Molecular epidemiology of major depressive disorder

Kiyohara, Chikako; Yoshimasu, Kouichi

doi:10.1007/s12199-008-0073-6

Cited by 41 publications

(24 citation statements)

References 172 publications

(173 reference statements)

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“…This may be a compensatory response to increased serotonin (Harris et al , 1998; Lin et al , 1992), as leptin has also been shown to inhibit serotonin synthesis in the brain (Yadav et al, 2009). Reduced central serotonin synthesis is consistently reported in humans diagnosed with anxiety (Spindelegger et al, 2009), depression (Kiyohara and Yoshimasu, 2009; Sullivan et al, 2006), Attention Deficit Hyperactivity Disorder (ADHD) (Oades et al, 2008), and Autism Spectrum Disorder (ASD) (Challier et al, 2008; Chugani et al, 1999) and these disorders are commonly treated with selective serotonin reuptake inhibitors, which increase serotonin concentration in synapses. Thus, leptin suppression of serotonin synthesis is a possible mechanism behind the comorbidity between obesity and mental health disorders.…”

Section: Leptin’s Role In Psychopathologymentioning

confidence: 99%

The impact of leptin on perinatal development and psychopathology

Valleau

Sullivan

2014

Journal of Chemical Neuroanatomy

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Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin’s role and profile during development is examined in available human studies and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where both high and low leptin levels have been correlated with symptomatology. Schizophrenia is also associated with both low and high leptin levels. However, as antipsychotics pharmacotherapy induces weight gain, which elevates leptin levels, drug-naïve populations are needed for further studies. Elevated circulating leptin is consistently found in childhood neurodevelopmental disorders including Autism Spectrum Disorders and Rhett disorder. Further studies on the impact of leptin and leptin resistance on psychopathology and neurodevelopmental disorders are important directions for future research. Studies examining the mechanisms by which exposure to maternal obesity and hyperleptinemia during fetal development impact brain development and behavior are critical for the health of future generations.

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Section: Leptin’s Role In Psychopathologymentioning

confidence: 99%

The impact of leptin on perinatal development and psychopathology

Valleau

Sullivan

2014

Journal of Chemical Neuroanatomy

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“…A suppression of central serotonin synthesis is consistently reported in humans with anxiety [144], depression [145, 146], ADHD [147], and ASD [148, 149]. Serotonin 1A receptors have been identified to play a role in anxiety [144, 150].…”

Section: Perturbations In Pathways That Regulate Behavior and Metabolmentioning

confidence: 99%

Unraveling the Mechanisms Responsible for the Comorbidity between Metabolic Syndrome and Mental Health Disorders

2013

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The increased prevalence and high comorbidity of metabolic syndrome (MetS) and mental health disorders (MHDs) have prompted investigation into the potential contributing mechanisms. There is a bidirectional association between MetS and MHDs including schizophrenia, bipolar disorder, depression, anxiety, attention-deficit/hyperactivity disorder, and autism spectrum disorders. Medication side effects and social repercussions are contributing environmental factors, but there are a number of shared underlying neurological and physiological mechanisms that explain the high comorbidity between these two disorders. Inflammation is a state shared by both disorders, and it contributes to disruptions of neuroregulatory systems (including the serotonergic, dopaminergic, and neuropeptide Y systems) as well as dysregulation of the hypothalamic-pituitary-adrenal axis. MetS in pregnant women also exposes the developing fetal brain to inflammatory factors that predispose the offspring to MetS and psychopathologies. Due to the shared nature of these conditions, treatment should address aspects of both mental health and metabolic disorders. Additionally, interventions that can interrupt the transfer of increased risk of the disorders to the next generation need to be developed.

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“…Maternal nutrition has long-term implications for the offspring's risk of developing mental health disorders. Perinatal exposure to a HFD may contribute to this association by altering the development of key pathways implicated in regulating mood and behavior such as the serotonin system [52]. Recently, maternal HFD consumption has been associated with increased anxiety in rodent [12] and nonhuman primate offspring [11].…”

Section: Hfd Programming Of Mental Health Disordersmentioning

confidence: 99%

Perinatal Exposure to High-Fat Diet Programs Energy Balance, Metabolism and Behavior in Adulthood

2010

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The perinatal environment plays an important role in programming many aspects of physiology and behavior including metabolism, body weight set point, energy balance regulation and predisposition to mental health-related disorders such as anxiety, depression and attention deficit hyperactivity disorder. Maternal health and nutritional status heavily influence the early environment and have a long-term impact on critical central pathways, including the melanocortinergic, serotonergic system and dopaminergic systems. Evidence from a variety of animal models including rodents and nonhuman primates indicates that exposure to maternal high-fat diet (HFD) consumption programs offspring for increased risk of adult obesity. Hyperphagia and increased preference for fatty and sugary foods are implicated as mechanisms for the increased obesity risk. The effects of maternal HFD consumption on energy expenditure are unclear, and future studies need to address the impact of perinatal HFD exposure on this important component of energy balance regulation. Recent evidence from animal models also indicates that maternal HFD consumption increases the risk of offspring developing mental health-related disorders such as anxiety. Potential mechanisms for perinatal HFD programming of neural pathways include circulating factors, such as hormones (leptin, insulin), nutrients (fatty acids, triglycerides and glucose) and inflammatory cytokines. As maternal HFD consumption and obesity are common and rapidly increasing, we speculate that future generations will be at increased risk for both metabolic and mental health disorders. Thus, it is critical that future studies identify therapeutic strategies that are effective at preventing maternal HFD-induced malprogramming.

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Molecular epidemiology of major depressive disorder

Cited by 41 publications

References 172 publications

The impact of leptin on perinatal development and psychopathology

The impact of leptin on perinatal development and psychopathology

Unraveling the Mechanisms Responsible for the Comorbidity between Metabolic Syndrome and Mental Health Disorders

Perinatal Exposure to High-Fat Diet Programs Energy Balance, Metabolism and Behavior in Adulthood

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