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BACKGROUND: Adolescents are susceptible to mental illness and have experienced substantial disruption owing to the COVID-19 pandemic. The digital environment is increasingly important in the context of a pandemic when in-person social connection is restricted. OBJECTIVE: This study aims to estimate whether depression and anxiety had worsened compared with the prepandemic period and examine potential associations with sociodemographic characteristics and behavioral factors, particularly digital behaviors. METHODS: We analyzed cross-sectional and longitudinal data from a large, representative Greater London adolescent cohort study: the Study of Cognition, Adolescents and Mobile Phones (SCAMP). Participants completed surveys at T1 between November 2016 and July 2018 (N=4978; aged 13 to 15 years) and at T2 between July 2020 and June 2021 (N=1328; aged 16 to 18 years). Depression and anxiety were measured using the Patient Health Questionnaire and Generalized Anxiety Disorder scale, respectively. Information on the duration of total mobile phone use, social network site use, and video gaming was also collected using questionnaires. Multivariable logistic regression was used to assess the cross-sectional and longitudinal associations of sociodemographic characteristics, digital technology use, and sleep duration with clinically significant depression and anxiety. RESULTS: The proportion of adolescents who had clinical depression and anxiety significantly increased at T2 (depression: 140/421, 33.3%; anxiety: 125/425, 29.4%) compared with the proportion of adolescents at T1 (depression: 57/421, 13.5%; anxiety: 58/425, 13.6%; P for 2-proportion z test <.001 for both depression and anxiety). Depression and anxiety levels were similar between the summer holiday, school opening, and school closures. Female participants had higher odds of new incident depression (odds ratio [OR] 2.5, 95% CI 1.5-4.18) and anxiety (OR 2.11, 95% CI 1.23-3.61) at T2. A high level of total mobile phone use at T1 was associated with developing depression at T2 (OR 1.89, 95% CI 1.02-3.49). Social network site use was associated with depression and anxiety cross-sectionally at T1 and T2 but did not appear to be associated with developing depression or anxiety longitudinally. Insufficient sleep at T1 was associated with developing depression at T2 (OR 2.26, 95% CI 1.31-3.91). CONCLUSIONS: The mental health of this large sample of adolescents from London deteriorated during the pandemic without noticeable variations relating to public health measures. The deterioration was exacerbated in girls, those with preexisting high total mobile phone use, and those with preexisting disrupted sleep. Our findings suggest the necessity for allocating resources to address these modifiable factors and target high-risk groups.
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COVID-19 , Tecnología Digital , Adolescente , Femenino , Humanos , Estudios de Cohortes , Estudios Longitudinales , Pandemias , Estudios Transversales , Depresión , AnsiedadRESUMEN
Converging global evidence highlights the dire consequences of climate change for human mental health and wellbeing. This paper summarises literature across relevant disciplines to provide a comprehensive narrative review of the multiple pathways through which climate change interacts with mental health and wellbeing. Climate change acts as a risk amplifier by disrupting the conditions known to support good mental health, including socioeconomic, cultural and environmental conditions, and living and working conditions. The disruptive influence of rising global temperatures and extreme weather events, such as experiencing a heatwave or water insecurity, compounds existing stressors experienced by individuals and communities. This has deleterious effects on people's mental health and is particularly acute for those groups already disadvantaged within and across countries. Awareness and experiences of escalating climate threats and climate inaction can generate understandable psychological distress; though strong emotional responses can also motivate climate action. We highlight opportunities to support individuals and communities to cope with and act on climate change. Consideration of the multiple and interconnected pathways of climate impacts and their influence on mental health determinants must inform evidence-based interventions. Appropriate action that centres climate justice can reduce the current and future mental health burden, while simultaneously improving the conditions that nurture wellbeing and equality. The presented evidence adds further weight to the need for decisive climate action by decision makers across all scales.
