RESUMEN
Ethanol's complete miscibility in water makes it a widely used solvent in various applications, such as organic compound synthesis, paint manufacture, chromatography, and cosmetics preservation. Studies suggest that ethanol's concentration at interfaces can be higher than in the bulk due to its amphiphilic nature, especially at lower concentrations, making it a surface-active agent. Accordingly, ethanol plays a crucial role in controlling the emulsion stability, foam formation, heat transfer, and coating adhesion. However, the precise concentration ranges up to which ethanol's surface activity dominates its interfacial properties, and the underlying molecular mechanism is not fully understood in the literature. In this context, our foamability experiments, coupled with film stability experiments conducted via ethanol drop impact on varying concentration ethanol-water mixture pools, indicate that the surface-active nature of ethanol is observed up to a maximum of 10% molar ethanol concentration in water. We next employ all-atom molecular dynamics simulations to reveal that the surface tension and other interfacial properties are most significantly affected only up to the molar concentration in the range of 0-10% of ethanol in water. This observation is further supported by free energy analyses, indicating that the stabilization free energy of an ethanol molecule at the interface becomes comparable to that in the bulk region beyond this concentration range. The transition from surface-active to a behavior resembling a homogeneous solution occurs when the molar concentration of ethanol in water exceeds 10%. This transition is attributed to distinctive alterations in the number and strength of ethanol-water hydrogen bonds. These findings provide valuable insights into the interfacial molecular structure, which can be suitably exploited to modulate interfacial properties and dynamic behavior in a wide array of industrial and scientific applications.
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Surfactants are amphiphilic additives primarily used to reduce the surface tension of water and manipulate its wettability on various surfaces. Recent reports suggest that volatile surfactants, such as aroma molecules, diffuse more quickly to the interface from the vapor-phase than conventional surfactants typically used in the aqueous phase. The ability to adsorb from the vapor phase, in addition to their use as cosurfactants, expands the potential applications of volatile surfactants, particularly in situations where adding surfactants from the liquid phase is difficult. Here, we present a molecular level understanding of the adsorption kinetics of linalool, a common aroma molecule, on the water interface using molecular dynamics simulations. We note that the value of surface tension while adsorption from vapor and liquid phases is dependent only on the surface coverage. A minimum surface tension of 32 ± 1.8 mN/m is obtained in both cases at a maximum surface coverage of 4.88 µmol/m2 at 300 K. We observe the extent of decrease of the H-bonds between linalool-water and linalool-linalool molecules at various surface coverages to explain the mechanism of surface tension reduction. We solve Gibb's adsorption equation to establish a correlation between the surface coverage of linalool and the corresponding bulk concentration in experiments. We investigate the free energy profile of linalool's adsorption behavior at different surface coverages and temperatures. Our report suggests that linalool adsorption onto the water interface is an enthalpy-driven process primarily dependent on the strength of the interaction between the hydroxyl group of linalool and water molecules. These insights are crucial for selecting a suitable aroma molecule for various applications that target the vapor-phase adsorption mechanism.
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BACKGROUND: P300 amplitude reduction is reliably seen in schizophrenia. Inconsistent reports of isolated frontal and/or parietal deficits in unaffected family members may be clarified using a task that places greater load on frontal function. METHOD: Go and No-Go versions of the auditory oddball task were performed by eighteen schizophrenia patients, age-matched unaffected siblings and healthy controls matched closely to unaffected siblings on age, sex, education, socioeconomic-status, handedness and ethnicity. Groups were compared on P300 and N100 amplitude and latency. Spearman correlations were used to test the relationship between ERP amplitudes and neuropsychological measures of executive function and memory. The relationship between schizotypy--as measured using the structured interview--and ERPs was explored in a combined group of siblings and controls. RESULTS: Independent of task, patients had lower P300 than controls and reduced parietal amplitude compared to siblings. Siblings had enhanced frontocentral N100 compared to controls. No-Go P300 amplitude and N100 latency was associated with executive function measures. There were significant intraclass correlations between patients and siblings for No-Go P300 amplitude, particularly at the central midline electrode. Frontocentral N100 and P300 amplitude were positively correlated with anxiety-related aspects of schizotypy. CONCLUSION: Enhanced N100 is present in unaffected siblings. Parietal P300 is intact in unaffected siblings, but reduced in patients. The No-Go-oddball is more sensitive than the Go-oddball to executive function deficits in patients and as an index of heritability.
