RESUMO
It is now widely accepted that there is a growing discrepancy between demand and access to adequate treatment for behavioral or mental health conditions in the United States. This results in immense personal, societal, and economic costs. One rapidly growing method of addressing this discrepancy is to integrate mental health services into the primary care setting, which has become the de facto service provider for these conditions. In this paper, we describe the development and implementation of a novel integrated care program in a large mid-western university-based healthcare system, drawn from the collaborative care model, and describe the benefits in terms of both health care utilization and depression outcomes. Limitations and proposed future directions are discussed.
Assuntos
Depressão , Reforma dos Serviços de Saúde , Serviços de Saúde Mental , Atenção Primária à Saúde , Humanos , Masculino , Feminino , Adulto , Serviços de Saúde Mental/organização & administração , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/organização & administração , Resultado do Tratamento , Depressão/diagnóstico , Depressão/psicologia , Depressão/terapia , Acessibilidade aos Serviços de Saúde , Reforma dos Serviços de Saúde/métodos , Reforma dos Serviços de Saúde/organização & administração , Inquéritos Epidemiológicos , Comorbidade , Pacientes Ambulatoriais , Serviço Hospitalar de Emergência , Aceitação pelo Paciente de Cuidados de Saúde , Meio-Oeste dos Estados UnidosRESUMO
ABSTRACT: Social distancing policies enacted during the COVID-19 pandemic altered our social interactions. People with schizophrenia, who already exhibit social deficits, may have been disproportionally impacted. In this pilot study, we a) compared prepandemic social functioning to functioning during the pandemic in people with schizophrenia ( n = 21) who had data at both time points; and b) examined if patterns of decline in schizophrenia differed from healthy controls ( n = 21) across a series of repeated-measures analyses of variance. We observed larger declines in social functioning in schizophrenia (η 2 = 0.07, medium effect size) during the pandemic compared with the control group. Between-group declines did not extend to other domains, suggesting that declines are specific to social functioning. Our findings signal that treatments focusing on reconnecting people with schizophrenia to their social networks should be prioritized. Future studies should continue tracking social functioning after the pandemic to illustrate patterns of recovery.
Assuntos
COVID-19 , Esquizofrenia , Humanos , Esquizofrenia/epidemiologia , Pandemias , Interação Social , Projetos PilotoRESUMO
Impairments in metacognition or the ability to form integrated senses of self and others have been linked to deficits in laboratory-based measures of social functioning in schizophrenia. This study examined whether self-reported social functioning was related to metacognition in 88 adults in a nonacute phase of schizophrenia. Concurrent assessments were made of metacognition with the Metacognition Assessment Scale-Abbreviated, social functioning with the Social Functioning Scale, symptoms with the Positive and Negative Syndrome Scale, and neurocognition with the Wisconsin Card Sorting Task. Univariate correlations revealed that self-reported social functioning was related to metacognition. Symptom severity was linked to interpersonal relationships, and overall metacognition was found to significantly moderate that relationship such that the effects of symptoms on function grew less as metacognitive capacity was stronger, independent of the effects of neurocognition. This may suggest the potential of metacognitive interventions to titrate the negative effects of symptoms on social function.
Assuntos
Relações Interpessoais , Metacognição , Psicologia do Esquizofrênico , Ajustamento Social , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Testes Psicológicos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Esquizofrenia/diagnóstico , Teste de Classificação de Cartas de WisconsinRESUMO
Despite historically pessimistic views from both the professional community and lay public, research is emerging that recovery from psychosis is possible. Recovery has evolved to include not only a reduction in symptoms and return to functioning, but a sense of agency and connection to meaningful roles in life. The development of a more comprehensive conceptualization of recovery has particular importance in the treatment of first-episode psychosis, because early intervention may avoid some of the prolonged dysfunction that may make recovery difficult. As the mental health field moves to intervene early in the course of psychosis and to support recovery for individuals with severe mental illness, it is essential to develop and assess interventions that may promote a more comprehensive recovery. This case illustration offers an account of a type of integrative psychotherapy that may assist individuals in achieving recovery: metacognitive reflection and insight therapy (MERIT).