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Cambio Climático , Salud Mental , Adaptación Psicológica , Emociones , HumanosRESUMEN
BACKGROUND: Despite a recent increase in engagement with environmental issues among young people, their impact upon adolescent mental health and wellbeing is not yet fully understood. Therefore, this study aimed to explore adolescents' thoughts and feelings about current environmental issues. METHODS: Semi-structured interviews were conducted with a convenience sample of 15 UK-based adolescents aged 14-18 years (66.7% female). Transcripts were inductively thematically analysed by the interviewing researcher and two adolescent co-researchers, with priority given to the co-researchers' impressions to strengthen interpretations of the personal experiences of the interviewees. RESULTS: Six themes were identified: the local environment, efficacy, challenging emotions, information, hindrances and perceptions of the future. The local environment was found to affect adolescents positively and negatively. Factors including greenspace and fresh air had a positive impact, and factors including noise and litter had a negative impact. Most participants reported feeling disempowered to personally influence environmental problems but were engaged with them and felt that trying to make a difference was beneficial for their wellbeing. Adolescents largely reported negative expectations about the environment's future. CONCLUSION: The UK adolescents interviewed appeared to be very engaged and emotionally affected by a perceived lack of care towards the environment, locally and globally. It is therefore imperative to amplify young people's voices and involve them in influencing environmental policy, for the benefit of young people and the planet. Further research should quantify the extent to which environmental issues affect young people's mental health and identify factors that could prevent or alleviate distress.
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Emociones , Salud Mental , Adolescente , Femenino , Humanos , Masculino , Investigación CualitativaRESUMEN
INTRODUCTION: The impact of age on hallucination-proneness within healthy adult cohorts and its relation to underlying cognitive mechanisms is underexplored. Based on previously researched trends in relation to cognitive ageing, we hypothesised that older and younger adults, when compared to a middle adult age group, would show differential relations between hallucination-proneness and cognitive performance. METHODS: A mixed methods, between-groups study was conducted with 30 young adults, 26 older adults, and 27 from a "middle adulthood" group. Participants completed a source memory task, jumbled speech task, Launay-Slade hallucination scale, unusual experiences schedule, and control measures of delusion-proneness and attitudes to mental health. RESULTS: Compared to older age-groups, younger participants demonstrated better scores on the source memory task, and reported hearing more words in jumbled speech. Additionally, younger cohorts rated higher on hallucination-proneness and disclosed more unusual experiences on a customised schedule designed to gather further qualitative data. Jumbled speech scores positively correlated with hallucination-proneness scores, particularly for the "middle" age group. Source memory performance unexpectedly correlated positively with hallucination-proneness, although this may be the product of age differences in task performance. CONCLUSIONS: Age differences in hallucination-proneness are evident on self-report and cognitive measures. Implications are discussed for potentially non-overlapping cognitive mechanisms underlying hallucination-proneness in non-clinical groups.
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Alucinaciones , Longevidad , Adulto , Anciano , Cognición , Humanos , Memoria , Autoinforme , Adulto JovenRESUMEN
Schizophrenia is a debilitating psychiatric disease with a strong genetic contribution, potentially linked to altered glutamatergic function in brain regions such as the prefrontal cortex (PFC). Here, we report converging evidence to support a functional candidate gene for schizophrenia. In post-mortem PFC from patients with schizophrenia, we detected decreased expression of MKK7/MAP2K7-a kinase activated by glutamatergic activity. While mice lacking one copy of the Map2k7 gene were overtly normal in a variety of behavioural tests, these mice showed a schizophrenia-like cognitive phenotype of impaired working memory. Additional support for MAP2K7 as a candidate gene came from a genetic association study. A substantial effect size (odds ratios: ~1.9) was observed for a common variant in a cohort of case and control samples collected in the Glasgow area and also in a replication cohort of samples of Northern European descent (most significant P-value: 3 × 10(-4)). While some caution is warranted until these association data are further replicated, these results are the first to implicate the candidate gene MAP2K7 in genetic risk for schizophrenia. Complete sequencing of all MAP2K7 exons did not reveal any non-synonymous mutations. However, the MAP2K7 haplotype appeared to have functional effects, in that it influenced the level of expression of MAP2K7 mRNA in human PFC. Taken together, the results imply that reduced function of the MAP2K7-c-Jun N-terminal kinase (JNK) signalling cascade may underlie some of the neurochemical changes and core symptoms in schizophrenia.
