Risk and protective factors for psychiatric illnesses and their joint impact on brain and behavior

Katharina Brosch Organizer
Feinstein Institutes for Medical Research
Institute of Behavioral Science, Zucker Hillside Hospital
Glen Oaks, NY 
United States
Thursday, Jun 27: 9:00 AM - 10:15 AM
Room: Grand Ballroom 103 
Certain risk factors predispose an individual to develop psychopathology. Risk factors span biopsychosocial dimensions and include stressful life events (childhood maltreatment, Covid-19 pandemic, experienced racism), genetic risk variants (polygenic risk scores, PRS) and personality traits (neuroticism), among others. However, not every person with risk factors will develop a psychiatric disorder, i.e., some are resilient. Therefore, other factors must be at play that simultaneously mitigate this risk and help individuals maintain mental wellbeing. Such protective factors include social support, cognitive flexibility, secure attachment, meditation, and exercise. Unfortunately, research in psychiatry has largely ignored these factors compared to risk factors. However, to reliably understand the complex etiology of psychiatric illnesses, it is essential to consider the independent and interdependent influences of risk and protective factors.
Both risk and protective factors for psychiatric illness are associated with distinct structural and functional brain changes. However, very few studies consider both impacts on the brain at the same time. Here, we will describe the interactive effect of risk and protective factors on (age-related) brain structure using findings from independent data collection efforts as well as large-scale consortia, such as ENIGMA. Additionally, we will present findings from a recent series of studies on the brain correlates of resilience. Finally, we will discuss the advantages of considering protective factors in research, such as enabling researchers to detect complex interactions and gain a comprehensive understanding of psychopathology and associated brain alterations.
Preventative and treatment interventions in psychiatry recognize the need to improve protective factors and behaviors, such as meditation, building stable relationships, increasing physical exercise, working on optimism and cognitive flexibility. Here, we will also describe clinical findings that further highlight this point, specifically addressing how meditation can impact behavior and brain and increase resilience. This real-life clinical example will further substantiate the necessity of including protective factors when studying psychiatric populations and related brain changes.


Participants will develop a comprehensive understanding of how risk and protective factors impact brain and behavior
Participants will learn about how fostering protective factors can improve mental health in healthy and psychiatric populations
Participants will learn how to meaningfully include protective factors in research 

Target Audience

As this symposium will address the importance of considering protective factors alongside risk factors in mental health research, it will be of interest to a diverse set of human brain mapping researchers including clinicians, cognitive neuroscientists, and psychologists.  


1. Brain Age in Major Depressive Disorder: Genetic and Environmental Risk and Resilience Factors from the ENIGMA MDD consortium

Recent research revealed a connection between major depressive disorder (MDD) and a higher brain age, potentially shedding light on the increased risk of premature mortality in individuals with MDD. However, brain aging and MDD are both individually complex phenomena, highlighting the important need to further dissect the nature and direction of their connections. If we can develop a deeper understanding of the etiology and drivers of biological aging in MDD, we can potentially develop early-intervention strategies to target underlying mechanisms. Progress in this field has been hampered by methodological heterogeneity. To further establish reliable connections between genetics, brain imaging phenotypes and behavior, it is imperative to employ large sample sizes. In my talk, I will share insights from a global research study involving >3,400 participants, providing ample statistical power to study multidimensional imaging phenotypes, genetic, and environmental factors. We have adopted standardized protocols for calculating polygenic risk scores and extracting imaging-derived data in 11 cohorts comprising 1,810 individuals with MDD from 4 different countries. I will discuss findings on age-related brain signatures and a wide range of polygenic risk scores (e.g., MDD, BMI, C-Reactive Protein), environmental exposures (e.g., childhood trauma, smoking) and protective factors (e.g., education). Finally, I will explore the relationship between brain age and other indicators of biological aging (i.e., epigenetic clocks). 


