales. But what are the ecological and evolutionary processes that underlie behavioural plasticity? The answer to this question is complex and requires experimental dissection of the physiological, neural and molecular mechanisms contributing to behavioural plasticity as well as an understanding of the ecological and evolutionary contexts under which behavioural plasticity is adaptive. Here, we discuss key insights that research with Trinidadian guppies has provided on the underpinnings of adaptive behavioural plasticity. First, we present evidence that guppies exhibit contextual, developmental and transgenerational behavioural plasticity. Next, we review work on behavioural plasticity in guppies spanning three ecological contexts (predation, parasitism and turbidity) and three underlying mechanisms (endocrinological, neurobiological and genetic). Finally, we provide three outstanding questions that could leverage guppies further as a study system and give suggestions for how this research could be done. Research on behavioural plasticity in guppies has provided, and will continue to provide, a valuable opportunity to improve understanding of the ecological and evolutionary causes and consequences of behavioural plasticity.
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Poecilia , Animais , Poecilia/fisiologia , Adaptação Fisiológica , Comportamento Predatório , Evolução BiológicaRESUMO
Behavioural syndromes are suites of behaviours that corelate between-individuals but the same behaviours may also show within-individual correlations owing to state dependency or trade-offs. Therefore, overall phenotypic behavioural correlations must be separated into their between- and within-individual components. We investigate how startle response duration (an index of boldness) and time taken to reject an inert item (an index of investigation thoroughness) covary in beadlet sea anemones, Actinia equina. Anemones took longer to reject a more complex item compared to a simpler one, validating this measure of investigation thoroughness. We then quantified between- and within-individual correlations using a Bayesian analysis and an alternative frequentist analysis, which returned the same results. Startle responses decreased with anemone size while thoroughness decreased across repeated observations, indicative of simple learning. For each behaviour, repeatability was significant but relatively low and there was no behavioural syndrome. Rather, the two behaviours showed a negative within-individual correlation in most individuals. Thus, boldness and thoroughness are unlikely to be under correlative selection, and they may instead be expressed independently, in line with the general pattern that cross-contextual behavioural syndromes are comparatively rare. It now appears that this pattern may extend broadly across animal diversity.
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Comportamento Animal , Individualidade , Anêmonas-do-Mar , Animais , Anêmonas-do-Mar/fisiologia , Teorema de Bayes , Reflexo de SobressaltoRESUMO
The evolution of flight is a rare event in vertebrate history, and one that demands functional integration across multiple anatomical/physiological systems. The neuroanatomical basis for such integration and the role that brain evolution assumes in behavioural transformations remain poorly understood. We make progress by (i) generating a positron emission tomography (PET)-based map of brain activity for pigeons during rest and flight, (ii) using these maps in a functional analysis of the brain during flight, and (iii) interpreting these data within a macroevolutionary context shaped by non-avian dinosaurs. Although neural activity is generally conserved from rest to flight, we found significant increases in the cerebellum as a whole and optic flow pathways. Conserved activity suggests processing of self-movement and image stabilization are critical when a bird takes to the air, while increased visual and cerebellar activity reflects the importance of integrating multimodal sensory information for flight-related movements. A derived cerebellar capability likely arose at the base of maniraptoran dinosaurs, where volumetric expansion and possible folding directly preceded paravian flight. These data represent an important step toward establishing how the brain of modern birds supports their unique behavioural repertoire and provide novel insights into the neurobiology of the bird-like dinosaurs that first achieved powered flight.
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Columbidae , Dinossauros , Animais , Evolução Biológica , Fósseis , Encéfalo/fisiologia , Dinossauros/anatomia & histologia , Filogenia , Voo AnimalRESUMO
Evolutionary biologists have long been interested in parsing out the roles of genetics, plasticity and their interaction on adaptive trait divergence. Since males and females often have different ecological and reproductive roles, separating how their traits are shaped by interactions between their genes and environment is necessary and important. Here, we disentangle the sex-specific effects of genetic divergence, developmental plasticity, social learning and contextual plasticity on foraging behaviour in Trinidadian guppies (Poecilia reticulata) adapted to high- or low-predation habitats. We reared second-generation siblings from both predation regimes with or without predator chemical cues, and with adult conspecifics from either high- or low-predation habitats. We then quantified their foraging behaviour in water with and without predator chemical cues. We found that high-predation guppies forage more efficiently than low-predation guppies, but this behavioural difference is context-dependent and shaped by different mechanisms in males and females. Higher foraging efficiency in high-predation females is largely genetically determined, and to a smaller extent socially learned from conspecifics. However, in high-predation males, higher foraging efficiency is plastically induced by predator cues during development. Our study demonstrates sex-specific differences in genetic versus plastic responses in foraging behaviour, a trait of significance in organismal fitness and ecosystem dynamics.
