Alterations In Neural Circuits Research Articles

Response inhibition related neural oscillatory patterns show reliable early identification of bipolar from unipolar depression in a Go/No-Go task

BackgroundResponse inhibition is a key neurocognitive factor contributing to impulsivity in mood disorders. Here, we explored the common and differential alterations of neural circuits associated with response inhibition in bipolar disorder (BD) and unipolar disorder (UD) and whether the oscillatory signatures can be used as early biomarkers in BD. Methods39 patients with BD, 36 patients with UD, 29 patients initially diagnosed with UD who later underwent diagnostic conversion to BD, and 36 healthy controls performed a Go/No-Go task during MEG scanning. We carried out time-frequency and connectivity analysis on MEG data. Further, we performed machine learning using oscillatory features as input to identify bipolar from unipolar depression at the early clinical stage. ResultsCompared to healthy controls, patients had reduced rIFG-to-pre-SMA connectivity and delayed activity of rIFG. Among patients, lower beta power and higher peak frequency were observed in BD patients than in UD patients. These changes enabled accurate classification between BD and UD with an accuracy of approximately 80 %. ConclusionsThe inefficiency of the prefrontal control network is a shared mechanism in mood disorders, while the abnormal activity of rIFG is more specific to BD. Neuronal responses during response inhibition could serve as a diagnostic biomarker for BD in early stage.

Assessing depression recurrence, cognitive burden, and neurobiological homeostasis in late life: Design and rationale of the REMBRANDT study

BackgroundLate-life depression is characterized by disability, cognitive impairment and decline, and a high risk of recurrence following remission. Aside from past psychiatric history, prognostic neurobiological and clinical factors influencing recurrence risk are unclear. Moreover, it is unclear if cognitive impairment predisposes to recurrence, or whether recurrent episodes may accelerate brain aging and cognitive decline. The purpose of the REMBRANDT study (Recurrence markers, cognitive burden, and neurobiological homeostasis in late-life depression) is to better elucidate these relationships and identify phenotypic, cognitive, environmental, and neurobiological factors contributing to and predictive of depression recurrence. MethodsAcross three sites, REMBRANDT will enroll 300 depressed elders who will receive antidepressant treatment. The goal is to enroll 210 remitted depressed participants and 75 participants with no mental health history into a two-year longitudinal phase focusing on depression recurrence. Participants are evaluated every 2 months with deeper assessments occurring every 8 months, including structural and functional neuroimaging, environmental stress assessments, deep symptom phenotyping, and two weeks of ‘burst’ ecological momentary assessments to elucidate variability in symptoms and cognitive performance. A broad neuropsychological test battery is completed at the beginning and end of the longitudinal study. SignificanceREMBRANDT will improve our understanding of how alterations in neural circuits and cognition that persist during remission contribute to depression recurrence vulnerability. It will also elucidate how these processes may contribute to cognitive impairment and decline. This project will obtain deep phenotypic data that will help identify vulnerability and resilience factors that can help stratify individual clinical risk.

Virtual brain simulations reveal network-specific parameters in neurodegenerative dementias.

Neural circuit alterations lay at the core of brain physiopathology, and yet are hard to unveil in living subjects. The Virtual Brain (TVB) modeling, by exploiting structural and functional magnetic resonance imaging (MRI), yields mesoscopic parameters of connectivity and synaptic transmission. We used TVB to simulate brain networks, which are key for human brain function, in Alzheimer's disease (AD) and frontotemporal dementia (FTD) patients, whose connectivity and synaptic parameters remain largely unknown; we then compared them to healthy controls, to reveal novel in vivo pathological hallmarks. The pattern of simulated parameter differed between AD and FTD, shedding light on disease-specific alterations in brain networks. Individual subjects displayed subtle differences in network parameter patterns that significantly correlated with their individual neuropsychological, clinical, and pharmacological profiles. These TVB simulations, by informing about a new personalized set of networks parameters, open new perspectives for understanding dementias mechanisms and design personalized therapeutic approaches.

