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1.
Physiol Rep ; 10(7): e15219, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35373929

RESUMO

Extracellular vesicles (EVs) transport biological content between cells to mediate physiological processes. The association between EVs and resilience, the ability to cope with stress, is unknown. Using unbiased machine learning approaches, we aimed to identify a biological profile of resilience. Twenty servicemen (27.8 ± 5.9 years) completed the Connor Davidson Resilience (CD-RISC) questionnaire and were exposed to daily physical and cognitive exertion with 48-hr sleep and caloric restriction. Blood samples from baseline and the second day of stress were analyzed for neuroendocrine biomarkers impacted by military stress. EVs were isolated from plasma and stained with antibodies associated with exosomes (CD63), microvesicles (VAMP3), and apoptotic bodies (THSD1). Individuals were separated into high (n = 10, CD-RISC > 90) and low (n = 10, CD-RISC < 79) resilience. EV features were stratified by size, then down-selected using regression trees and compared between groups. Diagnostic accuracy was assessed using receiver operating characteristic curves. Compared to low resilience, high resilience demonstrated a greater increase in variability of THSD1 local bright spot intensities among large-sized EVs in response to stress (p = 0.002, Hedges' g = 1.59). Among medium-sized EVs, high resilience exhibited a greater decrease in side scatter intensity (p = 0.014, Hedges' g = 1.17). Both features demonstrated high to moderate diagnostic accuracy for high resilience (AUC = 0.90 and 0.79). In contrast, neuroendocrine biomarker concentrations were similar between groups. The increase in variability among THSD1 + EVs in high, but not low, resilient individuals following stress may suggest high resilience is accompanied by stress-triggered apoptotic adaptations to the environment that are not detected in neuroendocrine biomarkers.


Assuntos
Vesículas Extracelulares , Militares , Resiliência Psicológica , Biomarcadores Ambientais , Humanos , Militares/psicologia , Inquéritos e Questionários
2.
J Appl Physiol (1985) ; 132(5): 1125-1136, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35297690

RESUMO

Extracellular vesicles (EVs) are mediators of physiological changes that occur during physical exertion. This study examined the effects of physical exertion with and without sleep and caloric restriction on EV size, concentration, and surface proteins in men and women. Twenty participants (10 men) completed a 5-day simulated military operational stress protocol with daily physical exertion. Blood was drawn before and immediately after exertion at baseline (D1) and following 48-h of sleep and caloric restriction (D3). EV size and concentration were assessed using nanoparticle tracking analysis. EVs were identified with markers associated with exosomes (CD63), microvesicles (VAMP3), apoptotic bodies (THSD1), and skeletal muscle-derived EVs (SGCA) and quantified using imaging flow cytometry. Interactive and main effects of sex, day, and time on EVs were assessed using three-way ANOVAs. EV concentration declined pre to postexertion in women on D1 and D3 but was stable in men. EV size increased from pre to postexertion and from D1 to D3 in men and women. Physical exertion following sleep and caloric restriction increased CD63+ EV concentration, proportion of total EVs, and CD63 surface protein expression regardless of sex. The proportion of SGCA+ EVs increased in men and women following exertion and from D1 to D3 but was higher in women than in men. No differences were observed in VAMP3+ and THSD1+ EVs. This study identified sexually dimorphic EV profiles in response to various stressors. Further investigations are necessary to determine if dimorphic EV responses affect health and performance outcomes during stress.NEW & NOTEWORTHY Sex is understudied in EV research, and most studies limit EV analysis to single stress conditions such as exercise. Multistress conditions consisting of physical exertion and sleep and caloric restriction are common in real-world settings. We demonstrate that physical exertion results in sex-specific EV signatures and that EV profiles vary according to single versus multistress conditions. Our data highlight important biological and ecological characteristics that should be considered in EV research.