Assuntos
Metacognição , Psicoterapia , Transtornos Psicóticos/terapia , Esquizofrenia/terapia , Adulto , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: Emerging integrative metacognitive therapies for schizophrenia seek to promote subjective aspects of recovery. Beyond symptom remission, they are concerned with shared meaning-making and intersubjective processes. It is unclear, however, how such therapies should understand and respond to psychotic content that threatens meaning-making in therapeutic contexts. Accordingly, we sought to understand what factors precede and potentially trigger psychotic content within psychotherapy and what aids in resolution and return to meaning-making. METHOD: Forty-eight transcripts from a single psychotherapy case were analyzed with thematic analysis. Passages of delusional or disorganized content were identified and themes present prior to the emergence and resolution of such material were identified and coded. RESULTS: Themes that preceded the emergence of psychotic content varied across early, middle, and late phases of therapy. Material related to the patient's experience of inadequacy and potential vulnerability, therapist setting boundaries within the therapeutic relationship and making challenges appeared to trigger psychotic content, especially early in treatment. CONCLUSIONS: Psychotic content may emerge in session following identifiable antecedents which change over phases of therapy. Attending to psychotic content by assuming a non-hierarchical stance and not dismissing psychotic content may aid in maintaining intersubjectivity and support patient's movements toward recovery in integrative metacognitive therapies.
Assuntos
Psicoterapia/métodos , Esquizofrenia/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa QualitativaRESUMO
BACKGROUND: Anger experience and expression are a common issue in those experiencing PTSD. However, it remains unclear what variables affect anger and its expression in PTSD. AIMS: To explore the relationships of synthetic forms of metacognition and metacognitive beliefs with anger experience and expression in PTSD, independent of the effects hyperarousal and depression symptoms. METHOD: Participants were 51 veterans with diagnosed with PTSD. Metacognition was assessed using the Metacognition Assessment Scale-Abbreviated (MAS-A) and the Metacognitions Questionnaire (MCQ). Depression, PTSD symptom severity, and seven domains of anger expression were also assessed. RESULTS: Correlations showed after controlling for overall levels of hyperarousal, higher MAS-A total scores were related to lower levels of State Anger, Feeling Angry, Expressing Anger Physically, and Anger Expression in. Lower MCQ scores were related to lower State anger, Expressing anger verbally, and Expressing anger physically. Higher levels of depression were related to higher levels of Trait anger, Expressing anger physically, Anger expression out, and Anger expression in. Multiple regressions suggested that the MAS-A and MCQ predicted unique portions of the variance in anger experience and expression. CONCLUSIONS: Metacognitive deficits may affect anger experience and expression in those with PTSD and may be an important treatment target.
Assuntos
Ira , Metacognição , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Nível de Alerta , Depressão/complicações , Feminino , Humanos , Masculino , Transtornos de Estresse Pós-Traumáticos/complicações , VeteranosRESUMO
BACKGROUND/AIMS: The onset response to a single tone as measured by electroencephalography (EEG) is diminished in power and synchrony in schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80 Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr) system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced similar deficits to tone stimuli in rats. METHODS: Experiment 1 tested the effect of a PCP dose (1.0, 2.5, and 4.5 mg/kg) on response to single tones on intracranial EEG recorded over the auditory cortex in rats. Experiment 2 evaluated the effect of PCP after acute administration of saline or PCP (5 mg/kg), after continuous subchronic administration of saline or PCP (5 mg/kg/day), and after a week of drug cessation. In both experiments, a time-frequency analysis quantified mean power (MP) and phase locking factor (PLF) between 1 and 80 Hz. Event-related potentials (ERPs) were also measured to tones, and EEG spectral power in the absence of auditory stimuli. RESULTS: Acute PCP increased PLF and MP between 10 and 30 Hz, while decreasing MP and PLF between approximately 50 and 70 Hz. Acute PCP produced a dose-dependent broad-band increase in EEG power that extended into gamma range frequencies. There were no consistent effects of subchronic administration on gamma range activity. Acute PCP increased ERP amplitudes for the P16 and N70 components. CONCLUSIONS: Findings suggest that acute PCP-induced NMDAr hypofunction has differential effects on neural power and synchrony which vary with dose, time course of administration and EEG frequency. EEG synchrony and power appear to be sensitive translational biomarkers for disrupted NMDAr function, which may contribute to the pathophysiology of schizophrenia and other neuropsychiatric disorders.
