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1.
Psychol Med ; 53(5): 2050-2059, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35441587

RESUMO

BACKGROUND: Progressive brain structural MRI changes are described in schizophrenia and have been ascribed to both illness progression and antipsychotic treatment. We investigated treatment effects, in terms of total cumulative antipsychotic dose, efficacy and tolerability, on brain structural changes over the first 24 months of treatment in schizophrenia. METHODS: A prospective, 24-month, single-site cohort study in 99 minimally treated patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder, and 98 matched healthy controls. We treated the patients according to a fixed protocol with flupenthixol decanoate, a long-acting injectable antipsychotic. We assessed psychopathology, cognition, extrapyramidal symptoms and BMI, and acquired MRI scans at months 0, 12 and 24. We selected global cortical thickness, white matter volume and basal ganglia volume as the regions of interest. RESULTS: The only significant group × time interaction was for basal ganglia volumes. However, patients, but not controls, displayed cortical thickness reductions and increases in white matter and basal ganglia volumes. Cortical thickness reductions were unrelated to treatment. White matter volume increases were associated with lower cumulative antipsychotic dose, greater improvements in psychopathology and cognition, and more extrapyramidal symptoms. Basal ganglia volume increases were associated with greater improvements in psychopathology, greater increases in BMI and more extrapyramidal symptoms. CONCLUSIONS: We provide evidence for plasticity in white matter and basal ganglia associated with antipsychotic treatment in schizophrenia, most likely linked to the dopamine blocking actions of these agents. Cortical changes may be more closely related to the neurodevelopmental, non-dopaminergic aspects of the illness.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Estudos de Coortes , Estudos Prospectivos , Encéfalo/patologia , Imageamento por Ressonância Magnética
2.
J Neurosci Res ; 100(7): 1452-1462, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35434795

RESUMO

The association between childhood trauma exposure and risk of developing psychopathology may in part be mediated by the effects of chronic stress on dopaminergic neurotransmission. However, little is known about the differential effects of distinct trauma types on reward processing, particularly in adults without concurrent medical or psychiatric disorders. We examined the association of childhood trauma exposure, including the differential effects of abuse and neglect, with reward processing in healthy adults (n = 114). Functional magnetic resonance imaging during a monetary incentive delay task was used to assess neural activity in the ventral striatum and orbitofrontal cortex in relation to reward anticipation and reward outcome, respectively. Exposure to childhood trauma, including abuse and neglect, was assessed using the Childhood Trauma Questionnaire-Short Form. We found a significant effect for abuse on ventral striatal activation during reward anticipation, adjusting for age, sex, scanner site, educational level, and household monthly income. There were no effects for abuse or neglect, independently or combined, on orbitofrontal cortex activation during reward outcome. Our findings suggest differential effects of childhood abuse on ventral striatum activation during reward anticipation in healthy adults.


Assuntos
Experiências Adversas da Infância , Estriado Ventral , Adulto , Criança , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Motivação , Recompensa , Estriado Ventral/diagnóstico por imagem
3.
Schizophr Bull ; 49(4): 1067-1077, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37043772

RESUMO

BACKGROUND AND HYPOTHESIS: Two machine learning derived neuroanatomical signatures were recently described. Signature 1 is associated with widespread grey matter volume reductions and signature 2 with larger basal ganglia and internal capsule volumes. We hypothesized that they represent the neurodevelopmental and treatment-responsive components of schizophrenia respectively. STUDY DESIGN: We assessed the expression strength trajectories of these signatures and evaluated their relationships with indicators of neurodevelopmental compromise and with antipsychotic treatment effects in 83 previously minimally treated individuals with a first episode of a schizophrenia spectrum disorder who received standardized treatment and underwent comprehensive clinical, cognitive and neuroimaging assessments over 24 months. Ninety-six matched healthy case-controls were included. STUDY RESULTS: Linear mixed effect repeated measures models indicated that the patients had stronger expression of signature 1 than controls that remained stable over time and was not related to treatment. Stronger signature 1 expression showed trend associations with lower educational attainment, poorer sensory integration, and worse cognitive performance for working memory, verbal learning and reasoning and problem solving. The most striking finding was that signature 2 expression was similar for patients and controls at baseline but increased significantly with treatment in the patients. Greater increase in signature 2 expression was associated with larger reductions in PANSS total score and increases in BMI and not associated with neurodevelopmental indices. CONCLUSIONS: These findings provide supporting evidence for two distinct neuroanatomical signatures representing the neurodevelopmental and treatment-responsive components of schizophrenia.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/efeitos adversos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Esquizofrenia/complicações , Substância Cinzenta , Córtex Cerebral , Neuroimagem , Imageamento por Ressonância Magnética
4.
Schizophr Res ; 243: 17-23, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35228035