Assuntos
Exossomos , Vesículas Extracelulares , Militares , Biomarcadores/metabolismo , Exossomos/metabolismo , Vesículas Extracelulares/fisiologia , Feminino , Humanos , Masculino , Proteínas de Membrana/metabolismo , Proteína 3 Associada à Membrana da Vesícula/metabolismo
3.
Brain Sci ; 12(2)2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35203996

RESUMO

Difficulty sleeping in a novel environment is a common phenomenon that is often described as the first night effect (FNE). Previous works have found FNE on sleep architecture and sleep power spectra parameters, especially during non-rapid eye movement (NREM) sleep. However, the impact of FNE on sleep parameters, including local differences in electroencephalographic (EEG) activity across nights, has not been systematically assessed. Here, we performed high-density EEG sleep recordings on 27 healthy individuals on two nights and examined differences in sleep architecture, NREM (stages 2 and 3) EEG power spectra, and NREM power topography across nights. We found higher wakefulness after sleep onset (WASO), reduced sleep efficiency, and less deep NREM sleep (stage 3), along with increased high-frequency NREM EEG power during the first night of sleep, corresponding to small to medium effect sizes (Cohen's d ≤ 0.5). Furthermore, study individuals showed significantly lower slow-wave activity in right frontal/prefrontal regions as well as higher sigma and beta activities in medial and left frontal/prefrontal areas, yielding medium to large effect sizes (Cohen's d ≥ 0.5). Altogether, these findings suggest the FNE is characterized by less efficient, more fragmented, shallower sleep that tends to affect especially certain brain regions. The magnitude and specificity of these effects should be considered when designing sleep studies aiming to compare across night effects.

4.
Sleep ; 45(2)2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-34432067

RESUMO

STUDY OBJECTIVES: Within-subject stability of certain sleep features across multiple nights is thought to reflect the trait-like behavior of sleep. However, to be considered a trait, a parameter must be both stable and robust. Here, we examined the stability (i.e. across the same sleep opportunity periods) and robustness (i.e. across sleep opportunity periods that varied in duration and timing) of different sleep parameters. METHODS: Sixty-eight military personnel (14 W) spent 5 nights in the sleep laboratory during a simulated military operational stress protocol. After an adaptation night, participants had an 8-hour sleep opportunity (23:00-07:00) followed by 2 consecutive nights of sleep restriction and disruption which included two 2-hour sleep opportunities (01:00-03:00; 05:00-07:00) and, lastly, another 8-hour sleep opportunity (23:00-07:00). Intra-class correlation coefficients were calculated to examine differences in stability and robustness across different sleep parameters. RESULTS: Sleep architecture parameters were less stable and robust than absolute and relative spectral activity parameters. Further, relative spectral activity parameters were less robust than absolute spectral activity. Absolute alpha and sigma activity demonstrated the highest levels of stability that were also robust across sleep opportunities of varying duration and timing. CONCLUSIONS: Stability and robustness varied across different sleep parameters, but absolute NREM alpha and sigma activity demonstrated robust trait-like behavior across variable sleep opportunities. Reduced stability of other sleep architecture and spectral parameters during shorter sleep episodes as well as across different sleep opportunities has important implications for study design and interpretation.


Assuntos
Militares , Eletroencefalografia/métodos , Humanos , Fenótipo , Polissonografia/métodos , Sono , Fases do Sono
5.
J Psychopathol Clin Sci ; 131(3): 287-300, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35230864

RESUMO

Patients with disorders of compulsivity show impairments in goal-directed behavior, which have been linked to orbitofrontal cortex (OFC) dysfunction. We recently showed that continuous theta burst stimulation (cTBS), which reduces OFC activity, had a beneficial effect on compulsive behaviors both immediately and at 1 week follow-up compared with inhibitory TBS (iTBS). In this same sample, we investigated whether two behavioral measures of goal-directed control (devaluation success on a habit override task; model-based planning on the two-step task) were also affected by acute modulation of OFC activity. Overall, model-based planning and devaluation success were significantly related to each other and (for devaluation success) to symptoms in our transdiagnostic clinical sample. These measures were moderately to highly stable across time. In individuals with low levels of model-based planning, active cTBS improved devaluation success. Analogous to previously reported clinical effects, this effect was specific to cTBS and not iTBS. Overall, results suggested that measures of goal directed behavior are reliable but less affected by cTBS than clinical self-report. Future research should continue to examine longitudinal changes in behavioral measures to determine their temporal relationship with symptom improvement after treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Objetivos , Estimulação Magnética Transcraniana , Método Duplo-Cego , Humanos , Motivação , Córtex Pré-Frontal , Estimulação Magnética Transcraniana/métodos
7.
Curr Neuropharmacol ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34852743

