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Manpreet Singh, MD, MS

  • Manpreet K Singh

Specialties

Child & Adolescent Psychiatry

Work and Education

Professional Education

Michigan State University College of Human Medicine, East Lansing, MI, 2002

Internship

Cincinnati Children's Hospital, Cincinnati, OH, 2003

Residency

Cincinnati Children's Hospital, Cincinnati, OH, 2007

Fellowship

Cincinnati Children's Hospital, Cincinnati, OH, 2007

Board Certifications

Child & Adolescent Psychiatry, American Board of Psychiatry and Neurology

Psychiatry, American Board of Psychiatry and Neurology

All Publications

Neural Aspects of Inhibition Following Emotional Primes in Depressed Adolescents JOURNAL OF CLINICAL CHILD AND ADOLESCENT PSYCHOLOGY Colich, N. L., Foland-Ross, L. C., Eggleston, C., Singh, M. K., Gotlib, I. H. 2016; 45 (1): 21-30

Abstract

Adults diagnosed with major depressive disorder (MDD) have been found to be characterized by selective attention to negative material and by impairments in their ability to disengage from, or inhibit the processing of, negative stimuli. Altered functioning in the frontal executive control network has been posited to underlie these deficits in cognitive functioning. We know little, however, about the neural underpinnings of inhibitory difficulties in depressed adolescents. We used functional magnetic resonance imaging in 18 adolescents diagnosed with MDD and 15 age- and gender-matched healthy controls (CTLs) while they performed a modified affective Go/No-Go task that was designed to measure inhibitory control in the presence of an emotional distractor. Participants were presented with either a happy or a sad face, followed by a go or a no-go target to which they either made or inhibited a motor response. A group (MDD, CTL) by valence (happy, sad) by condition (go, no-go) analysis of variance indicated that MDD adolescents showed attenuated BOLD response in the right dorsolateral prefrontal cortex (DLPFC) and in the occipital cortex bilaterally, to no-go targets that followed a sad, but not a happy, face. Adolescents diagnosed with MDD showed anomalous recruitment of prefrontal control regions during inhibition trials, suggesting depression-associated disruption in neural underpinnings of the inhibition of emotional distractors. Given that the DLPFC is associated with the maintenance of goal-relevant information, it is likely that sad faces differentially capture attention in adolescents with MDD and interfere with task demands requiring inhibition.

View details for DOI 10.1080/15374416.2014.982281

View details for Web of Science ID 000369298800003

View details for PubMedID 25635920

Predicting First Onset of Depression in Young Girls: Interaction of Diurnal Cortisol and Negative Life Events JOURNAL OF ABNORMAL PSYCHOLOGY LeMoult, J., Ordaz, S. J., Kircanski, K., Singh, M. K., Gotlib, I. H. 2015; 124 (4): 850-859

View details for DOI 10.1037/abn0000087

View details for Web of Science ID 000365609000007

Intrinsic Amygdala Functional Connectivity in Youth With Bipolar I Disorder JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Singh, M. K., Kelley, R. G., Chang, K. D., Gotlib, I. H. 2015; 54 (9): 763-770
Intrinsic Amygdala Functional Connectivity in Youth With Bipolar I Disorder. Journal of the American Academy of Child and Adolescent Psychiatry Singh, M. K., Kelley, R. G., Chang, K. D., Gotlib, I. H. 2015; 54 (9): 763-770

Abstract

Bipolar disorder (BD) commonly begins during adolescence and may continue into adulthood. Studies in adults with BD suggest that disruptions in amygdalar neural circuitry explain the pathophysiology underlying the disorder. Importantly, however, amygdala subregion networks have not yet been examined in youth close to mania onset. The goal of this study was to compare resting state functional connectivity patterns in amygdala subregions in youth with bipolar I disorder with patterns in healthy controls.Centromedial, laterobasal, and superficial amygdala subdivisions were assessed during rest and examined in relation to clinical measures of mania in youth (14-20 years old) with bipolar I disorder who experienced only a single episode of mania (BD; n= 20) and age-matched healthy comparison youth without any personal or family history of DSM-IV Axis I disorders (HC; n= 23).Relative to HC youth, youth with BD exhibited decreased connectivity between the laterobasal subdivision of the amygdala and the hippocampus and precentral gyrus, and increased connectivity between the laterobasal subdivision and the precuneus. Connectivity between the right laterobasal amygdala and right hippocampus was positively correlated with levels of anxiety in BD but not in HC youth, and connectivity between the right laterobasal amygdala and right precuneus was negatively correlated with insight about bipolar illness.Youth with BD have abnormal amygdala resting state network connections to regions that are critical for emotional processing and self-awareness. Longitudinal studies are needed to determine whether these aberrant patterns in youth with BD can be altered with intervention and can influence the course of disorder.

View details for DOI 10.1016/j.jaac.2015.06.016

View details for PubMedID 26299298

Using neuroimaging to evaluate and guide pharmacological and psychotherapeutic treatments for mood disorders in children CNS SPECTRUMS Singh, M. K., Garrett, A. S., Chang, K. D. 2015; 20 (4): 359-368

Abstract

Mood disorders are increasing in childhood, and often require multimodal and comprehensive treatment plans to address a complex array of symptoms and associated morbidities. Pharmacotherapy, in combination with psychotherapeutic interventions, is essential for treatment and stabilization. Current evidence supports the use of a number of interventions in children and adolescents diagnosed with DSM-5 mood spectrum disorders, which are associated with impairments in prefrontal-striatal-limbic networks, which are key for emotional functioning and regulation. Yet, little is known about the neurobiological effects of interventions on the developing brain. This chapter provides a synopsis of the literature demonstrating the neural effects of psychotropic medications and psychotherapy in youth with depressive or bipolar spectrum disorders. Additional longitudinal and biological studies are warranted to characterize the effects of these interventions on all phases and stages of mood illness development in children and adolescents.

View details for DOI 10.1017/S1092852914000819

View details for Web of Science ID 000359008300005

View details for PubMedID 25659836

Association of Anxiety Symptoms in Offspring of Bipolar Parents with Serotonin Transporter-Linked Polymorphic Region (5-HTTLPR) Genotype JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Park, M., Sanders, E., Howe, M., Singh, M., Hallmayer, J., Kim, E., Chang, K. 2015; 25 (6): 458-466

Abstract

Offspring of parents with bipolar disorder (BD) have been shown to be at high risk for BD. Anxiety symptoms, even at subclinical levels, have been associated with increased risk for BD in these youth. The s-allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) has been implicated in the pathophysiology of both BD and anxiety disorders and has been associated with pharmacological treatment response and increased risk for antidepressant side effects. Therefore, we aimed to explore 1) whether anxiety symptoms in offspring of BD parents were associated with presence of the 5-HTTLPR s-allele and 2) whether anxiety symptoms in the offspring of BD parents according to the 5-HTTLPR genotypes are related to antianxiety medication status.A total of 64 offspring of BD parents (mean age: 13.7 years) and 51 healthy controls (HC) (mean age: 13.7 years) were compared genetically and on the Multidimensional Anxiety Scale for Children (MASC).Offspring of BD parents showed higher levels of overall anxiety than did the HC group. Only antianxiety medication nave offspring of BD parents were found to have an association between 5-HTTLPR genotypes and anxiety symptoms. The antianxiety medication nave offspring of BD parents with the s-allele showed higher level of overall anxiety than offspring of BD parents with the l/l genotype. No significant differences in anxiety symptoms or their association with the 5-HTTLPR genotype were found in the HC group.This study indicated that there may be an association between 5-HTTLPR genotypes and anxiety symptoms in offspring of BD parents, and that antianxiety medication status may affect anxiety symptoms in the offspring of BD patients according to genotype.