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Corteza Cerebral/fisiopatología , Potenciales Evocados/fisiología , Lóbulo Frontal/fisiopatología , Pruebas Neuropsicológicas/estadística & datos numéricos , Esquizofrenia/genética , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Hermanos/psicología , Adulto , Mapeo Encefálico , Análisis por Conglomerados , Electroencefalografía/estadística & datos numéricos , Potenciales Relacionados con Evento P300/genética , Potenciales Relacionados con Evento P300/fisiología , Potenciales Evocados/genética , Potenciales Evocados Auditivos/genética , Potenciales Evocados Auditivos/fisiología , Femenino , Lateralidad Funcional/fisiología , Predisposición Genética a la Enfermedad/genética , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Lóbulo Parietal/fisiopatología , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Tiempo de Reacción/genética , Tiempo de Reacción/fisiología , Esquizofrenia/diagnósticoRESUMEN
BACKGROUND: Many studies have employed voxel-based morphometry (VBM) of MRI images as an automated method of investigating cortical gray matter differences in schizophrenia. However, results from these studies vary widely, likely due to different methodological or statistical approaches. OBJECTIVE: To use VBM to investigate gray matter differences in schizophrenia in a sample significantly larger than any published to date, and to increase statistical power sufficiently to reveal differences missed in smaller analyses. METHODS: Magnetic resonance whole brain images were acquired from four geographic sites, all using the same model 1.5T scanner and software version, and combined to form a sample of 200 patients with both first episode and chronic schizophrenia and 200 healthy controls, matched for age, gender and scanner location. Gray matter concentration was assessed and compared using optimized VBM. RESULTS: Compared to healthy controls, schizophrenia patients showed significantly less gray matter concentration in multiple cortical and subcortical regions, some previously unreported. Overall, we found lower concentrations of gray matter in regions identified in prior studies, most of which reported only subsets of the affected areas. CONCLUSIONS: Gray matter differences in schizophrenia are most comprehensively elucidated using a large, diverse and representative sample.
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Encéfalo/patología , Imagen por Resonancia Magnética , Esquizofrenia/patología , Adulto , Anciano , Análisis de Varianza , Mapeo Encefálico , Estudios de Casos y Controles , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana EdadRESUMEN
Neuropsychological function-brain structure relationships may differ as a function of illness stage because of progressive brain matter loss through the course of schizophrenia. In this study, we tested whether neuropsychological function-brain structure relationships differed as a function of illness stage. In addition, we tested whether these relationships differed between older and young healthy controls. Function-structure relationships were examined in 35 first-episode patients (31 with schizophrenia, 4 with schizoaffective disorder), 54 chronic schizophrenia patients, 21 older healthy controls and 20 young healthy controls. MRI volumes of frontal and temporal lobe structures, as well as the whole brain, were estimated using a region-of-interest approach. Hierarchical multiple regression analyses were performed between the MRI and neuropsychological measures. Stronger relationships of immediate memory-total prefrontal cortex (PFC) volume in chronic than first-episode patients, and in older than young controls were observed. The abstract reasoning (WCST perseverative errors)-total temporal lobe volume relationship was stronger in older than young controls. These function-structure relationships appeared unexplained by whole brain volume or age in chronic patients. A similar dissociation between young and older subjects of both healthy and patient groups suggests that a 'bigger-is-better' relationship style is present in older individuals regardless of a diagnosis of schizophrenia.
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Encéfalo/anatomía & histología , Encéfalo/fisiopatología , Trastornos del Conocimiento/epidemiología , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/fisiopatología , Esquizofrenia/epidemiología , Esquizofrenia/fisiopatología , Adulto , Enfermedad Crónica , Trastornos del Conocimiento/diagnóstico , Demografía , Femenino , Hipocampo/anatomía & histología , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Fonética , Trastornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Índice de Severidad de la Enfermedad , Conducta VerbalRESUMEN
In this study, response inhibition and associated neural activation during a motor inhibition paradigm were investigated in (i) men with antisocial personality disorder (APD) with a history of violence (n = 14), (ii) men with schizophrenia with a history of violence (n = 12), (iii) men with schizophrenia without a history of violence (n = 12), and (iv) healthy control subjects (n = 14) using functional magnetic resonance imaging (fMRI). At the behavioural level, individuals with schizophrenia showed impaired performance across all conditions, whereas an increased error rate was seen in the APD group only during the conditions requiring inhibition. At the neural level, both violent groups showed reduced thalamic activity, compared with controls, in association with modulation of inhibition by task demands. In addition, the violent schizophrenia group, compared with controls, showed reduced activity in the caudate nucleus during the condition requiring inhibition. It is concluded that violence may not be specifically associated with impaired voluntary inhibition in schizophrenia but this is likely in APD. Reduced thalamic function, perhaps due to its known association with sensorimotor disturbances, is implicated in violent behaviour across both disorders. In addition, caudate dysfunction may contribute, given its role in timing and temporal processing as well as suppression of motor actions, to deficient inhibition and violent behaviour in schizophrenia.