RESUMO

In Oncology, comprehensive Omics and functional enrichment studies led to an extensive profiling of (epi)genetic and neurobiological alterations that can be mapped onto a single tumor's clinical phenotype and divergent clinical phenotypes expressing common pathophysiological pathways. Consequently, molecular pathway-based therapeutic interventions for different cancer typologies, namely tumor type- and site-agnostic treatments, have been developed, encouraging real-world implementation of a paradigm shift in medicine. Given the breakthrough nature of the new-generation translational research and drug development in Oncology, there is an increasing rationale to transfertilize this blueprint to other medical fields including Psychiatry and Neurology. To illustrate the emerging paradigm shift in neuroscience, we provide a state-of-the-art review of translational studies on the ß-site amyloid precursor protein cleaving enzyme (BACE) and its most studied downstream effector, neuregulin, which are molecular orchestrators of distinct biological pathways involved in several neurological and psychiatric diseases. This body of data aligns with the evidence of a shared genetic/biological architecture among Alzheimer's disease, schizoaffective and autism spectrum disorders. We engage in a speculative intellectual exercise gravitating around the BACE-related science, here used as paradigmatic case, to facilitating a forward-looking discussion about a potential first step towards the adoption of biological pathway-based, clinical symptom agnostic, categorization models in clinical Neurology and Psychiatry for precision medicine solutions. We draw a perspective whereby pathway-based therapeutic strategies could be catalyzed by high-throughput techniques, embedded in systems-scaled biology, neuroscience, and pharmacology approaches that will help overcome the constraints of traditional descriptive clinical symptom and syndrome-focused constructs in Neurology and Psychiatry.

8.
J Psychiatr Res ; 141: 301-308, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34304033

RESUMO

Posttraumatic stress disorder-related sleep disturbances may increase daytime sleepiness and compromise performance in individuals with posttraumatic stress disorder. We investigated nighttime sleep predictors of sleepiness in Veterans with and without posttraumatic stress disorder. Thirty-seven post-9/11 Veterans with posttraumatic stress disorder and 47 without posttraumatic stress disorder (Control) completed a 48-h lab stay. Nighttime quantitative EEG and sleep architecture parameters were collected with polysomnography. Data from daytime sleepiness batteries assessing subjective sleepiness (global vigor questionnaire), objective sleepiness (Multiple Sleep Latency Tests) and alertness (psychomotor vigilance task) were included in analyses. Independent samples t-tests and linear regressions were performed to identify group differences in sleepiness and nighttime sleep predictors of sleepiness in the overall sample and within each group. Participants with posttraumatic stress disorder had higher subjective sleepiness (t = 4.20; p < .001) and lower alertness (psychomotor vigilance task reaction time (t = -3.70; p < .001) and lapses: t = -2.13; p = .04) than the control group. Objective daytime sleepiness did not differ between groups (t = -0.79, p = .43). In the whole sample, higher rapid eye movement delta power predicted lower alertness quantified by psychomotor vigilance task reaction time (ß = 0.372, p = .013) and lapses (ß = 0.388, p = .013). More fragmented sleep predicted higher objective sleepiness in the posttraumatic stress disorder group (ß = -.467, p = .005) but no other nighttime sleep measures influenced the relationship between group and sleepiness. Objective measures of sleep and sleepiness were not associated with the increased subjective sleepiness and reduced alertness of the posttraumatic stress disorder group.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Atenção , Humanos , Desempenho Psicomotor , Sono , Sonolência , Transtornos de Estresse Pós-Traumáticos/complicações , Vigília
9.
Artigo em Inglês | MEDLINE | ID: mdl-34129889

