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The Emerging Role of microRNAs in Schizophrenia and Autism Spectrum Disorders  [PDF]
Nikolaos Mellios,Mriganka Sur
Frontiers in Psychiatry , 2012, DOI: 10.3389/fpsyt.2012.00039
Abstract: MicroRNAs (miRNAs) are small non-coding RNAs conserved throughout evolution whose perceived importance for brain development and maturation is increasingly being understood. Although a plethora of new discoveries have provided novel insights into miRNA-mediated molecular mechanisms that influence brain plasticity, their relevance for neuropsychiatric diseases with known deficits in synaptic plasticity, such as schizophrenia and autism, has not been adequately explored. In this review we discuss the intersection between current and old knowledge on the role of miRNAs in brain plasticity and function with a focus in the potential involvement of brain expressed miRNAs in the pathophysiology of neuropsychiatric disorders.
Effects of age of onset on clinical characteristics in schizophrenia spectrum disorders
Yu-Chen Kao, Yia-Ping Liu
BMC Psychiatry , 2010, DOI: 10.1186/1471-244x-10-63
Abstract: Data were collected from 104 patients with schizophrenia and schizoaffective disorder. Diagnosis was made via structured clinical interviews. Assessments of psychiatric symptoms and social and global functioning were completed. The effect of age of onset on demographic and clinical variables was examined using correlation analyses and binary logistic regression models. We chose 17 years of age as the cut-off for early-onset schizophrenia spectrum disorders based on a recent clinical consensus. We further investigated differences in the severity of psychopathology and other clinical variables between the early- and adult-onset groups.The binary logistic regression analysis showed that age of onset was significantly related to the cognitive component of the Positive and Negative Syndrome Scale (PANSS) (odds ratio, OR = 0.58; 95% confidence interval, CI = 0.872-0.985; p < 0.001) and Barratt Impulsiveness Scale (BIS) score (OR = 0.94; 95% CI = 0.447-0.744; p = 0.015). Patients with early onset of schizophrenia spectrum disorders had significantly greater levels of cognitive impairment and higher impulsivity. There were significant differences between several demographic and clinical variables, including the negative symptom component of the PANSS (p < 0.001), cognitive component of the PANSS (p < 0.001), BIS score (p = 0.05), and psychological domain of quality of life (QOL) (p = 0.05), between patients with early- and adult-onset schizophrenia spectrum disorders, having controlled for the effect of the current age and duration of illness.Our findings support the hypothesis of an influence of age of onset on illness course in patients with schizophrenia spectrum disorders. This finding may in fact be part of a separate domain worthy of investigation for the development of interventions for early symptoms of schizophrenia.Schizophrenia is a complex, chronic, and disabling illness that presents with heterogeneity in its clinical appearance, in patterns of psychopharmacolo
Association testing of copy number variants in schizophrenia and autism spectrum disorders
Bernard J Crespi, Helen J Crofts
Journal of Neurodevelopmental Disorders , 2012, DOI: 10.1186/1866-1955-4-15
Abstract: We systematically evaluated three lines of evidence: (1) the statistical bases for associations of autism spectrum disorders and schizophrenia with a set of the primary CNVs thus far investigated, from previous studies; (2) data from case series studies on the occurrence of these CNVs in autism spectrum disorders, especially among children, and (3) data on the extent to which the CNVs were associated with intellectual disability and developmental, speech, or language delays. We also conducted new analyses of existing data on these CNVs in autism by pooling data from seven case control studies.Four of the CNVs considered, dup 1q21.1, dup 15q11-q13, del 16p11.2, and dup 22q11.21, showed clear statistical evidence as autism risk factors, whereas eight CNVs, del 1q21.1, del 3q29, del 15q11.2, del 15q13.3, dup 16p11.2, dup 16p13.1, del 17p12, and del 22q11.21, were strongly statistically supported as risk factors for schizophrenia. Three of the CNVs, dup 1q21.1, dup 16p11.2, and dup 16p13.1, exhibited statistical support as risk factors for both autism and schizophrenia, although for each of these CNVs statistical significance was nominal for tests involving one of the two disorders. For the CNVs that were statistically associated with schizophrenia but were not statistically associated with autism, a notable number of children with the CNVs have been diagnosed with autism or ASD; children with these CNVs also demonstrate a high incidence of intellectual disability and developmental, speech, or language delays.These findings suggest that although CNV loci notably overlap between autism and schizophrenia, the degree of strongly statistically supported overlap in specific CNVs at these loci remains limited. These analyses also suggest that relatively severe premorbidity to CNV-associated schizophrenia in children may sometimes be diagnosed as autism spectrum disorder.
Neurexin-1 and Frontal Lobe White Matter: An Overlapping Intermediate Phenotype for Schizophrenia and Autism Spectrum Disorders  [PDF]
Aristotle N. Voineskos,Tristram A. P. Lett,Jason P. Lerch,Arun K. Tiwari,Stephanie H. Ameis,Tarek K. Rajji,Daniel J. Müller,Benoit H. Mulsant,James L. Kennedy
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0020982
Abstract: Structural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown.
