Blaszczynski and Nower (2002) have theorized that there may be three potential subtypes of pathological gamblers who can be differentiated by the distinct pathways they take towards developing their gambling problems. This study sought to validate Blaszczynski and Nower's pathways model examining nationally representative data from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC; Grant, Dawson, & Hasin, 2001). Latent class analysis revealed three classes (or subtypes) of gamblers, similar to those proposed by Blaszczynski and Nower's behaviorally conditioned, emotionally vulnerable, and antisocial impulsivist pathological gamblers. Between group analyses demonstrated that the three classes differed with regard to gender composition and proportion of pathological gamblers. This study was unique in that it was the first of its kind to use a nationally representative sample to examine gambling subtypes using variables matched to the characteristics specifically proposed by Blaszczynski and Nower (2002). The validation of Blaszczynski and Nower's (2002) pathways model may eventually contribute to the development of more reliable and valid methods of identifying people who are at risk of developing gambling problems, in addition to the development of more refined treatments that take individual differences into consideration.

Blaszczynski and Nower (2002) have theorized that there may be three potential subtypes of pathological gamblers who can be differentiated by the distinct pathways they take towards developing their gambling problems. This study sought to validate Blaszczynski and Nower's pathways model examining nationally representative data from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC; Grant, Dawson, & Hasin, 2001). Latent class analysis revealed three classes (or subtypes) of gamblers, similar to those proposed by Blaszczynski and Nower's behaviorally conditioned, emotionally vulnerable, and antisocial impulsivist pathological gamblers. Between group analyses demonstrated that the three classes differed with regard to gender composition and proportion of pathological gamblers. This study was unique in that it was the first of its kind to use a nationally representative sample to examine gambling subtypes using variables matched to the characteristics specifically proposed by Blaszczynski and Nower (2002). The validation of Blaszczynski and Nower's (2002) pathways model may eventually contribute to the development of more reliable and valid methods of identifying people who are at risk of developing gambling problems, in addition to the development of more refined treatments that take individual differences into consideration.

The most effective and useful way to diagnose and subtype depression has been a long debated topic which even now does not have a definite answer. The biopsychosocial approach to diagnosis may be a solution to this problem by linking various etiologies to symptom presentation. The biopsychosocial model, in regard to depression, takes into account biological risk factors/contributors, psychological or cognitive risk factors/contributors, and social risk factors/contributors to depression when making diagnosis and subtyping determinations. However, the most effective way to use this model in the assessment, diagnosis, and treatment of depression is not yet clear. In this study, the utility of the biopsychosocial model as an effective approach to conceptualizing and treating depression was assessed by testing hypotheses that showed that etiological contributors are related to the presence and differential presentation of depression, and that these etiologically-based subtypes of depression respond differently to different forms of treatment. These hypotheses were tested using data from the National Comorbidity Survey - Replication (NCS-R). Results showed that the biopsychosocial model can effectively predict the presence, severity and chronicity of depression, and may inform specific biopsychosocially-based subtypes. No conclusions could be drawn regarding success in treatment based on the biopsychosocial model. Future directions for research based on the current study are discussed.

Autism spectrum disorders (ASDs) are a group of disorders that affect social, communication, and behavioral development. Identification of clinically distinct subtypes of ASDs, especially in the developmental period when delays or deficits are first recognized (i.e., in the first few years of life), can lend clues to etiology and trajectory and enhance current knowledge on early manifestations of the disorders. Moreover, identification of clinically distinct subtypes of ASDs may inform early identification efforts. Past research suggests that social relations, verbal abilities, nonverbal abilities, and the presence of certain stereotyped interests and behaviors (SIB) may be important factors in delineating subtypes of ASDs in toddlers. Yet there is no published study that examines empirically derived subtypes in a sample of such young children. Therefore, the purpose of this study was to determine whether clinically distinct subtypes can be derived from a sample of toddlers who fail an autism screen and are subsequently diagnosed with developmental concerns, including an ASD. Results found that subtypes delineated by social-communicative maturity were found in both of the aforementioned samples of children. Furthermore, the ASD only sample was also distinguished by rate and intensity of certain types of SIB. Implications for autism theory, early identification, and early intervention are discussed.

