Important Findings Published in Biological Psychiatry
By Caleb M. Adler, MD.
October 15, 2011
Commentary by Jacqueline F. McGinty and John E. Mendelson
D'Sa C, Fox HC, Hong AK, et al (2011). Increased serum brain-derived neurotrophic factor is predictive of cocaine relapse outcomes: a prospective study. Biol Psychiatry 70:706-711
The authors obtained three serial samples of brain-derived neurotrophic factor (BDNF) from a cohort of 3-week abstinent inpatients with cocaine dependence. They found that concentrations of BDNF were elevated in the cocaine users, compared with a group of healthy controls. After following the patients for up to 90 days, they found that higher serum levels of BDNF were predictive of shorter times to relapse and greater cocaine use. They suggest that BDNF may represent a biomarker for cocaine relapse. In the commentary, Drs. McGinty and Mendelson discuss the potential role of biomarkers in psychiatric research and treatment. They note that these findings warrant further follow-up studies of the relationship between BDNF and cocaine dependence.
Commentary by Arthur L. Brody and Ian A. Cook
Rose JE, McClernon FJ, Froeliger B, et al (2011). Repetitive transcranial magnetic stimulation of the superior frontal gyrus modulates craving for cigarettes. Biol Psychiatry 70:794-799
In this study, the authors report that high frequency (10 Hz) rTMS directed at the superior frontal gyrus (SFG) differentially affected craving in a group of smokers, compared with a low frequency (1 Hz) condition and rTMS directed at the motor cortex (control condition). Smokers described increased cravings in response to smoking cues with the high versus low frequency rTMS and the control condition, as well as decreased craving in response to neutral cues. With the high frequency rTMS, smokers also demonstrated smaller reductions in immediate craving with simulated cigarette exposure. These findings support suggestions that the SFG plays a role in drug-seeking behaviors. In the commentary, these findings are noted to be buttressed by neurobiological findings from a number of recent studies, and further avenues for research are suggested.
Commentary by Walter H. Kaye and Ursula F. Bailer
Gérard N, Pieters G, Goffin K, et al (2011). Brain type 1 cannabinoid receptor availability in patients with anorexia and bulimia nervosa. Biol Psychiatry 70:777-784
In the study described, Dr. Gérard and colleagues use positron emission tomography (PET) to study type 1 cannabinoid receptors (CB1R) in patients with anorexia (AN) and bulimia (BN) nervosa, as well as a group of healthy controls. Compared with healthy controls, patients with AN showed increased CB1R binding across both cortical and subcortical areas, as well as regional increases in the inferior frontal and temporal cortices; both patients with AN and those with BN showed increased receptor availability in the insula. Furthermore, binding in the superior temporal cortex of patients with AN correlated with the "drive for thinness" subscale of the Eating Disorder Inventory. In the commentary, these findings are placed in a larger neuroanatomical and physiological context- with particular emphasis on the possible integrative role being played by the insula. Although these findings cannot differentiate between cause and consequence with regard to the relationship between eating disorders and CB1R, the commentary notes that these findings provide new insights into suggestions that disturbances of reward and hedonic networks contribute to eating disorder behaviors.
November 1, 2011
Commentary by Randi Jenssen Hagerman
Bray S, Hirt M, Jo B, et al (2011). Aberrant Frontal Lobe Maturation in Adolescents with Fragile X Syndrome is Related to Delayed Cognitive Maturation. Biol Psychiatry 70:852-858
Fragile X syndrome (FXS) is a relatively common source of cognitive deficits linked to abnormalities in the fragile X mental retardation gene (FMR1). Although cognitive decline is typically first observed in childhood, deficits accelerate during adolescence and early adulthood. In this study, the authors used structural magnetic resonance imaging (sMRI) to compare a group of patients with FXS and normally developing healthy controls; in addition to the cross-sectional analysis of age-related changes, the authors followed a subset of these individuals over one to five years. They observed significantly larger caudate volumes in subjects with FXS regardless of age, as well as evidence for age- and gender-related changes in prefrontal volume. Cognitive deficits showed a similar age-related trajectory, suggesting that these prefrontal changes are at least partially responsible for the cognitive decline observed in adolescent patients with FSX.
Hessl D, Wang JM, Schneider A, et al (2011). Decreased fragile x mental retardation protein expression underlies amygdala dysfunction in carriers of the fragile x premutation. Biol Psychiatry 70:859-865
In this study, the authors applied functional magnetic resonance imaging (fMRI) to a group of 23 men who carried the FMR1 premutation. These men showed smaller amygdala volumes, as well as decreased neuronal activation in response to an emotion processing task compared with a group of healthy controls. Decreased amygdala activity was associated with deficits in processing social communication and information. Further analysis found that reduced levels of fragile X mental retardation protein (FMRP) were significantly associated with these decrements in amygdala activation. In the commentary, the findings from these two studies are linked and placed in the larger context of recent findings in FSX. Further, Dr. Hagerman observes that these findings emphasize the importance of intervening early in the disease process of FXS rather than after much of the neuropathology has occurred.