View details for DOI 10.1089/cap.2014.0115

View details for Web of Science ID 000359607900002

View details for PubMedID 26218602

Inattentive achievement: the challenges and opportunities of learning with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry Singh, M. K. 2015; 54 (5): 348-349

View details for DOI 10.1016/j.jaac.2015.02.014

View details for PubMedID 25901769

Is there validity to the bipolar prodrome? journal of clinical psychiatry Singh, M. K. 2015; 76 (5): e655-6

View details for DOI 10.4088/JCP.14com09502

View details for PubMedID 26035200

Preliminary study of anxiety symptoms, family dysfunction, and the brain-derived neurotrophic factor (BDNF) Val66Met genotype in offspring of parents with bipolar disorder JOURNAL OF PSYCHIATRIC RESEARCH Park, M., Chang, K. D., Hallmayer, J., Howe, M. E., Kim, E., Hong, S. C., Singh, M. K. 2015; 61: 81-88

Abstract

Several genetic and environmental factors place youth offspring of parents with bipolar disorder (BD) at high risk for developing mood and anxiety disorders. Recent studies suggest that anxiety symptoms, even at subclinical levels, have been associated with an increased risk for developing BD. The brain-derived neurotrophic factor (BDNF) gene has been implicated in the pathophysiology of both BD and anxiety disorders. We aimed to explore whether anxiety in BD offspring was associated with the BDNF Val66Met polymorphism. 64 BD offspring (mean age: 13.73 (S.D. 3.45) M=30, F=34) and 51 HC (mean age: 13.68 (S.D. 2.68) M=23, F=28) were compared on presence of the metallele and on scores from the Multidimensional Anxiety Scale for Children (MASC). To assess family function, we used the Family Adaptability and Cohesion Evaluation Scales (FACES-IV). The Baron & Kenny method was the statistical approach used to examine the moderating effects between variables. BD offspring showed higher levels of overall anxiety than did the HC group. BD offspring with the val/val genotype showed higher levels of anxiety than BD offspring with other genotypes. No significant levels of anxiety or its association with BDNF genotype were found in the HC group. BD offspring group showed significantly more family dysfunction when comparedwith the HC group and the family dysfunction moderated the association between the BDNF genotype and anxiety symptoms. This study demonstrated the potential interplay of three factors: BD offspring, anxiety symptoms and family dysfunction.

View details for DOI 10.1016/j.jpsychires.2014.11.013

View details for Web of Science ID 000349731000012

View details for PubMedID 25498133

Changes in brain activation following psychotherapy for youth with mood dysregulation at familial risk for bipolar disorder PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY Garrett, A. S., Miklowitz, D. J., Howe, M. E., Singh, M. K., Acquaye, T. K., Hawkey, C. G., Glover, G. H., Reiss, A. L., Chang, K. D. 2015; 56: 215-220
Association between insulin resistance and cognition in patients with depressive disorders: Exploratory analyses into age-specific effects JOURNAL OF PSYCHIATRIC RESEARCH Wroolie, T. E., Kenna, H. A., Singh, M. K., Rasgon, N. L. 2015; 60: 65-72
Distinguishing Bipolar Disorder From Other Psychiatric Disorders in Children CURRENT PSYCHIATRY REPORTS Singh, M. K., Ketter, T., Chang, K. D. 2014; 16 (12)
Distinguishing bipolar disorder from other psychiatric disorders in children. Current psychiatry reports Singh, M. K., Ketter, T., Chang, K. D. 2014; 16 (12): 516-?

Abstract

Pediatric onset bipolar disorder (BD) is a challenging diagnosis with potentially debilitating outcomes. This review aims to critically evaluate recently published literature relevant to the diagnosis of BD in youth, emphasizing interesting and important new findings characterizing pediatric BD and reporting updates in the diagnostic and statistical manual relevant to this disorder in youth. Challenges regarding the diagnosis of BD will be discussed, in addition to important distinctions with other childhood disorders, including other bipolar spectrum disorders; major depressive disorder; dysthymia; disruptive mood dysregulation disorder (DMDD); attention-deficit/hyperactivity disorder (ADHD) and other disruptive behavioral disorders; anxiety disorders, including post-traumatic stress disorder (PTSD); psychotic disorders; autism spectrum disorders; substance use disorders; and borderline personality disorder. The review concludes with a comment on past research limitations and future directions in the field.

View details for DOI 10.1007/s11920-014-0516-2

View details for PubMedID 25315116

Preparing and Presenting Effective Abstracts and Posters in Psychiatry ACADEMIC PSYCHIATRY Singh, M. K. 2014; 38 (6): 709-715

Abstract

Presenting an abstract and a poster gives scientists from all fields, including psychiatry, an important opportunity to introduce their research to others. Researchers and mental health professionals at all levels of career development can use several media resources to assist them with the technical aspects of preparing an abstract or a poster. This article will focus on major principles associated with preparing and presenting an abstract and a poster at a scientific meeting. A literature search using NIH PubMed was conducted to identify peer and nonpeer-reviewed articles that provide methods for effective abstract and poster presentation for the period of 1966 to June 2014. First, the author reviews the purpose and relative importance of abstracts and posters in academic settings. Next, the author describes the qualities of an effective abstract and poster and common pitfalls that may occur. Finally, the author presents a systematic approach to preparing and presenting an abstract and a poster in a scientific setting. Several sources consistently suggest that readability, organization, and succinctness are qualities that make an effective and successful abstract and poster. Mental health professionals in all stages of their career development may benefit from following these guidelines in presenting their scientific work.

View details for DOI 10.1007/s40596-014-0190-z

View details for Web of Science ID 000346794100012

View details for PubMedID 25085499

Early signs of anomalous neural functional connectivity in healthy offspring of parents with bipolar disorder BIPOLAR DISORDERS Singh, M. K., Chang, K. D., Kelley, R. G., Saggar, M., Reiss, A. L., Gotlib, I. H. 2014; 16 (7): 678-689

View details for DOI 10.1111/bdi.12221

View details for Web of Science ID 000344373100002

The neuroscience of depression: implications for assessment and intervention. Behaviour research and therapy Singh, M. K., Gotlib, I. H. 2014; 62: 60-73

Abstract

Major Depressive Disorder (MDD) is among the most prevalent of all psychiatric disorders and is the single most burdensome disease worldwide. In attempting to understand the profound deficits that characterize MDD across multiple domains of functioning, researchers have identified aberrations in brain structure and function in individuals diagnosed with this disorder. In this review we synthesize recent data from human neuroimaging studies in presenting an integrated neural network framework for understanding the impairments experienced by individuals with MDD. We discuss the implications of these findings for assessment of and intervention for MDD. We conclude by offering directions for future research that we believe will advance our understanding of neural factors that contribute to the etiology and course of depression, and to recovery from this debilitating disorder.

View details for DOI 10.1016/j.brat.2014.08.008

View details for PubMedID 25239242

The neuroscience of depression: Implications for assessment and intervention BEHAVIOUR RESEARCH AND THERAPY Singh, M. K., Gotlib, I. H. 2014; 62: 60-73
Early signs of anomalous neural functional connectivity in healthy offspring of parents with bipolar disorder. Bipolar disorders Singh, M. K., Chang, K. D., Kelley, R. G., Saggar, M., Reiss, A. L., Gotlib, I. H. 2014; 16 (7): 678-689

Abstract

Bipolar disorder (BD) has been associated with dysfunctional brain connectivity and with family chaos. It is not known whether aberrant connectivity occurs before illness onset, representing vulnerability for developing BD amidst family chaos. We used resting-state functional magnetic resonance imaging (fMRI) to examine neural network dysfunction in healthy offspring living with parents with BD and healthy comparison youth.Using two complementary methodologies [data-driven independent component analysis (ICA) and hypothesis-driven region-of-interest (ROI)-based intrinsic connectivity], we examined resting-state fMRI data in 8-17-year-old healthy offspring of a parent with BD (n=24; high risk) and age-matched healthy youth without any personal or family psychopathology (n=25; low risk).ICA revealed that, relative to low-risk youth, high-risk youth showed increased connectivity in the ventrolateral prefrontal cortex (VLPFC) subregion of the left executive control network (ECN), which includes frontoparietal regions important for emotion regulation. ROI-based analyses revealed that high-risk versus low-risk youth had decreased connectivities between the left amygdala and pregenual cingulate, between the subgenual cingulate and supplementary motor cortex, and between the left VLPFC and left caudate. High-risk youth showed stronger connections in the VLPFC with age and higher functioning, which may be neuroprotective, and weaker connections between the left VLPFC and caudate with more family chaos, suggesting an environmental influence on frontostriatal connectivity.Healthy offspring of parents with BD show atypical patterns of prefrontal and subcortical intrinsic connectivity that may be early markers of resilience to or vulnerability for developing BD. Longitudinal studies are needed to determine whether these patterns predict outcomes.

