RESUMO
Gamma-hydroxybutyrate acid (GHB) is a recreational drug with a high addictive potential. Severe side effects such as GHB-induced coma are common and linked to increased emergency room attendances. Task-based functional-imaging studies have revealed an association between the regular use of GHB and multiple GHB-induced comas, and altered neurocognitive function. However the effects of multiple GHB-induced comas and regular GHB-use on intrinsic brain connectivity during rest remain unknown. The study population consisted of 23 GHB-users with ≥4 GHB-induced comas (GHB-Coma), 22 GHB-users who never experienced a GHB-induced coma (GHB-NoComa) and 24 polydrug users who never used GHB (No-GHB). Resting-state scans were collected to assess resting-state functional-connectivity within and between the default mode network (DMN), the bilateral central executive network (CEN) and the salience network (SN). The GHB-NoComa group showed decreased rsFC of the right CEN with a region in the anterior cingulate cortex (pFWE = 0.048) and decreased rsFC between the right CEN and the DMN (pFWE = 0.048) when compared with the No-GHB group. These results suggest that regular GHB-use is associated with decreased rsFC within the right CEN and between the right CEN and the DMN. The presence of multiple GHB-induced comas is not associated with (additional) alterations in rsFC.
Assuntos
Anestésicos Intravenosos/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiopatologia , Coma/induzido quimicamente , Conectoma , Rede Nervosa/efeitos dos fármacos , Oxibato de Sódio/farmacologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adulto , Anestésicos Intravenosos/efeitos adversos , Córtex Cerebral/diagnóstico por imagem , Estudos Transversais , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Oxibato de Sódio/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Gamma-hydroxybutyric acid (GHB) is a drug of abuse associated with increased emergency room attendances, due to GHB-induced comas. Withdrawal from GHB often increases social anxiety and is linked to alterations in emotion processing. However, little is known about the effects of GHB-use and GHB-induced comas on affect regulation in humans. OBJECTIVES: We aimed to assess the effect of GHB-use and GHB-induced comas on the affective network. METHOD: We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without a GHB-induced coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants completed self-report questionnaires assessing negative affect (depression, anxiety and stress) and performed an emotional face matching task during functional magnetic resonance imaging to probe activity of the amygdala and the hippocampus. RESULTS: The GHB-Coma group reported higher levels of depression, anxiety, and stress; showed decreased activity of the hippocampus; and increased functional connectivity of the left hippocampus with the left fusiform gyrus and a cluster on the left temporal-parietal-occipital junction, when compared with the 2 other groups. The GHB-NoComa group showed decreased functional connectivity of the left hippocampus with the amygdala in comparison with the No-GHB group. CONCLUSIONS: GHB-use but in particular GHB-induced comas, are associated with altered emotion identification and hippocampal functioning. Awareness campaigns are required to raise consciousness about the adverse effects of GHB-induced comas on affect regulation, despite the absence of subjective side effects.
Assuntos
Sintomas Afetivos , Coma/etiologia , Emoções , Hidroxibutiratos/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adulto , Hipocampo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Países Baixos , Autorrelato , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIMS: The regular use of gamma-hydroxybutyrate acid (GHB) can induce GHB-induced comas. Other substance use disorders are associated with alterations in brain structure and impulsivity. Here we aim to investigate if these are also modulated by either regular GHB use or GHB-induced comas. METHODS: In a sample of human males, structural and diffusion neuroimaging data were collected for 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without GHB-induced comas (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). The structural brain parameters were analyzed macroscopically using voxel-based morphometry and microscopically using tract-based spatial statistics (TBSS) and tractography. Impulsivity was assessed with the Barrat Impulsivity Scale. RESULTS: In comparison to the other two groups, the GHB-Coma group showed a higher fractional anisotropy in the body of the corpus callosum and a lower mean diffusivity in the forceps minor (i.e., whole-brain TBSS analysis). No macrostructural differences nor microstructural differences, as assessed with tractography, were observed. The GHB-Coma group also reported higher impulsivity, which was more strongly associated with white matter volume and fractional anisotropy in tracts involved in impulse control (post-hoc analysis). GHB use per se was associated neither with differences in brain structure nor with impulsivity. CONCLUSIONS: The results suggest that multiple GHB-induced comas, but not GHB use per se, are associated with microstructural alterations in white matter and with higher self-reported impulsivity, which in turn was associated with white matter tracts involved in impulse control.
