Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04
  • 2024-05
  • 2024-06
  • 2024-07
  • ELA causes children to experience their environment

    2018-11-07

    ELA causes children to experience their environment as threatening, perceiving themselves as having no value and regarding the future as being not trustworthy (Dube et al., 2003). A history of ELA consequentially increases the risk of developing a psychiatric disorder in adulthood (Rojo-Moreno et al., 1999; Ritchie et al., 2009; Wright et al., 2009; Carr et al., 2013). Models of plasticity such as the allostatic load and reactive scope models have been useful to understand the mechanisms underlying psychopathology after ELA (Howell and Sanchez, 2011). In these models, the pathological consequences of ELA have been attributed to a dysfunction in glucose transporter of neural, endocrine, or immune functions. It has also been proposed that the effects of ELA on allostatic load can contribute to diathesis for stress-mediating disorders later in life (Grassi-Oliveira et al., 2008; Rogosch et al., 2011; Danese and McEwen, 2012). Notably, ELA-exposed individuals have an earlier age of onset for several disorders such as depression and substance abuse (Andersen and Teicher, 2008; Scott et al., 2012) compared to the general population. These individuals also have a greater risk of self-harm and have poorer response to treatment in comparison to non-maltreated people with same psychopathologies (Nemeroff et al., 2003). These findings are indicative of the major differences between individuals affected by ELA versus later stressors, and show a need to understand the underlying biology and behavior caused by ELA over a lifespan.
    Neuroinflammation and psychopathology The immune system has been implicated in vulnerability to psychopathologies over the lifespan. For example, many clinical studies have provided evidence for the influence of immunological activation during the prenatal or early postnatal period on behavioral, psychological and neurological consequences such as schizophrenia and Parkinson\'s disease (Brown et al., 2004; Bilbo and Schwarz, 2009; Kohman and Rhodes, 2013). This research has shed light on how the interactive influence of the hypothalamic pituitary axis (HPA), sympathetic nervous system, and immune system can contribute to the effects of ELA. The well-orchestrated mammalian immune system has two major kinds of immune responses: innate and adaptive. Both are responsible for detecting and regulating foreign threats, and inflammation resulting from both has been associated with psychopathology (Miuller and Schwarz, 2007; McNally et al., 2008; Raison and Miller, 2011). The innate immune system is the first line of the host defense, and involves a rapid response of patrolling cells such as macrophages and microglia. The adaptive system is uniquely associated with the production of immune memory responses that are protective and also can be easily activated upon later encounters with specific pathogens (Chaplin, 2006). When these responses are inappropriately provoked, harmful inflammation is induced from pro-inflammatory cytokines such as IL-1β, IL-2, IL-6 and TNF-α secreted by activated microglia, macrophages and lymphocytes (Miuller and Schwarz, 2007; Haroon et al., 2012). Inflammatory activity is countered by other subsets of astrocytes, T lymphocytes, macrophages and monocytes that secrete anti-inflammatory cytokines including IL-10, IL-5 and IL-4 (Muller et al., 2000; Raison et al., 2010; Haroon et al., 2012). Innate and adaptive immunity both play critical roles in early development and aging (Schwarz and Bilbo, 2011), but very few studies have looked at normative lifespan development of the immune system (Siegrist and Aspinall, 2009), which may impact pathogenesis of mental illnesses. Pro-inflammatory immune activation has been linked to psychiatric disorders such as depression, schizophrenia and obsessive–compulsive disorder (Jones and Thomsen, 2013; Valkanova et al., 2013). For example, a meta-analysis controlling for antipsychotics revealed consistently elevated levels of several immune molecules released from macrophages, such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-12 in cases with schizophrenia (Miller et al., 2011). Cell cultures obtained from individuals with schizophrenia also produced higher levels of circulating IL-8 and IL-1β, further implicating immunity in schizophrenia pathology. In obsessive–compulsive disorder studies, polymorphisms in the TNF-α gene have been described (Cappi et al., 2012), as well as both increases and decreases in plasma TNF-α cytokine levels (Monteleone et al., 1998; Denys et al., 2004; Konuk et al., 2007). It has been proposed that cytokine gene polymorphisms can have variable effects between individuals (Cappi et al., 2012). In another meta-analysis, raised levels of the pro-inflammatory proteins IL-6 and C-reactive protein were significantly associated with the later development of depressive symptoms in prospective studies. In order to understand how these changes in the immune response can lead to susceptibility to a number of psychopathologies, we review the two major ways in which neuroinflammation can affect the brain: neuronal damage and altered neurotransmission.