Neural Circuit Markers of Familial Risk for Depression Among Healthy Youths in the Adolescent Brain Cognitive Development Study

BackgroundFamily history of depression is a robust predictor of early-onset depression, which may confer risk through alterations in neural circuits that have been implicated in reward and emotional processing. These alterations may be evident in youths who are at familial risk for depression but who do not currently have depression. However, the identification of robust and replicable findings has been hindered by few studies and small sample sizes. In the current study, we sought to identify functional connectivity (FC) patterns associated with familial risk for depression. MethodsParticipants included healthy (i.e., no lifetime psychiatric diagnoses) youths at high familial risk for depression (HR) (n = 754; at least one parent with a history of depression) and healthy youths at low familial risk for psychiatric problems (LR) (n = 1745; no parental history of psychopathology) who were 9 to 10 years of age and from the Adolescent Brain Cognitive Development (ABCD) Study sample. We conducted whole-brain seed-to-voxel analyses to examine group differences in resting-state FC with the amygdala, caudate, nucleus accumbens, and putamen. We hypothesized that HR youths would exhibit global amygdala hyperconnectivity and striatal hypoconnectivity patterns primarily driven by maternal risk. ResultsHR youths exhibited weaker caudate–angular gyrus FC than LR youths (α = 0.04, Cohen’s d = 0.17). HR youths with a history of maternal depression specifically exhibited weaker caudate–angular gyrus FC (α = 0.03, Cohen’s d = 0.19) as well as weaker caudate–dorsolateral prefrontal cortex FC (α = 0.04, Cohen’s d = 0.21) than LR youths. ConclusionsWeaker striatal connectivity may be related to heightened familial risk for depression, primarily driven by maternal history. Identifying brain-based markers of depression risk in youths can inform approaches to improving early detection, diagnosis, and treatment.

Preferential pruning of inhibitory synapses by microglia contributes to alteration of the balance between excitatory and inhibitory synapses in the hippocampus in temporal lobe epilepsy.

A consensus has formed that neural circuits in the brain underlie the pathogenesis of temporal lobe epilepsy (TLE). In particular, the synaptic excitation/inhibition balance (E/I balance) has been implicated in shifting towards elevated excitation during the development of TLE. Sprague Dawley (SD) rats were intraperitoneally subjected to kainic acid (KA) to generate a model of TLE. Next, electroencephalography (EEG) recording was applied to verify the stability and detectability of spontaneous recurrent seizures (SRS) in rats. Moreover, hippocampal slices from rats and patients with mesial temporal lobe epilepsy (mTLE) were assessed using immunofluorescence to determine the alterations of excitatory and inhibitory synapses and microglial phagocytosis. We found that KA induced stable SRSs 14 days after status epilepticus (SE) onset. Furthermore, we discovered a continuous increase in excitatory synapses during epileptogenesis, where the total area of vesicular glutamate transporter 1 (vGluT1) rose considerably in the stratum radiatum (SR) of cornu ammonis 1 (CA1), the stratum lucidum (SL) of CA3, and the polymorphic layer (PML) of the dentate gyrus (DG). In contrast, inhibitory synapses decreased significantly, with the total area of glutamate decarboxylase 65 (GAD65) in the SL and PML diminishing enormously. Moreover, microglia conducted active synaptic phagocytosis after the formation of SRSs, especially in the SL and PML. Finally, microglia preferentially pruned inhibitory synapses during recurrent seizures in both rat and human hippocampal slices, which contributed to the synaptic alteration in hippocampal subregions. Our findings elaborately characterize the alteration of neural circuits and demonstrate the selectivity of synaptic phagocytosis mediated by microglia in TLE, which could strengthen the comprehension of the pathogenesis of TLE and inspire potential therapeutic targets for epilepsy treatment.

Remodeling of Neuronal Circuits in Chronic Pain

Chronic pain is associated with various brain malfunctions, such as allodynia and anxiety. The underlying mechanism is a long-term alteration of neural circuits in the related brain regions. Here, we focus on the contribution of glial cells to build up pathological circuits. In addition, an attempt to enhance the neuronal plasticity of the pathological circuits to repair them to relieve abnormal pain will be introduced. The possible clinical applications will also be discussed.

Fatty acid amide hydrolase inhibition and N-arachidonoylethanolamine modulation by isoflavonoids: A novel target for upcoming antidepressants.