RESUMO
BACKGROUND: Gamma-hydroxybutyric acid (GHB) is a recreational drug associated with increasing numbers of GHB-dependent patients and emergency attendances often related to GHB-induced comas. Working memory (WM) deficits have been reported in association with GHB use, and animal studies have shown that GHB induces oxidative stress in vulnerable WM-related brain areas such as the dorsolateral prefrontal cortex (DLPFC). However, the effects of chronic GHB use and multiple GHB-induced comas on WM-related brain function in humans remains unknown. METHODS: We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users who never experienced GHB-induced coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants performed an n-back WM task during functional magnetic resonance imaging (fMRI) to probe DLPFC functioning. RESULTS: The GHB-Coma group had lower premorbid IQ (pâ¯=â¯.006) than the GHB-NoComa group despite comparable age and education level. There were also group differences in the use of other drugs than GHB. Therefore, all group comparisons were adjusted for IQ and drug use other than GHB. Compared with the GHB-NoComa and the No-GHB groups, the GHB-Coma group showed increased activity in the right DLPFC (pSVCâ¯=â¯0.028) and increased functional connectivity of the right DLPFC with a cluster comprising the left anterior cingulate and medial frontal gyrus (pFWEâ¯=â¯0.003). No significant fMRI differences were observed between the GHB-NoComa and No-GHB groups. Due to technical problems, no behavioural data were collected. DISCUSSION: These results suggest that multiple GHB-induced comas, but not GHB-use per se, are associated with alterations in WM-related brain function. Public awareness campaigns are required to minimize the potential adverse effects induced by GHB recreational use, and especially GHB-induced comas, even if no immediate side effects are experienced.
Assuntos
Coma/diagnóstico por imagem , Hidroxibutiratos/efeitos adversos , Transtornos da Memória/diagnóstico por imagem , Memória de Curto Prazo/efeitos dos fármacos , Córtex Pré-Frontal/diagnóstico por imagem , Adolescente , Adulto , Mapeamento Encefálico/métodos , Coma/induzido quimicamente , Coma/fisiopatologia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos da Memória/fisiopatologia , Testes Neuropsicológicos , Córtex Pré-Frontal/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Gamma-Hydroxybutyric acid (GHB) is a drug of abuse associated with increasing numbers of GHB-dependent patients and emergency attendances often related to GHB-induced coma. Animal studies suggest that GHB induces oxidative stress in the hippocampus, resulting in memory impairments. However, the consequences of chronic GHB use and GHB-induced coma on human brain function and cognition are unknown. METHODS: We recruited 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without a coma (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). Participants completed verbal and spatial memory tests and an associative memory encoding task during functional magnetic resonance imaging (fMRI) to probe hippocampus functioning. RESULTS: The GHB-Coma group showed a lower premorbid IQ (pâ¯=â¯0.006) and performed worse on the verbal memory test (pâ¯=â¯0.017) compared to the GHB-NoComa group, despite exhibiting similar levels of education. Compared with the other two groups, the GHB-Coma group showed lower left hippocampus (pSVCâ¯=â¯0.044) and left lingual gyrus (pFWEâ¯=â¯0.017) activity, and a trend for lower hippocampal functional connectivity with the left superior temporal cortex during performance of the associative memory encoding task (pFWEâ¯=â¯0.063). No significant differences were observed between the GHB-NoComa group and the No-GHB group. CONCLUSIONS: These results suggest that multiple GHB-induced comas, but not the use of GHB per se, are associated with alterations of memory performance and memory-related brain, although no causal link can be inferred from this cross-sectional study. The results highlight the need for public awareness to minimize the negative health consequences of recreational GHB use, in particular when related with GHB-induced comas.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Coma/induzido quimicamente , Coma/diagnóstico por imagem , Hidroxibutiratos/efeitos adversos , Memória de Longo Prazo/efeitos dos fármacos , Adolescente , Adulto , Animais , Estudos Transversais , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/efeitos dos fármacos , Humanos , Drogas Ilícitas/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/diagnóstico por imagem , Memória de Longo Prazo/fisiologia , Adulto JovemRESUMO
The red flags raised by the 1990 clinical reports of increased suicidality associated with treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine were followed by anecdotal reports of similar symptoms with other antidepressants of the same class. Recent discussions by Healy have argued in favour of a suicidogenic potential of the SSRIs. This paper reviews the relevant literature addressing the epidemiological data of Western populations and the data accumulated from clinical trial databases in several countries. The evidence currently available does not support the hypothesis that antidepressants or, more specifically, SSRIs cause increased suicidality in patients with depression, nor do they appear to do so in patients treated with these drugs for other reasons.