RESUMO

Accumulating evidence points to neurophysiological abnormalities of the motor cortex in Schizophrenia (SCZ). However, whether these abnormalities represent a core biological feature of psychosis rather than a superimposed neurodegenerative process is yet to be defined, as it is their putative relationship with clinical symptoms. in this study, we used Transcranial Magnetic Stimulation coupled with electroencephalography (TMS-EEG) to probe the intrinsic oscillatory properties of motor (Brodmann Area 4, BA4) and non-motor (posterior parietal, BA7) cortical areas in twenty-three first-episode psychosis (FEP) patients and thirteen age and gender-matched healthy comparison (HC) subjects. Patients underwent clinical evaluation at baseline and six-months after the TMS-EEG session. We found that FEP patients had reduced EEG activity evoked by TMS of the motor cortex in the beta-2 (25-34 Hz) frequency band in a cluster of electrodes overlying BA4, relative to HC participants. Beta-2 deficits in the TMS-evoked EEG response correlated with worse positive psychotic symptoms at baseline and also predicted positive symptoms severity at six-month follow-up assessments. Altogether, these findings indicate that reduced TMS-evoked fast oscillatory activity in the motor cortex is an early neural abnormality that: 1) is present at illness onset; 2) may represent a state marker of psychosis; and 3) could play a role in the development of new tools of outcome prediction in psychotic patients.


Assuntos
Córtex Motor/fisiopatologia , Transtornos Psicóticos/diagnóstico , Estimulação Magnética Transcraniana , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino
10.
Physiol Behav ; 236: 113413, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33811909

RESUMO

PURPOSE: To study the impact of 48 h of simulated military operational stress (SMOS) on executive function, in addition to the role of trait resilience (RES) and aerobic fitness (FIT) on executive function performance. Associations between executive function and neuropeptide-Y (NPY), brain-derived neurotropic factor (BDNF), insulin-like growth factor-I (IGF-I), oxytocin, and α-klotho (klotho) were assessed to elucidate potential biomarkers that may contribute to cognitive performance during a multi-factorial stress scenario. METHODS: Fifty-four service members (SM) (26.4 ± 5.4 years, 178.0 ± 6.5 cm, 85.2 ± 14.0 kg) completed the 5-day protocol, including daily physical exertion and 48 h of restricted sleep and caloric intake. Each morning subjects completed a fasted blood draw followed by Cognition, a 10-part cognitive test battery assessing executive function. SMs were grouped into tertiles [low (L-), moderate (M-), high (H-)] based on Connor Davidson Resilience Score (RES) and V˙O2peak (FIT). Repeated measures ANOVA were run to analyze the effect of day on cognitive performance and biomarker concentration. Separate two-way mixed ANOVAs were run to determine the interaction of group by day on cognitive function. Friedman test with Bonferroni-corrected pairwise comparisons were used if assumptions for ANOVA were not met. Associations between changes in biomarkers and cognitive performance were analyzed using parametric and non-parametric correlation coefficients. RESULTS: SMOS reduced SM vigilance -11.3% (p < 0.001) and working memory -5.6% (p = 0.015), and increased risk propensity +9.5% (p = 0.005). H-RES and H-FIT SMs demonstrated stable vigilance across SMOS (p > 0.05). Vigilance was compromised during SMOS in L- and M-RES (p = 0.007 and p = 0.001, respectively) as well as L- and M-FIT (p = 0.001 and p = 0.031, respectively). SMOS reduced circulating concentrations of α-klotho -7.2% (p = 0.004), NPY -6.4% (p = 0.001), and IGF-I -8.1% (p < 0.001) from baseline through the end of the protocol. BDNF declined -19.2% after the onset of sleep and caloric restriction (p = 0.005) with subsequent recovery within 48 h. Oxytocin remained stable (p > 0.05). Several modest associations between neuroendocrine biomarkers and cognitive performance were identified. CONCLUSION: This study demonstrates H-FIT and H-RES may buffer the impact of SMOS on vigilance. SMOS negatively impacted circulating neuroendocrine biomarkers. While BDNF returned to baseline concentrations by the end of the 5 d protocol, NPY, IGF-I, and α-klotho may require a longer recovery period. These data suggest that the military may benefit by training and/or selection processes targeting at augmenting trait resilience and aerobic fitness for increased readiness.