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Trastorno de Personalidad Antisocial/psicología , Inhibición Psicológica , Psicología del Esquizofrénico , Violencia/psicología , Adolescente , Adulto , Análisis de Varianza , Trastorno de Personalidad Antisocial/diagnóstico por imagen , Trastorno de Personalidad Antisocial/fisiopatología , Estudios de Casos y Controles , Núcleo Caudado/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos Mentales , Persona de Mediana Edad , Neuronas , Escalas de Valoración Psiquiátrica , Radiografía , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/fisiopatología , Interfaz Usuario-ComputadorRESUMEN
Violent behavior is associated with antisocial personality disorder and to a lesser extent with schizophrenia. Neuroimaging studies have suggested that several biological systems are disturbed in schizophrenia, and structural changes in frontal and temporal lobe regions are reported in both antisocial personality disorder and schizophrenia. The neural substrates that underlie violent behavior specifically and their structural analogs, however, remain poorly understood. Nor is it known whether a common biological basis exists for aggressive, impulsive, and violent behavior across these clinical populations. To explore the correlates of violence with brain structure in antisocial personality disorder and schizophrenia, the authors used magnetic resonance imaging data to investigate for the first time, to the authors' knowledge, regional differences in cortical thickness in violent and nonviolent individuals with schizophrenia and/or antisocial personality disorder and in healthy comparison subjects. Subject groups included right-handed men closely matched for demographic variables (total number of subjects=56). Violence was associated with cortical thinning in the medial inferior frontal and lateral sensory motor cortex, particularly in the right hemisphere, and surrounding association areas (Brodmann's areas 10, 11, 12, and 32). Only violent subjects with antisocial personality disorder exhibited cortical thinning in inferior mesial frontal cortices. The biological underpinnings of violent behavior may therefore vary between these two violent subject groups in which the medial frontal cortex is compromised in antisocial personality disorder exclusively, but laminar abnormalities in sensorimotor cortices may relate to violent behavior in both antisocial personality disorder and schizophrenia.
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Trastorno de Personalidad Antisocial/patología , Trastorno de Personalidad Antisocial/psicología , Corteza Cerebral/patología , Esquizofrenia/patología , Psicología del Esquizofrénico , Violencia/psicología , Adolescente , Adulto , Trastorno de Personalidad Antisocial/diagnóstico , Atrofia/patología , Encéfalo/patología , Mapeo Encefálico/métodos , Lóbulo Frontal/patología , Lateralidad Funcional , Humanos , Imagenología Tridimensional/estadística & datos numéricos , Imagen por Resonancia Magnética/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Corteza Prefrontal/patología , Esquizofrenia/diagnósticoRESUMEN
Personality is known to influence cognitive and affective functioning as well as the risk of psychiatric disorders. Exploration of the neurobiological correlates of personality traits has the potential to enhance understanding of their significance in development of related psychopathological states. The authors examined the association between individual differences in neuroticism and brain activity in response to threat of electric shocks. Fourteen right-handed healthy men underwent functional MRI during a 5-min experiment that involved repeated presentations of two 30-s alternating conditions. In 1 of these conditions, subjects were told to expect mild but painful electric shocks; there was no possibility of receiving shocks in the other condition. The results revealed that neuroticism correlated positively with the ratings of fear of shock and negatively (indicating suppression) with brain activity from safe to shock conditions in the anterior and posterior cingulate, superior/middle temporal gyrus extending to the hippocampus, precuneus, putamen, thalamus, and middle occipital gyrus. The observations support recent psychophysiological research that has demonstrated reduced processing of pain in subjects with higher levels of neuroticism, especially the anxiety component of this trait.
