TBARS and BDNF levels in newborns exposed to crack/cocaine during pregnancy: a comparative study

Objectives: To compare levels of a marker of lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and brain-derived neurotrophic factor (BDNF) in umbilical cord blood (UCB) between newborns exposed to crack/cocaine in utero (exposed newborns [EN], n=57) and non-exposed newborns (NEN, n=99), as well as in maternal peripheral blood at delivery. Methods: This was a cross-sectional study. Potential confounders, including perinatal parameters, psychopathology, and use of other substances, were assessed. Results: After adjusting for potential confounders, adjusted mean BDNF was significantly higher in EN (3.86 ng/mL, 95% confidence interval [95%CI] 2.29-5.43) than in NEN (0.85 ng/mL, 95%CI 0.47-1.23; p < 0.001; Cohen effect size: 1.12), and significantly lower in crack/cocaine mothers than in control mothers (4.03 ng/mL, 95%CI 2.87-5.18 vs. 6.67 ng/mL, 95%CI 5.60-7.74; p = 0.006). The adjusted mean TBARS level was significantly lower in EN (63.97 µM MDA, 95%CI 39.43-88.50) than NEN (177.04 µM MDA, 95%CI 140.93-213.14; p < 0.001; effect size = 0.84), with no difference between mother groups (p = 0.86). Conclusions: The changes in TBARS levels observed in EN suggest that fetuses exposed to cocaine mobilize endogenous antioxidant routes since very early stages of development. The increase in BDNF levels in EN might indicate changes in fetal development, whereas the changes in BDNF levels in mothers provide evidence of the complex metabolic processes involved in drug use during pregnancy.

Serum concentrations of brain-derived neurotrophic factor and mental disorders in imprisoned women

Objective: Mental disorders and early trauma are highly prevalent in female inmates. Brain-derived neurotrophic factor (BDNF) plays an important role in learning, memory processes, and mood regulation. The aim of this study was to evaluate the relationship between serum BDNF levels and mental disorders among imprisoned women as compared with age- and education-matched controls. Methods: A consecutively recruited sample of 18 female prisoners with mental disorders was assessed for sociodemographic, criminal, and clinical variables using standardized instruments, the Mini International Neuropsychiatric Interview Plus (MINI Plus), and serum BDNF levels. Results: High rates of childhood sexual abuse and posttraumatic stress disorder (PTSD) were found in the group of forensic patients. Serum BDNF levels in the forensic group did not differ from those of healthy controls, and were significantly higher when compared with those of women with mental disorders hospitalized in a general hospital. Conclusion: Elevated serum BDNF levels were found in imprisoned women. The results of this study may suggest neurobiological mechanisms similar to those seen in previous clinical and preclinical studies showing the involvement of BDNF in the pathophysiology of PTSD. .

Pharmacological treatment and staging in bipolar disorder: evidence from clinical practice

Objectives: Staging models for medical diseases are widely used to guide treatment and prognosis. Bipolar disorder (BD) is a chronic condition and it is among the most disabling disorders in medicine. The staging model proposed by Kapczinski in 2009 presents four progressive clinical stages of BD. Our aim was to evaluate pharmacological maintenance treatment across these stages in patients with BD. Methods: One hundred and twenty-nine subjects who met DSM-IV criteria for BD were recruited from the Bipolar Disorders Program at Hospital de Clínicas de Porto Alegre, Brazil. All patients were in remission. The subjects were classified according to the staging model: 31 subjects were classified as stage I, 44 as stage II, 31 as stage III, and 23 as stage IV. Results: Patterns of pharmacological treatment differed among the four stages (p = 0.001). Monotherapy was more frequent in stage I, and two-drug combinations in stage II. Patients at stages III and IV needed three or more medications or clozapine. Impairment in functional status (Functioning Assessment Short Test [FAST] scale scores) correlated positively with the number of medications prescribed. Conclusions: This study demonstrated differences in pharmacological treatment in patients with stable BD depending on disease stage. Treatment response can change with progression of BD. Clinical guidelines could consider the staging model to guide treatment effectiveness. .

Histone deacetylase activity and brain-derived neurotrophic factor (BDNF) levels in a pharmacological model of mania

Objective: In the present study, we aimed to examine the effects of repeated D-amphetamine (AMPH) exposure, a well-accepted animal model of acute mania in bipolar disorder (BD), and histone deacetylase (HDAC) inhibitors on locomotor behavior and HDAC activity in the prefrontal cortex (PFC) and peripheral blood mononuclear cells (PBMCs) of rats. Moreover, we aimed to assess brain-derived neurotrophic factor (BDNF) protein and mRNA levels in these samples. Methods: We treated adult male Wistar rats with 2 mg/kg AMPH or saline intraperitoneally for 14 days. Between the 8th and 14th days, rats also received 47.5 mg/kg lithium (Li), 200 mg/kg sodium valproate (VPT), 2 mg/kg sodium butyrate (SB), or saline. We evaluated locomotor activity in the open-field task and assessed HDAC activity in the PFC and PBMCs, and BDNF levels in the PFC and plasma. Results: AMPH significantly increased locomotor activity, which was reversed by all drugs. This hyperactivity was associated with increased HDAC activity in the PFC, which was partially reversed by Li, VPT, and SB. No differences were found in BDNF levels. Conclusion: Repeated AMPH administration increases HDAC activity in the PFC without altering BDNF levels. The partial reversal of HDAC increase by Li, VPT, and SB may account for their ability to reverse AMPH-induced hyperactivity. .

Cognitive impairment in a Brazilian sample of patients with bipolar disorder / Prejuízo cognitivo em uma amostra brasileira de pacientes com transtorno do humor bipolar

OBJECTIVE: Persistent neurocognitive deficits have been described in bipolar mood disorder. As far as we are aware, no study have examined whether the cognitive impairment is presented in the same way in a Brazilian sample. METHOD: Cognitive function of 66 patients with bipolar disorder (32 with depressive symptoms and 34 euthymic) and 28 healthy subjects was examined using a complete cognitive battery. RESULTS: Patients with bipolar disorder presented a significantly poorer performance in eight of the 12 subtests when compared to healthy subjects. There was no significant difference between the subgroups of patients. These patients showed impairment in both verbal and non-verbal cognitive function. CONCLUSION: Cognitive impairment was found in both groups of patients with bipolar disorder. The findings described here suggest an overall impairment of cognitive function, independent of mood symptoms. This is in line with data showing that cognitive deficits may be a persistent characteristic of bipolar disorder.

OBJETIVO: Déficits neurocognitivos persistentes têm sido descritos no transtorno do humor bipolar; entretanto, não há estudos em amostras brasileiras para avaliar se o prejuízo se apresenta da mesma forma. MÉTODO: Foi realizada uma avaliação cognitiva em 66 pacientes bipolares (32 com sintomas depressivos e 34 eutímicos) e 28 controles, utilizando-se uma bateria cognitiva completa. RESULTADOS: Em oito dos 12 subtestes avaliados os pacientes apresentaram desempenho significativamente inferior em relação aos controles. Não houve diferença significativa entre os grupos de pacientes. Foram encontrados prejuízos cognitivos tanto na área verbal como na área não verbal da cognição. CONCLUSÃO: Foi observada uma performance inferior em ambos os grupos de pacientes com transtorno bipolar. As dificuldades cognitivas encontradas apontam para um prejuízo global no funcionamento cognitivo, independente da presença de sintomas, sugerindo estabilidade ou cronicidade dos déficits cognitivos.