RESUMO

BACKGROUND: Recent studies suggest a two-factor structure for negative symptoms as assessed by the Positive and Negative Syndrome Scale (PANSS) in schizophrenia, namely experiential and expressive subdomains. Little is known about their clinical correlates and treatment trajectories. OBJECTIVES: We sought to replicate the two factor-analysis derived subdomains for PANSS negative symptoms in schizophrenia and to assess their independent demographic, premorbid and treatment-related characteristics. METHODS: This was a longitudinal study of 106 minimally treated participants with a first episode of a schizophrenia spectrum disorder who received treatment with flupenthixol decanoate 2-weekly injections over two years. Factor analysis was used to characterize the PANSS negative symptom subdomains and linear mixed-effect models for continuous repeated measures were constructed to assess the temporal relations between the negative symptom subdomains and premorbid and treatment related variables. RESULTS: Factor analysis confirmed a two-factor solution for experiential and expressive subdomains of negative symptoms, although they were strongly correlated. The treatment response trajectories for the two subdomains did not differ significantly, and neither subdomain was significantly associated with our premorbid variables. We found significant main effects for disorganised symptoms and extrapyramidal symptoms on the expressive subdomain, and for disorganised symptoms and depressive symptoms on the experiential subdomain. Post-hoc testing indicated that reductions in HDL-cholesterol levels were associated with less improvement in both expressive and experiential subdomain scores. CONCLUSION: The two negative symptom subdomains are closely related, have similar premorbid correlates and respond similarly to antipsychotic treatment. Depression affects the experiential subdomain, whereas extrapyramidal symptoms affect the expressive subdomain.


Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Humanos , Estudos Longitudinais , Escalas de Graduação Psiquiátrica , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico
5.
Schizophr Res ; 243: 70-77, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35245704

RESUMO

BACKGROUND: It has been proposed that sex and gender differences described in schizophrenia can be explained from a neurodevelopmental perspective. AIM: In this study, we examined the associations of biological sex and gender role endorsement with putative indicators of neurodevelopmental compromise. METHODS: We used the Bem Sex Role Inventory to calculate masculinity scores in 77 patients with a first episode of a schizophrenia spectrum disorder, and selected the following indicators of neurodevelopmental compromise: family history of schizophrenia, obstetric complications, premorbid functioning, neurological soft signs, and cognitive function. Secondary objectives included the moderating effects of age of onset of illness, substance use and negative symptoms on these associations. RESULTS: There were no significant sex differences across any of the indicators of neurodevelopmental compromise. However, lower masculinity scores correlated significantly with poorer premorbid adjustment, sensory integration deficits and worse overall cognitive performance. Stepwise linear regression identified poorer premorbid adjustment in early adolescence and lower verbal learning scores as independent predictors of lower masculinity scores. In contrast to sex, gender showed several associations with indicators of neurodevelopmental compromise. CONCLUSIONS: Lower masculinity scores may represent part of a phenotype for a neurodevelopmental anomaly that places some individuals on a pathway to schizophrenia.


Assuntos
Esquizofrenia , Feminino , Humanos , Masculino , Gravidez , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico , Fatores Sexuais
6.
Schizophr Res ; 250: 196-202, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36436499