View details for DOI 10.1111/bdi.12221

View details for PubMedID 24938878

Reward Processing in Healthy Offspring of Parents With Bipolar Disorder JAMA PSYCHIATRY Singh, M. K., Kelley, R. G., Howe, M. E., Reiss, A. L., Gotlib, I. H., Chang, K. D. 2014; 71 (10): 1148-1156
Neurobiological Clues of Risk for Bipolar Disorder Development PSYCHIATRIC ANNALS Chang, K. D., Garrett, A., Singh, M. 2014; 44 (10): 466-470
Type and duration of subsyndromal symptoms in youth with bipolar I disorder prior to their first manic episode BIPOLAR DISORDERS Correll, C. U., Hauser, M., Penzner, J. B., Auther, A. M., Kafantaris, V., Saito, E., Olvet, D., Carrion, R. E., Birmaher, B., Chang, K. D., DelBello, M. P., Singh, M. K., Pavuluri, M., Cornblatt, B. A. 2014; 16 (5): 478-492

Abstract

The aim of the present study was to systematically evaluate the prodrome to mania in youth.New-onset/worsening symptoms/signs of moderate severity preceding first mania were systematically assessed in 52 youth (16.2 2.8 years) with a research diagnosis of bipolar I disorder (BD-I). Youth and/or caregivers underwent semi-structured interviews, using the Bipolar Prodrome Symptom Scale-Retrospective.The mania prodrome was reported to start gradually in most youth (88.5%), with either slow (59.6%) or rapid (28.8%) deterioration, while a rapid-onset-and-deterioration prodrome was rare (11.5%). The manic prodrome, conservatively defined as requiring 3 symptoms, lasted 10.3 14.4 months [95% confidence interval (CI): 6.3-14.4], being present for 4 months in 65.4% of subjects. Among prodromal symptoms reported in 50% of youth, three were subthreshold manic in nature (irritability: 61.5%, racing thoughts: 59.6%, increased energy/activity: 50.0%), two were nonspecific (decreased school/work functioning: 65.4%, mood swings/lability: 57.7%), and one each was depressive (depressed mood: 53.8%) or subthreshold manic/depressive (inattention: 51.9%). A decreasing number of youth had 1 (84.6%), 2 (48.1%), or 3 (26.9%) 'specific' subthreshold mania symptoms (i.e., elation, grandiosity, decreased need for sleep, racing thoughts, or hypersexuality), lasting 9.5 14.9 months (95% CI: 5.0-14.0), 3.5 3.5 months (95% CI: 2.0-4.9), and 3.0 3.2 months (95% CI: 1.0-5.0) for 1, 2, or 3 specific symptoms, respectively.In youth with BD-I, a relatively long, predominantly slow-onset mania prodrome appears to be common, including subthreshold manic and depressive psychopathology symptoms. This suggests that early clinical identification and intervention may be feasible in bipolar disorder. Identifying biological markers associated with clinical symptoms of impending mania may help to increase chances for early detection and prevention before full mania.

View details for DOI 10.1111/bdi.12194

View details for Web of Science ID 000340381500004

View details for PubMedID 24597782

Prospective neurochemical characterization of child offspring of parents with bipolar disorder PSYCHIATRY RESEARCH-NEUROIMAGING Singh, M. K., Jo, B., Adleman, N. E., Howe, M., Bararpour, L., Kelley, R. G., Spielman, D., Chang, K. D. 2013; 214 (2): 153-160

Abstract

We wished to determine whether decreases in N-acetyl aspartate (NAA) and increases in myoinositol (mI) concentrations as a ratio of creatine (Cr) occurred in the dorsolateral prefrontal cortex (DLPFC) of pediatric offspring of parents with bipolar disorder (BD) and a healthy comparison group (HC) over a 5-year period using proton magnetic resonance spectroscopy ((1)H-MRS). Paticipants comprised 64 offspring (9-18 years old) of parents with BD (36 with established BD, and 28 offspring with symptoms subsyndromal to mania) and 28 HCs, who were examined for group differences in NAA/Cr and mI/Cr in the DLPFC at baseline and follow-up at either 8, 10, 12, 52, 104, 156, 208, or 260 weeks. No significant group differences were found in metabolite concentrations at baseline or over time. At baseline, BD offspring had trends for higher mI/Cr concentrations in the right DLPFC than the HC group. mI/Cr concentrations increased with age, but no statistically significant group differences were found between groups on follow-up. It may be the case that with intervention youth at risk for BD are normalizing otherwise potentially aberrant neurochemical trajectories in the DLPFC. A longer period of follow-up may be required before observing any group differences.

View details for DOI 10.1016/j.pscychresns.2013.05.005

View details for Web of Science ID 000325432300009

View details for PubMedID 24028795

Prospective neurochemical characterization of child offspring of parents with bipolar disorder. Psychiatry research Singh, M. K., Jo, B., Adleman, N. E., Howe, M., Bararpour, L., Kelley, R. G., Spielman, D., Chang, K. D. 2013; 214 (2): 153-160

Abstract

We wished to determine whether decreases in N-acetyl aspartate (NAA) and increases in myoinositol (mI) concentrations as a ratio of creatine (Cr) occurred in the dorsolateral prefrontal cortex (DLPFC) of pediatric offspring of parents with bipolar disorder (BD) and a healthy comparison group (HC) over a 5-year period using proton magnetic resonance spectroscopy ((1)H-MRS). Paticipants comprised 64 offspring (9-18 years old) of parents with BD (36 with established BD, and 28 offspring with symptoms subsyndromal to mania) and 28 HCs, who were examined for group differences in NAA/Cr and mI/Cr in the DLPFC at baseline and follow-up at either 8, 10, 12, 52, 104, 156, 208, or 260 weeks. No significant group differences were found in metabolite concentrations at baseline or over time. At baseline, BD offspring had trends for higher mI/Cr concentrations in the right DLPFC than the HC group. mI/Cr concentrations increased with age, but no statistically significant group differences were found between groups on follow-up. It may be the case that with intervention youth at risk for BD are normalizing otherwise potentially aberrant neurochemical trajectories in the DLPFC. A longer period of follow-up may be required before observing any group differences.

View details for DOI 10.1016/j.pscychresns.2013.05.005

View details for PubMedID 24028795

Anomalous gray matter structural networks in major depressive disorder. Biological psychiatry Singh, M. K., Kesler, S. R., Hadi Hosseini, S. M., Kelley, R. G., Amatya, D., Hamilton, J. P., Chen, M. C., Gotlib, I. H. 2013; 74 (10): 777-785

Abstract

BACKGROUND: Major depressive disorder (MDD) is characterized by abnormalities in structure, function, and connectivity in several brain regions. Few studies have examined how these regions are organized in the brain or investigated network-level structural aberrations that might be associated with depression. METHODS: We used graph analysis to examine the gray matter structural networks of individuals diagnosed with MDD (n = 93) and a demographically similar healthy comparison group (n = 151) with no history of psychopathology. The efficiency of structural networks for processing information was determined by quantifying local interconnectivity (clustering) and global integration (path length). We also compared the groups on the contributions of high-degree nodes (i.e., hubs) and regional network measures, including degree (number of connections in a node) and betweenness (fraction of short path connections in a node). RESULTS: Depressed participants had significantly decreased clustering in their brain networks across a range of network densities. Compared with control subjects, depressed participants had fewer hubs primarily in medial frontal and medial temporal areas, had higher degree in the left supramarginal gyrus and right gyrus rectus, and had higher betweenness in the right amygdala and left medial orbitofrontal gyrus. CONCLUSIONS: Networks of depressed individuals are characterized by a less efficient organization involving decreased regional connectivity compared with control subjects. Regional connections in the amygdala and medial prefrontal cortex may play a role in maintaining or adapting to depressive pathology. This is the first report of anomalous large-scale gray matter structural networks in MDD and provides new insights concerning the neurobiological mechanisms associated with this disorder.