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Encéfalo/fisiopatología , Miedo/psicología , Trastornos Neuróticos/patología , Trastornos Neuróticos/psicología , Adulto , Encéfalo/irrigación sanguínea , Mapeo Encefálico , Emociones , Extraversión Psicológica , Frecuencia Cardíaca/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Oxígeno/sangre , Psicofísica , Análisis de RegresiónRESUMEN
Cognitive decline seen in the normal elderly is associated with selective loss of neuronal nicotinic acetylcholine receptors (nAChRs). Nicotine given either by inhalation or transdermally helps cognition, but unacceptable side effects limit its utility. The present study assessed the safety, tolerability and effect on cognition of ispronicline, a highly selective partial agonist at the 4beta2 nAChR, in elderly subjects (n =76) with age associated memory impairment (AAMI). This double-blind, placebo-controlled cross-over study explored ascending oral doses of ispronicline in the range 50-150 mg given as a single morning dose for a period of 3 weeks. Pharmacokinetics (PK) were assessed, as well as cognitive function measured by means of the Cognitive Drug Research (CDR) computerized test battery. Ispronicline had a favourable safety profile and was well tolerated at doses below 150 mg. No effect of clinical importance was seen on biochemistry, haematology, urine analysis, vital signs, electrocardiogram (ECG) or Holter monitoring. The most frequent drug induced adverse event was light-headedness (dizziness). A beneficial effect was seen on cognition across the dose range. This was most marked at 50 mg on factors measuring attention and episodic memory. PK analysis indicated a plasma Cmax range of 5-25/35 ng/ml ispronicline was associated with the most beneficial effect. These early results demonstrate ispronicline was well tolerated and did not display the side effects typical of nicotine. Ispronicline also had a beneficial effect on cognition in subjects with AAMI. This was seen most strongly in a Cmax range that had been predicted from pre-clinical animal studies.
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Cognición/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Agonistas Nicotínicos/uso terapéutico , Piridinas/uso terapéutico , Anciano , Estudios Cruzados , Mareo/inducido químicamente , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Electrocardiografía/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agonistas Nicotínicos/efectos adversos , Agonistas Nicotínicos/farmacocinética , Piridinas/efectos adversos , Piridinas/farmacocinética , Receptores Nicotínicos/efectos de los fármacosRESUMEN
Prepulse inhibition (PPI) of the startle reflex to binaural prepulse stimuli is reliably reported to be reduced in patients with schizophrenia. Monaural acoustic prestimuli produce more inhibition of the eye blink reflex than binaural prestimuli in healthy people. The effect of monaural prestimulation on reflex inhibition in patients with schizophrenia is not known. In this study, inhibition of the acoustic startle response by monaural and binaural acoustic prestimuli was assessed in 20 antipsychotic-naïve first episode schizophrenia patients and compared with 20 age and sex-matched healthy subjects. The results revealed less PPI, especially with binaural prestimuli, in patients than healthy subjects but both groups showed more PPI with monaural than binaural prestimuli. It is concluded that first episode schizophrenia patients show deficient sensorimotor gating but they are not impaired in the mechanism underlying stronger PPI with monaural than binaural prepulses.
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Atención/fisiología , Percepción Auditiva/fisiología , Parpadeo/fisiología , Dominancia Cerebral/fisiología , Reflejo de Sobresalto/fisiología , Estimulación Acústica , Adulto , Señales (Psicología) , Pruebas de Audición Dicótica , Electromiografía , Femenino , Humanos , Masculino , Inhibición Neural/fisiología , Tiempo de Reacción/fisiología , Valores de ReferenciaRESUMEN
BACKGROUND: Neurocognitive deficits are severe in first-episode psychosis. METHODS: Patients (N = 263) with first-episode psychosis (schizophrenia, schizoaffective, or schizophreniform disorders) were randomly assigned to double-blind treatment with olanzapine (mean 11.30 mg/day) or haloperidol (mean 4.87 mg/day) for 104 weeks. A neurocognitive battery was administered at baseline (n = 246) and 12 (n = 167), 24 (n = 126), 52 (n = 89), and 104 (n = 46) weeks during treatment. Weighted principal component and unweighted composite scores were derived from individual tests. RESULTS: Both treatment groups demonstrated significant improvement on both composite scores. On the basis of the weighted composite score, olanzapine had greater improvement than haloperidol only at 12 (p = .014) and 24 (p = .029) weeks. For the unweighted composite, olanzapine had significantly better improvement compared with haloperidol only at week 12 (p = .044). At week 12 only, olanzapine improved performance on the Digit Symbol and Continuous Performance Test significantly more than haloperidol. CONCLUSIONS: Both antipsychotic agents appeared to improve neurocognitive functioning among first-episode psychosis patients with schizophrenia. A significantly greater benefit in terms of neurocognitive improvement was found with olanzapine than with haloperidol at weeks 12 and 24.