Commentary by C. Sue Carter and Eric C. Porges
Laurent HK, Stevens A, Ablow JC (2011). Neural correlates of hypothalamic-pituitary-adrenal regulation of mothers with their infants. Biol Psychiatry 70:826-832
Hypothalamic-pituitary-adrenal (HPA) axis hormones have been widely implicated in parental response to child-related cues. In this study, the authors found a relationship between trajectories of HPA activity with induced stress in a group of new mothers. Lower levels of HPA axis reactivity were associated with increased neuronal activation during functional magnetic resonance imaging (fMRI) in response to hearing the cry of their baby. Associations were observed in prefrontal and paralimbic regions previously found to be involved in empathy and mother-child interaction. The commentary places these findings within the larger history of attachment studies while emphasizing the many questions that remain unanswered.
November 15, 2011
Commentary by Holly Moore and Ezra Susser
Escobar M, Crouzin N, Cavalier M, et al (2011). Early, time-dependent disturbances of hippocampal synaptic transmission and plasticity after in utero immune challenge. Biol Psychiatry 70:992-999
A variety of prenatal stresses have been identified with increased risk for schizophrenia. Maternal immune activation (MIA) in rodents, using lipopolysaccharide (LPS) has been observed to give rise to cognitive deficits and psychosis-like outcomes in offspring. In this paper, the authors report on a series of electrophysiological experiments on the CA1 hippocampal region of pups whose dams had been exposed to LPS. The investigators report that long term depression (LTD) induced by low frequency stimulation is accelerated in these offspring, compared with normal developmental changes. Further, pharmacological characterization of the LTD suggests dependence on metabotropic glutamate and protein kinase A activation. LPS was found to be linked to other hippocampal receptor changes, as well. In the commentary, it is observed that these findings support suggestions that MIA may be related to changes in the regulation of hippocampal synaptic plasticity that carry potentially functional consequences. Drs. Moore and Susser note that these and similar findings have been suggested to have implications for the pathogenesis of schizophrenia. The commentary explores the challenges to this interpretation and areas that need to be further investigated to clarify this potential link.
Commentary by Ryoko Hiroi and John F. Neumaier
Zeidan MA, Igoe SA, Linnman C, et al (2011). Estradiol modulates medial prefrontal cortex and amygdala activity during fear extinction in women and female rats. Biol Psychiatry 70:920-927
In this study, the authors utilized linked preclinical and clinical studies to investigate the role of estradiol in fear extinction. Administration of an estrogen receptor beta agonist and estradiol to rodents was associated with effects on extinction recall and memory consolidation, respectively. Estradiol was also associated with increased c-fos expression in the ventromedial prefrontal cortex (vmPFC) and decreased expression in the amygdala. In women, natural variations in estradiol were similarly associated with modulation of extinction recall and activity in the vmPFC. In the commentary, Drs. Hiroi and Neumaier discuss the complicated role of estrogen in fear learning and extinction, and the potential clinical implications of recent research.
Commentary by Hedy Kober and Kevin N. Ochsner
Light SN, Heller AS, Johnstone T, et al (2011). Reduced right ventrolateral prefrontal cortex activity while inhibiting positive affect is associated with improvement in hedonic capacity after 8 weeks of antidepressant treatment in major depressive disorder. Biol Psychiatry 70:962-968
In this study, groups of healthy and depressed subjects (diagnosed with major depressive disorder) participated in fMRI scans during which they viewed positively valenced pictures. Subjects were instructed to inhibit their emotional responses to some of the pictures. All subjects showed increased activity in the right ventrolateral prefrontal cortex (VLPFC) during emotional inhibition. In depressed subjects, RVLPFC activation contributed to changes in ratings on a measure of anhedonia- and lower levels of activation at baseline predicted greater reduction in anhedonia over eight weeks of treatment with an antidepressant. In the commentary, Drs. Kober and Ochsner put these findings into the larger context of recent studies of emotional regulation. While noting the importance of these findings, they suggest that some questions remain with regard to their interpretation; the commentary explores some possible alternatives.
December 1, 2011
Commentary by Christopher Pittenger
Shanahan NA, Velez LP, Masten VL, et al (2011). Essential Role for Orbitofrontal Serotonin 1B Receptors in Obsessive-Compulsive Disorder-Like Behavior and Serotonin Reuptake Inhibitor Response in Mice. Biol Psychiatry 70:1039-1048
In this study the authors further exam a rodent model of obsessive-compulsive disorder (OCD) involving the administration of a serotonin 1B receptor (5-HT1BR) agonist. They have previously observed that serotonin reuptake inhibitors clinically useful in treating OCD moderate the OCD-like effects of 5-HT1BR agonists. In this study, the authors demonstrated that clomipramine, an effective treatment for OCD, but not desipramine moderated the effects of a 5-HT1BR agonist as well as down regulating 5-HT1BR expression in the orbitofrontal cortex- a brain region hypothesized to be involved in OCD symptomatology. Furthermore, infra-orbital administration of a 5-HT1BR agonist induced OCD-like symptoms, while infra-orbital administration of a 5HT1BR antagonist blocked the effects of 5-HT1BR agonist administration. These findings were discussed in the commentary, and while some potential interpretative concerns were raised, the commentary author noted the importance of these findings in working toward a valid animal model of OCD.
Commentary by Jennifer C. Britton and Scott L. Rauch
Fox E, Zougkou K, Ridgewell A, et al (2011). The serotonin transporter gene alters sensitivity to attention bias modification: evidence for a plasticity gene. Biol Psychiatry 70:1049-1054
The authors found that carriers of the low expression form of the 4-HTTLPR gene showed stronger biases for both negative and positive stimuli after training with an attention bias modification technique, compared with carriers of the high expression form. The finding that allelic variation in the promoter region may modify attentional bias in an emotionally agnostic way suggests that increased sensitivity in carriers of the low expression form to stressful life events may be related to a general predisposition to altered attentional bias rather than a specific vulnerability. The commentary expands on these findings and notes their implications for treatment of relevant psychiatric disorders.
Commentary by Caitlin E. McOrnish and Jay A Gingrich
Benekareddy M, Vadodaria KC, Nair AR, et al (2011). Postnatal Serotonin Type 2 Receptor Blockade Prevents the Emergence of Anxiety Behavior, Dysregulated Stress-Induced Immediate Early Gene Responses, and Specific Transcriptional Changes that Arise Following Early Life Stress. Biol Psychiatry 70:1024-1032
The authors have previously observed that early maternal separation in rodents is associated with changes in 5-HT2 receptor function and anxiety-like adult phenotypes. In this study, the authors treated these stressed pups with ketanserin, a 5-HT2 receptor antagonist. They found that the receptor antagonist blocked stress-induced patterns of gene expression and 5-HT2A receptor messenger RNA expression. In addition, treated rodents did not demonstrate the long-term effects of maternal separation on anxiety behaviors. In the commentary, Drs. McOrnish and Gingrich place these findings in a larger context and emphasize the clinical importance of better understanding the developmental origins of neuropsychiatric disorders.
December 15, 2011
Commentary by Judith Rapoport and Kwangmi Ahn
Rees E, Moskvina V, Owen MJ, et al (2011). De novo rates and selection of schizophrenia-associated copy number variants. Biol Psychiatry 70:1109-1114
The authors endeavored to calculate the selection rate for several large copy number variants (CNVs) that have been implicated in the pathogenesis of schizophrenia and other neurodevelopmental disorders. Using a literature search, they determined the rate of these CNVs in the general population and of their de novo appearance. The authors found that all of these CMVs were under a high selection pressure, and estimated that all of these CMVs disappeared from the population in an average of less than five generations; some persisted less than two generations. They conclude that these risk-related CMVs show a high rate of de novo appearance.
Melhem N, Middleton F, McFadden K, et al (2011). Copy number variants for schizophrenia and related psychotic disorders in oceanic palau: risk and transmission in extended pedigrees. Biol Psychiatry 70:1115-1121
The authors studied CNVs associated with schizophrenia in a restricted population sample, from the island of Palau. The extended pedigrees available from this somewhat isolated population allowed them to confirm the association between several CMVs and psychopathology, as well as identify some novel variants. The authors note that the majority of the CMVs show incomplete penetrance and arise de novo in the population. Other CMVs however, particularly two potentially associated with sex-dependent risk appear to be present in the population over multiple generations. The commentary observes the importance of replicating CMV studies in more diverse population samples and echoes the manuscript in noting both the advantages and disadvantages of studying more insular groups. These findings are integrated with those of Rees and colleagues to extend our understanding of the role that CMVs may play in schizophrenia while also highlighting the non-specific nature of their impact on potential psychopathology. Finally, ideas for further research are described.
Commentary by Paul C. Fletcher
Zandbelt BB, van Buuren M, Kahn RS, et al (2011). Reduced proactive inhibition in schizophrenia is related to corticostriatal dysfunction and poor working memory. Biol Psychiatry 70:1151-1158
The authors utilize fMRI to examine both proactive and reactive inhibition in groups of schizophrenic patients, unaffected siblings and healthy controls. Proactive inhibition was impaired in schizophrenic patients, and to a lesser degree in unaffected siblings. This impairment was associated with decreased activity in several regions including portions of the prefrontal cortex, striatum, and temporoparietal junction. In contrast, the authors found no differences in reactive inhibition, or in associated functional activation. Working memory abilities in the schizophrenic patients correlated with proactive inhibition, and inversely correlated with reductions in activation across several brain regions.
Anticevic A, Repovs G, Corlett PR, et al (2011). Negative and nonemotional interference with visual working memory in schizophrenia. Biol Psychiatry 70:1159-1168
In this paper, the authors describe differences in the effects of distracting stimuli between patients with schizophrenia and healthy controls. Subjects were shown negative, neutral and task-related distractors during a working memory task. Patients with schizophrenia demonstrated a different pattern of brain activation in response to distractors, including increased response to non-emotional stimuli- suggesting problems with cognitive filtering. The authors observe that these findings are consistent with suggestions that schizophrenia is associated with deficits in salience processing. The commentary notes that taken in tandem with the work of Zandbelt and colleagues, these findings suggest that patients with schizophrenia show difficulties optimizing inhibitory processes. The commentary further notes the presence of decreased activity in the right prefrontal cortex across both studies. The implications of these finding for both the pathophysiology of schizophrenia and potential iPhone games are further explored.
Commentary by Martin P. van den Heuvel and René S. Kahn
Hinkley LB, Vinogradov S, Guggisberg AG, et al (2011). Clinical symptoms and alpha band resting-state functional connectivity imaging in patients with schizophrenia: implications for novel approaches to treatment. Biol Psychiatry 70:1134-1142
In this study, 30 patients with schizophrenia and 15 healthy controls participated in magnetoencephalography (MEG). The authors examined functional connectivity between brain regions and the remainder of the brain. Differences in connectivity were observed in several regions hypothesized to contribute to the pathophysiology of schizophrenia. Both the right superior temporal and left prefrontal cortex (PFC) showed decreased connectivity; the latter was associated with negative symptoms. In contrast, midline PFC functional connectivity inversely correlated with positive symptoms. Increased connectivity was observed in the left extrastriate and right inferior PFC; the latter associated with cognitive symptoms. The commentary places these findings in a larger context, and notes the importance of tying abnormal connectivity to clinical symptomatology.
January 1, 2012
Commentary by Ian H. Gotlib and J. Paul Hamilton
Glahn DC, Curran JE, Winkler AM, et al (2011). High dimensional endophenotype ranking in the search for major depression risk genes. Biol Psychiatry 71:6-14
The authors describe their application of endophenotype ranking value (ERV) to a large sample of previously studied individuals with well-defined pedigrees. The ERV combines the heritability of a putative endophenotype with the heritability of the associated illness and their genetic correlation to derive a value reflecting the genetic utility of a given endophenotype. The authors found top-ranked endophenotypes to be bilateral ventral encephalon size, score on the Beck depression inventory (BDI), and expression levels of the RNF123 transcript- RNF123 may be involved in hippocampal neurogenesis. At least near genome-wide significant quantitative trait loci (QTL) were identified for the presence of major depressive disorder (MDD) and the bilateral ventral encephalon. In addition, a bivariate linkage analysis suggested a pleiotropic effect on RNF-123 and MDD status of the former QTL. The commentary emphasizes the potential advantages of using ERV to select pertinent endophenotypes and discusses the findings in light of endophenotype characterization and the current understanding of depression.
Commentary by Robert Dantzer
Copeland WE, Shanahan L, Worthman C, et al (2011). Cumulative depression episodes predict later C-reactive protein levels: a prospective analysis. Biol Psychiatry 71:15-21
Although the association between depression and some markers of inflammation is long-standing, clarification of priority has been elusive. Cross-sectional studies do not answer whether depression precedes inflammation, or the reverse. In this paper, the authors describe a longitudinal study designed to address this question. They found that in children and adolescents followed up to age 21, depression symptoms, diagnoses and number of episodes predicted levels of C - reactive protein (CRP). The authors note that these findings suggest that the origins of some later, inflammation-related illnesses may lie in childhood emotional states. In the commentary, this study is placed in the context of previous psychoneuroimmunology/immunoneuropsychology research, and other potential implications of these data are discussed.
Members of SOBP receive Biological Psychiatry as part of their membership Click here to learn more about this prestigious journal.
Top 6 Reasons to Publish in Biological Psychiatry
1. High Impact Factor - 8.674
2. 4th of 126 Psychiatry Journals
3. 15th of 237 Neuroscience Journals
4. 1st Decision - 30 Days
5. ePubs - 6 Weeks
6. In Print - 4 Months