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Predisposición Genética a la Enfermedad , Variación Genética , MAP Quinasa Quinasa 7/genética , Esquizofrenia/genética , Alelos , Animales , Estudios de Casos y Controles , Expresión Génica , Genotipo , Humanos , Desequilibrio de Ligamiento , Ratones , Fenotipo , Polimorfismo de Nucleótido Simple , Corteza Prefrontal/metabolismoRESUMEN
This study explores how young people's mental health was affected by the COVID-19 pandemic using artwork and semi-structured interviews. The mental health impacts of the pandemic are important to understand so that policy and practice professionals can support those affected, prepare and respond to future crises, and support young people who are isolated and restricted in other contexts. Co-designed participatory art workshops and interviews were conducted with 16-18-year-olds (n = 21, 62% female) from the London-based Longitudinal cohort Study of Cognition, Adolescents and Mobile Phones (SCAMP). Artworks and interview transcripts were qualitatively co-and analysed with young people. From interviews, six themes were identified: adaptation, restriction, change, challenges, overcoming adversity, and lockdown life. From the artwork, four themes were identified: trapped, negative mental wellbeing, positive emotions, and technology. Everyday factors such as home environment, social support, hobbies, habits, and online education were key determinants of how challenged and restricted participants felt, and their capacity to overcome this. This demonstrates the importance of wider (social and environmental) determinants and supports a systems-level public health approach to young people's mental health. For example, young people's mental health services should collaborate with other sectors to address such determinants in a holistic way. Clearer guidance and support with occupation, relationships, environment, routine and activities could mitigate the negative mental health impacts of major environmental changes on young people.
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Adaptación Psicológica , COVID-19 , Salud Mental , Humanos , COVID-19/psicología , COVID-19/epidemiología , Adolescente , Femenino , Masculino , Londres , Estudios Longitudinales , SARS-CoV-2 , Arte , Entrevistas como Asunto , Pandemias , Apoyo SocialRESUMEN
BACKGROUND: There is increasing evidence that air pollution and noise may have detrimental psychological impacts, but there are few studies evaluating adolescents, ground-level ozone exposure, multi-exposure models, or metrics beyond outdoor residential exposure. This study aimed to address these gaps. METHODS: Annual air pollution and traffic noise exposure at home and school were modelled for adolescents in the Greater London SCAMP cohort (N=7555). Indoor, outdoor and hybrid environments were modelled for air pollution. Cognitive and mental health measures were self-completed at two timepoints (baseline aged 11-12 and follow-up aged 13-15). Associations were modelled using multi-level multivariate linear or ordinal logistic regression. RESULTS: This is the first study to investigate ground-level ozone exposure in relation to adolescent executive functioning, finding that a 1 interquartile range increase in outdoor ozone corresponded to -0.06 (pâ¯<â¯0.001) z-score between baseline and follow-up, 38â¯% less improvement than average (median developmentâ¯+â¯0.16). Exposure to nitrogen dioxide (NO2), 24-hour traffic noise, and particulate matterâ¯<â¯10⯵g/m3 (PM10) were also significantly associated with slower executive functioning development when adjusting for ozone. In two-pollutant models, particulate matter and ozone were associated with increased externalising problems. Daytime and evening noise were associated with higher anxiety symptoms, and 24-hour noise with worse speech-in-noise perception (auditory processing). Adjusting for air pollutants, 24-hour noise was also associated with higher anxiety symptoms and slower fluid intelligence development. CONCLUSIONS: Ozone's potentially detrimental effects on adolescent cognition have been overlooked in the literature. Our findings also suggest harmful impacts of other air pollutants and noise on mental health. Further research should attempt to replicate these findings and use mechanistic enquiry to enhance causal inference. Policy makers should carefully consider how to manage the public health impacts of ozone, as efforts to reduce other air pollutants such as NO2 can increase ozone levels, as will the progression of climate change.