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Poecilia , Aprendizado Social , Animais , Feminino , Masculino , Ecossistema , Poecilia/fisiologia , Comportamento Predatório , Evolução BiológicaRESUMO
All mobile organisms forage for resources, choosing how and when to search for new opportunities by comparing current returns with the average for the environment. In humans, nomadic lifestyles favouring exploration have been associated with genetic mutations implicated in attention deficit hyperactivity disorder (ADHD), inviting the hypothesis that this condition may impact foraging decisions in the general population. Here we tested this pre-registered hypothesis by examining how human participants collected resources in an online foraging task. On every trial, participants chose either to continue to collect rewards from a depleting patch of resources or to replenish the patch. Participants also completed a well-validated ADHD self-report screening assessment at the end of sessions. Participants departed resource patches sooner when travel times between patches were shorter than when they were longer, as predicted by optimal foraging theory. Participants whose scores on the ADHD scale crossed the threshold for a positive screen departed patches significantly sooner than participants who did not meet this criterion. Participants meeting this threshold for ADHD also achieved higher reward rates than individuals who did not. Our findings suggest that ADHD attributes may confer foraging advantages in some environments and invite the possibility that this condition may reflect an adaptation favouring exploration over exploitation.
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Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Recompensa , Estilo de Vida , AutorrelatoRESUMO
'Accounting for the sensory abilities of animals is critical in experimental design.' No researcher would disagree with this statement, yet it is often the case that we inadvertently fall for anthropocentric biases and use ourselves as the reference point. This paper discusses the risks of adopting an anthropocentric view when working with non-human animals, and the unintended consequences this has on our experimental designs and results. To this aim, we provide general examples of anthropocentric bias from different fields of animal research, with a particular focus on animal cognition and behaviour, and lay out the potential consequences of adopting a human-based perspective. Knowledge of the sensory abilities, both in terms of similarities to humans and peculiarities of the investigated species, is crucial to ensure solid conclusions. A more careful consideration of the diverse sensory systems of animals would improve many scientific fields and enhance animal welfare in the laboratory.
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Experimentação Animal , Animais , Humanos , Cognição , Sensação , Comportamento Animal , Projetos de Pesquisa , Bem-Estar do AnimalRESUMO
Behavioural and physiological resistance are key to slowing epidemic spread. We explore the evolutionary and epidemic consequences of their different costs for the evolution of tolerance that trades off with resistance. Behavioural resistance affects social cohesion, with associated group-level costs, while the cost of physiological resistance accrues only to the individual. Further, resistance, and the associated reduction in transmission, benefit susceptible hosts directly, whereas infected hosts only benefit indirectly, by reducing transmission to kin. We therefore model the coevolution of transmission-reducing resistance expressed in susceptible hosts with resistance expressed in infected hosts, as a function of kin association, and analyse the effect on population-level outcomes. Using parameter values for guppies, Poecilia reticulata, and their gyrodactylid parasites, we find that: (1) either susceptible or infected hosts should invest heavily in resistance, but not both; (2) kin association drives investment in physiological resistance more strongly than in behavioural resistance; and (3) even weak levels of kin association can favour altruistic infected hosts that invest heavily in resistance (versus selfish tolerance), eliminating parasites. Overall, our finding that weak kin association affects the coevolution of infected and susceptible investment in both behavioural and physiological resistance suggests that kin selection may affect disease dynamics across systems.
