RESUMO
OBJECTIVES: Melancholic depression is a type of depression which is closely related to biological variables than are other types of depression. Its clinical features can be assessed using six items on the Hamilton Depression Rating Scale (HAM-D6 ). Previous studies have shown, using item response theory, that the symptom depressed mood is the least severe melancholic feature; work and activities, somatic symptoms and psychic anxiety are of moderate severity; and feelings of guilt and psychomotor retardation are the most severe. We aimed to evaluate whether the more severe melancholic signs or symptoms were associated with decreases in brain-derived neurotrophic factor (BDNF) levels. METHODS: A total of 151 severely depressed inpatients had their BDNF levels analyzed by comparing those who presented with each HAM-D6 melancholic feature to those for whom the HAM-D6 feature was absent, using multiple linear regressions. The levels of BDNF of patients who presented with each melancholic feature were also compared with those of 100 healthy controls. RESULTS: Depressed patients' median BDNF level was 44.06 ng/mL (interquartile range [IQR]: 33.99-62.4 ng/mL), and controls' median BDNF level was 65.22 ng/mL (IQR: 49.87-76.08 ng/mL) (P < .001). The presence of depressed mood, work and activities, somatic symptoms, psychic anxiety, and guilty feelings was not associated with BDNF levels. However, the presence of psychomotor retardation was associated with reduced BDNF (median reduction -10.07 ng/mL; 95% confidence interval [CI]: -19.43 to -0.71; P = .03). CONCLUSIONS: To the best of our knowledge, this study is the first to associate BDNF levels with melancholic features in a sample of severely depressed inpatients. The main finding of this study was that severely depressed inpatients who presented the most severe melancholic feature, psychomotor retardation, had significantly reduced BDNF levels in the blood.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Transtorno Depressivo Maior/sangue , Transtornos Psicomotores/sangue , Adulto , Ansiedade/sangue , Ansiedade/fisiopatologia , Transtorno Bipolar/sangue , Transtorno Bipolar/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicomotores/fisiopatologiaRESUMO
BACKGROUND: Health effects of pesticides are easily diagnosed when acute poisonings occurs, nevertheless, consequences from chronic exposure can only be observed when neuropsychiatric, neurodegenerative or oncologic pathologies appear. Therefore, early monitoring of this type of exposure is especially relevant to avoid the consequences of pathologies previously described; especially concerning workers exposed to pesticides on the job. For acute organophosphate pesticides (OPP) exposure, two biomarkers have been validated: plasma cholinesterase (ChE) and acetylcholinesterase (AChE) from erythrocytes. These enzymes become inhibited when people are exposed to high doses of organophosphate pesticides, along with clear signs and symptoms of acute poisoning; therefore, they do not serve to identify risk from chronic exposure. This study aims to assess a novel biomarker that could reflect neuropsychological deterioration associated with long-term exposure to organophosphate pesticides via the enzyme acylpeptide-hydrolase (ACPH), which has been recently identified as a direct target of action for some organophosphate compounds. METHODS/DESIGN: Three population groups were recruited during three years (2011-2013): Group I having no exposure to pesticides, which included people living in Chilean coastal areas far from farms (external control); Group II included those individuals living within the rural and farming area (internal control) but not occupationally exposed to pesticides; and Group III living in rural areas, employed in agricultural labour and having had direct contact with pesticides for more than five years. Blood samples to assess biomarkers were taken and neuropsychological evaluations carried out seasonally; in three time frames for the occupationally exposed group (before, during and after fumigation period); in two time frames for internal control group (before and during fumigation), and only once for the external controls. Neuropsychological evaluations considered cognitive functions, affectivity and psychomotor activity. The biomarkers measured included ChE, AChE and ACPH. Statistical analysis and mathematical modelling used both laboratory results and neuropsychological testing outcomes in order to assess whether ACPH would be acceptable as biomarker for chronic exposure to OPP. DISCUSSION: This study protocol has been implemented successfully during the time frames mentioned above for seasons 2011, 2012 and 2013-2014.
Assuntos
Exposição Ambiental/análise , Doenças do Sistema Nervoso/etiologia , Compostos Organofosforados/toxicidade , Peptídeo Hidrolases/sangue , Praguicidas/intoxicação , População Rural , Acetilcolinesterase/sangue , Agricultura , Biomarcadores , Chile/epidemiologia , Colinesterases/sangue , Transtornos Cognitivos/sangue , Transtornos Cognitivos/etiologia , Humanos , Masculino , Doenças do Sistema Nervoso/sangue , Exposição Ocupacional/análise , Transtornos Psicomotores/sangue , Transtornos Psicomotores/etiologia , Projetos de Pesquisa , Fatores de RiscoRESUMO
Long-term exposure to low levels of organophosphate pesticides (OP) may produce neuropsychiatric symptoms. We performed clinical, neuropsychiatric, and laboratory evaluations of 37 workers involved in family agriculture of tobacco from southern Brazil who had been exposed to OP for 3 months, and in 25 of these workers, after 3 months without exposure to OP. Plasma acetylcholinesterase activity levels of all subjects were within the normal range (3.2 to 9.0 U/l) and were not different between on- and off-exposure periods (4.7 +/- 0.9 and 4.5 +/- 1.1 U/l, respectively). Clinically significant extrapyramidal symptoms were present in 12 of 25 subjects, which is unexpected in such a population. There was a significant reduction of extrapyramidal symptoms after 3 months without exposure to OP, but 10 subjects still had significant parkinsonism. Mini-mental and word span scores were within the expected range for this population and were not influenced by exposure to OP. Eighteen of the 37 subjects (48%) had current psychiatric diagnoses in the first interview (13 with generalized anxiety disorder and 8 with major depression). Among the 25 subjects who completed both evaluations, the total number of current psychiatric diagnoses, after 3 months without using OP, dropped from 24 to 13 and the number of affected individuals with any psychiatric diagnosis dropped from 11 to 7. In conclusion, this study reinforces the need for parameters other than acetylcholinesterase activity to monitor for chronic consequences of chronic low-dose OP exposure, and it suggests that subjects have not only transient motor and psychiatric consequences while exposed, but may also develop enduring extrapyramidal symptoms.
Assuntos
Doenças dos Trabalhadores Agrícolas/etiologia , Transtornos Cognitivos/etiologia , Inseticidas/efeitos adversos , Exposição Ocupacional , Compostos Organofosforados , Transtornos Psicomotores/etiologia , Acetilcolinesterase/sangue , Adulto , Doenças dos Trabalhadores Agrícolas/sangue , Doenças dos Trabalhadores Agrícolas/epidemiologia , Brasil/epidemiologia , Transtornos Cognitivos/sangue , Transtornos Cognitivos/epidemiologia , Estudos Epidemiológicos , Feminino , Humanos , Masculino , Transtornos Psicomotores/sangue , Transtornos Psicomotores/epidemiologiaRESUMO
The molecular nature of the glycine cleavage system was investigated in eight patients with typical (neonatal) and two patients with atypical (late onset) nonketotic hyperglycinemia (NKH). The overall activity of the glycine cleavage system was found to be decreased in all of the liver and brain tissue studied, but it was undetectable or extremely low in typical NKH, whereas there was some residual activity in atypical NKH. Six patients with typical NKH had a specific defect in the P protein, and one a defect in the T protein; the activity of the T protein was defective in one patient with atypical NKH.