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PubMed2000

Somatosensory amplification and affective inhibition are elevated in myofascial face pain.

OBJECTIVE: This study was designed to determine whether affective inhibition and somatosensory amplification are elevated in patients with a history of myofascial face pain (MFP). These processes may underlie a tendency to express distress in somatic rather than affective terms, leading to somatized or masked depression. DESIGN: Women (n = 162) with a history of MFP were compared with demographically equivalent women (n = 173) without MFP histories on self-report scales of affective inhibition and somatosensory amplification. Structured psychiatric interviews and health histories were conducted. In addition, a first-degree relative of 106 myofascial face pain subjects and 118 control subjects completed these same self-report scales. RESULTS: MFP cases and controls differed significantly on measures of affective inhibition and somatosensory amplification. History of depression or current psychological distress did not account for group differences. Elevated levels of somatosensory amplification were confined to MFP women with active symptoms. Finally, although both somatosensory amplification and affective inhibition showed a tendency to run in families, familial transmission did not account for case/control differences. CONCLUSIONS: Affective inhibition and somatosensory amplification are likely to be elevated in patients with MFP. Although not accounted for by psychiatric symptomatology, the possibility that these response styles are reactive to coping with chronic face pain cannot be ruled out.

Journal Article↗
PubMedDate not supplied

Assortative mating in the affective disorders: a systematic review and meta-analysis.

Assortative mating, or the tendency for individuals with similar phenotypes to mate more frequently than expected by chance, has been reported for a variety of complex traits, including many neuropsychiatric disorders. Although assortative mating has been reported in affective disorders, the studies done to date have been inconclusive. This study attempts to assess the degree of assortative mating in individuals with affective disorders using systematic review and meta-analytic techniques. Studies on assortative mating in affective disorders were identified by a computerized literature search and by bibliographic assessment of published studies and reviews. Studies were selected if they had a case-control design and if they reported rates of affective disorders in the spouses of probands and controls. Of the 17 studies reviewed, six were selected for meta-analysis. All studies were blinded. Details of study design, patient characteristics, and rates of affective disorders were assessed by two independent reviewers. Twelve of the 17 studies assessed reported an increase in assortative mating. Results of the meta-analysis supported these findings, and indicated that assortative mating occurs in both bipolar disorder and major depression. Although most studies examined reported an increase in assortative mating among individuals with affective disorders, the degree of assortative mating reported varied widely. Meta-analysis with six controlled studies showed evidence for assortative mating, and suggested that the degree of assortative mating is higher for individuals with bipolar disorder than for those with major depression. These results support the previously reported findings, and may have important implications for genetic studies.

Adult↗
PubMed1999

A comparison of the Faces Pain Scale and the Facial Affective Scale for children's estimates of the intensity and unpleasantness of needle pain during blood sampling.

To what degree can facial expression scales help children differentiate between the sensory and emotional aspects of the pain experience? This study examined the relationship between children's ratings on the Faces Pain Scale (an intensity measure), the Facial Affective Scale (an affective measure), and a paired mechanical visual analogue (MVAS) method for measuring the intensity and unpleasantness of pain. It was predicted that ratings on the Faces Pain Scale should correlate best with the MVAS measure of pain intensity rather than unpleasantness. Likewise, ratings on the Facial Affective Scale should correlate best with the MVAS measure of pain unpleasantness (assumed to reflect an emotional dimension) rather than intensity. Eighty children scheduled for blood sampling were selected in two age groups: 4 to 6, and 7 to 10 years. Children rated needle pain using each pain scale. As hypothesized, ratings on the Faces Pain Scale correlated more highly with the MVAS ratings for intensity (r =0.77) than for unpleasantness (r =0.52). A smaller reverse finding was confirmed for the Facial Affective Scale which correlated more highly with the MVAS for unpleasantness (r =0.64) than for intensity (r =0.51). Factor analysis indicated that 'pain dimension' (intensity vs affect) was a relatively weak factor as compared with shared instrument variance (two MVAS vs two face scales). No systematic age effects were observed. In conclusion, the Faces Pain Scale and the Facial Affective Scale may partly measure different aspects of the pain experience in children, although it remains to be determined to what degree the obtained differences are clinically meaningful. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗
PubMed1997

Affective Responses to Behavioral Interventions.