Assuntos
Córtex Auditivo/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Fenciclidina/farmacologia , Estimulação Acústica , Animais , Relação Dose-Resposta a Droga , Eletroencefalografia , Masculino , Psicoacústica , Ratos , Ratos Sprague-Dawley , Análise Espectral , Fatores de TempoRESUMO
OBJECTIVE: Poor functioning has long been observed in individuals with psychosis. Recent studies have identified metacognition - one's ability to form complex ideas about oneself and others and to use that information to respond to psychological and social challenges-as being an important determinant of functioning. However, the exact process by which deficits in metacognition lead to impaired functioning remains unclear. This study first examined whether low intrinsic motivation, or the tendency to pursue novel experiences and to engage in self-improvement, mediates the relationship between deficits in metacognition and impaired functioning. We then examined whether intrinsic motivation significantly mediated the relationship when controlling for age, education, symptoms, executive functioning, and social cognition. DESIGN: Mediation models were examined in a cross-sectional data set. METHODS: One hundred and seventy-five individuals with a psychotic disorder completed interview-based measures of metacognition, intrinsic motivation, symptoms, and functioning and performance-based measures of executive functioning and social cognition. RESULTS: Analyses revealed that intrinsic motivation mediated the relationship between metacognition deficits and impaired functioning (95% CI of indirect effect [0.12-0.43]), even after controlling for the aforesaid variables (95% CI of indirect effect [0.04-0.29]). CONCLUSIONS: Results suggest that intrinsic motivation may be a mechanism that underlies the link between deficits in metacognition and impaired functioning and indicate that metacognition and intrinsic motivation may be important treatment targets to improve functioning in individuals with psychosis. PRACTITIONER POINTS: The findings of this study suggest that deficits in metacognition may indirectly lead to impaired functioning through their effect on intrinsic motivation in individuals with psychosis. Psychological treatments that target deficits in both metacognition and intrinsic motivation may help to alleviate impaired functioning in individuals with psychosis. LIMITATIONS: The cross-sectional design of this study is a limitation, and additional longitudinal studies are needed to confirm the direction of the findings and rule out rival hypotheses. Generalization of the findings may be limited by the sample composition. It may be that different relationships exist between metacognition, intrinsic motivation, and functioning in those with early psychosis or among those in an acute phase or who decline treatment.
Assuntos
Função Executiva , Metacognição , Motivação , Transtornos Psicóticos/psicologia , Comportamento Social , Adulto , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Percepção SocialRESUMO
Impaired insight is common in the first episode of psychosis (FEP). Although considerable research has examined the factors that are associated with impaired insight in chronic psychosis, less is known about the factors that underlie and sustain poor insight in FEP. Impaired metacognition, or the ability to form integrated representations of self and others, is a promising potential contributor to poor insight in FEP. To explore this possibility, the authors assessed insight and metacognition in 40 individuals with FEP and then examined the relationship between these areas and social cognition domains, neurocognitive domains, and psychotic symptoms. Correlation analyses revealed that improved insight was associated with higher metacognition, better vocabulary and Theory of Mind scores, and fewer symptoms. The domain of metacognitive mastery also predicted clinical insight. Results support the need to develop an integrative therapeutic approach focused on improving metacognition, hence addressing poor insight in FEP.
Assuntos
Conscientização , Função Executiva , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Autoimagem , Teoria da Mente , Adolescente , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Prognóstico , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicometria , Transtornos Psicóticos/terapia , Esquizofrenia/terapia , Estatística como Assunto , Adulto JovemRESUMO
Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis.
Assuntos
Metacognição , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Adolescente , Adulto , Corpo Estriado/fisiopatologia , Feminino , Substância Cinzenta/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/fisiopatologia , Transtornos Psicóticos/diagnóstico , Esquizofrenia/diagnósticoRESUMO
Schizophrenia often involves a loss of metacognitive capacity, the ability to form complex and integrated representations of self and others. Independent of symptoms and neurocognition, deficits in synthetic metacognition are related to difficulties of engaging in goal-directed activities in social and vocational settings. Within this backdrop, we provide a case report of the effects of Metacognitive Reflective Insight Therapy (MERIT) that assisted a patient suffering from first episode schizophrenia during 2 years of individual psychotherapy. A total of 8 elements of MERIT that stimulate and promote metacognitive capacity are presented. As illustrated in this report, these procedures helped the patient move from a state in which he had virtually no complex ideas about himself or others to one in which he had developed integrated and realistic ideas about his own identity and the identity of others. He then could use these representations to understand and effectively respond to life challenges.