View details for DOI 10.1016/j.biopsych.2013.03.005

View details for PubMedID 23601854

Socio-emotional processing and functioning of youth at high risk for bipolar disorder JOURNAL OF AFFECTIVE DISORDERS Whitney, J., Howe, M., Shoemaker, V., Li, S., Sanders, E. M., Dijamco, C., Acquaye, T., Phillips, J., Singh, M., Chang, K. 2013; 148 (1): 112-117

Abstract

The goal of this study was to investigate differences in socio-emotional processing and functioning in children and adolescents at high risk for bipolar disorder (BD) and healthy control participants.Children and adolescents with a parent with bipolar disorder, who had mood dysregulation but not fully syndromal BD (high risk, HR, n=24), were compared to participants with no personal or family history of psychopathology (healthy control, HC, n=27) across several neuropsychological domains. Social reciprocity was measured by the Social Responsiveness Scale, theory of mind was measured by use of the NEPSY, and affect recognition was measured by the NEPSY and the Diagnostic Test of Nonverbal Accuracy 2 (DANVA).The HR group demonstrated significant impairment in social reciprocity, including impairments in social awareness, social cognition, social communication, social motivation, and autistic mannerisms. There were no significant group differences in performance on theory of mind or affect recognition tasks.Lack of impairment in tasks associated with theory of mind or affect recognition indicate that social functioning difficulties are not likely due to impairments in these areas, or that the measures employed were not sufficiently sensitive to detect group differences.Youth at high risk for BD demonstrated impairments in numerous social domains, which may be due to innate differences in brain development governing socio-emotional functioning or may be due to disruptions in normal development caused by mood regulation difficulties.

View details for DOI 10.1016/j.jad.2012.08.016

View details for Web of Science ID 000318563000016

View details for PubMedID 23123133

In this issue. Abstract thinking: adolescence and adversity. Journal of the American Academy of Child and Adolescent Psychiatry Singh, M. K. 2013; 52 (3): 215-216

View details for DOI 10.1016/j.jaac.2012.12.015

View details for PubMedID 23452674

Early Intervention for Symptomatic Youth at Risk for Bipolar Disorder: A Randomized Trial of Family-Focused Therapy JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Miklowitz, D. J., Schneck, C. D., Singh, M. K., Taylor, D. O., George, E. L., Cosgrove, V. E., Howe, M. E., Dickinson, L. M., Garber, J., Chang, K. D. 2013; 52 (2): 121-131

Abstract

Depression and brief periods of (hypo)mania are linked to an increased risk of progression to bipolar I or II disorder (BD) in children of bipolar parents. This randomized trial examined the effects of a 4-month family-focused therapy (FFT) program on the 1-year course of mood symptoms in youth at high familial risk for BD, and explored its comparative benefits among youth in families with high versus low expressed emotion (EE).Participants were 40 youth (mean 12.32.8 years, range 9-17) with BD not otherwise specified, major depressive disorder, or cyclothymic disorder who had a first-degree relative with BD I or II and active mood symptoms (Young Mania Rating Scale [YMRS]>11 or Child Depression Rating Scale>29). Participants were randomly allocated to FFT-High Risk version (FFT-HR; 12 sessions of psychoeducation and training in communication and problem-solving skills) or an education control (EC; 1-2 family sessions).Youth in FFT-HR had more rapid recovery from their initial mood symptoms (hazard ratio = 2.69, p = .047), more weeks in remission, and a more favorable trajectory of YMRS scores over 1 year than youth in EC. The magnitude of treatment effect was greater among youth in high-EE (versus low-EE) families.FFT-HR may hasten and help sustain recovery from mood symptoms among youth at high risk for BD. Longer follow-up will be necessary to determine whether early family intervention has downstream effects that contribute to the delay or prevention of full manic episodes in vulnerable youth.

View details for DOI 10.1016/j.jaac.2012.10.007

View details for Web of Science ID 000314430000004

View details for PubMedID 23357439

Brain structural response in individuals at familial risk for bipolar disorder: a tale of two outcomes. Biological psychiatry Singh, M. K., Chang, K. D. 2013; 73 (2): 109-110

View details for DOI 10.1016/j.biopsych.2012.11.005

View details for PubMedID 23245951

Reward Processing in Adolescents With Bipolar I Disorder JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Singh, M. K., Chang, K. D., Kelley, R. G., Cui, X., Sherdell, L., Howe, M. E., Gotlib, I. H., Reiss, A. L. 2013; 52 (1): 68-83

Abstract

Bipolar disorder (BD) is a debilitating psychiatric condition that commonly begins in adolescence, a developmental period that has been associated with increased reward seeking. Because youth with BD are especially vulnerable to negative risk-taking behaviors, understanding the neural mechanisms by which dysregulated affect interacts with the neurobehavioral processing of reward is clearly important. One way to clarify how manic symptoms evolve in BD is to "prime" the affect before presenting rewarding stimuli. The objective of this study was to investigate the neural effects of an affective priming task designed to positively induce mood before reward processing in adolescents with and without BD.Neural activity and behaviors during the anticipation of and response to monetary reward and loss after an affective prime were compared using functional magnetic resonance imaging in 13- to 18-year-old adolescents with a recent onset of BD-I (n = 24) and demographically matched healthy comparison youth (n = 24).Compared with the healthy control youth, youth with BD had speeded reaction times and showed decreased activation in the thalamus and inferior temporal gyrus while anticipating gains after priming but increased activations in the middle frontal gyrus and parietal cortices while anticipating losses after priming. Youth with BD also showed less activation in the inferior parietal lobule, thalamus, and superior frontal gyrus while receiving losses after priming.Aberrant prefrontal and subcortical activations during reward processing suggest mechanisms that may underlie disordered self-awareness during goal pursuit and motivation in BD. Longitudinal studies are needed to examine whether this pattern of neural activation predicts a poorer long-term outcome.

View details for DOI 10.1016/j.jaac.2012.10.004

View details for Web of Science ID 000313143400008

The Neural Effects of Psychotropic Medications in Children and Adolescents CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA Singh, M. K., Chang, K. D. 2012; 21 (4): 753-?

Abstract

Little is known about the neurobiological effects of psychotropic medications used in the treatment of children and adolescents diagnosed with a psychiatric disorder. This review provides a synopsis of the literature demonstrating the neural effects associated with exposure to psychotropic medication in youth using multimodal neuroimaging. The article concludes by illustrating how, taken together, these studies suggest that pharmacological interventions during childhood do indeed affect brain structure and function in a detectable manner, and the effects appear to be ameliorative.

View details for DOI 10.1016/j.chc.2012.07.010

View details for Web of Science ID 000311194100005

View details for PubMedID 23040900

Volumetric reductions in the subgenual anterior cingulate cortex in adolescents with bipolar I disorder BIPOLAR DISORDERS Singh, M. K., Chang, K. D., Chen, M. C., Kelley, R. G., Garrett, A., Mitsunaga, M. M., Bararpour, L., Howe, M., Reiss, A. L., Gotlib, I. H. 2012; 14 (6): 585-596

Abstract

A range of prefrontal and subcortical volumetric abnormalities have been found in adults and adolescents with bipolar disorder. It is unclear, however, if these deficits are present early in the onset of mania or are a consequence of multiple mood episodes or prolonged exposure to medication. The goal of this study was to examine whether youth with bipolar I disorder who recently experienced their first episode of mania are characterized by brain volumetric abnormalities.Anatomical images from magnetic resonance imaging of 26 13- to 18-year-old adolescents with bipolar I disorder and 24 age-comparable healthy controls with no personal or family history of psychopathology were analyzed using whole-brain voxel-based morphometry (VBM).Compared with healthy controls, adolescents with bipolar I disorder had significantly less gray matter volume in the left subgenual cingulate cortex [p<0.05, family-wise error (FWE)-corrected].Adolescents with a recent single episode of mania have smaller subgenual cingulate cortex volume than do their healthy counterparts, suggesting that this anomaly occurs early in the onset of, or may predate the disorder. Longitudinal studies are needed to examine the impact of this volumetric reduction on the course and outcome of this disorder.