Until recently, caregivers viewed problematic behaviors in nursing home residents with dementia as disruptive and sought to quell them through physical and chemical restraints. Recent behavioral intervention studies have reported efficacy of behavioral interventions as a reduction in problematic behaviors, an outcome that addresses the needs of the onlooker but not necessarily those of the person displaying the behaviors. In recently completed studies of behavioral interventions to promote dressing independence and manage problematic behaviors in elderly nursing home residents with dementia, we noticed a serendipitous change in participants' demeanor or affective state. Intervention studies generally report outcomes as changes in the target behavior, yet behavioral interventions can have a major impact on a resident's affective state. Therefore, affect may provide another means of measuring outcomes for persons with dementia. We are testing this theory in a third study by evaluating participants' affective behaviors from videotapes filmed during the problematic behaviors study. In this article, we discuss literature supporting the use of affect as an outcomes measure in intervention studies and then describe our studies and the development of an instrument for measuring affect.

Journal Article↗
PubMed2001

Sensory and affective dimensions of phasic pain are indistinguishable in the self-report and psychophysiology of normal laboratory subjects.

This study evaluated the discriminant validity of subjects differentially scaling the sensory and affective dimensions of pain. It sought to determine (1) whether subjects can differentially scale sensory and affective aspects of phasic laboratory pain in the absence of task demand bias that fosters apparent differential scaling; (2) whether psychophysiologic responses to painful stimuli can predict pain report (PR); and (3) whether such responses contribute more to affective than to sensory judgments. Fifty-six men and 44 women repeatedly experienced varied painful electrical fingertip stimuli at low, medium, and high intensities. On half of the trial blocks, subjects made sensory judgments; on the remainder they made affective judgments. Response measures included PR, pupil dilation, heart rate, respiration rate, skin conductance response (SCR), and late near field evoked potentials. Subjects did not rate the stimuli differently when making sensory versus affective judgments. The psychophysiologic variables, principally the SCR, accounted for 44% of the variance in the PR. Psychophysiologic response patterns did not differentiate affective and sensory judgment conditions. Noteworthy sources of individual differences included baseline PR levels and the linear effects of SCR on PR.

Journal Article↗
PubMed2001

Oxcarbazepine in affective and schizoaffective disorders.

Anticonvulsants have been successfully used in pharmacopsychiatry after their therapeutic value in affective and schizoaffective disorders had been documented in several clinical trials. As the authorities in several countries registered newer anticonvulsants with fewer side effects, their therapeutic value in psychiatric disorders was studied. Clinical studies from the early 80's onward have demonstrated the efficacy of oxcarbazepine (OCBZ), a keto derivative of carbamazepine, in treating mania in affective and schizoaffective disorders. In addition, OCBZ has a distinct pharmacokinetic profile concerning drug-drug interactions compared to carbamazepine and other anticonvulsants. Therefore, the value of OCBZ in the treatment of affective and schizoaffective disorders needs to be evaluated. We reviewed the literature with regard to pharmacokinetic and pharmacodynamic characteristics of OCBZ, drug-drug interactions relevant in pharmacopsychiatry, and the clinical effects of OCBZ in the treatment of patients with affective and schizoaffective disorders. According to the literature, OCBZ is regarded as effective in acute mania and appears to reduce the dosage of neuroleptics required for the treatment of affective and schizoaffective disorders. In addition, it has a preferable pharmacokinetic profile with less severe side effects compared to carbamazepine and neuroleptics. Furthermore, since OCBZ does not interact substantially with the cytochrome P450 enzyme system, co-administration with neuroleptics or antidepressants appears to be well tolerated in affective disorders. However, despite promising effects of OCBZ, few clinical studies have been published in the last 15 years. We conclude that further studies should validate the efficacy of OCBZ in treating mania and evaluate possible pharmacopsychiatric indications as well as limitations for this psychotropic compound.