Modulation of the endocannabinoid system (ECS) is a novel putative target for therapeutic intervention in depressive disorders. Altering concentrations of one of the principal endocannabinoids, N‐arachidonoylethanolamine, also known as anandamide (AEA) can affect depressive‐like behaviors through several mechanisms including anti‐inflammatory, hormonal, and neural circuit alterations. Recently, isoflavonoids, a class of plant‐derived compounds, have been of therapeutic interest given their ability to modulate the metabolism of the endogenous ligands of the ECS. To determine the therapeutic potential of isoflavonoids, we screened several candidate compounds (Genistein, Biochanin‐A, and 7‐hydroxyflavone) in silico to determine their binding properties with fatty acid amide hydrolase (FAAH), the primary degrative enzyme for AEA. We further validated the ability of these compounds to inhibit FAAH and determined their effects on depressive‐like and locomotor behaviors in the forced swim test (FST) and open field test in male and female mice. We found that while genistein was the most potent FAAH inhibitor, 7‐hydroxyflavone was most effective at reducing immobility time in the forced swim test. Finally, we measured blood corticosterone and prefrontal cortex AEA concentrations following the forced swim test and found that all tested compounds decreased corticosterone and increased AEA, demonstrating that isoflavonoids are promising therapeutic targets as FAAH inhibitors.

Exposure to either Bisphenol A or S Represents a Risk for Crucial Behaviors for Pup Survival, Such as Spontaneous Maternal Behavior in Mice

Introduction: Maternal behavior depends on a multitude of factors, including environmental ones, such as Endocrine Disrupting Chemicals (EDCs), which are increasingly attracting attention. Bisphenol A (BPA), an EDC present in plastic, is known to exert negative effects on maternal behavior. Bisphenol S (BPS), a BPA substitute, seems to share some endocrine disrupting properties. In this study, we focused on the analysis of the effects of low-dose (i.e., 4 µg/kg body weight/day, EFSA TDI for BPA) BPA or BPS exposure throughout pregnancy and lactation in mice. Methods: We administered adult C57BL/6 J females orally BPA, BPS, or vehicle from mating to offspring weaning. We assessed the number of pups at birth, the sex ratio, and the percentage of dead pups in each litter, and during the first postnatal week, we observed spontaneous maternal behavior. At the weaning of the pups, we sacrificed the dams and analyzed the oxytocin system, known to be involved in the control of maternal care, in the hypothalamic magnocellular nuclei. Results: At birth, pups from BPA-treated dams tended to have a lower male-to-female ratio compared to controls, while the opposite was observed among BPS-treated dams’ litters. During the first postnatal week, offspring mortality impacted differentially in the BPA and BPS litters, with more female dead pups among the BPA litters, while more male dead pups in the BPS litters, sharpening the difference in the sex ratio. BPA- and BPS-treated dams spent significantly less time in pup-related behaviors than controls. Oxytocin immunoreactivity in the paraventricular and supraoptic nuclei was increased only in the BPA-treated dams. Discussion/Conclusions: Alterations in maternal care, along with the treatment itself, may affect, later in life, the offspring’s physiology and behavior. Exposure to BPs during sensitive developmental periods represents a risk for both dams and offspring, even at low environmentally relevant doses, through the functional alteration of neural circuits controlling fundamental behaviors for pup survival, such as maternal behaviors.

Common and Distinct Neural Patterns of Attention-Deficit/Hyperactivity Disorder and Borderline Personality Disorder: A Multimodal Functional and Structural Meta-analysis

BackgroundAttention-deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) have partially overlapping symptom profiles and are highly comorbid in adults. However, whether the behavioral similarities correspond to shared neurobiological substrates is not known. MethodsAn overlapping meta-analysis of 58 ADHD and 66 BPD whole-brain articles incorporating observations from 3401 adult patients and 3238 healthy participants was performed by seed-based d mapping. Brain maps were subjected to meta-analytic connectivity modeling and data-driven functional decoding analyses to identify associated neural circuit alterations and relations to behavioral dimensions. ResultsBoth groups exhibited hypoactivated abnormalities in the left inferior parietal lobule, and altered clusters of the bilateral superior temporal gyrus were disjunctive in ADHD and BPD. No overlapping structural abnormalities were found. Multimodal alterations of ADHD were located in the right putamen and of BPD in the left orbitofrontal cortex. ConclusionsThe transdiagnostic neural bases of ADHD and BPD in temporoparietal circuitry may underlie overlapping problems of behavioral control, while disorder-specific substrates in frontostriatal circuitry may account for their distinguishing features in motor and emotion domains, respectively.