RESUMO

OBJECTIVE: Both cognitive impairment and alterations in white matter tissue microstructure are well recognised in schizophrenia. We investigated whether differences in white matter microstructure underpin cognitive impairments in patients with first-episode schizophrenia spectrum disorders when controlling for multiple confounding factors. METHODS: We employed a cross-sectional study design and compared fractional anisotropy (FA) between individuals diagnosed with first- episode schizophrenia spectrum disorders (FES) (n = 68) and matched healthy controls (n = 120). We conducted multiple analyses of covariance (ANCOVAs) to compare the mean FA values for patients and controls across 27 white matter tracts. We conducted exploratory correlation analyses to determine if white matter tract differences were associated with global cognitive impairment as well as deficits across seven cognitive domains. RESULTS: We found widespread reductions in FA in patients compared to controls, after controlling for confounding variables, such as age, biological sex, education, substances, and childhood adversities. We found a significant positive correlation between the attention/vigilance domain and the splenium of the corpus collosum and external capsule after correction for multiple comparisons. In the control group we found no significant correlations between FA and cognition. CONCLUSION: Our findings provide a neurobiological basis for attentional cognitive deficits in schizophrenia, highlighting a potential role for the splenium of the corpus collosum and external capsule.


Assuntos
Esquizofrenia , Substância Branca , Humanos , Criança , Substância Branca/diagnóstico por imagem , Esquizofrenia/complicações , Esquizofrenia/diagnóstico por imagem , Estudos Transversais , Anisotropia , Cognição , Encéfalo
7.
Psychiatry Res ; 298: 113767, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33545422

RESUMO

Depressive symptoms are common in schizophrenia and have been associated with both favourable and unfavourable outcomes. We studied the longitudinal course of depressive symptoms and explored their temporal relationships with other manifestations of the illness and its treatment. This longitudinal cohort study included 126 antipsychotic naïve or only briefly treated patients with first-episode schizophrenia spectrum disorders treated with a long-acting antipsychotic over 24 months. Depressive symptoms were assessed at three monthly intervals using the Calgary Depression Scale for Schizophrenia and changes over time were assessed using linear mixed-effect models for continuous repeated measures. Depressive symptoms were most prominent at baseline with highly significant reductions during the first three months of treatment and maintenance of improvement thereafter. Most improvement occurred with antipsychotic treatment alone, with few patients requiring additional antidepressants. We also found that depressive symptoms were associated with positive symptoms, better insight and poorer quality of life, but not with negative symptoms, extrapyramidal symptoms, substance use or cumulative antipsychotic dose.There were few differences between patients who met criteria for depression during the acute phase of treatment and those in the post-acute phase.


Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Depressão/etiologia , Humanos , Estudos Longitudinais , Qualidade de Vida , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico
9.
Psychiatry Res ; 161(3): 284-91, 2008 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-18962989

RESUMO

Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), are increasingly being used by psychiatric patients. Most studies have concentrated on efficacy aspects, while little is known about their safety and tolerability in psychiatric populations. This study aimed to assess the effects of EPA treatment on body mass, glucose metabolism, lipid profiles, prolactin secretion, bleeding time, haematology and liver functions. Eighty-four subjects with schizophrenia were treated with either EPA 2 g/day or placebo in addition to their antipsychotic medication for 12 weeks, in a randomized, controlled trial. Forty-seven entered a 40-week open-label extension phase of EPA 2 g/day. Seventy-four patients were included in the analysis. Six patients discontinued from the EPA group and 14 in the placebo group. Adverse event reporting was similar for the two groups. While there were no significant between-group differences, in the blinded phase the EPA group showed a significant increase in body mass index (BMI) and bleeding time. In the open-label extension, there was again a modest increase in BMI. Total cholesterol and HDL levels were significantly decreased. EPA 2 g/day is generally well tolerated. Clinicians should be aware of possible increases in bleeding time, as well as changes in weight and lipid metabolism.


Assuntos
Ácido Eicosapentaenoico/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Ácido Eicosapentaenoico/efeitos adversos , Ácidos Graxos Ômega-3/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Esquizofrenia/diagnóstico
11.
J Clin Psychiatry ; 65(5): 696-701, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15163258