Anticonvulsants↗
PubMed1989

Information storage in the nervous system of Aplysia: specific proteins affected by serotonin and cAMP.

To identify proteins that may be involved in the induction of long-term changes in the nervous system, we investigated whether specific proteins in pleural sensory neurons of Aplysia were affected by procedures that mimic those used to produce long-term sensitization. Using two-dimensional PAGE, we found that exposure to serotonin (5-hydroxytryptamine, 5-HT) for 2 or 3 hr appeared to increase incorporation of labeled amino acids into one protein (P9) and decrease incorporation into two other proteins (P19 and P20). These effects of 5-HT were observed whether the labeled amino acid was leucine or methionine. The same proteins that were affected by 5-HT were also altered by the adenylate cyclase activator forskolin and by the 8-bromo and 8-benzylthio analogs of cAMP. Addition of Co2+ to 5-HT did not seem to affect the action of 5-HT on P9 and P20, but it did seem to block the effect of 5-HT on P19. However, the effect of analogs of cAMP on P9, P19, and P20 was not altered by inclusion of Co2+. A phorbol ester that activates protein kinase C did not appear to affect the proteins that were modified by 5-HT, but phorbol ester did appear to increase the amount of labeled amino acids incorporated into another protein (P24). To investigate the specificity of these effects for pleural ganglion neurons, we examined the effect of 3- and 6-hr treatments of 5-HT on proteins in the abdominal ganglion. 5-HT affected at least nine proteins in the abdominal ganglion. One of these proteins (P9) appeared to be the same as one altered by 5-HT in the pleural sensory neurons. However, the occurrence of some proteins and some effects of 5-HT were specific for one ganglion or the other. The identified proteins that were affected by both 5-HT and changes in cAMP may be involved in the induction of long-term changes in the nervous system of Aplysia.

Animals↗
PubMed1993

Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase beta-subunit gene.

Irish setter dogs affected with a rod/cone dysplasia (locus designation, rcd1) display markedly elevated levels of retinal cGMP during postnatal development. The photoreceptor degeneration commences approximately 25 days after birth and culminates at about 1 year when the population of rods and cones is depleted. A histone-sensitive retinal cGMP phosphodiesterase (PDE; EC 3.1.4.35) activity, a marker for photoreceptor PDEs, was shown previously to be present in retinal homogenates of immature, affected Irish setters. Here we report that, as judged by HPLC separation, this activity originates exclusively from cone photoreceptors, whereas rod PDE activity is absent. An immunoreactive product the size of the PDE alpha subunit, but none the size of the beta subunit, can be detected on immunoblots of retinal extracts of affected dogs, suggesting a null mutation in the PDE beta-subunit gene. Using PCR amplification of Irish setter retinal cDNA, we determined the complete coding sequence of the PDE beta subunit in heterozygous and affected animals. The affected PDE beta-subunit mRNA contained a nonsense amber mutation at codon 807 (a G-->A transition converting TGG to TAG), which was confirmed to be present in putative exon 21 of the affected beta-subunit gene. The premature stop codon truncates the beta subunit by 49 residues, thus removing the C-terminal domain that is required for posttranslational processing and membrane association. These results suggest that the rcd1 gene encodes the rod photoreceptor PDE beta subunit and that a nonsense mutation in this gene is responsible for the production of a nonfunctional rod PDE and the photoreceptor degeneration in the rcd1/rcd1 Irish setter dogs.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Cognitive estimation and affective judgments in alcoholic Korsakoff patients.