View details for DOI 10.1111/j.1399-5618.2012.01043.x

View details for Web of Science ID 000308286800002

View details for PubMedID 22938166

Information processing in adolescents with bipolar I disorder JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY Whitney, J., Joormann, J., Gotlib, I. H., Kelley, R. G., Acquaye, T., Howe, M., Chang, K. D., Singh, M. K. 2012; 53 (9): 937-945

Abstract

Cognitive models of bipolar I disorder (BD) may aid in identification of children who are especially vulnerable to chronic mood dysregulation. Information-processing biases related to memory and attention likely play a role in the development and persistence of BD among adolescents; however, these biases have not been extensively studied in youth with BD.We administered the self-referent encoding task and the dot-probe task to adolescents with bipolar I disorder (BD, n = 35) and a demographically similar healthy comparison group (HC, n = 25) at baseline, and at a 1-year follow-up in a subset of this cohort (n = 22 per group).At both baseline and 1-year follow-up, there were significant interactions of group (BD, HC) and valence of stimulus (positive, negative adjective) on endorsement and recall of self-referent adjectives. HC adolescents endorsed and recalled more positive self-referent adjectives at baseline and follow-up while adolescents with BD endorsed and recalled more negative self-referent adjectives at baseline but not follow-up. Over time, depression symptomatology was associated with impaired memory for positive self-referent adjectives. There were no group differences in attentional bias at either time points.Adolescents with BD exhibit bias away from endorsement and recall of positive adjectives, which remained stable over time and independent of mood state.

View details for DOI 10.1111/j.1469-7610.2012.02543.x

View details for Web of Science ID 000307954500006

View details for PubMedID 22390273

In this issue/abstract thinking: update your socioeconomic status. Journal of the American Academy of Child and Adolescent Psychiatry Singh, M. K. 2012; 51 (9): 853-854

View details for DOI 10.1016/j.jaac.2012.06.015

View details for PubMedID 22917195

Abnormal Amygdala and Prefrontal Cortex Activation to Facial Expressions in Pediatric Bipolar Disorder JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Garrett, A. S., Reiss, A. L., Howe, M. E., Kelley, R. G., Singh, M. K., Adleman, N. E., Karchemskiy, A., Chang, K. D. 2012; 51 (8): 821-831

Abstract

Previous functional magnetic resonance imaging (fMRI) studies in pediatric bipolar disorder (BD) have reported greater amygdala and less dorsolateral prefrontal cortex (DLPFC) activation to facial expressions compared to healthy controls. The current study investigates whether these differences are associated with the early or late phase of activation, suggesting different temporal characteristics of brain responses.A total of 20 euthymic adolescents with familial BD (14 male) and 21 healthy control subjects (13 male) underwent fMRI scanning during presentation of happy, sad, and neutral facial expressions. Whole-brain voxelwise analyses were conducted in SPM5, using a three-way analysis of variance (ANOVA) with factors group (BD and healthy control [HC]), facial expression (happy, sad, and neutral versus scrambled), and phase (early and late, corresponding to the first and second half of each block of faces).There were no significant group differences in task performance, age, gender, or IQ. Significant activation from the main effect of group included greater DLPFC activation in the HC group, and greater amygdala/hippocampal activation in the BD group. The interaction of Group Phase identified clusters in the superior temporal sulcus/insula and visual cortex, where activation increased from the early to late phase of the block for the BD but not the HC group.These findings are consistent with previous studies that suggest deficient prefrontal cortex regulation of heightened amygdala response to emotional stimuli in pediatric BD. Increasing activation over time in superior temporal and visual cortices suggests difficulty processing or disengaging attention from emotional faces in BD.

View details for DOI 10.1016/j.jaac.2012.06.005

View details for Web of Science ID 000307128300010

View details for PubMedID 22840553

Altered Small-World Properties of Gray Matter Networks in Major Depression Singh, M. K., Kesler, S. R., Hosseini, H., Kelley, R. G., Amatya, D., Hamilton, P., Chen, M. C., Gotlib, I. H. ELSEVIER SCIENCE INC. 2012: 106S-106S
In this issue/abstract thinking: of mice, monkeys, and men. Journal of the American Academy of Child and Adolescent Psychiatry Singh, M. K. 2012; 51 (3): 231-232

View details for DOI 10.1016/j.jaac.2011.12.013

View details for PubMedID 22365457

Biological Evidence for a Neurodevelopmental Model of Pediatric Bipolar Disorder ISRAEL JOURNAL OF PSYCHIATRY AND RELATED SCIENCES Roybal, D. J., Singh, M. K., Cosgrove, V. E., Howe, M., Kelley, R., Barnea-Goraly, N., Chang, K. D. 2012; 49 (1): 28-43
Characterization and Factors Associated with Sleep Quality in Adolescents with Bipolar I Disorder CHILD PSYCHIATRY & HUMAN DEVELOPMENT Roybal, D. J., Chang, K. D., Chen, M. C., Howe, M. E., Gotlib, I. H., Singh, M. K. 2011; 42 (6): 724-740

Abstract

Sleep disturbance is an early marker for bipolar disorder (BD) onset in youth. We characterized sleep quality in adolescents experiencing mania within the last 6-12 months. We examined the association between mood and sleep in 27 adolescents with BD and 24 matched healthy controls (HC). Subjects were assessed by parent and teen report of sleep, a semi-structured clinical interview, the Young Mania Rating Scale (YMRS), and the Childhood Depression Rating Scale (CDRS-R). Average BD youth YMRS (mean 20.3 7.3) and CDRS-R (mean 42.4 14.1) scores indicated they were still ill at time of assessment. Compared to HCs, adolescents with BD have distinct patterns of prolonged sleep onset latency, frequent nighttime awakenings, and increased total time awake. Mood symptoms, specifically excessive guilt, self-injurious behavior, and worsening evening mood, interfered with sleep. Further studies are needed to determine whether early regulation of sleep would improve long-term outcome in BD youth.

View details for DOI 10.1007/s10578-011-0239-0

View details for Web of Science ID 000296879200008

View details for PubMedID 21701911

In this issue/abstract thinking: here, there, everywhere! Journal of the American Academy of Child and Adolescent Psychiatry Singh, M. K. 2011; 50 (9): 849-850

View details for DOI 10.1016/j.jaac.2011.06.014

View details for PubMedID 21871364

Changes in Brain Activation Following Family-Focused Treatment in Youth At-Risk for Bipolar Disorder Garrett, A. S., Reiss, A. L., Miklowitz, D. J., Acquaye, T. K., Cosgrove, V. E., Singh, M. K., Howe, M. E., Kelley, R. G., Taylor, D., George, E., Chang, K. ELSEVIER SCIENCE INC. 2011: 163S-163S
Neurochemical deficits in the cerebellar vermis in child offspring of parents with bipolar disorder BIPOLAR DISORDERS Singh, M. K., Spielman, D., Libby, A., Adams, E., Acquaye, T., Howe, M., Kelley, R., Reiss, A., Chang, K. D. 2011; 13 (2): 189-197

Abstract

We aimed to compare concentrations of N-acetyl aspartate, myo-inositol, and other neurometabolites in the cerebellar vermis of offspring at risk for bipolar disorder (BD) and healthy controls to examine whether changes in these neuronal metabolite concentrations occur in at-risk offspring prior to the onset of mania.A total of 22 children and adolescents aged 9-17 years with a familial risk for bipolar I or II disorder [at-risk offspring with non-bipolar I disorder mood symptoms (AR)], and 25 healthy controls (HC) were examined using proton magnetic resonance spectroscopy at 3T to study metabolite concentrations in an 8-cc voxel in the cerebellar vermis.Decreased myo-inositol and choline concentrations in the vermis were seen in the AR group compared to HC (p<0.01).Decreased cellular metabolism and interference with second messenger pathways may be present in the cerebellar vermis in youth at risk for BD as evident by decreased myo-inositol and choline concentrations in this region. These results may be limited by a cross-sectional design, co-occurring diagnoses, and medication exposure. Longitudinal studies are necessary to determine whether early neurochemical changes can predict the development of mania. Improved methods for identifying children with certain neurochemical vulnerabilities may inform preventive and early intervention strategies prior to the onset of mania.

