Browsing by Author "Sahakian, Barbara J."
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- Executive functions and insight in OCD : a comparative studyPublication . Manarte, Lucas; Andrade, António R.; Rosário, Linete do; Sampaio, Daniel; Figueira, Maria Luísa; Morgado, Pedro; Sahakian, Barbara J.Background: Around 25 to 30% of patients with obsessive-compulsive disorder (OCD) do not respond to treatment. These patients have the longest duration of disease and the worst prognosis. Following years of research on this topic, insight has emerged as a potential explanation for this therapeutic resistance. Therefore, it has become important to characterize OCD patients with poor insight. Few studies have focused on the neuropsychological and cognitive characteristics of these patients. Methods: To help fill this gap, we divided 57 patients into two groups, one with good insight and the other with poor insight, assessed their neuropsychological functions-through a Rey's figure test, a California verbal learning test, a Toulouse-Piéron test and a Wisconsin Card Sorting Test (WCST)-and compared the results with those of a paired control group. Results: The statistical analysis, with a significance level of 95%, revealed differences in the executive function tests, and particularly in the WCST (p ≤ 0.001) and trail-making-test (TMT A/B) (p = 0.002). Conclusions: These differences suggest that the neuropsychological profile of poor-insight patients is different from their good-insight counterparts, emphasize the role played by the executive functions in insight and highlights the need for more accurate neurocognitive research and treatment.
- Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington’s disease decades before clinical motor diagnosisPublication . Scahill, Rachael I.; Farag, Mena; Murphy, Michael J.; Hobbs, Nicola Z.; Leocadi, Michela; Langley, Christelle; Knights, Harry; Ciosi, Marc; Fayer, Kate; Nakajima, Mitsuko; Thackeray, Olivia; Gobom, Johan; Rönnholm, John; Weiner, Sophia; Hassan, Yara R.; Ponraj, Nehaa K. P.; Estevez-Fraga, Carlos; Parker, Christopher S.; Malone, Ian B.; Hyare, Harpreet; Long, Jeffrey D.; Heslegrave, Amanda; Sampaio, Cristina; Zhang, Hui; Robbins, Trevor W.; Zetterberg, Henrik; Wild, Edward J.; Rees, Geraint; Rowe, James B.; Sahakian, Barbara J.; Monckton, Darren G.; Langbehn, Douglas R.; Tabrizi, Sarah J.Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.5 years compared with 46 controls (false discovery rate (FDR) > 0.3). However, cerebrospinal fluid (CSF) markers showed very early signs of neurodegeneration in HDGE with elevated neurofilament light (NfL) protein, an indicator of neuroaxonal damage (FDR = 3.2 × 10-12), and reduced proenkephalin (PENK), a surrogate marker for the state of striatal medium spiny neurons (FDR = 2.6 × 10-3), accompanied by brain atrophy, predominantly in the caudate (FDR = 5.5 × 10-10) and putamen (FDR = 1.2 × 10-9). Longitudinal increase in somatic CAG repeat expansion ratio (SER) in blood was a significant predictor of subsequent caudate (FDR = 0.072) and putamen (FDR = 0.148) atrophy. Atypical loss of interruption HTT repeat structures, known to predict earlier age at clinical motor diagnosis, was associated with substantially faster caudate and putamen atrophy. We provide evidence in living humans that the influence of CAG length on HD neuropathology is mediated by somatic CAG repeat expansion. These critical mechanistic insights into the earliest neurodegenerative changes will inform the design of preventative clinical trials aimed at modulating somatic expansion.