A better understanding of the neural mechanisms associated with Attention Deficit Hyperactivity Disorder (ADHD) and related cognitive deficits can potentially clarify the neural circuits involved in ADHD symptoms, help define neurobiologically informed subtypes and aid in developing more refined treatments. Two neurotransmitter (NT) systems have been implicated in ADHD: Dopamine (DA), and Norepinephrine (NE), and the primary cognitive deficits associated with ADHD are in working memory, response inhibition, reaction time variability, and reward processing. Frank et al. (2007a) proposes, based on computational models, that DA is associated with deficits in reward-based learning and updating of working memory, while NE is associated with deficits in response inhibition and greater response variability. Therefore, it might be possible to learn more about the NT systems' specific roles in ADHD by studying the associated cognitive deficits. The primary goal of this study was to assess performance in adolescents with and without ADHD on a number of cognitive tasks. We expected that the Attention Deficit Hyperactivity Disorder - Inattentive Subtype (ADHD-I) group would perform the worst on NE tasks and that the Attention Deficit Hyperactivity Disorder - Combined Subtype (ADHD-C) group would perform the worst on DA tasks, and that both groups would perform worse than controls on all tasks. Instead, we found that the ADHD-I group performed the most poorly on updating of working memory, while the ADHD-C group performed the best on this variable. However, the ADHD-C group performed worst on overall working memory. Dimensional analyses revealed that hyperactivity/impulsivity is positively correlated with updating of working memory, while inattention is negatively correlated with updating of working memory. In addition, hyperactivity/impulsivity was positively correlated with reaction time variability. In conclusion, it is likely that the roles of these NT systems are not as mutually exclusive as initially expected. It is also possible that our ADHD group was performing more like control groups in other studies, which might be due to a more 'pure' ADHD sample with less comorbid Oppositional Defiant Disorder (ODD) and Conduct disorder (CD), or could be due to a less symptomatic ADHD group.

This study examined the role that rigid sex-role stereotyping and male socialization played in differentiating the three typologies of male batterers. The first purpose was to utilize a cluster analysis to determine whether the three male batterer clusters (Family Only (FO), Borderline-Dysphoric (BD) and Generally Violent- Antisocial (GVA)) theorized by Holtzworth-Munroe and Stuart (1994) could be reproduced using the MMPI-2. 101 adult court referred males on probation for domestic violence were given the MMPI-2, and three distinct batterer typologies emerged. Once the clusters were established, this study attempted to determine if the theoretical model proposed by Jennings and Murphy (2000), which emphasized male socialization and its potential effect on male-female interactions within intimate relationships, is influential in creating differentiation among the cluster typologies. Specifically, an emphasis was placed on examining how the FO male batterer cluster differed from the BD and GVA clusters. Four variables were theorized to best represent Jennings and Murphy'™s (2000) model, including: the Masculine-Feminine (MF) clinical scale, Social Introversion (Si) clinical scale, Gender-Masculine (GM) supplementary scale and Low Self-Esteem (LSE) content scale. A MANOVA was utilized to see if the three batterer typologies differed on the variables (MF, Si, GM, and LSE) that encompass the male socialization construct. Results indicated that statistically significant differentiation did exist between the three clusters. Furthermore, there was indication that the FO men adhered more closely to rigid traditional male roles and displayed higher self-esteem. Discussion focused on the importance of matching treatment to batterer typology and the importance of incorporating discussion of male socialization into group therapy treatment.