View details for DOI 10.1111/j.1399-5618.2011.00902.x

View details for Web of Science ID 000288863500008

View details for PubMedID 21443573

In this issue/abstract thinking: back to the future. Journal of the American Academy of Child and Adolescent Psychiatry Singh, M. K. 2011; 50 (3): 205-206

View details for DOI 10.1016/j.jaac.2010.12.011

View details for PubMedID 21334558

Early psychosocial intervention for youth at risk for bipolar I or II disorder: a one-year treatment development trial BIPOLAR DISORDERS Miklowitz, D. J., Chang, K. D., Taylor, D. O., George, E. L., Singh, M. K., Schneck, C. D., Dickinson, L. M., Howe, M. E., Garber, J. 2011; 13 (1): 67-75

Abstract

Previous studies have identified behavioral phenotypes that predispose genetically vulnerable youth to a later onset of bipolar I or II disorder, but few studies have examined whether early psychosocial intervention can reduce risk of syndromal conversion. In a one-year open trial, we tested a version of family-focused treatment adapted for youth at high risk for bipolar disorder (FFT-HR).A referred sample of 13 children (mean 13.42.69 years; 4 boys, 9 girls) who had a parent with bipolar I or II disorder participated at one of two outpatient specialty clinics. Youth met DSM-IV criteria for major depressive disorder (n=8), cyclothymic disorder (n=1), or bipolar disorder not otherwise specified (n=4), with active mood symptoms in the past month. Participants were offered FFT-HR (12 sessions in four months) with their parents, plus psychotropic medications as needed. Independent evaluators assessed depressive symptoms, hypomanic symptoms, and global functioning at baseline and then every four months for one year, with retrospective severity and impairment ratings made for each week of the follow-up interval.Families were mostly adherent to the treatment protocol (85% retention), and therapists administered the FFT-HR manual with high levels of fidelity. Youth showed significant improvements in depression, hypomania, and psychosocial functioning scores on the Adolescent Longitudinal Interval Follow-up Evaluation. They also showed significant improvements in Young Mania Rating Scale and Children's Depression Rating Scale scores.FFT-HR is a promising intervention for youth at high risk for BD. Larger-scale randomized trials that follow youth into young adulthood will be necessary to determine whether early psychosocial intervention can reduce the probability of developing bipolar I or II disorder among genetically vulnerable youth.

View details for DOI 10.1111/j.1399-5618.2011.00890.x

View details for Web of Science ID 000287311200007

View details for PubMedID 21320254

Antidepressants and Psychostimulants in Pediatric Populations Is there an Association with Mania? PEDIATRIC DRUGS Goldsmith, M., Singh, M., Chang, K. 2011; 13 (4): 225-243

Abstract

This article reviews the literature that examines whether exposure to psychostimulants or antidepressants precipitates or exacerbates manic symptoms, or decreases the age at onset of mania in pediatric populations. A PubMed search using relevant key words identified studies targeting five distinct clinical groups: (i) youth without a diagnosis of bipolar disorder (BD) at the time of exposure to psychostimulants; (ii) youth with a diagnosis of BD at the time of exposure to psychostimulants; (iii) youth without a diagnosis of BD at the time of exposure to antidepressants; (iv) youth with a diagnosis of BD at the time of exposure to antidepressants; and (v) youth who develop BD after exposure to these medications. In patients with attention-deficit hyperactivity disorder (ADHD), the risk for mania was found to be relatively low with the use of psychostimulants. For patients with BD and ADHD, effective mood stabilization is important prior to adding a stimulant. For children with depression and/or anxiety, the risk of antidepressant-induced mania (AIM) was generally low (<2%), but the risk of general 'activation' secondary to a selective serotonin reuptake inhibitor (SSRI) may be greater (2-10%). However, rates of AIM in specialty clinics appear to be much higher. SSRIs may be particularly problematic in specific populations, such as those with some symptoms of mania or a family history of BD, but the precise risk is unknown. There is no clear evidence that stimulants or SSRIs accelerate the natural course of BD development in overall samples, but in individual cases prescribers should proceed cautiously when using these agents in youth already at risk for developing BD, such as those with ADHD and mood dysregulation, a history of prior AIM, a history of psychosis, or a family history of BD.

View details for Web of Science ID 000292996000004

View details for PubMedID 21692547

Is Developmental and Behavioral Pediatrics Training Related to Perceived Responsibility for Treating Mental Health Problems? ACADEMIC PEDIATRICS Horwitz, S. M., Caspary, G., Storfer-Isser, A., Singh, M., Fremont, W., Golzari, M., Stein, R. E. 2010; 10 (4): 252-259

Abstract

The aim of this study was to investigate training in developmental and behavioral pediatrics (DBP) for graduating residents, their competencies in diagnosing and treating child mental health (MH) problems, and whether the amount of DBP training and/or perceived competencies are associated with perceived responsibility for treating 3 MH problems.Data were collected from 636 residents who completed the American Academy of Pediatrics's 2007 Graduating Residents Survey. The survey included questions on training and self-rated competencies in multiple MH skill areas and perceived responsibility for identifying and treating/managing children's MH problems. Weighted multivariable logistic regression analyses examined associations between training, competencies, and perceived responsibility for treating/managing attention-deficit/hyperactivity disorder (ADHD), anxiety, and depression.Ninety percent of respondents completed a DBP rotation, with 86% reporting >3 to 4 weeks of training. Duration of DBP rotation was related to training and perceived competencies in MH skill areas, and nearly all residents who reported high competencies were trained in those skill areas. However, <50% reported their competencies as "very good" or "excellent." Residents with training and high competency in dosing with medications were most likely to agree that pediatricians should be responsible for treating/managing ADHD, anxiety, and depression.DBP training is highly associated with self-rated MH competencies, and highly assessed competencies are related to perceived responsibility for treating/managing common MH problems; yet 14% of graduating residents have <3 to 4 weeks of DBP training. These results argue for providing more high-quality educational experience with proven effectiveness to produce confident pediatricians who will be more responsive to identifying and treating MH problems of their patients.

View details for Web of Science ID 000280074000010

View details for PubMedID 20554260

In this issue/Abstract thinking: Response to intervention in child psychiatry. Journal of the American Academy of Child and Adolescent Psychiatry Singh, M. K. 2010; 49 (7): 633-634

View details for DOI 10.1016/j.jaac.2010.04.007

View details for PubMedID 20610131

Brain glutamatergic characteristics of pediatric offspring of parents with bipolar disorder PSYCHIATRY RESEARCH-NEUROIMAGING Singh, M., Spielman, D., Adleman, N., Alegria, D., Howe, M., Reiss, A., Chang, K. 2010; 182 (2): 165-171

Abstract

We wished to determine whether decreases in prefrontal glutamate concentrations occur in offspring of parents with bipolar disorder with and at high risk for mania. Sixty children and adolescents, 9-18 years old, of parents with bipolar I or II disorder (20 offspring with established history of mania, "BD", 20 offspring with symptoms subsyndromal to mania, "SS", and 20 healthy controls "HC") were examined using proton magnetic resonance spectroscopy at 3T to study glutamatergic metabolite concentrations in the anterior cingulate cortex (ACC). A signal for reductions in absolute glutamate concentrations in the ACC was seen in the BD compared with HC and SS groups. No other statistically significant differences among groups were found. Offspring of parents with BD with prior histories of mania may have disruptions in glutamatergic function compared with HC or children at risk for BD who have not yet developed mania. Longitudinal studies are necessary to confirm whether prefrontal glutamate decreases only after the onset of full mania.