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Antipsicóticos/administración & dosificación , Trastornos del Conocimiento/diagnóstico , Haloperidol/administración & dosificación , Trastornos Psicóticos/tratamiento farmacológico , Adulto , Antipsicóticos/efectos adversos , Benzodiazepinas/administración & dosificación , Benzodiazepinas/efectos adversos , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/prevención & control , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Estudios de Seguimiento , Haloperidol/efectos adversos , Humanos , Masculino , Pruebas Neuropsicológicas , Olanzapina , Análisis de Componente Principal , Trastornos Psicóticos/psicología , Estadísticas no ParamétricasRESUMEN
RATIONALE: Schizophrenia patients display an excessive rate of smoking compared to the general population. Nicotine increases acoustic prepulse inhibition (PPI) in animals as well as healthy humans, suggesting that smoking may provide a way of restoring deficient sensorimotor gating in schizophrenia. No previous study has examined the neural mechanisms of the effect of nicotine on PPI in humans. OBJECTIVES: To investigate whether nicotine enhances tactile PPI in healthy subjects and patients with schizophrenia employing a double-blind, placebo-controlled, cross-over design and, if so, what are the neural correlates of nicotine-induced modulation of PPI. MATERIALS AND METHODS: In experiment 1, 12 healthy smokers, 12 healthy non-smokers and nine smoking schizophrenia patients underwent testing for tactile PPI on two occasions, 14 days apart, once after receiving (subcutaneously) 12 microg/kg body weight of nicotine and once after receiving saline (placebo). In experiment 2, six healthy subjects and five schizophrenia patients of the original sample (all male smokers) underwent functional magnetic resonance imaging (fMRI) under the same drug conditions and the same tactile PPI paradigm as in experiment 1. RESULTS: Nicotine enhanced PPI in both groups. A comparison of patterns of brain activation on nicotine vs placebo conditions showed increased activation of limbic regions and striatum in both groups after nicotine administration. Subsequent correlational analyses demonstrated that the PPI-enhancing effect of nicotine was related to increased hippocampal activity in both groups. CONCLUSIONS: Nicotine enhances tactile PPI in both healthy and schizophrenia groups. Our preliminary fMRI findings reveal that this effect is modulated by increased limbic activity.
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Atención/efectos de los fármacos , Encéfalo/efectos de los fármacos , Aumento de la Imagen , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Nicotina/administración & dosificación , Oxígeno/sangre , Reflejo de Sobresalto/efectos de los fármacos , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Fumar/fisiopatología , Tabaquismo/fisiopatología , Tacto/efectos de los fármacos , Adulto , Nivel de Alerta/efectos de los fármacos , Nivel de Alerta/fisiología , Atención/fisiología , Encéfalo/fisiopatología , Estudios Cruzados , Método Doble Ciego , Sinergismo Farmacológico , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Inhibición Neural/efectos de los fármacos , Inhibición Neural/fisiología , Nicotina/efectos adversos , Reflejo de Sobresalto/fisiología , Fumar/psicología , Tabaquismo/psicología , Tacto/fisiologíaRESUMEN
Cognitive impairment has the greatest impact on illness outcome in schizophrenia. The most significant challenge in schizophrenia therapeutics, thus, is to develop an efficacious treatment for cognitive impairments. Acetylcholinesterase inhibitors, such as Physostigmine and Rivastigmine, are considered effective treatments for cognitive decline in Alzheimer's Disease, where the loss of cholinergic neurons is thought to be responsible for various cognitive deficits. The current study investigated the cognitive effects of Rivastigmine given as an add-on therapy to antipsychotic-treated schizophrenia patients in a placebo-controlled double-blind design. The study initially involved 40 patients, of which 21 patients (11 assigned to Rivastigmine and 10 assigned to placebo) agreed to continued participation, remained on the study drug, and underwent assessment of executive functioning, verbal skills, verbal and spatial working memory, attention and psychomotor speed on three occasions: (i) at baseline, and then (ii) after 12 weeks and (iii) 24 weeks of treatment with placebo or Rivastigmine. The results failed to reveal significant improvement on any cognitive measure with Rivastigmine treatment, compared with the placebo treatment. Some cognitive variables showed significant practice effects in both the placebo and Rivastigmine groups. No effects were noted in symptoms or side effects ratings. The beneficial cognitive effects of Rivastigmine seen in an open-label preliminary study are not substantiated by this study. Future studies should investigate the effects of other procholinergic drugs, such as Galantamine, which also act on the nicotine receptors and may produce stronger cognitive effects in schizophrenia.