Metacognition in schizophrenia spectrum disorders: Methods of assessment and associations with neurocognition and function
Lysaker,Paul H.; Molly Erickson,M.A.; Buck,Kelly D.; Procacci,Michelle; Nicolò,Guiseppe; Dimaggio,Giancarlo;
The European Journal of Psychiatry , 2010, DOI: 10.4321/S0213-61632010000400004
Abstract: background and objectives: research has confirmed that many with schizophrenia experience deficits in metacognitive capacity defined as impairments in the ability to think about thinking, both with regards to their own thinking and the thinking of others. these difficulties are related to, but not reducible to symptoms. one question posed here regards how these deficits are linked to other forms of cognitive deficits, including deficits in neurocognition, and how they and other forms of cognitive deficits are related to the ability to function. as neurocognition is degraded in schizophrenia, does the ability to think about one′s own thinking diminish? do deficits in metacognition affect function in a manner semi-independent of deficits in neurocognition? methods: to explore these possibilities, this paper reviews recent studies of metacognition as assessed within personal narratives of self and illness spontaneously generated by adults with schizophrenia spectrum disorders. results: studies are reviewed which suggest that impairments in verbal memory and executive function may interfere with the ability to form and sustain representation of one′s own internal state as well as the internal states of others. additionally, results are detailed which suggest that metacognitive deficits directly affect function prospectively and may mediate the impact of neurocognitive deficits on functioning. conclusions: results are consistent with the possibility that a certain level of neurocognition is needed to think about thinking in a complex manner and that the ability to think about thinking is intimately related to the ability to work and relate to others among persons with schizophrenia.
Metacognition in schizophrenia spectrum disorders: Methods of assessment and associations with neurocognition and function  [cached]
Paul H. Lysaker,M.A. Molly Erickson,Kelly D. Buck,Michelle Procacci
The European Journal of Psychiatry , 2010,
Abstract: Background and Objectives: Research has confirmed that many with schizophrenia experience deficits in metacognitive capacity defined as impairments in the ability to think about thinking, both with regards to their own thinking and the thinking of others. These difficulties are related to, but not reducible to symptoms. One question posed here regards how these deficits are linked to other forms of cognitive deficits, including deficits in neurocognition, and how they and other forms of cognitive deficits are related to the ability to function. As neurocognition is degraded in schizophrenia, does the ability to think about one′s own thinking diminish? Do deficits in metacognition affect function in a manner semi-independent of deficits in neurocognition? Methods: To explore these possibilities, this paper reviews recent studies of metacognition as assessed within personal narratives of self and illness spontaneously generated by adults with schizophrenia spectrum disorders. Results: Studies are reviewed which suggest that impairments in verbal memory and executive function may interfere with the ability to form and sustain representation of one′s own internal state as well as the internal states of others. Additionally, results are detailed which suggest that metacognitive deficits directly affect function prospectively and may mediate the impact of neurocognitive deficits on functioning. Conclusions: Results are consistent with the possibility that a certain level of neurocognition is needed to think about thinking in a complex manner and that the ability to think about thinking is intimately related to the ability to work and relate to others among persons with schizophrenia.
Pilot study provides qualitative evidence for intrinsic motivation in schizophrenia spectrum disorders  [PDF]
Marian W. Roman, Lora Humphrey Beebe, Renee Burk
Open Journal of Psychiatry (OJPsych) , 2012, DOI: 10.4236/ojpsych.2012.224045
Abstract: Persons with schizophrenia spectrum disorders (SSDs) face multiple health barriers that are improved with exercise, but they seldom exercise due to a variety of barriers, of which amotivation is primary. In the current study, we investigated the subjective experiences of persons with SSDs following a formal exercise program. Twenty seven persons with SSDs who had taken part in a 16-week walking program provided feedback during exit interviews. Our purpose was to ascertain whether comments provided evidence of development of intrinsic motivation as defined by Ryan and Deci’s self determination of behavior theory. Our directed content analysis resulted in 5 thematic codes: autonomy, competence, relatedness, health benefits and personal enjoyment. Results highlight the importance of health-related group activities in supporting competence, relatedness and autonomy. Development and testing of interventions to support intrinsic motivation is critical to improving the health of this vulnerable group.