Alcoholic Korsakoff patients have their most marked deficits in memory, but may exhibit problems in further cognitive and behavioral domains, particularly in so-called frontal lobe functions and on the emotional level. Cognitive estimation is among the frontal lobe-associated functions; nevertheless, the underlying processes of estimation and estimation deficits are still unknown. Additionally, though affective judgments were found to be disturbed in Korsakoff patients one can question whether this result is due to a deficiency in emotional processing itself, or whether deteriorated basic processes underlying all kinds of judgment tasks result in affective judgment errors. In this study, possible relations and underlying cognitive processes of affective and nonaffective judgments (cognitive estimates) were analyzed in a large sample of 39 Korsakoff patients. A neuropsychological test battery was administered together with a new test for cognitive estimation consisting of four dimensions ('size,' 'weight,' 'quantity,' and 'time') and an affective judgment task comprising negative, neutral, and positive words. The Korsakoff patients' results showed marked deficits concerning both, cognitive estimation and affective judgments. These deficits were highly intercorrelated and performance in both tasks was related to basic (e.g., information processing speed) and higher cognitive functions (executive functions and memory), suggesting a common basis in cognitive estimation and in affective judgments in Korsakoff syndrome.

Aged↗
PubMedDate not supplied

Factors affecting morbidity and mortality in gangrenous cholecystitis.

INTRODUCTION: Gangrenous cholecystitis is a serious complication of acute cholecystitis. Male gender, older age, leukocytosis, cardio-vascular diseases and diabetes were reported as factors that increase the risk of gangrenous cholecystitis. The aim our study was to determine variables affecting morbidity and mortality as well as to define the independent risk factors in Gangrenous Cholecystitis. METHODS: Fifty three patients who had been treated for Gangrenous Cholecystitis were reviewed. The variables are defined as follows: age, gender, systemic diseases, Mannheim Peritonitis index, aspartate aminotransferase, alanine aminotransferase, white blood cell count and type of surgery. In order to determine the independent risk factors that might affect morbidity and mortality in Gangrenous Cholecystitis, we made use of multivariate logistic regression analysis. RESULTS: The independent risk factors affecting on morbidity were age (P = 0.037), existing systemic disease (P = 0.047) and > or = 29 Mannheim Peritonitis index (P = 0.008), and the independent risk factors affecting on mortality were age (P = 0.046), white blood cell count (P = 0.035). Pre-operative and post-operative third day aspartate amino-transferase and alanine aminotransferase average values were compared, there was a significant difference (P < 0.0001, P < 0.0001 respectively). CONCLUSIONS: We found that older age, > or = 29 Mannheim Peritonitis index and existence of systemic diseases were independent risk factors affecting morbidity. Older age and lower of white blood cell count were independent risk factors affecting mortality. We believe that further comprehensive studies, involving prospective, multi-center and a large number of patients, are needed.

Adult↗
PubMed1999

Negative affectivity: moderator or confound in emotional dissonance-outcome relationships?

This study was an examination of the impact of negative affectivity on relationships between emotional dissonance, job satisfaction, and emotional exhaustion. Negative affectivity is the predisposition to view life in negative terms. Emotional dissonance originates from the conflict between expressed and experienced emotions. In organizations that require the expression of positive emotions, high negative affectivity individuals may experience conflict between expressed, positive emotions and felt, negative emotions. A moderator effect exists when high negative affectivity individuals experience greater job dissatisfaction and emotional exhaustion. Alternatively, negative affectivity may exert a confounding effect through its relationship to both emotional dissonance and its outcomes. Empirical tests showed that negative affectivity moderated the emotional dissonance-job satisfaction relationship and confounded the emotional dissonance-emotional exhaustion relationship.

Adolescent↗
PubMedDate not supplied

Neurodevelopmental liabilities in schizophrenia and affective disorders.