Assuntos
Função Executiva , Militares , Biomarcadores , Cognição , Exercício Físico , Humanos , Memória de Curto Prazo , Aptidão Física
11.
Am J Psychiatry ; 178(5): 400-413, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33653120

RESUMO

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique uniquely equipped to both examine and modulate neural systems and related cognitive and behavioral functions in humans. As an examination tool, TMS can be used in combination with EEG (TMS-EEG) to elucidate directly, objectively, and noninvasively the intrinsic properties of a specific cortical region, including excitation, inhibition, reactivity, and oscillatory activity, irrespective of the individual's conscious effort. Additionally, when applied in repetitive patterns, TMS has been shown to modulate brain networks in healthy individuals, as well as ameliorate symptoms in individuals with psychiatric disorders. The key role of TMS in assessing and modulating neural dysfunctions and associated clinical and cognitive deficits in psychiatric populations is therefore becoming increasingly evident. In this article, the authors review TMS-EEG studies in schizophrenia and mood disorders, as most TMS-EEG studies to date have focused on individuals with these disorders. The authors present the evidence on the efficacy of repetitive TMS (rTMS) and theta burst stimulation (TBS), when targeting specific cortical areas, in modulating neural circuits and ameliorating symptoms and abnormal behaviors in individuals with psychiatric disorders, especially when informed by resting-state and task-related neuroimaging measures. Examples of how the combination of TMS-EEG assessments and rTMS and TBS paradigms can be utilized to both characterize and modulate neural circuit alterations in individuals with psychiatric disorders are also provided. This approach, along with the evaluation of the behavioral effects of TMS-related neuromodulation, has the potential to lead to the development of more effective and personalized interventions for individuals with psychiatric disorders.


Assuntos
Transtorno Bipolar/terapia , Encéfalo/fisiopatologia , Transtorno Depressivo Maior/terapia , Eletroencefalografia/métodos , Esquizofrenia/terapia , Estimulação Magnética Transcraniana/métodos , Transtorno Bipolar/fisiopatologia , Ondas Encefálicas , Córtex Cerebral/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Potenciais Evocados , Humanos , Transtornos Mentais/fisiopatologia , Transtornos Mentais/terapia , Inibição Neural , Vias Neurais/fisiopatologia , Esquizofrenia/fisiopatologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-33757792

RESUMO

BACKGROUND: Preliminary evidence indicates that non-rapid eye movement (NREM) sleep is implicated in enhancing working memory (WM) performance across days in healthy individuals. While REM sleep has been implicated in other forms of memory, its role in WM remains unclear. Further, the relationship between sleep changes and WM improvement is largely unknown in posttraumatic stress disorder (PTSD). Examining the relationship between changes in sleep and WM improvement in healthy participants and participants with PTSD may inform cognitive enhancement strategies and intervention targets. METHODS: Repeated assessments of WM and overnight measurement of NREM and REM sleep parameters were performed in 79 participants (participants with PTSD: n = 33) during a 48-hour laboratory stay. Relationships between sleep parameter changes, WM performance changes, and clinical characteristics were analyzed in PTSD and healthy groups. RESULTS: A between-night enhancement in both NREM and REM sleep parameters in frontoparietal areas predicted across-day better WM performance in healthy participants, particularly in those with improved performance. In contrast, in participants with PTSD, an enhancement of these sleep parameters predicted a worse WM performance and was also associated with more PTSD-related sleep disturbances. CONCLUSIONS: This study shows that higher sleep activity in frontoparietal areas leads to enhanced WM performance in healthy individuals, whereas in individuals with PTSD, it likely reflects the presence of sleep disturbances that interfere with WM improvement. Interventions focused on addressing sleep disturbances could therefore ameliorate cognitive impairments in individuals with PTSD.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Voluntários Saudáveis , Humanos , Memória de Curto Prazo , Polissonografia , Sono
13.
J Psychiatr Res ; 137: 328-334, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33744512

