Effects of the Bridges to Baccalaureate Program on Student Success

The Baccalaureate & Beyond (B&B) programs at Purchase College, State University of New York are designed to help underrepresented community college students successfully transition to and graduate from 4-year schools. These programs have been at the college for between 10 and 15 years and include an intensive 5-week summer program. In the current study we investigated whether students who participated in the programs and then transferred to Purchase College (n = 75) were more successful than similar community college students who did not participate in the programs before transferring to Purchase College (n = 75). Students were matched for Community College of origin, major and ethnicity. Post-graduate information was retrieved through the National Student Clearing House, and all other information was retrieved from the Purchase College institutional records. We examined major GPA, cumulative GPA, total credits completed, graduation rate, graduation major, graduate school attendance, and graduate degrees. We hypothesized that transfer students who participated in the program would have higher major GPAs and cumulative GPAs, more credits completed, and a higher rate of graduation and graduate school attendance compared to non-participating students. As of Spring 2015, data is being collected

Funktionelle Konsequenzen von Mutationen im Melanocortin-4-Rezeptorgen bei adipösen Kindern und Jugendlichen

Der Melanocortin-4-Rezeptor spielt eine zentrale Rolle in der Gewichtsregulation, er vermittelt (indirekt) die anorexigenen Effekte des Leptin, indem er nach Aktivierung eine Einstellung der Nahrungsaufnahme und eine Erhöhung der Stoffwechselrate bedingt. Er ist der Familie der G-Protein-gekoppelten-Rezeptoren zuzuordnen und koppelt an ein Gs-Protein, welches die Adenylylcyclase aktivieren kann. Das Rezeptorprotein besteht aus 332 Aminosäuren und wird durch ein einziges Exon in der humanen Chromosomen-region 18q22 kodiert. Den endogenen Agonisten am Melanocortin-4-Rezeptor stellt das alpha-MSH dar, welches dem Vorläuferprotein Proopiomelanocortin (POMC) entstammt. Zahlreiche Mutationen im MC4R-Gen konnten bis zum heutigen Tage gefunden werden, die Hoffnung, hierin eine Hauptursache für die extreme kindliche Adipositas gefunden zu haben, hat sich leider nicht bestätigen können. Im Rahmen der vorliegenden Arbeit wurde eine sehr große Patientenpopulation (808 Kinder und Jugendlich mit einem durchschnittlichen BMI> 30 kg/m2), sowie deren Eltern auf Mutationen im Melanocortin-4-Rezeptor-Gen hin untersucht. Dabei ergab sich ein signifikant höherer Anteil von Trägern relevanter Mutationen als in der unter- bis normalgewichtigen Kontrollgruppe. Um die funktionelle Relevanz der 16 neu detektierten Mutationen untersuchen zu können, wurden diese zunächst in den Expressionsvektor pSG5 kloniert. Im Anschluss transfizierten wir COS7-Zellen mit den entsprechenden Proben und führten den cAMP-Akkumulations-Assay durch. Im Rahmen dieser Untersuchung zeigten die 16 Mutationen sehr unterschiedliche Verhaltensweisen. Ein Teil zeigte eine deutliche Reduktion der cAMP-Spiegel unter Stimulation mit alpha-MSH gegenüber denen des Wildtyp-Rezeptors. Ein anderer Teil zeigte Konzentrations-Wirkungskurven, die der des Wildtyps entsprachen. Zwei der von uns untersuchten Rezeptorvarianten (S127L und P230L) zeigten gar ohne Stimulation durch den entsprechenden Liganden Basalwerte, die weit über dem des Wildtyp-Allels lagen, so dass wir hier eine konstitutive Aktivität der Rezeptorproteine postulierten. Gerade die physiologische oder gar die gesteigerte Aktivität der veränderten Rezeptorproteine unter Agonisten-Stimulation lässt sich dabei nur schwer zur Erklärung des adipösen Phänotyps des betroffenen Probanden heranziehen. Der von uns ebenfalls im cAMP-Assay untersuchte, weit verbreitete Polymorphismus V103I zeigte in seiner Dosis-Wirkungskurve nur geringe Abweichungen von den Werten des Wildtyp-Rezeptors. Da sich ein Teil der Ausfälle in der Funktionalität bei Mutationen des MC4R-Gens durch einen gestörten Transport der veränderten Proteine in die Plasmamembran erklären lässt, untersuchten wir einige der Rezeptoren außerdem im Zelloberflächen-ELISA. Im ELISA ergab sich eine Reduktion der Oberflächen-expression der Mutationen G181D und S94R (welche bereits im cAMP-Assay einen totalen Funktionsausfall gezeigt hatten). Die von uns als konstitutiv aktiv deklarierten Rezeptorvarianten S127L und P230L zeigten jedoch wider Erwarten keinen behinderten Transport an die Zelloberfläche, im Gegenteil erschien die Zelloberflächen-Expression gegenüber der des Wildtyp-Rezeptors eher erhöht. Die restlichen im ELISA untersuchten Rezeptorvarianten zeigten eine ähnliche Expression an der Zelloberfläche wie der Wildtyp-MC4R. Auch der intrazelluläre Verbleib der veränderten Rezeptorproteine reicht hier also zur Klärung der Ursache der Fettsucht des betroffenen Patienten nicht aus. Die Frage, welche Bedeutung bestehenden Mutationen im Melanocortin-4-Rezeptor-Gen im Hinblick auf den adipösen Phänotyp des betroffenen Individuums zukommt, konnte von uns nur teilweise gelöst werden: Die Annahme eines autosomal dominanten Erbganges kann vor dem Hintergrund der Ergebnisse der funktionellen Untersuchungen (und vorheriger Beschreibungen schlanker, heterozygoter Träger funktionell relevanter Mutationen) eindeutig verneint werden. Aufgrund der Tatsache, dass in unserer Studienpopulation signifikant mehr Träger einer funktionell relevanten Mutation (15) auftraten (gegenüber keiner funktionell relevanten Mutation innerhalb der Kontrollgruppe) und alle funktionell relevanten Mutationen zudem von den Eltern auf ihre Kinder weitervererbt worden waren, konnten wir einen „major-gene-effect“ von funktionell relevanten MC4R-Varianten auf den Phänotyp des betroffenen Individuums postulieren. Da Melanocortin-4-Rezeptor-Mutationen jedoch nur für einen sehr geringen Prozentsatz der Adipositas-Fälle verantwortlich gemacht werden können, haben sie eine geringe epidemiologische, bei gleichzeitiger hoher individueller Relevanz