There is now considerable evidence that both schizophrenia and affective disorders have their origin at least in part in events that occur during early pre- and post-natal development. In the case of schizophrenia, many observations, for example, increased risk for schizophrenia in the offspring of mothers who had influenza A during their second trimester of pregnancy and evidence for abnormal neuronal migration in the cerebral cortex of post mortem tissue from schizophrenic patients, suggest that a second trimester insult may have occurred and that this insult may have increased the risk for the development of schizophrenia in late adolescence or early adulthood. Animal studies have found that rats that undergo exocitotoxic damage to the ventral hippocampus on postnatal day 7 develop exaggerated sensitivity to dopamine-stimulating drugs or to stressful stimuli that becomes apparent after sexual maturity but not before, providing a neurodevelopmental model of schizophrenia. Similarly, post-weaning social isolation leads to enhanced responses to dopaminergic drugs and to stress that emerges after sexual maturity. These animal models are proving to be valuable tools to study the neurobiological mechanisms mediating the influence of early insults to the nervous system on later behavioural functions. In the case of affective disorders, although the evidence is not as strong, a number of the same observations have been made suggesting that an insult during early ontogeny may lead to the development of affective disorders later in life. For example, retrospective studies of people with affective disorders showed that they were more likely to have attained motor milestones at a later age and to have had poorer academic performance as children. There is a wealth of evidence suggesting hyperfunctioning of the hypothalamic-pituitary-adrenal (HPA) axis in affective disorders. Animal studies have shown that early maternal deprivation can lead to lasting changes in the reactivity of the HPA axis to stressful stimuli, providing another link from early experience to adult psychopathology. Continued studies of the effects of pre- and early post-natal events on the development of the nervous system and the relationships of these events to schizophrenia or affective disorder will provide new insights into the mechanisms underlying these common neuropsychiatric illnesses.

Journal Article↗
PubMed2002

The role of affect and reasoning in a patient with a delusion of misidentification.

INTRODUCTION: This study investigated a patient with a delusion of misidentification (DM) resembling a Capgras delusion. Instead of the typical Capgras delusion--the false belief that someone has been replaced by an almost identical impostor--patient MF misidentified his wife as his former business partner. METHOD: Detailed investigation of MF's face processing, affective response and affect perception, and ability to evaluate, and reject, implausible ideas was undertaken. RESULTS: MF's visual processing of identity, gender, and age of familiar and unknown faces was intact but he was unable to identify the facial expressions of anger, disgust, and fear, or to match faces across expressions. MF also showed a reduced affective responsiveness to his environment, and impaired reasoning ability. CONCLUSIONS: We propose that MF's delusion of misidentification resulted from a combination of affective deficits, including impairment of both affective response and affect perception, in addition to an inability to evaluate, and reject, implausible ideas. These deficits, in combination with specific life events at the time of onset of the delusion, may have contributed to the form and content of the delusion. In addition, the results raise the possibility that the processing of face identity and facial expression are not as independent as previously proposed in models of face processing.

Journal Article↗
PubMed2005

Murshidabad--one of the nine groundwater arsenic-affected districts of West Bengal, India. Part I: magnitude of contamination and population at risk.

INTRODUCTION: To understand the severity of the arsenic crisis in West Bengal, India, a detailed, 3-year study was undertaken in Murshidabad, one of the nine arsenic-affected districts in West Bengal. The district covers an area of 5324 km2 with a population of 5.3 million. METHODS: Hand tubewell water samples and biologic samples were collected from Murshidabad and analyzed for arsenic by FI-HG-AAS method. Inter laboratory analysis and analyses of standards were undertaken for quality assurance. RESULTS: During our survey we analyzed 29,612 hand tubewell water samples for arsenic from both contaminated and non-contaminated areas, and 26% of the tubewells were found to have arsenic above 50 microg/L while 53.8% had arsenic above 10 microg/L. Of the 26 blocks in Murshidabad, 24 were found to have arsenic above 50 microg/L. Based on our generated data we estimated that approximately 0.2 million hand tubewells are installed in all 26 blocks of Murshidabad and 1.8 million in nine arsenic-affected districts of West Bengal. It was estimated on the basis of our data that about 2.5 million and 1.2 million people were drinking arsenic-contaminated water with concentrations above 10 and 50 microg/L levels respectively in this district. The analysis of total 3800 biologic (nail, urine, and hair) samples from arsenic-affected villages revealed that 95% of the nail and 94% of the urine samples contained arsenic above the normal levels and 75% of the hair samples were found to have arsenic above the toxic level. Thus, many villagers in the affected areas of Murshidabad might be subclinically affected. DISCUSSION AND CONCLUSION: Comparing our extrapolated data with international dose response results, we estimated how many people may suffer from arsenical skin lesions and cancer. Finally, if the exposed population is provided safe water, better nutrition, and proper awareness about the arsenic problem, lives can be saved and countless suffering of the affected population can be avoided.