View details for DOI 10.1016/j.pscychresns.2010.01.003

View details for Web of Science ID 000278701500013

View details for PubMedID 20413280

Prefrontal Grey Matter Volume Abnormalities in Adolescent First Episode Mania Singh, M. K., Chang, K. D., Reiss, A. L., Gotlib, I. H. ELSEVIER SCIENCE INC. 2010: 222S-223S
Neural Processing of Reward and Loss in Girls at Risk for Major Depression ARCHIVES OF GENERAL PSYCHIATRY Gotlib, I. H., Hamilton, J. P., Cooney, R. E., Singh, M. K., Henry, M. L., Joormann, J. 2010; 67 (4): 380-387

Abstract

Deficits in reward processing and their neural correlates have been associated with major depression. However, it is unclear if these deficits precede the onset of depression or are a consequence of this disorder.To determine whether anomalous neural processing of reward characterizes children at familial risk for depression in the absence of a personal history of diagnosable disorder.Comparison of neural activity among children at low and high risk for depression as they process reward and loss.University functional magnetic resonance imaging facility.Thirteen 10- to 14-year-old never-disordered daughters of mothers with recurrent depression ("high risk") and 13 age-matched never-disordered daughters with no family history of depression ("low risk"). Main Outcome Measure Neural activity, as measured using functional magnetic resonance imaging, in key reward and attention neural circuitry during anticipation and receipt of reward and loss.While anticipating gains, high-risk participants showed less activation than did their low-risk counterparts in the putamen and left insula but showed greater activation in the right insula. When receiving punishment, high-risk participants showed greater activation in the dorsal anterior cingulate gyrus than did low-risk participants, who showed greater activation in the caudate and putamen.Familial risk for depression affects neural mechanisms underlying the processing of reward and loss; young girls at risk for depression exhibit anomalies in the processing of reward and loss before the onset of depressive symptoms. Longitudinal studies are needed to examine whether these characteristics predict the subsequent onset of depression.

View details for Web of Science ID 000276312800008

View details for PubMedID 20368513

Neural Correlates of Response Inhibition in Pediatric Bipolar Disorder JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Singh, M. K., Chang, K. D., Mazaika, P., Garrett, A., Adleman, N., Kelley, R., Howe, M., Reiss, A. 2010; 20 (1): 15-24

Abstract

Pediatric bipolar disorder is characterized by core deficits in mood and executive function and commonly co-occurs with attention-deficit/hyperactivity disorder (ADHD). We aimed to examine response inhibition in this population, as an element of executive function, which, if aberrant, may interfere with learning and information processing.Children (9-18 years) with bipolar I or II disorder (BD, n = 26) and age, gender, and intelligence quotient (IQ) comparable healthy children (HC, n = 22) without any psychopathology were given a standardized Go/NoGo computerized task measuring response inhibition. A whole-brain functional magnetic resonance imaging (MRI) group analysis was performed using statistical parametric mapping software (SPM2) for comparing NoGo to Go epochs.There were no statistically significant group differences between groups in age, gender, or ethnicity. The BD group had high rates of co-morbid disorders, including 81% with ADHD, 62% with oppositional defiant disorder (ODD), and 46% with anxiety disorders. This BD group had fewer correct responses on Go (84% vs. 96%, T[46] = 3.35, p = 0.002) and overall (85% vs. 94%, T[46] = 4.12, p = 0.0002) trials as compared to the HC group. However, there were no statistically significant group differences in response inhibition on NoGo trials (p = 0.11). In the NoGo-Go contrast, the BD group showed increased neural activation in the right dorsolateral prefrontal cortex (DLPFC) compared to HC (T[46] = 4.21, p < 0.001).During accurate NoGo but impaired Go trial performance, children with BD showed increased right DLPFC activation versus controls, suggesting increased recruitment of executive control regions for accurate response inhibition. Studies relating these results to mood regulation in pediatric BD are warranted.

View details for DOI 10.1089/cap.2009.0004

View details for Web of Science ID 000274636300003

View details for PubMedID 20166792

Atypical Antipsychotics for Acute Manic and Mixed Episodes in Children and Adolescents with Bipolar Disorder Efficacy and Tolerability DRUGS Singh, M. K., Ketter, T. A., Chang, K. D. 2010; 70 (4): 433-442

Abstract

The diagnosis of bipolar disorder (BD) in children is increasing, and often requires a comprehensive treatment plan to address a complex array of symptoms and associated morbidities. Pharmacotherapy, in combination with psychotherapeutic interventions, is essential for the treatment and stabilization of disrupted mood. Current evidence collectively demonstrates, by randomized controlled design, that atypical antipsychotics have efficacy for the treatment of acute manic or mixed symptoms in children and adolescents with BD. Additional longitudinal and biological studies are warranted to characterize the effects of atypical antipsychotics on all phases and stages of bipolar illness development in children and adolescents.

View details for Web of Science ID 000276278400004

View details for PubMedID 20205485

Neurochemical substrates of risk in pediatric offspring of parents with bipolar disorder Singh, M. K., Spielman, D., Kelley, R., ALEGRIA, D., Howe, M., Reiss, A., Chang, K. WILEY-BLACKWELL. 2009: 80-80
Inhibition and attention in adolescents with nonmanic mood disorders and a high risk for developing mania JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY Singh, M. K., DelBello, M. P., Fleck, D. E., Shear, P. K., Strakowski, S. M. 2009; 31 (1): 1-7

Abstract

This study examines psychomotor inhibition, sustained attention, and inhibitory attentional control in adolescents (ages 12-18 years) with a nonmanic mood disorder and with a first-degree relative with bipolar I disorder (MD, N = 20) and demographically matched healthy children of parents without any psychiatric disorder (HC, N = 13). MD participants showed abnormal performance in stop signal reaction time and latency (d = 1.28 and 1.64, respectively), sustained attention response bias (d = 0.75), and color naming speed (d = 0.88). The results indicate that MD participants exhibit psychomotor disinhibition, marginal cognitive slowing and cautious response biases, but no formal deficits in sustained or selective attention.

View details for DOI 10.1080/13803390801945038

View details for Web of Science ID 000261739200001

View details for PubMedID 18608697

Temperament in Child Offspring of Parents with Bipolar Disorder JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Singh, M. K., DelBello, M. P., Strakowski, S. M. 2008; 18 (6): 589-593

Abstract

The aim of this study was to examine the relationship between temperament and psychopathology in child offspring of parents with bipolar disorder.The Dimensions of Temperament-Revised (DOTS-R) and the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH U K-SADS) were used to assess temperament and psychopathology, respectively in offspring (8-18 years) of parents with bipolar I disorder (OBP, n = 31) and demographically similar healthy offspring of parents without any Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) diagnosis (OHC, n = 21).Compared to OHC, OBP had increased Activity Level-General scores (effect size, d = -0.78), and a trend for decreased Task Orientation (d = -0.78). OBP with mood disorders had trends for decreased Approach (d = 0.89), Flexibility-Rigidity (d = 1.01), Rhythmicity-Sleep (d = 0.79), and Task Orientation (d = 0.89) as compared to OBP without mood disorders. OBP with attention-deficit/hyperactivity disorder (ADHD) showed a trend for decreased Task Orientation scores compared with those without ADHD (d = 0.82).Although limited by parent report, specific temperaments may be important in characterizing offspring of parents with bipolar disorder. Longitudinal studies to determine if certain temperaments inform treatment response and prognosis in this population are needed.

View details for DOI 10.1089/cap.2007.142

View details for Web of Science ID 000261992900006

View details for PubMedID 19108663

Neuroanatornical characterization of child offspring of bipolar parents JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Singh, M. K., DelBello, M. P., Adler, C. M., Stanford, K. E., Strakowski, S. M. 2008; 47 (5): 526-531

Abstract

To examine structural differences in selected anterior limbic brain regions between at-risk children of parents with bipolar I disorder and children with healthy parents. We hypothesized that at-risk (AR) children would exhibit abnormalities in brain regions that are involved in mood regulation.Children (8-12 years old) of parents with bipolar I disorder (AR children, n = 21) and of parents without any DSM-IV Axis I disorder (healthy controls, n = 24) were evaluated using diagnostic assessments and brain magnetic resonance imaging. Morphometric analyses were used to examine group differences in the prefrontal cortical, thalamic, striatal, and amygdalar volumes.Nine (43%) of the AR children met DSM-IV-TR criteria for a nonbipolar mood disorder at the time of assessment. AR and healthy control children did not demonstrate statistically significant differences across regions of interest (Wilks lambda =.86, F4,39 = 1.64, p = .18; effect size, f = 0.19). Post hoc analyses of covariance showed the largest relative effect size was contributed by the prefrontal cortex (f = 0.26).Eight- to 12-year-old children with a familial risk for mania do not exhibit any statistically significant volumetric differences in the prefrontal cortex, thalamus, striatum, or amygdala as compared with age-matched children of parents without any psychopathology. Longitudinal studies examining whether structural changes over time may be associated with vulnerability for developing subsequent bipolar disorder are needed to clarify the underlying pathophysiology of this disorder.

