Cocaine facilitates Ca(2+) fluctuations in prefrontal cortex astrocytes via norepinephrine transmission in awake mice.

Executive functions (EFs) are high-level cognitive processing skills that are relevant for self-regulation and goal-directed behaviors. [] They support task initiation, performance, persistence, and completion and are therefore indispensable for occupational activities. [] Some core abilities comprised under the umbrella term EFs are set-shifting (i.e., alternating between tasks), working memory (i.e., holding on to relevant information for relatively short periods of time), and inhibitory control (i.e., preventing the manifestation of an inappropriate cognitive process or behavior). [] Although these abilities are separately identifiable, they share a top-level latent component named the common EF factor that explains most of the variability across them. [] EFs are presumed to be the result of the dynamic interplay between inherited factors and environmental influences, although they are also subject to independent influences of genes and environment separately. [] The genetic architecture behind EFs is responsible for their high heritability and has been extensively studied. For example, twin studies estimated the heritability in children and adolescents to be as high as 0.77–1.00, whereby the latter value was obtained when researchers used the common EF factor. [] Executive functioning involves activation of different neurotransmitters and circuits, including the serotoninergic, dopaminergic, and cholinergic systems, and changes in the genes related to the biosynthesis or transportation of these molecules are related to impairment of EFs. [, ] Recently, Hatoum et al. conducted the largest genome-wide association study (GWAS) on EFs to date. The study, which included more than 400 000 individuals in the UK biobank, found that genes related to inhibition (i.e., GABAergic processes) mediated EFs and also identified opposing genetic correlations between EFs and psychiatric disorders. [] Environmental adversities throughout the neurodevelopmental landscape contribute further to the shaping of EF. [] The consequences of these exposures depend on various factors as their duration or severity, sensitive neurodevelopmental periods, and individual resiliency. Some examples include prenatal exposure to maternal distress, substance use or psychiatric disorders, perinatal hypoxia-ischemia, and adverse childhood experiences (ACEs). It is known that late childhood and adolescence are critical periods for the development of EFs, [] therefore ACEs as physical abuse, sexual abuse, emotional or physical neglect during these periods of life can negatively impact EFs (mostly overall measures or working memory) into early and middle adulthood, and in the absence or presence of additional psychopathology (i.e., patients with bipolar disorder or schizophrenia). [, ] In adulthood, aging has mostly negative effects on EFs, although inhibitory control may increase with age. [] EFs are also affected by chronic diseases, including cardiovascular and metabolic conditions. [] Importantly, lower EF scores are found in most psychiatric diseases, including major depressive disorder (MDD), [] bipolar disorder, [] schizophrenia, [] and post-traumatic stress disorder. [] EFs are moldable skills and susceptible to improvement by cognitive remediation interventions, which are additionally effective for negative symptoms and overall functioning in patients with schizophrenia, in whom greater symptom severity and later onset-age do not prevent gains. [, ] Furthermore, meta-analyses showed that cognitive remediation is effective for improving EFs in adults with MDD, [] and reducing symptoms severity and enhancing working memory in patients with anxiety disorders. [] In summary, EFs are affected by genetic and environmental factors and are highly plastic and sensitive to rehabilitation.