RESUMO

Youth at clinical high risk (CHR) represent a unique population enriched for precursors of major psychiatric disorders. Sleep disturbances are consistently reported in CHR individuals. However, there is a dearth of studies investigating quantifiable objective measures of sleep dysfunction in CHR youth. In this study, sleep high density (hd)-EEG recordings were collected in twenty-two CHR and twenty healthy control (HC) subjects. Sleep architecture parameters, as well as sleep EEG power spectra in five frequency bands, were computed and compared between CHR and HC groups during non-rapid eye movement (NREM) sleep. Furthermore, correlation analyses between sleep EEG power spectra, sleep architecture parameters, and clinical symptoms, assessed with the scale of prodromal symptoms (SOPS), were conducted in CHR participants. Our results show that CHR individuals had more wakefulness after sleep onset (WASO) compared to HC participants. CHR also showed a higher NREM sleep gamma EEG power, which was observed in a large fronto-parieto-occipital area, relative to HC. Additionally, higher NREM gamma activity in lateral fronto-occipital regions was associated with more WASO, and increased NREM gamma power in medial fronto/parietal areas correlated with worse SOPS negative symptoms. Altogether, these findings suggest that topographically specific increases in EEG gamma activity during NREM sleep represent neurophysiological signatures underlying some of the objectively assessed sleep disturbances and clinical symptoms of CHR individuals.


Assuntos
Transtornos Psicóticos , Adolescente , Eletroencefalografia , Humanos , Polissonografia , Transtornos Psicóticos/complicações , Sono , Fases do Sono , Sono REM
14.
Am J Psychiatry ; 178(5): 459-468, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33726523

RESUMO

OBJECTIVE: Compulsive behaviors are a core feature of obsessive-compulsive spectrum disorders but appear across a broad spectrum of psychological conditions. It is thought that compulsions reflect a failure to override habitual behaviors "stamped in" through repeated practice and short-term distress reduction. Animal models suggest a possible causal role of the orbitofrontal cortex (OFC) in compulsive behaviors, but human studies have largely been limited by correlational designs. The goal of this study was to establish the first experimental evidence in humans for a mechanistic model in order to inform further experimental work and the eventual development of novel mechanistic treatments involving synergistic biological-behavioral pairings. METHODS: After a baseline assessment, 69 individuals with compulsive behavior disorders were randomly assigned, in a double-blind, between-subjects design, to receive a single session of one of two active stimulation conditions targeting the left OFC: intermittent theta burst stimulation (iTBS), expected to increase OFC activity, or continuous TBS (cTBS), expected to decrease activity (both conditions, 600 pulses at 110% of target resting motor threshold). In both conditions, brain modulation was paired with a subsequent computer task providing practice in overriding a clinically relevant habit (an overlearned shock avoidance behavior), delivered during the expected window of OFC increase or decrease. Pre- and post-TBS functional MRI assessments were conducted of target engagement and compulsive behaviors performed in response to an idiographically designed stressful laboratory probe. RESULTS: cTBS and iTBS modulated OFC activation in the expected directions. cTBS, relative to iTBS, exhibited a beneficial impact on acute laboratory assessments of compulsive behaviors 90 minutes after TBS. These acute behavioral effects persisted 1 week after cTBS. CONCLUSIONS: Experimental modulation of the OFC, within the behavioral context of habit override training, affected short-term markers of compulsive behavior vulnerability. The findings help delineate a causal translational model, serving as an initial precursor to mechanistic intervention development.


Assuntos
Comportamento Compulsivo/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Ritmo Teta , Estimulação Magnética Transcraniana/métodos , Adolescente , Adulto , Transtornos Dismórficos Corporais/fisiopatologia , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Distribuição Aleatória , Tricotilomania/fisiopatologia , Adulto Jovem
15.
Am J Psychiatry ; 178(10): 903-913, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33726524

RESUMO

Sleep disturbances are commonly observed in schizophrenia, including in chronic, early-course, and first-episode patients. This has generated considerable interest, both in clinical and research endeavors, in characterizing the relationship between disturbed sleep and schizophrenia. Sleep features can be objectively assessed with EEG recordings. Traditionally, EEG studies have focused on sleep architecture, which includes non-REM and REM sleep stages. More recently, numerous studies have investigated alterations in sleep-specific rhythms, including EEG oscillations, such as sleep spindles and slow waves, in individuals with schizophrenia compared with control subjects. In this article, the author reviews state-of-the-art evidence of disturbed sleep in schizophrenia, starting from the relationship between sleep disturbances and clinical symptoms. First, the author presents studies demonstrating abnormalities in sleep architecture and sleep-oscillatory rhythms in schizophrenia and related psychotic disorders, with an emphasis on recent work demonstrating sleep spindles and slow-wave deficits in early-course and first-episode schizophrenia. Next, the author shows how these sleep abnormalities relate to the cognitive impairments in patients diagnosed with schizophrenia and point to dysfunctions in underlying thalamocortical circuits, Ca+ channel activity, and GABA-glutamate neurotransmission. Finally, the author discusses some of the next steps needed to further establish the role of altered sleep in schizophrenia, including the need to investigate sleep abnormalities across the psychotic spectrum and to establish their relationship with circadian disturbances, which in turn will contribute to the development of novel sleep-informed treatment interventions.