Randomized Controlled Trial of Individualized Arousal-Biofeedback for children and adolescents with Disruptive Behavior Disorders (DBD)

Background: Disruptive behavior disorders (including conduct disorder (CD) and oppositional defiant disorder (ODD)) are common childhood and adolescent psychiatric conditions often linked to altered arousal. The recommended first-line treatment is multi-modal therapy and includes psychosocial and behavioral interventions. Their modest effect sizes along with clinically and biologically heterogeneous phenotypes, emphasize the need for innovative personalized treatment targeting impaired functions such as arousal dysregulation. Methods: A total of 37 children aged 8-14 years diagnosed with ODD/CD were randomized to 20 sessions of individualized arousal biofeedback using skin conductance levels (SCL-BF) or active treatment as usual (TAU) including psychoeducation and cognitive-behavioral elements. The primary outcome was the change in parents´ ratings of aggressive behavior measured by the Modified Overt Aggression Scale. Secondary outcome measures were subscales from the Child Behavior Checklist, the Inventory of Callous-Unemotional traits and the Reactive-Proactive Aggression Questionnaire. Results: The SCL-BF treatment was neither superior nor inferior to the active TAU. Both groups showed reduced aggression after treatment with small effects for the primary outcome and large effects for some secondary outcomes. Importantly, successful learning of SCL self-regulation was related to reduced aggression at post-assessment. Conclusions: Individualized SCL-BF was not inferior to active TAU for any treatment outcome with improvements in aggression. Further, participants were on average able to self-regulate their SCL, and those who best learned self-regulation showed the highest clinical improvement, pointing to specificity of SCL-BF regulation for improving aggression. Further studies with larger samples and improved methods, for example by developing BF for mobile use in ecologically more valid settings are warranted

Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity

We initially performed a mutation screen of the coding region of the MC4R in 808 extremely obese children and adolescents and 327 underweight or normal-weight controls allowing for a case-control study. A total of 16 different missense, nonsense, and frameshift mutations were found in the obese study group; five of these have not been observed previously. In vitro assays revealed that nine [the haplotype (Y35X; D37V) was counted as one mutation] of the 16 mutations led to impaired cAMP responses, compared with wild-type receptor constructs. In contrast, only one novel missense mutation was detected in the controls, which did not alter receptor function. The association test based on functionally relevant mutations was positive (P = 0.006, Fisher's exact test, one-sided). We proceeded by screening a total of 1040 parents of 520 of the aforementioned obese young index patients to perform transmission disequilibrium tests. The 11 parental carriers of functionally relevant mutations transmitted the mutation in 81.8% (P = 0.033; exact one-sided McNemar test). These results support the hypothesis that these MC4R mutations represent major gene effects for obesity

Processing of social and monetary rewards in autism spectrum disorders

Background: Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD. Aims: Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD. Method: Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.6 years of age) and 181 typically developing participants (7.6-30.8 years of age). Results: Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD. Conclusions: Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD

Peer victimization and its impact on adolescent brain development and psychopathology

Chronic peer victimization has long-term impacts on mental health; however, the biological mediators of this adverse relationship are unknown. We sought to determine whether adolescent brain development is involved in mediating the effect of peer victimization on psychopathology. We included participants (n = 682) from the longitudinal IMAGEN study with both peer victimization and neuroimaging data. Latent profile analysis identified groups of adolescents with different experiential patterns of victimization. We then associated the victimization trajectories and brain volume changes with depression, generalized anxiety, and hyperactivity symptoms at age 19. Repeated measures ANOVA revealed time-by victimization interactions on left putamen volume (F = 4.38, p = 0.037). Changes in left putamen volume were negatively associated with generalized anxiety (t = −2.32, p = 0.020). Notably, peer victimization was indirectly associated with generalized anxiety via decreases in putamen volume (95% CI = 0.004–0.109). This was also true for the left caudate (95% CI = 0.002–0.099). These data suggest that the experience of chronic peer victimization during adolescence might induce psychopathology-relevant deviations from normative brain development. Early peer victimization interventions could prevent such pathological changes