Assuntos
Conscientização/fisiologia , Psicoterapia/métodos , Transtornos Psicóticos/terapia , Esquizofrenia/terapia , Teoria da Mente/fisiologia , Adulto , Humanos , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
Deficits in intrinsic motivation (IM) have been linked to poorer outcome in schizophrenia, but its proximal mechanisms remain poorly understood. This study examined whether metacognitive mastery, or the capacity to use knowledge of self, others, and context to identify and cope with psychological difficulties, predicted levels of IM for 6 months among 75 participants with prolonged schizophrenia. Repeated-measures analysis of variance revealed that high metacognitive mastery predicted consistently higher levels of IM; however, intermediate and low mastery did not produce unique IM profiles. The findings suggest that metacognitive mastery may have an important role in IM over time and could be a meaningful treatment target.
Assuntos
Adaptação Psicológica , Transtornos Cognitivos/psicologia , Cognição , Motivação , Transtornos Psicóticos/psicologia , Esquizofrenia , Psicologia do Esquizofrênico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação PsiquiátricaRESUMO
Clinical High Risk for psychosis (CHR) refers to a phase of heightened risk for developing overt psychosis. CHR often emerges during adolescence or early adulthood. CHR has been identified as a group to target for intervention, with the hope that early intervention can both stave off prolonged suffering and intervene before mental health challenges become part of an individual's identity. However, there are few treatment modalities that can address some of the specific needs of CHR. Metacognitive Reflection and Insight Therapy (MERIT) is an integrative psychotherapy that can be applied to the CHR population. MERIT offers unique advantages to working with the CHR population as it aims to improve self-direction and recovery through stimulation of metacognitive capacity, a phenomenon that has been associated with recovery. This paper explores unique aspects of the CHR population and how MERIT can address barriers to recovery for individuals experiencing psychosis-like symptoms. Several case examples and a clinical vignette using MERIT to support patients with CHR are offered to exemplify this approach. MERIT offers a way to assist persons with CHR to address barriers to their personal recovery and to develop nuanced understandings of ways to master challenges.
RESUMO
Social anhedonia is a hallmark symptom of schizophrenia. Discrepancies in anticipated versus consummatory pleasure for non-social stimuli are well-documented. Thus, a similar emotional paradox may underlie social anhedonia. If so, our understanding of social anhedonia-including how to treat it in schizophrenia-could be enhanced. This project used a 5-day experience sampling method (ESM) to measure discrepancies between anticipated and consummatory pleasure for real-world social activities in people with schizophrenia and healthy controls (n = 30/group). ESM results were compared to laboratory assessments of negative symptoms and neurocognition. The schizophrenia group exhibited similar levels of anticipated and consummatory social pleasure as controls throughout daily life, and both groups were accurate in their short-term predictions of pleasure. Clinical interviews revealed those with schizophrenia showed significant deficits in long-term social pleasure prediction (i.e., a 1-week timeframe). Thus, people with schizophrenia may exhibit differences in ability to predict pleasure in the short-term versus the long-term. Negative symptoms and neurocognition were related to anticipated, but not consummatory, social pleasure, suggesting anhedonia is driven by deficits in thinking about pleasure, rather than inability to experience pleasure. Clinical implications include focusing on building upon short-term ability to predict pleasure in therapy to increase social motivation in schizophrenia.
RESUMO
OBJECTIVE: The prevalence of mental health conditions in pediatric patients in the United States is approximately 15%. Concerningly, nearly half go untreated, with lower treatment rates among children of color. Collaborative care can increase access to care and has an emerging evidence base for pediatrics. We present retrospective results from a collaborative care program that accepted referrals for a variety of conditions. METHODS: Pediatric patients seen in an academic, urban collaborative care program from July 2019 to December 2021 were tracked in a registry. Demographics, presenting problem(s), symptoms, treatment, and discharge dispositions were examined. Descriptive data were analyzed, including changes in reported symptoms via paired t-tests. RESULTS: Three hundred nineteen patients were seen. Racial and ethnic diversity in our clinic's population was similar to that of the surrounding community, with half belonging to a minoritized racial or ethnic group. Symptom comparisons demonstrated clinically and statistically significant improvements from intake to discharge. CONCLUSION: Collaborative care can improve access to care and outcomes for a diverse pediatric population. Our clinic served racial and ethnic patient populations that were representative of the demographics of the metropolitan area. Further study is necessary to determine if collaborative care increases access for these underserved groups.