Arsenic Poisoning↗
PubMed2005

Murshidabad--one of the nine groundwater arsenic-affected districts of West Bengal, India. Part II: dermatological, neurological, and obstetric findings.

INTRODUCTION: To understand the severity of related health effects of chronic arsenic exposure in West Bengal, a detailed 3-year study was carried out in Murshidabad, one of the nine arsenic-affected districts in West Bengal. METHODS: We screened 25,274 people from 139 arsenic-affected villages in Murshidabad to identify patients suffering from chronic arsenic toxicity for evidence of multisystemic features and collected biological samples such as head hair, nail, and spot urine from the patients along with the tubewell water they were consuming. RESULTS: Out of 25,274 people screened, 4813 (19%) were registered with arsenical skin lesions. A case series involving arsenical skin lesions resulting in cancer and gangrene were noted during this study. Representative histopathological pictures of skin biopsy of different types of lesions were also presented. Out of 2595 children we examined for arsenical skin lesions, 122 (4%) were registered with arsenical skin lesions, melanosis with or without keratosis. Different clinical and electrophysiological neurological features were noticed among the arsenic-affected villagers. Both the arsenic content in the drinking water and duration of exposure may be responsible in increasing the susceptibility of pregnant women to spontaneous abortions, stillbirths, preterm births, low birth weights, and neonatal deaths. Some additional multisystemic features such as weakness and lethargy, chronic respiratory problems, gastrointestinal symptoms, and anemia were also recorded in the affected population. DISCUSSION: The findings from this survey on different health effects of arsenic exposure were compared to those from previous studies carried out on arsenic-affected populations in India and Bangladesh as well as other affected countries. CONCLUSION: Multisystemic disorders, including dermal effects, neurological complications, and adverse obstetric outcomes, were observed to be associated with chronic arsenic exposure in the study population in Murshidabad, West Bengal. The magnitude of severity was related to the concentration of arsenic in water as well as duration of the exposure.

Arsenic Poisoning↗
PubMed2004

Association analysis of brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism in schizophrenia and bipolar affective disorder.

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of schizophrenia and bipolar disorder. A functional polymorphism Val66Met of BDNF gene was studied in patients with schizophrenia (n=336), bipolar affective disorder (n=352) and healthy controls (n=375). Consensus diagnosis by at least two psychiatrists, according to DSM-IV and ICD-10 criteria, was made for each patient using a structured clinical interview for DSM-IV Axis I disorders (SCID). No association was found between the studied polymorphism and schizophrenia or bipolar affective disorder either for genotype or allele distribution (for genotype: p=0.210 in schizophrenia, p=0.400 in bipolar disorder; for alleles: p=0.260 in schizophrenia, p=0.406 in bipolar disorder). Results were also not significant when analysed by gender. For males genotype distribution and allele frequency were (respectively): p=0.480 and p=0.312 in schizophrenia, p=0.819 and p=0.673 in bipolar affective disorder. Genotype distribution and allele frequency observed in the female group were: p=0.258 for genotypes, p=0.482 for alleles in schizophrenia; p=0.432 for genotypes, p=0.464 for alleles in bipolar affective disorder. A subgroup of schizophrenic (n=62) and bipolar affective patients (n=28) with early age at onset (18 years or younger) was analysed (p=0.328 for genotypes, p=0.253 for alleles in schizophrenia; p=0.032 for genotypes, p=0.858 for alleles in bipolar affective disorder).