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Antipsicóticos/uso terapéutico , Inhibidores de la Colinesterasa/uso terapéutico , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/epidemiología , Fenilcarbamatos/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/epidemiología , Adulto , Inhibidores de la Colinesterasa/farmacología , Trastornos del Conocimiento/diagnóstico , Método Doble Ciego , Femenino , Estimulantes Ganglionares/farmacología , Estimulantes Ganglionares/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Nicotina/farmacología , Nicotina/uso terapéutico , Fenilcarbamatos/farmacología , Fisostigmina/farmacología , Fisostigmina/uso terapéutico , Desempeño Psicomotor/efectos de los fármacos , Rivastigmina , Índice de Severidad de la Enfermedad , Conducta Verbal/efectos de los fármacosRESUMEN
Contemporary theories and evidence implicate frontal lobe dysfunction in violent behaviour as well as in schizophrenia. We applied functional magnetic resonance imaging (fMRI) to investigate and compare brain activation during an 'n-back' working memory task in groups of men with (i) schizophrenia and a history of serious physical violence (VS; n=13), (ii) schizophrenia without a history of violence (NVS: n=12), (iii) antisocial personality disorder (APD) and a history of serious physical violence (n=10), and (iv) no history of violence or a mental disorder (n=13). We observed comparable performance in all four groups during the control (0-back) condition. Subtle working memory deficits were seen in the NVS and APD groups but severe deficits emerged in the VS group relative to the healthy group. The VS group showed activation deficit bilaterally in the frontal lobe and precuneus when compared to the healthy group, and in the right inferior parietal region when compared to the NVS group during the working memory load condition. Frontal (bilateral) as well as right inferior parietal activity was negatively associated with the ratings of violence across all schizophrenia patients, with the right parietal region showing this association most strongly. APD patients, relative to healthy subjects, showed activation deficit in the left frontal gyrus, anterior cingulate and precuneus. It is concluded that reduced functional response in the frontal and inferior parietal regions leads to serious violence in schizophrenia perhaps via impaired executive functioning.
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Encéfalo/fisiopatología , Imagen por Resonancia Magnética , Esquizofrenia/epidemiología , Esquizofrenia/fisiopatología , Violencia/psicología , Violencia/estadística & datos numéricos , Trastorno de Personalidad Antisocial/diagnóstico , Trastorno de Personalidad Antisocial/epidemiología , Estudios Transversales , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Lóbulo Frontal/fisiopatología , Lateralidad Funcional/fisiología , Humanos , Masculino , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/epidemiología , Lóbulo Parietal/fisiopatología , Prevalencia , Esquizofrenia/diagnóstico , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Many patients recovering from a first psychotic episode will discontinue medication against medical advice, even before a 1-year treatment course is completed. Factors associated with treatment adherence in patients with chronic schizophrenia include beliefs about severity of illness and need for treatment, treatment with typical versus atypical antipsychotic and medication side effects. METHOD: In this 2-year prospective study of 254 patients recovering from a first episode of schizophrenia, schizophreniform, or schizoaffective disorder we examined the relationship between antipsychotic medication non-adherence and patient beliefs about: need for treatment, antipsychotic medication benefits, and negative aspects of antipsychotic medication treatment. We also examined the relationship between medication non-adherence and treatment with either haloperidol or olanzapine, and objective measures of symptom response and side effects. RESULTS: The likelihood of becoming medication non-adherent for 1 week or longer was greater in subjects whose belief in need for treatment was less (HR=1.75, 95% CI 1.16, 2.65, p=0.0077) or who believed medications were of low benefit (HR=2.88, 95 CI 1.79-4.65, p<0.0001). Subjects randomized to haloperidol were more likely to become medication non-adherent for >or=1 week than subjects randomized to olanzapine (HR-1.51, 95% CI 1.01, 2.27, p=0.045). CONCLUSION: Beliefs about need for treatment and the benefits of antipsychotic medication may be intervention targets to improve likelihood of long-term medication adherence in patients recovering from a first episode of schizophrenia, schizoaffective, or schizophreniform disorder.
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Antipsicóticos/uso terapéutico , Haloperidol/uso terapéutico , Cooperación del Paciente , Esquizofrenia/tratamiento farmacológico , Adulto , Antipsicóticos/efectos adversos , Actitud Frente a la Salud , Benzodiazepinas/efectos adversos , Benzodiazepinas/uso terapéutico , Enfermedad Crónica , Método Doble Ciego , Femenino , Haloperidol/efectos adversos , Humanos , Masculino , Modelos Psicológicos , Olanzapina , Cooperación del Paciente/psicología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Psicología del EsquizofrénicoRESUMEN
While the changes in the volume of the temporal lobe and its sub-regions over the course of illness have been studied in patients with schizophrenia, few studies have examined changes in the frontal lobe between the first episode and the chronic stage. In this study, we focussed on the effect of illness stage and duration of illness on the volume of frontal lobe regions, though we also examined several other regions to establish the specificity of any effects, if observed, in this region. We compared the volumes of brain regions among 34 first-episode schizophrenia patients, 49 chronic schizophrenia patients, 18 healthy controls matched, on average, to the first-episode patients and 21 healthy controls matched, on average, to the chronic patients. Logarithmic regression analyses examined the relationships between the duration of illness and the brain regional volumes in the patient group. The results showed that chronic patients had smaller prefrontal cortical grey matter volumes, but larger premotor cortical and putamen volumes compared to first-episode patients and matched healthy controls. Although there were significant patient-by-control group interactions in the cerebellum and sensori-motor cortical grey matter volumes, these did not survive correction for multiple comparisons. There was a significant exponential relation between the duration of illness and the volumes of prefrontal cortex, parieto-occipital cortex grey matter, thalamus and putamen, suggesting that these regions are susceptible to change as the disorder persists. The enlargement of the premotor cortex and putamen are likely to be a result of antipsychotic medication.
Asunto(s)
Lóbulo Frontal/patología , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Esquizofrenia/diagnóstico , Adulto , Encéfalo/patología , Enfermedad Crónica , Dominancia Cerebral/fisiología , Femenino , Humanos , Masculino , Valores de ReferenciaRESUMEN
Brain abnormalities are found in association with antisocial personality disorder and schizophrenia, the two mental disorders most implicated in violent behaviour. Structural magnetic resonance imaging was used to investigate the whole brain, cerebellum, temporal lobe, lateral ventricles, caudate nucleus, putamen, thalamus, hippocampus, amygdala and the prefrontal, pre-motor, sensorimotor, occipito-parietal regions in 13 men with antisocial personality disorder, 13 men with schizophrenia and a history of violence, 15 men with schizophrenia without violent history and 15 healthy non-violent men. Compared to controls, the antisocial personality disorder group displayed reductions in whole brain volume and temporal lobe as well as increases in putamen volume. Both schizophrenia groups regardless of violence history exhibited increased lateral ventricle volume, while the schizophrenia group with violent history showed further abnormalities including reduced whole brain and hippocampal volumes and increased putamen size. The findings suggest that individuals with antisocial personality disorder as well as those with schizophrenia and a history of violence have common neural abnormalities, but also show neuro-anatomical differences. The processes by which they came to apparently common ground may, however, differ. The finding of temporal lobe reductions prevalent among those with antisocial personality disorder and hippocampal reduction in the violent men with schizophrenia contributes support for the importance of this region in mediating violent behaviour.
Asunto(s)
Trastorno de Personalidad Antisocial/patología , Esquizofrenia/patología , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Humanos , Pruebas de Inteligencia/estadística & datos numéricos , Imagen por Resonancia Magnética/métodos , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricos , Escalas de Valoración Psiquiátrica/estadística & datos numéricosRESUMEN
Symptoms are known to account for a small variance in some cognitive functions in schizophrenia, but the influence of self-perceived mood remains largely unknown. The authors examined the influence of subjective mood states, psychopathology, and depressive symptoms in cognitive performance in a single investigation in schizophrenia. A group of 40 stable medicated patients with schizophrenia (20 men, 20 women) and 30 healthy comparison subjects (15 men, 15 women) were assessed on neurocognitive measures of verbal abilities, attention, executive functioning, language, memory, motor functioning, and information processing. All subjects provided self-ratings of mood prior to cognitive testing. Patients were also rated on psychopathology and depressive symptoms. Patients performed worse than comparison subjects on most cognitive domains. Within the patient group, subjective feelings of depression-dejection, fatigue-inertia, confusion, and tension-anxiety predicted (controlling for symptoms) poor performance on measures of attention, executive function, and verbal memory. In the same group of patients, clinician-rated symptoms of psychopathology and depression predicted significantly poor performance only on tests of motor function. In comparison subjects, vigor related to better, and fatigue and inertia to worse, spatial motor performance. Self-perceived negative mood state may be a better predictor of cognitive deficits than clinician-rated symptoms in chronic schizophrenia patients.
Asunto(s)
Afecto , Trastornos del Conocimiento/diagnóstico , Pruebas Neuropsicológicas/estadística & datos numéricos , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Autoimagen , Adulto , Ansiedad/diagnóstico , Ansiedad/psicología , Trastornos del Conocimiento/psicología , Depresión/diagnóstico , Depresión/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Psicometría , PsicopatologíaRESUMEN
BACKGROUND: Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described. Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome. This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia. OBJECTIVE: To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patients and that gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition. DESIGN: Longitudinal, randomized, controlled, multisite, double-blind study. Patients treated and followed up for up to 104 weeks. Neurocognitive and magnetic resonance imaging (MRI) assessments performed at weeks 0 (baseline), 12, 24, 52, and 104. Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI, psychopathologic, and neurocognitive outcomes. SETTING: Fourteen academic medical centers (United States, 11; Canada, 1; Netherlands, 1; England, 1). PARTICIPANTS: Patients with first-episode psychosis (DSM-IV) and healthy volunteers. INTERVENTIONS: Random allocation to a conventional antipsychotic, haloperidol (2-20 mg/d), or an atypical antipsychotic, olanzapine (5-20 mg/d). MAIN OUTCOME MEASURES: Brain volume changes assessed by MRI. RESULTS: Of 263 randomized patients, 161 had baseline and at least 1 postbaseline MRI evaluation. Haloperidol-treated patients exhibited significant decreases in gray matter volume, whereas olanzapine-treated patients did not. A matched sample of healthy volunteers (n = 58) examined contemporaneously showed no change in gray matter volume. CONCLUSIONS: Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes. Haloperidol was associated with significant reductions in gray matter volume, whereas olanzapine was not. Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated. The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine.
Asunto(s)
Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Encéfalo/anatomía & histología , Encéfalo/efectos de los fármacos , Esquizofrenia/tratamiento farmacológico , Adulto , Benzodiazepinas/farmacología , Benzodiazepinas/uso terapéutico , Núcleo Caudado/anatomía & histología , Núcleo Caudado/efectos de los fármacos , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/psicología , Femenino , Haloperidol/farmacología , Haloperidol/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Olanzapina , Escalas de Valoración Psiquiátrica , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Resultado del TratamientoRESUMEN
Neurocognitive impairment in schizophrenia is well established, though sex differences on cognitive tasks have produced equivocal findings. The present study was designed to examine performance of schizophrenia patients on a sexually dimorphic cognitive battery. The cognitive battery comprising tests of spatial (mental rotation, computerized version of the Benton Judgment of Line Orientation) and verbal abilities (phonological and semantic fluency) was administered to men (n = 22) and women (n = 21) with schizophrenia and healthy controls (n = 21 men and 21 women). A series of multivariate analyses showed that the patient group performed worse than controls on all the cognitive tasks. Cognitive sexual dimorphism on all spatial tasks favoring men and verbal tasks favoring women remained. Within the patient sample, correlational data demonstrated that earlier age at onset of illness related to poorer spatial performance. It is concluded that normal sexual dimorphism is undisturbed on both spatial and verbal tasks by the schizophrenia disease process.