Assuntos
Administração dos Cuidados ao Paciente/métodos , Esquizofrenia , Transtornos do Sono-Vigília , Ritmo Circadiano , Humanos , Esquizofrenia/fisiopatologia , Esquizofrenia/terapia , Transtornos do Sono-Vigília/psicologia , Transtornos do Sono-Vigília/terapia , Transmissão Sináptica
16.
Schizophr Res ; 228: 36-42, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33434730

RESUMO

Abnormalities in resting-state electroencephalogram (rs-EEG) activity have been previously reported in schizophrenia. While most rs-EEG recordings were performed in patients with chronic schizophrenia during eyes closed (EC), only a handful of studies have investigated rs-EEG activity during both EC and eyes open (EO) conditions. It is also unknown whether EC and EO rs-EEG alterations are present at illness onset, and whether they change during the day. Here, we performed EC and EO rs-EEG recordings in the morning (AM) and evening (PM) in twenty-six first-episode psychosis (FEP) patients and seventeen matched healthy controls (HC). In AM/EC rs-EEG, a widespread reduction was found in low alpha power in FEP relative to HC. In PM/EC, the FEP group demonstrated a trend toward decreased theta power in parietal regions, while decreased high alpha power in frontal and left parietal regions was present during PM/EO. Moreover, reduced low alpha power during AM/EC was associated with worse positive symptoms. Altogether, those findings indicate that rs-EEG alterations are present in FEP patients at illness onset, that they are linked to the severity of their psychosis, and that distinct RS abnormalities can be detected in different conditions of visual alertness and time of the day. Future work should therefore account for those factors, which will help reduce variability of rs-EEG findings across studies and may serve as monitoring biomarkers of illness severity in schizophrenia and related psychotic disorders.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Eletroencefalografia , Humanos
17.
Neuropsychopharmacology ; 46(6): 1133-1139, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33273706

RESUMO

Youth at clinical high risk (CHR) are a unique population enriched for precursors of major psychiatric disorders, especially schizophrenia (SCZ). Recent neuroimaging findings point to abnormalities in the thalamus of patients with SCZ, including chronic and early course patients, as well as in CHR individuals relative to healthy comparison groups, thus suggesting that thalamic dysfunctions are present even before illness onset. Furthermore, modeling data indicate that alteration between excitatory and inhibitory control, as reflected by alteration in GABAergic and glutamatergic balance (i.e., GABA/Glu), may underlie thalamic deficits linked to the risk and development of psychosis. There is, however, a lack of in vivo evidence of GABA/Glu thalamic abnormalities in the CHR state. Magnetic resonance spectroscopic imaging (MRSI) 7 Tesla (7 T) provides enhanced resolution to quantify GABA and Glu levels in the thalamus of CHR individuals. In this study, we performed 7 T MRSI in 15 CHR and 20 healthy control (HC) participants. We found that GABA/Glu was significantly reduced in the right medial anterior and right medial posterior thalamus of CHR relative to HC groups. The GABA/Glu reduction was negatively correlated with general symptoms in the right medial anterior thalamus, as well as with disorganization symptoms in the right medial posterior thalamus. Altogether, these findings indicate that GABA/Glu abnormalities are present in the thalamus before the onset of full-blown psychosis and are associated with symptom severity, thus providing putative molecular and neuronal targets for early interventions in youth at CHR.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Adolescente , Ácido Glutâmico , Humanos , Imageamento por Ressonância Magnética , Transtornos Psicóticos/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Ácido gama-Aminobutírico
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