“…Several mechanisms have been proposed to account for that, such as: the Dopaminergic system for which pharmacological evidence suggests that excessive dopamine neurotransmission is involved in the development of manic symptoms; the Glutamatergic systems, purported to be related when mood stabilizers were shown to modulate glutamate levels which may have therapeutic value; neurotrophins like BDNF (Fernandes et al 2011), bcl-2, neurotrophin-3 (NT-3) (Walz et al 2007), and neurotrophin-4/5 (NT-4/5) (Walz et al 2009), glial-derived neurotrophic factor (GDNF) (Rosa et al 2006), and vascular endothelial growth factor that play a vital role in neuronal survival and proliferation; oxidative stress, which is linked to a fundamental abnormality in oxidative energy generation (Kato 2007, Bauer et al 2014; life stress and trauma that have been shown to be associated with a decrease in serum BDNF levels among BD patients (Kauer-Sant'anna et al 2008); accelerated aging and disease trajectories (McEwen 2003, Juster et al 2010; and inflammation (e.g., Bauer et al 2014). Of the various biological mechanisms purported to underlie cognitive impairment (Berk et al 2011a, Bauer et al 2014 inflammation was the most potent one.…”