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In a genome-wide survey of large, rare structural genomic variants (copy number variants [CNVs]), Grozeva et al found that schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Their data suggest that in individuals at risk of psychosis, CNVs may modify the clinical phenotype, with those possessing them more likely to be diagnosed with schizophrenia and those without them being more likely to be diagnosed with bipolar disorder.
In a birth cohort of twins, Polanczyk et al found that self-reported psychotic symptoms at age 12 years are familial and heritable and share many of the same risk factors and clinical correlates with adult schizophrenia, including neurodevelopmental, social, and behavioral risks as well as self-harm. The results support the hypothesis that childhood psychotic symptoms are often a marker of an impaired developmental process and suggest that the continuum model of psychosis may apply to preadolescents.
Solomon et al examined the duration of 8 different types of bipolar I mood episodes. The data consisted of prospective observations of psychopathology in 219 subjects assessed annually for up to 25 years. Mixed-effects analyses revealed that cycling mood episodes, characterized by switching from one pole to the other without an intervening period of recovery, lasted significantly longer than episodes of pure major depression. This finding helps validate the concept of cycling episodes, which presently are not recognized by DSM-IV or International Statistical Classification of Diseases, 10th Revision.
Kohli et al report independent single-nucleotide polymorphisms within the NTRK2 gene being associated with lifetime attempted suicide among depressed patients in the Munich Antidepressant Response Signature study. These associations could be confirmed in both the German and African American replication samples (N = 2172). The odds ratio was 4.5 when patients carrying risk genotypes in all 3 markers were compared with those without any of the 3 risk genotypes.
Andreazza et al demonstrate decreased levels of the electron transport chain complex I subunit NDUFS7, decreased activity of complex I, and increased oxidative damage to mitochondrial proteins in the prefrontal cortex of subjects with bipolar disorder. Increased tyrosine nitration was also found in both the bipolar disorder and schizophrenia groups.
Binder et al show that a single-nucleotide polymorphism, rs10473984, within the corticotropin-releasing factor binding protein (CRHBP) locus is associated with antidepressant treatment response to citalopram in African American and Hispanic patients in the STAR*D cohort. The association was most pronounced in patients with anxious depression. These data suggest a role for this gene and the corticotropin-releasing factor system in antidepressant treatment response, most evident in anxious depression.
Gotlib et al examined the neural circuitry of reward and loss processing in healthy 10- to 14-year-old daughters of mothers with recurrent depression. Compared with age-matched controls, daughters of depressed mothers showed less activation in the putamen and left insula while anticipating reward and greater activation in the dorsal anterior cingulate gyrus during loss. Familial risk for depression affects neural mechanisms underlying the processing of reward and loss.
Ohashi et al studied hyperactivity in 62 boys with attention-deficit/hyperactivity disorder and 62 age-matched controls (9-12 years). Boys with attention-deficit/hyperactivity disorder had an impaired ability to inhibit activity to low levels and even greater difficulty maintaining positional stability as reflected in chaotic dynamics. Ability to inhibit activity was normalized by methylphenidate but positional stability was not, suggesting that they may be mediated by different neural circuits.
To assess the relevance of the fusiform-amygdala system to the pathophysiology of autism, Dziobek et al applied whole-brain cortical thickness mapping and manual tracing of the amygdala in individuals with autism and controls. They found a specific local increase in cortical thickness of the fusiform gyrus and associated impairments in face processing in individuals with autism. Anatomical covariance between amygdala volume and the fusiform gyrus was significantly smaller in the group with autism.
Using the twin method, Rijsdijk et al demonstrated that variations in gray matter concentration in the posterior cingulate and dorsal anterior cingulate reflect genetic vulnerability for psychopathic traits. These brain areas are implicated in empathy, moral processing, and introspection and constitute candidate endophenotypes for psychopathic traits.
Jessen et al studied the prediction of dementia by the presence of subjective memory impairment in 2423 older subjects without cognitive impairment over 2 follow-up waves (1.5 and 3 years). Subjective memory impairment at baseline predicted dementia over 3 years, particularly if the impairment was associated with worry. The greatest risk for Alzheimer dementia at follow-up 2 (odds ratio, 60.28) was for those with subjective memory impairment at baseline and amnestic mild cognitive impairment at follow-up 1.
Lindell et al report that loss-of-function variation in the rhesus NPY regulatory region predicts decreased stress resilience and escalated alcohol intake. Early stress-exposed carriers of the variant fail to adapt to protracted stress and exhibit increased alcohol consumption, particularly following cycles of deprivation. The results suggest a role for human NPY variation in alcohol dependence.
THIS MONTH IN ARCHIVES OF GENERAL PSYCHIATRY. Arch Gen Psychiatry. 2010;67(4):316. doi:10.1001/archgenpsychiatry.2010.27