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Contaminantes Atmosféricos , Contaminación del Aire , Cognición , Exposición a Riesgos Ambientales , Salud Mental , Ozono , Material Particulado , Humanos , Adolescente , Londres , Contaminación del Aire/estadística & datos numéricos , Contaminación del Aire/efectos adversos , Masculino , Estudios Longitudinales , Femenino , Cognición/efectos de los fármacos , Ozono/análisis , Material Particulado/análisis , Niño , Contaminantes Atmosféricos/análisis , Ruido del Transporte/efectos adversos , Estudios de Cohortes , Dióxido de Nitrógeno/análisis , Ruido/efectos adversosRESUMEN
BACKGROUND: Increasing evidence indicates that ambient outdoor temperature could affect mental health, which is especially concerning in the context of climate change. We aimed to comprehensively analyse the current evidence regarding the associations between ambient temperature and mental health outcomes. METHODS: We did a systematic review and meta-analysis of the evidence regarding associations between ambient outdoor temperature and changes in mental health outcomes. We searched WebOfScience, Embase, PsychINFO, and PubMed for articles published from database origin up to April 7, 2022. Eligible articles were epidemiological, observational studies in humans of all ages, which evaluated real-world responses to ambient outdoor temperature, and had mental health as a documented outcome; studies of manipulated or controlled temperature or those with only physical health outcomes were excluded. All eligible studies were synthesised qualitatively. If three or more studies reported the same or equivalent effect statistics and if they had equivalent exposure, outcome, and metrics, the studies were pooled in a random-effects meta-analysis. The risk of bias for individual studies was assessed using the Newcastle-Ottawa Scale. The quality of evidence across studies was assessed using the Office of Health Assessment and Translation (OHAT) approach. FINDINGS: 114 studies were included in the systematic review, of which 19 were suitable for meta-analysis. Three meta-analyses were conducted for suicide outcomes: a 1°C increase in mean monthly temperature was associated with an increase in incidence of 1·5% (95% CI 0·8-2·2, p<0·001; n=1â563â109, seven effects pooled from three studies); a 1°C increase in mean daily temperature was associated with an increase in incidence of 1·7% (0·3-3·0, p=0·014; n=113â523, five effects pooled from five studies); and a 1°C increase in mean monthly temperature was associated with a risk ratio of 1·01 (95% CI 1·00-1·01, p<0·001; n=111â794, six effects pooled from three studies). Three meta-analyses were conducted for hospital attendance or admission for mental illness: heatwaves versus non-heatwave periods were associated with an increase in incidence of 9·7% (95% CI 7·6-11·9, p<0·001; n=362â086, three studies); the risk ratio at the 99th percentile of daily mean temperature compared with the 50th percentile was 1·02 (95% CI 1·01-1·03, p=0·006; n=532â296, three studies); and no significant association was found between a 10°C increase in daily mean temperature and hospital attendance. In a qualitative narrative synthesis, we found that ambient outdoor temperature (including absolute temperatures, temperature variability, and heatwaves) was positively associated with attempted and completed suicides (86 studies), hospital attendance or admission for mental illness (43 studies), and worse outcomes for community mental health and wellbeing (19 studies), but much of the evidence was of low certainty with high heterogeneity. INTERPRETATION: Increased temperature and temperature variability could be associated with increased cases of suicide and suicidal behaviour, hospital attendance or admission for mental illness, and poor community health and wellbeing. Climate change is likely to increase temperature anomalies, variability, and heatwaves as well as average temperatures; as such, health system leaders and policy makers must be adequately prepared and should develop adaptation strategies. More high-quality, standardised research is required to improve our understanding of these effects. FUNDING: None.
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Salud Mental , Suicidio , Temperatura , Humanos , Benchmarking , Cambio Climático , Exposición a Riesgos Ambientales/estadística & datos numéricosRESUMEN
BACKGROUND: This systematic review summarises and evaluates the literature investigating associations between exposure to air pollution and general population cognition, which has important implications for health, social and economic inequalities, and human productivity. METHODS: The engines MEDLINE, Embase Classic+Embase, APA PsycInfo, and SCOPUS were searched up to May 2022. Our inclusion criteria focus on the following pollutants: particulate matter, NOx, and ozone. The cognitive abilities of interest are: general/global cognition, executive function, attention, working memory, learning, memory, intelligence and IQ, reasoning, reaction times, and processing speed. The collective evidence was assessed using the NTP-OHAT framework and random-effects meta-analyses. RESULTS: Eighty-six studies were identified, the results of which were generally supportive of associations between exposures and worsened cognition, but the literature was varied and sometimes contradictory. There was moderate certainty support for detrimental associations between PM2.5 and general cognition in adults 40+, and PM2.5, NOx, and PM10 and executive function (especially working memory) in children. There was moderate certainty evidence against associations between ozone and general cognition in adults age 40+, and NOx and reasoning/IQ in children. Some associations were also supported by meta-analysis (N = 14 studies, all in adults aged 40+). A 1 µg/m3 increase in NO2 was associated with reduced performance on general cognitive batteries (ß = -0.02, p < 0.05) as was a 1 µg/m3 increase in PM2.5 exposure (ß = -0.02, p < 0.05). A 1µgm3 increase in PM2.5 was significantly associated with lower verbal fluency by -0.05 words (p = 0.01) and a decrease in executive function task performance of -0.02 points (p < 0.001). DISCUSSION: Evidence was found in support of some exposure-outcome associations, however more good quality research is required, particularly with older teenagers and young adults (14-40 years), using multi-exposure modelling, incorporating mechanistic investigation, and in South America, Africa, South Asia and Australasia.