Analysis of neural circuit alterations caused by chronic social stress

Analysis of neural circuit alterations caused by chronic social stress

The importance of fasciculation and elongation protein zeta-1 in neural circuit establishment and neurological disorders

The human brain contains an estimated 100 billion neurons that must be systematically organized into functional neural circuits for it to function properly. These circuits range from short-range local signaling networks between neighboring neurons to long-range networks formed between various brain regions. Compelling converging evidence indicates that alterations in neural circuits arising from abnormalities during early neuronal development or neurodegeneration contribute significantly to the etiology of neurological disorders. Supporting this notion, efforts to identify genetic causes of these disorders have uncovered an over-representation of genes encoding proteins involved in the processes of neuronal differentiation, maturation, synaptogenesis and synaptic function. Fasciculation and elongation protein zeta-1, a Kinesin-1 adapter, has emerged as a key central player involved in many of these processes. Fasciculation and elongation protein zeta-1-dependent transport of synaptic cargoes and mitochondria is essential for neuronal development and synapse establishment. Furthermore, it acts downstream of guidance cue pathways to regulate axo-dendritic development. Significantly, perturbing its function causes abnormalities in neuronal development and synapse formation both in the brain as well as the peripheral nervous system. Mutations and deletions of the fasciculation and elongation protein zeta-1 gene are linked to neurodevelopmental disorders. Moreover, altered phosphorylation of the protein contributes to neurodegenerative disorders. Together, these findings strongly implicate the importance of fasciculation and elongation protein zeta-1 in the establishment of neuronal circuits and its maintenance.

Dissociative and analgesic properties of ketamine are independent and unaltered by sevoflurane general anesthesia.

Ketamine, an anesthetic adjunct, is routinely administered as part of a balanced general anesthetic technique. We recently showed that the acute analgesic and dissociation properties of ketamine are separable to suggest that distinct neural circuits underlie these states. We aimed to study whether this finding is robust to the substantial neural circuit alterations associated with general anesthesia. We conducted a single-site, open-label, randomized controlled, cross-over study of sevoflurane and sevoflurane-plus-ketamine (SK) general anesthesia in healthy subjects (n = 12). Before and after general anesthesia, we assessed precalibrated cuff pain intensity and nociceptive pain quality as well as dissociation using the Clinician-Administered Dissociative States Scale (CADSS). For statistical inference, we ran a variation of backward elimination repeated-measures analysis of covariance. Models with CADSS as a covariate term were used to assess whether dissociation mediated the effect of ketamine on pain intensity and quality. Sevoflurane-plus-ketamine general anesthesia was associated with a significant (P = 0.0002) pain intensity decline of 3 (SE, 0.44). There was an order effect for dissociation such that SK was associated with a significant (P = 0.0043) CADSS increase of 17.8 (3.2) when the SK treatment came first. When the pain intensity model was reanalyzed with CADSS as an additional covariate, the effect of CADSS was not significant. These results were also conserved for pain quality. Our findings suggest that the analgesic and dissociation properties of ketamine remain separable despite general anesthesia. Thus, ketamine may be used as a probe to advance our knowledge of dissociation independent pain circuits.

Altered Anxiety Neural Circuit in Combat Veterans With PTSD

Post-traumatic stress disorder (PTSD) affects more than 30% of Veterans returning from modern wars. Unfortunately, PTSD is often resistant to current treatments, such as SSRIs and exposure therapy, that target fear neurocircuitry. One possible explanation is that the neurobiology of PTSD extends beyond fear neurocircuitry and includes alterations in neural circuits that underlie anxiety. In this study, we investigated the bed nucleus of the stria terminalis (BNST), a brain region implicated in the anxiety, hypervigilance and threat anticipation response that is characteristic of PTSD.

