@article {127,
	title = {Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder.},
	journal = {Nature},
	volume = {527},
	year = {2015},
	month = {2015 Nov 5},
	pages = {95-9},
	abstract = {<p>Bipolar disorder is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression; without treatment, 15\% of patients commit suicide. Hence, it has been ranked by the World Health Organization as a top disorder of morbidity and lost productivity. Previous neuropathological studies have revealed a series of alterations in the brains of patients with bipolar disorder or animal models, such as reduced glial cell number in the prefrontal cortex of patients, upregulated activities of the protein kinase A and C pathways and changes in neurotransmission. However, the roles and causation of these changes in bipolar disorder have been too complex to exactly determine the pathology of the disease. Furthermore, although some patients show remarkable improvement with lithium treatment for yet unknown reasons, others are refractory to lithium treatment. Therefore, developing an accurate and powerful biological model for bipolar disorder has been a challenge. The introduction of induced pluripotent stem-cell (iPSC) technology has provided a new approach. Here we have developed an iPSC model for human bipolar disorder and investigated the cellular phenotypes of hippocampal dentate gyrus-like neurons derived from iPSCs of patients with bipolar disorder. Guided by RNA sequencing expression profiling, we have detected mitochondrial abnormalities in young neurons from patients with bipolar disorder by using mitochondrial assays; in addition, using both patch-clamp recording and somatic Ca(2+) imaging, we have observed hyperactive action-potential firing. This hyperexcitability phenotype of young neurons in bipolar disorder was selectively reversed by lithium treatment only in neurons derived from patients who also responded to lithium treatment. Therefore, hyperexcitability is one early endophenotype of bipolar disorder, and our model of iPSCs in this disease might be useful in developing new therapies and drugs aimed at its clinical treatment.</p>
},
	keywords = {Action Potentials, Antipsychotic Agents, Bipolar Disorder, Calcium Signaling, Dentate Gyrus, Endophenotypes, Humans, Induced Pluripotent Stem Cells, Lithium Compounds, Male, Mitochondria, Neurons, Patch-Clamp Techniques},
	issn = {1476-4687},
	doi = {10.1038/nature15526},
	author = {Mertens, Jerome and Wang, Qiu-Wen and Kim, Yongsung and Yu, Diana X and Pham, Son and Yang, Bo and Zheng, Yi and Diffenderfer, Kenneth E and Zhang, Jian and Soltani, Sheila and Eames, Tameji and Schafer, Simon T and Boyer, Leah and Marchetto, Maria C and Nurnberger, John I and Calabrese, Joseph R and {\O}degaard, Ketil J and McCarthy, Michael J and Zandi, Peter P and Alda, Martin and Alba, Martin and Nievergelt, Caroline M and Mi, Shuangli and Brennand, Kristen J and Kelsoe, John R and Gage, Fred H and Yao, Jun}
}
@article {181,
	title = {Atypical social referencing in infant siblings of children with autism spectrum disorders.},
	journal = {J Autism Dev Disord},
	volume = {42},
	year = {2012},
	month = {2012 Dec},
	pages = {2611-21},
	abstract = {<p>Social referencing was investigated in 18-month-old siblings of children with autism spectrum disorders (ASD; "high-risk infants"). Infants were exposed to novel toys, which were emotionally tagged via adults{\textquoteright} facial and vocal signals. Infants{\textquoteright} information seeking (initiation of joint attention with an adult) and their approach/withdrawal behavior toward the toys before versus after the adults{\textquoteright} emotional signals was measured. Compared to both typically developing infants and high-risk infants without ASD, infants later diagnosed with ASD engaged in slower information seeking, suggesting that this aspect of referencing may be an early indicator of ASD. High-risk infants, both those who were and those who were not later diagnosed with ASD, exhibited impairments in regulating their behavior based on the adults{\textquoteright} emotional signals, suggesting that this aspect of social referencing may reflect an endophenotype for ASD.</p>
},
	keywords = {Attention, Child, Child Development, Child Development Disorders, Pervasive, Child, Preschool, Emotions, Endophenotypes, Female, Humans, Infant, Infant Behavior, Male, Risk Factors, Siblings, Social Behavior},
	issn = {1573-3432},
	doi = {10.1007/s10803-012-1518-8},
	author = {Cornew, Lauren and Dobkins, Karen R and Akshoomoff, Natacha and McCleery, Joseph P and Carver, Leslie J}
}