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Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Niño , Adolescente , Adulto Joven , Humanos , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/análisis , Contaminación del Aire/análisis , Material Particulado/efectos adversos , Material Particulado/análisis , Ozono/análisis , CogniciónRESUMEN
BACKGROUND: The COVID-19 pandemic and climate change are both significant and pressing global challenges, posing threats to public health and wellbeing. Young people are particularly vulnerable to the distress both crises can cause, but understanding of the varied psychological responses to both issues is poor. We aimed to investigate these responses and their links with mental health conditions and feelings of agency. METHODS: We conducted an online survey between Aug 5 and Oct 26, 2020, targeting a diverse sample of young people (aged 16-24 years, n=530) in the UK. The survey was distributed using a combination of a survey panel (panel sample) and direct approaches to youth groups and schools who shared the survey with young people in their networks (community sample). We collected data on respondents' psychological responses to both climate change and the COVID-19 pandemic, their sense of agency to respond to each crisis, and the range of impacts on their lives. We also collected demographics data and screened for mental health and wellbeing indicators. We used non-parametric tests for most statistical comparisons. For paired samples, we used Wilcoxon's signed-rank test, and used Mann-Whitney U-tests or Kruskal-Wallis tests for two or more independent samples. Summed scale scores were considered as interval-level data and analysed with Student's t tests and ANOVAs. Effect sizes are reported as Cohen's d and partial eta-squared (η·2p), respectively. FINDINGS: After excluding 18 suspected bots and 94 incomplete responses, 530 responses were retained for analysis. Of the 518 respondents who provided demographic data, 63% were female, 71·4% were White, and the mean family affluence score was 8·22 (SD 2·29). Most participants (n=343; 70%) did not report a history of diagnosis or treatment for a mental health disorder, but mental health scores indicated a common experience of (relatively mild) symptoms of anxiety, depression, and stress. Although UK youth reported more life disruption and concern for their future due to the COVID-19 pandemic, climate change was associated with significantly greater distress overall, particularly for individuals with low levels of generalised anxiety. The COVID-19 pandemic was more associated with feelings of anxiety, isolation, disconnection, and frustration; distress around loss and grief; and effects on quality of life. Climate change was more likely to evoke emotions such as interest and engagement, guilt, shame, anger, and disgust. The greater distress attributed to climate change overall was due, in particular, to higher levels of guilt, sense of personal responsibility, and greater distress triggered by upsetting media coverage. Agency to address climate change was associated with greater climate distress, but pandemic-related distress and agency were unrelated. INTERPRETATION: The COVID-19 pandemic and climate change are affecting the wellbeing of UK young people in distinct ways, with implications for health service, policy, and research responses. There is a need for mental health practitioners, policy makers, and other societal actors to account for the complex relationship between climate agency, distress, and mental wellbeing in young people. FUNDING: Imperial College London.
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COVID-19 , Salud Mental , Adolescente , COVID-19/epidemiología , COVID-19/psicología , Cambio Climático , Femenino , Humanos , Masculino , Pandemias , Calidad de Vida , Encuestas y Cuestionarios , Reino Unido/epidemiología , Adulto JovenRESUMEN
BACKGROUND: This systematic review provides a comprehensive synthesis of recent epidemiological evidence that environmental noise negatively impacts human cognition. METHODS: We update a prior review with recent publications (PROSPERO CRD42019151923). The strength of evidence for associations was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework. We also conducted random-effects meta-analyses where suitable. RESULTS: 16 studies were identified and reviewed in tandem with 32 studies previously reviewed by Clark & Paunovic (2018). A meta-analysis from 3 studies found that reading comprehension scores in quiet classrooms were 0.80 (95% confidence interval: 0.40; 1.20) points higher than children in noisier classrooms. Meta-analysis of the impact of 1 dB (dB) increase in environmental noise on reading and language abilities gave a pooled beta coefficient of -0.11(95% confidence interval: -0.32; 0.10). A meta-analysis of Odds Ratios (OR) from 3 studies found higher odds of cognitive impairment in people aged 45 + with higher residential noise exposure (OR 1.40, 95% CI: 1.18;1.61). After qualitative synthesis of remaining studies, there was high quality evidence for an association between environmental noise and cognitive impairment in middle-to-older adults, moderate quality evidence for an association between aircraft noise and reading and language in children, and moderate quality evidence against an association between aircraft noise and executive functioning in children. Generally the literature was supportive for other cognitive outcomes, but with low or very low-quality evidence. DISCUSSION: The evidence so far suggests that noise exposure is associated with cognition, but more good quality research using standardised methodology is required to corroborate these results and to allow for precise risk estimation by larger meta-analyses. There is also a need for more research with older teenagers and young-to-middle aged adults, on the synergistic effects of noise and air pollution, and in Africa, Central and South America, South Asia and Australasia.