Autism Spectrum Disorders and Schizophrenia: Meta-Analysis of the Neural Correlates of Social Cognition  [PDF]
Gisela Sugranyes, Marinos Kyriakopoulos, Richard Corrigall, Eric Taylor, Sophia Frangou
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025322
Abstract: Context Impaired social cognition is a cardinal feature of Autism Spectrum Disorders (ASD) and Schizophrenia (SZ). However, the functional neuroanatomy of social cognition in either disorder remains unclear due to variability in primary literature. Additionally, it is not known whether deficits in ASD and SZ arise from similar or disease-specific disruption of the social cognition network. Objective To identify regions most robustly implicated in social cognition processing in SZ and ASD. Data Sources Systematic review of English language articles using MEDLINE (1995–2010) and reference lists. Study Selection Studies were required to use fMRI to compare ASD or SZ subjects to a matched healthy control group, provide coordinates in standard stereotactic space, and employ standardized facial emotion recognition (FER) or theory of mind (TOM) paradigms. Data Extraction Activation foci from studies meeting inclusion criteria (n = 33) were subjected to a quantitative voxel-based meta-analysis using activation likelihood estimation, and encompassed 146 subjects with ASD, 336 SZ patients and 492 healthy controls. Results Both SZ and ASD showed medial prefrontal hypoactivation, which was more pronounced in ASD, while ventrolateral prefrontal dysfunction was associated mostly with SZ. Amygdala hypoactivation was observed in SZ patients during FER and in ASD during more complex ToM tasks. Both disorders were associated with hypoactivation within the Superior Temporal Sulcus (STS) during ToM tasks, but activation in these regions was increased in ASD during affect processing. Disease-specific differences were noted in somatosensory engagement, which was increased in SZ and decreased in ASD. Reduced thalamic activation was uniquely seen in SZ. Conclusions Reduced frontolimbic and STS engagement emerged as a shared feature of social cognition deficits in SZ and ASD. However, there were disease- and stimulus-specific differences. These findings may aid future studies on SZ and ASD and facilitate the formulation of new hypotheses regarding their pathophysiology.
Do patients think cannabis causes schizophrenia? - A qualitative study on the causal beliefs of cannabis using patients with schizophrenia
Anna Buadze, Rudolf Stohler, Beate Schulze, Michael Schaub, Michael Liebrenz
Harm Reduction Journal , 2010, DOI: 10.1186/1477-7517-7-22
Abstract: We recruited ten consecutive patients fulfilling criteria for paranoid schizophrenia and for a harmful use of/dependence from cannabis (ICD-10 F20.0 + F12.1 or F12.2) from the in- and outpatient clinic of the Psychiatric University Hospital Zurich. They were interviewed using qualitative methodology. Furthermore, information on amount, frequency, and effects of use was obtained. A grounded theory approach to data analysis was taken to evaluate findings.None of the patients described a causal link between the use of cannabis and their schizophrenia. Disease models included upbringing under difficult circumstances (5) or use of substances other than cannabis (e. g. hallucinogens, 3). Two patients gave other reasons. Four patients considered cannabis a therapeutic aid and reported that positive effects (reduction of anxiety and tension) prevailed over its possible disadvantages (exacerbation of positive symptoms).Patients with schizophrenia did not establish a causal link between schizophrenia and the use of cannabis. We suggest that clinicians consider our findings in their work with patients suffering from these co-occurring disorders. Withholding treatment or excluding patients from certain treatment settings like day-care facilities or in patient care because of their use of cannabis, may cause additional harm to this already heavily burdened patient group.There still is a debate among the research community whether cannabis use may cause schizophrenia [1,2] and whether cannabis use of patients with schizophrenia might lead to a more untoward outcome like earlier and more frequent relapses [3].Arguments in this debate primarily stem from cohort studies [4], systematic reviews [5], and meta analyses [6]. Considering that studies exploring patients' view on a controversial topic have contributed to our knowledge of important clinical issues [7], such as patients' reasons for following or refusing medical recommendations [8,9], and patients needs and wishes at the end
A case-linkage study of crime victimisation in schizophrenia-spectrum disorders over a period of deinstitutionalisation
Tamsin B Short, Stuart Thomas, Stefan Luebbers, Paul Mullen, James R Ogloff
BMC Psychiatry , 2013, DOI: 10.1186/1471-244x-13-66
Abstract: The schizophrenia-spectrum cases were drawn from a state-wide public mental health register, comprising all persons first diagnosed with a schizophrenic illness in five year cohorts between 1975 -- 2005. The criminal histories of 4,168 persons diagnosed with schizophrenic-spectrum disorders were compared to those of a randomly selected community sample of 4,641 individuals.Compared to community controls, patients with schizophrenia-spectrum disorders were significantly more likely to have a record of violent (10.1% vs. 6.6%, odds ratio 1.4) and sexually violent victimisation (1.7% vs. 0.3%, odds ratio 2.77), but less likely to have an official record of victimisation overall (28.7% vs. 39.1%, odds ratio 0.5). Over the approximate period of deinstitutionalisation, the rate of recorded victimisation has more than doubled in schizophrenia-spectrum patients, but stayed relatively constant in the general community.People with schizophrenic-spectrum disorders are particularly vulnerable to violent crime victimisation; although co-morbid substance misuse and criminality both heighten the chances of victimisation, they cannot fully account for the increased rates. Deinstitutionalisation may have, in part, contributed to an unintended consequence of increasing rates of victimisation amongst the seriously mentally ill.
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