RESUMO
Electrophysiological methods have demonstrated disturbances of neural synchrony and oscillations in schizophrenia which affect a broad range of sensory and cognitive processes. These disturbances may account for a loss of neural integration and effective connectivity in the disorder. The mechanisms responsible for alterations in synchrony are not well delineated, but may reflect disturbed interactions within GABAergic and glutamatergic circuits, particularly in the gamma range. Auditory steady-state responses (ASSRs) provide a non-invasive technique used to assess neural synchrony in schizophrenia and in animal models at specific response frequencies. ASSRs are electrophysiological responses entrained to the frequency and phase of a periodic auditory stimulus generated by auditory pathway and auditory cortex activity. Patients with schizophrenia show reduced ASSR power and phase locking to gamma range stimulation. We review alterations of ASSRs in schizophrenia, schizotypal personality disorder, and first-degree relatives of patients with schizophrenia. In vitro and in vivo approaches have been used to test cellular mechanisms for this pattern of findings. This translational, cross-species approach provides support for the role of N-methyl-D-aspartate and GABAergic dysregulation in the genesis of perturbed ASSRs in schizophrenia and persons at risk.
Assuntos
Biomarcadores , Potenciais Evocados Auditivos/fisiologia , Esquizofrenia/fisiopatologia , Estimulação Acústica , Animais , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Vias Auditivas/efeitos dos fármacos , Vias Auditivas/fisiopatologia , Modelos Animais de Doenças , Eletroencefalografia , Potenciais Evocados Auditivos/efeitos dos fármacos , Análise de Fourier , Humanos , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Esquizofrenia/tratamento farmacológico , Fatores de TempoRESUMO
AIM: Individuals experiencing early phase psychosis (EPP) are at increased risk for legal involvement. In prior studies, between 14% and 75% of individuals with EPP reported a history of criminal offending behaviour, criminal charges, or criminal convictions. To better understand the frequency of criminal conviction in a specialty treatment clinic serving EPP clients, the research team supplemented self-reported data from the clinic intake with information from publicly available databases. METHODS: In this sample of 309 adults, approximately one quarter of patients (n = 76) self-reported a history of arrest, incarceration, probation, or parole within 6 months of enrolment in a treatment clinic. The research team expanded upon this and collected data from a public database of court proceedings in Indiana for all clinic participants before and after enrolment. RESULTS: Thirty-nine percent (n = 122) had three or more traffic tickets or a conviction for an ordinance violation, misdemeanour, or felony in the state of Indiana as an adult. This is over two times the national average. Drug and alcohol related convictions were the most common single conviction type, and 29% (n = 89) of subjects experienced at least one incarceration. CONCLUSIONS: These data highlight the need for specialty clinics to partner with professionals with expertise in the prevention and management of criminal behaviour. Future studies should examine risk factors for individuals experiencing EPP and criminal conviction.
RESUMO
INTRODUCTION: Poor insight, or unawareness of morbid changes in cognition, emotional states, or behavior, is commonly observed among people with schizophrenia. Poor insight represents a persistent barrier to wellness because it interferes with treatment and self-direction. Paradoxically, good insight may also be a barrier to health when awareness of these changes leads to depression or self-stigma. AREAS COVERED: This paper builds upon this previous work by exploring these issues in schizophrenia separately as they have appeared in published research over the last three years in three different kinds of insight: clinical, cognition, and introspective accuracy. Specifically, studies are reviewed that address: the adverse effects of poor insight, the paradoxical effects of good insight, correlates with other forms of cognition, and emerging treatments. EXPERT OPINION: The evidence continues to offer a nuanced picture of the complex effects of good insight in schizophrenia. Incremental improvements were also found in the development of novel integrative treatment approaches. This work also highlights the intricacy of the concept of insight, the need for further exploration of the effects of culture, and conceptual work that distinguishes the points of convergence and divergence of these forms of insight.