Examining and Modulating Neural Circuits in Psychiatric Disorders With Transcranial Magnetic Stimulation and Electroencephalography: Present Practices and Future Developments.

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique uniquely equipped to both examine and modulate neural systems and related cognitive and behavioral functions in humans. As an examination tool, TMS can be used in combination with EEG (TMS-EEG) to elucidate directly, objectively, and noninvasively the intrinsic properties of a specific cortical region, including excitation, inhibition, reactivity, and oscillatory activity, irrespective of the individual's conscious effort. Additionally, when applied in repetitive patterns, TMS has been shown to modulate brain networks in healthy individuals, as well as ameliorate symptoms in individuals with psychiatric disorders. The key role of TMS in assessing and modulating neural dysfunctions and associated clinical and cognitive deficits in psychiatric populations is therefore becoming increasingly evident. In this article, the authors review TMS-EEG studies in schizophrenia and mood disorders, as most TMS-EEG studies to date have focused on individuals with these disorders. The authors present the evidence on the efficacy of repetitive TMS (rTMS) and theta burst stimulation (TBS), when targeting specific cortical areas, in modulating neural circuits and ameliorating symptoms and abnormal behaviors in individuals with psychiatric disorders, especially when informed by resting-state and task-related neuroimaging measures. Examples of how the combination of TMS-EEG assessments and rTMS and TBS paradigms can be utilized to both characterize and modulate neural circuit alterations in individuals with psychiatric disorders are also provided. This approach, along with the evaluation of the behavioral effects of TMS-related neuromodulation, has the potential to lead to the development of more effective and personalized interventions for individuals with psychiatric disorders.

Effect of chronic alcohol intake on motor functions on the elderly

Alcohol use disorder (AUD) is a chronic and progressive disease influenced by genetic, psychosocial, and environmental factors. The consequences of alcohol consumption involve alterations in neural circuits of emotion and cognition, as well as in the motor planning circuit. Furthermore, during the natural aging process, several biochemical and functional alterations are also observed with neurological consequences. Thus, considering the consequences of chronic alcohol consumption on neural systems and natural aging process, we aimed to analyze the degree of motor and functional impairment in elderly with chronic alcohol consumption. Sixty elderly underwent an analysis of alcohol consumption profile (Alcohol Use Disorders Identification Test – AUDIT) that divided them into a control group (CON) and an alcohol group (ALC). The analysis of quality of life was performed using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the analysis of motor function was performed using the Borg Scale, the Six-Minute Walk Test (6MWT) and the Motor Scale for Elderly (MSE). We were able to conclude that the misuse of alcohol by the elderly promotes significant physical limitations. These limitations result in a worsening of functional capacity of walking and various dimensions of motor ability: fine motor skill, global coordination, balance, body scheme, spatial organization, temporal organization, and general motor aptitude. Besides the physical limitations caused by alcohol use, the quality of life in their physical, mental, and social aspects was reduced. Thus, actions are required to help the elderly understand these losses and exercise control over alcohol misuse.

Chronic unpredictable early-life stress (CUELS) protocol: Early-life stress changes anxiety levels of adult zebrafish

Early-life stress can lead to two different behavioral responses: (1) increased susceptibility to psychiatric disorders or (2) resilience. Here, we created a chronic unpredictable early-life stress (CUELS) protocol to assess the effects of early experiences in adult zebrafish. Animals were exposed to mild stressors twice a day and the duration was varied between groups (0, 1, 3, 7 and 14 days of stress). The stressor consisted of light/dark cycle changes; social isolation; overcrowding; water changes; water cooling; mechanical stirring; water heating; and immersion in shallow water. Behavior was assessed at young stages (21 days post-fertilization – open field analysis) and adulthood (4-months-old - novel tank diving test, light/dark task, shoaling, free movement pattern Y-maze and Pavlovian fear conditioning). Cortisol levels were assessed to evaluate the impact of CUELS in the HPI axis. Zebrafish exposed to 7 days of CUELS showed a decreased anxiety-like phenotype in two behavioral tasks, presenting increased time spent in top and decreased time spent in the dark area. Animals exposed to 14 days of CUELS showed an opposite anxious phenotype compared to 3 and 7 days of CUELS. No significant changes were observed in memory and cognition, social behavior and cortisol levels. In general, 7 days of CUELS protocol decreased anxiety in young and adult zebrafish, and could be used to understand the mechanisms underlying early-life experiences-derived alterations in neural circuits of anxiety.