View details for DOI 10.1097/CHI.0b013e318167655a

View details for Web of Science ID 000255261000008

View details for PubMedID 18356766

Prospective neurochemical characterization of child offspring of parents with bipolar disorder Singh, M. K., Chang, K. D., Spielman, D. M. ELSEVIER SCIENCE INC. 2008: 191S-191S
Obstetrical complications in children at high risk for bipolar disorder JOURNAL OF PSYCHIATRIC RESEARCH Singh, M. K., DelBello, M. P., Soutullo, C., Stanford, K. E., McDonough-Ryan, P., Strakowski, S. M. 2007; 41 (8): 680-685

Abstract

To examine obstetrical complications as a risk factor for developing bipolar disorder (BPD). We hypothesized that children with a bipolar parent would be at greater risk for obstetrical complications than demographically matched children of healthy adults. Additionally, within this "at-risk" (AR) sample, we hypothesized that obstetrical complications would be associated with the development of psychiatric disorders.The Washington University in St. Louis Kiddie-Schedule for Affective Disorders and Schizophrenia (WASH-U KSADS) was administered to children (AR) who had at least one parent with BPD (N=36) and children of healthy parents (HC) (N=27), by raters who were blind to diagnostic category. To assess obstetrical risk history, the Rochester Research Obstetrical Scale (ROS) was administered to parents of AR and HC children.Children at familial risk for BPD had greater total (p=0.02) and prenatal (p=0.006) obstetrical complication scores than children of healthy parents. However, obstetrical complications were not associated with the development of affective, anxiety, or disruptive behavioral disorders within the at-risk group.Our data suggest that compared with children of families without BPD, children of parents with BPD may be at greater risk for obstetrical complications, particularly those that occur during the prenatal period; however, at this early follow-up period factors other than obstetrical complications appear to contribute to the differences in rates of psychiatric disorders between these groups.

View details for DOI 10.1016/j.jpsychires.2006.02.009

View details for Web of Science ID 000246242900009

View details for PubMedID 16698037

Psychopathology in children of bipolar parents JOURNAL OF AFFECTIVE DISORDERS Singh, M. K., DelBello, M. P., Stanford, K. E., Soutullo, C., McDonough-Ryan, P., McElroy, S. L., Strakowski, S. M. 2007; 102 (1-3): 131-136

Abstract

Few studies have examined the psychopathological profiles of child offspring of bipolar parents. Such investigations are useful as a first step to identifying potential prodromal manifestations of bipolar disorder.The presence of psychopathology in 37 children with at least one parent with bipolar I disorder and 29 demographically matched children with parents free of any DSM-IV Axis I psychopathology was evaluated using the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U KSADS).Twenty-nine (78%) of 37 high-risk children were diagnosed with at least one DSM-IV Axis I diagnosis as compared to seven (24%) of 29 children of healthy control parents (Fisher's exact test, p < 0.0001, odds ratio=11, 95% CI=3.33, 33). Sixteen percent (N=6) of high-risk offspring met DSM-IV criteria for bipolar I disorder as compared to none of the healthy control offspring (Fisher's exact test, p < 0.03). High-risk offspring also had statistically significant elevations in rates of other affective and disruptive behavior disorders as well as subsyndromal manifestations of psychopathology.Children of bipolar parents had an elevated risk for developing bipolar and other psychiatric disorders. The study of children of bipolar parents who are at high risk for developing bipolar disorder themselves is essential to identify potential prodromal manifestations of the disorder and to eventually establish targeted early intervention strategies. Longitudinal studies to confirm the prodromal manifestations of bipolar disorder and risk factors associated with the development of specific diagnoses in children are needed.

View details for DOI 10.1016/j.jad.2007.01.004

View details for Web of Science ID 000248823300016

View details for PubMedID 17275096

Medical management of pediatric mood disorders PEDIATRIC ANNALS Singh, M. K., Pfeifer, J. C., Barzman, D. H., Kowatch, R. A., DelBello, M. P. 2007; 36 (9): 552-563

View details for Web of Science ID 000249411000006

View details for PubMedID 17910203

Pharmacotherapy for child and adolescent mood disorders PSYCHIATRIC ANNALS Singh, M. K., Pfeifer, J. C., Barzman, D., Kowatch, R. A., DelBello, M. P. 2007; 37 (7): 465-476
Acute dystonia associated with aripiprazole in a child JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Singh, M. K., DelBello, M. P., Adler, C. M. 2007; 46 (3): 306-307

View details for DOI 10.1097/chi.0b013e31802ed925

View details for Web of Science ID 000244428800004

View details for PubMedID 17314714

Co-occurrence of bipolar and attention-deficit hyperactivity disorders in children BIPOLAR DISORDERS Singh, M. K., DelBello, M. P., Kowatch, R. A., Strakowski, S. M. 2006; 8 (6): 710-720

Abstract

Pediatric bipolar disorder (BPD) and attention-deficit hyperactivity disorder (ADHD) co-occur more frequently than expected by chance. In this review, we examine 4 potential explanations for the high rate of this common co-occurrence: (i) BPD symptom expression leads to overdiagnosis of ADHD in BPD youth; (ii) ADHD is a prodromal or early manifestation of pediatric-onset BPD; (iii) ADHD and associated factors (e.g., psychostimulants) lead to the onset of pediatric BPD; and (iv) ADHD and BPD share an underlying biological etiology (i.e., a common familial or genetic risk or underlying neurophysiology).Peer-reviewed publications of studies of children and adolescents with comorbid BPD and ADHD were reviewed.There is a bidirectional overlap between BPD and ADHD in youth, with high rates of ADHD present in children with BPD (up to 85%), and elevated rates of BPD in children with ADHD (up to 22%). Phenomenologic, genetic, family, neuroimaging, and treatment studies revealed that BPD and ADHD have both common and distinct characteristics. While there are data to support all 4 explanations postulated in this paper, the literature most strongly suggests that ADHD symptoms represent a prodromal or early manifestation of pediatric-onset BPD in certain at-risk individuals. Bipolar disorder with comorbid ADHD may thus represent a developmentally specific phenotype of early-onset BPD.The etiology of comorbid BPD and ADHD is likely multifactorial. Additional longitudinal and biological studies are warranted to clarify the relationships between BPD and ADHD since they may have important diagnostic and treatment implications.

View details for Web of Science ID 000242373200007

View details for PubMedID 17156157

Pain insensitivity in schizophrenia: trait or state marker? Journal of psychiatric practice Singh, M. K., Giles, L. L., Nasrallah, H. A. 2006; 12 (2): 90-102

Abstract

As early as the turn of the 20th century, clinicians observed patients with schizophrenia failing to respond to the pain of a myocardial infarction, ruptured appendix, or perforated bowel. Although this pain insensitivity in individuals with psychosis has been described in the literature for many years, the phenomenon is still poorly understood. We therefore reviewed the literature for findings concerning whether pain insensitivity in schizophrenia represents a state or a trait marker.A comprehensive Medline search of the literature on pain insensitivity in subjects with schizophrenia was conducted.While the literature contains anecdotal observations, case reports, and a few rigorous clinical studies concerning patients with schizophrenia being relatively indifferent to pain, there is a dearth of empirical, well-controlled studies in this area. Although early studies that examined the response of individuals with schizophrenia to thermal or electrical pain were constrained by a variety of methodological confounders, studies on this topic suggest that the higher pain thresholds observed in schizophrenia are best explained by a complex, multifactorial model. Most intriguing are the results of one recent study that found pain insensitivity in family members of persons with schizophrenia, suggesting that this phenomenon may be a trait or endophenotype rather than being due to a psychotic state.Pain insensitivity in individuals with schizophrenia, which is associated with increased morbidity and mortality, is poorly understood. It is possible that pain insensitivity might serve as a prodromal predictor of susceptibility for schizophrenia. Future studies are needed to further clarify the neurobiology, pathophysiology, and practical clinical implications of this phenomenon.

View details for PubMedID 16728905