RESUMO

BACKGROUND: While the atypical antipsychotics should ultimately reduce the prevalence of tardive dyskinesia, it is likely to remain a significant clinical problem for a long time to come. No strategy has clearly emerged as the treatment of choice for tardive dyskinesia. Atypical antipsychotics have reduced propensities for producing acute extrapyramidal symptoms (EPS) and possibly tardive dyskinesia and may be effective in treating patients with established tardive dyskinesia. METHOD: This 12-month, randomized, investigator-blinded study compared the efficacy of quetiapine (N = 22) and haloperidol (N = 23) in treating patients with DSM-IV schizophrenia or schizoaffective disorder and established tardive dyskinesia. Dyskinesia was assessed using the Extrapyramidal Symptom Rating Scale (ESRS) dyskinesia subscale scores and the Clinical Global Impression (CGI) dyskinesia scores. Other EPS, weight, serum prolactin level, and glycosylated hemoglobin level were also assessed. Subjects were enrolled in the study between April 2000 and March 2002. RESULTS: Mean endpoint doses were 400 mg/day of quetiapine and 8.5 mg/day of haloperidol. Compared with the haloperidol group, the quetiapine group showed significantly greater improvements in ESRS dyskinesia (6 and 9 months [p or= 50% symptom reduction) was greater with quetiapine than haloperidol (64% [9/14] and 37% [6/16] at 6 months; 55% [6/11] and 28% [4/14] at 12 months). Other EPS decreased significantly with quetiapine at 3 (p =.01), 6 (p =.01), and 9 (p =.002) months. Serum prolactin levels decreased with quetiapine but increased with haloperidol, differing significantly between the groups at endpoint (p =.005). No significant changes in weight or glucose metabolism were recorded in either group. CONCLUSION: Quetiapine effectively reduces the severity of tardive dyskinesia and is well tolerated in patients with established tardive dyskinesia.


Assuntos
Antipsicóticos/uso terapêutico , Dibenzotiazepinas/uso terapêutico , Discinesia Induzida por Medicamentos/tratamento farmacológico , Haloperidol/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Dibenzotiazepinas/administração & dosagem , Esquema de Medicação , Discinesia Induzida por Medicamentos/etiologia , Discinesia Induzida por Medicamentos/prevenção & controle , Feminino , Haloperidol/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/psicologia , Fumarato de Quetiapina , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Índice de Gravidade de Doença , Método Simples-Cego , Resultado do Tratamento
12.
Int J Neuropsychopharmacol ; 8(2): 175-82, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15737251

RESUMO

The topic of antipsychotic-induced weight-gain and its relationship to glucose metabolism is under-studied. We evaluated the long-term effects of a new-generation antipsychotic, quetiapine and a conventional antipsychotic, haloperidol on body mass index (BMI) and glycaemic control in patients with schizophrenia previously treated with conventional antipsychotics. Forty-five clinically stable patients with schizophrenia participated in this randomized, investigator-blinded, parallel-group comparison of flexible doses of quetiapine and haloperidol treatment over 52 wk. Primary outcome measures were change from baseline in BMI and glycosylated haemoglobin (HBA1c) levels. There were no between-group differences at any of the time-points for BMI (F = 1.90, p = 0.1) and HBA1c (F = 1.17, p = 0.3) values, and there were no significant changes in BMI from baseline for either group. HBA1c levels decreased significantly at end-point for the haloperidol group (-1.5%, p = 0.04), but not for the quetiapine group (-0.3%, p = 0.5). Although the sample was not generally obese (mean baseline BMI 25.5 +/- 6.3 kg/m2), a large proportion exhibited evidence of abnormal glycaemic control prior to randomization (mean HBA1c 6.7 +/- 1.9%), with 48% having values that were at least mildly elevated (HBA1c > 6.1%) and 19% markedly elevated (HBA1c > 7%). The number of subjects with elevated HBA1c values decreased from baseline in both the haloperidol and quetiapine treatment groups. These findings suggest that switching treatment from a conventional antipsychotic to quetiapine is not associated with weight gain or worsening of glycaemic control, even in the long term. The study also highlights the high incidence of unrecognized glucose dysregulation in patients with schizophrenia receiving conventional antipsychotic treatment.


Assuntos
Antipsicóticos/farmacologia , Índice de Massa Corporal , Dibenzotiazepinas/farmacologia , Índice Glicêmico/efeitos dos fármacos , Haloperidol/farmacologia , Adolescente , Adulto , Idoso , Análise de Variância , Antipsicóticos/uso terapêutico , Dibenzotiazepinas/uso terapêutico , Método Duplo-Cego , Feminino , Hemoglobinas Glicadas/metabolismo , Haloperidol/uso terapêutico , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fumarato de Quetiapina , Esquizofrenia/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento
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