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Resistência à Doença , Interações Hospedeiro-Parasita , Poecilia , Animais , Poecilia/fisiologia , Poecilia/parasitologia , Doenças dos Peixes/parasitologia , Evolução Biológica , Modelos BiológicosRESUMO
OBJECTIVES: Our objective was to obtain long-term data on the incidence of sexually transmitted infections (STIs) and their association with behavioural factors after widespread pre-exposure prophylaxis (PrEP) implementation. METHODS: This was a time-to-event analysis of a national PrEP cohort in Switzerland (SwissPrEPared study). Participants were people without HIV interested in taking PrEP with at least two STI screening visits. Primary outcomes were incidence rate of gonorrhoea, chlamydia, and syphilis. The association between behavioural factors and STI diagnosis was expressed using hazard ratios. We adjusted for testing frequency and calendar year. RESULTS: This analysis included 3907 participants enrolled between April 2019 and April 2022, yielding 3815.7 person-years of follow-up for gonorrhoea (15 134 screenings), 3802.5 for chlamydia (15 141 screenings), and 3858.6 for syphilis (15 001 screenings). The median age was 39 years (interquartile range [IQR] 32-47), 93.8% (n = 3664) identified as men who have sex with men (MSM). The incidence was 22.8 (95% confidence interval [CI] 21.3-24.4) per 100 person-years for gonorrhoea, 26.3 (95% CI 24.7-28.0) for chlamydia, and 4.4 (95% CI 3.8-5.1) for syphilis. Yearly incidence rates decreased between 2019 (all bacterial STIs: 81.6; 95% CI 59.1-109.9) and 2022 (all bacterial STIs: 49.8; 95% CI 44.6-55.3). Participants reporting chemsex substance use were at higher risk of incident STIs, as were those reporting multiple sexual partners. Younger age was associated with a higher risk of gonorrhoea and chlamydia. CONCLUSIONS: Incidence rates of bacterial STIs decreased over time. Young MSM, those with multiple partners, and those using chemsex substances were at increased risk of STIs.
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Gonorreia , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Doenças Bacterianas Sexualmente Transmissíveis , Infecções Sexualmente Transmissíveis , Sífilis , Masculino , Humanos , Adulto , Incidência , Homossexualidade Masculina , Sífilis/epidemiologia , Gonorreia/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Doenças Bacterianas Sexualmente Transmissíveis/epidemiologiaRESUMO
BACKGROUND: Impulse control disorders (ICDs) are known psychiatric conditions in Parkinson's disease (PD), especially as a side effect of antiparkinsonian therapy. Screening for vulnerable patients and avoiding high-risk treatments can be an effective approach to reduce the ICD burden in patients with PD. Thus, our goal was to identify risk factors for ICDs in PD in the Swedish total population. METHODS: Our longitudinal study was based on records of all patients with PD in the Swedish National Patient Registries and the Prescribed Drug Register (n=55 235). Patients with incident gambling disorder and other ICDs were compared with a control group on demographic factors, psychiatric comorbidity, antiparkinsonian dopaminergic treatment and therapies for advanced disease. Potential risk factors were analysed using logistic regressions and relative frequency comparisons (Fisher's exact test). RESULTS: Main predictors for incident gambling disorder were treatment with dopamine agonists (Frequency ratio 1.4, p=0.058), monoamine oxidase B (MAO-B) inhibitors (Frequency ratio 1.8, p=0.006) and a prescription for drugs used in addictive disorders (OR 5.85, 95% CI 2.00 to 17.10). Main predictors for other ICDs were dopamine agonist treatment (frequency ratio 1.6, p=0.003), anxiety disorders (OR 7.04, 95% CI 2.96 to 16.71) and substance use disorders other than alcohol (OR 5.66, 95% CI 1.75 to 18.23). CONCLUSIONS: Our results support possible risk factors for incident ICDs that had previously been identified, like dopamine agonist treatment and raise additional attention for risk factors like MAO-B inhibitor treatment and specific psychiatric comorbidities. These findings enable tailoring antiparkinsonian therapy to individual patient-specific risk profiles.
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BACKGROUND: Childhood trauma is a major risk factor for chronic depression. It has been suggested that adults with chronic depression who have experienced childhood trauma may require long-term treatment owing to a breakdown of basic trust and related difficulties in developing a productive therapeutic relationship. AIMS: As empirical studies have been preliminary and scarce, we studied the effects of psychoanalytic therapy (PAT) versus cognitive-behavioural therapy (CBT) for chronic depression in adults with a history of childhood trauma. In this subgroup, we expected a greater symptom reduction in PAT compared with CBT. METHOD: In a large trial of long-term psychotherapies for chronic depression (LAC-Study; Clinical Trial Register ISRCTN91956346), 210 adults received open-ended CBT or PAT in an out-patient setting and were examined yearly over 5 years on the Beck Depression Inventory - II (BDI-II). Based on a linear mixed model approach, we tested participant-reported childhood trauma based on the Childhood Trauma Questionnaire (CTQ) as a predictor and moderator of treatment outcome. CTQ subscales were examined exploratively. RESULTS: Depressive symptoms decreased over time (b = -4.55, s.e. = 0.90, 95% CI -6.32 to -2.81, T = -5.08; P < 0.001). A significant three-way interaction between childhood trauma, time and therapy group (b = -0.05, s.e. = 0.02, 95% CI -0.09 to -0.01, T = -2.42; P = 0.016) indicated that participants with childhood trauma profited especially well from PATs. CONCLUSIONS: Our results indicate differential benefits from PAT compared with CBT among adults with chronic depression and a history of childhood trauma. The results have important implications for differential indication and policy.
