Nicotine dependence and serum BDNF levels in male patients with schizophrenia
ABSTRACT Schizophrenia is associated with a significantly high prevalence of smoking. Upregulation of neurotrophins by nicotine is well established. Accumulating evidence shows that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. The purposes of this study were to compare BDNF levels in smokers to nonsmokers with schizophrenia and examine the association between BDNF levels and psychopathological symptoms.
Serum BDNF levels were measured in 139 male inpatients with DSM-IV schizophrenia: 102 smokers and 37 nonsmokers. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS).
The positive PANSS symptoms were lower in smokers than in nonsmokers, while the negative symptoms were lower in those who smoked more cigarettes. BDNF levels were significantly higher in smokers than in nonsmokers (p < 0.05). Higher BDNF levels correlated with fewer negative symptoms and with smoking more cigarettes.
The fewer positive symptoms in smokers and fewer negative symptoms in those who smoked more cigarettes may be associated with nicotine-induced upregulation of BDNF.
- SourceAvailable from: Kayla A Chase
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- "BDNF is a neurotrophic factor involved in synaptic plasticity inducible by activity dependent processes and is highly epigenetically regulated (Roth et al., 2009; Tian et al., 2010). The reduction in the expression of this neuroplasticity gene in schizophrenia has been previously reported by several labs (Thompson Ray et al., 2011; Zhang et al., 2010). Furthermore, the schizophrenia candidate gene involved in synaptic plasticity, reelin, may be downregulated in schizophrenia perhaps via increased promoter DNA methylation (Abdolmaleky et al., 2005; Fatemi et al., 2005; Grayson et al., 2005). "
ABSTRACT: Over the last several years proteins involved in base excision repair (BER) have been implicated in active DNA demethylation. We review the literature supporting BER as a means of active DNA demethylation, and explain how the various components function and cooperate to remove the potentially most enduring means of epigenetic gene regulation. Recent evidence indicates that the same pathways implicated during periods of widespread DNA demethylation, such as the erasure of methyl marks in the paternal pronucleus soon after fertilization, are operational in post-mitotic neurons. Neuronal functional identities, defined here as the result of a combination of neuronal subtype, location, and synaptic connections are largely maintained through DNA methylation. Chronic mental illnesses, such as schizophrenia, may be the result of both altered neurotransmitter levels and neurons that have assumed dysfunctional neuronal identities. A limitation of most current psychopharmacological agents is their focus on the former, while not addressing the more profound latter pathophysiological process. Previously, it was believed that active DNA demethylation in post-mitotic neurons was rare if not impossible. If this were the case, then reversing the factors that maintain neuronal identity, would be highly unlikely. The emergence of an active DNA demethylation pathway in the brain is a reason for great optimism in psychiatry as it provides a means by which previously pathological neurons may be reprogrammed into a more favorable role. Agents targeting epigenetic processes have shown much promise in this regard, and may lead to substantial gains over traditional pharmacological approaches.Neuropharmacology 08/2013; 75. DOI:10.1016/j.neuropharm.2013.07.036 · 4.82 Impact Factor
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ABSTRACT: This study investigated nicotine place conditioning in early postweanling and adolescent male and female rats neonatally treated with quinpirole, a dopamine D(2)/D(3) agonist. Previous research has shown that neonatal quinpirole treatment results in an increase of dopamine D(2)-like receptor sensitivity that persists throughout the animal's lifetime, relevant to psychosis. Rats were neonatally treated with quinpirole or saline from postnatal day (P)1-21, and animals were conditioned with nicotine or saline daily from P23-30 as early postweanlings or P32-39 as adolescents in a two- or three-chambered place conditioning apparatus. A drug free test was given on P31 for early postweanlings, and P40 for adolescents. Results on the two chamber apparatus revealed that nicotine increased time spent in the drug-paired context at both ages tested. Neonatal quinpirole treatment resulted in less time spent in the drug-paired context in early postweanling males and increased time spent in the drug-paired context in adolescent females conditioned with nicotine. Adolescent females neonatally treated with saline and conditioned with nicotine on the two chamber apparatus did not differ from controls. On the three-chambered apparatus, nicotine increased time spent in the drug-paired context in both ages tested, which was blocked by neonatal quinpirole in early postweanling males, but enhanced by neonatal quinpirole treatment in adolescents. These results demonstrate both age and sex differences in the effects of nicotine and point to significant differences in performance depending on the apparatus used. Additionally, neonatal quinpirole enhanced the effects of nicotine, but this is true only in adolescents and task-dependent.Behavioural brain research 02/2011; 220(1):254-61. DOI:10.1016/j.bbr.2011.02.004 · 3.39 Impact Factor
- European Neuropsychopharmacology 09/2011; 21. DOI:10.1016/S0924-977X(11)70622-8 · 5.40 Impact Factor