Stress induces insertion of calcium-permeable AMPA receptors in the OFC\u2013BLA synapse and modulates emotional behaviours in mice

Stress increases the risk of neuropsychiatric disorders, such as major depression. Exposure to stress has been reported to induce various neuronal changes, such as alterations in synaptic transmission and structure. However, a causal link between stress-induced neural circuit alterations and changes in emotional behaviours is not well understood. In the present study, we focused on a projection pathway from the orbitofrontal cortex (OFC) to the basolateral nucleus of the amygdala (BLA) as a crucial circuit for negative emotions and examined the effect of stress on OFC–BLA excitatory synaptic transmission using optogenetic and whole-cell patch-clamp methods in mice. As a stress-inducing procedure, we used repeated tail-shock, which increased stress-related behaviours. We found greater α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N-methyl-d-aspartate current ratios and insertion of calcium-permeable AMPA receptors (AMPARs) in the OFC–BLA synapse after stress. These stress-induced synaptic and behavioural changes were reduced by a blockade of protein kinase A, which plays a principal role in stress-induced targeting of AMPARs into the synaptic membrane. To examine a possible causal relationship between alterations in synaptic transmission in the OFC–BLA pathway and stress-related behaviour, we performed optogenetic activation or chemogenetic inactivation of OFC–BLA transmission in mice. We found that optogenetic activation and chemogenetic inactivation of OFC–BLA transmission increased and decreased stress-related behaviour, respectively. In conclusion, we have demonstrated that stress altered the postsynaptic properties of the OFC–BLA pathway. These synaptic changes might be one of the underlying mechanisms of stress-induced behavioural alterations.

Alterations in neural circuits underlying emotion regulation following child maltreatment: a mechanism underlying trauma-related psychopathology.

Disruptions in neural circuits underlying emotion regulation (ER) may be a mechanism linking child maltreatment with psychopathology. We examined the associations of maltreatment with neural responses during passive viewing of negative emotional stimuli and attempts to modulate emotional responses. We investigated whether the influence of maltreatment on neural activation during ER differed across development and whether alterations in brain function mediated the association between maltreatment and a latent general psychopathology ('p') factor. Youth aged 8-16 years with (n = 79) and without (n = 72) exposure to maltreatment completed an ER task assessing neural responses during passive viewing of negative and neutral images and effortful attempts to regulate emotional responses to negative stimuli. P-factor scores were defined by a bi-factor model encompassing internalizing and externalizing psychopathology. Maltreated youth had greater activation in left amygdala and salience processing regions and reduced activation in multiple regions involved in cognitive control (bilateral superior frontal gyrus, middle frontal gyrus, and dorsal anterior cingulate cortex) when viewing negative v. neutral images than youth without maltreatment exposure. Reduced neural recruitment in cognitive control regions mediated the association of maltreatment with p-factor in whole-brain analysis. Maltreated youth exhibited increasing recruitment with age in ventrolateral prefrontal cortex during reappraisal while control participants exhibited decreasing recruitment with age. Findings were similar after adjusting for co-occurring neglect. Child maltreatment influences the development of regions associated with salience processing and cognitive control during ER in ways that contribute to psychopathology.

Neuroimaging and electroencephalographic (EEG) methods for investigating neural circuits in mental disorders

It is increasingly recognised that dysfunction in neural circuits plays a key role in the neurobiological basis of mental disorders. The efficacy of pharmacological and behavioural treatments for mental disorders could therefore be improved by targeting dysfunctions in neurocircuits. However, to achieve this, a better understanding of the specific alterations in neural circuits involved in different mental disorders is required. Such understanding can be acquired by using advanced neuroscience methods to examine the pathways and function of neurocircuits in both typically developing individuals and in those with mental disorders. This article provides an overview of currently available neuroscience methods of investigating neural circuits, including advantages and limitations of different techniques, and highlights the importance of using multi-modal imaging in future research