Drinking Motives, Personality Traits, Life Stressors - Identifying Pathways to Harmful Alcohol Use in Adolescence Using a Panel Network Approach

BACKGROUND AND AIMS: Models of alcohol use risk suggest that drinking motives represent the most proximal risk factors on which more distal factors converge. However, little is known about how distinct risk factors influence each other and alcohol use on different temporal scales (within a given moment vs. over time). We aimed to estimate the dynamic associations of distal (personality and life stressors) and proximal (drinking motives) risk factors, and their relationship to alcohol use in adolescence and early adulthood using a novel graphical vector autoregressive (GVAR) panel network approach.DESIGN, SETTING, AND CASES: We estimated panel networks on data from the IMAGEN study, a longitudinal European cohort study following adolescents across three waves (ages 16, 19, 22). Our sample consisted of 1829 adolescents (51% females) who reported alcohol use on at least one assessment wave.MEASUREMENTS: Risk factors included personality traits (NEO-FFI: neuroticism, extraversion, openness, agreeableness, and conscientiousness; SURPS: impulsivity and sensation seeking), stressful life events (LEQ: sum scores of stressful life events), and drinking motives (DMQ: social, enhancement, conformity, coping anxiety, coping depression). We assessed alcohol use (AUDIT: quantity and frequency) and alcohol-related problems (AUDIT: related problems).FINDINGS: Within a given moment, social (partial correlation (pcor) =0.17) and enhancement motives (pcor=0.15) co-occurred most strongly with drinking quantity and frequency, while coping depression motives (pcor=0.13), openness (pcor=0.05), and impulsivity (pcor=0.09) were related to alcohol-related problems. The temporal network showed no predictive associations between distal risk factors and drinking motives. Social motives (beta=0.21), previous alcohol use (beta=0.11), and openness (beta=0.10) predicted alcohol-related problems over time (all p&lt;0.01).CONCLUSIONS: Heavy and frequent alcohol use, along with social drinking motives, appear to be key targets for preventing the development of alcohol-related problems throughout late adolescence. We found no evidence for personality traits and life stressors predisposing towards distinct drinking motives over time.</p

The interaction of child abuse and rs1360780 of the FKBP5 gene is associated with amygdala resting-state functional connectivity in young adults

Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early-life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion-processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity (rsFC) between the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p < .025, FWE-corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology

Drinking motives, personality traits and life stressors-identifying pathways to harmful alcohol use in adolescence using a panel network approach

BACKGROUND AND AIMS: Models of alcohol use risk suggest that drinking motives represent the most proximal risk factors on which more distal factors converge. However, little is known about how distinct risk factors influence each other and alcohol use on different temporal scales (within a given moment versus over time). We aimed to estimate the dynamic associations of distal (personality and life stressors) and proximal (drinking motives) risk factors, and their relationship to alcohol use in adolescence and early adulthood using a novel graphical vector autoregressive (GVAR) panel network approach.DESIGN, SETTING AND CASES: We estimated panel networks on data from the IMAGEN study, a longitudinal European cohort study following adolescents across three waves (aged 16, 19 and 22 years). Our sample consisted of 1829 adolescents (51% females) who reported alcohol use on at least one assessment wave.MEASUREMENTS: Risk factors included personality traits (NEO-FFI: neuroticism, extraversion, openness, agreeableness and conscientiousness; SURPS: impulsivity and sensation-seeking), stressful life events (LEQ: sum scores of stressful life events), and drinking motives [drinking motives questionnaire (DMQ): social, enhancement, conformity, coping anxiety and coping depression]. We assessed alcohol use [alcohol use disorders identification test (AUDIT): quantity and frequency] and alcohol-related problems (AUDIT: related problems).FINDINGS: Within a given moment, social [partial correlation (pcor) = 0.17] and enhancement motives (pcor = 0.15) co-occurred most strongly with drinking quantity and frequency, while coping depression motives (pcor = 0.13), openness (pcor = 0.05) and impulsivity (pcor = 0.09) were related to alcohol-related problems. The temporal network showed no predictive associations between distal risk factors and drinking motives. Social motives (beta = 0.21), previous alcohol use (beta = 0.11) and openness (beta = 0.10) predicted alcohol-related problems over time (all P  &lt; 0.01).CONCLUSIONS: Heavy and frequent alcohol use, along with social drinking motives, appear to be key targets for preventing the development of alcohol-related problems throughout late adolescence. We found no evidence for personality traits and life stressors predisposingtowards distinct drinking motives over time.</div

The interaction of child abuse and rs1360780 of the FKBP5 gene is associated with amygdala resting‐state functional connectivity in young adults

Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early-life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion-processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity (rsFC) between the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p < .025, FWE-corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology