Message from the Editor

It was a truly wonderful year for the Society of Biological Psychiatry (SOBP), with the wrap up of the Annual Meeting, held this year in Philadelphia from May 3-5, at the Sheraton City Center.  In many ways, this year's meeting continued many of the trends established at prior meetings.  Thus, the meeting continues to be amazingly well attended.  This year's attendance of 1380 represents another banner year for us, showing a trend of steadily increasing numbers.  Moreover, as in prior years, the program was filled with an exciting combination of morning plenary sessions, led by the world's leading scientists, focused symposia in the afternoon and evening poster sessions.  However, in other ways, aspects of this year's meeting were unique.  Two aspects of the meeting really stood out, relative to meetings of the Society in recent years, in terms of uniqueness.

First, the theme for this year's meeting was "Systems Neuroscience: Applications to Psychiatric Illness".  The themes were designed to bring together sections of SOBP focused on relatively basic themes with sections focused on more clinical themes.  The plenary sessions provided an excellent fulcrum upon which to bring together these sections of the SOBP, using two distinct approaches.  Thus, for one approach, two of the sessions focused in depth on specific methodologies, applied across illnesses, where unusual opportunities abound for integration.  In one of these, on Friday, May 4, Drs. Nikos Logothetis, Marcus Raichle, Cameron Carter, and Leslie Ungerleider focused on the promise of brain imaging for understanding psychiatric illness.  In the other, on Saturday, May 5, Drs. Ronald McKay and Ricardo Dolmetsch focused on the promise of iPS Cell techniques.  For the other approach, two sessions focused on specific areas of science, applied across methodologies, where similar opportunities abound.  Thus, in one of these, on Thursday, May 3, Drs. Larry Young, Sarah-Jayne Blakemore, Elizabeth Phelps, and Alison Doupe focused on social cognition, studied with a focus on societies, circuits, cells, and molecules.  In the other, on Saturday, May 5, Drs. Amy Arnsten and Randall O'Reilly adopted a similarly deep approach, applied to reward processing.  Across all four sessions, the promise of an integrative approach, so central to SOBP, was richly illustrated through state-of-the-art techniques, applied to vital clinical issues.  Of note, this theme was further reflected in the many symposia and posters focused in even more depth on many of the same vital issues.

Second, this year's meeting continued a trend to reach out to young investigators.  Thus, a large proportion of attendees were scientists in a relatively early stage in their career, and SOBP made explicit efforts to recognize their importance to the field and to SOBP more generally.  Aspects of the meeting that have been a staple for years were subtly changed in an attempt to capitalize on this infusion of youth.  Such changes were reflected in the expanded attendance at this year's President's Reception and by attempts to increase the breadth and depth of our active mentorship program.  Moreover, plans to continue this trend in future meetings also were hatched, plans that would both lead to continued changes in existing, key aspects of the meeting as well as the creation of new program activities explicitly designed to appeal to young investigators.

Society of Biological Psychiatry's 68th Annual Meeting

May 16-18, 2013 

Hilton San Francisco - Union Square 

San Francisco, California 

Important Findings Published in Biological Psychiatry

By Caleb M. Adler, MD.  

April 1, 2012

Commentary by Hilary P. Blumberg

Hulvershorn LA, Karne H, Gunn AD, et al (2012). Neural activation during facial emotion processing in unmedicated bipolar depression, euthymia, and mania. Biol Psychiatry 71:603-610

The investigators address the lack of studies comparing bipolar patients across mood states by recruiting groups of unmedicated bipolar I and II patients in depressive, manic or hypomanic, and euthymic mood states, as well as healthy controls to participate in an fMRI study involving a negative facial emotion matching task. They report that while bipolar patients showed increased subcortical activity versus healthy controls across mood states, increased amygdala activity was observed only in depressed and euthymic individuals; manic/hypomanic patients did not exhibit significant amygdala response. Increased insula activity was observed in manic/hypomanic and euthymic patients but was absent with depression. Manic/hypomanic patients also showed mood-state specific findings-increased anterior cingulate and dorsolateral prefrontal cortical activity versus depressed patients and all other groups, respectively. Manic/hypomanic patients also showed decreased orbitofrontal activity versus both euthymic patients and healthy controls. The authors and commentary note that these findings support suggestions that the underlying neuropatholophysiology of bipolar disorder may vary across mood states. In addition, Dr. Blumberg puts these findings into the larger context of previous research into the neurophysiology of affective switch.

Commentary by Boris Tabakoff and Paula L. Hoffman

Joeyen-Waldorf J, Nikolova YS, Edgar N, et al (2012). Adenylate cyclase 7 is implicated in the biology of depression and modulation of affective neural circuitry. Biol Psychiatry 71:627-632

In this innovative series of experiments the investigators have utilized comparative gene analysis to implicate the adenylate cyclase 7 gene (ADCY7) in individual vulnerability to mood disorders, and to test its neurophysiological effects in a group of healthy adults. Knock-out mice lacking the Sert gene (sertko) have been observed to replicate some features of major depression. Sertko and wild type mice were compared, and a selection of candidate genes identified. Cross-referencing these findings with genes derived from humans diagnosed with depression revealed a number of overlapping, evolutionarily conserved genes.The authors focus in particular on ADCY7, a gene which has been previously associated with depression in both rodents and humans. Two groups of healthy adults were then genotyped and asked to participate in fMRI scans during which they performed a threat-related matching faces task. The investigators found that a single nucleotide polymorphism (SNP) in ADCY7 (the T allele) was associated with increased amygdala reactivity. Although the authors noted that the T allele is not associated with increased risk of depression and that they were unable to identify evidence of increased expression, these findings further support the role of adenylate cyclases in mood regulation. In the commentary, Drs. Tabakoff and Hoffman expand on the putative role of adenylate cyclase enzymes in depression and anxiety disorders-and offer further interpretation of the authors' findings.

April 15, 2012

Commentary by Patrick D. Skosnik, Mohini Ranganathan, and Deepak Cyril D'Souza

Bossong MG, Jansma JM, van Hell HH, et al (2012). Effects of δ9-tetrahydrocannabinol on human working memory function. Biol Psychiatry 71:693-699

Several lines of evidence suggest the involvement of the endocannabinoid (eCB) system in working memory deficits observed in schizophrenia. In this study, the investigators employed fMRI to measure the effects of an eCB agonist, Δ9-tetrahydrocannabinol during performance of a parametric working memory task in healthy individuals. The authors report that the eCB agonist reduced working memory performance, and affected activation of the dorsolateral prefrontal cortex, left inferior temporal gyrus, left inferior parietal gyrus, and cerebellum. The Δ9-tetrahydrocannabinol disrupted the linear change in activity with increasing working memory task difficulty observed during placebo administration, and was associated with increased activity during lower cognitive demand. The authors conclude that these findings suggest that the eCB system is involved in performing working memory tasks. They further link these findings to neuropathological findings in schizophrenia. In the commentary, the background for this experiment elaborated upon, and the investigators' findings discussed more fully. While some limitations are noted, the commentators agree that these findings shed light on fundamental neurocognitive processes and might ultimately have important clinical implications.

Commentary by John C. Churchwell, Melissa Lopez-Larson, and Deborah A. Yurgelun-Todd

Cheetham A, Allen NB, Whittle S, et al (2012). Orbitofrontal volumes in early adolescence predict initiation of cannabus use: A 4-year longitudinal and prospective study. Biol Psychiatry 71:684-692

Several recent studies have identified neurostructural changes in cannabis users, often interpreted as suggesting that marijuana use may be neurotoxic. The cross-sectional nature of these studies however, has not allowed disambiguation of causality; it may be that the neurostructural changes observed represent vulnerability markers rather than consequences of use. In this study, the investigators obtained structural MRI scans from a cohort of 12 year-olds; a subset were assessed for cannabis use four years later. Of the 121 subjects who were assessed, 28 were found to have used cannabis at least once. The investigators found that smaller left and right orbitofrontal cortical (OFC) volumes were predictive of later cannabis use. Subdividing the OFC showed significant relationships between later use and volume of the right lateral and left medial OFC. While the findings on the left did not survive controlling for alcohol use, findings on the right remained significant. The authors discuss how structural abnormalities in the OFC might contribute to cannabis use. The commentary discusses potential mechanisms that might underlie these findings, and implications for other psychopathology including mood disorders. In addition, potential caveats and areas for future research are elaborated upon.

May 1, 2012

Commentary by Marsel Mesulam

Grothe M, Heinsen H, Teipel SJ, et al (2012). Atrophy of the cholinergic basal forebrain over the adult age range and in the early stages of Alzheimer's disease. Biol Psychiatry 71:805-813

Although the appearance of neurodegenerative changes in the basal forebrain cholinergic system (BFCS) of patients with Alzheimer's disease (AD) has been well documented, the extent of changes in early stages of the disorder remains controversial. In this study, the investigators examined structural MRI scans from a large group of healthy adults, and smaller groups of adults with mild or questionable AD or more advanced AD. Volumes of the BFSC and hippocampus were obtained using automated techniques. They report that healthy adults show a decline in volume that begins early and accelerates with more advanced age. The BFCS is affected in even mild AD and more extensively atrophic in full AD. Changes in patients with more advanced AD (but not mild AD) rival those seen in the hippocampus. In the commentary, the role of cholinergic innervation of the cortex is discussed more extensively, and particularly that of cholinergic axons arising from the basolateral cortical strip. Dr. Mesulam reviews the link between degeneration of these neurons and AD, and discusses the investigators' data within these larger findings.

Commentary by David C. Steffens

Lee GJ, Lu PH, Hua X, et al (2012). Depressive symptoms in mild cognitive impairment predict greater atrophy in Alzheimer's disease-related regions. Biol Psychiatry 71:814-821

Depression has long been reported to be a risk factor for conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). In this study, investigators used MRI to examine neurostructural changes over two years in 243 patients with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative. Patients were classified by the presence of depressive or non-depressive neuropsychiatric symptoms. MCI patients found to be depressed at baseline showed greater frontal, parietal, and temporal white matter atrophy than MCI patients with neither depression nor non-depressive neuropsychiatric symptoms. In contrast, patients with non-depressive neuropsychiatric symptoms did not differ from unaffected MCI patients. The investigators also noted that the subset of depressed patients who remained symptomatic over the two years showed a higher rate of conversion to AD than did a stable cohort without depression or other psychiatric symptoms. The commentary discusses the apparent relationship between depression and conversion from MCI to AD, and speculates on possible interpretations of these findings.

Commentary by P. Murali Doraiswamy

Valenzuela MJ, Matthews FE, Brayne C, et al (2012). Multiple biological pathways link cognitive lifestyle to protection from dementia. Biol Psychiatry 71:783-791

The notion that maintaining an active cognitive lifestyle might have neuroprotective effects in aging brains has gained considerable currency over the last few years. Several recent studies lend at least some support to this suggestion, linking increased cognitive function to lower rates of dementia. In this study, the investigators sought to explore possible mechanisms underlying the potential effects of cognitive lifestyle on the development of Alzheimer's disease (AD). Over thirteen thousand elderly subjects were followed for fourteen years. A Cognitive Lifestyle Score (CLS) was calculated and subjects divided into low, middle or high CLS groups. 329 of these subjects died and made their brain available for autopsy. The investigators found that CLS groups did not differ on any marker of Alzheimer's disease including diffuse and neuritic plaques, neurofibrillary tangles, hippocampal atrophy, or cerebral amyloid angiopathy. CLS was similarly not associated with neuroprotective effects on the hippocampus. Individuals with higher CLS did however, show greater neuronal density and cortical thickness in Brodmann area 9, a part of the dorsolateral prefrontal cortex involved in a range of cognitive domains-suggesting a role for some compensatory brain changes. In addition, men with higher CLS showed less evidence of cerebrovascular disease, while women had increased brain weight. The commentary discusses these findings at length, noting that the authors' observations suggest that the effects of cognitive ability on dementia may be complex and far from unitary. Further, our understanding of what constitutes cognitive activity may be problematically flawed.

May 15, 2012

Commentary by Peter Dayan and Mark E. Walton

Wassum KM, Ostlund SB, Maidment NT (2012). Phasic mesolimbic dopamine signaling precedes and predicts performance of a self-initiated action sequence task. Biol Psychiatry 71:846-854

In sequential operations, tasks may be performed that will ultimately lead to a reward but in themselves carry little positive reinforcement. The application of temporal difference learning to phasic dopamine release has helped illuminate the neurophysiological underpinnings of this phenomenon. In this study, investigators use fast-scan cyclic voltammetry to monitor phasic mesolimbic dopamine release in rats performing a sequential lever-pressing task to obtain a sucrose reward. They found that after learning the task, rats showed increased dopamine release prior to the initial lever press in the task sequence with back propagation in the task sequence with increased experience. Phasic dopamine was found to predict task performance and dopamine blockade negatively impacted learning and performance. The commentary expands on the investigators' discussion of these findings and addresses alternate interpretations of the results observed.

Commentary by Ed Bullmore

Meda SA, Gill A, Stevens MC, et al (2012). Differences in resting-state functional magnetic resonance imaging functional network connectivity between schizophrenia and psychotic bipolar probands and their unaffected first-degree relatives. Biol Psychiatry 71:881-889

The investigators sought to use resting state fMRI to compare default networks relationships between groups of patients with schizophrenia and bipolar disorder with psychosis, as well as unaffected first-degree relatives of both. Dr. Meda and colleagues found a combination of shared and unique network pairs in the patient groups. Bipolar patients showed abnormal connections between the meso/paralimbic and fronto-temporal/paralimbic networks, and between the fronto/occipital and anterior default mode/prefrontal networks. Schizophrenic patients echoed the latter finding, and showed abnormal pair-wise connections between the meso/paralimbic and sensory-motor networks. This abnormality was also observed in relatives of bipolar patients, as was the fronto/occipital and anterior default mode/prefrontal abnormality. No significantly abnormal pair-wise network connections were identified in the relatives of schizophrenic patients. The investigators note that the abnormal circuits uniquely found in bipolar patients involve regions thought to be involved in emotional expression and regulation; further, different network findings correlated significantly with PANSS scores in bipolar and schizophrenic patients. In the commentary, Dr. Bullmore places this study into a larger, historical perspective and discusses the potential neurobiological implications of these findings for our understanding of network pathology in psychotic disorders.

June 1, 2012

Commentary by John H. Krystal

de Kleine RA, Hendriks GJ, Kusters WJ, et al (2012). A randomized placebo-controlled trial of D-cycloserine to enhance exposure therapy for posttraumatic stress disorder. Biol Psychiatry 71:962-968

The NMDA glycine site agonist, d-cycloserine (DCS) has been observed to be effective in enhancing fear extinction in a variety of anxiety disorders. In this double-blind, placebo controlled study, the investigators test the efficacy of DCS in combination with a standardized exposure therapy for patients with post-traumatic stress disorder (PTSD). The investigators report that they did not observe any overall time by treatment effect of DCS. On further analysis however, they found evidence for greater rates of response, though not remission in the DCS group. Further, they noted increased symptom response in patients who required the full course of treatment. They suggest that their findings support the use of adjunctive DCS with extinction therapy in patients who do not rapidly respond to psychotherapy alone. The commentary elaborates on possible mechanisms for the observed response and suggests further pharmacologic interventions that, based on these findings, might also be tested for efficacy in patients with PTSD.

Commentary by Olivia M. Dean, Ashley I. Bush, and Michael Berk

Hardan AY, Fung LK, Libove RA, et al (2012). A randomized controlled pilot trial of oral A-acetylcysteine in children with autism. Biol Psychiatry 71:956-961

Several lines of evidence potentially implicate multiple neurobiological deficits in the pathophysiology of autism, including glutamatergic dysfunction and oxidative stress. N-acetylcysteine (NAC) has been advanced as a potential clinical intervention in patients with autism based on its role in reducing oxidative stress and its effect on glutamatergic pathways. In this study, the investigators found that autistic children randomized to receive NAC as part of a 12-week double-blind, placebo-controlled trial showed significant improvements on the irritability subscale of the Aberrant Behavior Checklist (ABC) while experience only minimal adverse effects. Significant improvements were observed as early as week four. While effects on secondary measures were mixed, there was evidence of large decline in hyperactivity at week twelve. The investigators concede the preliminary nature of these findings but suggest that NAC might represent a useful pharmacological intervention for patients with autism.

Gunduz-Bruce H, Reinhart RMG, Roach BJ, et al (2012). Glutamatergic modulation of auditory processing in the human brain. Biol Psychiatry 71:969-977

Patients with schizophrenia have been widely reported to demonstrate decreased mis-match negativity (MMN) and P300 event-related potentials (ERPs). Similarly, healthy subjects given the N-methyl-d-aspartate receptor antagonist (NMDAR), ketamine show both behavioral effects reminiscent of schizophrenia and changes in MMN and P300 ERPs. In rodents, the behavioral and cognitive effects of another NMDAR were attenuated by N-acetylcysteine (NAC). The investigators hypothesized that NAC would reduce changes in MMN and P300 associated with ketamine administration in healthy subjects. Instead they found that NAC reduced MMN amplitude while increasing P300. NAC did not however, significantly impact the behavioral effects of ketamine, or the effects of ketamine on MMN and P300. The investigators discuss possible explanations for the effects observed, and for the disparate effects of NAC in preclinical and clinical populations. In the commentary, Drs. Dean, Bush and Berk emphasize the complex effects of NAC and the potential clinical implications of these findings.

Commentary by Dikoma C. Shungu

das Neves Duarte JM, Kulak A, Mohammad M, et al (2012). N-acetylcysteine normalizes neurochemical changes in the glutathione-deficient schizophrenia mouse model during development. Biol Psychiatry 71:1006-1014

In this study, investigators obtained blood levels and used (1H)MRS of the anterior cortex (AC) to measure neurochemical concentrations in wild type and glutamate-cysteine ligase modulatory subunit knock-out mice. They found that the loss of the key glutathione (GSH) synthesizing enzyme was associated with decreased GSH and changes in levels of neurochemicals previously found to be abnormal in patients with schizophrenia, particularly during the prepubertal period. Administration of N-acetylcysteine, a chemical moiety associated with increased cysteine, a rate limiting precursor to GSH, was associated with normalization of neurochemical concentrations. GSH levels in the AC however, were not affected in either wild-type or knock-out mice-presumably because tight feedback coupling between GSH levels and enzyme activity in the former limited elevations of GSH, and the lack of synthesizing enzyme in the latter. The investigators theorize that the observed effects of NAC are through an alternate anti-oxidative pathway. The commentary discussed the impact of these and other findings on theoretical underpinnings for the use of NAC to treat schizophrenia. Dr. Shungu further suggests human studies that may help clarify these preclinical findings.

June 15, 2012

Commentary by Thomas R. Insel and Michelle Freund

"Shedding Light on Brain Circuits"

In their commentary directed at the contents of this special issue of Biological Psychiatry, the authors discuss some of the promises and limitations of optogenetics. They note that while the technique has not generated revolutionary new concepts it has improved understanding of the cellular architecture underlying complex behaviors. Further, the commentary notes that while optogenetics is not readily adaptable to the direct study of human subjects, there are a host of neuroscience questions that may be answered with improved optogenetic methodologies.

Commentary by Karl Deisseroth

"Optogenetics and Psychiatry: Applications, Challenges, and Opportunities"

In this commentary the author describes the development of optogenetics and highlights some of the recent advances reported in this issue of Biological Psychiatry. These studies are placed into a larger context and the author suggests future research directions, including a potential non-optogenetic technique to track temporally precise neuronal activity.

XXth World Congress of Psychiatric Genetics: Confronting the Complexity of Brain and Behavior 

Hamburg, Germany

A Joint Congress of Psychiatry 

Athens, Greece

• World Psychiatric Association Thematic Conference on Intersectional Collaboration: The Multidisciplinary Facets of Psychiatry
• Fourth European Congress of the International Neuropsychiatric Association: Overlap and Integration in Neuropsychiatry
• First Interdisciplinary Congress on Psychiatry and Related Sciences

ACNP Annual Meeting 

Hollywood, Florida