New AJP Editor Sees Translational Research As Central to Journal’s Future

Back to table of contents Next article Association NewsFull AccessNew AJP Editor Sees Translational Research As Central to Journal’s FutureMark MoranMark MoranSearch for more papers by this authorPublished Online:18 Jul 2018https://doi.org/10.1176/appi.pn.2018.7b6AbstractNed Kalin, M.D., has had a distinguished career in research, focusing on the early life mechanisms underlying the development of anxiety and depression.“Translational behavioral neuroscience”—that’s the future of scientific publishing in psychiatry, says Ned Kalin, M.D., the next editor of the American Journal of Psychiatry (AJP). He succeeds Robert Freedman, M.D., Ph.D., who steps down after 13 years as editor on December 31, 2018. “The most important trend I see is the effort to understand the factors that increase risk for various psychiatric illness,” says Ned Kalin, M.D.Photo: Ned Kalin“AJP is an outstanding journal; it is widely read and has a high impact factor,” Kalin told Psychiatric News. “Robert Freedman has done an extraordinary job of making AJP one of the most widely read and cited scientific periodicals. My vision going forward will be around bringing together the best clinical research in our field with more basic research, in what I think of as translational behavioral neuroscience.“The opportunity we have today is in linking treatment-focused research studies with research in relevant animal models that are focused on altered neural circuitry and molecular mechanisms. There are also exciting new advances using neurons in culture, including those that can be derived from stem cells. By bringing together findings from these diverse approaches, we can better understand important mechanisms that underlie the onset and maintenance of psychiatric illnesses and also shed light on new treatment approaches.“I want to make these types of findings accessible to the readership of AJP and help integrate them in a way that can best inform patient care.”Kalin said he would like to see discrete editions of the journal dedicated to a particular topic, with all of the original research addressing that topic at different levels of analysis—genetic, molecular, neuroanatomical, and behavioral. “Editorials and commentary would then integrate these separate papers in an accessible way to help the reader understand what they mean together collectively for patient care,” he said. Last year APA convened a search committee chaired by past APA President Alan Schatzberg, M.D., to recommend a successor to Freedman and allow adequate time for a smooth transition. Twelve individuals applied for the position, and five were selected for interviews. After these interviews, the search committee submitted the top two choices to APA CEO and Medical Director Saul Levin, M.D., M.P.A., and then APA President Anita Everett, M.D. The Board of Trustees approved Kalin’s appointment in March.“We anticipate that the journal, under Dr. Kalin’s leadership, will lead the field and reflect where it is headed in research and treatment,” said Levin. “We are very excited about Dr. Kalin’s appointment as editor of AJP.” Kalin is the Hedberg Professor and chair of the Department of Psychiatry at the University of Wisconsin School of Medicine. He is also director of the HealthEmotions Research Institute at the University of Wisconsin and director of the Lane Neuroimaging Laboratory there. Additionally, Kalin is a principal investigator on numerous NIMH-funded grants, including a grant for an NIMH Conte Center study focused on the early life development of anxiety disorders. He has led a robust research effort at the University of Wisconsin that encompasses molecular, preclinical, and human neuroimaging approaches in an effort to elucidate molecular and neural circuit alterations that underlie the childhood risk for anxiety and depression. Kalin said that the trends in anxiety disorders research are common to those that are emerging in research across psychiatric diagnoses—especially the search for risk factors. “One of the most important trends that I see is the effort to understand the factors that increase the risk for various psychiatric illnesses, trying to understand which factors are specific to one illness and which may be more generic and may increase the risk for a variety of illnesses,” he said. “By translating new findings relevant to the early development of psychopathology, we can begin to think about interventions at younger ages and earlier in the disease process to help prevent the long-term recurrent and chronic trajectories that are so disabling for our patients—whether it’s with anxiety, depression, bipolar disorder, or schizophrenia.”Kalin said that in addition to publishing the best science in the field of psychiatry, the journal, through its editorials, can be a voice for funding of research and for policies that improve the delivery of care. “I believe we are at a really exciting point of evolution in the way we think about treatment for our patients,” Kalin said. “I’m honored to be editor at this point of evolution when we can expect exciting new developments for our practitioners and our patients.” ■ ISSUES NewArchived