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BACKGROUND: Tightly connected symptom networks have previously been linked to treatment resistance, but most findings come from small-sample studies comparing single responder v. non-responder networks. We aimed to estimate the association between baseline network connectivity and treatment response in a large sample and benchmark its prognostic value against baseline symptom severity and variance. METHODS: N = 40 518 patients receiving treatment for depression in routine care in England from 2015-2020 were analysed. Cross-sectional networks were constructed using the Patient Health Questionnaire-9 (PHQ-9) for responders and non-responders (N = 20 259 each). To conduct parametric tests investigating the contribution of PHQ-9 sum score mean and variance to connectivity differences, networks were constructed for 160 independent subsamples of responders and non-responders (80 each, n = 250 per sample). RESULTS: The baseline non-responder network was more connected than responders (3.15 v. 2.70, S = 0.44, p < 0.001), but effects were small, requiring n = 750 per group to have 85% power. Parametric analyses revealed baseline network connectivity, PHQ-9 sum score mean, and PHQ-9 sum score variance were correlated (r = 0.20-0.58, all p < 0.001). Both PHQ-9 sum score mean (ß = -1.79, s.e. = 0.07, p < 0.001), and PHQ-9 sum score variance (ß = -1.67, s.e. = 0.09, p < 0.001) had larger effect sizes for predicting response than connectivity (ß = -1.35, s.e. = 0.12, p < 0.001). The association between connectivity and response disappeared when PHQ-9 sum score variance was accounted for (ß = -0.28, s.e. = 0.19, p = 0.14). We replicated these results in patients completing longer treatment (8-12 weeks, N = 22 952) and using anxiety symptom networks (N = 70 620). CONCLUSIONS: The association between baseline network connectivity and treatment response may be largely due to differences in baseline score variance.
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Ansiedade , Depressão , Humanos , Prognóstico , Depressão/terapia , Estudos Transversais , Questionário de Saúde do PacienteRESUMO
The evolutionary repercussions of parental effects-the impact of the developmental environment provided by parents on offspring-are often discussed as static effects that can have negative influences on offspring fitness that may even persist across generations. However, individuals are not passive recipients and may mitigate the persistence of parental effects through their behaviour. Here, we tested how the burying beetle, Nicrophorus orbicollis, a species with complex parental care, responded to poor parenting. We cross-fostered young and manipulated the duration of parental care received and measured the impact on traits of both F1 and F2 offspring to experimentally extricate the effect of poor parenting from other parental effects. As expected, reducing parental care negatively affected traits that are ecologically important for burying beetles, including F1 offspring development time and body size. However, F1 parents that received reduced care as larvae spent more time feeding F2 offspring than parents that received full care as larvae. As a result, both the number and mass of F2 offspring were unaffected by the developmental experience of their parents. Our results show that flexible parental care may be able to overcome poor developmental environments and limit negative parental effects to a single generation.
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Besouros , Poder Familiar , Animais , Larva , Besouros/genética , Comportamento Animal , Evolução BiológicaRESUMO
Artificial intelligence (AI) is often used to describe the automation of complex tasks that we would attribute intelligence to. Machine learning (ML) is commonly understood as a set of methods used to develop an AI. Both have seen a recent boom in usage, both in scientific and commercial fields. For the scientific community, ML can solve bottle necks created by complex, multi-dimensional data generated, for example, by functional brain imaging or *omics approaches. ML can here identify patterns that could not have been found using traditional statistic approaches. However, ML comes with serious limitations that need to be kept in mind: their tendency to optimise solutions for the input data means it is of crucial importance to externally validate any findings before considering them more than a hypothesis. Their black-box nature implies that their decisions usually cannot be understood, which renders their use in medical decision making problematic and can lead to ethical issues. Here, we present an introduction for the curious to the field of ML/AI. We explain the principles as commonly used methods as well as recent methodological advancements before we discuss risks and what we see as future directions of the field. Finally, we show practical examples of neuroscience to illustrate the use and limitations of ML.