| | Alzheimer’s disease | Parkinson’s disease | ADHD | Schizophrenia |
| | Functional/anatomical changes in NE/LC system | (i)Decreased LC volume and cell numbers with a rostrocaudal gradient [27, 44, 99](ii)Tau protein assembles in LC into neurofibrillary tangles starting in early adulthood [95, 96](iii)Decreased CNS levels of NE [92, 93, 102–105](iv)Impaired hippocampal neurogenesis [101](v)Impaired synaptic plasticity [104, 105] | (i)General destruction of LC without pattern topography [27, 44, 99](ii)α-synuclein accumulation in LC [120](iii)Loss of protective effect of α2AR on NE/DA system [122, 123] | (i)Imbalances in DA/NE monoamine systems [132](ii)PI3Kγ deficiency [130, 131](iii)Impairment of NE transmission in PFC [71, 135, 137, 138](iv)Improvement in behavioral symptoms by modulators of NE transmission [8, 10, 134, 135](v)Dysregulation of signaling at the α2A receptor [71, 135, 137] | (i)Orbitofrontal cortex in DISC1+/+ mice contain shorter tyrosine hydroxylase (TH) positive fibers compared to wild-type mice [165, 166](ii)Impaired α1 receptor-dependent LTD [76](iii)Decreased binding of adrenergic probe to β1AR [166, 173] |
| | NE-related behavioral changes | (i)Early sensory deficits: impaired olfactory discrimination [56, 124](ii)Behavioral perseveration modulated by innervation of medial PFC [5, 7, 8, 53, 125, 126](iii)Memory decline [18, 85, 104, 105, 124, 127] | (i)Deficits in working memory, sustained attention, hyperactivity, impulsivity, behavioral flexibility [44, 134] | (i)Positive symptoms associated with high NE state [142, 153–155, 169, 170](ii)Impaired spatial working memory [158–161, 170] |
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