Adult↗
PubMed2000

Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population.

Acquired cerebellar lesions in adults have been shown to produce impairments in higher function as exemplified by the cerebellar cognitive affective syndrome. It is not yet known whether similar findings occur in children with acquired cerebellar lesions, and whether developmental factors influence their presentation. In studies to date, survivors of childhood cerebellar tumours who demonstrate long-term deficits in cognitive functions have undergone surgery as well as cranial irradiation or methotrexate treatment. Investigation of the effects of the cerebellar lesion independent of the known deleterious effects of these agents is important for understanding the role of the cerebellum in cognitive and affective development and for informing treatment and rehabilitation strategies. If the cerebellar contribution to cognition and affect is significant, then damage in childhood may influence a wide range of psychological processes, both as an immediate consequence and as these processes fail to develop normally later on. In this study we evaluated neuropsychological data in 19 children who underwent resection of cerebellar tumours but who received neither cranial irradiation nor methotrexate chemotherapy. Impairments were noted in executive function, including planning and sequencing, and in visual-spatial function, expressive language, verbal memory and modulation of affect. These deficits were common and in some cases could be dissociated from motor deficits. Lesions of the vermis in particular were associated with dysregulation of affect. Behavioural deficits were more apparent in older than younger children. These results reveal that clinically relevant neuropsychological changes may occur following cerebellar tumour resection in children. Age at the time of surgery and the site of the cerebellar lesion influence the neurobehavioural outcome. The results of the present study indicate that the cerebellar cognitive affective syndrome is evident in children as well as in adults, and they provide further clinical evidence that the cerebellum is an essential node in the distributed neural circuitry subserving higher-order behaviours.

Adolescent↗
PubMed2005

CHRM2 gene predisposes to alcohol dependence, drug dependence and affective disorders: results from an extended case-control structured association study.

Cholinergic muscarinic 2 receptor (CHRM2) is implicated in memory and cognition, functions impaired in many neuropsychiatric disorders. Wang et al. [Wang, J.C., Hinrichs, A.L., Stock, H., Budde, J., Allen, R., Bertelsen, S., Kwon, J.M., Wu, W., Dick, D.M., Rice, J. et al. (2004) Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum. Mol. Genet., 13, 1903-1911] reported that variation in CHRM2 gene predisposed to alcohol dependence (AD) and major depressive syndrome. We examined the relationships between variation in CHRM2 and AD, drug dependence (DD) and affective disorders, using a novel extended case-control structured association (SA) method. Six markers at CHRM2 and 38 ancestry-informative markers (AIMs) were genotyped in a sample of 871 subjects, including 333 healthy controls [287 European-Americans (EAs) and 46 African-Americans (AAs)] and 538 AD and/or DD subjects (415 with AD and 346 with DD and 382 EAs and 156 AAs). The same CHRM2 markers were genotyped in a sample of 137 EA subjects with affective disorders. All of the six markers were in Hardy-Weinberg equilibrium in controls, but SNP3 (rs1824024) was in Hardy-Weinberg disequilibrium in the AD and DD groups. Using conventional case-control comparisons, some markers were nominally significantly or suggestively associated with phenotypes before or after controlling for population stratification and admixture effects, but these associations were not significant after multiple test correction. However, regression analysis identified specific alleles, genotypes, haplotypes and diplotypes that were significantly associated with risk for each disorder. We conclude that variation in CHRM2 predisposes to AD, DD and affective disorders. One haplotype block within the 5'-UTR of CHRM2 may be more important for the development of these disorders than other regions. Interaction between two specific alleles within this block and interaction between two specific diplotypes covering this block multiplicatively increased risk for AD and DD. Although interaction between these two diplotypes also increased risk for affective disorders, the magnitude of the increased risk was less than the sum of the individual risks. In addition, a specific diplotype might inversely affect risk for AD and DD and risk for affective disorders.

Adult↗