Unravelling the pathophysiology of depression is a unique challenge. Not only are depressive syndromes heterogeneous and their aetiologies diverse, but symptoms such as guilt and suicidality are impossible to reproduce in animal models. Nevertheless, other symptoms have been accurately modelled, and these, together with clinical data, are providing insight into the neurobiology of depression. Recent studies combining behavioural, molecular and electrophysiological techniques reveal that certain aspects of depression result from maladaptive stress-induced neuroplastic changes in specific neural circuits. They also show that understanding the mechanisms of resilience to stress offers a crucial new dimension for the development of fundamentally novel antidepressant treatments.

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The molecular neurobiology of depression

Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression.

The role of inflammation in depression: from evolutionary imperative to modern treatment target

Most physiology and behavior of mammalian organisms follow daily oscillations. These rhythmic processes are governed by environmental cues (e.g., fluctuations in light intensity and temperature), an internal circadian timing system, and the interaction between this timekeeping system and environmental signals. In mammals, the circadian timekeeping system has a complex architecture, composed of a central pacemaker in the brain's suprachiasmatic nuclei (SCN) and subsidiary clocks in nearly every body cell. The central clock is synchronized to geophysical time mainly via photic cues perceived by the retina and transmitted by electrical signals to SCN neurons. In turn, the SCN influences circadian physiology and behavior via neuronal and humoral cues and via the synchronization of local oscillators that are operative in the cells of most organs and tissues. Thus, some of the SCN output pathways serve as input pathways for peripheral tissues. Here we discuss knowledge acquired during the past few years on the complex structure and function of the mammalian circadian timing system.

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The mammalian circadian timing system: organization and coordination of central and peripheral clocks.

Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions

The Mesolimbic Dopamine Reward Circuit in Depression

Ursodiol Prescriptions Following Bariatric Surgery: National Prescribing Trends and Outcomes

Disability in patients with epilepsy (PWEs) is multifactorial: beyond seizure frequency/severity, PWEs are prone to a range of neuropsychiatric, cognitive, and somatic comorbidities that significantly affect quality of life. Here, we explored how variations in seizure severity and the burden of self‐reported somatic/neuropsychiatric symptoms correlate with disruptions to 24 h activity patterns (rest‐activity rhythms [RARs]), determined through wrist accelerometry/actigraphy.

Actigraphic correlates of neuropsychiatric symptoms in adults with focal epilepsy

By Vaishnavi Krishnan, Christopher W. Seder & 2 more. A study to understand the effect of Medicaid Expansion under the Affordable Care Act (ACA) on patterns of surgical care on low-income patients with lung cancer. 

Medicaid Expansion and Access to Surgical Treatment Among Patients with Non Small Cell Lung Cancer

9578 Background: Several barriers to care exist for melanoma patients including distance to specialty care, transportation, and cost. Additionally, differences in rural and urban melanoma incidence have not been fully investigated. Using a large nationwide database, we aim to investigate the relationship between urban and rural locations in stage of melanoma presentation and access to adjuvant systemic treatment. Methods: The National Cancer Database (NCDB) was queried for all adult patients (≥ 18 years old) with diagnosis of cutaneous melanoma from 1/1/2011 – 12/31/2020. For receipt of adjuvant immunotherapy, diagnosis from only 1/1/2017 - 12/31/2020 was analyzed. Demographic, socioeconomic, tumor-related, and treatment-related factors were analyzed using SPSS Statistics, with Chi-square analysis performed for categorical variables and ANOVA performed for continuous. Results: Between 2011 and 2020, 558,445 patient cases were identified and included in the analyses. The average age was 63.7 years, and patients predominantly identified as White (97.6%) and non-Hispanic (96.2%). Patients in urban areas were more likely to present with melanoma of the extremities (40.8% vs 36.2%, p < 0.001), while patients in rural areas presented with head and neck melanoma (26.2% vs 31.0%, p < 0.001). Additionally, patients in urban areas were more likely to have an early-stage melanoma (0, 1, or 2) melanoma (51.4% vs 48.5%, p < 0.001). Patients in rural areas traveled an average of 68 miles for care, in contrast to urban patients who traveled an average of 20 miles (p < 0.001). There was no significant difference when comparing receipt of immunotherapy for stage 3 or stage 4 patients. Conclusions: In rural areas, patients with melanoma tended to present with a higher portion of head and neck melanoma and of later stage. Rural patients also had to travel farther for care. However, these differences did not result in fewer patients in rural areas receiving immunotherapy for appropriate treatment. Further studies are needed to evaluate how these presentation differences influence care outcomes.

Melanoma disparities in urban vs rural communities in the era of immunotherapy: An NCDB analysis.

Vaishnav Krishnan *, Erick Tarula , Matthew P. Anderson , Khalid A. Hanafy , Susan T. Herman d Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, United States Department of Neuropathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, United States Division of Neurocritical Care, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, United States Division of Epilepsy, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, United States

Vaishnav Krishnan

Papers

Ursodiol Prescriptions Following Bariatric Surgery: National Prescribing Trends and Outcomes

Actigraphic correlates of neuropsychiatric symptoms in adults with focal epilepsy

Medicaid Expansion and Access to Surgical Treatment Among Patients with Non Small Cell Lung Cancer

Melanoma disparities in urban vs rural communities in the era of immunotherapy: An NCDB analysis.

Postictal bradyarrhythmia following an isolated seizure in a patient with left hemisphere stroke.