Childhood insulin resistance and neural stem cell dysfunction in psychiatric disorders: Role of de novo lipogenesis and treatment perspectives

Table 1 Markers of de novo lipogenesis, substrates of gluconeogenesis, and metabolic parameters/abnormalities in patients with psychiatric disorders

Parameters	Psychosis	Depression
DNL markers
SFAs	Increased[32,36-39]	Increased[40,41]
MUFAs	Increased[32,36-39]	Increased[40,41]
PUFAs1	Reduced[32,36-39]	Reduced[40,41]
Ceramides	Increased[42]	Increased[42]
Triglycerides	Increased[48,60]	Increased[55,61]
GLN substrates
Lactate	Increased[56]	Increased[57]
Citrate	Increased[33]	Unknown
Pyruvate	Increased[54]	Unknown
GluAA	Increased[4,54]	Increased[55]
Metabolic parameters
Blood glucose	Increased[9,10,47,48]	Increased[10,51]
IR/insulin level	Increased[9,10,47,48]	Increased[10,51]
Obesity (BMI)	Increased[6,47]	Increased[10,51]
Diabetes	Increased[9,10,47]	Increased[10,51]

¹Obtained through diet and not synthesized via de novo lipogenesis in the body.

DNL: De novo lipogenesis; SFAs: Saturated fatty acids; MUFAs: Monounsaturated fatty acids; PUFAs: Polyunsaturated fatty acids; GLN: Gluconeogenesis; GluAA: Glucogenic amino acids; IR: Insulin resistance; BMI: Body mass index.

Table 2 Effects of selective adjunctive drugs/therapies on symptoms of psychosis and depression in patients with psychiatric disorders

Drugs/therapies	Psychosis1	Depression2
Aspirin	Reduced[122]	Reduced[130]
N-acetylcysteine	Reduced[123]	Reduced[131]
Minocycline	Reduced[122]	No effect[132]
Pregnenolone	Reduced[122]	Reduced[133]
Estrogens	Reduced[122,124]	Deteriorated[134]
Raloxifene	Reduced[122]	No effect[135]
Curcumin	Reduced[125]	Reduced[136]
Pioglitazone	Reduced[126]	Reduced[137]
Celecoxib	Reduced[127]	Reduced[138]
ω3-PUFAs	Reduced[128]	Reduced[139]
Aerobic exercise	Reduced[129]	Reduced[140]
Resistance exercise	May reduce[129]	Reduced [141]
MSC therapy	Unknown	Unknown

¹Measure of Positive and Negative Syndrome Scale score.

²Measure of Hamilton Depression Rating Scale total scores.

ω3-PUFAs: ω-3 polyunsaturated fatty acids; MSC: Mesenchymal stem cell.

Table 3 Effects of selected adjunctive drugs/therapies on insulin resistance, neural stem cell proliferation/neurogenesis, and cognition in animals and/or human subjects

Drugs/therapies	Insulin resistance	Neurogenesis	Cognition
Aspirin	Reduced[142]	Increased[157]	Improved[157]
N-acetylcysteine	Reduced[143]	Increased[158]	Improved[172]
Minocycline	Reduced[144]	Increased[159]	Improved[173]
Pregnenolone	May reduce[145]	Increased[160]	Improved[174]
Estrogens	Reduced[146]	Increased[161]	Improved[175]
Raloxifene	Reduced[147]	Increased[162]	Improved[176]
Tamoxifen	Increased[148]	Increased[163]	Improved[177]
Curcumin	Reduced[149]	Increased[164]	Improved[164]
Pioglitazone	Reduced[150]	Increased[165]	Improved[178]
Celecoxib	Reduced[151]	May reduce[166]	Improved[179]
ω3-PUFAs	Reduced[152]	Increased[167]	Improved[180]
SIRT1-A	Reduced[153]	Increased[168]	Improved[181]
Aerobic exercise	Reduced[154]	Increased[169]	Improved[182]
Resistance exercise	May reduce[155]	Increased[170]	Improved[183]
MSC therapy	Reduced[156]	Increased[171]	Improved[184]

ω3-PUFAs: ω-3 polyunsaturated fatty acids; SIRT1-A: Sirtuin 1-agonist; MSC: Mesenchymal stem cell.