Catatonic and Psychotic Symptoms Owing to the Trauma of Captivity in a Cult Environment

Judicious Toggling of mTOR Activity to Combat Insulin Resistance and Cancer: Current Evidence and Perspectives

“…Conversely, constitutive activation of mTORC1/S6K1 through overexpression of RHEB or deletion of TSC1/2 led to a downregulation as well as enhanced proteosomal degradation of IRS1 and IRS2 (Shah et al, 2004). This reduces the signaling between insulin receptor and PI3K, thereby inducing IR (Hotamisligil et al, 1996; Liu et al, 2004; Shah et al, 2004; Tremblay et al, 2007; Blagosklonny, 2012). The sustained feedback via the mTORC1/S6K1 route has been confirmed by many others as a single most important mechanism for inducing IR (Tremblay and Marette, 2001; Harrington et al, 2004; Shah et al, 2004; Um et al, 2004; Nyman et al, 2014).…”

“…As a result, it has been suggested that inhibition of the mTOR pathway may potentially reduce IR and thus improve glucose homeostasis (Blagosklonny, 2012, 2013). However, the modulation of the mTOR pathway using mTOR inhibitors is unquestionably complicated.…”

“…This apparent contradiction has been postulated to be due to the U-shaped profile of mTOR activity where its deficiency or abundance is detrimental to the overall balance of cellular metabolism (Laplante and Sabatini, 2012). With this preamble, it has since been suggested that low dose intermittent administration of rapamycin may have beneficial effects in combating IR while minimizing the long term metabolic toxicities associated with its chronic continuous use (Blagosklonny, 2012, 2013). …”

“…Acute rapamycin treatment inhibited mTORC1-mediated S6K1-IRS negative feedback loop and has been found to restore insulin signaling (Tremblay et al, 2005; Tzatsos and Kandror, 2006). Low dose intermittent rapamycin use may thus be useful in the management of IR as it avoids its mTORC2-mediated IR as well as other potential IR inducing effects such as inhibition of mitochondria biogenesis and decrease in YY1 gene expression following long term mTORC1 inhibition (Morino et al, 2006; Blagosklonny, 2012, 2013; Blättler et al, 2012)]. Indeed, this has been clearly observed in myotubes in vitro where acute treatment with rapamycin (< 1 h) resulted in increased insulin sensitivity through mTORC1 disruption while prolonged exposure (>24 h) render cells refractory to the actions of insulin via mTORC2 inhibition (Ye et al, 2012).…”

Can Trauma Condition Vulnerable Individuals to Develop Catatonic Symptoms?

“…According to her family, she had no mental health issues prior to her captivity. The authors reported, “Her initial symptoms were fear and startle responses on encountering loud stimuli and flashbacks in which she would lose all awareness of her current surroundings and speak about what occurred in the motel” [ 4 ]. It seems that these flashbacks were brought on by the internal thoughts that pulled her back into the motel, and she developed catatonic symptoms that were primed during her captivity.…”