Most neonates and infants acquire HIV-1 infection as a result of mother-to-infant (vertical) transmission and are infected with the minor genotype with macrophage-tropic (R5) phenotype of the mother. Several studies suggest that infected infants have a higher viral load and develop AIDS more rapidly than infected adults, but the mechanisms of this differential HIV-1 infection are not known. The hypothesis of my dissertation is that viral determinants and differential cellular gene expression profiles influence differential HIV-1 replication and disease progression seen in neonates vs. adults. This work includes characterization of viral determinants, including reverse transcriptase (RT) and envelope gp120, and host determinants, including cellular transcription factors and cytokines that may be associated with differential HIV-1 replication in infants and adults. The characterization of HIV-1 RT gene from five mother-infant pairs following vertical transmission revealed a low degree of viral heterogeneity and a high conservation of intact open reading frames comprising functional domains and CTL epitopes. Biological characterization of HIV-1 subtype C envelope gp120 from infected patients from India was performed by constructing chimeras with HIV-1 subtype B. Infection of cell lines and primary cells with chimeric subtype C/B virus showed that the subtype C env gp120 from patients contributed to an increased rate of virus entry, which correlated with higher replication efficiencies and virus production in subtype C env chimeras compared with subtype B env chimeras and subtype B primary isolates. Higher level of viremia with subtype C infection compared with subtype B may be responsible for its rapid disease progression and spread. The mechanisms of HIV-1 replication in neonatal and adult cells was determined and found that differential HIV-1 replication in neonatal and adult cells is influenced at the level of HIV-1 gene expression. Evaluation of cellular gene expression profile of neonatal and adult mononuclear cells performed by microarray analysis identified several factors, including transcription factors, cytokines and matrix metalloproteinases that may be associated with increased HIV-1 gene expression and replication in neonates and infants. Taken together, these results provide new insights into the understanding of mecahnsims of HIV-1 vertical transmission, pathogenesis and disease progression in infected neonates and infants.

Magister Scientiae (Medical Bioscience) - MSc(MBS) / The present study describes molecular aspects of inherited congenital cataract in captive-bred Vervet monkeys. Congenital cataracts are lens opacities that are present at birth or soon after birth and include hereditary cataracts or cataracts caused by infectious agents. The MRC Primate Unit is housing a colony of captive-bred Vervet monkeys in which 7.5% is suffering from congenital cataract. However, the parents of the affected individuals were asymptomatic. Six families within the colony have been identified to be affected by two types of morphologies (Y-sutural and total cataract). Based on the evidence provided above, it was speculated that the colony was affected with autosomal recessive cataract. The main aim of this study was to facilitate a strategy for managing breeding programs by minimizing cataract occurrences in captive-bred Vervet monkeys. Integrated combination of clinical, molecular and bioinformatic strategies were used to identify and assess reciprocal candidate susceptibility genes for cataracts. The genes that are known to be responsible for most human congenital cataract cases were prioritized. The genes include Heat shock transcription factor 4 (HSF4), Crystalline Alpha A (CRYAA), glucosaminyl (N-acetyl) transferase 2 (GCNT2) and Lens intrinsic membrane protein 2 (LIM2). Twenty two subjects were selected based on their morphology (5 carriers, 5 controls and 12 cataracts). 2ml of blood was collected for Deoxyribonucleic acid (DNA) extraction. Coding exons and flanking regions were screened by polymerase chain reaction (PCR) amplification and sequenced. The CLC DNA workbench was used for results analysis. The screening of four genes revealed 20 sequence variants which were not present in the control individuals. Sequencing of HSF4 revealed three mutations: R116R, L245>L and P421>L in exon 5, 10 and 14, respectively. The coding exons for CRYAA showed two sequence variants: S134W and K166N in exon 3. Twelve mutations were identified in exon one of all three GCNT2 transcripts (A, B and C). These mutations include: G212G, H256>H, M258>V, N275>N, V16>I, Y122>F, S15>S, S24>N, S38>S, I118>I, D194>D and Y373>Y which was found in exon three of all transcripts. There were no mutations in LIM2, however, three single nucleotide polymorphisms (SNPs) were identified in exon 2 (P66>P) and 3 (I118>T and A127>T). The above mutations were conserved when aligned with other species. The sequence variations vary among the families and those individuals with the same or different cataract phenotype. Based on these findings, it can be concluded that the four candidate genes harbour mutations that are responsible for both phenotypes. The effect of these mutations in Vervet monkeys is not yet understood, however, their impact will be further investigated. For future studies, it will be of absolute importance to screen the entire family to verify that indeed cataract formation in this colony is inherited in an autosomal recessive manner.

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