PLAIN LANGUAGE SUMMARYMany people diagnosed with schizophrenia are unaware that they have a mental illness. This is referred to as having poor clinical insight. People struggle to form ideas about themselves or doubt what they think. This is referred to as having poor cognitive insight. Finally, many people diagnosed with schizophrenia may significantly overestimate their abilities. This is referred to as having poor introspective accuracy. This review shares research that shows that problems with these kinds of self-awareness can make it difficult for those with schizophrenia to manage their lives and the challenges of having a mental illness. At the same time, these problems with awareness may also protect people with schizophrenia from feeling depressed and at odds with the world. We discuss how these forms of unawareness result from many different factors and how new treatments may help individuals develop awareness without being vulnerable to significant emotional pain.
Assuntos
Transtornos Cognitivos , Esquizofrenia , Conscientização , Cognição , Transtornos Cognitivos/etiologia , Humanos , Esquizofrenia/complicações , Esquizofrenia/terapia , Psicologia do EsquizofrênicoRESUMO
Several lines of evidence have implicated white matter (WM) deficits in schizophrenia, including microstructural alterations from diffusion tensor (DTI) brain imaging studies. It has been proposed that dysregulated inflammatory processes, including heightened activity of circulating lymphocytes, may contribute to WM pathology in this illness. Fingolimod is a sphingosine-1-phosphate (S1P) receptor agonist that is approved for the treatment of relapsing multiple sclerosis (MS). Fingolimod robustly decreases the number of circulating lymphocytes through sequestration of these cells in lymph tissue. In addition, this agent improved WM microstructure as shown by increases in DTI fractional anisotropy (FA). In this pilot study, we assessed the effects of fingolimod on WM microstructure, cognition and symptoms in an eight-week, double-blind trial. Forty subjects with schizophrenia or schizoaffective disorder were randomized 1:1 to fingolimod (0.5 mg/day) and placebo. Fingolimod caused significant reductions in circulating lymphocytes (p < .001). In addition, there was a statistically non-significant association (p = .089) between DTI-FA change in the WM skeleton and fingolimod. There were significant relationships between the degree of lymphocyte reductions and increases in FA in the corpus collosum (p = .004) and right superior longitudinal fasciculus ( p = .02), and a non-significant correlation with the WM skeleton. There were no significant fingolimod versus placebo interactions on cognitive or symptom measures. There were no serious adverse events related to fingolimod treatment. Future studies with larger samples and treatment durations are needed to further establish fingolimod's potential therapeutic effects in schizophrenia.
Assuntos
Esquizofrenia , Substância Branca , Anisotropia , Encéfalo/diagnóstico por imagem , Cognição , Imagem de Tensor de Difusão , Cloridrato de Fingolimode/uso terapêutico , Humanos , Lisofosfolipídeos , Imageamento por Ressonância Magnética , Projetos Piloto , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Esfingosina/análogos & derivados , Substância Branca/diagnóstico por imagemRESUMO
Auditory steady-state auditory responses (ASSRs), in which the evoked potential entrains to stimulus frequency and phase, are reduced in magnitude in patients with schizophrenia, particularly at 40 Hz. While the neural mechanisms responsible for ASSR generation and its perturbation in schizophrenia are unknown, it has been hypothesized that the GABAA receptor subtype may have an important role. Using an established rat model of schizophrenia, the neonatal ventral hippocampal lesion (NVHL) model, 40-Hz ASSRs were elicited from NVHL and sham rats to determine if NVHL rats show deficits comparable to schizophrenia, and to examine the role of GABAA receptors in ASSR generation. ASSR parameters were found to be stable across time in both NVHL and sham rats. Manipulation of the GABAA receptor by muscimol, a GABAA agonist, yielded a strong lesion x drug interaction, with ASSR magnitude and synchronization decreased in NVHL and increased in sham rats. The lesion x muscimol interaction was blocked by a GABAA receptor antagonist when given prior to muscimol administration, confirming the observed interaction was GABAA mediated. Together, these data suggest an alteration involving GABAA receptor function, and hence inhibitory transmission, in the neuronal networks responsible for ASSR generation in NVHL rats. These findings are consistent with prior evidence for alterations in GABA neurotransmitter systems in the NVHL model and suggest the utility of this animal modelling approach for exploring neurobiological mechanisms that generate or modulate ASSRs.