Laura Han, University of Melbourne
Melbourne, VIC 

2. Hold me tight – The protective effects of secure attachment despite childhood maltreatment on behavioral phenotype and brain structure

Childhood maltreatment is a traumatic interpersonal experience and survivors may struggle to form secure attachments even as adults. Securely attached individuals with childhood maltreatment can thus be described as interpersonally resilient. In my talk I will describe the interactive effects of attachment style and childhood maltreatment on phenotype and brain structural data using a sample of N = 1317 healthy adults with and without a history of depression. On a phenotypic level, interpersonally resilient individuals showed significantly lower self-reported (Beck Depression Inventory, BDI) and rater-based (Hamilton Depression Rating Scale, HAM-D) depressive scores. Interpersonally resilient individuals further presented with significantly larger gray matter volumes in the left supramarginal gyrus, part of the somatosensory association cortex and further considered to be part of the mirror neuron system. Increased volume in this area might constitute a neural compensatory mechanism to childhood maltreatment and aid securely attached, maltreated individuals in more adaptively processing semantic information and tactile sensory integration. Interpersonally resilient individuals had lower depressive scores, highlighting the importance of secure attachment as a resilience factor in mitigating the negative effects of childhood maltreatment. In my talk, I will discuss the implication of these findings and the necessity of including protective factors in research. 


Katharina Brosch, Feinstein Institutes for Medical Research
Institute of Behavioral Science, Zucker Hillside Hospital
Glen Oaks, NY 
United States

3. Biological basis of stress resilience

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts to unravel protective factors and mechanisms and use its insights for the development of preventative interventions in individuals at risk for acquiring stress-related dysfunctions. Based on an extensive literature review and a critical methods evaluation, I will provide an up-to-date overview of biological findings in adults, with a focus on neuroimaging. There is preliminary evidence that hippocampal-based pattern separation and prefrontal-based cognitive control functions protect against the development of pathological fears in the aftermath of singular, event-type stressors (as found in fear-related disorders, including simpler forms of post-traumatic stress disorder, PTSD), by facilitating the perception of safety. Reward system-based pursuit and savoring of positive reinforcers appear to protect against the development of more generalized dysfunctions of the anxious-depressive spectrum resulting from more severe or longer-lasting stressors (as in depression, generalized or comorbid anxiety, or severe PTSD). Links between preserved functioning of these neural systems under stress and neuroplasticity, immunoregulation, gut microbiome composition, and integrity of the gut barrier and the blood-brain barrier are beginning to emerge. On this basis, avenues for biological interventions are pointed out. 


Raffael Kalisch, Leibniz Institute for Resilience Research (LIR), Johannes Gutenberg University of Mainz Mainz, Rhineland-Palatinate 

4. Beyond "mindfulness" and toward a science of advanced meditation: Neurophenomenological investigations of absorption and cessation

Meditation includes contemplative practices that are informed by ancient wisdom traditions. Mindfulness is the best-known meditation technique, and includes the development of present-focused awareness and non-judgment of experience. Interest in meditation is burgeoning, and it has been shown to be effective in improving mental and physical health in clinical and non-clinical contexts. Our Meditation Research Program at Massachusetts General Hospital and Harvard Medical School is leading investigations into advanced meditation, that is, states and stages of practice that unfold with expertise over time. We will present several of our recent findings including using human electrophysiology and MRI combined with a neurophenomenological approach to examine the neural signatures of advanced concentration and mindfulness meditation practices including jhana, or ‘absorption’, and nirodha, or ‘cessation’. Absorption is characterized by profound joy, clarity, and openness, whereas cessation is described as complete discontinuation in awareness similar to the loss of consciousness. We intensively sampled these states and events as experienced by a single advanced meditator (with over 23,000 h of meditation training). Our results include spectral and connectivity analyses of the EEG data, and whole-brain 7T fMRI regional homogeneity (assessing the cortex, subcortex, brainstem, and cerebellum). By relating jhana and cessation to objective and intrinsic measures of brain activity (including EEG and MRI metrics) that are related to consciousness and high-level psychological functioning, these results provide evidence for the ability of experienced meditators to voluntarily modulate their state of consciousness and lay the foundation for studying these unique states using a neuroscientific approach toward health-related applications in both clinical and non-clinical contexts. 


Matthew Sacchet, Meditation Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medic Boston, MA 
United States