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Contaminación del Aire , Disfunción Cognitiva , Adolescente , Anciano , Aeronaves , Niño , Cognición , Humanos , Persona de Mediana Edad , Ruido/efectos adversosRESUMEN
c-Jun N-terminal kinase (JNK) signaling contributes to functional plasticity in the brain and cognition. Accumulating evidence implicates a role for MAP kinase kinase 7 (MAP2K7), a JNK activator encoded by the Map2k7 gene, and other JNK pathway components in schizophrenia (ScZ). Mice haploinsufficient for Map2k7 (Map2k7+/- mice) display ScZ-relevant cognitive deficits, although the mechanisms are unclear. Here we show that Map2k7+/- mice display translationally relevant alterations in brain function, including hippocampal and mesolimbic system hypermetabolism with a contrasting prefrontal cortex (PFC) hypometabolism, reminiscent of patients with ScZ. In addition Map2k7+/- mice show alterations in functional brain network connectivity paralleling those reported in early ScZ, including PFC and hippocampal hyperconnectivity and compromised mesolimbic system functional connectivity. We also show that although the cerebral metabolic response to ketamine is preserved, the response to dextroamphetamine (d-amphetamine) is significantly attenuated in Map2k7+/- mice, supporting monoamine neurotransmitter system dysfunction but not glutamate/NMDA receptor (NMDA-R) dysfunction as a consequence of Map2k7 haploinsufficiency. These effects are mirrored behaviorally with an attenuated impact of d-amphetamine on sensorimotor gating and locomotion, whereas similar deficits produced by ketamine are preserved, in Map2k7+/- mice. In addition, Map2k7+/- mice show a basal hyperactivity and sensorimotor gating deficit. Overall, these data suggest that Map2k7 modifies brain and monoamine neurotransmitter system function in a manner relevant to the positive and cognitive symptoms of ScZ.
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Conducta Animal/fisiología , Encéfalo , Conectoma , Endofenotipos , Locomoción/fisiología , MAP Quinasa Quinasa 7 , Red Nerviosa , Esquizofrenia , Filtrado Sensorial/fisiología , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatología , Dextroanfetamina/farmacología , Modelos Animales de Enfermedad , Inhibidores de Captación de Dopamina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Haploinsuficiencia , Ketamina/farmacología , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/efectos de los fármacos , Red Nerviosa/metabolismo , Red Nerviosa/fisiopatología , Esquizofrenia/genética , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatologíaRESUMEN
OBJECTIVE: In the present study, we employ mathematical modeling (partial least squares regression, PLSR) to elucidate the functional connectivity signatures of discrete brain regions in order to identify the functional networks subserving PCP-induced disruption of distinct cognitive functions and their restoration by the procognitive drug modafinil. METHODS: We examine the functional connectivity signatures of discrete brain regions that show overt alterations in metabolism, as measured by semiquantitative 2-deoxyglucose autoradiography, in an animal model (subchronic phencyclidine [PCP] treatment), which shows cognitive inflexibility with relevance to the cognitive deficits seen in schizophrenia. RESULTS: We identify the specific components of functional connectivity that contribute to the rescue of this cognitive inflexibility and to the restoration of overt cerebral metabolism by modafinil. We demonstrate that modafinil reversed both the PCP-induced deficit in the ability to switch attentional set and the PCP-induced hypometabolism in the prefrontal (anterior prelimbic) and retrosplenial cortices. Furthermore, modafinil selectively enhanced metabolism in the medial prelimbic cortex. The functional connectivity signatures of these regions identified a unifying functional subsystem underlying the influence of modafinil on cerebral metabolism and cognitive flexibility that included the nucleus accumbens core and locus coeruleus. In addition, these functional connectivity signatures identified coupling events specific to each brain region, which relate to known anatomical connectivity. CONCLUSIONS: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction.